Electronically controlled regioselective hydroarylation of gem-difluoroallenes

Abstract

All-carbon quaternary centers are ubiquitous structural motifs in natural products, bioactive molecules, and pharmaceuticals. The formation of these crowded carbon centers is well known to be challenging, and methods to access them remain in high demand. Transition-metal-based strategies have emerged as a powerful approach to quaternary carbons, primarily relying on cross-coupling reactions and olefin arylation processes. Herein is presented a straightforward method to create benzylic all-carbon quaternary centers employing gem -difluoroallenes. Features of this method include room temperature C–H functionalization, excellent regioselectivity in the insertion of gem -difluoroallenes, and generation of gem -difluoroalkene products, which have widespread applications in synthesis and pharmaceutical sciences. Mechanistic studies support a turnover limiting rhodium-catalyzed C–H cleavage that likely proceeds via a concerted metalation deprotonation pathway. Regioselective insertion of the gem -difluoroallene is controlled by electronic effects. • Efficient and facile construction of all-carbon quaternary benzylic centers • Preparation of versatile gem -difluoroalkenes via hydroarylation is shown • Regioselective insertion of 1,1-difluoroallene is controlled by electronic effects • Gram-scale synthesis and diverse synthetic transformations are observed Efficient construction of all-carbon quaternary centers is vital owing to their ubiquity in natural products, bioactive molecules, and drugs. Here, Wang et al. develop an example of hydroarylation of gem -difluoroallenes to prepare versatile gem -difluoroalkenes with an all-carbon quaternary center.