Catalytic Wittig Approach to the Piperacase Family of Natural Products

Amides typically prove to be poor nucleophiles, thus limiting their use in the classic Aldol and Wittig reactions. As such, over the past 30 years, few examples of amides being used in the Wittig or Horner-Wadsworth-Emmons reaction have appeared in the literature. Recent advances in the Wittig reaction, particularly the development of high activity, low temperature catalysis, spurred our interest in exploring its application to tertiary amides. Herein we will report on our success of our method that makes use of an air stable catalytic phosphine first reported by Werner and co-workers, applying catalytic Wittig conditions using bromoacetyl tertiary amides to stereoselectively afford alpha-beta unsaturated amides. The utility of this approach is illustrated by the preparation of a variety of alkenes as well as the one step stereoselective preparation of Illepimide and other members of the Piperaceae family of natural products.