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

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.