Organotin Nucleophiles. 6. Palladium-Catalyzed Allylic Etherification with Tin Alkoxides

Article abstract of DOI:10.1021/jo00219a023

Tin alkoxides, although mildly nucleophilic, were found to be highly reactive nucleophiles toward ?-allyl palladium intermediates.Providing a chemoselective approach to allylic etherification, these organotin reagents substitute allylic acetates in the presence of the other electrophilic functional groups such as primary halides.With respect to the two termini of the allylic system, the regioselectivity of nucleophilic attack by tin alkoxides was found to follow the characteristic behavior of stabilized carbanions and amines, namely, preferred attack at the less sterically hindered position and/or at the position remote from an electron-withdrawing substituent.The stereochemical course of the allylic etherification was examined by using an indicator substrate 22b and following the reaction by 1H NMR.Tin phenoxide was found to substitute 10 times faster than epimerization of either starting material or product in a mildly stereospecific manner, the major product retaining the configuration of the starting material.This method has been applied to protect hydroxyl groups of carbohydrates and for selective glycosidation of allylic aglycons.This approach complements the more common Koenigs-Knorr method, providing the α-stereoisomer as the major product.Dialkyloxydialkyltin reagents were found to be as reactive nucleophiles as the monoalkoxide varieties providing a short and useful synthetic approach for obtaining macrocyclic unsaturated polyethers.