Mild and Practical Method for the α-Arylation of Nitriles with Heteroaryl Halides

• Published in: Journal of organic chemistry Vol. 70; no. 24; pp. 10186 - 10189
• Main Authors: Klapars, Artis, Waldman, Jacob H, Campos, Kevin R, Jensen, Mark S, McLaughlin, Mark, Chung, John Y. L, Cvetovich, Raymond J, Chen, Cheng-yi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.11.2005; Amer Chemical Soc
• Subjects: Alkylation; Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Hydrocarbons, Halogenated - chemistry; Molecular Structure; Nitriles - chemical synthesis; Nitriles - chemistry; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; CARBONYL; CARBANIONS; HALOPYRIDINES; MECHANISM; NUCLEOPHILIC-SUBSTITUTION; Arylation; Sulfur nitrogen heterocycle; Nitrile; Mild operating conditions; Nitrogen heterocycle; Organic halogen compounds; Heterocyclic compound; Oxygen nitrogen heterocycle
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo051737f

A mild and transition-metal-free method for the α-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 α-heteroaryl carbonitriles.