Asymmetric Catalytic 1,6‐Conjugate Addition/Aromatization of <i>para</i>‐Quinone Methides: Enantioselective Introduction of Functionalized Diarylmethine Stereogenic Centers

Chu, Wen‐Dao; Zhang, Le-Fen; Bao, Xu; Zhao, Xianhe; Zeng, Chao; Du, Ji‐Yuan; Zhang, Guo‐Biao; Wang, Fang‐Xin; Ma, Xiaoyan; Fan, Chun‐An

doi:10.1002/ange.201303928

Cited by 70 publications

(8 citation statements)

References 100 publications

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“…This phenomenon may be attributed to a severe steric repulsion between the Me and the Ar 2 CH moiety in the staggered Newman projection of the cationic intermediate generated from cis ‐ 11 (Scheme ). In the visually stable anti conformer adopted by trans ‐ 11 , the proximity of the hydroxy group with the newly generated diarylmethyl carbon cation allows the subsequent S N 1 cyclization to proceed with a low energy barrier 14. 15…”

Section: Methodsmentioning

confidence: 99%

Exploiting the Hydrophobic Terrain in Fucosidases with Aryl‐Substituted Pyrrolidine Iminosugars

et al. 2014

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Fucosidase inhibition shows potential in numerous therapeutic contexts. Substitution of fucose-like iminosugars with hydrophobic "aglycons" yields significant improvements in potency of fucosidase inhibition. Here we have prepared three new 2-aryl-3,4-dihydroxy-5-methylpyrrolidines featuring phenyl substituents in variable orientations with respect to the iminocyclitol core and at various distances from it to explore the key binding interactions that stabilise the enzyme-inhibitor complex. The presence of a triazole linker in one structure resulted in nanomolar inhibition of the fucosidase from bovine kidney (Ki =4.8 nM), thus giving rise to one of the most potent pyrrolidine-type inhibitors of this enzyme known to date.

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Section: Methodsmentioning

confidence: 99%

Exploiting the Hydrophobic Terrain in Fucosidases with Aryl‐Substituted Pyrrolidine Iminosugars

et al. 2014

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“…Despite substantial advances, enantiomerically enriched nonspirocyclic 3,3-disubstituted oxindoles remain challenging to access. [70][71][72][73][74][75][76][77][78][79] During our continuous efforts devoted to the development of NHC-catalyzed 1,6-additions, 80 a model reaction of the p-quinone methide [81][82][83] 1a as 1,6-Michael acceptor and the isatin-derived enal 84,85 2a was investigated under NHC catalysis (Scheme 2). We were pleased to find that the reaction catalyzed using precatalyst A, in the presence of N,N-diisopropylethylamine (DIPEA) as the base, furnished the desired nonspirocyclic quaternary oxindole 3a in 45% yield with 3∶1 diastereomeric ratio (dr) and 67% enantiomeric excess (ee).…”

Section: Introductionmentioning

confidence: 99%

N-Heterocyclic Carbene-Catalyzed 1,6-Addition of Homoenolate Equivalent Intermediates: Asymmetric Synthesis of Nonspirocyclic Quaternary Oxindoles

Chen¹,

Zhao²,

Liu³

et al. 2019

CCS Chem

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Although there is a growing interest in developing asymmetric 1,6-addition reactions of carbon nucleophiles to Michael acceptors, the corresponding 1,6-addition of homoenolates remains an unsolved problem. Currently, the N-heterocyclic carbene (NHC)-catalyzed cycloadditions of homoenolate equivalent intermediates have achieved widespread success. However, considerable limitations still exist for the linear reactions with electron-deficient alkenes, which are limited to 1,4-Michael acceptors. This report presents the first NHC-catalyzed asymmetric homoenolate addition of enals to 1,6-Michael acceptors. The strategy leads to the challenging * * linear reactions quaternary oxindoles homoenolate equivlent intermediates

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“…In this regard, the 1,6-conjugated addition reaction catalyzed by Brønsted acids or Lewis acids for new chemical bond formation can provide a variety of bioactive compounds, and has complete atom economy [11]. Thus, the 1,6-conjugated addition reaction is attracting much research interest in academia [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

An Economical, Sustainable Pathway to Indole-Containing Oxindoles: Iron-Catalyzed 1,6-Conjugate Addition in Glycerol

Tan

Rahman

2018

Sustainability

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Abstract:The search for economical, sustainable and practical pathways in synthetic science would contribute to improving resource efficiency, developing a recycling economy and driving new-type urbanization. Green synthesis has established firm ground providing the right green yardstick for development of a sustainable approach to bioactive high-added value molecules and drug discovery, and further development of sustainable manufacturing processes in the pharmaceutical industry toward a green resource efficient economy. In this study, the combination of FeCl 3 and glycerol exhibits a versatile and high catalytic activity in the atom economical 1,6-conjugated addition of para-quinone methides derived from isatins with indoles using the right green yardstick. The sustainable pathway provides the preparation of bioactive indole-containing oxindoles in excellent yields with superior advantages, such as the ready availability, low price and environmentally benign character of iron catalysis, easy product separation, cheap and safe bio-renewable glycerol as a green solvent, and catalytic system recycling under mild conditions.

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Asymmetric Catalytic 1,6‐Conjugate Addition/Aromatization of para‐Quinone Methides: Enantioselective Introduction of Functionalized Diarylmethine Stereogenic Centers

Cited by 70 publications

References 100 publications

Exploiting the Hydrophobic Terrain in Fucosidases with Aryl‐Substituted Pyrrolidine Iminosugars

Exploiting the Hydrophobic Terrain in Fucosidases with Aryl‐Substituted Pyrrolidine Iminosugars

N-Heterocyclic Carbene-Catalyzed 1,6-Addition of Homoenolate Equivalent Intermediates: Asymmetric Synthesis of Nonspirocyclic Quaternary Oxindoles

An Economical, Sustainable Pathway to Indole-Containing Oxindoles: Iron-Catalyzed 1,6-Conjugate Addition in Glycerol

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