Low-Valent Cobalt Catalysis: New Opportunities for C–H Functionalization

Rapid progress in the fields of organometallic chemistry and homogeneous catalysis has made it possible for synthetic chemists to consider using ubiquitous yet unreactive C–H bonds as starting points to construct complex organic molecules. However, a majority of the C–H functionalization reactions currently in use require noble transition metal catalysts and harsh reaction conditions, so researchers have placed a priority on the development of mild and cost-effective catalysts. Given this situation, we wondered whether earth-abundant first-row transition metals could emulate the reactivity of a noble transition metal catalyst and carry out similar C–H functionalization reactions at a lower cost and under milder conditions. We also wondered whether we could use first-row transition metals to achieve hitherto unknown, but useful, C–H functionalization reactions.This Account summarizes our research on the development of three different types of C–H functionalization reactions using low-valent cobalt catalysts: (1) hydroarylation of alkynes and olefins, (2) ortho C–H functionalization with electrophiles, and (3) addition of arylzinc reagents to alkynes involving 1,4-cobalt migration. Although synthetic chemists have previously paid little attention to cobalt in designing catalytic C–H functionalization reactions, earlier studies, particularly those on stoichiometric cyclometalation, inspired us as we developed the hydroarylation and ortho C–H functionalization reactions.In these transformations, we combined a cobalt precatalyst, a ligand (such as phosphine or N-heterocyclic carbene (NHC)), and Grignard reagent to generate low-valent cobalt catalysts. These novel catalysts promoted a series of pyridine- and imine-directed hydroarylation reactions of alkynes and olefins at mild temperatures. Notably, we observed branched-selective addition to styrenes, which highlights a distinct regioselectivity of the cobalt catalyst compared with typical rhodium and ruthenium catalysts. The combination of a cobalt–NHC catalyst and a Grignard reagent allows directed aromatic C–H functionalizations with electrophiles such as aldimines, aryl chlorides, and alkyl chlorides or bromides. This second reaction has a particularly broad scope, allowing us to introduce secondary alkyl groups at the ortho position of aryl imines, a difficult reaction to carry out by other means.Serendipitously, we found that a cobalt–Xantphos complex catalyzed the third type of C–H functionalization: the addition of an arylzinc reagent to an alkyne to afford ortho-alkenylarylzinc species through a 1,4-cobalt migration. This "migratory arylzincation" allowed us to quickly construct a diverse group of functionalized benzothiophenes and benzoselenophenes. Collectively, our studies of cobalt catalysis have provided cost-effective catalysts and milder conditions for existing C–H functionalizations and have led to some unprecedented, attractive chemical transformations.