Synthesis Of Five-Membered Cyclic Nitrone And Dihydroazines By Palladium-Catalyzed Cyclization Of ?,?-Alkenyl Oximes

Cyclic nitrones and dihydrooxazine are two very important heterocyclic compounds.Cyclic nitrone has important application value in biomedicine,free radical chemistry,polymer industry et.al.In the field of organic synthesis,cyclic nitrones are often used as valuable synthetic intermediates.Dihydroazines and their aza analouges are important structural component of natural products,herbicides and broad-spectrum fungicides,and also serve as key synthetic intermediates.In this thesis,we studied the Pd-catalyzed intramolecular carbocyclization of vinyl oximes.Under the catalysis of Pd(0)/xantphos systems,a series of five-membered cyclic nitrone and dihydrooxazine derivatives were synthesized from the carbocyclization of ?,?-unsaturated vinyl oxime with aryl and alkenyl halides.The structure of the substrate is found to play an important role in controlling the regioselectivity of the reaction.Substrate bearing germinal dimethyl substitution at ?-position of the oxime delivered five-membered cyclic nitrone,in other substrates six-membered cyclic oxime ether are formed.Reactions of these two types of substrates demonstrated different requirements for ligand structure.The reason for the selectivity difference may rise from a change in mechanism.We speculate that the formation of dihydroxazine may proceed via through the innier-sphere cis-oxypalladation mechanism,while the five-membered cyclic nitrones may be generated via an outer-sphere trans-aminopalladation.These transformations hinge on catalyst-controlled events to synthesize these important heterocyclic compounds.Mechanistic insights gleaned from this study paved the way for the development of catalytic asymmetric versions.