Asymmetric Decarboxylative Cycloaddition Of Vinylethylene Carbonates With ?-nitroolefins By Cooperative Catalysis Of Palladium Complex And Squaramide

The tetrahydronfuran heterocycle is a commonly found structure in natural products and medicinally relevant compounds.So the methodology of synthesis of multisubstituted tetrahydrofuran is very important.Transition-metal-catalyzed stereoselective intermolecular [3+2] cycloaddition is a powerful method for the construction of chiral multisubstituted tetrahydrofuran derivatives.The cycloaddition of C,O-1,3-dipole with activated alkenes is reported.However,two activators are needed for alkenes.Developing an asymmetric [3+2] cycloaddition of C,O-1,3-dipole with electron-deficient alkenes bearing a single activator remains a challenge.Most recently,we have developed a more stable and readily available substrate vinylethylene carbonates(VECs),which easily underwent decarboxylation in the presence of Palladium catalyst to generate C,O-1,3-dipole.Based on our methodologies in construction of quaternary stereocenters via Pd-catalyzed asymmetric decarboxylative cycloaddition of vinylethylene carbonates(VECs),we envisioned a novel cooperative catalysis strategy using palladium complex and squaramide to achieve the decarboxylative cycloaddition of VECs with nitroolefins.After the condition optimizations,we found the best chiral ligand and chiral squaramide for this methodology.The process provided multisubstituted tetrahydrofurans bearing three continuous chiral centers in good to high yields with acceptably high enantio-and diastereoselectivities.For confirming the utility of this methodology,the study of substrate scope,gram-scale transformation and product derivatization were also finished.