Mild and practical method for the α-arylation of nitriles with heteroaryl halides

ORGN 768

Jacob H. Waldman, jacob_waldman@merck.com1, Artis Klapars1, Kevin R. Campos1, Mark S. Jensen1, Mark McLaughlin1, John Y. L. Chung, john_chung@merck.com2, Raymond J. Cvetovich, Raymond_Cvetovich@Merck.com3, and Cheng-yi Chen1. (1) Merck & Co., Inc, P. O. Box 2000, Rahway, NJ 07065, (2) Department of Process Research, Merck Research Laboratories, PO Box 2000, R800-C369, Rahway, NJ 07065-0900, (3) Process Research, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065
A mild and transition-metal-free method for the á-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 á-heteroaryl carbonitriles.

 

Combinatorial, Parallel and Process Chemistry, Heterocycles, Aromatics, New Reactions and Methodology
8:00 PM-10:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Organic Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007