Unusual 1,5-Hydride Shifts in Lewis Acid Mediated Reactions of Benzylated Sugars. Synthesis of 3-Alkylisochroman Derivatives

Article abstract of DOI:10.1021/jo00249a028

Tin(IV) chloride mediated reactions of methyl 3,5-di-O-(4-chlorobenzyl)-2-O-(3-methoxybenzyl)-D-arabino- and -D-xylofuranosides 5 and 13 afforded unexpectedly, in one step, 3-alkyl-7-methoxyisochroman derivatives 7 and 14, respectively.These products are formed, most probably, by way of a complex process involving the intramolecular Friedel-Crafts alkylation of the activated benzyl group at O-2, leading to an internal aryl C-furanoside (e.g. 6), followed by an in situ reductive opening of the tetrahydrofuranyl ring of the intermediate C-furanoside.An experiment with a deuterium-labeled substrate demonstrated that this reductive step occurred by way of a stereospecific, tin(IV) chloride promoted 1,5 shift of a hydride ion from the 4-chlorobenzyl substituent at O-3 to the "anomeric" position of the C-furanoside, with retention of configuration at the migration terminus, and formation (after aqueous processing) of 4-chlorobenzaldehyde as a byproduct.This process provides a convenient methodology for the synthesis of enantiomerically pure isochroman derivatives from readily available carbohydrate precursors.