title: Low-valent cobalt catalysis: new opportunities for C-H functionalization.
abstract: 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.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University , Singapore 637371, Singapore.
authors.forename: Ke
authors.initials: K
authors.lastname: Gao
authors.forename: Naohiko
authors.initials: N
authors.lastname: Yoshikai