An unexpected rearrangement during Mitsunobu epimerization reaction of sugar derivatives

Mitsunobu reaction on the glucose derivative (3S,4R,5R,6R)-3,4,5,7-tetraben zyloxy-6-hydroxy-1-heptene yielded an unexpected rearrangement major produc t. Its structure was determined as (3R,4R,5R,6S)-4,5,6,7-tetrabenzyloxy-3-h ydroxy-1-heptene. The suggested rearrangement mechanism involves an initial intramolecular cyclization, followed by ring opening by the nucleophile p- nitrobenzoate. Product distribution of the Mitsunobu reaction was substrate -dependent, with the corresponding mannose derivative (the 3R epimer) givin g less of the initial intramolecular reaction products and the correspondin g galactose derivative (the 5S epimer) yielding almost exclusively the expe cted epimerization product. Varying the Mitsunobu reaction conditions (addi tion of base and using nonpolar solvent) led to the expected epimerization product of the glucose derivative.