AN ASYMMETRIC ROUTE TO THE CONANINE BCDE RING-SYSTEM - A FORMAL TOTALSYNTHESIS OF (-CONESSINE())

The first enantioselective synthesis of the known (+)-conessine precur sor (+)-benzohydrindan 23 from the chiral nonracemic bicyclic lactam 1 is described, The key transformation was the highly diastereoselectiv e (3 + 2) cycloaddition of azomethine ylide 11a to lactam 7 in order t o construct the pyrrolidine E ring system at any early stage in the sy nthesis. The requisite pyrrolidine methyl group at C-21 was stereosele ctively installed late in the synthesis by lithiation of N-Boc-pyrroli dine intermediate 20 with sec-BuLi/TMEDA followed by quenching at -90 degrees C with iodomethane, furnishing the tetracyclic pyrrolidine 21. Reduction of t-Boc 21 with lithium aluminum hydride; affords (+)-N-me thyl tetracycle 23 in a concise 13-step synthesis from 1.