Mild and Efficient C2-Alkenylation of Indoles with Alkynes Catalyzed by a Cobalt Complex

摘要

Indole represents a privileged core structural motif that occurs in biologically active natural and unnatural products. Consequently, direct functionalization of the indole nucleus has long attracted interest of synthetic chemists. While the C3-position of indole is the inherently reactive site for Friedel-Crafts-type chemistry, the recent emergence of transition-metal-catalyzed C-H bond functionalization has not only expanded the scope of C3 -functionalization but also has opened the door to a variety of methods for C2-functionalization. Nevertheless, compared with arylation, catalysts that allow alkenylation of the C2-position are still limited despite the potential utility of such products. While disubstituted and trisubstituted olefin products have been accessed by oxidative Heck olefination and hydroarylation of internal alkynes, respectively, there remain significant limitations that warrant further catalyst development, particularly for the latter type of reaction. For example, the nickel catalysis of Nakao, Hiyama et al. needs an electron-withdrawing substituent at the C3-position, while the rhodium catalysis of Schipper, Hutchinson, and Fagnou does not allow the use of dialkylacetylenes. We report herein efficient C2-alkenylation of indoles bearing an easily removable N-pyrimidyl group under room-temperature conditions with a versatile cobalt catalyst. The alkenylated indoles serve as useful platforms for further synthetic manipulations, such as cycloaddition, Friedel-Crafts condensation, and direct C-H functionalization reactions.