Stereoselective Total Synthesis of Natural (+)-Streptazolin via a Palladium-Catalyzed Enyne Bicyclization Approach

The natural Z isomer of (+)-streptazolin (1), isolated from cultures of Streptomyces viridochromogenes, was synthesized in an optically pure form for the first time on the basis of a palladium-catalyzed enyne bicyclization approach in 12 steps and 4.3% overall yield from (3R,4R)-3,4-bis(benzyloxy)succinimide (5). The requisite enyne 13 for palladium-catalyzed bicyclization was prepared from 5 via N-acyliminium ion cyclization of the acetoxy lactam 9, partial reduction of 10 with DIBALH−BuLi, and conversion to the dibromo olefin 12. The best result in the palladium-catalyzed bicyclization was obtained when treated with 30 mol % Pd(OAc)2 and N,N ‘-bis(benzylidene)ethylenediamine (BBEDA) as the ligand in benzene at reflux, thus affording a 93:7 mixture of the 1,2,4a,7a,6,7-hexahydro-5H-1-pyrindine (Z)-14 along with its isomerized product (Z)-15 in 84% total yield. The isomerization of the 1,4-diene in (Z)-14 to the 1,3-diene was achieved by treatment with triiron dodecacarbonyl to generate the stable tricarb...