Search results
Search for "hydrogen peroxide" in Full Text gives 119 result(s) in Beilstein Journal of Organic Chemistry.
Methodology for awakening the potential secondary metabolic capacity in actinomycetes
- Shun Saito and
- Midori A. Arai
Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69
- ), which upon sensing ROS, release their repression and activate the expression of various genes [93][94][95]. Wei et al. reported that the production of validamycin A (25) by Streptomyces hygroscopicus 5008 could be activated at the transcriptional level by simply adding hydrogen peroxide (H2O2; which
Graphical Abstract
Figure 1: Schematic diagram of methods to activate silent genes in actinomycetes as presented in this review....
Figure 2: Structures of secondary metabolites obtained from actinomycetes using artificial methods.
Figure 3: Structures of secondary metabolites obtained from actinomycetes by adjusting culture conditions.
Figure 4: Structures of secondary metabolites obtained by high-temperature culture of actinomycetes.
Figure 5: Structures of secondary metabolites obtained by co-culture of actinomycetes with other microorganis...
Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target
- Milandip Karak,
- Cian R. Cloonan,
- Brad R. Baker,
- Rachel V. K. Cochrane and
- Stephen A. Cochrane
Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22
- -phosphite intermediate was then oxidized with hydrogen peroxide to yield dibenzyl α-phosphate 6, achieving an overall yield of 89% for these two steps. Removal of the 2-(phenylsulfonyl)ethanol protecting group in compound 6 was successfully achieved through treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene
Graphical Abstract
Figure 1: Structure of lipid II, with variable positions shown in red and antimicrobial-binding motifs highli...
Figure 2: List of i) glycosyl donors and ii) glycosyl acceptors used in this study.
Scheme 1: Synthesis of disaccharide pentapeptide core 7.
Scheme 2: Synthesis of lipid II (11) and its analogues 8–10.
Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions
- Karolis Leitonas,
- Brigita Vigante,
- Dmytro Volyniuk,
- Audrius Bucinskas,
- Pavels Dimitrijevs,
- Sindija Lapcinska,
- Pavel Arsenyan and
- Juozas Vidas Grazulevicius
Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139
- the photocatalytic production of H2 while the nanospheres produced hydrogen peroxide (H2O2). The introduction of the additional carbazolylphenyl moiety in the CPC molecule [4] allowed us to improve the EQEmax of an OLED to 25% [7]. In continuation of our studies in the field of the development of new
Graphical Abstract
Figure 1: Chemical structures of pyridine-3,5-dicarbonitrile-based TADF emitters.
Scheme 1: Synthesis of dicyanocarbazole 6. Reaction conditions: a) cyanoacetamide, piperidine, methanol, 40 °...
Scheme 2: Synthesis of dicyanocarbazoles 7–9. Reaction conditions: a) corresponding ethynyl arene, Pd(Ph3P)4 ...
Figure 2: Absorption (a, b) and PL (c, d) spectra of dilute toluene, THF, and chloroform solutions (10−5 M) a...
Figure 3: PL spectra (a) and PL decay curves (b) of air-equilibrated (as prepared) and deoxygenated toluene s...
Figure 4: Non-normalized (a) and normalized (b) PL spectra and PL decay curves (c) of the film of a 10 wt % m...
Figure 5: TGA (a) and DSC 2nd heating (b) curves of compounds 6–9.
Figure 6: CV curves of compounds 6–9.
Figure 7: Photoelectron emission spectra of the vacuum-deposited films of compounds 6–9 on glass substrates c...
Figure 8: The current transients (a) for electrons recorded at the different voltages for the vacuum-deposite...
Radical chemistry in polymer science: an overview and recent advances
- Zixiao Wang,
- Feichen Cui,
- Yang Sui and
- Jiajun Yan
Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116
- , such as organic peroxides, hydrogen peroxide, persulfates undergo homolysis of O–O bonds generating radicals that can break C–H bonds followed by a hydrogen abstraction reaction. Phenolic compounds can be oxidized by molecular oxygen in the presence of laccase, and the resulting phenolic radical reacts
Graphical Abstract
Scheme 1: Oxidation of catechol and subsequent cross-linking. Scheme 1 redrawn from [3].
Scheme 2: (A) Structure of typical urushiol in Chinese lacquer, and (B) schematic process of laccase-catalyze...
Scheme 3: A) Primary amino acid sequence of mfp-1, mfp-3, and mfp-5 (Y: DOPA, K: lysine). B) Scheme showing e...
Scheme 4: Activation–deactivation equilibrium in nitroxide-mediated polymerizations. Bicomponent initiating s...
Scheme 5: Mechanism of a transition metal complex-mediated ATRP. Scheme 5 redrawn from [14].
Scheme 6: Mechanism of RAFT polymerization. Scheme 6 redrawn from [68].
Scheme 7: Degenerative transfer (a) and reversible termination (b) mechanism of OMRP. Scheme 7 redrawn from [70].
Scheme 8: Simplified mechanism of a RITP. Scheme 8 redrawn from [21].
Scheme 9: (A) Structures of π-conjugated conductive polymers. (B) Examples of conductive polymer synthesis vi...
Scheme 10: Possible regiochemical couplings in PATs. Scheme 10 redrawn from [79].
Scheme 11: General thiol-ene photopolymerization process. Scheme 11 redrawn from [81].
Scheme 12: (a) Three generations of Grubbs catalysts. (b) Proposed mechanism for photo-ROMP via a reductive qu...
Scheme 13: Pyrylium and thiopyrylium salts studied by Boydston et al. Scheme 13 redrawn from [91].
Scheme 14: A general illustration of post-polymerization modification by thiol–ene chemistry.
Scheme 15: Introduction of functionalities by nitroxide radical coupling of HO-TEMPO derivatives.
Scheme 16: Chemical reaction process scheme of DCP-induced crosslinking of LDPE. Scheme 16 redrawn from [126].
Scheme 17: A probable mechanism of radical-induced hydrosilylation.
Scheme 18: Polymer surface modification by homolytic dediazonation of diazonium salts.
Scheme 19: Photoinduced polymer surface modification or surface grafting using benzophenone.
Scheme 20: Depolymerization mechanism of common photoresists. (a) A possible mechanism of radiation decomposit...
Scheme 21: Proposed mechanisms of photooxidative depolymerization of polystyrene. (a) Scheme 21a was reprinted with perm...
Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration
- Ghenwa Nasr,
- Hélène Greige-Gerges,
- Sophie Fourmentin,
- Abdelhamid Elaissari and
- Nathalie Khreich
Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115
- . Triton X-100, sodium chloride (NaCl), and Sephadex G25 gel were purchased from Sigma-Aldrich, Belgium. Ammonium molybdate, hydrogen peroxide, potassium dihydrogen phosphate, sodium sulfite, sodium bisulfite, chloroform, and methanol were purchased from Sigma-Aldrich, Germany. Cholesterol and
Graphical Abstract
Figure 1: The chemical structure of the native CDs, their three-dimensional structure, and their dimensions (n...
Figure 2: Structures of β-CD derivatives and their degrees of substitution (DS).
Figure 3: The instantaneous effect of CDs on the various liposome membranes at different CD/DPPC molar ratios...
Figure 4: The permeabilizing effect of CDs on the various liposome membranes at different CD/DPPC molar ratio...
Figure 5: The permeabilizing effect of CDs on the various liposome membranes at different CD/DPPC molar ratio...
Synthesis of ether lipids: natural compounds and analogues
- Marco Antônio G. B. Gomes,
- Alicia Bauduin,
- Chloé Le Roux,
- Romain Fouinneteau,
- Wilfried Berthe,
- Mathieu Berchel,
- Hélène Couthon and
- Paul-Alain Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
Graphical Abstract
Figure 1: Chemical structure of some natural ether lipids (ELs).
Figure 2: Synthesis of lyso-PAF and PAF from 1-O-alkylglycerol [64].
Figure 3: Synthesis of lyso-PAF from 1,3-benzylideneglycerol 3.1 [69].
Figure 4: A) Synthesis of the two enantiomers of octadecylglycerol (4.6 and 4.10) from ᴅ-mannitol (4.1); B) s...
Figure 5: Four-step synthesis of PAF 5.6 from (S)-glycidol [73].
Figure 6: Synthesis of 1-O-alkylglycerol A) from solketal, B) from ᴅ- or ʟ-tartaric acid and the intermediate ...
Figure 7: Synthesis of EL building blocks starting from substituted glycidol 7.1a–c [82].
Figure 8: Synthesis of PAF 8.5 by using phosphoramidite 8.2 [86].
Figure 9: Synthesis of oleyl-PAF 9.7 from ʟ-serine [88].
Figure 10: Synthesis of racemic analogues of lyso-PAF 10.8 and PAF 10.9 featuring a phenyl group between the g...
Figure 11: Synthesis of racemic deoxy-lyso-PAF 11.7 and deoxy-PAF 11.8 [91].
Figure 12: Synthesis of racemic thio-PAF 12.8 [93].
Figure 13: Racemic synthesis of 13.6 to illustrate the modification of the glycerol backbone by adding a methy...
Figure 14: Racemic synthesis of 14.5 as an illustration of the introduction of methyl substituents on the glyc...
Figure 15: Synthesis of functionalized sn-2-acyl chains of PC-EL; A) Steglich esterification or acylation reac...
Figure 16: Synthesis of racemic mc-PAF (16.3), a carbamate analogue of PAF [102].
Figure 17: A) Synthesis of (R)-17.2 and (S)-17.6 starting from (S)-solketal (17.1); B) synthesis of N3-PAF (17...
Figure 18: Modification of the phosphocholine polar head to produce PAF analogues [81].
Figure 19: Racemic PAF analogues 19.3 and 19.5 characterized by the absence of the phosphate group [107].
Figure 20: Synthesis of PIP3-PAF (20.7) [108].
Figure 21: Large-scale synthesis of C18-edelfosine (21.8) [116].
Figure 22: Synthesis of C16-edelfosine (22.10) starting from isopropylidene-ʟ-glyceric acid methyl ester (22.1...
Figure 23: Phosphocholine moiety installation by the use of chlorophosphite 23.2 as key reagent [119].
Figure 24: Synthesis of rac-1-alkyl-2-O-methylglycerol (AMG) [120].
Figure 25: Synthesis of stereocontrolled 1-alkyl-2-O-methyl glycerol 25.9 (AMG) from dimethyl ᴅ-tartrate [81].
Figure 26: A) Racemic synthesis of thioether 26.4 [129,130], B) structure of sulfone analogue 26.5 [129].
Figure 27: Stereocontrolled synthesis of C18-edelfosine thioether analogue 27.8 [118].
Figure 28: Synthesis of thioether 28.4 that include a thiophosphate function [134].
Figure 29: Synthesis of ammonium thioether 29.4 and 29.6 [135].
Figure 30: Synthesis of the N-methylamino analogue of edelfosine 30.6 (BN52211) [138].
Figure 31: Synthesis of 1-desoxy analogues of edelfosine; A) with a saturated alkyl chain; B) synthesis of the...
Figure 32: Stereocontrolled synthesis of edelfosine analogue (S)-32.8 featuring a C18:1 lipid chain [142].
Figure 33: Synthesis of edelfosine analogues with modulation of the lipid chain; A) illustration with the synt...
Figure 34: Synthesis of phospholipid featuring a carbamate function to link the lipid chain to the glycerol un...
Figure 35: Synthesis of sesquiterpene conjugates of phospho glycero ether lipids [148].
Figure 36: Racemic synthesis of methyl-substituted glycerol analogues 36.7 and 36.10: A) synthesis of diether ...
Figure 37: Racemic synthesis of ilmofosine (37.6) [155,156].
Figure 38: A) Stereoselective synthesis of 38.5 via a stereoselective hydroboration reaction; B) synthesis of ...
Figure 39: Racemic synthesis of SRI62-834 (39.6) featuring a spiro-tetrahydrofurane heterocycle in position 2 ...
Figure 40: Racemic synthesis of edelfosine analogue 40.5 featuring an imidazole moiety in sn-2 position [160].
Figure 41: Racemic synthesis of fluorine-functionalized EL: A) Synthesis of 41.6 and B) synthesis of 41.8 [161-163].
Figure 42: A) Synthesis of the β-keto-ester 42.6 that also features a decyl linker between the phosphate and t...
Figure 43: Synthesis of phosphonate-based ether lipids; A) edelfosine phosphonate analogue 43.7 and B) thioeth...
Figure 44: Enantioselective synthesis of phosphonates 44.3 and 44.4 [171].
Figure 45: Racemic synthesis of phosphinate-based ether lipid 45.10 [172].
Figure 46: Racemic synthesis of edelfosine arsonium analogue 46.5 [173].
Figure 47: Synthesis of edelfosine dimethylammonium analogue 47.2 [118].
Figure 48: Synthesis of rac-C18-edelfosine methylammonium analogue 48.4 [176].
Figure 49: A) Synthesis of edelfosine N-methylpyrrolidinium analogue 49.2 or N-methylmorpholinium analogue 49.3...
Figure 50: A) Synthesis of edelfosine’s analogue 50.4 with a PE polar group; B) illustration of a pyridinium d...
Figure 51: A) Synthesis of 51.4 featuring a thiazolium cationic moiety; B) synthesis of thiazolium-based EL 51...
Figure 52: Synthesis of cationic ether lipids 52.3, 52.4 and 52.6 [135,183].
Figure 53: Synthesis of cationic carbamate ether lipid 53.5 [184].
Figure 54: Synthesis of cationic sulfonamide 54.5 [185].
Figure 55: Chemical structure of ONO-6240 (55.1) and SRI-63-119 (55.2).
Figure 56: Synthesis of non-ionic ether lipids 56.2–56.9 [188].
Figure 57: Synthesis of ether lipid conjugated to foscarnet 57.6 [189].
Figure 58: A) Synthesis of ether lipid conjugated to arabinofuranosylcytosine; B) synthesis of AZT conjugated ...
Figure 59: Synthesis of quercetin conjugate to edelfosine [191].
Figure 60: Synthesis of 60.8 (Glc-PAF) [194].
Figure 61: A) Synthesis of amino ether lipid 61.7 functionalized with a rhamnose unit and its amide analogue 6...
Figure 62: A) Synthesis of glucose ether lipid 62.4; B) structure of ether lipid 62.5 possessing a maltose uni...
Figure 63: A) Synthesis of glucuronic methyl ester 63.8; B) structure of cellobiose 63.9 and maltose 63.10 ana...
Figure 64: A) Synthesis of maltosyl glycerolipid 64.7; B) structure of lactose analogue 64.8 prepared followin...
Figure 65: A) Asymmetric synthesis of the aglycone moiety starting from allyl 4-methoxyphenyl ether; B) glycos...
Figure 66: A) Synthesis of ohmline possessing a lactose moiety. B) Structure of other glyco glycero lipids pre...
Figure 67: A) Synthesis of lactose-glycerol ether lipid 67.5; B) analogues possessing a maltose (67.6) or meli...
Figure 68: Synthesis of digalactosyl EL 68.6, A) by using trityl, benzyl and acetyl protecting groups, B) by u...
Figure 69: A) Synthesis of α-ohmline; B) structure of disaccharide ether lipids prepared by using similar meth...
Figure 70: Synthesis of lactose ether lipid 70.3 and its analogue 70.6 featuring a carbamate function as linke...
Figure 71: Synthesis of rhamnopyranoside diether 71.4 [196].
Figure 72: Synthesis of 1-O-hexadecyl-2-O-methyl-3-S-(α-ᴅ-1'-thioglucopyranosyl)-sn-glycerol (72.5) [225].
Figure 73: A) Preparation of lipid intermediate 73.4; B) synthesis of 2-desoxy-C-glycoside 73.10 [226].
Figure 74: Synthesis of galactose-pyridinium salt 74.3 [228].
Figure 75: Synthesis of myo-inositol derivative Ino-C2-PAF (75.10) [230].
Figure 76: A) Synthesis of myo-inositol phosphate building block 76.7; B) synthesis of myo-inositolphosphate d...
Figure 77: A) Synthesis of phosphatidyl-3-desoxy-inositol 77.4; B) synthesis of phosphono-3-desoxyinositol 77.9...
Figure 78: A) Structure of diether phosphatidyl-myo-inositol-3,4-diphosphate 78.1; B) synthesis of phosphatidy...
Figure 79: A) Synthesis of diether-phosphatidyl derivative 79.4 featuring a hydroxymethyl group in place of a ...
Figure 80: Synthesis of Glc-amine-PAF [78].
Figure 81: Synthesis of glucosamine ether lipid 81.4 and its analogues functionalized in position 3 of the ami...
Figure 82: Synthesis of fully deprotected aminoglucoside ether lipid 82.5 [246].
Figure 83: Synthesis of C-aminoglycoside 83.12 using Ramberg–Bäcklund rearrangement as a key step [250].
Figure 84: A) List of the most important glyco lipids and amino glyco lipids included in the study of Arthur a...
Figure 85: Synthesis of mannosamine ether lipid 85.6 [254].
Figure 86: A) Synthesis of glucosamine ether lipids with a non-natural ʟ-glucosamine moiety; B) synthesis of e...
Figure 87: A) Structure of the most efficient anticancer agents 87.1–87.4 featuring a diamino glyco ether lipi...
Figure 88: A) Synthesis of diamino glyco ether lipid 87.4; B) synthesis of bis-glycosylated ether lipid 88.10 [256]....
Figure 89: Synthesis of triamino ether lipid 89.4 [260].
Figure 90: Synthesis of chlorambucil conjugate 90.7 [261].
Figure 91: Three main methods for the preparation of glycerol ether lipid 91.3; A) from solketal and via a tri...
Figure 92: Four different methods for the installation of the phosphocholine polar head group; A) method using...
Figure 93: Illustration of two methods for the installation of saccharides or aminosaccharides; A) O-glycosyla...
Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light
- Damiano Diprima,
- Hannes Gemoets,
- Stefano Bonciolini and
- Koen Van Aken
Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82
- selectivity and safety. Traditional oxidants, such as Oxone, CrO3, NaIO4, or KMnO4, produce significant amounts of toxic waste, exacerbating these issues (Scheme 1A) [1]. As environmental concerns and economic factors increasingly affect chemical processes, hydrogen peroxide and oxygen (or air) are becoming
- more popular as oxidants due to their low cost and minimal side products. However, these reagents have practical limitations. Hydrogen peroxide is typically produced off-site and requires transportation and storage, and is commonly obtained through the non-sustainable anthraquinone process (Scheme 1B
- ) [2][3][4]. Additionally, practical implementation of hydrogen peroxide can be challenging due to requirements for precise dosing to avoid issues such as dismutation, overoxidation, and catalyst degradation [5]. In this respect, oxygen, or preferably air, represents a better alternative to traditional
Graphical Abstract
Scheme 1: Oxidation of heteroatoms.
Scheme 2: Graphical representation comparing A electrochemistry and B photoredox catalysis using a semiconduc...
Figure 1: Study of additives. A) Effect of the addition of 1 equiv of various acids and bases to the standard...
Scheme 3: Substrate scope with reaction times and isolated yields. 1 mmol (1 equiv) substrate was reacted in ...
Scheme 4: Setup used in the flow experiment for the triphenylphosphine oxidation.
Scheme 5: Proposed extra alternative pathway.
An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides
- Shubham Sharma,
- Dharmender Singh,
- Sunit Kumar,
- Vaishali,
- Rahul Jamra,
- Naveen Banyal,
- Deepika,
- Chandi C. Malakar and
- Virender Singh
Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22
- , metal-free and easy to perform reaction conditions. Moreover, the pyrazole C-3/5-linked amide conjugates were also synthesized via an oxidative amination of pyrazole carbaldehydes and 2-aminopyridines using hydrogen peroxide as an oxidant. Keywords: C–S/O bond formation; metal-free; oxidative amidation
- (entry 16, Table 2). From the above screening experiments, it was concluded that 10.0 equiv of hydrogen peroxide in THF at 70 °C proved to be the optimal conditions for the construction of the pyrazole-pyridine conjugate with an amide linkage (entry 16, Table 2). Having the optimized conditions in hand
- available substituted 2-aminopyridines and hydrogen peroxide as an oxidant. The biological evaluation of the thioamide and amide conjugates is underway in our laboratory. Experimental General information All chemicals and reagents were purchased from Sigma-Aldrich, Acros, Avera Synthesis, Spectrochem Pvt
Graphical Abstract
Figure 1: Representative drug molecules based on pyrazole, thioamide, and amide derivatives.
Figure 2: Previous and present findings for the synthesis of thioamide derivatives.
Scheme 1: Synthesis of pyrazole C-3-tethered thioamides.
Scheme 2: Synthesis of pyrazole C-4-tethered thioamides.
Scheme 3: Metal- and catalyst-free preparation of pyrazole C-5-linked thioamide conjugates.
Scheme 4: Synthesis of 4-iodopyrazole C-3-tethered thioamides.
Scheme 5: Gram-scale scope of the current protocol.
Scheme 6: Control experiment.
Scheme 7: H2O2-mediated synthesis of pyrazole-pyridine conjugates with amide tethers.
Scheme 8: Synthesis of pyrazole-pyridine conjugates 9F and 10F having amide tethers.
Scheme 9: A tentative mechanism for the formation of pyrazole conjugates with thioamide and amide linkage.
Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field
- Elena R. Lopat’eva,
- Igor B. Krylov,
- Dmitry A. Lapshin and
- Alexander O. Terent’ev
Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179
- , the acidic and basic sites of the catalyst are suggested to be involved in the activation of only hydrogen peroxide within a well-defined and deep chiral cavity. The enantioselective approach of sulfide to H2O2 is ensured by the sterically demanding structure of the catalyst. It should also be noted
Graphical Abstract
Scheme 1: Organocatalysis classification used in the present perspective.
Scheme 2: Oxidative processes catalyzed by amines.
Scheme 3: N-Heterocyclic carbene (NHC) catalysis in oxidative functionalization of aldehydes.
Scheme 4: Examples of asymmetric oxidative processes catalyzed by chiral Brønsted acids.
Scheme 5: Asymmetric aerobic α-hydroxylation of lactams under phase-transfer organocatalysis conditions emplo...
Scheme 6: Selective CH-oxidation of methylarenes to aldehydes or carboxylic acids.
Scheme 7: An example of the regioselective CH-amination by a sterically hindered imide-N-oxyl radical precurs...
Scheme 8: CH-amination of ethylbenzene and CH-fluorination of aldehydes catalyzed by N-hydroxybenzimidazoles,...
Scheme 9: Mixed hetero-/homogeneous TiO2/N-hydroxyimide photocatalysis in the selective benzylic oxidation.
Scheme 10: Electrochemical benzylic iodination and benzylation of pyridine by benzyl iodides generated in situ...
Scheme 11: Electrochemical oxidative C–O/C–N coupling of alkylarenes with NHPI. Electrolysis conditions: Const...
Scheme 12: Chemoselective alcohol oxidation catalyzed by TEMPO.
Scheme 13: ABNO-catalyzed oxidative C–N coupling of primary alcohols with primary amines.
Scheme 14: ACT-catalyzed electrochemical oxidation of primary alcohols and aldehydes to carboxylic acids.
Scheme 15: Electrocatalytic oxidation of benzylic alcohols by a TEMPO derivative immobilized on a graphite ano...
Scheme 16: Electrochemical oxidation of carbamates of cyclic amines to lactams and oxidative cyanation of amin...
Scheme 17: Hydrogen atom transfer (HAT) and single-electron transfer (SET) as basic principles of amine cation...
Scheme 18: Electrochemical quinuclidine-catalyzed oxidation involving unactivated C–H bonds.
Scheme 19: DABCO-mediated photocatalytic C–C cross-coupling involving aldehyde C–H bond cleavage.
Scheme 20: DABCO-derived cationic catalysts in inactivated C–H bond cleavage for alkyl radical addition to ele...
Scheme 21: Electrochemical diamination and dioxygenation of vinylarenes catalyzed by triarylamines.
Scheme 22: Electrochemical benzylic oxidation mediated by triarylimidazoles.
Scheme 23: Thiyl radical-catalyzed CH-arylation of allylic substrates by aryl cyanides.
Scheme 24: Synthesis of redox-active alkyl tetrafluoropyridinyl sulfides by unactivated C–H bond cleavage by t...
Scheme 25: Main intermediates in quinone oxidative organocatalysis.
Scheme 26: Electrochemical DDQ-catalyzed intramolecular dehydrogenative aryl–aryl coupling.
Scheme 27: DDQ-mediated cross-dehydrogenative C–N coupling of benzylic substrates with azoles.
Scheme 28: Biomimetic o-quinone-catalyzed benzylic alcohol oxidation.
Scheme 29: Electrochemical synthesis of secondary amines by oxidative coupling of primary amines and benzylic ...
Scheme 30: General scheme of dioxirane and oxaziridine oxidative organocatalysis.
Scheme 31: Dioxirane organocatalyzed CH-hydroxylation involving aliphatic C(sp3)–H bonds.
Scheme 32: Enantioselective hydroxylation of CH-acids catalyzed by chiral oxaziridines.
Scheme 33: Iodoarene-organocatalyzed vinylarene diamination.
Scheme 34: Iodoarene-organocatalyzed asymmetric CH-hydroxylation of benzylic substrates.
Scheme 35: Iodoarene-organocatalyzed asymmetric difluorination of alkenes with migration of aryl or methyl gro...
Scheme 36: Examples of 1,2-diiodo-4,5-dimethoxybenzene-catalyzed electrochemical oxidative heterocyclizations.
Scheme 37: Electrochemical N-ammonium ylide-catalyzed CH-oxidation.
Scheme 38: Oxidative dimerization of aryl- and alkenylmagnesium compounds catalyzed by quinonediimines.
Scheme 39: FLP-catalyzed dehydrogenation of N-substituted indolines.
Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts
- Karen R. Winters and
- Jean-Luc Montchamp
Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154
- synthesized from 2-aminobiphenyl according to the literature [47]. Subsequent reaction with phosphorus trichloride and electrophilic aromatic substitution gave a chlorophosphine intermediate, which was directly reacted with (S)-1-phenylethylamine, then hydrogen peroxide. Phosphonamide diastereoisomers 17 were
Graphical Abstract
Figure 1: Chiral phosphorus acids (CPAs) derived from BINOL, VAPOL, and SPINOL. R = H, Ph, 4-PhC6H4-, 4-β-nap...
Scheme 1: The thiolic/thionic tautomeric equilibrium in thiophosphorus acids.
Figure 2: Project strategy and requirements for C1-symmetrical CPAs.
Figure 3: BINOL CPA and C1-symmetrical CPA targets 1–4.
Scheme 2: Synthesis of tryptophol-derived thiophosphorus acid 1.
Scheme 3: Synthesis of indole-derived thiophosphorus acid 2.
Scheme 4: Synthesis of N-biphenyl-DOPO CPA 4.
Scheme 5: Transfer hydrogenation of 2-phenylquinoline and transition-state proposed by Guinchard and coworker...
Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides
- Jiaxi Xu
Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90
- derivatives 83 followed by an intramolecular cyclization via the intramolecular Arbuzov reaction under heating generated 1,2-azaphospholidine 2-oxides 89. Compounds 89 were further transformed into N-phosphoryl- and N-thiophosphoryl-1,2-azaphospholidine 2-oxides 90/2-sulfides 91 via oxidation with hydrogen
- peroxide and sulfurization with sulfur, respectively (Scheme 16) [37][38]. Synthesis via formation of the C–C bond neighboring at the ring phosphorus atom In 1984, Collins and co-workers attempted the synthesis of benzo-γ-phosphonolactams 56a and 93 from (chloromethyl)(phenyl)-N-methyl-N
Graphical Abstract
Figure 1: Biologically active 1,2-azaphospholine 2-oxide derivatives.
Figure 2: Diverse synthetic strategies for the preparation of 1,2-azaphospholidine and 1,2-azaphospholine 2-o...
Scheme 1: Synthesis of 1-phenyl-2-phenylamino-γ-phosphonolactam (2) from N,N’-diphenyl 3-chloropropylphosphon...
Scheme 2: Synthesis of 2-ethoxy-1-methyl-γ-phosphonolactam (6) from ethyl N-methyl-(3-bromopropyl)phosphonami...
Scheme 3: Synthesis of 2-aryl-1-methyl-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 13 from N-aryl-2-chlorom...
Scheme 4: Synthesis of 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides from alkylarylphosphinyl or diarylphosph...
Scheme 5: Synthesis of 3-arylmethylidene-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides via the TBAF-mediated ...
Scheme 6: Synthesis of 2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxides via the metal-free intramolecular oxida...
Scheme 7: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 42 and 44 from ethyl/benzyl 2-bromobenzy...
Scheme 8: Synthesis of azaphospholidine 2-oxides/sulfide from 1,2-oxaphospholane 2-oxides/sulfides and 1,2-th...
Scheme 9: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides/sulfides from 2-aminobenzyl(phenyl)phosp...
Scheme 10: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfide (59) from zwitterionic 2-aminobenzyl(ph...
Scheme 11: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides from 2-aminobenzyl(methyl/phenyl)phosphi...
Scheme 12: Synthesis of ethyl 2-methyl-1,2-azaphospholidine-5-carboxylate 2-oxide 69 from 2-amino-4-(hydroxy(m...
Scheme 13: Synthesis of 2-methoxy-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxide 71 from dimethyl 2-(methylamino...
Scheme 14: Synthesis of tricyclic γ-phosphonolactams via formation of the P–C bond.
Scheme 15: Synthesis of γ-phosphonolactams 85 from ethyl 2-(3-chloropropyl)aminoalkanoates with diethyl chloro...
Scheme 16: Synthesis of N-phosphoryl- and N-thiophosphoryl-1,2-azaphospholidine 2-oxides 90/2-sulfides 91 from...
Scheme 17: Synthesis of 1-methyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 56a and 93 from P-(chloromethyl...
Scheme 18: Synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N’-diallyl-vinylphosphonodia...
Scheme 19: Diastereoselective synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N’-dially...
Scheme 20: Synthesis of 1-alkyl-3-benzoyl-2-ethoxy-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 106 from ethy...
Scheme 21: Synthesis of cyclohexadiene-fused γ-phosphinolactams from diphenyl-N-benzyl-N-methylphosphinamide (...
Scheme 22: Synthesis of cyclohexadiene-fused γ-phosphinolactams from diphenyl-N-alkyl-N-benzylphosphinamides.
Scheme 23: Synthesis of cyclohexadiene-fused γ-phosphinolactams from diphenyl-N-methyl-N-(1-phenylethyl)phosph...
Scheme 24: Synthesis of benzocyclohexadiene-fused γ-phosphinolactams from dinaphth-1-yl-N-alkyl-N-benzylphosph...
Scheme 25: Synthesis of benzocyclohexadiene-fused γ-phosphinolactams from dinaphth-1-yl-N-benzyl-N-methylphosp...
Scheme 26: Synthesis of carbonyl-containing benzocyclohexadiene-fused γ-phosphinolactams from dinaphth-1-yl-N-...
Scheme 27: Synthesis of benzocyclohexadiene-fused γ-phosphinolactams from dinaphthyl-N-benzyl-N-methylphosphin...
Scheme 28: Synthesis of cyclohexadiene-fused 1-(N-benzyl-N-methyl)amino-γ-phosphinolactams from aryl-N,N’-dibe...
Scheme 29: Synthesis of bis(cyclohexadiene-fused γ-phosphinolactam)s from bis(diphenyl-N-benzylphosphinamide)s....
Scheme 30: Synthesis of bis(hydroxymethyl-derived cyclohexadiene-fused γ-phosphinolactam)s from tetramethylene...
Scheme 31: Synthesis of 2-aryl/dimethylamino-1-ethoxy-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxides from ethy...
Scheme 32: Synthesis of ethyl 2-ethoxy-1,2-azaphospholidine-4-carboxylate 2-oxides from ethyl 2-((chloro(ethox...
Scheme 33: Synthesis of (1S,3R)-2-(tert-butyldiphenylsilyl)-3-methyl-1-phenyl-2,3-dihydrobenzo[c][1,2]azaphosp...
Scheme 34: Synthesis of 2,3,3a,9a-tetrahydro-4H-1,2-azaphospholo[5,4-b]chromen-4-one (215) from 3-(phenylamino...
Scheme 35: Synthesis of quinoline-fused 1,2-azaphospholine 2-oxides from 2-azidoquinoline-3-carbaldehydes and ...
Scheme 36: Synthesis of 1-hydro-1,2-azaphosphol-5-one 2-oxide from cyanoacetohydrazide with phosphonic acid an...
Scheme 37: Synthesis of chromene-fused 5-oxo-1,2-azaphospolidine 2-oxides.
Scheme 38: Synthesis of (R)-1-phenyl-2-((R)-1-phenylethyl)-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxide (239)...
Scheme 39: Synthesis of dihydro[1,2]azaphosphole 1-oxides from aryl/vinyl-N-phenylphosphonamidates and aryl-N-...
Scheme 40: Synthesis of 1,3-dihydro-[1,2]azaphospholo[5,4-b]pyridine 2-oxides.
Synthesis of odorants in flow and their applications in perfumery
- Merlin Kleoff,
- Paul Kiler and
- Philipp Heretsch
Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76
- flowers of orchids among with the structurally related and better known Ambrettolide [(Z)-7-hexadecen-16-olide], having a sweet odor with “great tenacity and fixative power” [9][48]. Notably, and already in 1970, Story and co-workers described that cyclic ketones can be reacted with hydrogen peroxide
- safe two-step synthesis of 56 from cyclohexanone. In the first step, a solution of cyclohexanone in dodecane is mixed in a Q-piece with hydrogen peroxide, nitric acid, and formic acid and subsequently pumped at room temperature through a PTFE tube reactor with a residence time of 93 min. The resulting
Graphical Abstract
Figure 1: The olfactory spectrum wheel ordering different types of odorants from fruity to musky.
Figure 2: Classification of odorants as “top note”, “middle note” and “base note” depending on their substant...
Scheme 1: Synthesis of raspberry ketone (5) and raspberry ketone methyl ether (6) in two steps in flow.
Scheme 2: Autoxidation of (+)-valencene (7) to (+)-nootkatone (8) under catalyst and solvent-free conditions ...
Scheme 3: Enzyme-catalyzed acetylation of isoamyl alcohol (9) in a biphasic n-heptane/water mixture utilizing...
Scheme 4: Esterification of alcohols by transesterification, catalyzed by immobilized acyltransferase in a pa...
Scheme 5: Synthesis of homologated alcohols 20 by iterative homologation of terpenyl boronate esters 17 follo...
Scheme 6: Sequential three-step synthesis of (S)-α-phellandrene (30) from (R)-carvone (25) via selective hydr...
Scheme 7: Selective hydrogenation of alkyne 31 to “leaf alcohol” 32 employing a solid-supported palladium cat...
Scheme 8: A) Synthesis of jasmonal (35) by crossed aldol condensation of benzaldehyde (33) and heptanal (34) ...
Scheme 9: Synthesis of thymol (41) from m-cresol (39) and isopropyl alcohol via Fries-type rearrangement of e...
Scheme 10: Preparation of coumarin (46) by reaction of salicylaldehyde (44) with potassium acetate, acetic aci...
Scheme 11: Synthesis of phthalide (50) by photoinduced decatungstate catalysis.
Scheme 12: Synthesis of woody acetate (54) by reduction of cyclohexanone 51 and subsequent acetylation; ADH200...
Scheme 13: Synthesis of juniper lactone (56) by pyrolysis of triperoxide 55 generated by oxidation of cyclohex...
Scheme 14: Synthesis of macrocyclic olefine 60 by ring-closing metathesis of diene 58 in a continuously stirre...
Scheme 15: Synthesis of macrocycles 65 and 66 by ring-closing metathesis of dienes 62 or 63, respectively, in ...
Scheme 16: Z-Selective synthesis of civetone (69) enabled by metathesis catalyst 68 in a tube-in-tube reactor.
Scheme 17: Synthesis of macrocyclic olefine 72 by ring-closing metathesis of diene 70.
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
- •−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and hydroperoxyl radical (•OOH) (Figure 3) [35]. Additionally, the menadione semiquinone radical can participate in another redox cycle, such as, the Fenton reaction, also resulting in the production of hydroxyl and hydroperoxyl radicals (Figure 3) [39][40
- menadione (10), as was demonstrated by Minisci and co-workers [66]. In this work, the oxidation of 17 with 60% aqueous hydrogen peroxide, using bromine and sulfuric acid as catalysts, provided menadione in 90% yield (Table 2, entry 1) [66]. According to the proposed mechanism, the first step involves the
- different benzylamines (1:1:2.2) (Table 2, entry 7). The reaction was carried out in tert-amyl alcohol (TAA), which led to product 10 in 55% yield and 99% conversion of 17 [55]. In addition to hydrogen peroxide, other oxidizing agents can be used in the synthesis of menadione (10) from 17 and include
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.
Recent advances and perspectives in ruthenium-catalyzed cyanation reactions
- Thaipparambil Aneeja,
- Cheriya Mukkolakkal Abdulla Afsina,
- Padinjare Veetil Saranya and
- Gopinathan Anilkumar
Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4
- the cyanation reaction. This strategy utilized eco-friendly hydrogen peroxide and molecular oxygen as the oxidant system. This method was found highly favorable to tertiary amines with electron-donating substituents. The first report on an MCM-41-immobilized N-alkylethylenediamine Ru(III) complex (MCM
- to furnish the desired products in good yields. In 2008, they described the scope and mechanism of the oxidative cyanation of tertiary amines using H2O2 and O2 [34]. They pointed out the fact that the hydrogen peroxide system was found to be more efficient in catalyzing the cyanation reaction of
- cyclic amines than the aerobic oxidation system. The catalytic cycle for the hydrogen peroxide system involves the formation of the oxoruthenium species (A) and the low-valent ruthenium species (B), whereas the aerobic oxidation system includes C–H activation and a subsequent reaction with molecular
Graphical Abstract
Scheme 1: Starch-immobilized ruthenium trichloride-catalyzed cyanation of tertiary amines.
Scheme 2: Proposed mechanism for the cyanation of tertiary amines using starch-immobilized ruthenium trichlor...
Scheme 3: Cyanation of tertiary amines using heterogeneous Ru/C catalyst.
Scheme 4: Proposed mechanism for cyanation of tertiary amines using a heterogeneous Ru/C catalyst.
Scheme 5: Ruthenium-carbamato complex-catalyzed oxidative cyanation of tertiary amines.
Scheme 6: Cyanation of tertiary amines using immobilized MCM-41-2N-RuCl3 as the catalyst.
Scheme 7: Cyanation of tertiary amines using RuCl3·nH2O as the catalyst and molecular oxygen as oxidant.
Scheme 8: RuCl3-catalyzed cyanation of tertiary amines using NaCN/HCN and H2O2 as oxidant.
Scheme 9: Proposed mechanism for the ruthenium-catalyzed oxidative cyanation using H2O2.
Scheme 10: Proposed mechanism for the ruthenium-catalyzed aerobic oxidative cyanation.
Scheme 11: RuCl3-catalyzed oxidative cyanation of tertiary amines using acetone cyanohydrin as the cyanating a...
Scheme 12: Cyanation of indoles using K4[Fe(CN)6] as cyano source and Ru(III)-exchanged NaY zeolite (RuY) as c...
Scheme 13: Cyanation of arenes and heteroarenes using a ruthenium(II) catalyst and N-cyano-N-phenyl-p-toluenes...
Scheme 14: Proposed mechanism for the cyanation of arenes and heteroarenes using ruthenium(II) as catalyst and...
Scheme 15: Synthesis of N-(2-cyanoaryl)-7-azaindoles.
Figure 1: Structure of the TiO2-immobilized ruthenium polyazine complex.
Scheme 16: Visible-light-induced oxidative cyanation of aza-Baylis–Hillman adducts.
Scheme 17: Synthesis of 1° alkyl nitriles using [Ru(bpy)3](PF6)2 as the photocatalyst.
Scheme 18: Synthesis of 2° and 3° alkyl nitriles using [Ru(bpy)3](PF6)2 as the photocatalyst.
Scheme 19: Photoredox cross coupling reaction.
Scheme 20: Synthesis of α-amino nitriles from amines via a one-pot strategy.
Scheme 21: Proposed mechanistic pathway for the cyanation of the aldimine intermediate.
Scheme 22: Strecker-type functionalization of N-aryl-substituted tetrahydroisoquinolines under flow conditions....
Scheme 23: One-pot synthesis of α-aminonitriles using RuCl3 as catalyst.
Scheme 24: Synthesis of alkyl nitriles using (Ru(TMHD)3) as the catalyst.
Scheme 25: Synthesis of cyanated isoxazolines from alkenyl oximes catalyzed by [RuCl2(p-cymene)]2 in the prese...
Scheme 26: Proposed mechanism for the synthesis of cyanated isoxazolines from alkenyl oximes.
Scheme 27: Oxidative cyanation of differently substituted alcohols.
Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents
- Rodolfo H. V. Nishimura,
- Thiago dos Santos,
- Valter E. Murie,
- Luciana C. Furtado,
- Leticia V. Costa-Lotufo and
- Giuliano C. Clososki
Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206
- . While anthranilamide (5) bromination with N-bromosuccinimide in acetonitrile at room temperature [29] furnished 2-amino-5-bromobenzamide (6a) in 78% yield, iodination of 5 with iodine in the presence of hydrogen peroxide in water [30] at 50 °C provided 2-amino-5-iodobenzamide (6b) in 89% yield. After
Graphical Abstract
Figure 1: Some antitumor agents containing the 4-anilinoquinazoline moiety.
Scheme 1: Examples of N-arylation reactions using 4-chloroquinazolines as substrates.
Scheme 2: Synthesis of verubulin analog.
Scheme 3: Synthesis of 4-chloro-6-halo-2-phenylquinazolines 8a and 8b. Conditions: a) NBS, CH3CN, 30 min, 25 ...
Scheme 4: N-Arylation reactions using ortho-, meta-, and para-substituted primary anilines of type 14 followe...
Scheme 5: N-Arylation reactions using 4-chloroquinazoline (16) and 4-chloro-2-methylquinazoline (17) to achie...
Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation
- Lukáš Ďurina,
- Anna Ďurinová,
- František Trejtnar,
- Ľuboš Janotka,
- Lucia Messingerová,
- Jana Doháňošová,
- Ján Moncol and
- Róbert Fischer
Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188
- hydrogen peroxide catalyzed by phosphotungstic heteropoly acid. Each of the key reactions proceeded with an excellent diastereoselectivity (dr > 95:5). (±)-Codonopsinol B was prepared in 10 steps with overall 8.4% yield. The antiproliferative effect of (±)-codonopsinol B and its N-nor-methyl analogue was
- 1, page S25). Although the syn selectivity was further improved (80:20) by using the in situ-generated trifluoroperoxyacetic acid [28], the reaction suffered from formation of a high level of impurities. Gratifyingly, this issue has been overcome by the use of hydrogen peroxide in the presence of
- formation. Since the aqueous tungstic acid-catalyzed hydrogen peroxide epoxidations of monosubstituted allylic alcohols usually proceed in anti (erythro) stereoselective fashion [32], we propose that the high syn selectivity can be attributed to the presence of the unprotected hydroxy group in the
Graphical Abstract
Figure 1: (−)-Codonopsinol B (1) and its N-nor-methyl analogue 2; known inhibition activities against α-gluco...
Scheme 1: Synthetic approach towards (±)-codonopsinol B (1) and its N-nor-methyl analogue 2.
Scheme 2: Synthesis of isoxazolidine-4,5-diol (±)-3. Reagents and conditions: (a) ᴅʟ-proline, CHCl3, rt, 48 h...
Scheme 3: Synthesis of final pyrrolidines (±)-1 and (±)-2. Reagents and conditions: (a) vinyl-MgBr, CeCl3, TH...
Figure 2: Molecular structure of N-Cbz-protected pyrrolidine 12 confirmed by single-crystal X-ray crystallogr...
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
- iron-based small molecule catalyst and hydrogen peroxide as oxidizing agent (Scheme 25A and B) [156]. This pioneering methodology changed the way how complex molecules and pharmaceuticals are synthesized, by using the steric and electronic properties of the substrates to achieve selectivity, without
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...
Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring
- Cansu Esen and
- Baris Kumru
Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92
- , ascorbic acid/hydrogen peroxide, respectively. The mixture was immediately placed in a Petri dish to complete the gelation via free radical polymerization under dark conditions. After 3 hours, the resulting hydrogel was purified with water to remove the unreacted species (monomers and redox mediators
- isothiocyanate conjugate (FITC-Albumin, Sigma-Aldrich), calcium chloride (CaCl2, 97%, Alfa Aesar), cyanuric acid (98%, Sigma-Aldrich), fluoresceinisothiocyanat-dextran (FITC–Dextran, 10.000 Mw), hydrochloric acid (HCl, 37%, Sigma-Aldrich), hydrochloric acid (1 M solution, Sigma-Aldrich), hydrogen peroxide (30
- -W). 9 g freshly prepared CM-W, 0.8 g DMA, 0.150 g MBA and 0.150 g AsA were weighted into a flask, mixed for 5 minutes, then sonicated for 20 seconds. Following that, 1.5 mL hydrogen peroxide solution was injected into the mixture and placed in a Petri dish after mixing thoroughly. The Petri dish was
Graphical Abstract
Scheme 1: Schematic overview of g-CN-embedded hydrogel fabrication and its subsequent photoinduced post-modif...
Scheme 2: Hydrophobic hydrogel via photoinduced surface modification over embedded g-CN nanosheets in hydroge...
Figure 1: a) FTIR spectra of freeze-dried HGCM-vTA, HGCM and HG. b) UV spectra of freeze-dried HGCM-vTA, HGCM...
Figure 2: Scanning electron microscopy (SEM) images of a) HGCM and b) HGCM-vTA in combination with their elem...
Figure 3: a) Equilibrium swelling ratios of HG, HGCM, HGCM-vTA at specified time intervals. b) Thermogravimet...
Scheme 3: Overview of pore substructuring via photoinduced free radical polymerization over embedded g-CN nan...
Figure 4: FTIR spectra of freeze-dried HGCM-PAA, HGCM-PAAM, HGCM-PEGMEMA in comparison with HGCM.
Figure 5: Scanning electron microscopy (SEM) images of a) HGCM-PAA, b) HGCM-PAAM, and c) HGCM-PEGMEMA.
Figure 6: a) Thermogravimetric analysis of HGCM, HGCM-PAA, HGCM-PAAM and HGCM-PEGMEMA. b) Equilibrium swellin...
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.
Synthetic accesses to biguanide compounds
- Oleksandr Grytsai,
- Cyril Ronco and
- Rachid Benhida
Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82
- such as lead tetraacetate, potassium permanganate, or refluxing hydrogen peroxide were shown to produce urea-derived degradation products [3]. Biguanides also possess a remarkable capability to form stable metal complexes, a property that was already noticed by B. Rathke in 1879 [4]. Indeed, he relied
Graphical Abstract
Figure 1: Tautomeric forms of biguanide.
Figure 2: Illustrations of neutral, monoprotonated, and diprotonated structures biguanide.
Figure 3: The main approaches for the synthesis of biguanides. The core structure is obtained via the additio...
Scheme 1: The three main preparations of biguanides from cyanoguanidine.
Scheme 2: Synthesis of butylbiguanide using CuCl2 [16].
Scheme 3: Synthesis of biguanides by the direct fusion of cyanoguanidine and amine hydrochlorides [17,18].
Scheme 4: Synthesis of ethylbiguanide and phenylbiguanide as reported by Smolka and Friedreich [14].
Scheme 5: Synthesis of arylbiguanides through the reaction of cyanoguanidine with anilines in water [19].
Scheme 6: Synthesis of aryl- and alkylbiguanides by adaptations of Cohn’s procedure [20,21].
Scheme 7: Microwave-assisted synthesis of N1-aryl and -dialkylbiguanides [22,23].
Scheme 8: Synthesis of aryl- and alkylbiguanides by trimethylsilyl activation [24,26].
Scheme 9: Synthesis of phenformin analogs by TMSOTf activation [27].
Scheme 10: Synthesis of N1-(1,2,4-triazolyl)biguanides [28].
Scheme 11: Synthesis of 2-guanidinobenzazoles by addition of ortho-substituted anilines to cyanoguanidine [30,32] and...
Scheme 12: Synthesis of 2,4-diaminoquinazolines by the addition of 2-cyanoaniline to cyanoguanidine and from 3...
Scheme 13: Reactions of anthranilic acid and 2-mercaptobenzoic acid with cyanoguanidine [24,36,37].
Scheme 14: Synthesis of disubstituted biguanides with Cu(II) salts [38].
Scheme 15: Synthesis of an N1,N2,N5-trisubstituted biguanide by fusion of an amine hydrochloride and 2-cyano-1...
Scheme 16: Synthesis of N1,N5-disubstituted biguanides by the addition of anilines to cyanoguanidine derivativ...
Scheme 17: Microwave-assisted additions of piperazine and aniline hydrochloride to substituted cyanoguanidines ...
Scheme 18: Synthesis of N1,N5-alkyl-substituted biguanides by TMSOTf activation [27].
Scheme 19: Additions of oxoamines hydrochlorides to dimethylcyanoguanidine [49].
Scheme 20: Unexpected cyclization of pyridylcyanoguanidines under acidic conditions [50].
Scheme 21: Example of industrial synthesis of chlorhexidine [51].
Scheme 22: Synthesis of symmetrical N1,N5-diarylbiguanides from sodium dicyanamide [52,53].
Scheme 23: Synthesis of symmetrical N1,N5-dialkylbiguanides from sodium dicyanamide [54-56].
Scheme 24: Stepwise synthesis of unsymmetrical N1,N5-trisubstituted biguanides from sodium dicyanamide [57].
Scheme 25: Examples for the synthesis of unsymmetrical biguanides [58].
Scheme 26: Examples for the synthesis of an 1,3-diaminobenzoquinazoline derivative by the SEAr cyclization of ...
Scheme 27: Major isomers formed by the SEAr cyclization of symmetric biguanides derived from 2- and 3-aminophe...
Scheme 28: Lewis acid-catalyzed synthesis of 8H-pyrrolo[3,2-g]quinazoline-2,4-diamine [63].
Scheme 29: Synthesis of [1,2,4]oxadiazoles by the addition of hydroxylamine to dicyanamide [49,64].
Scheme 30: Principle of “bisamidine transfer” and analogy between the reactions with N-amidinopyrazole and N-a...
Scheme 31: Representative syntheses of N-amidino-amidinopyrazole hydrochloride [68,69].
Scheme 32: First examples of biguanide syntheses using N-amidino-amidinopyrazole [66].
Scheme 33: Example of “biguanidylation” of a hydrazide substrate [70].
Scheme 34: Example for the synthesis of biguanides using S-methylguanylisothiouronium iodide as “bisamidine tr...
Scheme 35: Synthesis of N-substituted N1-cyano-S-methylisothiourea precursors.
Scheme 36: Addition routes on N1-cyano-S-methylisothioureas.
Scheme 37: Synthesis of an hydroxybiguanidine from N1-cyano-S-methylisothiourea [77].
Scheme 38: Synthesis of an N1,N2,N3,N4,N5-pentaarylbiguanide from the corresponding triarylguanidine and carbo...
Scheme 39: Reactions of N,N,N’,N’-tetramethylguanidine (TMG) with carbodiimides to synthesize hexasubstituted ...
Scheme 40: Microwave-assisted addition of N,N,N’,N’-tetramethylguanidine to carbodiimides [80].
Scheme 41: Synthesis of N1-aryl heptasubstituted biguanides via a one-pot biguanide formation–copper-catalyzed ...
Scheme 42: Formation of 1,2-dihydro-1,3,5-triazine derivatives by the reaction of guanidine with excess carbod...
Scheme 43: Plausible mechanism for the spontaneous cyclization of triguanides [82].
Scheme 44: a) Formation of mono- and disubstituted (iso)melamine derivatives by the reaction of biguanides and...
Scheme 45: Reactions of 2-aminopyrimidine with carbodiimides to synthesize 2-guanidinopyrimidines as “biguanid...
Scheme 46: Non-catalyzed alternatives for the addition of 2-aminopyrimidine derivatives to carbodiimides. A) h...
Scheme 47: Addition of guanidinomagnesium halides to substituted cyanamides [90].
Scheme 48: Microwave-assisted synthesis of [11C]metformin by the reaction of 11C-labelled dimethylcyanamide an...
Scheme 49: Formation of 4-amino-6-dimethylamino[1,3,5]triazin-2-ol through the reaction of Boc-guanidine and d...
Scheme 50: Formation of 1,3,5-triazine derivatives via the addition of guanidines to substituted cyanamides [92].
Scheme 51: Synthesis of biguanide by the reaction of O-alkylisourea and guanidine [93].
Scheme 52: Aromatic nucleophilic substitution of guanidine on 2-O-ethyl-1,3,5-triazine [95].
Scheme 53: Synthesis of N1,N2-disubstituted biguanides by the reaction of guanidine and thioureas in the prese...
Scheme 54: Cyclization reactions involving condensations of guanidine(-like) structures with thioureas [97,98].
Scheme 55: Condensations of guanidine-like structures with thioureas [99,100].
Scheme 56: Condensations of guanidines with S-methylisothioureas [101,102].
Scheme 57: Addition of 2-amino-1,3-diazaaromatics to S-alkylisothioureas [103,104].
Scheme 58: Addition of guanidines to 2-(methylsulfonyl)pyrimidines [105].
Scheme 59: An example of a cyclodesulfurization reaction to a fused 3,5-diamino-1,2,4-triazole [106].
Scheme 60: Ring-opening reactions of 1,3-diaryl-2,4-bis(arylimino)-1,3-diazetidines [107].
Scheme 61: Formation of 3,5-diamino-1,2,4-triazole derivatives via addition of hydrazines to 1,3-diazetidine-2...
Scheme 62: Formation of a biguanide via the addition of aniline to 1,2,4-thiadiazol-3,5-diamines, ring opening...
Figure 4: Substitution pattern of biguanides accessible by synthetic pathways a–h.
Synthesis, structural characterization, and optical properties of benzo[f]naphtho[2,3-b]phosphoindoles
- Mio Matsumura,
- Takahiro Teramoto,
- Masato Kawakubo,
- Masatoshi Kawahata,
- Yuki Murata,
- Kentaro Yamaguchi,
- Masanobu Uchiyama and
- Shuji Yasuike
Beilstein J. Org. Chem. 2021, 17, 671–677, doi:10.3762/bjoc.17.56
- phosphorus atom of 2 was carried out; the results are shown in Scheme 1. The reaction of 2 with hydrogen peroxide or elemental sulfur afforded the corresponding phosphine oxide 3 and sulfide 4 in 92% and 88% yield, respectively. Treatment of 2 with methyl triflate afforded phospholium triflate 5 in 81% yield
Graphical Abstract
Figure 1: Benzonaphthophosphindoles.
Scheme 1: Synthesis of benzo[f]naphtho[2,3-b]phosphoindoles.
Figure 2: Crystal structure of 2: different views.
Figure 3: a) Absorption spectra and b) normalized fluorescence spectra for selected compounds in CHCl3.
Figure 4: The spatial plots of the HOMO−3 to LUMO of compounds 3 and 4. The calculations were performed at th...
Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents
- Anuj Kumar Chhalodia and
- Jeroen S. Dickschat
Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51
- minutes, 30% hydrogen peroxide solution (0.52 mL, 0.57 g, 5.0 mmol, 2.0 equiv) was added dropwise. The color of the reaction mixture changed from colorless to yellow. The reaction mixture was stirred for 30 minutes at room temperature. After completion of the reaction, EtOAc (10 mL) was added, causing
Graphical Abstract
Scheme 1: Volatile allyl sulfides. A) Compounds known from garlic oil, B) mechanism of formation from alliin (...
Scheme 2: Degradation of DMSP by marine bacteria. A) Hydrolysis or lysis to DMS, B) demethylation pathway lea...
Scheme 3: Synthesis of DMSP derivatives.
Figure 1: Sulfur volatiles released by agar plate cultures of marine bacteria fed with DAllSP or AllMSP.
Figure 2: Total ion chromatograms of CLSA extracts obtained from feeding experiments with DAllSP fed to A) P....
Scheme 4: Proposed mechanisms for the formation of sulfur volatiles from DAllSP and AllMSP.
Figure 3: EI mass spectrum and fragmentation pattern of the unknown volatiles A) methyl 3-(allyldisulfanyl)pr...
Scheme 5: Synthesis of A) methyl 3-(allyldisulfanyl)propanoate (26) and B) methyl 3-(methylsulfonyl)propanoat...
Figure 4: Total ion chromatograms of CLSA extracts obtained from the feeding experiments with AllMSP fed to A...
A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles
- Lucía Rossi-Fernández,
- Viviana Dorn and
- Gabriel Radivoy
Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46
- greener oxidizing agents as molecular oxygen, hydrogen peroxide or tert-butyl hydroperoxide (TBHP) [14][15][16][17]. However, using any of these oxidants alone results in considerable low reactivity and selectivity in olefin epoxidation reactions. Thus, several transition-metal-based catalytic methods
Graphical Abstract
Figure 1: TEM micrograph and size distribution graphic for CoNPs@MgO catalyst (scale bar = 20 nm).
Scheme 1: Plausible mechanistic pathway for olefin epoxidation catalyzed by CoNPs/MgO in the presence of t-Bu...
19F NMR as a tool in chemical biology
- Diana Gimenez,
- Aoife Phelan,
- Cormac D. Murphy and
- Steven L. Cobb
Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28
Graphical Abstract
Figure 1: Selected examples of 19F-labelled amino acid analogues used as probes in chemical biology.
Figure 2: (a) Sequences of the antimicrobial peptide MSI-78 and pFtBSer-containing analogs and cartoon repres...
Figure 3: (a) Chemical structures of a selection of trifluoromethyl tags. (b) Comparative analysis showing th...
Figure 4: (a) First bromodomain of Brd4 with all three tryptophan residues displayed in blue and labelled by ...
Figure 5: (a) Enzymatic hydroxylation of GBBNF in the presence of hBBOX (b) 19F NMR spectra showing the conve...
Figure 6: (a) In-cell enzymatic hydrolysis of the fluorinated anandamide analogue ARN1203 catalyzed by hFAAH....
Figure 7: (a) X-ray crystal structure of CAM highlighting the location the phenylalanine residues replaced by...
Figure 8: 19F PREs of 4-F, 5-F, 6-F, 7-FTrp49 containing MTSL-modified S52CCV-N. The 19F NMR resonances of ox...
Figure 9: 19F NMR as a direct probe of Ud NS1A ED homodimerization. Schematic representation showing the loca...
Figure 10: (a) Representative spectrum of a 182 μM sample of Aβ1-40-tfM35 at varying times indicating the majo...
Figure 11: Illustration of the conformational switch induced by SDS in 4-tfmF-labelled α-Syn. Also shown are t...
Figure 12: (a) Structural models of the Myc‐Max (left), Myc‐Max‐DNA (middle) and Myc‐Max‐BRCA1 complexes (righ...
Figure 13: (a) Side (left) and bottom (right) views of the pentameric apo ELIC X-ray structure (PDB ID: 3RQU) ...
Figure 14: (a) General structure of a selection of recently developed 19F-labelled nucleotides for their use a...
Figure 15: Monitoring biotransformation of the fluorinated pesticide cyhalothrin by the fungus C. elegans. The...
Figure 16: Following the biodegradation of emerging fluorinated pollutants by 19F NMR. The spectra are from cu...
Figure 17: Discovery of new fluorinated natural products by 19F NMR. The spectrum is of the culture supernatan...
Figure 18: Application of 19F NMR to investigate the biosynthesis of nucleocidin. The spectra are from culture...
Figure 19: Detection of new fluorofengycins (indicated by arrows) in culture supernatants of Bacillus sp. CS93...
Figure 20: Measurement of β-galactosidase activity in MCF7 cancer cells expressing lacZ using 19F NMR. The deg...
Figure 21: Detection of ions using 19F NMR. (a) Structure of TF-BAPTA and its 19F iCEST spectra in the presenc...
Figure 22: (a) The ONOO−-mediated decarbonylation of 5-fluoroisatin and 6-fluoroisatin. The selectivity of (b)...
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
- piperidine (17). The synthetic sequence performed by the authors is described in Scheme 3. Oxidation of 17 in the presence of hydrogen peroxide, catalyzed by selenium dioxide provided tetrahydropyridine N-oxide 18 in 88% yield. 18 was treated with (R)-p-tolylsulfinylmethyllithium 25 in THF at −78 °C to
- provide β-sulfinyl hydroxylamine 19 in a diastereoisomeric ratio of 67:33 in 52% yield. Oxidation of 19 to nitrone 20 occurred chemoselectivelly through treatment with a solution of hydrogen peroxide in 3 mol % of 5-ethyluminiflavin perchlorate (FIEt+.ClO4) as a catalyst in 55% yield. The reaction of β
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(...
