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Collective synthesis of acetylenic pharmaceuticals via enantioselective Nickel/Lewis acid-catalyzed propargylic alkylation.

ABSTRACT: Chiral acetylenic derivatives are found in many bioactive compounds and are versatile functional groups in organic chemistry. Here, we describe an enantioselective nickel/Lewis acid-catalyzed asymmetric propargylic substitution reaction from simple achiral materials under mild condition. The introduction of a Lewis acid cocatalyst is crucial to the efficiency of the transformation. Notably, we investigate this asymmetric propargylic substitution reaction for the development of a range of structurally diverse natural products. The power of this strategy is highlighted by the collective synthesis of seven biologically active compounds: (-)-Thiohexital, (+)-Thiopental, (+)-Pentobarbital, (-)-AMG 837, (+)-Phenoxanol, (+)-Citralis, and (-)-Citralis Nitrile.

SUBMITTER: Chang X

PROVIDER: S-EPMC7803749 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Collective synthesis of acetylenic pharmaceuticals via enantioselective Nickel/Lewis acid-catalyzed propargylic alkylation.

Chang Xihao X Zhang Jiayin J Peng Lingzi L Guo Chang C

Nature communications 20210112 1

Chiral acetylenic derivatives are found in many bioactive compounds and are versatile functional groups in organic chemistry. Here, we describe an enantioselective nickel/Lewis acid-catalyzed asymmetric propargylic substitution reaction from simple achiral materials under mild condition. The introduction of a Lewis acid cocatalyst is crucial to the efficiency of the transformation. Notably, we investigate this asymmetric propargylic substitution reaction for the development of a range of structu ...[more]

PMID: 33436637

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