Synthesis of Bicyclo[2.1.1]hexan-5-ones via a Sequential Simmons-Smith Cyclopropanation and an Acid-Catalyzed Pinacol Rearrangement of & alpha;-Hydroxy Silyl Enol Ethers

A synthetic strategy involving a Simmons-Smith cyclopropanation, followed by an acid-catalyzed pinacol rearrangement, was developed to transform & alpha;-hydroxy silyl enol ethers into 1-substituted bicyclo[2.1.1]hexan-5-ones. These bicyclic ketones underwent further synthetic manipulations to generate various 1,5-disubstituted bicyclo[2.1.1]hexanes, which could serve as potential bioisosteres of ortho-substituted arenes.

Automated summary

A synthetic strategy involving Simmons-Smith cyclopropanation and acid-catalyzed pinacol rearrangement was developed to transform α-hydroxy silyl enol ethers into 1-substituted bicyclo[2.1.1]hexan-5-ones. These bicyclic ketones underwent further synthetic manipulations to generate various 1,5-disubstituted bicyclo[2.1.1]hexanes, which could serve as potential bioisosteres of ortho-substituted arenes.