Enantio- and diastereo-convergent synthesis of (2R,5R)- and (2R,5S)-pityolthrough enzyme-triggered ring closure

A short chemoenzymatic synthesis of the (2R,5S)- and (2R,5R)-stereoisomer o f the bark beetle pheromone Pityol 1 was achieved from (+/-)-Sulcatol 2 in an enantio- and diastereo-convergent fashion without the formation of any ' unwanted' stereoisomer. The key steps include: (i) lipase-catalyzed deracem ization of (+/-)-2 using kinetic resolution coupled to an in-situ inversion or alternatively, dynamic resolution using combined lipase- and Ru-catalys is: and (ii) creation of the second stereogenic center by an epoxide hydrol ase-catalyzed diastereo-convergent hydrolysis of a haloalkyl oxirane, follo wed by spontaneous ring Closure to form 1 in a stereoselective fashion. (C) 2001 Published by Elsevier Science Ltd.