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.

Manganese‐Catalyzed Synthesis of cis‐β‐Amino Acid Esters through Organometallic CH Activation of Ketimines

“…In stark contrast, the potential of naturally abundant 3d metal complexes as catalysts for C À H functionalizations is largely untapped. [3] Despite of recent advances with nickel, cobalt, and iron catalysts, [3] manganese complexes are still scarcely employed as catalysts in organometallic CÀH activations, [4] although manganese is the third most abundant transition metal after iron and titanium. Thus far, manganese catalysis has been dominated by outer-sphere radical oxygenations or halogenations by high-valent manganese species.…”

General Aspects of the Cobalt Chemistry

“…Their work brought out novel difficulties and possibilities. It was necessary to fully understand the reaction mechanism and the nature of the catalyst due to further growth in this area [35]. (2).…”

RhIII‐Catalyzed Hydroarylation of Internal Alkynes through C−H Bond Activation

“…[3] In 1979, Hong and coworkers reported an elegant method of rhodium-catalyzed non-coordination-assisted hydroarylation of alkynes under carbon monoxide; however, this reaction gave rise to a mixture of triphenylethylene and 2,3-diphenylindenone. [4a] Shortly after that, the same group discovered [Rh 4 (CO) 12 ]-catalyzed addition of five-membered aromatic heterocyclic compounds to internal alkynes, thus affording the vinylation products in moderate to good yields.…”

“…With other solvents, such as THF, 1,4-dioxane, and t-AmOH, results were inferior compared with that of dimethoxyethane (DME), and to our pleasure the isolated yield of the desired product was increased to 78 % in the case of dichloroethene (DCE; Table 1, entries [3][4][5][6]. To further optimize the reaction conditions, a variety of additives were screened in the hope of a positive effect on this transformation.…”