A practical synthesis of enantiomerically pure (-)-geosmin via highly diastereoselective reduction of (4aS,8S)-4,4a,5,6,7,8-hexahydro-4a,8-dimethyl-2(3H)-naphthalenone

An asymmetric synthesis of (-)-geosmin 1 via highly diastereoselective reduction of the enantiomerically pure title ketone 3 is described. Diisobutylaluminum hydride reduction of 3 in a mixed solvent of tetrahydrofuran and 1,2-dimethoxyethane led to allylic alcohol 4 in 96% d.e., which by recrystallization from hexane, afforded a diastereomerically pure sample. This was then converted to 1 in high overall yield through a five-step reaction sequence including a completely stereoselective epoxidation of silyl ether 6 and a one-pot process of epoxy silyl ether 7 to mesylate 9. Copyright (C) 1996 Published by Elsevier Science Ltd