Unlocking the 5-exo Pathway with the AuI -Catalyzed Alkoxycyclization of 1,3-Dien-5-ynes.

Abstract

The first general regio- and stereoselective 5-exo gold(I)-catalyzed alkoxycyclization of a specific class of 1,5-enynes such as 1,3-dien-5-ynes has been described, despite 1,5-enynes being known to almost invariably proceed via endo cyclizations under gold-catalysis. The configuration of the terminal alkene in the starting 1,3-dien-5-yne plays a crucial role on the regiochemical outcome of the reaction. A wide variety of interesting alkoxy-functionalized alkylidenecyclopentenes have been synthesized from 1-monosubstituted (E)-1,3-dien-5-ynes. On the contrary, the corresponding Z isomers evolve affording formal 6-endo cyclization products. In addition, mechanistic exploration supports a highly stabilized carbocation as a key intermediate instead of a highly constrained cyclopropyl gold carbene from E isomers, and also accounts for the well differentiated reactivity observed between both E/Z geometrical isomers as well as for the stereochemical outcome of the reaction.