Mild and practical method for the alpha-arylation of nitriles with heteroaryl halides.
[reaction: see text] A mild and transition-metal-free method for the alpha-arylation of aliphatic nitriles with activated heteroaryl halides was developed using NaHMDS or KHMDS as base at ambient temperature. The key to the success of this method is generation of the nitrile anion in the presence of the heteroaryl halide. The method is applicable to both primary and secondary carbonitriles and a wide range of heteroaryl halides. Selective monoarylation was observed with primary carbonitriles. The operational simplicity and the mild reaction conditions add to the value of this method as a practical alternative to the preparation of alpha-heteroaryl carbonitriles.
Klapars
Artis
A
Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. artis_klapars@merck.com
Waldman
Jacob H
JH
Campos
Kevin R
KR
Jensen
Mark S
MS
McLaughlin
Mark
M
Chung
John Y L
JY
Cvetovich
Raymond J
RJ
Chen
Cheng-Yi
CY
D000478:Alkylation; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D006846:Hydrocarbons, Halogenated; D009570:Nitriles