Metalated nitriles: chelation-controlled cyclizations to cis and trans hydrindanes and decalins

J Org Chem. 2007 Feb 16;72(4):1431-6. doi: 10.1021/jo062270r. Epub 2007 Jan 24.

Abstract

Chelation provides a powerful means of stereocontrol in alkylations of metalated nitriles. Doubly deprotonating a series of cyclic beta-hydroxynitriles triggers cyclizations that implicate metalated nitrile intermediates having configurations imposed by chelation with an adjacent, chiral lithium alkoxide. Identifying chelation as a general stereocontrol element explains several previously anomalous alkylations of metalated nitriles and provides a potential solution to the long-standing difficulty of synthesizing trans-hydrindanes. Employing chelation to control the metalated nitrile geometry permits selective cyclizations to cis and trans hydrindanes and decalins and provides key insight into the geometrical requirements of these demanding cyclizations.