Divergent Synthesis of Bicyclo[2.1.1]hexanes and Bicyclo[3.1.1]heptenes via Controllable Tandem Annulation/Rearrangement of Bicyclo[1.1.0]butanes and Vinyl Diazo Compounds

A divergent and practical one-pot synthesis of bicyclo[2.1.1]hexanes and bicyclo[3.1.1]heptenes from bicyclo[1.1.0]butanes and vinyl diazo compounds is reported. The tandem sequence is initiated with a Lewis acid-catalyzed formal [2σ + 2π] cycloaddition to generate valuable diazobicyclo[2.1.1]hexane. Subsequent chemoselective rearrangement of diazobicyclo[2.1.1]hexane, controlled by either rhodium catalysis or thermal promotion, affords 2-alkylidenebicyclo[2.1.1]hexanes or bicyclo[3.1.1]heptenes, respectively. The synthetic utilities of this protocol are highlighted by scale-up reactions, diversified product derivatization, detailed geometric characterization, and preliminary pharmacological evaluations.