Stereoselective Synthesis of the Decahydroquinoline Alkaloid cis-195J.

Abstract

The first enantioselective synthesis of two C-5 diastereomers of the proposed structure of the decahydroquinoline alkaloid cis-195J has been achieved. The key step of our strategy is the highly stereoselective vinylogous Mukaiyama-Mannich reaction (VMMR), which gave rise to the first two stereogenic centers at the ring fusion with excellent diastereo- and enantiocontrol. Through alkyne cyclization and enamine reduction the correct cis-configuration between C-2, C-4a, and C-8a in the decahydroquinoline backbone was established. Subsequently, a radical cyclization of a tethered alkyl iodide onto the enoate assembled the bicyclic cis-decahydroquinoline as a mixture of two C-5 diastereomers. Further elaboration of the C-5 side chain eventually provided both diastereomers of cis-195J, which were readily separated, and their constitution and configuration were thus unambiguously proven for the first time.