Open AccessEnantioselective Catalytic Dearomative Addition of Grignard Reagents to 4-Methoxypyridinium Ions
Author(s) -
Yafei Guo,
Marta Castiñeira Reis,
Johanan Kootstra,
Syuzanna R. Harutyunyan
Publication year - 2021
Publication title -
acs catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.898
H-Index - 198
ISSN - 2155-5435
DOI - 10.1021/acscatal.1c01544
Subject(s) - enantioselective synthesis , enantiopure drug , reagent , reactivity (psychology) , catalysis , alkylation , nucleophile , chemistry , combinatorial chemistry , organic chemistry , pyridine , alkyl , medicine , alternative medicine , pathology
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.