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Synfacts 2006(4): 0309-0309  
DOI: 10.1055/s-2006-932039
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (±)-Verapamil

Contributor(s): Philip Kocienski
L. Wu, J. F. Hartwig*
Yale University, New Haven, USA
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Publication History

Publication Date:
24 March 2006 (online)

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Significance

A very mild method for the synthesis of benzylic nitriles entails the Pd(0)-catalyzed monoarylation of secondary zinc cyanoalkyl reagents. The reaction tolerates base-sensitive functional groups such as esters and ketones. A related method using α-silylnitriles in the presence of zinc fluoride is also reported. An enantioselective synthesis of Verapamil based on nucleophile-catalyzed asymmetric acylation of a silyl ketene imine was recently reported (A. H. Mermerian, G. C. Fu Angew. Chem. Int. Ed. 2005, 44, 949-952). For a scaleable route to the pure enantiomers by resolution, see: R. M. Bannister et al. Org. Process Res. Dev. 2000, 4, 467-472.