Mn(I)-Catalyzed Mechanochemical C-H Bond Activation: C-2 Selective Alkenylation of Indoles

An efficient mechanochemical method for manganese-catalyzed regioselective C-H bond alkenylation of indoles with alkynes is developed. Recently, mechanochemical C-H bond activation has received due attention and the use of low-valent first-row transition metals in C-C cross-coupling via C-H activation under mechanochemical conditions is an additional feather to the cost-effectiveness of such useful synthetic protocols. The present method allows direct C-2 alkenylation of indoles in a mixer mill, employing a commercially available low-valent manganese catalyst, MnBr(CO)(5), providing a sustainable route to hydroindolation on alkynes. The developed protocol is highly C-2-selective by the presence of a heteroaromatic N atom as a directing group (namely, pyridyl) and tolerant of structural variations with electron-rich and electron-deficient substituents both in the indoles and in the alkynes. Silica as the grinding media and the presence of a catalytic amount of acid and DIPEA as the base worked favorably to afford a variety of 2-alkenyl indoles in excellent yields at ambient conditions. The terminal alkynes offered better results than internal alkynes in terms of yields and reactivity. The scalability of the reaction was demonstrated by conducting the reactions in the gram scale. A short study indicated that a little tweak in conditions can be useful for double alkenylation to afford carbazole derivatives in moderate yields. A low E-factor along with a clean reaction profile, an easy experimental setup, the absence of an anhydrous condition, and being devoid of toxic organic solvents proclaims its advantage over the available conventional methods.