Ternary catalytic systems consisting of cobalt salts, phosphine ligands, and Grignard reagents promote addition of arylpyridines and imines to unactivated internal alkynes with high regio- and stereoselectivities. Deuterium-labeling experiments suggest that the reaction involves chelation-assisted oxidative addition of the aryl C-H bond to the cobalt center and insertion of the C-C triple bond into the Co-H bond, followed by reductive elimination of the resulting diorganocobalt species.

A quaternary catalytic system consisting of a cobalt salt, a triarylphosphine ligand, a Grignard reagent, and pyridine has been developed for chelation-assisted C-H bond activation of an aromatic imine, followed by insertion of an unactivated internal alkyne that occurs at ambient temperature. The reaction not only tolerates potentially senstitive functional groups (e.g., Cl, Br, CN, and tertiary amide), but also displays a unique regioselectivity. Thus, the presence of substituents such as methoxy, halogen, and cyano groups at the meta-position of the imino group led to selective C-C bond formation at the more sterically hindered ortho positions. Under acidic conditions, the hydroarylation products of dialkyl- and alkylarylacetylenes underwent cyclization to afford benzofulvene derivatives, while those of diarylacetylenes afforded the corresponding ketones in moderate to good yields. A mechanistic investigation into the reaction with the aid of deuterium-labeling experiments and kinetic analysis has indicated that oxidative addition of the ortho C-H bond is the rate-limiting step of the reaction. The kinetic analysis has also shed light on the complexity of the quaternary catalytic system.

A cobalt-chiral phosphoramidite catalyst promotes enantioselective imine-directed C2-alkylation of Boc-protected indoles with styrenes. The reaction affords 1,1-diarylethane products in moderate to good yields with good enantioselectivities under mild conditions. A deuterium-labeling experiment suggests that the enantioselectivity is controlled by both the styrene insertion and the C-C reductive elimination steps.

An ortho-arylation reaction of aromatic imines with aryl chlorides has been achieved using a cobalt-N-heterocyclic carbene catalyst in combination with a neopentyl Grignard reagent. The reaction takes place at room temperature to afford biaryl products in moderate to good yields.

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An improved cobalt-based catalytic system has been developed for the branched-selective addition of aromatic ketimines to styrenes. With an appropriate combination of triarylphosphine and the Grignard reagent, the reaction takes place smoothly at room temperature to afford 1,1-diarylethane derivatives with high regioselectivity.Given the importance of 1,1-diarylalkane skeletons in pharmacologically active compounds, 1 methods for their efficient construction have attracted increasing interest in recent years. Among various approaches, 26 addition of an aromatic compound to the ¡-position of a styrene derivative (i.e., branched-selective styrene hydroarylation) is attractive because of the perfect atom economy and the ready availability of the starting materials.710 Such transformations can be achieved either through activation of the styrene C=C bond with a Lewis acid 8 or through activation of the aromatic CH bond with a low-valent transition-metal catalyst.911 While these two types of reactions can potentially serve as complementary methods, the scope of the latter type of reaction has been relatively limited, because transition-metal-catalyzed styrene hydroarylation often exhibits selectivity toward the linear 1,2-diarylethane rather than 1,1-diarylethane.12,13 Recently, we developed cobaltphosphine catalytic systems for the branched-selective addition of 2-arylpyridines and aromatic aldimines to styrenes.10 Unfortunately, these catalytic systems showed only modest activity in the reaction of an aromatic ketimine. By reinvestigation of the reaction conditions, we have now established a significantly improved catalytic system that allows for the desired transformation under mild conditions with a broad substrate scope, which is reported herein.Scheme 1 and Table 1 illustrate the significant improvement made for the reaction of acetophenone ketimine 1a and styrene 2a. As reported previously, 10a the reaction with the CoBr 2 PCy 3 Me 3 SiCH 2 MgCl system, which was developed for 2-arylpyridines, was sluggish even with a high catalyst loading (20 mol %) and at an elevated temperature (60°C), affording the product 3aa in moderate yield (Scheme 1 (top) and Table 1, Entry 1). The CoBr 2 P(p-Tol) 3 Me 3 SiCH 2 MgCl system (10 mol %), 10b which was optimized for aromatic aldimines, also met with limited success (Entry 2), while the use of P(4-FC 6 H 4 ) 3 instead of P(p-Tol) 3 improved the reaction (Entry 3). The reaction with a lower catalyst loading of 5 mol % at room temperature led to further improvement, affording 3aa in 83% yield with a branched/linear (b/l) ratio of 99:1 (Entry 4). Throughout examination of Grignard reagents other than Me 3 SiCH 2 MgCl (Entries 58), the highest yield of 90% was achieved using cyclohexylmagnesium bromide (CyMgBr; Scheme 1 bottom and Entry 8). P(4-FC 6 H 4 ) 3 was confirmed to be the best ligand, as other triarylphosphine ligands gave poorer results under otherwise identical conditions (Entries 915). Interestingly, the use of P(2-MeOC 6 H 4 ) 3 resulted in reversal of the regios...

We report herein an ortho-C-H alkenylation reactiono fa ryl imines with alkenyl phosphates promoted by ac obalt-N-heterocyclic carbene (NHC)c atalytic system. While commercially available bulky NHC ligands exhibited only modest catalytic activity,e laborationo ft he nitrogen substituents and backbone of the NHC enabled the desired transformation to proceed in high yield at am ild temper-ature.T he newC o-NHC system proveda pplicable to av ariety of aryl iminesa nd alkenyl phosphates to afford ortho-alkenylated aryl imines,w hich serve as precursors to benzofulvene derivatives.