Copper-Catalyzed Enantioconvergent Cross-Coupling of Racemic Alkyl Bromides with Azole C(sp(2))-H Bonds

摘要

The development of enantioconvergent cross-coupling of racemic alkyl halides directly with heteroarene C(sp(2))-H bonds has been impeded by the use of a base at elevated temperature that leads to racemization. We herein report a copper(I)/cinchona-alkaloid-derived N,N,P-ligand catalytic system that enables oxidative addition with racemic alkyl bromides under mild conditions. Thus, coupling with azole C(sp(2))-H bonds has been achieved in high enantioselectivity, affording a number of potentially useful alpha-chiral alkylated azoles, such as 1,3,4-oxadiazoles, oxazoles, and benzo[d]oxazoles as well as 1,3,4-triazoles, for drug discovery. Mechanistic experiments indicated facile deprotonation of an azole C(sp(2))-H bond and the involvement of alkyl radical species under the reaction conditions.