Dearomative Mislow–Braverman–Evans Rearrangement of Aryl Sulfoxides

Abstract

The Mislow–Braverman–Evans rearrangement, the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides to allylic sulfenate esters, finds widespread applications in organic synthesis and medicinal chemistry. However, the products of this powerful strategy have primarily been limited to derivatives of allylic alcohols. In contrast, access to structurally similar benzylic alcohols has not yet been established. Described herein is an unprecedented dearomative Mislow–Braverman–Evans rearrangement of aryl sulfoxides to afford benzylic alcohols. A variety of heteroaryl sulfoxides as well as α-naphthyl sulfoxides could be tolerated, and a diverse range of primary, secondary, and tertiary alcohols possessing either alkyl or aryl substituents can be prepared by our protocol with broad functional group tolerance. A patented bioactive molecule could be prepared using our protocol as the key step with exclusive diastereoselectivity, highlighting its potential utility in organic synthesis. Key to the success of the transformation is the dearomative tautomerization to shift the reactive alkene to the exocyclic position enabled by the reversible deprotonation of the benzylic C–H bond, setting the stage for the subsequent [2,3]-sigmatropic rearrangement. Density functional theory (DFT) calculations reveal that protonation of the α-carbon of the sulfoxide is the stereocontrolling step, generating the intermediate that undergoes [2,3]-sigmatropic rearrangement. The full reaction profile is outlined, showing the reversible nature of each step, which causes the observed erosion of the enantiopurity.