Several synthetic routes to the analgesic alkaloid epibatidine have been ex
plored. Approaches starting from tropinone, involving either ring-cleavage
followed by intramolecular aldol reaction, or Favorskii ring-contraction, w
ere not successful. A successful route was established, involving cycloaddi
tion of an N-protected pyrrole with ethynyl p-tolyl sulfone to prepare the
required azabicyclo[2.2.1] skeleton. Completion of the synthesis required s
ubsequent partial hydrogenation, addition of a metallated pyridine to an al
kenyl sulfone, desulfonylation and brief functional group interchange and n
itrogen deprotection. The synthesis proceeds in only six steps from the sta
rting N-Boc pyrrole and furnishes the natural product in about 24% yield ov
erall.