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Enantioselective Catalytic Dearomative Addition of Grignard Reagents to 4-Methoxypyridinium Ions.

ABSTRACT: We describe a general catalytic methodology for the enantioselective dearomative alkylation of pyridine derivatives with Grignard reagents, allowing direct access to nearly enantiopure chiral dihydro-4-pyridones with yields up to 98%. The methodology involves dearomatization of in situ-formed N-acylpyridinium salts, employing alkyl organomagnesium reagents as nucleophiles and a chiral copper (I) complex as the catalyst. Computational and mechanistic studies provide insights into the origin of the reactivity and enantioselectivity of the catalytic process.

SUBMITTER: Guo Y

PROVIDER: S-EPMC8291581 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Enantioselective Catalytic Dearomative Addition of Grignard Reagents to 4-Methoxypyridinium Ions.

Guo Yafei Y Castiñeira Reis Marta M Kootstra Johanan J Harutyunyan Syuzanna R SR

ACS catalysis 20210628 14

We describe a general catalytic methodology for the enantioselective dearomative alkylation of pyridine derivatives with Grignard reagents, allowing direct access to nearly enantiopure chiral dihydro-4-pyridones with yields up to 98%. The methodology involves dearomatization of in situ-formed <i>N</i>-acylpyridinium salts, employing alkyl organomagnesium reagents as nucleophiles and a chiral copper (I) complex as the catalyst. Computational and mechanistic studies provide insights into the origi ...[more]

PMID: 34306813

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