Borane/Transition Metal–Catalyzed Allenylic and Allylic Alkylation of Unactivated 2-Alkylbenzoxazoles

Asymmetric functionalization of unactivated alkyl-substituted azaarenes at the α-position of the alkyl substituent is challenging because deprotonation of the weakly acidic α-C-H bonds requires a strong base. This requirement often impedes effective enantiocontrol by chiral catalysts. As a result, the few reactions that have been reported have narrow substrate scopes. Herein, we report a method for highly diastereo- and enantioselective allenylic alkylation reactions of unactivated 2-alkylbenzoxazoles with conjugated enynes, enabled by synergistic borane/nickel catalysis. The success of this method hinges on catalytic activation of the 2-alkylbenzoxazoles by a triarylborane, which permits deprotonation by triethylamine and thus is crucial for achieving both high yields and diastereo- and enantioselectivities. Extending the utility of synergistic borane/transition metal catalysis, we also demonstrate that a borane/palladium system effectively overcomes the limitations of palladium-catalyzed allylic alkylation reactions of unactivated azaarenes. In particular, previously unreactive acyclic 1,3-disubstituted allylic esters are rendered viable electrophiles, enabling the construction of products bearing two adjacent stereocenters.