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Search for "tert-butyl" in Full Text gives 616 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
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
- 1H-tetrazole to produce the trialkyl phosphite 8.3 that was oxidized with tert-butyl hydroperoxide to produce phosphate 8.4. Then, β-elimination of the cyanoethyl protecting group produced PAF with a global yield of 70%. The limit of this method arises from the instability of the precursor 8.1 for
- polyunsaturated analogues, the reaction started with the metalation of tert-butyl methyl ether according to the conditions reported by Corey and Eckrich [140], followed by the nucleophilic addition on unsaturated or polyunsaturated aldehyde to produce, as an example, 31.5. Then, the alkylation of the secondary
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...
Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp3)–H to construct C–C bonds
- Hui Yu and
- Feng Xu
Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94
- benzothiazole, in which benzothiazole compounds have higher reactivity and regioselectivity than thiazole. In 2014, Lei et al. successfully realized the copper-catalyzed oxidative alkenylation of simple ethers to construct allyl ethers in the presence of di-tert-butyl peroxide and KI (Scheme 10) [60]. The
- in combination with di-tert-butyl peroxide (DTBP) as an oxidant enables the CDC of the C(sp3)–H bond in the α-position to oxygen of various ethers with the active methylene C(sp3)–H bond in 1,3-diketones (Scheme 17) [78]. This method can generate various functionalized molecules and is expected to
- 2010, Schnürch et al. utilized Fe(NO3)3 as the catalyst and TBHP (tert-butyl hydroperoxide) as the oxidant to realize the CDC of C(sp3)–H/C(sp2)–H bonds under solvent-free conditions (Scheme 21) [82]. However, the desired coupling products were obtained in low to moderate yields. The C–H oxidative
Graphical Abstract
Scheme 1: Research progress of coupling reactions and active compounds containing α-C(sp3)-functionalized eth...
Scheme 2: Transition-metal-catalyzed CDC pathways.
Scheme 3: CDC of active methylene compounds in the α-C(sp3) position of ethers.
Scheme 4: InCl3/Cu(OTf)2/NHPI co-catalyzed CDC reaction.
Scheme 5: CDC of cyclic benzyl ethers with aldehydes.
Scheme 6: Cu-catalyzed CDC of (a) unactivated C(sp3)–H ethers with simple ketones and (b) double C(sp3)−H fun...
Scheme 7: Cu-catalyzed CDC of C(sp3)–H/C(sp3)–H bonds.
Scheme 8: Cu-catalyzed synthesis of chiral 2-substituted tetrahydropyrans.
Scheme 9: CDC of thiazole with cyclic ethers.
Scheme 10: Cu(I)-catalyzed oxidative alkenylation of simple ethers.
Scheme 11: Cross-dehydrogenation coupling of isochroman C(sp3)–H bonds with anisole C(sp2)–H bonds.
Scheme 12: Pd(OAc)2/Cu(OTf)2-catalyzed arylation of α-C(sp3)–H bonds of ethers.
Scheme 13: Cu-catalyzed C(sp3)–H/C(sp2)–H activation strategies to construct C(sp3)–C(sp2) bonds.
Scheme 14: Cu(I)-catalyzed C(sp2)–H alkylation.
Scheme 15: Cu-catalyzed C(sp3)–H/C(sp)–H activation to construct C(sp3)–C(sp) bonds (H2BIP: 2,6-bis(benzimidaz...
Scheme 16: Fe-catalyzed CDC reaction pathways.
Scheme 17: Fe2(CO)9-catalyzed functionalization of C–H bonds.
Scheme 18: Ligand-promoted Fe-catalyzed CDC reaction of N-methylaniline with ethers.
Scheme 19: Fe-catalyzed CDC of C(sp3)–H/C(sp3)–H bonds.
Scheme 20: Fe-catalyzed hydroalkylation of α,β-unsaturated ketones with ethers.
Scheme 21: Solvent-free Fe(NO3)3-catalyzed CDC of C(sp3)–H/C(sp2)–H bonds.
Scheme 22: Alkylation of disulfide compounds to afford tetrasubstituted alkenes.
Scheme 23: Fe-catalyzed formation of 1,1-bis-indolylmethane derivatives.
Scheme 24: Alkylation of coumarins and flavonoids.
Scheme 25: Direct CDC α-arylation of azoles with ethers.
Scheme 26: CDC of terminal alkynes with C(sp3)–H bonds adjacent to oxygen, sulfur or nitrogen atoms.
Scheme 27: Alkylation of terminal alkynes.
Scheme 28: Co-catalyzed functionalization of glycine esters.
Scheme 29: Co-catalyzed construction of C(sp2)–C(sp3) bonds.
Scheme 30: Co-catalyzed CDC of imidazo[1,2-a]pyridines with isochroman.
Scheme 31: Co-catalyzed C–H alkylation of (benz)oxazoles with ethers.
Scheme 32: Cobalt-catalyzed CDC between unactivated C(sp2)–H and C(sp3)–H bonds.
Scheme 33: MnO2-catalyzed CDC of the inactive C(sp3)-H.
Scheme 34: Oxidative cross-coupling of ethers with enamides.
Scheme 35: Ni(II)-catalyzed CDC of indoles with 1,4-dioxane.
Scheme 36: Chemo- and regioselective ortho- or para-alkylation of pyridines.
Scheme 37: Asymmetric CDC of 3,6-dihydro-2H-pyrans with aldehydes.
Scheme 38: CDC of heterocyclic aromatics with ethers.
Scheme 39: Indium-catalyzed alkylation of DHPs with 1,3-dicarbonyl compounds.
Scheme 40: Rare earth-metal-catalyzed CDC reaction.
Scheme 41: Visible-light-driven CDC of cycloalkanes with benzazoles.
Scheme 42: Photoinduced alkylation of quinoline with cyclic ethers.
Scheme 43: Photocatalyzed CDC reactions between α-C(sp3)–H bonds of ethers and C(sp2)–H bonds of aromatics.
Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors
- Grace A. Lowe
Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88
Graphical Abstract
Figure 1: Diagram comparing the two reaction pathways for sacrificial electron donors (SD) in photocatalyzed ...
Figure 2: Diagram showing water-splitting systems developed by Girault, Scanlon, and co-workers that employ i...
Figure 3: Diagram illustrating the transfer of electrons in a photocatalytic particulate suspensions Z-scheme...
Figure 4: A. Structures of the molecules represented in part B. The numbers in brackets correspond to the com...
Figure 5: A. Structures of the molecules represented in part B. The numbers in brackets correspond to the com...
Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control
- Carlee A. Montgomery and
- Graham K. Murphy
Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86
- ]. The authors discounted a free carbene-based C–H insertion because conducting the reaction in the presence of the radical trap phenyl N-tert-butyl nitrone (PBN) and the radical scavenger TEMPO resulted in decreased yields and isolation of their iodonium ylide adducts. Additional kinetic isotope effect
Graphical Abstract
Figure 1: Generic representation of halogen bonding.
Figure 2: Quantitative evaluation of σ-holes in monovalent iodine-containing compounds; and, qualitative mole...
Figure 3: Quantitative evaluation of σ-holes in hypervalent iodine-containing molecules; and, qualitative MEP...
Figure 4: Quantitative evaluation of σ-holes in iodonium ylides; and, qualitative MEP map of I-12 from −0.083...
Scheme 1: Outline of possible reaction pathways between iodonium ylides and Lewis basic nucleophiles (top); a...
Scheme 2: Metal-free cyclopropanations of iodonium ylides, either as intermolecular (a) or intramolecular pro...
Figure 5: Zwitterionic mechanism for intramolecular cyclopropanation of iodonium ylides (left); and, stepwise...
Scheme 3: Metal-free intramolecular cyclopropanation of iodonium ylides.
Figure 6: Concerted cycloaddition pathway for the metal-free, intramolecular cyclopropanation of iodonium yli...
Scheme 4: Reaction of ylide 6 with diphenylketene to form lactone 24 and 25.
Figure 7: Nucleophilic (top) and electrophilic (bottom) addition pathways proposed by Koser and Hadjiarapoglo...
Scheme 5: Indoline synthesis from acyclic iodonium ylide 31 and tertiary amines.
Scheme 6: N-Heterocycle synthesis from acyclic iodonium ylide 31 and secondary amines.
Figure 8: Proposed mechanism for the formation of 33a from iodonium ylides and amines, involving an initial h...
Scheme 7: Indoline synthesis from acyclic iodonium ylides 39 and tertiary amines under blue light photocataly...
Scheme 8: Metal-free cycloproponation of iodonium ylides under blue LED irradiation. aUsing trans-β-methylsty...
Figure 9: Proposed mechanism of the cyclopropanation between iodonium ylides and alkenes under blue LED irrad...
Scheme 9: Formal C–H alkylation of iodonium ylides by nucleophilic heterocycles under blue LED irradiation.
Figure 10: Proposed mechanism of the formal C–H insertion of pyrrole under blue LED irradiation.
Scheme 10: X–H insertions between iodonium ylides and carboxylic acids, phenols and thiophenols.
Figure 11: Mechanistic proposal for the X–H insertion reactions of iodonium ylides.
Scheme 11: Radiofluorination of biphenyl using iodonium ylides 54a–e derived from various β-dicarbonyl auxilia...
Scheme 12: Radiofluorination of arenes using spirocycle-derived iodonium ylides 56.
Scheme 13: Radiofluorination of arenes using SPIAd-derived iodonium ylides 58.
Figure 12: Calculated reaction coordinate for the radiofluorination of iodonium ylide 60.
Scheme 14: Radiofluorination of iodonium ylides possessing various ortho- and para-substituents on the iodoare...
Figure 13: Difference in Gibbs activation energy for ortho- or para-anisyl derived iodonium ylides 63a and 63b....
Figure 14: Proposed equilibration of intermediates to transit between 64a (the initial adduct formed between 6...
Scheme 15: Comparison of 31 and ortho-methoxy iodonium ylide 39 in rhodium-catalyzed cyclopropanation and cycl...
Figure 15: X-ray crystal structure of dimeric 39 [6], (CCDC# 893474) [143,144].
Scheme 16: Enaminone synthesis using diazonium and iodonium ylides.
Figure 16: Transition state calculations for enaminone synthesis from iodonium ylides and thioamides.
Scheme 17: The reaction between ylides 73a–f and N-methylpyrrole under 365 nm UV irradiation.
Figure 17: Crystal structures of 76c (top) and 76e (bottom) [101], (CCDC# 2104180 & 2104181) [143,144].
Photoredox catalysis harvesting multiple photon or electrochemical energies
- Mattia Lepori,
- Simon Schmid and
- Joshua P. Barham
Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81
- hydroarylation of tert-butyl vinylcarbamate and unactivated alkenes like 1-octene and 3-buten-1-ol although the vinyl carbamate substrate (Epred = −2.2 V vs SCE) is significantly easier to reduce than most aryl chlorides. This selectivity, especially considering the need for an excess of the vinyl carbamate
Graphical Abstract
Figure 1: Oxidative and reductive activations of organic compounds harvesting photoredox catalysis.
Figure 2: General catalytic cycles of radical ion conPET (left) and radical ion e-PRC (right).
Figure 3: “Beginner’s guide”: comparison between advantages, capacities, and prospectives of conPET and PEC.
Figure 4: A) conPET reductive dehalogenation of aryl halides with PDI. B) Reductive C–H arylation with pyrrol...
Figure 5: A) Chromoselective mono- and disubstitution or polybrominated pyrimidines with pyrroles. B) Sequent...
Figure 6: A) Synthesis of pyrrolo[1,2-a]quinolines. B) Synthesis of ullazines.
Figure 7: A) Reductive phosphorylation of aryl halides via conPET. B) Selected examples from the substrate sc...
Figure 8: A) Reductive dehalogenation of aryl halides via conPET and selected examples from the substrate sco...
Figure 9: A) Reductive C–H arylation of aryl halides via conPET (top) and selected examples from the substrat...
Figure 10: A) Reductive hydrodehalogenation of aryl halides with Mes-Acr-BF4. B) Selected examples from the su...
Figure 11: A) Reductive hydrodechlorination of aryl chlorides with 4-DPAIPN. B) Proposed formation of CO2•−. C...
Figure 12: A) Reductive conPET borylation with 3CzEPAIPN (top) and selected examples from the substrate scope ...
Figure 13: Scale-up of conPET phosphorylation with 3CzEPAIPN.
Figure 14: A) Borylation of 1d. B) Characteristics and structure of PC1 with green and red parts showing the l...
Figure 15: A) Reductive C–H arylation scope with polysulfide conPET (top) and selected examples from the subst...
Figure 16: Scale-up of A) C–H arylation and B) dehaloborylation with polysulfide photocatalysis in continuous-...
Figure 17: A) Formation of [Ir1]0 and [Ir2]0 upon PET between [Ir1]+ and Et3N. B) Mechanism of multi-photon ta...
Figure 18: A) Reductive hydrodehalogenation of aryl halides via multi-photon tandem photocatalysis. B) Selecte...
Figure 19: A) Carbonylative amidation of aryl halides in continuous flow. B) Selected examples from the substr...
Figure 20: A) General scheme for reductive (RQ) and oxidative quenching (OQ) protocols using [FeIII(btz)3](PF6)...
Figure 21: A) Carbonylative amidation of alkyl iodides with [IrIII(ppy)2(dtbbpy)]PF6. B) Selected examples fro...
Figure 22: A) Carboxylative C–N bond cleavage in cyclic amines. B) Selected examples from the substrate scope....
Figure 23: A) Formal reduction of alkenes to alkanes via transfer hydrogenation. B) Selected examples from the...
Figure 24: A) Birch-type reduction of benzenes with PMP-BPI. B) Selected examples from the substrate scope (sc...
Figure 25: Proposed mechanism of the OH− mediated conPET Birch-type reduction of benzene via generation of sol...
Figure 26: Reductive detosylation of N-tosylated amides with Mes-Acr-BF4. B) Selected examples from the substr...
Figure 27: A) Reductive detosylation of N-tosyl amides by dual PRC. B) Selected examples from the substrate sc...
Figure 28: A) Mechanism of the dual PRC based on PET between [Cu(dap)2]+ and DCA. B) Mechanism of the dual PRC...
Figure 29: A) N–O bond cleavage in Weinreb amides with anthracene. B) N–O bond cleavage in Weinreb amides rely...
Figure 30: A) Pentafluorosulfanylation and fluoride elimination. B) Mechanism of the pentafluorosulfanylation ...
Figure 31: A) α-Alkoxypentafluorosulfanylation (top) and selected examples from the substrate scope (bottom). ...
Figure 32: A) Oxidative amination of arenes with azoles catalyzed by N-Ph PTZ. B) Selected examples from the s...
Figure 33: A) C(sp3)–H bond activation by HAT via chloride oxidation by *N-Ph PTZ•+. B) Proposed mechanism for...
Figure 34: A) Recycling e-PRC C–H azolation of electron-rich arenes with pyrazoles using Mes-Acr+ as a photoca...
Figure 35: A) Radical ion e-PRC direct oxidation of unactivated arenes using TAC+ as an electro-activated phot...
Figure 36: A) Radical ion e-PRC direct oxidation of unactivated arenes using TPA as an electro-activated photo...
Figure 37: Proposed mechanism (top) and mode of preassembly (bottom).
Figure 38: A) Possible preassemblies of reactive (left) vs unreactive (right) arenes. B) Calculated spin densi...
Figure 39: A) Recycling e-PRC C(sp2 )–H acetoxylation of arenes using DDQ as a photocatalyst. B) Proposed cata...
Figure 40: Gram scale hydroxylation of benzene in a recirculated flow setup.
Figure 41: A) Radical ion e-PRC vicinal diamination of alkylarenes using TAC+ as an electro-activated photocat...
Figure 42: A) Sequential oxygenation of multiple adjacent C–H bonds under radical ion e-PRC using TAC+ as an e...
Figure 43: A) Enantioselective recycling e-PRC cyanation of benzylic C–H bonds using ADQS as photocatalyst. B)...
Figure 44: Proposed tandem mechanism by Xu and co-workers.
Figure 45: A) Enantioselective recycling e-PRC decarboxylative cyanation using Cu(acac)2, Ce(OTf)3 and a box l...
Figure 46: A) Enantioselective recycling e-PRC benzylic cyanation using Cu(MeCN)4BF4, box ligand and anthraqui...
Figure 47: A) Radical ion e-PRC acetoxyhydroxylation of aryl olefins using TAC+ as an electro-activated photoc...
Figure 48: Selected examples from the substrate scope.
Figure 49: Photoelectrochemical acetoxyhydroxylation in a recirculated flow setup.
Figure 50: A) Radical ion e-PRC aminooxygenation of aryl olefins using TAC+ as an electro-activated photocatal...
Figure 51: A) Recycling e-PRC C–H alkylation of heteroarenes with organic trifluoroborates using Mes-Acr+ as p...
Figure 52: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using CeCl3·7H2O as catalyst. B) ...
Figure 53: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using Fe(NH4)2(SO4)2·6H2O as cata...
Figure 54: A) Recycling e-PRC C–H alkylation of heteroarenes with alkyl oxalates and 4CzIPN as photocatalyst. ...
Figure 55: A) Recycling e-PRC decarboxylative C–H carbamoylation of heteroarenes using 4CzIPN as photocatalyst...
Figure 56: A) Photoelectrochemical HAT-mediated hydrocarbon activation via the chlorine radical. B) Proposed m...
Figure 57: A) Selected examples from the substrate scope. B) Gram and decagram scale semi-continuous flow PEC ...
Figure 58: A) Photoelectrochemical HAT-mediated dehydrogenative coupling of benzothiazoles with aliphatic C–H ...
Figure 59: A) Photoelectrochemical HAT activation of ethers using electro-activated TAC+ as photocatalyst. B) ...
Figure 60: Selected examples from the substrate scope.
Figure 61: A) Photoelectrochemical HAT-mediated synthesis of alkylated benzimidazo-fused isoquinolinones using...
Figure 62: A) Decoupled photoelectrochemical cerium-catalyzed oxydichlorination of alkynes using CeCl3 as cata...
Figure 63: Proposed decoupled photoelectrochemical mechanism.
Figure 64: A) Decoupled photoelectrochemical ring-opening bromination of tertiary cycloalkanols using MgBr2 as...
Figure 65: A) Recycling e-PRC ring-opening functionalization of cycloalkanols using CeCl3 as catalyst. B) Prop...
Figure 66: Selected examples from the substrate scope of the PEC ring-opening functionalization.
Figure 67: A) Radical ion e-PRC reduction of chloro- and bromoarenes using DCA as catalyst and various accepto...
Figure 68: A) Screening of different phthalimide derivatives as catalyst for the e-PRC reduction of aryl halid...
Figure 69: Screening of different organic catalysts for the e-PRC reduction of trialkylanilium salts.
Figure 70: A) e-PRC reduction of phosphonated phenols and anilinium salts. B) Selected examples from the subst...
Figure 71: A) ConPET and e-PRC reduction of 4-bromobenzonitrile using a naphthalene diimide (NDI) precatalyst ...
Figure 72: A) Radical ion e-PRC reduction of phosphinated aliphatic alcohols with n-BuO-NpMI as catalyst. B) C...
Figure 73: Selected examples from the substrate scope.
Figure 74: A) Recycling e-PRC reductive dimerization of benzylic chlorides using a [Cu2] catalyst. B) Proposed...
Figure 75: A) Decoupled photoelectrochemical C–H alkylation of heteroarenes through deamination of Katritzky s...
Figure 76: Proposed mechanism by Chen and co-workers.
Pyridine C(sp2)–H bond functionalization under transition-metal and rare earth metal catalysis
- Haritha Sindhe,
- Malladi Mounika Reddy,
- Karthikeyan Rajkumar,
- Akshay Kamble,
- Amardeep Singh,
- Anand Kumar and
- Satyasheel Sharma
Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62
Graphical Abstract
Figure 1: Representative examples of bioactive natural products and FDA-approved drugs containing a pyridine ...
Scheme 1: Classical and traditional methods for the synthesis of functionalized pyridines.
Scheme 2: Rare earth metal (Ln)-catalyzed pyridine C–H alkylation.
Scheme 3: Pd-catalyzed C–H alkylation of pyridine N-oxide.
Scheme 4: CuI-catalyzed C–H alkylation of N-iminopyridinium ylides with tosylhydrazones (A) and a plausible r...
Scheme 5: Zirconium complex-catalyzed pyridine C–H alkylation.
Scheme 6: Rare earth metal-catalyzed pyridine C–H alkylation with nonpolar unsaturated substrates.
Scheme 7: Heterobimetallic Rh–Al complex-catalyzed ortho-C–H monoalkylation of pyridines.
Scheme 8: Mono(phosphinoamido)-rare earth complex-catalyzed pyridine C–H alkylation.
Scheme 9: Rhodium-catalyzed pyridine C–H alkylation with acrylates and acrylamides.
Scheme 10: Ni–Al bimetallic system-catalyzed pyridine C–H alkylation.
Scheme 11: Iridium-catalyzed pyridine C–H alkylation.
Scheme 12: para-C(sp2)–H Alkylation of pyridines with alkenes.
Scheme 13: Enantioselective pyridine C–H alkylation.
Scheme 14: Pd-catalyzed C2-olefination of pyridines.
Scheme 15: Ru-catalyzed C-6 (C-2)-propenylation of 2-arylated pyridines.
Scheme 16: C–H addition of allenes to pyridines catalyzed by half-sandwich Sc metal complex.
Scheme 17: Pd-catalyzed stereodivergent synthesis of alkenylated pyridines.
Scheme 18: Pd-catalyzed ligand-promoted selective C3-olefination of pyridines.
Scheme 19: Mono-N-protected amino acids in Pd-catalyzed C3-alkenylation of pyridines.
Scheme 20: Amide-directed and rhodium-catalyzed C3-alkenylation of pyridines.
Scheme 21: Bimetallic Ni–Al-catalyzed para-selective alkenylation of pyridine.
Scheme 22: Arylboronic ester-assisted pyridine direct C–H arylation.
Scheme 23: Pd-catalyzed C–H arylation/benzylation with toluene.
Scheme 24: Pd-catalyzed pyridine C–H arylation with potassium aryl- and heteroaryltrifluoroborates.
Scheme 25: Transient activator strategy in pyridine C–H biarylation.
Scheme 26: Ligand-promoted C3-arylation of pyridine.
Scheme 27: Pd-catalyzed arylation of nicotinic and isonicotinic acids.
Scheme 28: Iron-catalyzed and imine-directed C–H arylation of pyridines.
Scheme 29: Pd–(bipy-6-OH) cooperative system-mediated direct pyridine C3-arylation.
Scheme 30: Pd-catalyzed pyridine N-oxide C–H arylation with heteroarylcarboxylic acids.
Scheme 31: Pd-catalyzed C–H cross-coupling of pyridine N-oxides with five-membered heterocycles.
Scheme 32: Cu-catalyzed dehydrative biaryl coupling of azine(pyridine) N-oxides and oxazoles.
Scheme 33: Rh(III)-catalyzed cross dehydrogenative C3-heteroarylation of pyridines.
Scheme 34: Pd-catalyzed C3-selective arylation of pyridines.
Scheme 35: Rhodium-catalyzed oxidative C–H annulation of pyridines to quinolines.
Scheme 36: Rhodium-catalyzed and NHC-directed C–H annulation of pyridine.
Scheme 37: Ni/NHC-catalyzed regio- and enantioselective C–H cyclization of pyridines.
Scheme 38: Rare earth metal-catalyzed intramolecular C–H cyclization of pyridine to azaindolines.
Scheme 39: Rh-catalyzed alkenylation of bipyridine with terminal silylacetylenes.
Scheme 40: Rollover cyclometallation in Rh-catalyzed pyridine C–H functionalization.
Scheme 41: Rollover pathway in Rh-catalyzed C–H functionalization of N,N,N-tridentate chelating compounds.
Scheme 42: Pd-catalyzed rollover pathway in bipyridine-6-carboxamides C–H arylation.
Scheme 43: Rh-catalyzed C3-acylmethylation of bipyridine-6-carboxamides with sulfoxonium ylides.
Scheme 44: Rh-catalyzed C–H functionalization of bipyridines with alkynes.
Scheme 45: Rh-catalyzed C–H acylmethylation and annulation of bipyridine with sulfoxonium ylides.
Scheme 46: Iridium-catalyzed C4-borylation of pyridines.
Scheme 47: C3-Borylation of pyridines.
Scheme 48: Pd-catalyzed regioselective synthesis of silylated dihydropyridines.
Construction of hexabenzocoronene-based chiral nanographenes
- Ranran Li,
- Di Wang,
- Shengtao Li and
- Peng An
Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54
- reaction. To prevent planarization during the final oxidative cyclodehydrogenation reaction step, Jux and co-workers synthesized hexaarylbenzene precursor 3 with sterically demanding tert-butyl groups through a standard [4 + 2] Diels–Alder reaction of tetra-tert-butyltolane 1 and tetracyclone 2 in an 81
- pursuit of HBC-tetramer-based supertwistacene (compound 115 in Scheme 12), Wang and co-workers synthesized a chiral HBC-dimer 46 [46], in which two HBC units structurally shared one benzene ring (Scheme 6). 1,4-Bis((4-(tert-butyl)phenyl)ethynyl)benzene reacted with tetracyclone 2 through a two-fold Diels
- –Alder cycloaddition to afford compound 45 in a 79% yield. Due to the steric hindrance from two bulky tert-butyl groups on the benzene rings in the adjacent hexaphenylbenzene monomers in precursor 45, two [5]helicenes were formed in the oxidative cyclodehydrognation reaction, which gave compound 46 as
Graphical Abstract
Scheme 1: Construction of HBC by Scholl reaction from hexaphenylbenzene.
Scheme 2: Synthesis of seco-HBC-based chiral nanographenes.
Scheme 3: Synthesis of nitrogen-doped, seco-HBC-based chiral nanographenes.
Scheme 4: Synthesis of π-extended [7]- and [9]helicene containing chiral nanographenes.
Scheme 5: Synthesis of “HBC-dimer”-based chiral nanographenes.
Scheme 6: Synthesis of “HBC-dimer”-based chiral nanographenes.
Scheme 7: Synthesis of axis-based chiral nanographenes.
Scheme 8: Synthesis of “HBC-trimers”-based nanoribbons.
Scheme 9: Synthesis of “HBC-trimers”-based, triangle-shaped chiral nanographenes.
Scheme 10: Synthesis of “HBC-trimers”-based, triangle-shaped chiral nanographenes.
Scheme 11: Synthesis of HBC-based multilayer nanographenes.
Scheme 12: Synthesis of a chiral nanographene constructed by “HBC-tetramers”.
Scheme 13: Synthesis of a triskelion-shaped nanographene constructed by four HBCs.
Scheme 14: Synthesis of a three-dimensional nanographene bearing four HBCs.
Scheme 15: Synthesis of a chiral nanographene constructed by five HBC units.
Scheme 16: Synthesis of a chiral nanographene constructed by seven HBC units.
Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions
- Oleksandr V. Kolomiiets,
- Alexander V. Tsygankov,
- Maryna N. Kornet,
- Aleksander A. Brazhko,
- Vladimir I. Musatov and
- Valentyn A. Chebanov
Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53
- reaction between 2-amino-5-chloropyridine (1a), 2-(3-formylphenoxy)acetic acid (2) and tert-butyl isocyanide (3a) was chosen for the first step (Scheme 3). In one of the previous works [34], our group has shown that the optimal conditions for this type of reactions are stirring the starting materials for
- heterocyclic acid 8a was obtained by a three-component reaction of 2-amino-5-chloropyridine (1a), 4-formylbenzoic acid (5f), and tert-butyl isocyanide (3a) according to the procedure described above (Scheme 3). In another step, we attempted to introduce the acid 8a into the Ugi four-component reaction with 4
- -chlorobenzaldehyde (5b), 4-methoxyaniline (6a) and tert-butyl isocyanide (3a). It should be especially noted that the solubility of compound 8a is very low (soluble in DMSO and N-methyl-2-pyrrolidone (NMP), slightly soluble in methanol, 1- and 2-propanol, acetone, DMF and insoluble in water, ethanol, acetonitrile
Graphical Abstract
Scheme 1: Diversity of structures synthesized by combining IMCR’s.
Figure 1: Drugs possessing imidazo[1,2-a]pyridine unit.
Figure 2: Drugs possessing peptide unit.
Scheme 2: Diversity of GBB reaction products as precursors for Ugi reaction.
Scheme 3: Synthesis of new acids containing a substituted imidazo[1,2-a]pyridine fragment.
Scheme 4: Synthesis of new peptidomimetics containing a substituted imidazo[1,2-a]pyridine fragment.
Scheme 5: Synthesis and reactivity of new acids containing a substituted imidazo[1,2-a]pyridine fragment with...
Synthesis of medium and large phostams, phostones, and phostines
- Jiaxi Xu
Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50
- synthesis of 1,2-oxaphosphaheterocycle 2-oxides. tert-Butyl 2-(bis(allyloxy)phosphoryl)pent-4-enoate (11) generated tert-butyl 2-(allyloxy)-3,4,7-trihydro-1,2-oxaphosphepine-3-carboxylate 2-oxide (12) in excellent 94% yield in the presence of the Grubbs catalyst in DCM. After further allylation with allyl
- bromide, its allylated product 13 further cyclized into bis(1,2-oxaphosphepine 2-oxide) derivative tert-butyl 2,5,5a,6,9-pentahydro-[1,2]oxaphosphepino[2,3-b][1,2]oxaphosphepine-5a-carboxylate 11-oxide (14) in 97% yield under the same conditions (Scheme 2) [27]. The Grubbs 1st generation catalyst-promoted
- from tert-butyl 2-(bis(allyloxy)phosphoryl)pent-4-enoate. Synthesis of 2-ethoxy-5H-benzo[f][1,2]oxaphosphepine 2-oxides from 2-allylphenyl ethyl vinylphosphonates. Synthesis of 2-ethoxy-3,6-dihydrobenzo[g][1,2]oxaphosphocine 2-oxides from 2-allylphenyl ethyl allylphosphonates. Synthesis of
Graphical Abstract
Figure 1: Biologically active agents and chiral ligands containing medium and large phostams, phostones, and ...
Figure 2: Synthetic strategies for the preparation of medium and large phostams, phostones, and phostines.
Scheme 1: Synthesis of 1,2-azaphosphepine 2-oxide, 1,2-azaphosphocine 2-oxide, 1,2-azaphosphepane 2-oxide, an...
Scheme 2: Synthesis of bis[1,2]oxaphosphepine 2-oxide from tert-butyl 2-(bis(allyloxy)phosphoryl)pent-4-enoat...
Scheme 3: Synthesis of 2-ethoxy-5H-benzo[f][1,2]oxaphosphepine 2-oxides from 2-allylphenyl ethyl vinylphospho...
Scheme 4: Synthesis of 2-ethoxy-3,6-dihydrobenzo[g][1,2]oxaphosphocine 2-oxides from 2-allylphenyl ethyl ally...
Scheme 5: Synthesis of benzothiophene-fused 2-hydroxy-1,2-oxaphosphecane 2-oxide from (4-allyl-2-(4-methylphe...
Scheme 6: Synthesis of benzothiophene-fused 2-hydroxy-1,2-oxaphosphecane 2-oxide from benzyl hydrogen ((4-all...
Scheme 7: Synthesis of benzothiophene-fused 2-hydroxy-1-oxa-2-phosphacycloundecane 2-oxide from benzyl hydrog...
Scheme 8: Synthesis of 5,6,7-trihydro-1,2-oxaphosphepine 2-oxide and its benzo derivatives from 3-bromobut-3-...
Scheme 9: Synthesis of thieno[2,3-d]pyrimidine-fused 2-hydroxy-1,2-oxaphosphonane 2-oxide from benzyl hydroge...
Scheme 10: Synthesis of 3-phenoxybenzo[f]pyreno[1,10-cd][1,2]oxaphosphepine 3-oxide from diphenyl pyren-1-ylph...
Scheme 11: Synthesis of 1,2-oxaphosphepane 2-oxides and 1,2-oxaphosphocane 2-oxide from hydrogen methyl hex-5-...
Scheme 12: Synthesis of 2-methoxy-1,2-oxaphosphinane 2-oxides, 1,2-oxaphosphepine 2-oxides, 1,2-oxaphosphepane...
Scheme 13: Synthesis of 1,2-azaphosphepane 2-oxide and its benzo derivatives from 5-bromohex-5-en-1-yl methylp...
Scheme 14: Synthesis of 4-phenyl-1,2-dihydronaphtho[2,1-c][1,2]oxaphosphinine 4-oxide and 1-phenyl-3,4-dihydro...
Scheme 15: Synthesis of 2-alkoxy-3,5-dimethylene-1,2-oxaphosphepane 2-oxides from dialkyl 2-bromo-1-methylethy...
Scheme 16: Synthesis of 14-methyl-2-phenoxy-1-oxa-2-phosphacyclotetradecane 2-oxide from phenyl hydrogen (12-h...
Scheme 17: Synthesis of 5-oxo-1,3,5-trihydrobenzo[f][1,2]azaphosphepine 2-oxides from 1,2-dihydro-4H-benzo[d][...
Scheme 18: Synthesis of 3-hydrobenzo[f][1,2]oxaphosphepin-5(4H)-one 2-oxides from 2-phenyl/alkoxy-4H-benzo[d][...
Scheme 19: Synthesis of bicyclic seven- and eight-membered phosphotones from cycloalk-2-enones and dimethyl ph...
Scheme 20: Synthesis of binaphthylene-fused phosphotones from (M)-2'-methyl-[1,1'-binaphthalen]-2-ol and pheny...
Scheme 21: Synthesis of bicyclic phosphotone from (1S,2R)-2-methyl-3-(phenylsulfonyl)cyclohept-3-en-1-ol and d...
Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles
- Ekaterina A. Lystsova,
- Maksim V. Dmitriev,
- Andrey N. Maslivets and
- Ekaterina E. Khramtsova
Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46
- , benzylamine, and arylamines 11, while alkylamines are unsuitable for it. Notable, the use of bulky nucleophiles (tert-butyl alcohol (16a), benzyl alcohol (16b), benzhydrol (16c), 2-aminobenzothiazole (16d), HCl) makes it possible to obtain pyrrolobenzothiazoles 17 from compounds 1, but their formation
Graphical Abstract
Figure 1: Biologically active PBTAs.
Scheme 1: Approaches to PBTAs via annulation of benzothiazoles.
Scheme 2: Approaches to PBTAs via annulation of o-aminothiophenols.
Scheme 3: Approach to PBTAs via radical substitution reaction in 1-(2-bromophenyl)-5-(butylsulfanyl)pyrrolidi...
Scheme 4: Approach to PBTAs via intramolecular cyclizations of 1-(2-thiophenyl)pyrroles.
Scheme 5: A new approach to PBTAs via nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazin...
Figure 2: Electrophilic centers in FPDs.
Scheme 6: Reaction of APBTT 1a with methanol (2a).
Scheme 7: Derivatization of PBTA 3aa.
Scheme 8: Reaction of APBTTs 1a–h with alcohols 2a–c. Isolated yields are given; reaction scale: a mixture of ...
Scheme 9: Side-reaction of APBTTs 1 with alcohols 2.
Scheme 10: Transformations of compounds 5 in solutions.
Scheme 11: Reaction of APBTT 1a with benzylamine.
Scheme 12: Derivatization of PBTA 7a.
Scheme 13: Reaction of APBTTs 1a–h and benzylamine. Isolated yields are given; reaction scale: a mixture of 1 ...
Scheme 14: Reaction of APBTT 1a with an excess of benzylamine.
Scheme 15: Reaction of APBTT 1a with morpholine.
Scheme 16: Reaction of APBTT 1a with aniline (11a).
Scheme 17: Derivatization of PBTA 12aa.
Scheme 18: Reaction of APBTTs 1a–h and arylamines 11a–d. Isolated yields are given; reaction scale: a mixture ...
Scheme 19: Side-reaction of APBTT 1a with arylamine 11b.
Scheme 20: Reaction of APBTT 1a with compounds 16a–d.
Scheme 21: Formation of compounds 17 as an undesired process during the synthesis of APBTTs 1.
Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles
- Péter Kisszékelyi and
- Radovan Šebesta
Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44
- synthesis of enantiomerically enriched cyclobutanes 77 [52]. Their strategy employed a three-component process in which tert-butyl (E)-2-diazo-5-arylpent-4-enoates 74 were treated with the chiral rhodium catalyst C1 to provide enantiomerically enriched bicyclobutanes 75. These highly strained compounds then
Graphical Abstract
Scheme 1: General scheme depicting tandem reactions based on an asymmetric conjugate addition followed by an ...
Scheme 2: Cu-catalyzed tandem conjugate addition of R2Zn/aldol reaction with chiral acetals.
Scheme 3: Cu-catalyzed asymmetric desymmetrization of cyclopentene-1,3-diones using a tandem conjugate additi...
Scheme 4: Stereocontrolled assembly of dialkylzincs, cyclic enones, and sulfinylimines utilizing a Cu-catalyz...
Scheme 5: Cu-catalyzed tandem conjugate addition/Mannich reaction (A). Access to chiral isoindolinones and tr...
Scheme 6: Cu-catalyzed tandem conjugate addition/nitro-Mannich reaction (A) with syn–anti or syn–syn selectiv...
Figure 1: Various chiral ligands utilized for the tandem conjugate addition/Michael reaction sequences.
Scheme 7: Cu-catalyzed tandem conjugate addition/Michael reaction: side-product formation with chalcone (A) a...
Scheme 8: Zn enolate trapping using allyl iodides (A), Stork–Jung vinylsilane reagents (B), and allyl bromide...
Scheme 9: Cu-catalyzed tandem conjugate addition/acylation through Li R2Zn enolate (A). A four-component coup...
Scheme 10: Selected examples for the Cu-catalyzed tandem conjugate addition/trifluoromethylthiolation sequence....
Scheme 11: Zn enolates trapped by vinyloxiranes: synthesis of allylic alcohols.
Scheme 12: Stereoselective cyclopropanation of Mg enolates formed by ACA of Grignard reagents to chlorocrotona...
Scheme 13: Domino aldol reactions of Mg enolates formed from coumarin and chromone.
Scheme 14: Oxidative coupling of ACA-produced Mg enolates.
Scheme 15: Tandem ACA of Grignard reagents to enones and Mannich reaction.
Scheme 16: Diastereodivergent Mannich reaction of Mg enolates with differently N-protected imines.
Scheme 17: Tandem Grignard–ACA–Mannich using Taddol-based phosphine-phosphite ligands.
Scheme 18: Tandem reaction of Mg enolates with aminomethylating reagents.
Scheme 19: Tandem reaction composed of Grignard ACA to alkynyl enones.
Scheme 20: Rh/Cu-catalyzed tandem reaction of diazo enoates leading to cyclobutanes.
Scheme 21: Tandem Grignard-ACA of cyclopentenones and alkylation of enolates.
Scheme 22: Tandem ACA of Grignard reagents followed by enolate trapping reaction with onium compounds.
Scheme 23: Mg enolates generated from unsaturated lactones in reaction with activated alkenes.
Scheme 24: Lewis acid mediated ACA to amides and SN2 cyclization of a Br-appended enolate.
Scheme 25: Trapping reactions of aza-enolates with Michael acceptors.
Scheme 26: Si enolates generated by TMSOTf-mediated ACA of Grignard reagents and enolate trapping reaction wit...
Scheme 27: Trapping reactions of enolates generated from alkenyl heterocycles (A) and carboxylic acids (B) wit...
Scheme 28: Reactions of heterocyclic Mg enolates with onium compounds.
Scheme 29: Synthetic transformations of cycloheptatrienyl and benzodithiolyl substituents.
Scheme 30: Aminomethylation of Al enolates generated by ACA of trialkylaluminum reagents.
Scheme 31: Trapping reactions of enolates with activated alkenes.
Scheme 32: Alkynylation of racemic aluminum or magnesium enolates.
Scheme 33: Trapping reactions of Zr enolates generated by Cu-ACA of organozirconium reagents.
Scheme 34: Chloromethylation of Zr enolates using the Vilsmeier–Haack reagent.
Scheme 35: Tandem conjugate borylation with subsequent protonation or enolate trapping by an electrophile.
Scheme 36: Tandem conjugate borylation/aldol reaction of cyclohexenones.
Scheme 37: Selected examples for the tandem asymmetric borylation/intramolecular aldol reaction; synthesis of ...
Scheme 38: Cu-catalyzed tandem methylborylation of α,β-unsaturated phosphine oxide in the presence of (R,Sp)-J...
Scheme 39: Cu-catalyzed tandem transannular conjugated borylation/aldol cyclization of macrocycles containing ...
Scheme 40: Stereoselective tandem conjugate borylation/Mannich cyclization: selected examples (A) and a multi-...
Scheme 41: Some examples of Cu-catalyzed asymmetric tandem borylation/aldol cyclization (A). Application to di...
Scheme 42: Atropisomeric P,N-ligands used in tandem conjugate borylation/aldol cyclization sequence.
Scheme 43: Selected examples for the enantioselective Cu-catalyzed borylation/intramolecular Michael addition ...
Scheme 44: Selected examples for the preparation of enantioenriched spiroindanes using a Cu-catalyzed tandem c...
Scheme 45: Enantioselective conjugate borylation of cyclobutene-1-carboxylic acid diphenylmethyl ester 175 wit...
Scheme 46: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 47: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 48: Cu-catalyzed tandem conjugate silylation/aldol condensation. The diastereoselectivity is controlled...
Scheme 49: Chiral Ru-catalyzed three-component coupling reaction.
Scheme 50: Rh-Phebox complex-catalyzed reductive cyclization and subsequent reaction with Michael acceptors th...
Scheme 51: Rh-catalyzed tandem asymmetric conjugate alkynylation/aldol reaction (A) and subsequent spiro-cycli...
Scheme 52: Rh-bod complex-catalyzed tandem asymmetric conjugate arylation/intramolecular aldol addition (A). S...
Scheme 53: Co-catalyzed C–H-bond activation/asymmetric conjugate addition/aldol reaction.
Scheme 54: (Diisopinocampheyl)borane-promoted 1,4-hydroboration of α,β-unsaturated morpholine carboxamides and...
Figure 2: Some examples of total syntheses that have been recently reviewed.
Scheme 55: Stereoselective synthesis of antimalarial prodrug (+)-artemisinin utilizing a tandem conjugate addi...
Scheme 56: Amphilectane and serrulatane diterpenoids: preparation of chiral starting material via asymmetric t...
Scheme 57: Various asymmetric syntheses of pleuromutilin and related compounds based on a tandem conjugate add...
Scheme 58: Total synthesis of glaucocalyxin A utilizing a tandem conjugate addition/acylation reaction sequenc...
Scheme 59: Installation of the exocyclic double bond using a tandem conjugate addition/aminomethylation sequen...
Scheme 60: Synthesis of the taxol core using a tandem conjugate addition/enolate trapping sequence with Vilsme...
Scheme 61: Synthesis of the tricyclic core of 12-epi-JBIR-23/24 utilizing a Rh-catalyzed asymmetric conjugate ...
Scheme 62: Total synthesis of (−)-peyssonoside A utilizing a Cu-catalyzed enantioselective tandem conjugate ad...
A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes
- Alena V. Dmitrieva,
- Oleg A. Levitskiy,
- Yuri K. Grishin and
- Tatiana V. Magdesieva
Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41
- )-1-benzylpyrrolidine-2-carboxamide) and its Ni(II)–Schiff base complexes formed of glycine, serine, and dehydroalanine are reported. A bulky tert-butyl substituent in the phenylene fragment precludes unwanted oxidative dimerization of the Schiff base complex, making it suitable for targeted
- electrochemically induced oxidative modification of the amino acid side chain. Experimental and DFT studies showed that the additional tert-butyl group increases the dispersion interactions in the Ni coordination environment making the complexes more conformationally rigid and provides a higher level of
- thermodynamically controlled stereoselectivity as compared to the parent Belokon complex. Additionally, functionalization with the tert-butyl group significantly enhances the reactivity of the deprotonated glycine complex towards electrophiles as compared to the anionic species formed from the original Belokon
Graphical Abstract
Scheme 1: Selected examples of the chiral ligands used for synthesis of the Ni(II)–Schiff base complexes.
Scheme 2: Synthesis of the chiral ligand L7 and its Ni(II) complexes with glycine, serine, dehydroalanine, an...
Figure 1: Fragment of the NOESY spectrum of the ʟ-(oBrCysNi)L7 complex indicating the correlation between the...
Figure 2: Low-gradient isosurfaces with low densities (blue color of the isosurface corresponds to the hydrog...
Figure 3: Saturated solutions of (GlyNi)L1 (left) and (GlyNi)L7 (right) in diethyl ether.
Figure 4: The CV curves observed for (GlyNi)L7 and (ΔAlaNi)L7 in the anodic and cathodic regions (Pt, CH3CN, ...
Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups
- Ita Hajdin,
- Romana Pajkert,
- Mira Keßler,
- Jianlin Han,
- Haibo Mei and
- Gerd-Volker Röschenthaler
Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39
- (5). This compound was synthesized smoothly within three steps in 16.6% overall yield. The synthetic route commenced from the preparation of N-protected amine 3, followed by the deprotection of benzylamine 3 to furnish 4 and ended with the diazotization of 4 using tert-butyl nitrite. As a result, the
- the reaction with tert-butyl-N-allyl carbamate 7g (1:6) while the reaction with allylcyclohexane resulted with the lowest yield (7f, 28%), probably due to the steric hindrance of the reagents. In the case of N-Boc-allylamine, improved diastereoselectivity might result from the coordination of the
Graphical Abstract
Scheme 1: Previous works (A–D) and the extension (this work).
Scheme 2: Synthesis of diethyl 2-diazo-1,1,3,3,3-pentafluoropropylphosphonate (5).
Scheme 3: Scope of the cyclopropanation. Reaction conditions: alkene (0.15 mmol), diazo compound 5 (0.1 mmol)...
Figure 1: 19F,1H-HOESY spectrum of compound 6c.
Scheme 4: Scope of the cyclopropanation. Reaction conditions: alkene (0.15 mmol), diazo compound 5 (0.1 mmol)...
Scheme 5: Addition of CuI to the diazo compound 5.
Scheme 6: Possible addition of styrene to Int2 yielding Int4_1 and Int4_2 through Int3_1 and Int3_2.
Scheme 7: Possible addition of styrene to Int2 yielding Int4_3 and Int4_4 without further intermediates.
Scheme 8: Formation of the products Pr1 to Pr4.
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
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.
Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds
- Kah Yean Lum,
- Jonathan M. White,
- Daniel J. G. Johnson,
- Vicky M. Avery and
- Rohan A. Davis
Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11
- -difluoroethanesulfinate (DFES) and zinc difluoromethanesulfinate (DFMS). In brief, a mixture of the respective scaffold, Diversinate™ (2 equiv), and TFA (5 equiv) in DMSO/CH2Cl2/H2O (5:5:2) was stirred for 30 min at room temperature and cooled to 4 °C. Then, aqueous tert-butyl hydroperoxide (TBHP, 70%, 3 equiv) was
Graphical Abstract
Scheme 1: Synthesis of ether triazolopyrazine derivatives 4–9.
Scheme 2: Synthesis of fluorinated triazolopyrazine compounds (10–18) via Diversinate™ chemistry.
Figure 1: Key HMBC, COSY and ROESY correlations, and ORTEP drawing of 18.
NaI/PPh3-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles
- Dan Liu,
- Yue Zhao and
- Frederic W. Patureau
Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5
- similar efficiency, affording oxindole 3aj as a 1:1.1 mixture of diastereomers. Interestingly, this method also enabled the synthesis of the highly sterically demanding oxindole 3ak in good yield when using a tert-butyl N-hydroxyphthalimide ester as the tert-butyl radical precursor. Importantly, a redox
Graphical Abstract
Figure 1: Representative natural products and biologically active molecules containing an oxindole moiety [7-13].
Scheme 1: Selected photocatalytic decarboxylative radical cascade reactions of N-arylamides.
Scheme 2: Arylamide substrate scope with isolated yields of products.
Scheme 3: Alkyl radical precursor scope with isolated yields of products.
Scheme 4: Selected mechanistic experiments.
A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition
- Anastasia Vepreva,
- Alexander Yanovich,
- Dmitry Dar’in,
- Grigory Kantin,
- Alexander Bunev and
- Mikhail Krasavin
Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177
- Discussion The initial attempt to involve DAS 1b in the Rh2(esp)2-catalyzed insertion reaction with 4-(tert-butyl)phenol was successful. The initial adduct 5b was not purified and was heated at 140 °C in toluene to give compound 6b in 47% yield over two steps (Scheme 2). No further optimization of the
Graphical Abstract
Figure 1: Examples of approved spirocyclic drugs.
Scheme 1: (a) Earlier reported Rh(II)-catalyzed spirocyclization of DAS with the formation of minor enol ethe...
Scheme 2: Initial attempt at Rh(II)-catalyzed O–H insertion/Claisen rearrangement.
Scheme 3: Rh2(esp)2-catalyzed O–H insertion reactions between various DAS 1 and phenols.
Scheme 4: Two-step, one-pot sequence of the Claisen rearrangement/intramolecular Michael-type spirocyclizatio...
Scheme 5: Tentative rationalization of the diastereoselectivity observed in all 5→7 transformations (shown fo...
Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone
- Motoyuki Isoda,
- Kazuyuki Sato,
- Kenta Kameda,
- Kana Wakabayashi,
- Ryota Sato,
- Hideki Minami,
- Yukiko Karuo,
- Atsushi Tarui,
- Kentaro Kawai and
- Masaaki Omote
Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176
- . Mechanistic investigation of the intramolecular cyclization The reaction mechanism of the intramolecular cyclization can only be speculative at this stage. We have already reported the generation of a rhodium hydride (Rh–H) complex from RhCl(PPh3)3 and Et2Zn, in which the reaction with tert-butyl acrylate
Graphical Abstract
Scheme 1: Previous works and this work.
Scheme 2: Scope and limitation of the rhodium-catalyzed reductive aldol-type cyclization. aIsolated yield. bD...
Scheme 3: Detection of metal-enolate and proposed mechanism of intramolecular cyclization.
Figure 1: Bioactive natural products bearing a 3-hydroxy-2-methyllactone scaffold.
Figure 2: Monocrotaline and its structural components.
Scheme 4: Synthetic route towards chiral necic acid lactone (2S,3S,4R)-2j. Conditions: a) CH3SO2NH2, AD-mix-β...
Figure 3: Molecular structure of necic acid lactone (2S,3S,4R)-2j in the crystal.
A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine
- Raphael Bereiter,
- Marco Oberlechner and
- Ronald Micura
Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172
- methanol (20 mL), then 5% hydrochloric acid (5 mL) was added and stirred for 2 hours at 50 °C. After complete deprotection (TLC reaction control!), the solvent and all volatiles were removed under reduced pressure and the crude residue was suspended in dichloromethane (6.5 mL). Afterwards, di-tert-butyl
Graphical Abstract
Scheme 1: Syntheses of C4-substituted diethyl 2,6-pyridinedicarbamates 4, passing hazardous and explosive dia...
Scheme 2: Synthesis of 1-deazaguanine (11) described by Markees and Kidder in 1956 [18].
Scheme 3: Synthesis of 1-deazaguanine (11) described by Gorton and Shive in 1957 [19].
Scheme 4: Six-step synthesis of 1-deazaguanine (11). Abbreviations: p-toluenesulfonic acid (TsOH), 4-(dimethy...
Scheme 5: 1-Deazahypoxanthine (30) synthesis described by Kubo and Hirao in 2019 [29]. For reason of simplicity o...
Scheme 6: Synthesis of 1-deazahypoxanthine (30).
Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A
- Takumi Matsumoto,
- Takefumi Kuranaga,
- Yuto Taniguchi,
- Weicheng Wang and
- Hideaki Kakeya
Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166
- determined using the modified Mosher’s method [21]. Protection of diol 25 by tert-butyl(dimethyl)silyl (TBS) group followed by selective deprotection of the primary alcohol led to 27. Finally, acid 7 was obtained from alcohol 27 through the same two-step oxidation used to obtain compound 10. Having
Graphical Abstract
Figure 1: Structures of longicatenamides A–D (1–4).
Scheme 1: Retrosynthesis of longicatenamycin A (1).
Scheme 2: Synthesis of building block 10.
Scheme 3: Synthesis of building block 7.
Scheme 4: Total synthesis of longicatenamycin A (1).
Figure 2: LC–MS extracted ion chromatograms (EICs) of synthesized and natural 1. Column: Imtakt Cadenza CD-C1...
1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes
- Artem N. Semakin,
- Ivan S. Golovanov,
- Yulia V. Nelyubina and
- Alexey Yu. Sukhorukov
Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148
- stabilization of the complex through weak hydrophobic interactions of with tert-butyl groups of Boc. We believe that by adjustment of the substituents on the amide/carbamate groups, receptors for supramolecular sensing of alcohols [44] could be designed based on 3N-TAADs of type 4. Further research in this
Graphical Abstract
Figure 1: Adamantane-based tripodal scaffolds and current work.
Scheme 1: A general strategy for the assembly of TAAD derivatives.
Scheme 2: Synthesis of acyclic precursors to 3N-TAADs, 2N,1O-TAADs, and 1N,2O-TAADs.
Scheme 3: Synthesis of 3N-TAADs, 2N,1O-TAADs, and 1N,2O-TAADs. *Yield based on compound 14.
Scheme 4: Deprotection of TAAD 8b and subsequent complexation with phenylboronic acid.
Scheme 5: Quaternization of TAADs 4c, 4e, 6a, and 8a followed by deprotection of N-Boc groups.
Figure 2: General view of the 1,4,6,10-tetraazaadamantane motif in X-ray structures of the obtained N-TAAD de...
Figure 3: (a) General structure of host–guest complexes of 3N-TAADs with water. (b) The general structure of ...
Figure 4: (a) Dynamic processes in TAADs 4 and complexation with ROH. (b) Fragment of 1H NMR spectra of Bn-4c...
Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides
- Shengli Zuo,
- Shuxiang Zheng,
- Jianjun Liu and
- Ang Zuo
Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147
- ethylenediamine monohydrochlorides were grinded with a half equivalent of 4-diethylamino (Et2N‒), 3,5-dichloro (Cl‒), or 3,5-di-tert-butyl (t-Bu‒) salicylaldehydes (blue moieties in Scheme 2) for 10 minutes. The synthesis of diamine monohydrochlorides and characterization data of mono-imine ammonium salts were
- ), half equivalent of 5-bromo (Br‒), 5-methyl, 4-diethylamino (Et2N‒), 3,5-dichloro (Cl‒), or 3,5-di-tert-butyl (t-Bu‒) salicylaldehydes (red moieties in Scheme 2), and trace methanol, followed by grinding for 20 minutes for the second reaction step to complete, monitored by TLC. A trace amount of
- between 1g (81%) and 1h (76%). Yields of 1d (79%), 1e (81%), and 1f (72%) were less than 1a‒c, caused by the steric hindrance of di-tert-butyl groups. In the aspect of characterization of salens, two singlets were shown at around 8 ppm in the 1H NMR spectrum, indicating two unsymmetrical imines. The broad
Graphical Abstract
Figure 1: Representative asymmetric Co–salen catalysts.
Scheme 1: Synthetic approach to our unsymmetrical Co–salen catalyst 2f for the asymmetric synthesis of α-aryl...
Scheme 2: Mechanochemical one-pot two-step synthesis of unsymmetrical salens 1a–h. Reaction conditions: salic...
Scheme 3: Synthesis of unsymmetrical metal–salen complexes 2. Reaction conditions a: metal acetate hydrate (1...
Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition
- Anaïs Rousseau,
- Guillaume Vincent and
- Cyrille Kouklovsky
Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143
- /z): [M + H]+ calcd 407.2377; found, 407.2359. (6R)-tert-Butyl 5-(diethoxyphosphoryloxy)-6-(2-((triisopropylsilyl)oxy)ethyl)-3,6-dihydro-2H-1,2-oxazine-2-carboxylate (10b): A solution of the enol phosphate 17 (420 mg, 1.03 mmol) in chloroform (1.8 mL) was added to a solution of the Wightman reagent 6
- ppm; HRMS (m/z): [M + Na]+ calcd 560.2779; found, 560.2775; [α]20D : +5.8 (c 1.0, CH2Cl2); ee: 8% (Whelk-O1, 1 mL/min, 95:5 hexane/EtOH, tr (R) = 14.9 min, tr (S) = 16.2 min). (6R)-tert-Butyl 5-oxo-6-(2-((triisopropylsilyl)oxy)ethyl)-1,2-oxazinane-2-carboxylate (11b): A solution of the cycloadduct 10b
- %). tert-Butyl (6R)-5-((E)-2-((2S,3S)-3-ethyl-6-oxo-3,6-dihydro-2H-pyran-2-yl)vinyl)-5-hydroxy-6-(2-((triisopropylsilyl)oxy)ethyl)-1,2-oxazinane-2-carboxylate (25): Data for 25: Rf: 0.10 (30% AcOEt/cyclohexane); 1H NMR (360 MHz, CDCl3) δ 6.97 (dd, J = 9.7, 5.5 Hz, 1H), 6.05 (d, J = 9.7 Hz, 1H), 5.95 (dd, J
Graphical Abstract
Figure 1: Structures of leustroducsins and phoslactomycins.
Figure 2: Synthetic strategy for the leustroducins and phoslactomycins.
Figure 3: strategy for the synthesis of central fragment 4: nitroso Diels–Alder reaction.
Scheme 1: A highly regio-and stereoselective nitroso Diels–Alder cycloaddition between Wightman’s reagent 6 a...
Scheme 2: Hydrolysis of enol phosphate in the unprotected cycloadduct.
Scheme 3: Attempts for hydrolysis of the enol phosphate under basic conditions.
Scheme 4: Cleavage of enol phosphate with Red-Al.
Scheme 5: Synthesis of the protected central fragment 11b.
Scheme 6: Synthesis and derivatization of the lactone fragment.
Scheme 7: Coupling reaction between alkyne 19 and ketone 11b.
Scheme 8: Coupling reaction between vinyl iodide 20 and ketone 11b.
Scheme 9: Oxidation of the acetal to the lactone.
A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH4I
- Shang-Feng Yang,
- Pei Li,
- Zi-Lin Fang,
- Sen Liang,
- Hong-Yu Tian,
- Bao-Guo Sun,
- Kun Xu and
- Cheng-Chu Zeng
Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130
- 1b). Alternatively, the oxidation of α-C–H of active methylene ketones generate α-carbon-centered radicals, thus providing another way to obtain thiazoles. Recently, Sun et al. reported a tert-butyl hydroperoxide/azodiisobutyronitrile-mediated synthesis of 2-aminothiazoles from active methylene
- presence of ᴅʟ-alanine (Table 1, entry 24). Under the optimized reaction conditions (entry 24, Table 1), the scope of the electrochemical reaction was studied using a series of active methylene ketones (Scheme 2). Various linear and branched alkyl acetoacetates including methyl, ethyl, tert-butyl, and amyl
- ethyl, n-propyl, isopropyl, n-butyl, tert-butyl and cyclohexyl moieties were also compatible with the optimized conditions, providing the corresponding 2-aminothiazoles in 24% to 65% yields (3g–l). As shown in Scheme 2, when the R1 group changed from alkyl to aryl, the target products could also be
Graphical Abstract
Scheme 1: Methods for the synthesis of thiazoles using active methylene ketones as starting materials.
Scheme 2: Substrate scope. Reaction conditions: 1 (2 mmol), 2 (1 mmol), NH4I (0.1 mmol), ᴅʟ-alanine (1 mmol),...
Scheme 3: Up-scaling experiment.
Scheme 4: Control experiments.
Scheme 5: The proposed mechanism for the one-pot electrochemical synthesis of 2-aminothiazoles mediated by NH4...
Vicinal ketoesters – key intermediates in the total synthesis of natural products
- Marc Paul Beller and
- Ulrich Koert
Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129
- thermodynamically controlled basic intramolecular aldol addition of compound 108 using the bulky amine base 2,6-di-tert-butyl-4-methylpyridine (DTBMP) led to epimerization of the methyl group and cyclization, giving preussochromone F (109) as single isolable diastereomer probably via transition state XII. The
Graphical Abstract
Scheme 1: Structures of vicinal ketoesters and examples for their typical reactivity.
Scheme 2: Doyle’s diastereoselective intramolecular aldol addition of α,β-diketoester.
Scheme 3: Synthesis of euphorikanin A (16) by intramolecular, nucleophilic addition [6].
Scheme 4: Ketoester cycloisomerization for the synthesis of preussochromone A (24) [10].
Scheme 5: Diastereoselective, intramolecular aldol reaction of an α-ketoester 28 in the synthesis of (−)-preu...
Scheme 6: Synthesis of an α-ketoester through Riley oxidation and its use in an α-ketol rearrangement in the ...
Scheme 7: Azomethine imine cycloaddition towards the synthesis of the proposed structure of palau’amine (44) [19]....
Scheme 8: Intramolecular diastereoselective carbonyl-ene reaction of an α-ketoester in the synthesis of jatro...
Scheme 9: Grignard addition to an α-ketoester and subsequent Friedel–Crafts cyclization in the synthesis of (...
Scheme 10: Diastereoselective addition to an auxiliary modified α-ketoester in the formal synthesis of (+)-cam...
Scheme 11: Intramolecular photoreduction of an α-ketoester in the synthesis of (rac)-isoretronecanol (69) [26].
Scheme 12: α-Ketoester as nucleophile in a Tsuji–Trost reaction in the synthesis of (rac)-corynoxine (76) [27].
Scheme 13: Mannich reaction of an α-ketoester in the synthesis of (+)-gracilamine (83) [28].
Scheme 14: Enantioselective aldol reaction using an α-ketoester in the synthesis of (−)-irofulven (87) [29].
Scheme 15: Allylboration of a mesoxalic acid ester in the synthesis of (+)-awajanomycin (92) [30,31].
Scheme 16: Condensation of a diamine with mesoxolate in the synthesis of (−)-aplaminal (96) [32].
Scheme 17: Synthesis of mesoxalic ester amide 102 and its use in the synthesis of (rac)-cladoniamide G (103) [33].
Scheme 18: The thermodynamically controlled, intramolecular aldol addition of a vic-tricarbonyl compound in th...
