Catalytic Asymmetric[4+2] Cycloaddition Reaction For The Construction Of Enantioenriched Nitrogen Heterocycles

Enantioenriched nitrogen heterocycles exist widely in numerous natural products and chiral bioactive pharmaceutical molecules.Catalytic asymmetric annulation reaction is one of the commonly used and effective methods for the synthesis of chiral nitrogen heterocycles.For the purpose of developing efficient methodologies for the constructing of chiral six-membered nitrogenous heterocycles,we have accomplished two following research works:1)An unprecedented Cu(?)/tBu-BOX catalyzed cascade 1,6-Michael addition/1,4-Michael addition reaction of 2-silloxyl furan with in situ generated aza-alkene was developed successfully for the first time.An array of optically active tetrahydrofuro[3,2-c]pyridazine containing multiple stereocenters was generally obtained in high yields with excellent diastereo-and enantioselectivities.Studies on the Carbon isotope effects of 2-silloxyl furan in the reaction revealed a stepwise mechanism for this annulation process;2)A highly efficient enantioselective Nitroso Diels-Alder reaction of aryl-nitroso compounds with various 1,3-dienes was successfully developed under the catalysis of Cu(?)and chiral ligand TF-BiphamPhos which was designed and synthezed by our laboratory recently.A series of multi-substituted dihydro 1,2-oxazines derivatives was obtained in good yields with excellent enantioselectivities and diastereoselectivities.Based on the absolute configuration of the cycloaddition products,a possible transition state was proposed to rationalize the stereoselectivity of this Nitroso Diels-Alder reaction.