Rapid Synthesis of the epi -Biotin Sulfone via Tandem S , N -Carbonyl Migration/aza-Michael/Spirocyclization and Haller-Bauer Reaction.

A synthesis of 2- epi -biotin sulfone was accomplished from commercially available l-cysteine. The synthesis features an unprecedented tandem S , N -carbonyl migration/aza-Michael/spirocyclization reaction from an l-cysteine-derived enone with aq. ammonia, in which three new sigma bonds and two rings are formed. In addition, the synthesis includes a highly diastereoselective late-stage Haller-Bauer reaction of sulfone for direct introduction of the carbon side chain.