Search results
Search for "tertiary alcohol" in Full Text gives 79 result(s) in Beilstein Journal of Organic Chemistry.
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...
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
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.
Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine
- Alessio Regni,
- Francesca Bartoccini and
- Giovanni Piersanti
Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70
- ), and, finally for 10, dehydration of the tertiary alcohol (mesylation and elimination) (Scheme 3), we decided to test their roles in the photoredox-catalyzed decarboxylative cyclization. With 8 and 10 in hand with the C4-prenyl side-chain already oxidized/functionalized, we recognized that this
Graphical Abstract
Figure 1: (a) Transformations of DMAT to different classes of ergot alkaloids. (b) and (c) Strategies for the...
Scheme 1: Synthesis of compound 5.
Scheme 2: Photoredox-catalyzed radical decarboxylative cyclization of 5.
Figure 2: Proposed reaction mechanism for photoredox-catalyzed radical decarboxylative cyclization.
Scheme 3: Synthesis of tryptophan derivatives 8 and 10.
Figure 3: Proposed reaction mechanism for photoredox-catalyzed radical decarboxylative cyclization.
Scheme 4: Methylation of 11 and the formal total synthesis of (±)-6,7-secoagroclavine.
Transition-metal-catalyzed domino reactions of strained bicyclic alkenes
- Austin Pounder,
- Eric Neufeld,
- Peter Myler and
- William Tam
Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38
- allylic alcohol isomerization in 137 resulting in the aldehyde 138. This aldehyde, in close proximity to the tertiary alcohol, leads to the production of the hemiacetal 139 which can finally undergo an oxidation producing the final bicyclo[2.2.2]lactone product 136. In 2011, the Radhakrishnan laboratory
Graphical Abstract
Figure 1: Ring-strain energies of homobicyclic and heterobicyclic alkenes in kcal mol−1. a) [2.2.1]-Bicyclic ...
Figure 2: a) Exo and endo face descriptions of bicyclic alkenes. b) Reactivity comparisons for different β-at...
Scheme 1: Ni-catalyzed ring-opening/cyclization cascade of heterobicyclic alkenes 1 with alkyl propiolates 2 ...
Scheme 2: Ni-catalyzed ring-opening/cyclization cascade of heterobicyclic alkenes 8 with β-iodo-(Z)-propenoat...
Scheme 3: Ni-catalyzed two- and three-component difunctionalizations of norbornene derivatives 15 with alkyne...
Scheme 4: Ni-catalyzed intermolecular three-component difunctionalization of oxabicyclic alkenes 1 with alkyn...
Scheme 5: Ni-catalyzed intermolecular three-component carboacylation of norbornene derivatives 15.
Scheme 6: Photoredox/Ni dual-catalyzed coupling of 4-alkyl-1,4-dihydropyridines 31 with heterobicyclic alkene...
Scheme 7: Photoredox/Ni dual-catalyzed coupling of α-amino radicals with heterobicyclic alkenes 30.
Scheme 8: Cu-catalyzed rearrangement/allylic alkylation of 2,3-diazabicyclo[2.2.1]heptenes 47 with Grignard r...
Scheme 9: Cu-catalyzed aminoboration of bicyclic alkenes 1 with bis(pinacolato)diboron (B2pin2) (53) and O-be...
Scheme 10: Cu-catalyzed borylalkynylation of oxabenzonorbornadiene (30b) with B2pin2 (53) and bromoalkynes 62.
Scheme 11: Cu-catalyzed borylacylation of bicyclic alkenes 1.
Scheme 12: Cu-catalyzed diastereoselective 1,2-difunctionalization of oxabenzonorbornadienes 30 for the synthe...
Scheme 13: Fe-catalyzed carbozincation of heterobicyclic alkenes 1 with arylzinc reagents 74.
Scheme 14: Co-catalyzed addition of arylzinc reagents of norbornene derivatives 15.
Scheme 15: Co-catalyzed ring-opening/dehydration of oxabicyclic alkenes 30 via C–H activation of arenes.
Scheme 16: Co-catalyzed [3 + 2] annulation/ring-opening/dehydration domino reaction of oxabicyclic alkenes 1 w...
Scheme 17: Co-catalyzed enantioselective carboamination of bicyclic alkenes 1 via C–H functionalization.
Scheme 18: Ru-catalyzed cyclization of oxabenzonorbornene derivatives with propargylic alcohols for the synthe...
Scheme 19: Ru-catalyzed coupling of oxabenzonorbornene derivatives 30 with propargylic alcohols and ethers 106...
Scheme 20: Ru-catalyzed ring-opening/dehydration of oxabicyclic alkenes via the C–H activation of anilides.
Scheme 21: Ru-catalyzed of azabenzonorbornadiene derivatives with arylamides.
Scheme 22: Rh-catalyzed cyclization of bicyclic alkenes with arylboronate esters 118.
Scheme 23: Rh-catalyzed cyclization of bicyclic alkenes with dienyl- and heteroaromatic boronate esters.
Scheme 24: Rh-catalyzed domino lactonization of doubly bridgehead-substituted oxabicyclic alkenes with seconda...
Scheme 25: Rh-catalyzed domino carboannulation of diazabicyclic alkenes with 2-cyanophenylboronic acid and 2-f...
Scheme 26: Rh-catalyzed synthesis of oxazolidinone scaffolds 147 through a domino ARO/cyclization of oxabicycl...
Scheme 27: Rh-catalyzed oxidative coupling of salicylaldehyde derivatives 151 with diazabicyclic alkenes 130a.
Scheme 28: Rh-catalyzed reaction of O-acetyl ketoximes with bicyclic alkenes for the synthesis of isoquinoline...
Scheme 29: Rh-catalyzed domino coupling reaction of 2-phenylpyridines 165 with oxa- and azabicyclic alkenes 30....
Scheme 30: Rh-catalyzed domino dehydrative naphthylation of oxabenzonorbornadienes 30 with N-sulfonyl 2-aminob...
Scheme 31: Rh-catalyzed domino dehydrative naphthylation of oxabenzonorbornadienes 30 with arylphosphine deriv...
Scheme 32: Rh-catalyzed domino ring-opening coupling reaction of azaspirotricyclic alkenes using arylboronic a...
Scheme 33: Tandem Rh(III)/Sc(III)-catalyzed domino reaction of oxabenzonorbornadienes 30 with alkynols 184 dir...
Scheme 34: Rh-catalyzed asymmetric domino cyclization and addition reaction of 1,6-enynes 194 and oxa/azabenzo...
Scheme 35: Rh/Zn-catalyzed domino ARO/cyclization of oxabenzonorbornadienes 30 with phosphorus ylides 201.
Scheme 36: Rh-catalyzed domino ring opening/lactonization of oxabenzonorbornadienes 30 with 2-nitrobenzenesulf...
Scheme 37: Rh-catalyzed domino C–C/C–N bond formation of azabenzonorbornadienes 30 with aryl-2H-indazoles 210.
Scheme 38: Rh/Pd-catalyzed domino synthesis of indole derivatives with 2-(phenylethynyl)anilines 212 and oxabe...
Scheme 39: Rh-catalyzed domino carborhodation of heterobicyclic alkenes 30 with B2pin2 (53).
Scheme 40: Rh-catalyzed three-component 1,2-carboamidation reaction of bicyclic alkenes 30 with aromatic and h...
Scheme 41: Pd-catalyzed diarylation and dialkenylation reactions of norbornene derivatives.
Scheme 42: Three-component Pd-catalyzed arylalkynylation reactions of bicyclic alkenes.
Scheme 43: Three-component Pd-catalyzed arylalkynylation reactions of norbornene and DFT mechanistic study.
Scheme 44: Pd-catalyzed three-component coupling N-tosylhydrazones 236, aryl halides 66, and norbornene (15a).
Scheme 45: Pd-catalyzed arylboration and allylboration of bicyclic alkenes.
Scheme 46: Pd-catalyzed, three-component annulation of aryl iodides 66, alkenyl bromides 241, and bicyclic alk...
Scheme 47: Pd-catalyzed double insertion/annulation reaction for synthesizing tetrasubstituted olefins.
Scheme 48: Pd-catalyzed aminocyclopropanation of bicyclic alkenes 1 with 5-iodopent-4-enylamine derivatives 249...
Scheme 49: Pd-catalyzed, three-component coupling of alkynyl bromides 62 and norbornene derivatives 15 with el...
Scheme 50: Pd-catalyzed intramolecular cyclization/ring-opening reaction of heterobicyclic alkenes 30 with 2-i...
Scheme 51: Pd-catalyzed dimer- and trimerization of oxabenzonorbornadiene derivatives 30 with anhydrides 268.
Scheme 52: Pd-catalyzed Catellani-type annulation and retro-Diels–Alder of norbornadiene 15b yielding fused xa...
Scheme 53: Pd-catalyzed hydroarylation and heteroannulation of urea-derived bicyclic alkenes 158 and aryl iodi...
Scheme 54: Access to fused 8-membered sulfoximine heterocycles 284/285 via Pd-catalyzed Catellani annulation c...
Scheme 55: Pd-catalyzed 2,2-bifunctionalization of bicyclic alkenes 1 generating spirobicyclic xanthone deriva...
Scheme 56: Pd-catalyzed Catellani-type annulation and retro-Diels–Alder of norbornadiene (15b) producing subst...
Scheme 57: Pd-catalyzed [2 + 2 + 1] annulation furnishing bicyclic-fused indanes 281 and 283.
Scheme 58: Pd-catalyzed ring-opening/ring-closing cascade of diazabicyclic alkenes 130a.
Scheme 59: Pd-NHC-catalyzed cyclopentannulation of diazabicyclic alkenes 130a.
Scheme 60: Pd-catalyzed annulation cascade generating diazabicyclic-fused indanones 292 and indanols 294.
Scheme 61: Pd-catalyzed skeletal rearrangement of spirotricyclic alkenes 176 towards large polycyclic benzofur...
Scheme 62: Pd-catalyzed oxidative annulation of aromatic enamides 298 and diazabicyclic alkenes 130a.
Scheme 63: Accessing 3,4,5-trisubstituted cyclopentenes 300, 301, 302 via the Pd-catalyzed domino reaction of ...
Scheme 64: Palladacycle-catalyzed ring-expansion/cyclization domino reactions of terminal alkynes and bicyclic...
Scheme 65: Pd-catalyzed carboesterification of norbornene (15a) with alkynes, furnishing α-methylene γ-lactone...
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
- formation of the central eight-membered ring. To achieve this goal, a model study was first conducted to define the best reaction conditions. Thus, coupling of the lithio-derivative of 89 to hydrindanone 87 proceeded smoothly to furnish the expected tertiary alcohol 90 with a high stereo- and
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.
Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones
- Benedikt Kolb,
- Daniela Silva dos Santos,
- Sanja Krause,
- Anna Zens and
- Sabine Laschat
Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17
- deprotonated with LDA at −78 °C in THF and subsequently methylated to give 34 in 99%, followed by treatment with alkynyl Grignard reagent to give the tertiary alcohol 35 in 71% yield. Final elimination with MsCl and NEt3 yielded the desired enyne 25q (49%). When terpene enynes 25p and 25q were submitted to the
Graphical Abstract
Scheme 1: Examples of biologically active compounds with (2Ε,4E)-unsaturated ketone units.
Scheme 2: Selected examples for the synthesis of conjugated dienones from the literature [6-21].
Scheme 3: Previous work of hydrozirconations with Schwartz's reagent and our work [54,55,57,58,61,62].
Scheme 4: Synthesis of substituted enynes 25f–o via Corey–Fuchs reaction and Hunsdiecker reaction.
Scheme 5: Synthesis of non-natural (a) and natural (b) dienone-containing terpenes: synthesis of β-ionone (3)....
Synthetic study toward tridachiapyrone B
- Morgan Cormier,
- Florian Hernvann and
- Michaël De Paolis
Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183
- oxidative anionic oxy-Cope rearrangement of the tertiary alcohol arising from the 1,2-addition of a 1,3-dimethylallyl reagent to 2,5-cyclohexadienone connected to the α’-methoxy-γ-pyrone motif. Keywords: α’-methoxy-γ-pyrone; 2,5-cyclohexadienone; oxy-Cope; quaternary carbon; Robinson-type annulation
Graphical Abstract
Scheme 1: Routes to crispatene, photodeoxytridachione, aureothin, and tridachiapyrone B.
Scheme 2: Desymmetrization of 2.
Scheme 3: Addition of lithiocyclopentadiene to pyrone 2.
Scheme 4: Plan to reach 2,5-cyclohexadienone 5.
Scheme 5: Preparation of 2,5-cyclohexadienone 5.
Scheme 6: Attempts to perform the conjugate addition.
Scheme 7: Updated route to tridachiapyrone B.
Total synthesis of grayanane natural products
- Nicolas Fay,
- Rémi Blieck,
- Cyrille Kouklovsky and
- Aurélien de la Torre
Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181
- -disubstituted olefin and reductive epoxide ring-opening giving triol 18. After oxidation of the primary and the secondary alcohols with Dess–Martin periodinane, the remaining tertiary alcohol was protected as a MOM ether and the silyl ether protecting group was removed. The obtained intermediate 19 was then a
- corresponding ketone was achieved using Dess–Martin periodinane with a pyridine buffer. Addition of Me3SiCH2Li efficiently afforded the Peterson adduct 33. The 1,1-disubtituted alkene was then submitted to Mukaiyma hydration to form the tertiary alcohol, in presence of Mn(dpm)3, PhSiH3 and O2. Then, the ketone
- secondary alcohol was oxidized by DMP, the tertiary alcohol was triflated, 4-phenylpyridine was added and the mixture was heated at 80 °C for 14 h. The intermediate carbocation was trapped by the terminal olefin, generating a dienone 51 after deprotonation at the relatively acidic position C2. A singlet
Graphical Abstract
Figure 1: General structure of grayanane natural products.
Scheme 1: Grayanane biosynthesis.
Scheme 2: Matsumoto’s relay approach.
Scheme 3: Shirahama’s total synthesis of (–)-grayanotoxin III.
Scheme 4: Newhouse’s syntheses of fragments 25 and 29.
Scheme 5: Newhouse’s total synthesis of principinol D.
Scheme 6: Ding’s total synthesis of rhodomolleins XX and XXII.
Scheme 7: First key step of Luo’s strategy.
Scheme 8: Luo’s total synthesis of grayanotoxin III.
Scheme 9: Synthesis of principinol E and rhodomollein XX.
Scheme 10: William’s synthetic effort towards pierisformaside C.
Scheme 11: Hong’s synthetic effort towards rhodojaponin III.
Scheme 12: Recent strategies for grayanane synthesis.
Synthesis of (−)-halichonic acid and (−)-halichonic acid B
- Keith P. Reber and
- Emma L. Niner
Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174
- a tertiary alcohol. The structures of compounds (+)-1 and (+)-2 were elucidated through a combination of HRMS and NMR spectroscopy, while the relative configuration of each compound was established through nuclear Overhauser effect (NOE) correlations. Additionally, the absolute configuration of each
Graphical Abstract
Figure 1: Structures of halichonic acid ((+)-1) and halichonic acid B ((+)-2).
Scheme 1: Synthesis of (−)-7-amino-7,8-dihydrobisabolene (4) and its conversion to cyclization precursor 7.
Scheme 2: Synthesis of the halichonic acids via a key intramolecular aza-Prins cyclization.
Scheme 3: Proposed intermediates for the intramolecular aza-Prins reaction leading to the formation of ethyl ...
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
- have therefore completed a quick, efficient and selective access to the central core of leustroducsins/phoslactomycins using an asymmetric nitroso Diels–Alder reaction. This fragment displays a ketone function that will be used for coupling with the lactone fragment 3 by generation of the tertiary
- alcohol. Studies in fragment coupling We have previously reported the synthesis of the lactone fragment by catalytic asymmetric [2 + 2] cycloaddition followed by ring extension [18]. The initial product was the TMS-acetylene 18 which could be easily desilylated to give 21. However, model studies for
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.
Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure
- Irene Torres-García,
- Josefa L. López-Martínez,
- Rocío López-Domene,
- Manuel Muñoz-Dorado,
- Ignacio Rodríguez-García and
- Miriam Álvarez-Corral
Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132
- compound 2. The isopropenyl residue of the target compound 1 was assembled through a two-step sequence. The first one was the addition of an excess of methylmagnesium bromide to the ester 2, that completed the carbon skeleton. The second step was the pH-controlled regioselective dehydration of the tertiary
- alcohol 6 with amberlyst-15® leading to the monoterpene 1. Other systems tested for the elimination of the hydroxy group in 6 were pyridinium p-toluenesulfonate (PPTS) and camphorsulfonic acid (CSA), that gave poorer results, failing to afford a single product. On the other hand, lactone 5 could also be
Graphical Abstract
Scheme 1: Retrosynthetic scheme of the target molecule 1.
Scheme 2: Synthesis of dihydrofuran-monoterpenoid 1. a) i. O3, −78 °C; ii. PPh3, rt, 76%; b) 1-bromobut-2-yne...
Scheme 3: Racemic resolution of allenol 3 and synthesis of derivatives. a) Lipase AK, vinyl acetate, t-BuOMe,...
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
- precursor for an intramolecular Friedel–Crafts cyclization (Scheme 9) [24]. Therefore, phenylacetaldehyde 52 was converted to the alcohol 53, which was esterified with the α-ketoacid 54 to give ketoester 55. Grignard addition to the keto carbonyl and subsequent TBS deprotection delivered the tertiary
- alcohol 56, which was dehydroxylated to the diastereomeric cations VIII and IX. Friedel–Crafts reaction gave diastereomeric lactones 57 and 58. The major diastereomer 58 could be converted to the complex polyphenol (−)-hopeanol (59) in seven further steps. (+)-Camptothecin In the formal synthesis of 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...
A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions
- Tommaso Lorenzetto,
- Fabrizio Fabris and
- Alessandro Scarso
Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38
- alkene in the side chain [56] for which the reaction catalyzed by the same capsule led to the protonation of the alkene unit with an intramolecular nucleophilic attack by the alcohol moiety forming a final cyclic ether product. In the latter case the tertiary alcohol could not easily eliminate water and
Graphical Abstract
Scheme 1: Resorcin[4]arene 1 forming the corresponding hexameric capsule 16 and the species used for control ...
Scheme 2: Carbonyl–ene intramolecular cyclization of (S)-citronellal to the corresponding diastereoisomeric c...
Figure 1: 1H NMR spectra in water-saturated CDCl3 except for G. A: [16] (7.5 mM); B: citronellal; C: citronel...
Scheme 3: Dehydration reaction of 1,1-diphenylethanol to 1,1-diphenylethylene.
Figure 2: 1H NMR spectra in water-saturated CDCl3 except for G. A: [16] (7.5 mM); B: 1,1-diphenylethanol; C: ...
Scheme 4: Possible isomerization products from β-pinene and α-pinene.
Figure 3: 1H NMR spectra in water-saturated CDCl3 except for G. A: [16] (7.5 mM); B: α-pinene; C: α-pinene (7...
Figure 4: 1H NMR spectra in water-saturated CDCl3 except for G. A: [16] (7.5 mM); B: β-pinene; C: β-pinene (7...
Figure 5: 1H NMR spectra in water-saturated CDCl3, except for E. A: [16] (7.5 mM); B: β-pinene; C: β-pinene (...
The enzyme mechanism of patchoulol synthase
- Houchao Xu,
- Bernd Goldfuss,
- Gregor Schnakenburg and
- Jeroen S. Dickschat
Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2
- three Me groups, four olefinic carbons (two quarternary, one CH and one CH2), and a tertiary alcohol, suggesting the structure of an oxidised (dehydrogenated) bicyclic sesquiterpene alcohol (Figure 4). The 1H,1H-COSY spectrum revealed one large contiguous spin system C-2-3-4(15)-5-6-7-8-9. HMBC
Graphical Abstract
Figure 1: Initially assigned structures for patchoulol by Treibs (1) and by Büchi (2). Structures of patchoul...
Scheme 1: Biosynthesis of patchoulol (part I). A) Cyclisation mechanism from FPP to 3 as suggested by Croteau...
Scheme 2: Biosynthesis of patchoulol (part II). A) Cyclisation mechanism from FPP to 3 as suggested by Akhila...
Scheme 3: Biosynthesis of patchoulol (part III). A) Cyclisation mechanism from FPP to 3 as suggested by Faral...
Figure 2: ORTEP representation of patchoulol (3). Cu Kα, Flack parameter: −0.1(2); P2(true) = 1.000, P3(false...
Scheme 4: Determination of the absolute configurations of compounds 3 and 12 through stereoselective labellin...
Scheme 5: Labelling experiments on the biosynthesis of patchoulol (3, part 1). Black dots indicate 13C-labell...
Scheme 6: Labelling experiments on the biosynthesis of patchoulol (3, part 2). Black dots indicate 13C-labell...
Figure 3: Energy profile from DFT calculations (Gibbs energies at 298 K, mPW1PW91/6-311 + G(d,p)//B97D3/6-31G...
Figure 4: Structure elucidation of (2S,3S,7S,10R)-guaia-1,11-dien-10-ol (17) and structure of its known stere...
α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions
- Scott Benz and
- Andrew S. Murkin
Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172
- (Figure 15). Next, ring-expanding rearrangement is proposed to form 75. Finally, the C7 ketone is reduced, the C8–C9 bond is oxidized back to an alkene, the C5–C6 double bond is oxidized to an epoxide, and C15 is oxidized to a tertiary alcohol to yield 72. The authors not only structurally characterized
Graphical Abstract
Figure 1: Generalized α-ketol or α-iminol rearrangement.
Figure 2: Nickel(II)-catalyzed enantioselective rearrangement of ketol 3 to form the ring-expanded and chiral...
Figure 3: Enantioselective ring expansion of β-hydroxy-α-dicarbonyl 6 catalyzed by a chiral copper-bisoxazoli...
Figure 4: Enantioselective rearrangement of ketols 9 and 12 and hydroxyaldimine 14 catalyzed by Al(III) or Sc...
Figure 5: Asymmetric rearrangement of α,α-dialkyl-α-siloxyaldehydes 16 to α-siloxyketones 17 catalyzed by chi...
Figure 6: BF3-promoted diastereospecific rearrangement of α-ketol 21 to difluoroalkoxyborane 22.
Figure 7: In the presence of a gold catalyst and water in 1,4-dioxane, 1-alkynylbutanol derivatives undergo t...
Figure 8: The diastereospecific α-ketol rearrangement of 32 to 33, part of the total synthesis of periconiano...
Figure 9: Two α-ketol rearrangements, one catalyzed by silica gel on 38 and the other by NaOMe on both 38 and ...
Figure 10: α-Ketol rearrangement of triumphalone (41) to isotriumphalone (42) via ring contraction.
Figure 11: Tandem reaction of strophasterol A synthetic intermediate 43 to 44 through a vinylogous α-ketol rea...
Figure 12: Tandem reaction consisting of a Diels–Alder cycloaddition followed by an α-ketol rearrangement, par...
Figure 13: Single-pot reaction consisting of Claisen and α-ketol rearrangements, part of the total synthesis o...
Figure 14: Enzyme-catalyzed α-ketol rearrangements. a) Ketol-acid reductoisomerase (KAR) catalyzes the rearran...
Figure 15: The conversion of asperfloroid (73) to asperflotone (72), featuring the ring-expanding α-ketol rear...
Figure 16: Hypothetical interconversion of natural products prekinamycin (76) and isoprekinamycin (77) and che...
Figure 17: Proposed biosynthetic pathway converting acylphloroglucinol (87) to isolated elodeoidins A–H 92–96....
Figure 18: α-Iminol rearrangements catalyzed by VANOL Zr (99). The rearrangement can be conducted with preform...
Figure 19: α-Iminol rearrangements catalyzed by silica gel and montmorillonite K 10. a) For 102a (102 with R =...
Figure 20: Synthesis of tryptamines 110 via a ring-contracting α‑iminol rearrangement. A mechanism for the fin...
Figure 21: Tandem synthesis of functionalized α-amino cyclopentanones 119 from heteroarenes 115 and cyclobutan...
Figure 22: Four eburnane-type alkaloid natural products 122–125 were synthesized from common intermediate 127,...
Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines
- Matthew J. Fleming and
- David M. Hodgson
Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155
- , α-methoxyhexyllithium derived from stannane 7 [14][15] was reacted with terminal epoxide 5, which gave the allylic alcohol 8 (79%, E/Z = 73:27, Scheme 4). This organolithium also proved reactive with 2,2-disubstituted epoxide 9, giving allylic tertiary alcohol 10 (72%, E/Z = 82:18). A trisubstituted
Graphical Abstract
Scheme 1: Dimerisation of α-lithio epoxides or aziridines [3-5].
Scheme 2: Proposed eliminative cross-coupling of carbenoids to allylic alcohols (X = O) or allylic amines (X ...
Scheme 3: Allylic alcohol 6 by one-carbon homologation from epoxide 5.
Scheme 4: Internal allylic alcohols from epoxides and stannane 7.
Scheme 5: Cyclopropylidene synthesis from epoxide 5.
Scheme 6: Synthesis of vinylsilane 14.
Scheme 7: Allylic alcohol 8 from epoxide 5 and sulfone 15.
Scheme 8: Allylic amines from aziridine 17.
Scheme 9: Cyclopropylidene synthesis from aziridine 20.
Scheme 10: Cinnamylamine 23 synthesis from aziridine 17.
Scheme 11: Cinnamylamine 23 synthesis from isopropyl or neopentyl benzylic ethers 26 and 27.
Recent advances in Cu-catalyzed C(sp3)–Si and C(sp3)–B bond formation
- Balaram S. Takale,
- Ruchita R. Thakore,
- Elham Etemadi-Davan and
- Bruce H. Lipshutz
Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67
Graphical Abstract
Scheme 1: Pharmaceuticals possessing a silicon or boron atom.
Scheme 2: The first Cu-catalyzed C(sp3)–Si bond formation.
Scheme 3: Conversion of benzylic phosphate 6 to the corresponding silane.
Scheme 4: Conversion of alkyl triflates to alkylsilanes.
Scheme 5: Conversion of secondary alkyl triflates to alkylsilanes.
Scheme 6: Conversion of alkyl iodides to alkylsilanes.
Scheme 7: Trapping of intermediate radical through cascade reaction.
Scheme 8: Radical pathway for conversion of alkyl iodides to alkylsilanes.
Scheme 9: Conversion of alkyl ester of N-hydroxyphthalimide to alkylsilanes.
Scheme 10: Conversion of gem-dibromides to bis-silylalkanes.
Scheme 11: Conversion of imines to α-silylated amines (A) and the reaction pathway (B).
Scheme 12: Conversion of N-tosylimines to α-silylated amines.
Scheme 13: Screening of diamine ligands.
Scheme 14: Conversion of N-tert-butylsulfonylimines to α-silylated amines.
Scheme 15: Conversion of aldimines to nonracemic α-silylated amines.
Scheme 16: Conversion of N-tosylimines to α-silylated amines.
Scheme 17: Reaction pathway [A] and conversion of aldehydes to α-silylated alcohols [B].
Scheme 18: Conversion of aldehydes to benzhydryl silyl ethers.
Scheme 19: Conversion of ketones to 1,2-diols (A) and conversion of imines to 1,2-amino alcohols (B).
Scheme 20: Ligand screening (A) and conversion of aldehydes to α-silylated alcohols (B).
Scheme 21: Conversion of aldehydes to α-silylated alcohols.
Scheme 22: 1,4-Additions to α,β-unsaturated ketones.
Scheme 23: 1,4-Additions to unsaturated ketones to give β-silylated derivatives.
Scheme 24: Additions onto α,β-unsaturated lactones to give β-silylated lactones.
Scheme 25: Conversion of α,β-unsaturated to β-silylated lactams.
Scheme 26: Conversion of N-arylacrylamides to silylated oxindoles.
Scheme 27: Conversion of α,β-unsaturated carbonyl compounds to silylated tert-butylperoxides.
Scheme 28: Catalytic cycle for Cu(I) catalyzed α,β-unsaturated compounds.
Scheme 29: Conversion of p-quinone methides to benzylic silanes.
Scheme 30: Conversion of α,β-unsaturated ketimines to regio- and stereocontrolled allylic silanes.
Scheme 31: Conversion of α,β-unsaturated ketimines to enantioenriched allylic silanes.
Scheme 32: Regioselective conversion of dienedioates to allylic silanes.
Scheme 33: Conversion of alkenyl-substituted azaarenes to β-silylated adducts.
Scheme 34: Conversion of conjugated benzoxazoles to enantioenriched β-silylated adducts.
Scheme 35: Conversion of α,β-unsaturated carbonyl indoles to α-silylated N-alkylated indoles.
Scheme 36: Conversion of β-amidoacrylates to α-aminosilanes.
Scheme 37: Conversion of α,β-unsaturated ketones to enantioenriched β-silylated ketones, nitriles, and nitro d...
Scheme 38: Regio-divergent silacarboxylation of allenes.
Scheme 39: Silylation of diazocarbonyl compounds, (A) asymmetric and (B) racemic.
Scheme 40: Enantioselective hydrosilylation of alkenes.
Scheme 41: Conversion of 3-acylindoles to indolino-silanes.
Scheme 42: Proposed mechanism for the silylation of 3-acylindoles.
Scheme 43: Silyation of N-chlorosulfonamides.
Scheme 44: Conversion of acyl silanes to α-silyl alcohols.
Scheme 45: Conversion of N-tosylaziridines to β-silylated N-tosylamines.
Scheme 46: Conversion of N-tosylaziridines to silylated N-tosylamines.
Scheme 47: Conversion of 3,3-disubstituted cyclopropenes to silylated cyclopropanes.
Scheme 48: Conversion of conjugated enynes to 1,3-bis(silyl)propenes.
Scheme 49: Proposed sequence for the Cu-catalyzed borylation of substituted alkenes.
Scheme 50: Cu-catalyzed synthesis of nonracemic allylic boronates.
Scheme 51: Cu–NHC catalyzed synthesis of α-substituted allylboronates.
Scheme 52: Synthesis of α-chiral (γ-alkoxyallyl)boronates.
Scheme 53: Cu-mediated formation of nonracemic cis- or trans- 2-substituted cyclopropylboronates.
Scheme 54: Cu-catalyzed synthesis of γ,γ-gem-difluoroallylboronates.
Scheme 55: Cu-catalyzed hydrofunctionalization of internal alkenes and vinylarenes.
Scheme 56: Cu-catalyzed Markovnikov and anti-Markovnikov borylation of alkenes.
Scheme 57: Cu-catalyzed borylation/ortho-cyanation/Cope rearrangement.
Scheme 58: Borylfluoromethylation of alkenes.
Scheme 59: Cu-catalyzed synthesis of tertiary nonracemic alcohols.
Scheme 60: Synthesis of densely functionalized and synthetically versatile 1,2- or 4,3-borocyanated 1,3-butadi...
Scheme 61: Cu-catalyzed trifunctionalization of allenes.
Scheme 62: Cu-catalyzed selective arylborylation of arenes.
Scheme 63: Asymmetric borylative coupling between styrenes and imines.
Scheme 64: Regio-divergent aminoboration of unactivated terminal alkenes.
Scheme 65: Cu-catalyzed 1,4-borylation of α,β-unsaturated ketones.
Scheme 66: Cu-catalyzed protodeboronation of α,β-unsaturated ketones.
Scheme 67: Cu-catalyzed β-borylation of α,β-unsaturated imines.
Scheme 68: Cu-catalyzed synthesis of β-trifluoroborato carbonyl compounds.
Scheme 69: Asymmetric 1,4-borylation of α,β-unsaturated carbonyl compounds.
Scheme 70: Cu-catalyzed ACB and ACA reactions of α,β-unsaturated 2-acyl-N-methylimidazoles.
Scheme 71: Cu-catalyzed diborylation of aldehydes.
Scheme 72: Umpolung pathway for chiral, nonracemic tertiary alcohol synthesis (top) and proposed mechanism for...
Scheme 73: Cu-catalyzed synthesis of α-hydroxyboronates.
Scheme 74: Cu-catalyzed borylation of ketones.
Scheme 75: Cu-catalyzed borylation of unactivated alkyl halides.
Scheme 76: Cu-catalyzed borylation of allylic difluorides.
Scheme 77: Cu-catalyzed borylation of cyclic and acyclic alkyl halides.
Scheme 78: Cu-catalyzed borylation of unactivated alkyl chlorides and bromides.
Scheme 79: Cu-catalyzed decarboxylative borylation of carboxylic acids.
Scheme 80: Cu-catalyzed borylation of benzylic, allylic, and propargylic alcohols.
Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands
- Shohei Mimura,
- Sho Mizushima,
- Yohei Shimizu and
- Masaya Sawamura
Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50
- silane PMHS gave only trace amounts of the product. The nature of the alcoholic protonation reagent also had a strong impact. The presence of a tertiary alcohol, t-AmOH or t-BuOH, was essential for the reaction to occur with a reasonable yield, while iPrOH and MeOH markedly suppressed the reaction (Table
Combination of multicomponent KA2 and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones
- Riccardo Innocenti,
- Elena Lenci,
- Gloria Menchi and
- Andrea Trabocchi
Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23
- one-pot, resulting in the generation of the stereochemically dense epoxyalcohol 37 in 68% overall yield. The treatment of compound 5 with EtMgBr as a Grignard reagent in the presence of CeCl3 gave the corresponding tertiary alcohol 38 with similar stereochemical features as of 36 in the formation of
Graphical Abstract
Figure 1: Chemical structure of representative approved drugs containing a spirocyclic moiety.
Scheme 1: Synthetic strategies for accessing pyrrolocyclopentenone derivatives, including the novel couple/pa...
Scheme 2: Couple/pair approach using combined KA2 and Pauson–Khand multicomponent reactions.
Scheme 3: Follow-up chemistry on compound 5 taking advantage of the enone chemistry. Reaction conditions. (i)...
Figure 2: Top: Selected NOE contacts from NOESY 1D spectra of compound 36; bottom: low energy conformer of 36...
Figure 3: PCA plot resulting from the correlation between PC1 vs PC2, showing the positioning in the chemical...
Figure 4: PMI plot showing the skeletal diversity of compounds 3–39 (blue diamonds) with respect to the refer...
[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides
- Katarzyna Włodarczyk,
- Piotr Borowski and
- Marek Stankevič
Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11
- dissociation are ca. 34.6 kcal/mol for the secondary alcohol 8, ca. 23.3 kcal/mol for the mesylate 60, and ca. 25.0 kcal/mol for the tertiary alcohol 20, as estimated by DFT calculations. The value for mesylate roughly fitted the range according to which the reaction may proceed at room temperature. For
- , leading to intermediate I, and the overall transformation proceeded with remarkable stabilization. In the next step, dissociation of the C−O bond occurred through transition state II, finally leading to alkene III. The activation energy for the C−O bond cleavage in 20, a tertiary alcohol, was similar to
- , mesylate (SP)-60, and alkenylphosphine sulfide (SP)-65 were subjected to the reaction with Lewis-acidic AlCl3 (Scheme 12). Rearrangement of the tertiary alcohol (SP)-17 proceeded very efficiently, affording the corresponding product in high yield. Unfortunately, the stereoselectivity of the reaction
Graphical Abstract
Scheme 1: Arbusov, phospha-Fries, and phospha-Brook rearrangements.
Scheme 2: Cyclization of 1a and 1b under acidic conditions.
Scheme 3: The synthesis of P-stereogenic β-hydroxyalkylphosphine sulfides.
Scheme 4: Cyclization of 8 and 19 in the presence of H3PO4.
Scheme 5: Cyclization of (SP)-19 in the presence of H3PO4.
Figure 1: 1H NMR spectra of compounds 12 and 29.
Figure 2: 13C NMR spectra of compounds 12 and 29.
Scheme 6: Synthesis of the alkenylphosphine sulfides used in study.
Scheme 7: The reaction of mesylate compounds with Lewis-acidic AlCl3.
Scheme 8: The reaction of alkenylphosphine sulfides with AlCl3.
Scheme 9: Rearrangement of 20 in the presence of Brønsted acid. The calculated energies next to the arrows ar...
Scheme 10: Rearrangement of 20 in the presence of Lewis acid. The calculated energies next to the arrows are r...
Scheme 11: The synthesis of chiral substrates for rearrangement reactions.
Scheme 12: The reaction of (SP)-60 and (SP)-65 with AlCl3.
Scheme 13: Reaction of chiral β-hydroxyalkylphosphine sulfides with Brønsted acid.
Scheme 14: Attempted cyclization of enantiomerically enriched 53 and 46.
Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.
- Annika Stein,
- Dave Compera,
- Bianka Karge,
- Mark Brönstrup and
- Jakob Franke
Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196
- (δH 3.37 (H-6)), and a tertiary alcohol at C-14 (δC 80.9 ppm). COSY correlations supported by HMBC analysis (Figure 2A) revealed an intact ABCD ring system with a substitution pattern identical to 4β-hydroxywithanolide E (1). Only a single, striking difference was noted: C-17 was shifted from 87.8 to
Graphical Abstract
Figure 1: Withanolides from Physalis peruviana. A) Structures of the newly characterised truncated withanolid...
Figure 2: Key NMR correlations. (A) COSY and HMBC correlations for irinan A (2). (B) COSY and HMBC correlatio...
Figure 3: Structures and biosynthesis of androstanes. (A) Androstane backbone and androsterone (7) as a typic...
Figure 4: Intrinsic reactivity of 4ß-hydroxywithanolide E (1) under acidic/basic and oxidative conditions, re...
A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates
- András György Németh,
- György Miklós Keserű and
- Péter Ábrányi-Balogh
Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155
- %, respectively) that might be attributed either to steric hindrance or the growing instability of the conjugate base of the secondary and tertiary alcohol, respectively. The present method provided the allylic derivative 3j in 72% yield, however, applying ethylene glycol resulted in 3k in 34% yield only. In the
Graphical Abstract
Scheme 1: Synthetic routes to O-thiocarbamates and dithiocarbamates.
Scheme 2: Substrate scope of isocyanides. aReaction conditions: 1 (1 mmol), S8 (2 mmol), 2a (2mmol), NaH (2 m...
Scheme 3: Substrate scope of alcohols. Reaction conditions: 1a (1 mmol), S8 (2 mmol), 2 (2mmol), NaH (2 mmol)...
Scheme 4: Substrate scope of thiols. Reaction conditions: 1a (1 mmol), S8 (1.2 mmol), 4 (2 mmol), NaOH (2 mmo...
Scheme 5: Scaled-up synthesis for 3a.
Scheme 6: Multicomponent domino synthesis of quinazolinone 7.
Scheme 7: Control experiments.
Scheme 8: Proposed mechanism.
Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids
- Herman O. Sintim,
- Hamad H. Al Mamari,
- Hasanain A. A. Almohseni,
- Younes Fegheh-Hassanpour and
- David M. Hodgson
Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116
- selective deprotection in α-diazo ester 23 in the presence of the tertiary TBS ether. It was considered important that the tertiary alcohol remain masked during projected oxidation of the released secondary alcohol to give the ketone functionality in the cycloaddition substrate, as otherwise essentially
- group strategy led us to TES protection at both alcohols, on the basis that this group should be robust enough to withstand the enolate manipulation chemistry, that desilylation of the secondary TES ether during acetonide removal could be restored in the subsequent tertiary alcohol silylation step, that
Graphical Abstract
Figure 1: Squalestatin S1/zaragozic acid A (1) and DDSQ (2).
Scheme 1: Carbonyl ylide cycloaddition–rearrangement to the squalestatin core [12,13].
Scheme 2: Tartrate alkylation strategy to cycloaddition substrate.
Scheme 3: Conversion of α-ketoester to α-diazoester.
Scheme 4: Seebach’s tartrate alkylation and rationalisation of stereoselectivity [17-19].
Scheme 5: Tartrate alkylation with a non-activated alkyl iodide.
Scheme 6: Alkylated tartrate to diazoester sequence.
Scheme 7: TES protection approach to the squalestatin core.
Scheme 8: Tartrate acetonide methylation.
Scheme 9: Tartrate alkylation with various alkyl halides.
Scheme 10: Rationalisation of dialkylation observations.
Scheme 11: Tartrate alkylation chemistry with more complex alkyl iodides [12,13].
Figure 2: Natural product examples containing the monoalkylated tartaric acid motif.
Scheme 12: Epimerisation of monoalkylated tartrates.
Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety
- Alex Frichert,
- Peter G. Jones and
- Thomas Lindel
Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222
- 3). For the synthesis of 25, we started from the known limonene oxide-derived diol 20 [24] that was hydrogenated, oxidized, and silylated at the tertiary alcohol moiety (81%). Reaction of deprotonated 21 with ethyl cyanoformate afforded cyanohydrin 22 by attack of liberated cyanide at the carbonyl
- the relative configuration shown in Scheme 4. From cyanohydrin 22 HCN was eliminated by treatment with diluted NaOH (100%, Scheme 3). The resulting ketone 23 reacted with lithiated alkyne 12 affording diastereomerically pure tertiary alcohol 24 (63%) that showed a broad hydroxy signal in the 1H NMR
- , treatment of 25 with TiCl4/Zn did not lead to pinacol cyclization and we have evidence that the aldehyde group stayed in place and the keto group had been reduced. Installation of a TMS group at the tertiary alcohol moiety of 25 (TMSOTf, 2,6-lutidine) formed 26, which was simply reduced at the keto function
Graphical Abstract
Figure 1: Bicyclic eunicellane-type diterpenes.
Figure 2: Synthetic eunicellane-type compounds with benzene partial structure.
Scheme 1: Access to ketoester 14 that did not cyclize to the ethyl vinyl ether under McMurry conditions.
Scheme 2: Synthesis of the 1,3-cyclohexadiene-containing eunicellane-type [8.4.0]bicycle 18 by McMurry coupli...
Figure 3: Preferred conformations of diastereomeric diols 18 and 19 including decisive NOESY correlations.
Scheme 3: Assembly of the envisaged cyclization precursor 27.
Scheme 4: Structure analysis of diastereomeric cyanohydrins 29 and 30.
Scheme 5: Formation of allenes 32 and 34 from sterically crowded propargylic alcohol 31.
Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source
- Tetsuaki Fujihara and
- Yasushi Tsuji
Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221
- 2c, respectively, were compatible with the reaction conditions. For the carboxylation of tertiary-alcohol-derived acetates to the corresponding carboxylic acids 2d,e, CoI2(bpy) was found to be an effective catalyst. The yields of product 2 decreased when less bulky substituents (R1) were used. Thus
Graphical Abstract
Scheme 1: Optimization of the Co-catalyzed carboxylation of 1a.
Scheme 2: Co-catalyzed carboxylation of propargyl acetates 1.
Scheme 3: Plausible reaction mechanism for the Co-catalyzed carboxylation of propargyl acetates 1.
Scheme 4: Optimization of the Co-catalyzed carboxylation of 3a.
Scheme 5: Co-catalyzed carboxylation of vinyl triflates 3.
Scheme 6: Co-catalyzed carboxylation of a sterically hindered aryl triflate 5.
Scheme 7: Optimization of the Co-catalyzed carboxylation of 7a.
Scheme 8: Scope of the reductive carboxylation of α,β-unsaturated nitriles 7.
Scheme 9: Scope of the carboxylation of α,β-unsaturated carboxamides 9.
Scheme 10: Optimization of the Co-catalyzed carboxylation of 11a.
Scheme 11: Scope of the carboxylation of allylarenes 11.
Scheme 12: Scope of the carboxylation of 1,4-diene derivatives 14.
Scheme 13: Plausible reaction mechanism for the Co-catalyzed C(sp3)–H carboxylation of allylarenes.
Scheme 14: Optimization of the Co-catalyzed carboxyzincation of 16a.
Scheme 15: Derivatization of the carboxyzincated product.
Scheme 16: Co-catalyzed carboxyzincation of alkynes 16.
Scheme 17: Plausible reaction mechanism for the Co-catalyzed carboxyzincation of alkynes 16.
Scheme 18: Co-catalyzed four-component coupling of alkynes 16, acrylates 18, CO2, and zinc.
Scheme 19: Proposed reaction mechanism for the Co-catalyzed four-component coupling.
Scheme 20: Visible-light-driven hydrocarboxylation of alkynes.
Scheme 21: Visible-light-driven synthesis of γ-hydroxybutenolides from ortho-ester-substituted aryl alkynes.
Scheme 22: One-pot synthesis of coumarines and 2-quinolones via hydrocarboxylation/alkyne isomerization/cycliz...
Scheme 23: Proposed reaction mechanism for the Co-catalyzed carboxylative cyclization of ortho-substituted aro...
Scheme 24: Rh-catalyzed carboxylation of arylboronic esters 25.
Scheme 25: Rh-catalyzed carboxylation of alkenylboronic esters 27.
Scheme 26: Plausible reaction mechanism for the Rh-catalyzed carboxylation of arylboronic esters 25.
Scheme 27: Ligand effect on the Rh-catalyzed carboxylation of 2-phenylpyridine 29a.
Scheme 28: Rh-catalyzed chelation-assisted C(sp2)–H bond carboxylation with CO2.
Scheme 29: Reaction mechanism for the Rh-catalyzed C(sp2)–H carboxylation of 2-pyridylarenes 29.
Scheme 30: Carboxylation of C(sp2)–H bond with CO2.
Scheme 31: Carboxylation of C(sp2)–H bond with CO2.
Scheme 32: Reaction mechanism for the Rh-catalyzed C(sp2)–H carboxylation of 2-arylphenols 34.
Scheme 33: Hydrocarboxylation of styrene derivatives with CO2.
Scheme 34: Hydrocarboxylation of α,β-unsaturated esters with CO2.
Scheme 35: Asymmetric hydrocarboxylation of α,β-unsaturated esters with CO2.
Scheme 36: Proposed reaction mechanism for the Rh-catalyzed hydrocarboxylation of C–C double bonds with CO2.
Scheme 37: Visible-light-driven hydrocarboxylation with CO2.
Scheme 38: Visible-light-driven Rh-catalyzed hydrocarboxylation of C–C double bonds with CO2.
Scheme 39: Optimization of reaction conditions on the Rh-catalyzed [2 + 2 + 2] cycloaddition of diyne 42a and ...
Scheme 40: [2 + 2 + 2] Cycloaddition of diyne and CO2.
Scheme 41: Proposed reaction pathways for the Rh-catalyzed [2 + 2 + 2] cycloaddition of diyne and CO2.
