Copper(I)‐Catalyzed Asymmetric Conjugate 1,6‐, 1,8‐, and 1,10‐Borylation

Abstract

Catalytic asymmetric remote conjugate borylation is challenging as the control of regioselectivity is not trivial, the electrophilicity of remote sites is extenuated, and the remote asymmetric induction away from the carbonyl group is difficult. Herein, catalytic asymmetric conjugate 1,6‐, 1,8‐ and 1,10‐borylation was developed with excellent regioselectivity, which delivered α‐chiral boronates in moderate to high yields with high enantioselectivity. The produced chiral boronate smoothly underwent oxidation, cross‐coupling, and one‐carbon homologation to give synthetically versatile chiral compounds in moderate yields with excellent stereoretention. Furthermore, a stereomechanistic analysis was conducted using DFT calculations, which provides insights into the origins of the regioselectivity. Finally, the present 1,6‐borylation was successfully applied in an efficient one‐pot asymmetric synthesis of (−)‐7,8‐dihydrokavain.

Umpolung Asymmetric 1,5‐Conjugate Addition via Palladium Hydride Catalysis

“…[5,6] This widely accepted reaction model has been demonstrated by a series of elegant studies, and enantioselective pathways have also been realized via diverse catalytic systems, including transition metals and organocatalysts (Scheme 1a). [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] This 100 % atom-economic process can be used to construct enantioenriched stereogenic centers remote from versatile electron-deficient functional groups and thus represents a highly valuable route to build intriguing chiral skeletons. However, overturning the aforementioned classical viewpoint, that is, the introduction of a nucleophile to the electronically mismatched C5position via umpolung 1,5-addition, is very challenging, and a related general protocol remains absent.…”

“…Nucleophilic 1,6‐conjugate addition is a well‐known transformation, and generally involves sequential electronically matched nucleophilic addition and protonation [5, 6] . This widely accepted reaction model has been demonstrated by a series of elegant studies, and enantioselective pathways have also been realized via diverse catalytic systems, including transition metals and organocatalysts (Scheme 1a) [7–21] . This 100 % atom‐economic process can be used to construct enantioenriched stereogenic centers remote from versatile electron‐deficient functional groups and thus represents a highly valuable route to build intriguing chiral skeletons.…”