Development of a generic activation mode: nucleophilic alpha -substitution of ketones viaoxy-allyl cations

Oxy-allyl cations have been known as transient electrophilic species since they were first proposed as intermediates in the Favorskii rearrangement in 1894. Since that time, they also have been used as a mode of activation for [4 + 3] cycloadditions in a variety of natural product syntheses. In this manuscript, we describe a method for the interception of oxy-allyl cations with a diverse range of common nucleophiles, thereby demonstrating the value of this intermediate as a generic mode of activation. This simple, mild, room temperature protocol allows for the formation of a variety of high value carbon-carbon and carbon-heteroatom bonds that are readily incorporated within a series of cyclic and acyclic ketone systems. Initial efforts into the development of an enantioselective catalytic variant are also described.