3-Acyloxy-1,4-enyne: A new five-carbon synthon for rhodium-catalyzed [5 + 2] cycloadditions

Abstract

Seven-membered rings are ubiquitous in natural products and pharmaceutical agents, and their syntheses continue to stimulate the development of novel synthetic methods. The [5 + 2] cycloaddition is one of the most efficient ways to access seven-membered rings since the two-carbon components (alkenes, alkynes, or allenes) are readily available. Prior to our study, however, there was only one type of transition-metal-catalyzed [5 + 2] cycloaddition: the reaction between vinylcyclopropanes and alkenes, alkynes, or allenes. We recently developed a new type of transition-metal-catalyzed [5 + 2] cycloaddition, where the five-carbon building block is 3-acyloxy-1,4-enyne (ACE). Our recent progress on Rh-catalyzed intra-and intermolecular [5 + 2] cycloadditions of ACEs and alkynes is summarized in this article. Using chiral propargylic esters, bicyclic products were prepared in high optical purity by the intramolecular [5 + 2] cycloadditions. Monocyclic seven-membered rings were synthesized by intermolecular [5 + 2] cycloaddition of ACEs and alkynes. Kinetic studies indicated that the rate of this intermolecular cycloaddition was significantly accelerated when the acetate was replaced by dimethylaminobenzoate. DFT calculations suggested that novel metallacycles were generated by a Rh-promoted oxidative cycloaddition of 1,4-enynes accompanied by a 1,2-acyloxy migration of propargylic esters. © 2014 IUPAC.