Application of an Organozinc Reagent Derived from (S)-Pyroglutamic Acid: A Formal Synthesis of Epibatidine.

A formal total synthesis of natural (−)-epibatidine has been developed. Key steps in the synthesis are a copper(I)-mediated coupling of an (S)-pyroglutamic acid-derived organozinc reagent with 1-iodo-3-trimethylsilyl-1-propyne and an N-acyl- or N-sulfonyliminium ion cyclization. Following this route, various N-protected hydroxylactams were converted into 7-azabicylo[2.2.1]heptane derivatives.