Aldimine-Directed Branched-Selective Hydroarylation of Styrenes

摘要

Efficient and selective construction of a 1,1-diarylethane core structure has received considerable attention because of its occurrence in a variety of pharmacologically active compounds. Among various synthetic approaches to 1,1-diaryl-ethanes, hydroarylation of styrene derivatives with branched regioselectivity is attractive for the inherently perfect atom economy. Such transformations can be achieved through two mechanistically distinct modes of substrate activation: activation of the styrene C=C bond with a Lewis acid followed by a Friedel-Crafts-type aromatic alkylation, and activation of the aromatic C—H bond with a low-valent transition-metal catalyst and subsequent insertion of styrene. The former type of reaction is applicable to electron-rich arenes with exclusive branched selectivity, but is often accompanied by imperfect regioselectivity with respect to the arene substrate. In contrast, the latter type of reaction typically leads to 1,2-diarylethanes rather than 1,1-diarylethanes as the major products. Some exceptions to this trend include the ruthenium-catalyzed reaction of the ortho position of N-methylaniline and the nickel-catalyzed reaction of the C2 position of electron-deficient heteroarenes such as azole derivatives. As such, significant limitations remain in the synthetic scope of the hydroarylation approach to 1,1-diarylethanes.