Gold(i)-catalyzed cycloisomerization of alcohol or amine tethered-vinylidenecyclopropanes providing access to morpholine, piperazine or oxazepane derivatives: a carbene versus non-carbene process

Abstract

A gold(I)-catalyzed intramolecular cyclization of alcohol or amine tethered-vinylidenecyclopropanes via a carbene or non-carbene process was developed to afford functionalized morpholines, piperazines and oxazepanes in good yields with a broad scope and excellent functional group tolerance under mild conditions. The steric bulkiness or chain length can modulate the reaction pathway. Substrates with a less sterically hindered group located at the allene moiety afford morpholines or piperazines containing an alkylidenecyclopropane via the non-carbene process, while sterically bulky ones give morpholines or piperazines containing a cyclobutene unit through the carbene process. Moreover, extending the carbon chain length of vinylidenecyclopropane enables the formation of seven-membered oxazepane via the carbene process. The synthetic utility of this protocol was also highlighted by its gram-scale synthesis and various transformations of the cyclization products.