Directed Cobalt-Catalyzed C-H Bond Activation To Form C-C And C-O Bonds Via Three-Component Coupling

In recent years,transition metal-catalyzed C-H bond activation has been considered as one of the most effective strategies to achieve various organic transformations.However,there are few reports on C-H bond activation to construct C-C and C-X(X=N,O,S,etc.)bonds concurrently via three-component coupling.Therefore,it would be meaningful to develop a synthesis method combining C-H bond activation and three-component reaction to realize the construction of C-C and C-X(X=N,O,S,etc.)bonds in one pot.In this paper,we used the N-(quinolin-8-yl)benzamides as substrates,3-diazoindole-2-ketones and tert-butyl hydroperoxide as coupling reagents,and the commercially available cobalt salts as catalysts.Under the standard conditions,the C(sp2)-H bond of benzamides could be activated to realize the construction of C-C and C-O bonds in one step.This strategy features room temperature,simple operation,and the avoidance of extra additives.This transformation could be performed smoothly with only 4 mol%Co(acac)2 loading,affording the three-component coupling compound efficiently with good regioselectivity and high yield.The experimental mechanism was explored through a series of control experiments,and the possible reaction mechanism was proposed.In addition,tert-butyl hydroperoxide may play a triple role in the reaction and the cleavage of the C-H bond may be involved the rate-limiting step.Then,the synthetic applications were carried out.This strategy provided the target product in high yield when the reaction was performed on gram-scale,and the product was readily transformed to the unexpected spirolide compound,which further demonstrates the synthetic versatility and utility of this protocol.