Abstract
AbstractTransition metal-catalyzed asymmetric allylic substitution with a suitably pre-stored leaving group in the substrate is widely used in organic synthesis. In contrast, the enantioselective allylic C(sp3)-H functionalization is more straightforward but far less explored. Here we report a catalytic protocol for the long-standing challenging enantioselective allylic C(sp3)-H functionalization. Through palladium hydride-catalyzed chain-walking and allylic substitution, allylic C-H functionalization of a wide range of acyclic nonconjugated dienes is achieved in high yields (up to 93% yield), high enantioselectivities (up to 98:2 er), and with 100% atom efficiency. Exploring the reactivity of substrates with varying pKa values uncovers a reasonable scope of nucleophiles and potential factors controlling the reaction. A set of efficient downstream transformations to enantiopure skeletons showcase the practical value of the methodology. Mechanistic experiments corroborate the PdH-catalyzed asymmetric migratory allylic substitution process.
Funder
National Natural Science Foundation of China
Science and Technology Commission of Shanghai Municipality
the Strategic Priority Research Program of the Chinese Academy of Sciences
Shanghai Rising-Star program
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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