Synthesis and conformational study of chiral oxepines: the Baylis-Hillman reaction and RCM approach with sugar aldehyde

Abstract

The Baylis-Hillman reaction of 3-O-allyl-α-D-xylo-pentodialdo-1,4-furanose 3 afforded a diastereomeric mixture of d-gluco- and l-ido-configured a-methylene-ß-hydroxy esters 4a and 4b, respectively, in a ratio of 2:3. Reduction of the ester functionality in 4a/4b gave alcohols 5a/5b. The diene thus formed in 5a/5b was subjected to ring-closing metathesis (Grubbs' second-generation catalyst) to afford oxa-bicyclic ring system 6a/6b in high yield. Further manipulation of the acetonide functionality in 6a and 6b afforded new polyhydroxylated oxepines 1a/2a and 1b/2b, respectively. The ¹H NMR of oxepines 1a and 1b in D₂O showed doubling of signals indicating their existence in two different rotamers/conformers. This fact was substantiated by calculating energetics of 1 and 2 conformers using the density functional theory and correlating the calculated ¹H NMR chemical shift pattern with that of the experimental spectra.