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Search for "chromium" in Full Text gives 61 result(s) in Beilstein Journal of Organic Chemistry.
Tying a knot between crown ethers and porphyrins
- Maksym Matviyishyn and
- Bartosz Szyszko
Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120
- (II) compounds 16-Pd–19-Pd exhibited conformations with the characteristic Pacman clefts, resembling their postulated solution structures and typical square-planar geometry around the palladium(II) centres. Titanium(III), vanadium(III), and chromium(III) complexes were synthesised through salt
Graphical Abstract
Figure 1: Porphyrin and crown ether.
Figure 2: Timeline demonstrating the contributions into the crown ether–porphyrin chemistry.
Figure 3: Tetra-crowned porphyrin 1 and dimer 2 formed upon K+ binding.
Figure 4: meso-Crowned 25-oxasmaragdyrins 3a–c and their boron(III) complexes (3a–c)-BF2.
Scheme 1: CsF ion-pair binding of 4. The molecular structure of 4-CsF is shown on the right [101].
Figure 5: CsF ion pair binding by 5. The molecular structure of 5-CsF is shown on the right [102].
Scheme 2: Ion-pair binding by 6. The molecular structure of (6-CsCl)2 is shown on the right [103].
Scheme 3: Hydrated fluoride binding by 7 [104].
Figure 6: β-Crowned porphyrin 8.
Figure 7: Crown ether-capped porphyrins 9.
Figure 8: The capped porphyrin 10 and complex [10-PQ](PF6)2.
Figure 9: The double-capped porphyrin 11.
Figure 10: Selected examples of iminoporphyrinoids [58,122].
Scheme 4: The synthesis of 13.
Scheme 5: Tripyrrane-based crown ether-embedding porphyrinoid 15.
Figure 11: Macrocycles 16–19 and their coordination compounds.
Scheme 6: The flexibility of 16-Co [66].
Figure 12: Hexagonal wheel composed of six 16-Co(III) monomers [66].
Scheme 7: The synthesis of 16-V [67].
Figure 13: The molecular structure of dimers [16-Mn]2 [67].
Scheme 8: Synthesis of crownphyrins 28–33. Compounds 23a/b and 29a/b were obtained from 4,7,10-trioxa-1,13-tr...
Figure 14: The molecular structures of 22a, 34a·(HCl)2, and 29b [69].
Figure 15: Molecular structures of 22a-Pb and (29b)2-Zn [69].
Scheme 9: Reactivity of 29a/b.
Scheme 10: Synthesis of 36 and 37 [131].
Scheme 11: Synthesis of 40–45.
Figure 16: Potential applications of porphyrin-crown ether hybrids.
Strategies in the synthesis of dibenzo[b,f]heteropines
- David I. H. Maier,
- Barend C. B. Bezuidenhoudt and
- Charlene Marais
Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51
- . Knell et al. [40][41] reported a comparison of several catalysts, which included potassium-promoted iron, cobalt and manganese oxide catalysts, for the synthesis of 1a. Industrially, 1a is produced by the vapour phase dehydration of 2a over an iron/potassium/chromium catalyst system (Scheme 4) [42]. 2
Graphical Abstract
Figure 1: Dibenzo[b,f]azepine (1a), -oxepine (1b) and -thiepine (1c) as examples of dibenzo[b,f]heteropines (1...
Figure 2: Selected pharmaceuticals with the dibenzo[b,f]azepine skeleton.
Figure 3: Examples of 10,11-dihydrodibenzo[b,f]azepine-based ligands.
Figure 4: The dibenzo[b,f]azepine moiety in dyes with properties suitable for the use in organic light emitti...
Figure 5: Selective bioactive natural products (13–18) containing the dibenzo[b,f]oxepine scaffold and Novart...
Scheme 1: Retrosynthetic approach to 5H-dibenzo[b,f]azepine (1a) from nitrotoluene (22).
Scheme 2: Oxidative coupling of o-nitrotoluene (22) and reduction of 2,2'-dinitrobibenzyl (21) to form 2,2'-d...
Scheme 3: Synthesis of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a) via amine condensation.
Scheme 4: Catalytic reduction of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a).
Scheme 5: The Wagner–Meerwein rearrangement of acridin-9-ylmethanol (23) into 5H-dibenzo[b,f]azepine (1a).
Scheme 6: Oxidative ring expansion of 2-(9-xanthenyl)malonates 24.
Scheme 7: Ring expansion via C–H functionalisation.
Scheme 8: The synthesis of fluorinated 5H-dibenzo[b,f]azepine 38 from isatin (32).
Scheme 9: The synthesis of substituted dibenzo[b,f]azepines 43 from indoles 39.
Scheme 10: Retrosynthetic pathways to dibenzo[b,f]azepines via Buchwald–Hartwig amination.
Scheme 11: Synthesis of dibenzo[b,f]oxepine 54 and -azepine 55 derivatives via (i) Heck reaction and (ii) Buch...
Scheme 12: Double Buchwald–Hartwig amination and thioetherification in the synthesis of tricyclic azepines 60 ...
Scheme 13: Double Buchwald–Hartwig amination towards substituted dibenzoazepines 62.
Scheme 14: Double Buchwald–Hartwig amination towards 10,11-dihydro-5H-dibenzo[b,f]azepine derivatives 71.
Scheme 15: One-pot Suzuki coupling–Buchwald–Hartwig amination.
Scheme 16: One-pot Rh/Pd-catalysed synthesis of dihydropyridobenzazepines.
Scheme 17: A retrosynthetic pathway to dibenzo[b,f]azepines via Mizoroki–Heck reaction.
Scheme 18: One-pot domino Pd-catalyzed Mizoroki–Heck–Buchwald–Hartwig synthesis of dibenzo[b,f]azepines.
Scheme 19: Dibenzo[b,f]thiapine and -oxepine synthesis via SNAr (thio)etherification, Wittig methylenation and...
Scheme 20: A retrosynthetic pathway to dibenzo[b,f]oxepines via Ullmann coupling.
Scheme 21: Ullmann-type coupling in dibenzo[b,f]oxepine synthesis.
Scheme 22: Wittig reaction and Ullmann coupling as key steps in dihydrobenz[b,f]oxepine synthesis.
Scheme 23: Pd-catalysed dibenzo[b,f]azepine synthesis via norbornene azepine intermediate 109.
Scheme 24: A simple representation of olefin metathesis resulting in transalkylidenation.
Scheme 25: Ring-closing metathesis as key step in the synthesis of dibenzo[b,f]heteropines.
Scheme 26: Alkyne–aldehyde metathesis in the synthesis of dibenzo[b,f]heteropines.
Scheme 27: Hydroarylation of 9-(2-alkynylphenyl)-9H-carbazole derivatives.
Scheme 28: Oxidative coupling of bisphonium ylide intermediate to give pacharin (13).
Scheme 29: Preparation of 10,11-dihydrodibenzo[b,f]heteropines via intramolecular Wurtz reaction.
Scheme 30: Phenol deprotonation and intramolecular etherification in the synthesis of bauhinoxepine J.
Figure 6: Functionalisation of dibenzo[b,f]azepine.
Scheme 31: Palladium-catalysed N-arylation of dibenzo[b,f]azepine.
Scheme 32: Cu- and Ni-catalysed N-arylation.
Scheme 33: N-Alkylation of dibenzo[b,f]azepine (1a) and dihydrodibenzo[b,f]azepine (2a).
Scheme 34: Preparation of methoxyiminosilbene.
Scheme 35: Synthesis of oxcarbazepine (153) from methoxy iminostilbene 151.
Scheme 36: Ring functionalisation of dihydrodibenzo[b,f]azepine.
Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series
- Cécile Alleman,
- Charlène Gadais,
- Laurent Legentil and
- François-Hugues Porée
Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23
- –Hiyama–Kishi (NHK) reaction is an interesting coupling reaction involving the addition of a halogeno derivative (either bromide or iodide) to an aldehyde in the presence of nickel and chromium salts, typically NiCl2/CrCl2, generating an alcohol. In its original version, the stereochemistry of the adduct
Graphical Abstract
Figure 1: Examples of terpenes containing a bicyclo[3.6.0]undecane motif.
Figure 2: Commercially available first and second generation Grubbs and Hoveyda–Grubbs catalysts.
Figure 3: Examples of strategies to access the fusicoccan and ophiobolin tricyclic core structure by RCM.
Scheme 1: Synthesis of bicyclic core structure 12 of ophiobolin M (13) and cycloaraneosene (14).
Scheme 2: Synthesis of the core structure 21 of ophiobolins and fusicoccanes.
Scheme 3: Ring-closing metathesis attempts starting from thioester 22.
Scheme 4: Total synthesis of ent-fusicoauritone (28).
Figure 4: General structure of ophiobolins and congeners.
Scheme 5: Total synthesis of (+)-ophiobolin A (8).
Scheme 6: Investigation of RCM for the synthesis of ophiobolin A (8). Path A) RCM with TBDPS-protected alcoho...
Scheme 7: Synthesis of the core structure of cotylenin A aglycon, cotylenol (50).
Scheme 8: Synthesis of tricyclic core structure of fusicoccans.
Scheme 9: Total synthesis of (−)-teubrevin G (59).
Scheme 10: Synthesis of the core skeleton 63 of the basmane family.
Scheme 11: Total synthesis of (±)-schindilactone A (68).
Scheme 12: Total synthesis of dactylol (72).
Scheme 13: Ring-closing metathesis for the total synthesis of (±)-asteriscanolide (2).
Scheme 14: Synthesis of the simplified skeleton of pleuromutilin (1).
Scheme 15: Total synthesis of (−)-nitidasin (93) using a ring-closing metathesis to construct the eight-member...
Scheme 16: Total synthesis of (±)-naupliolide (97).
Scheme 17: Synthesis of the A-B ring structure of fusicoccane (101).
Scheme 18: First attempts of TRCM of dienyne substrates.
Scheme 19: TRCM on optimized substrates towards the synthesis of ophiobolin A (8).
Scheme 20: Tandem ring-closing metathesis for the synthesis of variecolin intermediates 114 and 115.
Scheme 21: Synthesis of poitediol (118) using the allylsilane ring-closing metathesis.
Scheme 22: Access to scaffold 122 by a NHK coupling reaction.
Scheme 23: Key step to construct the [5-8] bicyclooctanone core of aquatolide (4).
Scheme 24: Initial strategy to access aquatolide (4).
Scheme 25: Synthetic plan to cotylenin A (130).
Scheme 26: [5-8] Bicyclic structure of brachialactone (7) constructed by a Mizoroki–Heck reaction.
Scheme 27: Influence of the replacement of the allylic alcohol moiety.
Scheme 28: Formation of variecolin intermediate 140 through a SmI2-mediated Barbier-type reaction.
Scheme 29: SmI2-mediated ketyl addition. Pleuromutilin (1) eight-membered ring closure via C5–C14 bond formati...
Scheme 30: SmI2-mediated dialdehyde cyclization cascade of [5-8-6] pleuromutilin scaffold 149.
Scheme 31: A) Modular synthetic route to mutilin and pleuromutilin family members by Herzon’s group. B) Scaffo...
Scheme 32: Photocatalyzed oxidative ring expansion in pleuromutilin (1) total synthesis.
Scheme 33: Reductive radical cascade cyclization route towards (−)-6-epi-ophiobolin N (168).
Scheme 34: Reductive radical cascade cyclization route towards (+)-6-epi-ophiobolin A (173).
Scheme 35: Radical 8-endo-trig-cyclization of a xanthate precursor.
Figure 5: Structural representations of hypoestin A (177), albolic acid (178), and ceroplastol II (179) beari...
Scheme 36: Synthesis of the common [5-8-5] tricyclic intermediate of hypoestin A (177), albolic acid (178), an...
Scheme 37: Asymmetric synthesis of hypoestin A (177), albolic acid (178), and ceroplastol II (179).
Figure 6: Scope of the Pauson–Khand reaction.
Scheme 38: Nazarov cyclization revealing the fusicoauritone core structure 192.
Scheme 39: Synthesis of fusicoauritone (28) through Nazarov cyclization.
Scheme 40: (+)-Epoxydictymene (5) synthesis through a Nicholas cyclization followed by a Pauson–Khand reaction...
Scheme 41: Synthesis of aquatolide (4) by a Mukaiyama-type aldolisation.
Scheme 42: Tandem Wolff/Cope rearrangement furnishing the A-B bicyclic moiety 204 of variecolin.
Scheme 43: Asymmetric synthesis of the A-B bicyclic core 205 and 206 of variecolin.
Scheme 44: Formation of [5-8]-fused rings by cyclization under thermal activation.
Scheme 45: Construction of the [5-8-6] tricyclic core structure of variecolin (3) by Diels–Alder reaction.
Scheme 46: Synthesis of the [6-4-8-5]-tetracyclic skeleton by palladium-mediated cyclization.
Scheme 47: Access to the [5-8] bicyclic core structure of asteriscanolide (227) through rhodium-catalyzed cycl...
Scheme 48: Total syntheses of asterisca-3(15),6-diene (230) and asteriscanolide (2) with a Rh-catalyzed cycliz...
Scheme 49: Photocyclization of 2-pyridones to access the [5-8-5] backbone of fusicoccanes.
Scheme 50: Total synthesis of (+)-asteriscunolide D (245) and (+)-aquatolide (4) through photocyclization.
Scheme 51: Biocatalysis pathway to construct the [5-8-5] tricyclic scaffold of brassicicenes.
Scheme 52: Influence of the CotB2 mutant over the cyclization’s outcome of GGDP.
Menadione: a platform and a target to valuable compounds synthesis
- Acácio S. de Souza,
- Ruan Carlos B. Ribeiro,
- Dora C. S. Costa,
- Fernanda P. Pauli,
- David R. Pinho,
- Matheus G. de Moraes,
- Fernando de C. da Silva,
- Luana da S. M. Forezi and
- Vitor F. Ferreira
Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43
- discussed in this section. In a pioneering study, Fieser reported the use of chromium(IV) oxide in glacial acetic acid for the oxidation of 2-methylnaphthalene (16) and obtained menadione (10) in 38–42% yield (Table 1, entry 1) [47]. A similar process was developed by Li and Elliot, who used sodium
- ). However, this process is not ecofriendly, once, in this reaction, 18 kg of inorganic salts were obtained as a byproduct per kg of product and it was necessary to treat the wastewater containing chromium. In this context, alternative approaches with a broad range of catalysts and oxidizing agents were
- studied [63]. Yamazaki reported the use of 10 mol % of chromium(VI) oxide and orthoperiodic acid, as a terminal oxidant, to obtain menadione (10) in 61% yield (Table 1, entry 3) [49]. Alternatives to chromium(VI) compounds to oxidize 2-methylnaphthalene (16) to menadione (10) have also been evaluated and
Graphical Abstract
Figure 1: Natural bioactive naphthoquinones.
Figure 2: Chemical structures of vitamins K.
Figure 3: Redox cycle of menadione.
Scheme 1: Selected approaches for menadione synthesis using silver(I) as a catalyst.
Scheme 2: Methylation approaches for the preparation of menadione from 1,4-naphthoquinone using tert-butyl hy...
Scheme 3: Methylation approach of 1,4-naphthoquinone using i) rhodium complexes/methylboronic acid and ii) bi...
Scheme 4: Synthesis of menadione (10) from itaconic acid.
Scheme 5: Menadione synthesis via Diels–Alder reaction.
Scheme 6: Synthesis of menadione (10) using p-cresol as a synthetic precursor.
Scheme 7: Synthesis of menadione (10) via demethoxycarbonylating annulation of methyl methacrylate.
Scheme 8: Furan 34 used as a diene in a Diels–Alder reaction for the synthesis of menadione (10).
Scheme 9: o-Toluidine as a dienophile in a Diels–Alder reaction for the synthesis of menadione (10).
Scheme 10: Representation of electrochemical synthesis of menadione.
Figure 4: Reaction sites and reaction types of menadione as substrate.
Scheme 11: DBU-catalyzed epoxidation of menadione (10).
Scheme 12: Phase-transfer catalysis for the epoxidation of menadione.
Scheme 13: Menadione epoxidation using a hydroperoxide derived from (+)-norcamphor.
Scheme 14: Enantioselective Diels–Alder reaction for the synthesis of asymmetric quinone 50 catalyzed by a chi...
Scheme 15: Optimized reaction conditions for the synthesis of anthra[9,1-bc]pyranone.
Scheme 16: Synthesis of anthra[9,1-bc]furanone, anthra[9,1-bc]pyridine, and anthra[9,1-bc]pyrrole derivatives.
Scheme 17: Synthesis of derivatives employing protected trienes.
Scheme 18: Synthesis of cyclobutene derivatives of menadione.
Scheme 19: Menadione reduction reactions using sodium hydrosulfite.
Scheme 20: Green methodology for menadiol synthesis and pegylation.
Scheme 21: Menadione reduction by 5,6-O-isopropylidene-ʟ-ascorbic acid under UV light irradiation.
Scheme 22: Selected approaches of menadione hydroacetylation to diacetylated menadiol.
Scheme 23: Thiele–Winter reaction catalyzed by Bi(OTf)3.
Scheme 24: Carbonyl condensation of menadione using resorcinol and a hydrazone derivative.
Scheme 25: Condensation reaction of menadione with thiosemicarbazide.
Scheme 26: Condensation reaction of menadione with acylhydrazides.
Scheme 27: Menadione derivatives functionalized with organochalcogens.
Scheme 28: Synthesis of selenium-menadione conjugates derived from chloromethylated menadione 84.
Scheme 29: Menadione alkylation by the Kochi–Anderson method.
Scheme 30: Menadione alkylation by diacids.
Scheme 31: Menadione alkylation by heterocycles-substituted carboxylic acids.
Scheme 32: Menadione alkylation by bromoalkyl-substituted carboxylic acids.
Scheme 33: Menadione alkylation by complex carboxylic acids.
Scheme 34: Kochi–Anderson method variations for the menadione alkylation via oxidative decarboxylation of carb...
Scheme 35: Copper-catalyzed menadione alkylation via free radicals.
Scheme 36: Nickel-catalyzed menadione cyanoalkylation.
Scheme 37: Iron-catalyzed alkylation of menadione.
Scheme 38: Selected approaches to menadione alkylation.
Scheme 39: Menadione acylation by photo-Friedel–Crafts acylation reported by Waske and co-workers.
Scheme 40: Menadione acylation by Westwood procedure.
Scheme 41: Synthesis of 3-benzoylmenadione via metal-free TBAI/TBHP system.
Scheme 42: Michael-type addition of amines to menadione reported by Kallmayer.
Scheme 43: Synthesis of amino-menadione derivatives using polyalkylamines.
Scheme 44: Selected examples for the synthesis of different amino-substituted menadione derivatives.
Scheme 45: Selected examples of Michael-type addition of complex amines to menadione (10).
Scheme 46: Addition of different natural α-amino acids to menadione.
Scheme 47: Michael-type addition of amines to menadione using silica-supported perchloric acid.
Scheme 48: Indolylnaphthoquinone or indolylnaphthalene-1,4-diol synthesis reported by Yadav et al.
Scheme 49: Indolylnaphthoquinone synthesis reported by Tanoue and co-workers.
Scheme 50: Indolylnaphthoquinone synthesis from menadione by Escobeto-González and co-workers.
Scheme 51: Synthesis of menadione analogues functionalized with thiols.
Scheme 52: Synthesis of menadione-derived symmetrical derivatives through reaction with dithiols.
Scheme 53: Mercaptoalkyl acids as nucleophiles in Michael-type addition reaction to menadione.
Scheme 54: Reactions of menadione (10) with cysteine derivatives for the synthesis of quinoproteins.
Scheme 55: Synthesis of menadione-glutathione conjugate 152 by Michael-type addition.
Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF3·OEt2 catalysis
- Karthikeyan Soundararajan,
- Helen Ratna Monica Jeyarajan,
- Raju Subimol Kamarajapurathu and
- Karthik Krishna Kumar Ayyanoth
Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140
- -substituted-1H-indenes from unique substrates of Morita–Baylis–Hillman adducts via an easy operating practical procedure. Keywords: boron trifluoride etherate; chiral (salen)chromium(III); intramolecular Friedel–Crafts cyclization; Morita–Baylis–Hillman adducts; substituted-1H-indenes; Introduction
- convinced us to explore them as suitable chiral Lewis acid catalysts for the Friedel–Crafts cyclization of MBH adducts. Mononuclear(salen) complexes of aluminium, chromium, manganese and cobalt were chosen and screened for the current investigation. Results and Discussion To evaluate the scope of the
- adduct 5a (1 mmol) and chromium(salen)(III) complex 3a (15 mol %) were dissolved in 10 mL of dichloromethane in a flame dried 50 mL RB flask. To the reaction mixture BF3·OEt2 (2.5 mol %) was added drop-wise over 10–15 min using a well-dried glass syringe. The reaction mixture was stirred for 12 hours at
Graphical Abstract
Scheme 1: Literature-reported approaches to synthesise indene from MBH adducts [10-14].
Scheme 2: Proposed model for the intramolecular Friedel–Crafts cyclization.
Scheme 3: Reactions of azomethine imine 7a with 2-substituted 1H-indenes 6a and 6b.
On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets
- Renato L. Carvalho,
- Amanda S. de Miranda,
- Mateus P. Nunes,
- Roberto S. Gomes,
- Guilherme A. M. Jardim and
- Eufrânio N. da Silva Júnior
Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126
- in a cheaper way leading to an easier access of currently expensive treatments to the general population. Chromium-catalyzed C–H activation Chromium is a relatively abundant transition metal that has been used for oxidative reactions, including cross-coupling and carbon–carbon bond formation
- were found to be unreactive, probably due to steric hindrance. The one-pot difunctionalization of arenes involving a sequential C–O cleavage and C(sp2)–H activation mediated by chromium was recently reported by Luo and Zeng [124]. The reaction allows an ortho-directed diarylation of o
- reaction was kept at room temperature to avoid the difunctionalization, and the oxidant was added only in the second step. Following this route, six examples were obtained with moderate yields (56–70%, Scheme 16C). Although the use of chromium catalysis is still considered challenging due to the high
Graphical Abstract
Scheme 1: Schematic overview of transition metals studied in C–H activation processes.
Scheme 2: (A) Known biological activities related to benzimidazole-based compounds; (B and C) an example of a...
Scheme 3: (A) Known biological activities related to quinoline-based compounds; (B and C) an example of a sca...
Scheme 4: (A) Known biological activities related to sulfur-containing compounds; (B and C) an example of a s...
Scheme 5: (A) Known biological activities related to aminoindane derivatives; (B and C) an example of a scand...
Scheme 6: (A) Known biological activities related to norbornane derivatives; (B and C) an example of a scandi...
Scheme 7: (A) Known biological activities related to aniline derivatives; (B and C) an example of a titanium-...
Scheme 8: (A) Known biological activities related to cyclohexylamine derivatives; (B) an example of an intram...
Scheme 9: (A) Known biologically active benzophenone derivatives; (B and C) photocatalytic oxidation of benzy...
Scheme 10: (A) Known bioactive fluorine-containing compounds; (B and C) vanadium-mediated C(sp3)–H fluorinatio...
Scheme 11: (A) Known biologically active Lythraceae alkaloids; (B) synthesis of (±)-decinine (30).
Scheme 12: (A) Synthesis of (R)- and (S)-boehmeriasin (31); (B) synthesis of phenanthroindolizidines by vanadi...
Scheme 13: (A) Known bioactive BINOL derivatives; (B and C) vanadium-mediated oxidative coupling of 2-naphthol...
Scheme 14: (A) Known antiplasmodial imidazopyridazines; (B) practical synthesis of 41.
Scheme 15: (A) Gold-catalyzed drug-release mechanism using 2-alkynylbenzamides; (B and C) chromium-mediated al...
Scheme 16: (A) Examples of anti-inflammatory benzaldehyde derivatives; (B and C) chromium-mediated difunctiona...
Scheme 17: (A and B) Manganese-catalyzed chemoselective intramolecular C(sp3)–H amination; (C) late-stage modi...
Scheme 18: (A and B) Manganese-catalyzed C(sp3)–H amination; (C) late-stage modification of a leelamine deriva...
Scheme 19: (A) Known bioactive compounds containing substituted N-heterocycles; (B and C) manganese-catalyzed ...
Scheme 20: (A) Known indoles that present GPR40 full agonist activity; (B and C) manganese-catalyzed C–H alkyl...
Scheme 21: (A) Examples of known biaryl-containing drugs; (B and C) manganese-catalyzed C–H arylation through ...
Scheme 22: (A) Known zidovudine derivatives with potent anti-HIV properties; (B and C) manganese-catalyzed C–H...
Scheme 23: (A and B) Manganese-catalyzed C–H organic photo-electrosynthesis; (C) late-stage modification.
Scheme 24: (A) Example of a known antibacterial silylated dendrimer; (B and C) manganese-catalyzed C–H silylat...
Scheme 25: (A and B) Fe-based small molecule catalyst applied for selective aliphatic C–H oxidations; (C) late...
Scheme 26: (A) Examples of naturally occurring gracilioethers; (B) the first total synthesis of gracilioether ...
Scheme 27: (A and B) Selective aliphatic C–H oxidation of amino acids; (C) late-stage modification of proline-...
Scheme 28: (A) Examples of Illicium sesquiterpenes; (B) first chemical synthesis of (+)-pseudoanisatin (80) in...
Scheme 29: (A and B) Fe-catalyzed deuteration; (C) late-stage modification of pharmaceuticals.
Scheme 30: (A and B) Biomimetic Fe-catalyzed aerobic oxidation of methylarenes to benzaldehydes (PMHS, polymet...
Scheme 31: (A) Known tetrahydroquinolines with potential biological activities; (B and C) redox-selective Fe c...
Scheme 32: (A) Known drugs containing a benzofuran unit; (B and C) Fe/Cu-catalyzed tandem O-arylation to acces...
Scheme 33: (A) Known azaindolines that act as M4 muscarinic acetylcholine receptor agonists; (B and C) intramo...
Scheme 34: (A) Known indolinones with anticholinesterase activity; (B and C) oxidative C(sp3)–H cross coupling...
Scheme 35: (A and B) Cobalt-catalyzed C–H alkenylation of C-3-peptide-containing indoles; (C) derivatization b...
Scheme 36: (A) Cobalt-Cp*-catalyzed C–H methylation of known drugs; (B and C) scope of the o-methylated deriva...
Scheme 37: (A) Known lasalocid A analogues; (B and C) three-component cobalt-catalyzed C–H bond addition; (D) ...
Scheme 38: (A and B) Cobalt-catalyzed C(sp2)–H amidation of thiostrepton.
Scheme 39: (A) Known 4H-benzo[d][1,3]oxazin-4-one derivatives with hypolipidemic activity; (B and C) cobalt-ca...
Scheme 40: (A and B) Cobalt-catalyzed C–H arylation of pyrrole derivatives; (C) application for the synthesis ...
Scheme 41: (A) Known 2-phenoxypyridine derivatives with potent herbicidal activity; (B and C) cobalt-catalyzed...
Scheme 42: (A) Natural cinnamic acid derivatives; (B and C) cobalt-catalyzed C–H carboxylation of terminal alk...
Scheme 43: (A and B) Cobalt-catalyzed C–H borylation; (C) application to the synthesis of flurbiprofen.
Scheme 44: (A) Benzothiazoles known to present anticonvulsant activities; (B and C) cobalt/ruthenium-catalyzed...
Scheme 45: (A and B) Cobalt-catalyzed oxygenation of methylene groups towards ketone synthesis; (C) synthesis ...
Scheme 46: (A) Known anticancer tetralone derivatives; (B and C) cobalt-catalyzed C–H difluoroalkylation of ar...
Scheme 47: (A and B) Cobalt-catalyzed C–H thiolation; (C) application in the synthesis of quetiapine (153).
Scheme 48: (A) Known benzoxazole derivatives with anticancer, antifungal, and antibacterial activities; (B and...
Scheme 49: (A and B) Cobalt-catalyzed C–H carbonylation of naphthylamides; (C) BET inhibitors 158 and 159 tota...
Scheme 50: (A) Known bioactive pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives; (B and C) cobalt-catalyzed C–H ...
Scheme 51: (A) Known antibacterial cyclic sulfonamides; (B and C) cobalt-catalyzed C–H amination of propargyli...
Scheme 52: (A and B) Cobalt-catalyzed intramolecular 1,5-C(sp3)–H amination; (C) late-stage functionalization ...
Scheme 53: (A and B) Cobalt-catalyzed C–H/C–H cross-coupling between benzamides and oximes; (C) late-state syn...
Scheme 54: (A) Known anticancer natural isoquinoline derivatives; (B and C) cobalt-catalyzed C(sp2)–H annulati...
Scheme 55: (A) Enantioselective intramolecular nickel-catalyzed C–H activation; (B) bioactive obtained motifs;...
Scheme 56: (A and B) Nickel-catalyzed α-C(sp3)–H arylation of ketones; (C) application of the method using kno...
Scheme 57: (A and B) Nickel-catalyzed C(sp3)–H acylation of pyrrolidine derivatives; (C) exploring the use of ...
Scheme 58: (A) Nickel-catalyzed C(sp3)–H arylation of dioxolane; (B) library of products obtained from biologi...
Scheme 59: (A) Intramolecular enantioselective nickel-catalyzed C–H cycloalkylation; (B) product examples, inc...
Scheme 60: (A and B) Nickel-catalyzed C–H deoxy-arylation of azole derivatives; (C) late-stage functionalizati...
Scheme 61: (A and B) Nickel-catalyzed decarbonylative C–H arylation of azole derivatives; (C) application of t...
Scheme 62: (A and B) Another important example of nickel-catalyzed C–H arylation of azole derivatives; (C) app...
Scheme 63: (A and B) Another notable example of a nickel-catalyzed C–H arylation of azole derivatives; (C) lat...
Scheme 64: (A and B) Nickel-based metalorganic framework (MOF-74-Ni)-catalyzed C–H arylation of azole derivati...
Scheme 65: (A) Known commercially available benzothiophene-based drugs; (B and C) nickel-catalyzed C–H arylati...
Scheme 66: (A) Known natural tetrahydrofuran-containing substances; (B and C) nickel-catalyzed photoredox C(sp3...
Scheme 67: (A and B) Another notable example of a nickel-catalyzed photoredox C(sp3)–H alkylation/arylation; (...
Scheme 68: (A) Electrochemical/nickel-catalyzed C–H alkoxylation; (B) achieved scope, including three using na...
Scheme 69: (A) Enantioselective photoredox/nickel catalyzed C(sp3)–H arylation; (B) achieved scope, including ...
Scheme 70: (A) Known commercially available trifluoromethylated drugs; (B and C) nickel-catalyzed C–H trifluor...
Scheme 71: (A and B) Stereoselective nickel-catalyzed C–H difluoroalkylation; (C) late-stage functionalization...
Scheme 72: (A) Cu-mediated ortho-amination of oxalamides; (B) achieved scope, including derivatives obtained f...
Scheme 73: (A) Electro-oxidative copper-mediated amination of 8-aminoquinoline-derived amides; (B) achieved sc...
Scheme 74: (A and B) Cu(I)-mediated C–H amination with oximes; (C) derivatization using telmisartan (241) as s...
Scheme 75: (A and B) Cu-mediated amination of aryl amides using ammonia; (C) late-stage modification of proben...
Scheme 76: (A and B) Synthesis of purine nucleoside analogues using copper-mediated C(sp2)–H activation.
Scheme 77: (A) Copper-mediated annulation of acrylamide; (B) achieved scope, including the synthesis of the co...
Scheme 78: (A) Known bioactive compounds containing a naphthyl aryl ether motif; (B and C) copper-mediated eth...
Scheme 79: (A and B) Cu-mediated alkylation of N-oxide-heteroarenes; (C) late-stage modification.
Scheme 80: (A) Cu-mediated cross-dehydrogenative coupling of polyfluoroarenes and alkanes; (B) scope from know...
Scheme 81: (A) Known anticancer acrylonitrile compounds; (B and C) Copper-mediated cyanation of unactivated al...
Scheme 82: (A) Cu-mediated radiofluorination of 8-aminoquinoline-derived aryl amides; (B) achieved scope, incl...
Scheme 83: (A) Examples of natural β-carbolines; (B and C) an example of a zinc-catalyzed C–H functionalizatio...
Scheme 84: (A) Examples of anticancer α-aminophosphonic acid derivatives; (B and C) an example of a zinc-catal...
Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones
- Girish Suresh Yedase,
- Sumit Kumar,
- Jessica Stahl,
- Burkhard König and
- Veera Reddy Yatham
Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121
- Br2, MnO2, hypervalent iodine reagents, chromium-based reagents, activated dimethyl sulfoxide, KMnO4, OsO4, or metal-based catalysts and peroxide were used [7][8][9][10][11][12][13][14][15][16][17]. Most of these protocols produce harmful waste and some of the oxidizing reagents are considered toxic
Graphical Abstract
Scheme 1: Photocatalyzed aerobic oxidation of aromatic alcohols.
Scheme 2: Substrate scope. Reaction conditions as given in Table 1 (entry 1). Yields are isolated yields, average of...
Scheme 3: Selective oxidation of 3-bromobenzyl alcohol in the presence of 3-phenylpropanol. Compound 1af was ...
Figure 1: Mechanistic studies. (A): UV–vis spectra of the CeIV(OBn)Cln complex in CH3CN under blue light irra...
Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances
- Thiago S. Silva and
- Fernando Coelho
Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112
- an MHAT process. In 2008, Norton and co-workers [76] developed a pioneering radical cascade approach based on the generation of carbon free radicals from an MHAT process. The rates (kH) of hydrogen atom transfer (HAT) from the chromium metal hydride CpCr(CO)3H to olefins with diverse substitution
- developed by Norton employed somewhat unattractive conditions, such as the necessity of maintaining a pressured hydrogen atmosphere in the case of the generation of chromium hydride, the requirement of stoichiometric amounts of vanadium hydride, and the necessity of synthesis and storage (under inert
Graphical Abstract
Figure 1: Some examples of natural products and drugs containing quaternary carbon centers.
Scheme 1: Simplified mechanism for olefin hydrofunctionalization using an electrophilic transition metal as a...
Scheme 2: Selected examples of quaternary carbon centers formed by the intramolecular hydroalkylation of β-di...
Scheme 3: Control experiments and the proposed mechanism for the Pd(II)-catalyzed intermolecular hydroalkylat...
Scheme 4: Intermolecular olefin hydroalkylation of less reactive ketones under Pd(II) catalysis using HCl as ...
Scheme 5: A) Selected examples of Pd(II)-mediated quaternary carbon center synthesis by intermolecular hydroa...
Scheme 6: Selected examples of quaternary carbon center synthesis by gold(III) catalysis. This is the first r...
Scheme 7: Selected examples of inter- (A) and intramolecular (B) olefin hydroalkylations promoted by a silver...
Scheme 8: A) Intermolecular hydroalkylation of N-alkenyl β-ketoamides under Au(I) catalysis in the synthesis ...
Scheme 9: Asymmetric pyrrolidine synthesis through intramolecular hydroalkylation of α-substituted N-alkenyl ...
Scheme 10: Proposed mechanism for the chiral gold(I) complex promotion of the intermolecular olefin hydroalkyl...
Scheme 11: Selected examples of carbon quaternary center synthesis by gold and evidence of catalytic system pa...
Scheme 12: Synthesis of a spiro compound via an aza-Michael addition/olefin hydroalkylation cascade promoted b...
Scheme 13: A selected example of quaternary carbon center synthesis using an Fe(III) salt as a catalyst for th...
Scheme 14: Intermolecular hydroalkylation catalyzed by a cationic iridium complex (Fuji (2019) [47]).
Scheme 15: Generic example of an olefin hydrofunctionalization via MHAT (Shenvi (2016) [51]).
Scheme 16: The first examples of olefin hydrofunctionalization run under neutral conditions (Mukaiyama (1989) [56]...
Scheme 17: A) Aryl olefin dimerization catalyzed by vitamin B12 and triggered by HAT. B) Control experiment to...
Scheme 18: Generic example of MHAT diolefin cycloisomerization and possible competitive pathways. Shenvi (2014...
Scheme 19: Selected examples of the MHAT-promoted cycloisomerization reaction of unactivated olefins leading t...
Scheme 20: Regioselective carbocyclizations promoted by an MHAT process (Norton (2008) [76]).
Scheme 21: Selected examples of quaternary carbon centers synthetized via intra- (A) and intermolecular (B) MH...
Scheme 22: A) Proposed mechanism for the Fe(III)/PhSiH3-promoted radical conjugate addition between olefins an...
Scheme 23: Examples of cascade reactions triggered by HAT for the construction of trans-decalin backbone uniti...
Scheme 24: A) Selected examples of the MHAT-promoted radical conjugate addition between olefins and p-quinone ...
Scheme 25: A) MHAT triggered radical conjugate addition/E1cB/lactonization (in some cases) cascade between ole...
Scheme 26: A) Spirocyclization promoted by Fe(III) hydroalkylation of unactivated olefins. B) Simplified mecha...
Scheme 27: A) Selected examples of the construction of a carbon quaternary center by the MHAT-triggered radica...
Scheme 28: Hydromethylation of unactivated olefins under iron-mediated MHAT (Baran (2015) [95]).
Scheme 29: The hydroalkylation of unactivated olefins via iron-mediated reductive coupling with hydrazones (Br...
Scheme 30: Selected examples of the Co(II)-catalyzed bicyclization of dialkenylarenes through the olefin hydro...
Scheme 31: Proposed mechanism for the bicyclization of dialkenylarenes triggered by a MHAT process (Vanderwal ...
Scheme 32: Enantioconvergent cross-coupling between olefins and tertiary halides (Fu (2018) [108]).
Scheme 33: Proposed mechanism for the Ni-catalyzed cross-coupling reaction between olefins and tertiary halide...
Scheme 34: Proposed catalytic cycles for a MHAT/Ni cross-coupling reaction between olefins and halides (Shenvi...
Scheme 35: Selected examples of the hydroalkylation of olefins by a dual catalytic Mn/Ni system (Shenvi (2019) ...
Scheme 36: A) Selected examples of quaternary carbon center synthesis by reductive atom transfer; TBC: 4-tert-...
Scheme 37: A) Selected examples of quaternary carbon centers synthetized by radical addition to unactivated ol...
Scheme 38: A) Selected examples of organophotocatalysis-mediated radical polyene cyclization via a PET process...
Scheme 39: A) Sc(OTf)3-mediated carbocyclization approach for the synthesis of vicinal quaternary carbon cente...
Scheme 40: Scope of the Lewis acid-catalyzed methallylation of electron-rich styrenes. Method A: B(C6F5)3 (5.0...
Scheme 41: The proposed mechanism for styrene methallylation (Oestreich (2019) [123]).
A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries
- Guido Gambacorta,
- James S. Sharley and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
Valorisation of plastic waste via metal-catalysed depolymerisation
- Francesca Liguori,
- Carmen Moreno-Marrodán and
- Pierluigi Barbaro
Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53
Graphical Abstract
Figure 1: Potential classification of plastic recycling processes. The area covered by the present review is ...
Figure 2: EG produced during glycolytic depolymerisation of PET using DEG + DPG as solvent and titanium(IV) n...
Scheme 1: Simplified representation of the conversion of 1,4-PBD to C16–C44 macrocycles using Ru metathesis c...
Figure 3: Main added-value monomers obtainable by catalytic depolymerisation of PET via chemolytic methods.
Scheme 2: Hydrogenolytic depolymerisation of PET by ruthenium complexes.
Scheme 3: Depolymerisation of PET via catalytic hydrosilylation by Ir(III) pincer complex.
Scheme 4: Catalytic hydrolysis (top) and methanolysis (bottom) reactions of PET.
Scheme 5: Depolymerisation of PET by glycolysis with ethylene glycol.
Figure 4: Glycolysis of PET: evolution of BHET yield over time, with and without zinc acetate catalyst (196 °...
Scheme 6: Potential activated complex for the glycolysis reaction of PET catalysed by metallated ILs and evol...
Scheme 7: One-pot, two-step process for PET repurposing via chemical recycling.
Scheme 8: Synthetic routes to PLA.
Scheme 9: Structures of the zinc molecular catalysts used for PLA-methanolysis in various works. a) See [265], b) ...
Scheme 10: Depolymerisation of PLLA by Zn–N-heterocyclic carbene complex.
Scheme 11: Salalen ligands.
Scheme 12: Catalytic hydrogenolysis of PLA.
Scheme 13: Catalytic hydrosilylation of PLA.
Scheme 14: Hydrogenative depolymerisation of PBT and PCL by molecular Ru catalysts.
Scheme 15: Glycolysis reaction of PCT by diethylene glycol.
Scheme 16: Polymerisation–depolymerisation cycle of 3,4-T6GBL.
Scheme 17: Polymerisation–depolymerisation cycle of 2,3-HDB.
Scheme 18: Hydrogenative depolymerisation of PBPAC by molecular Ru catalysts.
Scheme 19: Catalytic hydrolysis (top), alcoholysis (middle) and aminolysis (bottom) reactions of PBPAC.
Scheme 20: Hydrogenative depolymerisation of PPC (top) and PEC (bottom) by molecular Ru catalysts.
Scheme 21: Polymerisation-depolymerisation cycle of BEP.
Scheme 22: Hydrogenolysis of polyamides using soluble Ru catalysts.
Scheme 23: Catalytic depolymerisation of epoxy resin/carbon fibres composite.
Scheme 24: Depolymerisation of polyethers with metal salt catalysts and acyl chlorides.
Scheme 25: Proposed mechanism for the iron-catalysed depolymerisation reaction of polyethers. Adapted with per...
Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine
- Dimas J. P. Lima,
- Antonio E. G. Santana,
- Michael A. Birkett and
- Ricardo S. Porto
Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4
- converted to oximes 11 and 12 via oxidation with chromium trioxide followed by treatment with hydroxylamine hydrochloride. 11 and 12 were reduced by sodium cyanoborohydride and the resulting hydroxylamines were converted in nitrones, after heating under reflux. These nitrones were not isolated but subjected
Graphical Abstract
Figure 1: Homotropane (azabicyclononane) systems.
Figure 2: Alkaloids (−)-adaline (1), (+)-euphococcinine (2) and (+)-N-methyleuphococcinine (3).
Scheme 1: Synthetic strategies before 1995.
Scheme 2: Synthesis (±)-adaline (1) and (±)-euphococcinine (2). Reagents and conditions: i) 1. dihydropyran, ...
Scheme 3: Synthesis (+)-euphococcinine (2). Reagents and conditions: i) H2O2, SeO2 (cat), acetone, rt, 88%; i...
Scheme 4: Synthesis (+)-euphococcinine (2). Reagents and conditions: i) 2,4-bis(4-phenoxyphenyl)-1,3-dithia-2...
Scheme 5: Synthesis of (±)-euphococcinine precursor (±)-42. Reagents and conditions: i) Bu3SnH, AIBN, toluene...
Scheme 6: Synthesis of (−)-adaline (1). Reagents and conditions: i) LiH2NBH3, THF, 40 °C, 88%; ii) TPAP, NMO,...
Scheme 7: Synthesis of (−)-adaline (1) and (−)-euphococcinine (2). Reagents and conditions: i) 1. BuLi, t-BuO...
Scheme 8: Synthesis of (−)-adaline (1). Reagents and conditions: i) Ref. [52]; ii) Et3N, TBDMSOTf, CH2Cl2, 0 °C t...
Scheme 9: Synthesis of (+)-euphococcinine (2). Reagents and conditions: i) 1. Cp2ZrCl2,AlMe3, CH2Cl2; 2. p-me...
Scheme 10: Synthesis of (−)-adaline 1. Reagents and conditions: i) 1. CuBr.DMS, Et2O/DMS, -42 ºC; 2. 1-heptyne...
Scheme 11: Synthesis of (−)-euphococcinine (2) and (−)-adaline (1). Reagents and conditions: i) 102, KHMDS, Et2...
Scheme 12: Synthesis of N-methyleuphococcinine 3. Reagents and conditions: i) 108 (1.5 equiv), 3,5-di-F-C6H3B(...
Recent developments in enantioselective photocatalysis
- Callum Prentice,
- James Morrisson,
- Andrew D. Smith and
- Eli Zysman-Colman
Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197
Graphical Abstract
Scheme 1: Amine/photoredox-catalysed α-alkylation of aldehydes with alkyl bromides bearing electron-withdrawi...
Scheme 2: Amine/HAT/photoredox-catalysed α-functionalisation of aldehydes using alkenes.
Scheme 3: Amine/cobalt/photoredox-catalysed α-functionalisation of ketones and THIQs.
Scheme 4: Amine/photoredox-catalysed α-functionalisation of aldehydes or ketones with imines. (a) Using keton...
Scheme 5: Bifunctional amine/photoredox-catalysed enantioselective α-functionalisation of aldehydes.
Scheme 6: Bifunctional amine/photoredox-catalysed α-functionalisation of aldehydes using amine catalysts via ...
Scheme 7: Amine/photoredox-catalysed RCA of iminium ion intermediates. (a) Synthesis of quaternary stereocent...
Scheme 8: Bifunctional amine/photoredox-catalysed RCA of enones in a radical chain reaction initiated by an i...
Scheme 9: Bifunctional amine/photoredox-catalysed RCA reactions of iminium ions with different radical precur...
Scheme 10: Bifunctional amine/photoredox-catalysed radical cascade reactions between enones and alkenes with a...
Scheme 11: Amine/photocatalysed photocycloadditions of iminium ion intermediates. (a) External photocatalyst u...
Scheme 12: Amine/photoredox-catalysed addition of acrolein (94) to iminium ions.
Scheme 13: Dual NHC/photoredox-catalysed acylation of THIQs.
Scheme 14: NHC/photocatalysed spirocyclisation via photoisomerisation of an extended Breslow intermediate.
Scheme 15: CPA/photoredox-catalysed aza-pinacol cyclisation.
Scheme 16: CPA/photoredox-catalysed Minisci-type reaction between azaarenes and α-amino radicals.
Scheme 17: CPA/photoredox-catalysed radical additions to azaarenes. (a) α-Amino radical or ketyl radical addit...
Scheme 18: CPA/photoredox-catalysed reduction of azaarene-derived substrates. (a) Reduction of ketones. (b) Ex...
Scheme 19: CPA/photoredox-catalysed radical coupling reactions of α-amino radicals with α-carbonyl radicals. (...
Scheme 20: CPA/photoredox-catalysed Povarov reaction.
Scheme 21: CPA/photoredox-catalysed reactions with imines. (a) Decarboxylative imine generation followed by Po...
Scheme 22: Bifunctional CPA/photocatalysed [2 + 2] photocycloadditions.
Scheme 23: PTC/photocatalysed oxygenation of 1-indanone-derived β-keto esters.
Scheme 24: PTC/photoredox-catalysed perfluoroalkylation of 1-indanone-derived β-keto esters via a radical chai...
Scheme 25: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloadditions of quinolon...
Scheme 26: Bifunctional hydrogen bonding/photocatalysed intramolecular RCA cyclisation of a quinolone.
Scheme 27: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloadditions of quinolon...
Scheme 28: Bifunctional hydrogen bonding/photocatalysed [2 + 2] photocycloaddition reactions. (a) First use of...
Scheme 29: Bifunctional hydrogen bonding/photocatalysed deracemisation of allenes.
Scheme 30: Bifunctional hydrogen bonding/photocatalysed deracemisation reactions. (a) Deracemisation of sulfox...
Scheme 31: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloaddition of coumarins....
Scheme 32: Bifunctional hydrogen bonding/photocatalysed [2 + 2] photocycloadditions of quinolones. (a) Intramo...
Scheme 33: Hydrogen bonding/photocatalysed formal arylation of benzofuranones.
Scheme 34: Hydrogen bonding/photoredox-catalysed dehalogenative protonation of α,α-chlorofluoro ketones.
Scheme 35: Hydrogen bonding/photoredox-catalysed reductions. (a) Reduction of 1,2-diketones. (b) Reduction of ...
Scheme 36: Hydrogen bonding/HAT/photocatalysed deracemisation of cyclic ureas.
Scheme 37: Hydrogen bonding/HAT/photoredox-catalysed synthesis of cyclic sulfonamides.
Scheme 38: Hydrogen bonding/photoredox-catalysed reaction between imines and indoles.
Scheme 39: Chiral cation/photoredox-catalysed radical coupling of two α-amino radicals.
Scheme 40: Chiral phosphate/photoredox-catalysed hydroetherfication of alkenols.
Scheme 41: Chiral phosphate/photoredox-catalysed synthesis of pyrroloindolines.
Scheme 42: Chiral anion/photoredox-catalysed radical cation Diels–Alder reaction.
Scheme 43: Lewis acid/photoredox-catalysed cycloadditions of carbonyls. (a) Formal [2 + 2] cycloaddition of en...
Scheme 44: Lewis acid/photoredox-catalysed RCA reaction using a scandium Lewis acid between α-amino radicals a...
Scheme 45: Lewis acid/photoredox-catalysed RCA reaction using a copper Lewis acid between α-amino radicals and...
Scheme 46: Lewis acid/photoredox-catalysed synthesis of 1,2-amino alcohols from aldehydes and nitrones using a...
Scheme 47: Lewis acid/photocatalysed [2 + 2] photocycloadditions of enones and alkenes.
Scheme 48: Meggers’s chiral-at-metal catalysts.
Scheme 49: Lewis acid/photoredox-catalysed α-functionalisation of ketones with alkyl bromides bearing electron...
Scheme 50: Bifunctional Lewis acid/photoredox-catalysed radical coupling reaction using α-chloroketones and α-...
Scheme 51: Lewis acid/photocatalysed RCA of enones. (a) Using aldehydes as acyl radical precursors. (b) Other ...
Scheme 52: Bifunctional Lewis acid/photocatalysis for a photocycloaddition of enones.
Scheme 53: Lewis acid/photoredox-catalysed RCA reactions of enones using DHPs as radical precursors.
Scheme 54: Lewis acid/photoredox-catalysed functionalisation of β-ketoesters. (a) Hydroxylation reaction catal...
Scheme 55: Bifunctional copper-photocatalysed alkylation of imines.
Scheme 56: Copper/photocatalysed alkylation of imines. (a) Bifunctional copper catalysis using α-silyl amines....
Scheme 57: Bifunctional Lewis acid/photocatalysed intramolecular [2 + 2] photocycloaddition.
Scheme 58: Bifunctional Lewis acid/photocatalysed [2 + 2] photocycloadditions (a) Intramolecular cycloaddition...
Scheme 59: Bifunctional Lewis acid/photocatalysed rearrangement of 2,4-dieneones.
Scheme 60: Lewis acid/photocatalysed [2 + 2] cycloadditions of cinnamate esters and styrenes.
Scheme 61: Nickel/photoredox-catalysed arylation of α-amino acids using aryl bromides.
Scheme 62: Nickel/photoredox catalysis. (a) Desymmetrisation of cyclic meso-anhydrides using benzyl trifluorob...
Scheme 63: Nickel/photoredox catalysis for the acyl-carbamoylation of alkenes with aldehydes using TBADT as a ...
Scheme 64: Bifunctional copper/photoredox-catalysed C–N coupling between α-chloro amides and carbazoles or ind...
Scheme 65: Bifunctional copper/photoredox-catalysed difunctionalisation of alkenes with alkynes and alkyl or a...
Scheme 66: Copper/photoredox-catalysed decarboxylative cyanation of benzyl phthalimide esters.
Scheme 67: Copper/photoredox-catalysed cyanation reactions using TMSCN. (a) Propargylic cyanation (b) Ring ope...
Scheme 68: Palladium/photoredox-catalysed allylic alkylation reactions. (a) Using alkyl DHPs as radical precur...
Scheme 69: Manganese/photoredox-catalysed epoxidation of terminal alkenes.
Scheme 70: Chromium/photoredox-catalysed allylation of aldehydes.
Scheme 71: Enzyme/photoredox-catalysed dehalogenation of halolactones.
Scheme 72: Enzyme/photoredox-catalysed dehalogenative cyclisation.
Scheme 73: Enzyme/photoredox-catalysed reduction of cyclic imines.
Scheme 74: Enzyme/photocatalysed enantioselective reduction of electron-deficient alkenes as mixtures of (E)/(Z...
Scheme 75: Enzyme/photoredox catalysis. (a) Deacetoxylation of cyclic ketones. (b) Reduction of heteroaromatic...
Scheme 76: Enzyme/photoredox-catalysed synthesis of indole-3-ones from 2-arylindoles.
Scheme 77: Enzyme/HAT/photoredox catalysis for the DKR of primary amines.
Scheme 78: Bifunctional enzyme/photoredox-catalysed benzylic C–H hydroxylation of trifluoromethylated arenes.
The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization
- Sharna-kay Daley and
- Nadale Downer-Riley
Beilstein J. Org. Chem. 2020, 16, 2026–2031, doi:10.3762/bjoc.16.169
- ], and chromium trioxide (CrO3), which, based on its Cr(VI) oxidation state, should be able to facilitate single-electron transfer in the presence of electron-rich arenes. The dimerization of 1,2,4-trimethoxynaphthalene (17) in the presence of the metal oxidants CAN, V2O5, and CrO3, afforded binaphthyl
Graphical Abstract
Figure 1: Selected natural products synthesized via oxidative dimerization.
Scheme 1: Proposed biosynthesis of balsaminone A (4) [19].
Scheme 2: Proposed biosynthesis of ellagic acid (5) [20].
Scheme 3: Previous syntheses of balsaminone A (4) [22] and ellagic acid (5) [23].
Scheme 4: Attempted synthesis of the biomimetic precursor 9. [O]: Act-C, K3[Fe(CN)6], or p-benzoquinone.
Scheme 5: Biomimetic synthesis of balsaminone A (4).
Scheme 6: Concise and efficient biomimetic synthesis of ellagic acid (5).
When metal-catalyzed C–H functionalization meets visible-light photocatalysis
- Lucas Guillemard and
- Joanna Wencel-Delord
Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147
Graphical Abstract
Figure 1: Concept of dual synergistic catalysis.
Figure 2: Classification of catalytic systems involving two catalysts.
Figure 3: General mechanism for the dual nickel/photoredox catalytic system.
Figure 4: General mechanisms for C–H activation catalysis involving different reoxidation strategies.
Figure 5: Indole synthesis via dual C–H activation/photoredox catalysis.
Figure 6: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 7: Oxidative Heck reaction on arenes via the dual catalysis.
Figure 8: Proposed mechanism for the Heck reaction on arenes via dual catalysis.
Figure 9: Oxidative Heck reaction on phenols via the dual catalysis.
Figure 10: Proposed mechanism for the Heck reaction on phenols via dual catalysis.
Figure 11: Carbazole synthesis via dual C–H activation/photoredox catalysis.
Figure 12: Proposed mechanism for the carbazole synthesis via dual catalysis.
Figure 13: Carbonylation of enamides via the dual C–H activation/photoredox catalysis.
Figure 14: Proposed mechanism for carbonylation of enamides via dual catalysis.
Figure 15: Annulation of benzamides via the dual C–H activation/photoredox catalysis.
Figure 16: Proposed mechanism for the annulation of benzamides via dual catalysis.
Figure 17: Synthesis of indoles via the dual C–H activation/photoredox catalysis.
Figure 18: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 19: General concept of dual catalysis merging C–H activation and photoredox catalysis.
Figure 20: The first example of dual catalysis merging C–H activation and photoredox catalysis.
Figure 21: Proposed mechanism for the C–H arylation with diazonium salts via dual catalysis.
Figure 22: Dual catalysis merging C–H activation/photoredox using diaryliodonium salts.
Figure 23: Direct arylation via the dual catalytic system reported by Xu.
Figure 24: Direct arylation via dual catalytic system reported by Balaraman.
Figure 25: Direct arylation via dual catalytic system reported by Guo.
Figure 26: C(sp3)–H bond arylation via the dual Pd/photoredox catalytic system.
Figure 27: Acetanilide derivatives acylation via the dual C–H activation/photoredox catalysis.
Figure 28: Proposed mechanism for the C–H acylation with α-ketoacids via dual catalysis.
Figure 29: Acylation of azobenzenes via the dual catalysis C–H activation/photoredox.
Figure 30: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 31: Proposed mechanism for the C2-acylation of indoles with aldehydes via dual catalysis.
Figure 32: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 33: Perfluoroalkylation of arenes via the dual C–H activation/photoredox catalysis.
Figure 34: Proposed mechanism for perfluoroalkylation of arenes via dual catalysis.
Figure 35: Sulfonylation of 1-naphthylamides via the dual C–H activation/photoredox catalysis.
Figure 36: Proposed mechanism for sulfonylation of 1-naphthylamides via dual catalysis.
Figure 37: meta-C–H Alkylation of arenes via visible-light metallaphotocatalysis.
Figure 38: Alternative procedure for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 39: Proposed mechanism for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 40: C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 41: Proposed mechanism for C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 42: Undirected C–H aryl–aryl cross coupling via dual gold/photoredox catalysis.
Figure 43: Proposed mechanism for the undirected C–H aryl–aryl cross-coupling via dual catalysis.
Figure 44: Undirected C–H arylation of (hetero)arenes via dual manganese/photoredox catalysis.
Figure 45: Proposed mechanism for the undirected arylation of (hetero)arenes via dual catalysis.
Figure 46: Photoinduced C–H arylation of azoles via copper catalysis.
Figure 47: Photo-induced C–H chalcogenation of azoles via copper catalysis.
Figure 48: Decarboxylative C–H adamantylation of azoles via dual cobalt/photoredox catalysis.
Figure 49: Proposed mechanism for the C–H adamantylation of azoles via dual catalysis.
Figure 50: General mechanisms for the “classical” (left) and Cu-free variant (right) Sonogoshira reaction.
Figure 51: First example of a dual palladium/photoredox catalysis for Sonogashira-type couplings.
Figure 52: Arylation of terminal alkynes with diazonium salts via dual gold/photoredox catalysis.
Figure 53: Proposed mechanism for the arylation of terminal alkynes via dual catalysis.
Figure 54: C–H Alkylation of alcohols promoted by H-atom transfer (HAT).
Figure 55: Proposed mechanism for the C–H alkylation of alcohols promoted by HAT.
Figure 56: C(sp3)–H arylation of latent nucleophiles promoted by H-atom transfer.
Figure 57: Proposed mechanism for the C(sp3)–H arylation of latent nucleophiles promoted by HAT.
Figure 58: Direct α-arylation of alcohols promoted by H-atom transfer.
Figure 59: Proposed mechanism for the direct α-arylation of alcohols promoted by HAT.
Figure 60: C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 61: Proposed mechanism for the C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 62: C–H functionalization of nucleophiles via excited ketone/nickel dual catalysis.
Figure 63: Proposed mechanism for the C–H functionalization enabled by excited ketones.
Figure 64: Selective sp3–sp3 cross-coupling promoted by H-atom transfer.
Figure 65: Proposed mechanism for the selective sp3–sp3 cross-coupling promoted by HAT.
Figure 66: Direct C(sp3)–H acylation of amines via dual Ni/photoredox catalysis.
Figure 67: Proposed mechanism for the C–H acylation of amines via dual Ni/photoredox catalysis.
Figure 68: C–H hydroalkylation of internal alkynes via dual Ni/photoredox catalysis.
Figure 69: Proposed mechanism for the C–H hydroalkylation of internal alkynes.
Figure 70: Alternative procedure for the C–H hydroalkylation of ynones, ynoates, and ynamides.
Figure 71: Allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 72: Proposed mechanism for the allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 73: Asymmetric allylation of aldehydes via dual Cr/photoredox catalysis.
Figure 74: Proposed mechanism for the asymmetric allylation of aldehydes via dual catalysis.
Figure 75: Aldehyde C–H functionalization promoted by H-atom transfer.
Figure 76: Proposed mechanism for the C–H functionalization of aldehydes promoted by HAT.
Figure 77: Direct C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 78: Proposed mechanism for the C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 79: Direct C–H trifluoromethylation of strong aliphatic bonds promoted by HAT.
Figure 80: Proposed mechanism for the C–H trifluoromethylation of strong aliphatic bonds.
Preparation of anthracene-based tetraperimidine hexafluorophosphate and selective recognition of chromium(III) ions
- Qing-Xiang Liu,
- Feng Yang,
- Zhi-Xiang Zhao,
- Shao-Cong Yu and
- Yue Ding
Beilstein J. Org. Chem. 2019, 15, 2847–2855, doi:10.3762/bjoc.15.278
- ; chromium(III) ion; tetraperimidine; Introduction Fluorescent chemosensors are an attractive and efficient tool for the detection of metal ions in environmental and biological science because of their high sensitivity, selectivity, and simple usage [1][2][3][4][5][6][7][8]. Among metal ions, the detection
- of Cr3+ ions occupies an important position. Chromium(III) is an essential microelement for humans and animals, and it plays an important role in glucose and lipid metabolism in the body [9][10]. The deficiency of chromium(III) in the human body leads to various diseases, such as diabetes as well as
- autoimmune and cardiovascular diseases [11]. On the other hand, the excessive incorporation of chromium(III) is toxic to humans, and can cause cancer through the oxidation of DNA and some proteins [12][13][14]. Therefore, the detection of chromium(III) has a vital practical significance for human health
Graphical Abstract
Scheme 1: Synthetic route to compound 3.
Figure 1: View of the molecular structure of the cationic moiety of 3 in the crystal. Selected bond angles an...
Figure 2: Fluorescence spectra of 3 (c = 5.0⋅10−6 M) upon addition of 30 equiv of salts of K+, Na+, Li+, Ag+,...
Figure 3: Fluorescence spectra of 3 (c = 5⋅10−6 M) upon addition of various amounts of Cr3+. cCr3+ for curves...
Scheme 2: Illustration of interactions between 3 and Cr3+ in 3⋅Cr3+.
Figure 4: 1H NMR spectra of 3 in the presence of Cr3+ in DMSO-d6. (i) 3. (ii) 3 + 0.25 equiv of Cr3+. (iii) 3...
Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues
- Leon Buschbeck,
- Aleksandra Markovic,
- Gunther Wittstock and
- Jens Christoffers
Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96
- cleaned glass slides as the support by depositing 0.5 nm of chromium by electron-beam evaporation as adhesion layer and 200 nm of gold by resistive heating using an evaporation chamber (minicoater, Tectra GmbH, Frankfurt, Germany). The thickness was monitored by means of a quartz crystal microbalance
Graphical Abstract
Figure 1: Bifunctional DAT as a cross-linker for proteins. The compound is a turn-on-probe, i.e., the fluores...
Scheme 1: Preparation of DAT–ALA conjugate 3 with fluorinated benzyl residue.
Scheme 2: Preparation of conjugate 7 consisting of fluorinated DAT and ALA moieties with an additional propyl...
Figure 2: High-resolution XPS of SAM 3.
Figure 3: High-resolution XPS of SAM 7.
Copolymerization of epoxides with cyclic anhydrides catalyzed by dinuclear cobalt complexes
- Yo Hiranoi and
- Koji Nakano
Beilstein J. Org. Chem. 2018, 14, 2779–2788, doi:10.3762/bjoc.14.255
- -workers reported that the dinuclear chromium–salan complex showed a much higher catalytic activity than the corresponding mononuclear chromium–salan complex in the copolymerization of epoxides with maleic anhydride (MA) [31]. Following this report, some dinuclear metal complexes have been reported to
Graphical Abstract
Figure 1: Structures of cobalt–salen complexes 1–4.
Scheme 1: Synthesis of dinuclear cobalt–salen complexes (R,R,S,S)-2 and (R,R,R,R)-2.
Figure 2: MALDI–TOF mass spectrum of the PO/PA copolymer. The low molecular weight copolymer for MS analysis ...
Scheme 2: Terpolymerization of PO, HO, and PA with (R,R,R,R)-1.
Anomeric modification of carbohydrates using the Mitsunobu reaction
- Julia Hain,
- Patrick Rollin,
- Werner Klaffke and
- Thisbe K. Lindhorst
Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138
- outcome of the reaction towards β-configured products [53]. In this case, phenolic chromium tricarbonyl complexes of weaker acids such as p-cresol were employed to improve the yield. The challenge of glycoside synthesis using sugars devoid of a C-2 participating group is also highlighted by a total
Graphical Abstract
Scheme 1: Left: The Mitsunobu reaction is essentially a nucleophilic substitution of alcohols occurring with ...
Scheme 2: Mechanistic considerations on the Mitsunobu reaction with carbohydrate hemiacetals (depicted in sim...
Scheme 3: Anomeric esterification using the Mitsunobu procedure [29].
Scheme 4: Conversion of allyl glucuronate into various 1-O-esterified allyl glucuronates using anomeric Mitsu...
Scheme 5: Synthesis of anomeric glycosyl esters as substrates for Au-catalyzed glycosylation [40].
Scheme 6: Correlation between pKa value of the employed acids (or alcohol) and the favoured anomeric configur...
Scheme 7: Synthesis of the β-mannosyl phosphates for the synthesis of HBP 43 by anomeric phosphorylation acco...
Scheme 8: Synthesis of phenyl glycosides 44 and 45 from unprotected sugars [24].
Scheme 9: Synthesis of azobenzene mannosides 47 and 48 without protecting group chemistry [46].
Scheme 10: Synthesis of various aryl sialosides using Mitsunobu glycosylation [25].
Scheme 11: Mitsunobu synthesis of different jadomycins [54,55]. BOM: benzyloxymethyl.
Scheme 12: Stereoselectivity in the Mitsunobu synthesis of catechol glycosides in the gluco- and manno-series [56]....
Scheme 13: Formation of a 1,2-cis glycoside 80 assisted by steric hindrance of the β-face of the disaccharide ...
Scheme 14: Stereoselective β-D-mannoside synthesis [60].
Scheme 15: TIPS-assisted synthesis of 1,2-cis arabinofuranosides [63]. TIPS: triisopropylsilyl.
Scheme 16: The Mitsunobu reaction with glycals leads to interesting rearrangement products [69].
Scheme 17: Synthesis of disaccharides using mercury(II) bromide as co-activator in the Mitsunobu reaction [75].
Scheme 18: Synthesis of various fructofuranosides according to Mitsunobu and proposed neighbouring group parti...
Scheme 19: The Mitsunobu reaction allows stereoslective acetalization of dihydroartemisinin [77].
Scheme 20: Synthesis of alkyl thioglycosides by Mitsunobu reaction [81].
Scheme 21: Preparation of iminoglycosylphthalimide 115 from 114 [85].
Scheme 22: Mitsunobu reaction as a key step in the total synthesis of aurantoside G [87].
Scheme 23: Utilization of an N–H acid in the Mitsunobu reaction [88].
Scheme 24: Mitsunobu reaction with 1H-tetrazole [89].
Scheme 25: Formation of a rebeccamycin analogue using the Mitsunobu reaction [101].
Scheme 26: Synthesis of carbohydrates with an alkoxyamine bond [114].
Scheme 27: Synthesis of glycosyl fluorides and glycosyl azides according to Mitsunobu [118,119].
Scheme 28: Anomeric oxidation under Mitsunobu conditions [122].
Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst
- Kimihiro Komeyama,
- Shunsuke Sakiyama,
- Kento Iwashita,
- Itaru Osaka and
- Ken Takaki
Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118
- Kimihiro Komeyama Shunsuke Sakiyama Kento Iwashita Itaru Osaka Ken Takaki Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University, 1-4-1 Higashi-Hiroshima City 739-8527, Japan 10.3762/bjoc.14.118 Abstract The cobalt/chromium-catalyzed three-component coupling of aryl
- , whereas the chromium salt generates highly nucleophilic allylchromium intermediates from allylcobalt species, without the loss of stereochemical information, to allow the addition to aldehydes. Keywords: chromium; cobalt; diastereoselective; homoallyl alcohols; hybrid catalyst; three-component coupling
- organometallics, involving a wide range of transition metal-catalyzed reactions. For example, transmetalation between an organonickel (or organocobalt) complex and chromium salt results in the formation of a highly nucleophilic organochromium species, which enables efficient addition to aldehydes to give
Graphical Abstract
Scheme 1: Nucleophilic and π-electrophilic characters of organometallics depending on the central metals.
Scheme 2: Ni/Cr or Co/Cr-catalyzed NHK reaction.
Scheme 3: Functionalization of alkynes via carbocobaltation.
Scheme 4: Cyclization/borylation of alkynyl iodoarenes using the Co/Cr catalyst.
Scheme 5: Three-component coupling of aryl iodides, arenes, and aldehydes using Co/Cr catalyst (this work).
Scheme 6: Screening of aldehydes in the Co/Cr-catalyzed three-component coupling reaction. All yields are det...
Scheme 7: Screening of aryl iodides in the Co/Cr-catalyzed three-component coupling reaction. All yields are ...
Scheme 8: Screening of allenes in the Co/Cr-catalyzed three-component coupling reaction. All yields are deter...
Scheme 9: Reversed diastereoselectivity using allenyl ethers 5 and 6. a4-chlorobenzaldehyde was used instead ...
Scheme 10: Stoichiometric reaction of phenylchromium(II or III) reagents (reaction 1) and the three-component ...
Scheme 11: The origin of the diastereoselectivity in the present three-component coupling.
Scheme 12: Plausible reaction mechanism of the three-component coupling.
One hundred years of benzotropone chemistry
- Arif Dastan,
- Haydar Kilic and
- Nurullah Saracoglu
Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98
Graphical Abstract
Scheme 1: Tropone (1), tropolone (2) and their resonance structures.
Figure 1: Natural products containing a tropone nucleus.
Figure 2: Possible isomers 11–13 of benzotropone.
Scheme 2: Synthesis of benzotropones 11 and 12.
Scheme 3: Oxidation products of benzotropylium fluoroborate (16).
Scheme 4: Oxidation of 7-bromo-5H-benzo[7]annulene (22).
Scheme 5: Synthesis of 4,5-benzotropone (11) using o-phthalaldehyde (27).
Scheme 6: Synthesis of 4,5-benzotropone (11) starting from oxobenzonorbornadiene 31.
Scheme 7: Acid-catalyzed cleavage of oxo-bridge of 34.
Scheme 8: Synthesis of 4,5-benzotropone (11) from o-xylylene dibromide (38).
Scheme 9: Synthesis of 4,5-benzotropone (11) via the carbene adduct 41.
Scheme 10: Heck coupling strategy for the synthesis of 11.
Scheme 11: Synthesis of benzofulvalenes via carbonyl group of 4,5-benzotropone (11).
Figure 3: Some cycloheptatrienylium cations.
Scheme 12: Synthesis of condensation product 63 and its subsequent oxidative cyclization products.
Figure 4: A novel series of benzo[7]annulenes prepared from 4,5-benzotropone (11).
Scheme 13: Preparation of substituted benzo[7]annulene 72 using the Mukaiyama-Michael reaction.
Figure 5: Possible benzo[7]annulenylidenes 73–75.
Scheme 14: Thermal and photochemical decomposition of 7-diazo-7H-benzo[7]annulene (76) and the trapping of int...
Scheme 15: Synthesis of benzoheptafulvalene 86.
Scheme 16: Synthesis of 7-(diphenylmethylene)-7H-benzo[7]annulene (89).
Scheme 17: Reaction of 4,5-benzotropone (11) with dimethyl diazomethane.
Scheme 18: Synthesis of dihydrobenzomethoxyazocine 103.
Scheme 19: Synthesis and reducibility of benzo-homo-2-methoxyazocines.
Scheme 20: Synthesis of 4,5-benzohomotropones 104 and 115 from 4,5-benzotropones 11 and 113.
Scheme 21: A catalytic deuterogenation of 4,5-benzotropone (11) and synthesis of 5-monosubstituted benzo[7]ann...
Scheme 22: Synthesis of methyl benzo[7]annulenes 131 and 132.
Scheme 23: Ambident reactivity of halobenzo[7]annulenylium cations 133a/b.
Scheme 24: Preparation of benzo[7]annulenylidene–iron complexes 147.
Scheme 25: Synthesis of 1-ethynylbenzotropone (150) and the etheric compound 152 from 4,5-benzotropone (11) wi...
Scheme 26: Thermal decomposition of 4,5-benzotropone (11).
Scheme 27: Reaction of 4,5-benzotropone (11) with 1,2-ethanediol and 1,2-ethanedithiol.
Scheme 28: Conversions of 1-benzosuberone (162) to 2,3-benzotropone (12).
Scheme 29: Synthesis strategies for 2,3-bezotropone (12) using 1-benzosuberones.
Scheme 30: Oxidation-based synthesis of 2,3-benzotropone (12) via 1-benzosuberone (162).
Scheme 31: Synthesis of 2,3-benzotropone (12) from α-tetralone (171) via ring-expansion.
Scheme 32: Preparation of 2,3-benzotropone (12) by using of benzotropolone 174.
Figure 6: Benzoheptafulvenes as condensation products of 2,3-benzotropone (12).
Scheme 33: Conversion of 2,3-benzotropone (12) to tosylhydrazone salt 182 and gem-dichloride 187.
Figure 7: Benzohomoazocines 191–193 and benzoazocines 194–197.
Scheme 34: From 2,3-benzotropone (12) to carbonium ions 198–201.
Scheme 35: Cycloaddition reactions of 2,3-benzotropone (12).
Scheme 36: Reaction of 2,3-benzotropone (12) with various reagents and compounds.
Figure 8: 3,4-Benzotropone (13) and its resonance structure.
Scheme 37: Synthesis of 6,7-benzobicyclo[3.2.0]hepta-3,6-dien-2-one (230).
Figure 9: Photolysis and thermolysis products of 230.
Figure 10: Benzotropolones and their tautomeric structures.
Scheme 38: Synthesis strategies of 4,5-benzotropolone (238).
Scheme 39: Synthesis protocol for 2-hydroxy-4,5-benzotropone (238) using oxazole-benzo[7]annulene 247.
Figure 11: Some quinoxaline and pyrazine derivatives 254–256 prepared from 4,5-benzotropolone (238).
Scheme 40: Nitration product of 4,5-benzotropolone (238) and its isomerization to 1-nitro-naphthoic acid (259)....
Scheme 41: Synthesis protocol for 6-hydroxy-2,3-benzotropone (239) from benzosuberone (162).
Scheme 42: Various reactions via 6-hydroxy-2,3-benzotropone (239).
Scheme 43: Photoreaction of 6-hydroxy-2,3-benzotropone (239).
Scheme 44: Synthesis of 7-hydroxy-2,3-benzotropone (241) from benzosuberone (162).
Scheme 45: Synthesis strategy for 7-hydroxy-2,3-benzotropone (241) from ketone 276.
Scheme 46: Synthesis of 7-hydroxy-2,3-benzotropone (241) from β-naphthoquinone (280).
Scheme 47: Synthesis of 7-hydroxy-2,3-benzotropone (241) from bicyclic endoperoxide 213.
Scheme 48: Synthesis of 7-hydroxy-2,3-benzotropone (241) by ring-closing metathesis.
Figure 12: Various monosubstitution products 289–291 of 7-hydroxy-2,3-benzotropone (241).
Scheme 49: Reaction of 7-hydroxy-2,3-benzotropone (241) with various reagents.
Scheme 50: Synthesis of 4-hydroxy-2,3-benzotropones 174 and 304 from diketones 300/301.
Scheme 51: Catalytic hydrogenation of diketones 300 and 174.
Scheme 52: Synthesis of halo-benzotropones from alkoxy-naphthalenes 306, 307 and 310.
Figure 13: Unexpected byproducts 313–315 during synthesis of chlorobenzotropone 309.
Figure 14: Some halobenzotropones and their cycloadducts.
Scheme 53: Multisep synthesis of 2-chlorobenzotropone 309.
Scheme 54: A multistep synthesis of 2-bromo-benzotropone 26.
Scheme 55: A multistep synthesis of bromo-2,3-benzotropones 311 and 316.
Scheme 56: Oxidation reactions of 8-bromo-5H-benzo[7]annulene (329) with some oxidants.
Scheme 57: Synthesis of 2-bromo-4,5-benzotropone (26).
Scheme 58: Synthesis of 6-chloro-2,3-benzotropone (335) using LiCl and proposed intermediate 336.
Scheme 59: Reaction of 7-bromo-2,3-benzotropone (316) with methylamine.
Scheme 60: Reactions of bromo-2,3-benzotropones 26 and 311 with dimethylamine.
Scheme 61: Reactions of bromobenzotropones 311 and 26 with NaOMe.
Scheme 62: Reactions of bromobenzotropones 26 and 312 with t-BuOK in the presence of DPIBF.
Scheme 63: Cobalt-catalyzed reductive cross-couplings of 7-bromo-2,3-benzotropone (316) with cyclic α-bromo en...
Figure 15: Cycloadduct 357 and its di-π-methane rearrangement product 358.
Scheme 64: Catalytic hydrogenation of 2-chloro-4,5-benzotropone (311).
Scheme 65: Synthesis of dibromo-benzotropones from benzotropones.
Scheme 66: Bromination/dehydrobromination of benzosuberone (162).
Scheme 67: Some transformations of isomeric dibromo-benzotropones 261A/B.
Scheme 68: Transformations of benzotropolone 239B to halobenzotropolones 369–371.
Figure 16: Bromobenzotropolones 372–376 and 290 prepared via bromination/dehydrobromination strategy.
Scheme 69: Synthesis of some halobenzotropolones 289, 377 and 378.
Figure 17: Bromo-chloro-derivatives 379–381 prepared via chlorination.
Scheme 70: Synthesis of 7-iodo-3,4-benzotropolone (382).
Scheme 71: Hydrogenation of bromobenzotropolones 369 and 370.
Scheme 72: Debromination reactions of mono- and dibromides 290 and 375.
Figure 18: Nitratation and oxidation products of some halobenzotropolenes.
Scheme 73: Azo-coupling reactions of some halobenzotropolones 294, 375 and 378.
Figure 19: Four possible isomers of dibenzotropones 396–399.
Figure 20: Resonance structures of tribenzotropone (400).
Scheme 74: Two synthetic pathways for tribenzotropone (400).
Scheme 75: Synthesis of tribenzotropone (400) from dibenzotropone 399.
Scheme 76: Synthesis of tribenzotropone (400) from 9,10-phenanthraquinone (406).
Scheme 77: Synthesis of tribenzotropone (400) from trifluoromethyl-substituted arene 411.
Figure 21: Dibenzosuberone (414).
Figure 22: Reduction products 415 and 416 of tribenzotropone (400).
Figure 23: Structures of tribenzotropone dimethyl ketal 417 and 4-phenylfluorenone (412) and proposed intermed...
Figure 24: Structures of benzylidene- and methylene-9H-tribenzo[a,c,e][7]annulenes 419 and 420 and chiral phos...
Figure 25: Structures of tetracyclic alcohol 422, p-quinone methide 423 and cation 424.
Figure 26: Structures of host molecules 425–427.
Scheme 78: Synthesis of non-helical overcrowded derivatives syn/anti-431.
Figure 27: Hexabenzooctalene 432.
Figure 28: Structures of possible eight isomers 433–440 of naphthotropone.
Scheme 79: Synthesis of naphthotropone 437 starting from 1-phenylcycloheptene (441).
Scheme 80: Synthesis of 10-hydroxy-11H-cyclohepta[a]naphthalen-11-one (448) from diester 445.
Scheme 81: Synthesis of naphthotropone 433.
Scheme 82: Synthesis of naphthotropones 433 and 434 via cycloaddition reaction.
Scheme 83: Synthesis of naphthotropone 434 starting from 452.
Figure 29: Structures of tricarbonyl(tropone)irons 458, and possible cycloadducts 459.
Scheme 84: Synthesis of naphthotropone 436.
Scheme 85: Synthesis of precursor 465 for naphthotropone 435.
Scheme 86: Generation of naphthotropone 435 from 465.
Figure 30: Structures of tropylium cations 469 and 470.
Figure 31: Structures of tropylium ions 471+.BF4−, 472+.BF4−, and 473+.BF4−.
Scheme 87: Synthesis of tropylium ions 471+.BF4− and 479+.ClO4−.
Scheme 88: Synthesis of 1- and 2-methylanthracene (481 and 482) via carbene–carbene rearrangement.
Figure 32: Trapping products 488–490.
Scheme 89: Generation and chemistry of a naphthoannelated cycloheptatrienylidene-cycloheptatetraene intermedia...
Scheme 90: Proposed intermediates and reaction pathways for adduct 498.
Scheme 91: Exited-state intramolecular proton transfer of 505.
Figure 33: Benzoditropones 506 and 507.
Scheme 92: Synthesis of benzoditropone 506e.
Scheme 93: Synthetic approaches for dibenzotropone 507 via tropone (1).
Scheme 94: Formation mechanisms of benzoditropone 507 and 516 via 515.
Scheme 95: Synthesis of benzoditropones 525 and 526 from pyromellitic dianhydride (527).
Figure 34: Possible three benzocyclobutatropones 534–536.
Scheme 96: Synthesis of benzocyclobutatropones 534 and 539.
Scheme 97: Synthesis attempts for benzocyclobutatropone 545.
Scheme 98: Generation and trapping of symmetric benzocyclobutatropone 536.
Scheme 99: Synthesis of chloro-benzocyclobutatropone 552 and proposed mechanism of fluorenone derivatives.
Scheme 100: Synthesis of tropolone analogue 559.
Scheme 101: Synthesis of tropolones 561 and 562.
Figure 35: o/p-Tropoquinone rings (563 and 564) and benzotropoquinones (565–567).
Scheme 102: Synthesis of benzotropoquinone 566.
Scheme 103: Synthesis of benzotropoquinone 567 via a Diels–Alder reaction.
Figure 36: Products 575–577 through 1,2,3-benzotropoquinone hydrate 569.
Scheme 104: Structures 578–582 prepared from tropoquinone 567.
Figure 37: Two possible structures 583 and 584 for dibenzotropoquinone, and precursor compound 585 for 583.
Scheme 105: Synthesis of saddle-shaped ketone 592 using dibenzotropoquinone 584.
2-Iodo-N-isopropyl-5-methoxybenzamide as a highly reactive and environmentally benign catalyst for alcohol oxidation
- Takayuki Yakura,
- Tomoya Fujiwara,
- Akihiro Yamada and
- Hisanori Nambu
Beilstein J. Org. Chem. 2018, 14, 971–978, doi:10.3762/bjoc.14.82
- fundamental and frequently used transformation in organic synthesis. Heavy metal-based oxidants such as chromium(VI), lead(IV), and mercury(II) have been extensively used for this purpose for a long time. However, these oxidants are highly toxic and produce hazardous waste. Recently, hypervalent iodine
Graphical Abstract
Figure 1: Structures of pentavalent iodine oxidants 1 and 2, and iodine catalysts 3–13.
Figure 2: Structures of the catalysts 16–25.
Scheme 1: Oxidation of the monovalent iodine derivatives 17 and 3 to the pentavalent iodine derivatives 29 an...
Figure 3: Reaction profile of the oxidation of (a) iodobenzamide 17 and (b) 2-iodobenzoic acid (3) with Oxone®...
Scheme 2: Plausible reaction mechanism for the oxidation of alcohols catalyzed by the 2-iodobenzamides.
Mechanochemistry of nucleosides, nucleotides and related materials
- Olga Eguaogie,
- Joseph S. Vyle,
- Patrick F. Conlon,
- Manuela A. Gîlea and
- Yipei Liang
Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81
- under ball-milling conditions, Lamaty and co-workers showed that deterioration of vessels and balls by physical abrasion and/or chemical leaching gave products in which (depending upon the nature of the jar) iron, chromium, zirconia or PTFE were detected [20]. This has influenced the choice of vessel
Graphical Abstract
Figure 1: Examples of equipment used to perform mechanochemistry on nucleoside and nucleotide substrates (not...
Figure 2: Ganciclovir.
Scheme 1: Nucleoside tritylation effected by hand grinding in a heated mortar and pestle.
Scheme 2: Persilylation of ribonucleoside hydroxy groups (and in situ acylation of cytidine) in a MBM.
Scheme 3: Nucleoside amine and carboxylic acid Boc protection using an improvised attritor-type mill.
Scheme 4: Nucleobase Boc protection via transient silylation using an improvised attritor-type mill.
Scheme 5: Chemoselective N-acylation of an aminonucleoside using LAG in a MBM.
Scheme 6: Azide–alkyne cycloaddition reactions performed in a copper vessel in a MBM.
Figure 3: a) Custom-machined copper vessel and zirconia balls used to perform CuAAC reactions (showing: upper...
Scheme 7: Thiolate displacement reactions of nucleoside derivatives in a MBM.
Scheme 8: Selenocyanate displacement reactions of nucleoside derivatives in a MBM.
Scheme 9: Nucleobase glycosidation reactions and subsequent deacetylation performed in a MBM.
Scheme 10: Regioselective phosphorylation of nicotinamide riboside in a MBM.
Scheme 11: Preparation of nucleoside phosphoramidites in a MBM using ionic liquid-stabilised chlorophosphorami...
Scheme 12: Preparation of a nucleoside phosphite triester using LAG in a MBM.
Scheme 13: Internucleoside phosphate coupling linkages in a MBM.
Scheme 14: Preparation of ADPR analogues using in a MBM.
Scheme 15: Synthesis of pyrophosphorothiolate-linked dinucleoside cap analogues in a MBM to effect hydrolytic ...
Figure 4: Early low temperature mechanised ball mill as described by Mudd et al. – adapted from reference [78].
Scheme 16: Co-crystal grinding of alkylated nucleobases in an amalgam mill (N.B. no frequency was recorded in ...
Figure 5: Materials used to prepare a smectic phase.
Figure 6: Structures of 5-fluorouracil (5FU) and nucleoside analogue prodrugs subject to mechanochemical co-c...
Scheme 17: Preparation of DNA-SWNT complex in a MBM.
Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review
- Fabio Tonin and
- Isabel W. C. E. Arends
Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33
- aspects. Conclusion The organic synthesis of CDCA and UDCA starting from taurinated and glycinated cholic acid is a long process, complicated and risky due to the nature and toxicity of the reagents used, the costs of disposal of large amounts of sodium hydroxide, chromium salts and organic solvents, and
Graphical Abstract
Figure 1: Chemical structure of UDCA.
Figure 2: Chemical structures of bile acids and salts.
Figure 3: Comparison between Wolff–Kishner and Mozingo reduction. Notably the overall chemical reaction is th...
Figure 4: Reaction catalysed by the 12α-HSDH; the 12-OH group of CA or UCA is oxidized yielding 12-oxo-CDCA o...
Figure 5: Epimerization reaction catalysed by the 7α-HSDH and 7β-HSDH; the 7α-OH group of CA (R = OH) or CDCA...
Figure 6: Overview of the chemoenzymatic process for the production of UDCA from CA: The oxidation, reduction...
Figure 7: Schematic representation of the flow reactor for the continuous conversion of CDCA to UDCA [93].
Figure 8: Chemoenzymatic pathways for the formation of UDCA from CA that profit by the C7 hydroxylation activ...
Recent developments in the asymmetric Reformatsky-type reaction
- Hélène Pellissier
Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21
- previously reported syntheses by the fact that it included for the first time as key step a totally diastereoselective chromium-mediated macrolactonization. The same year, Schulze et al. reported the synthesis of chiral β-hydroxy-α-methyl-δ-trichloromethyl-δ-valerolactone (39) through a diastereoselective Sm
Graphical Abstract
Scheme 1: Reformatsky-type reaction.
Scheme 2: First total synthesis of prunustatin A based on a Zn-mediated Reformatsky reaction [17].
Scheme 3: Synthesis of a γ-hydroxylysine derivative through a Zn-mediated nitrile Reformatsky-type reaction [18].
Scheme 4: Synthesis of apratoxin E and its C30 epimer through a Zn-mediated Reformatsky reaction. Fmoc = 9-fl...
Scheme 5: Synthesis of the eastern fragment of jatrophane diterpene Pl-3 through a SmI2-mediated Reformatsky ...
Scheme 6: First total synthesis of prebiscibactin through a SmI2-mediated Reformatsky reaction. Boc = tert-bu...
Scheme 7: Synthesis of prostaglandin E2 methyl ester through a SmI2-mediated Reformatsky reaction [23].
Scheme 8: Synthesis of the C1–C11 fragment of tedanolide C through a SnCl2-mediated Reformatsky reaction. PMB...
Scheme 9: Synthesis of β-trifluoromethyl β-(N-tert-butylsulfinyl)amino esters exhibiting a quaternary stereoc...
Scheme 10: Synthesis of α,α-difluoro-β-(N-tert-butylsulfinyl)amino esters through Zn(II)-mediated aza-Reformat...
Scheme 11: Synthesis of a common fragment to anti-apoptotic protein inhibitors through a Zn-mediated aza-Refor...
Scheme 12: Synthesis of α,α-difluoro-β-(N-tert-butylsulfinyl)amino ketones through a Zn-mediated aza-Reformats...
Scheme 13: Synthesis of (2-oxoindolin-3-yl)amino esters through a Zn-mediated aza-Reformatsky reaction [30].
Scheme 14: Synthesis of a precursor of sacubitril through a Zn-mediated aza-Reformatsky reaction [31].
Scheme 15: Synthesis of epothilone D through a Cr(II)-mediated Reformatsky reaction. TFA = trifluoroacetic aci...
Scheme 16: Synthesis of β-hydroxy-α-methyl-δ-trichloromethyl-δ-valerolactone through a Sm(II)- or Yb(II)-media...
Scheme 17: Synthesis of cebulactam A1 through a Sm(II)-mediated Reformatsky reaction. MOM = methoxymethyl [34].
Scheme 18: Synthesis of ansamacrolactams (+)-Q-1047H-A-A and (+)-Q-1047H-R-A through a Sm(II)-mediated Reforma...
Scheme 19: Reformatsky reaction of aldehydes with ethyl iodoacetate in the presence of a chiral 1,2-amino alco...
Scheme 20: Reformatsky reaction of aldehydes with ethyl bromoacetate in the presence of a chiral amide ligand [44]....
Scheme 21: Reformatsky reaction of cinnamaldehyde with ethyl bromozinc-α,α-difluoroacetate in the presence of ...
Scheme 22: Reformatsky reaction of aldehydes with an enolate equivalent prepared from phenyl isocyanate and CH2...
Scheme 23: Domino aza-Reformatsky/cyclization reactions of imines with ethyl dibromofluoroacetate in the prese...
Scheme 24: Domino aza-Reformatsky/cyclization reactions of imines with ethyl bromodifluoroacetate in the prese...
Scheme 25: Aza-Reformatsky reactions of cyclic imines with ethyl iodoacetate in the presence of a chiral diary...
Scheme 26: Mechanism for aza-Reformatsky reaction of cyclic imines with ethyl iodoacetate in the presence of a...
Scheme 27: Aza-Reformatsky reaction of dibenzo[b,f][1,4]oxazepines and dibenzo[b,f][1,4]thiazepine with ethyl ...
Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres
- Myriam Drouin and
- Jean-François Paquin
Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262
- bond isostere [6]. Using this strategy, a mutant tripeptide containing two different peptide bond isosteres could be synthesized (Figure 3). In 2016, Konno and co-workers developed a stereoselective chromium-mediated C–F bond cleavage followed by a C–C bond formation to access (Z)-monofluoroalkenes
- with excellent selectivity (Scheme 4) [28]. The chromium-mediated coupling of 1-bromo-4-(tert-butyldiphenylsiloxy)-1,1-difluorobutane (15) with aldehyde 16 led to the formation of monofluoroalkene 17. This was then reacted with sodium azide and a further Staudinger reduction gave 18. Boc protection of
- co-workers. Synthesis of Phth-Gly-ψ[CF=CH]-Gly using the Julia–Kocienski olefination by Lequeux and co-workers. Synthesis of Boc-Nva-ψ[(Z)-CF=CH]-Gly by Taguchi and co-workers. Chromium-mediated synthesis of Boc-Ser(PMB)-ψ[(Z)-CF=CH]-Gly-OMe by Konno and co-workers. Synthesis of Cbz-Gly-ψ[(E)-CF=C
Graphical Abstract
Figure 1: Selected amide bond isosteres.
Figure 2: Monofluoroalkene as an amide bond isostere.
Scheme 1: Synthesis of Cbz-Gly-ψ[(Z)-CF=CH]-Gly using a HWE olefination by Sano and co-workers.
Scheme 2: Synthesis of Phth-Gly-ψ[CF=CH]-Gly using the Julia–Kocienski olefination by Lequeux and co-workers.
Scheme 3: Synthesis of Boc-Nva-ψ[(Z)-CF=CH]-Gly by Taguchi and co-workers.
Figure 3: Mutant tripeptide containing two different peptide bond isosteres.
Scheme 4: Chromium-mediated synthesis of Boc-Ser(PMB)-ψ[(Z)-CF=CH]-Gly-OMe by Konno and co-workers.
Scheme 5: Synthesis of Cbz-Gly-ψ[(E)-CF=C]-Pro by Sano and co-workers.
Scheme 6: Synthesis of Cbz-Gly-ψ[(Z)-CF=C]-Pro by Sano and co-workers.
Scheme 7: Stereoselective synthesis of Fmoc-Gly-ψ[(Z)-CF=CH]-Phe by Pannecoucke and co-workers.
Scheme 8: Ring-closure metathesis to prepare Gly-ψ[(E)-CF=CH]-Phg by Couve-Bonnaire and co-workers.
Scheme 9: Stereoselective synthesis of Fmoc-Gly-ψ[(Z)-CF=CH]-Phe by Dory and co-workers.
Scheme 10: Diastereoselective addition of Grignard reagents to sulfinylamines derived from α-fluoroenals by Pa...
Scheme 11: NHC-mediated synthesis of monofluoroalkenes by Otaka and co-workers.
Scheme 12: Stereoselective synthesis of Boc-Tyr-ψ[(Z)-CF=CH]-Gly by Altman and co-workers.
Scheme 13: Synthesis of the tripeptide Boc-Asp(OBn)-Pro-ψ[(Z)-CF=CH)-Val-CH2OH by Miller and co-workers.
Scheme 14: Copper-catalyzed synthesis of monofluoralkenes by Taguchi and co-workers.
Scheme 15: One-pot intramolecular redox reaction to access amide-type isosteres by Otaka and co-workers.
Scheme 16: Copper-mediated reduction, transmetalation and asymmetric alkylation by Fujii and co-workers.
Scheme 17: Synthesis of (E)-monofluoroalkene-based dipeptide isostere by Fujii and co-workers.
Scheme 18: Diastereoselective synthesis of MeOCO-Val-ψ[(Z)-CF=C]-Pro isostere by Chang and co-workers.
Scheme 19: Asymmetric synthesis of Fmoc-Ala-ψ[(Z)-CF=C]-Pro by Pannecoucke and co-workers.
Scheme 20: Synthesis of Fmoc-Val-ψ[(E)-CF=C]-Pro by Pannecoucke and co-workers.
Figure 4: BMS-790052 and its fluorinated analogue.
Figure 5: Bioactivities of pentapeptide analogues based on the relative maximum agonistic activity at 10 nM o...
Figure 6: Structures and affinities of the Leu-enkephalin and its fluorinated analogue. The affinity towards ...
Figure 7: Activation of the opioid receptor DOPr by Leu-enkephaline and a fluorinated analogue.
