Nickel-Catalyzed Regioselective C(2)-H Difluoroalkylation of Indoles with Difluoroalkyl Bromides.

Regioselective C(2)-H difluoroalkylation of C-3 unsubstituted indoles with commonly available fluoroalkyl bromides is successfully achieved employing a simple nickel catalyst system, (DME)NiCl2 /Xantphos. This methodology shows excellent regioselectivity and exhibits a broad substrate scope. Various functional groups, such as -OMe, -F, and -Br, are tolerated on the indole backbone to give the difluoroalkylated products in moderate to good yields. Preliminary mechanistic findings demonstrate that the reaction is homogeneous in nature and involves a radical manifold. Synthetic utility of this nickel-catalyzed method is demonstrated by synthesizing melatonin receptor antagonist Luzindole derivative.