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

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 alpha-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.

Automated summary

A catalytic asymmetric remote conjugate borylation was developed with excellent regioselectivity and high enantioselectivity, leading to the synthesis of versatile chiral compounds in moderate to high yields. Stereomechanistic analysis using DFT calculations provided insights into the origins of regioselectivity. Moreover, the 1,6-borylation reaction was successfully applied in an efficient one-pot asymmetric synthesis of (-)-7,8-dihydrokavain.