Reversal of Diastereoselection in the Conjugate Addition of Cuprates to Unsaturated Lactams
Stephen W Wright1, Chulho Choi1, Seungwon Chung1
1Worldwide Medicinal Chemistry, Pfizer Global Research and Development , 445 Eastern Point Road, Groton, Connecticut 06340, United States.
Abstract:
We report that the stereochemical outcome of the conjugate addition of organocopper reagents to bicyclic α,β-unsaturated lactams derived from pyroglutaminol is determined by the nature of the aminal group. Bicyclic α,β-unsaturated lactams in which the aminal is derived from a ketone have been found to afford products of syn conjugate addition. By contrast, bicyclic α,β-unsaturated lactams in which the aminal is derived from an aldehyde afford products of anti conjugate addition. These remarkably different results obtained from very similar starting materials are unexpected.
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