Asymmetric Total Synthesis of (<i>S</i>)-(+)-Cocaine and the First Synthesis of Cocaine C-1 Analogs from <i>N</i>-Sulfinyl β-Amino Ester Ketals

Abstract

Sulfinimine-derived α,β-unsaturated pyrrolidine nitrones, on heating with Al(O-t-Bu)3, undergo a highly stereoselective intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines, which are transformed in three-steps to give C-1 substituted cocaine analogs