Palladium-catalyzed Asymmetric Allylic Etherification Of Vinylethylene Carbonates With Alcohols

Many natural products and drug molecules contain motifs of chiral teriary alcohols.The construction of chiral teriary alcohols is a significant objective in the field of organic synthesis.The most common method to construct chiral teriary alcohols includes transition-metal-or organocatalyzed asymmetric addition of carbon nucleophiles to ketones.However,this method has some difficulties such as relatively low reactivity and challenging carbonyl enantiofacial differentiation.Asymmetric catalytic dihydroxylation and epoxidation of 1,1-disubstituted alkenes are also useful methods for the construction of chiral teriary alcohols.However,unsatisfied enantioselectivities are usually obtained when the two alkene substituents are of similar steric demand.So it is very important to develop new methods to construct chiral tertiary alcohol detivatives.Transition-metal-catalyzed enantioselective allylic etherification is a powerful method for the construction of secondary allylic alcohol derivatives.However,regioselective construction of tertiary allylic ethers using this method for 1,1-or 3,3-disubstituted allylic electrophiles is still a challenging task.This research disclosed the palladium-catalyzed asymmetric allylic etherification of quaternary vinylethylene carbonates(VECs)with alcohols.The reaction has some difficulties such as the normal poor reactivity of alcohols as nucleophiles.Some measures must be taken to make the alcohols react regioselectively to give the vicinal hydroxyether.The reaction must be controlled carefully to prevent the product primary alcohol to compete effectively with the reactant alcohol.And diastereomeric interconversion of the ?-allylpalladium intermediates should occur faster than nucleophilic attack.In order to overcome the difficulties,triethylborane was used as a co-catalyst.Products containing quaternary stereocenters were obtained with good yield and enantioselectivity.Varies of VECs and alcohols were used in this reaction to expand the scope of substitutions.