Chelation-assisted regioselective C-O bond cleavage reactions of acetals by Grignard reagents. A general procedure for the regioselective synthesis of protected polyols having one free hydroxy group

Acetals containing a neighboring heteroatom react with the Grignard reagent in aromatic hydrocarbon solvents regioselectively. The auxiliary moiety ca n be hydroxy, alkoxy, or amino but not sulfur. Chelation plays a key role i n directing the regioselectivity of this ring opening reaction. The reactio ns of acetonide derivatives of monosaccharides under these conditions affor d the corresponding products having only one free hydroxy group at the spec ific position. Fully protected mannosamine derivative is prepared in good y ield. The stereochemistry of the carbon center where auxiliary group is att ached can be either syn or anti to the acetal oxygen moiety where cleavage of the C-O bond occurs. However, difference in reactivity has been found in the reaction of tris-acetonide of sorbitol with MeMgI. Regioselective ring opening of the acetal group at the anomeric carbon generates a hemiacetal which underwent further nucleophilic addition to furnish the corresponding alcohol stereoselectively.