Kinetic Resolution Of Allylic Alcohols Under Palladium/Sulfonyl Hydrazide Catalysis

Enantioenriched allylic alcohols present as important structural motif in various natural products and potential therapeutic agents. It is of great theoretical significance and application value to synthesis these compounds. Asymmetric synthesis and kinetic resolution are the most useful methods for the synthesis of chiral allylic alcohols. Previous reports about kinetic resolution of allylic alcohols were focused on the reactions of C=C bond, O-H bond and allylic C-H bond. However, those reactions had limitations on substrate scope and enantioselectivity. In this dissertation, we realized the resolution of allylic alcohols through the cleavage of C-O bond via asymmetric allylic substitution of allylic alcohols.Under 2,5-dicholobenzenesulfonyl hydrazide/[Pd(allyl)Cl]2/(S)-SEGPHOS catalysis, a series of racemic allylic alcohols were resolved through asymmetric direct allylic substitution of allylic alcohols with protected hydrazides. Chiral allylic alcohols and chiral allylic hydrazides were obtained with moderate to excellent yield and enantioselectivity with the selectlvity factors up to 698. These reactions also had high regioselectivity. The resolution results were much better with the a-alkyl and y-aryl substitutional allylic alcohols. When ?-substitutional allylic alcohols were used, the reaction could not smoothly proceeded. Compared with the reported methods, this method was more suitable for the allylic alcohols with large steric goup. As with the symmetric substrate (a=y=phenyl), the allylic alcohol can also be obtained with excellent enantioselectivity. The reaction condition was mild and could be operated simply. It is also a good method for the synthesis of chiral allylic alcohols and chiral allylic hydrazides.Mechanism study indicated that the sulfonyl hydrazide decomposed into sulfinic acid and sulfonic acid which together activated the hydroxyl of the allylic alcohols and assisted the chiral palladium complex which generated in situ to catalyze the reaction of allylic alcohols with protected hydrazides in high stereoselectivity via the cleavage of C-O bond. In this way, allylic alcohols were resolved with excellent eanatioselectivity. The regioselectivity of the reaction was depended on the nature of the ?-and ?-substituent and the conjugated production was preferential.