Application of Intramolecular Enyne Metathesis to the Synthesis of Aza[4.2.1]bicyclics: Enantiospecific Total Synthesis of (+)-Anatoxin-a

A concise synthesis of the potent nAChR agonist (+)-anatoxin-a (1) has been completed in a series of only nine chemical operations and 27% overall yield from commercially available D-methyl pyroglutamate (4). The synthesis features a novel procedure for the diastereoselective preparation of cis-2,5-disubstituted pyrrolidines leading to 10, which underwent an intramolecular enyne metathesis to afford a bridged azabicyclic intermediate that was transformed into 1. [reaction: see text]