Asymmetric Construction Of α-substituted β-hydroxy Lactones Via Ni Catalyzed Decarboxylative Addition Reaction

Enantioenriched Butyrolactones and Dihydrocoumarins specificallyα-functionalized scaffolds symbolize significant lactone moieties which are wildly found in natural products and pharmaceuticals as exemplified by microtermolides B,virginiae butanolides and salprzelactone.Retrosynthetic analys is indicated the direct catalytic asymmetricα-functionalization of lactones would be an ideal approach to enantioenriched α-substituted lactones.However,the high p Ka value of lactones’ α-proton makes them difficult to enolize under mild conditions;besides,the ring-opening possibility of cyclic ester moiety brings additional difficulties to the target.Accordingly,multiple operations were always required for the asymmetric synthesis of α-substituted lactones.developments of direct catalytic α-functionalizations of lactones are constantly in high demand,which may provide a general and convenient access to versatile α-substituted lactones from simple starting materials.Based on the nickel-chiral oxazoline catalysis,we explored the asymmetric highly enantio-and diastereoselective decarboxylative aldol reaction of 2-oxotetrahydrofuran-3-carboxylic acid /2-oxochromane-3-carboxylic acid derivatives with different kinds of carbonyls such as α,β,γ unsaturated ketoesters,isatin,and aromatic aldehydes.Addition decarboxylation reaction.After screening a series of reaction conditions,a series of α-substituted β-hydroxy lactone products were finally constructed with good yield and up to 99% ee.This asymmetric α-position functionalization of lactones provides an important way to obtain multifunctional α-substituted lactones from simple starting materials,and expands the application of the nickel-oxazoline catalytic system in asymmetric decarboxylative addition reactions...