Chiral Alkyl Amine Synthesis via Catalytic Enantioselective Hydroalkylation of Enamides

16 October 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Chiral alkyl amines are omnipresent as bio-active molecules and synthetic intermediates. Catalytic and enantioselective synthesis of alkyl amines from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble a wide range of chiral alkyl amines from enamides and alkyl halides in high regio- and enantioselectivity. The method works for both non-activated and activated alkyl halides, and is able to produce enantiomerically enriched amines with two minimally differentiated alpha-alkyl substituents. The mild conditions lead to high functional group tolerance, which is demonstrated in the post-product functionalization of many natural products and drug molecules, as well as the synthesis of chiral building blocks and key intermediates to bio-active compounds.

Keywords

hydroalkylation reaction
nickel hydride catalyst
enamine derivatives
Enamide
chiral alkyl amines
enantioselectivitie

Supplementary materials

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Actions
Title
SI-Hu2-all
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