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Diverse synthesis of α-tertiary amines and tertiary alcohols via desymmetric reduction of malonic esters.

ABSTRACT: Amines and alcohols with a fully substituted α-carbon are structures of great value in organic synthesis and drug discovery. While conventional methods towards these motifs often rely on enantioselective carbon-carbon or carbon-heteroatom bond formation reactions, a desymmetric method is developed here by selectively hydrosilylating one of the esters of easily accessible α-substituted α-amino- and -oxymalonic esters. The desymmetrization is enabled by a suite of dinuclear zinc catalysts with pipecolinol-derived tetradentate ligands and can accommodate a diverse panel of heteroatom substituents, including secondary amides, tertiary amines, and ethers of different sizes. The polyfunctionalized reduction products, in return, have provided expeditious approaches to enantioenriched nitrogen- and oxygen-containing molecules, including dipeptides, vitamin analogs, and natural metabolites.

SUBMITTER: Liu H

PROVIDER: S-EPMC9376102 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Diverse synthesis of α-tertiary amines and tertiary alcohols via desymmetric reduction of malonic esters.

Liu Haichao H Lau Vincent Ho Man VHM Xu Pan P Chan Tsz Hin TH Huang Zhongxing Z

Nature communications 20220813 1

Amines and alcohols with a fully substituted α-carbon are structures of great value in organic synthesis and drug discovery. While conventional methods towards these motifs often rely on enantioselective carbon-carbon or carbon-heteroatom bond formation reactions, a desymmetric method is developed here by selectively hydrosilylating one of the esters of easily accessible α-substituted α-amino- and -oxymalonic esters. The desymmetrization is enabled by a suite of dinuclear zinc catalysts with pip ...[more]

PMID: 35963867

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