Phosphine-Mediated Reductive Condensation of -Acyloxy Butynoates: A Diversity Oriented Strategy for the Construction of Substituted Furans

摘要

Derivatives of furan occur ubiquitously in nature, appear in the structure of diverse therapeutic agents (e.g., ranitidine or zantac), and serve as useful intermediates in organic synthesis. While numerous strategies for furan synthesis exist, convergent annulation strategies are uncommon. Inspired by accounts of the thermally promoted isomerization of allenic ketones to furans under the conditions of flash vacuum thermolysis, as well as Marshall's seminal finding that such transformations may be catalyzed by Rh(I) or Ag(I) salts, a convergent method for the in situ generation and isomerization of allenic carbonyl compounds to furans under metal-free conditions was sought. Here, we report that exposure of γ-acyloxy butynoates to stoichiometric quantities of triarylphosphine results in reductive condensation to afford substituted furans, by way of allenic ester intermediates.8,9 As γ-acyloxy butynoates are readily obtained through condensation of ethyl propiolate with aldehydes followed by acylation, this method represents a powerful diversity oriented protocol for the convergent construction of substituted furans.