Reagent-controlled stereoselective synthesis of lignan-related tetrahydrofurans.

The reaction of ring-closing metathesis-derived cyclic allylsiloxanes 3 with aldehydes in the presence of a Lewis acid gives 2,3,4-trisubstituted tetrahydrofurans related to the furanolignan family of natural products. The reactions proceed with complete 3,4-trans stereoselectivity, whereas the C-2 stereochemistry depends on both the aldehyde and Lewis acid used. When boron trifluoride etherate is used with aliphatic or electronically neutral aryl aldehydes, the reactions favor the production of the 2,3-cis isomer 8, whereas electron-rich aryl aldehydes lead to the 2,3-trans isomer 9 by Lewis acid-mediated isomerization of the kinetically favored cis isomer. The isomerization can be avoided by use of TMSOTf as a promoter, and hence, the stereochemistry can be tuned by appropriate choice of reagent. Cleavage of the pendant 3-ethenyl group installs the 3-hydroxymethyl group common to the furanolignans. Copyright 2004 American Chemical Society