Copper-Mediated sp ² C–H Chlorination with Trichloroacetamide Using a Removable Directing Group

Dedicated to Prof. David R. Williams at Indiana University

Abstract

2-Aminophenyl-1H-pyrazole was discovered as a removable, bidentate directing group for copper-mediated aerobic oxidative sp ² C–H bond chlorination employing trichloroacetamide as a new chlorine source. When Cu(OAc)₂ was employed as the copper source, 1,1,3,3-­tetramethylguanidine (TMG) as an organic base, the reaction, optimally carried out overnight in DMSO at 80 °C in open air, produced a variety of mono- and dichlorinated products in moderate to excellent yields. This directing group can be removed oxidatively with cerium ammonium nitrate (CAN).

Key words

C–H chlorination - copper-mediated - trichloroacetamide - removable directing group - 2-aminophenyl-1H-pyrazole

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