Total synthesis of sufentanil

Sufentanil, a potent anilidopiperidine analgesic, was synthesized from a simple thiophenylethylamine via six step sequence. The key parts of this synthesis involved an efficient construction of thiophenylethylpiperidone by aminomethano desilylation-cyclization followed by Swern oxidation and a direct regioselective N-nucleophilic spiral epoxide cleavage with aniline promoted by Lewis acids.