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Nickel‐Catalyzed Regioselective C(2)−H Difluoroalkylation of Indoles with Difluoroalkyl Bromides
Author(s) -
Soni Vineeta,
Sharma Dipesh M.,
Punji Benudhar
Publication year - 2018
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201800504
Subject(s) - regioselectivity , luzindole , catalysis , chemistry , nickel , indole test , xantphos , combinatorial chemistry , substrate (aquarium) , medicinal chemistry , melatonin receptor , stereochemistry , organic chemistry , palladium , receptor , biochemistry , oceanography , geology
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)NiCl 2 /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.