Palladium-catalyzed enantioselective cyclization of silyloxy-1,6-enynes.

Transition-metal-catalyzed cycloisomerization and cyclization reactions of enynes have emerged as powerful methods for the construction of heteroand carbocyclic compounds.1 More recently, enantioselective cycloisomerization of 1,6and 1,7-enynes has been employed in the preparation of enantioenriched 1,4-diene containing structures.2-4 Despite its potential utility, the related enantioselective cycloisomerization of heteroatom-substituted alkenes5 has not been reported. Herein we report the first enantioselective cyclization reactions of 1,6-enynes containing silyloxy-substituted olefins. On the basis of our recent report on palladium-catalyzed enantioselective 5-exo-dig addition of 1,3-dicarbonyl compounds to alkynes,6 we hypothesized that similar catalysts might promote the enantioselective cycloisomerization of silyl enol ethers. To this end, reaction of silyl enol ethers 1a (3:1 Z:E) and 1b (2:1 Z:E) catalyzed by 10 mol % of ((R)-DTBM-Segphos)Pd(OTf)2 (A) cleanly afforded methylene cyclopentane 2 in 63 and 77% ee, respectively (eq 1). Furthermore, diastereomerically pure (E)-1b afforded 2 with greater enantioselectivity (81% ee) than the corresponding (Z)-isomer (74% ee). The enantioselectivity was further improved to 91% ee by employing tert-butyldimethylsilyl enol ether (E)-1c.