Asymmetric Synthesis Of 1,2-Oxzaetidines And Their Synthetic Application Research

1,2-Oxazetidines are important heteocyclic compounds containing both nitrogen and oxygen atoms within a compact four-membered ring.These compounds could be potentially utilized for the development of novel reactions or even the conventionally difficult-to-access chemical transformations due to their intrinsic high energy embedded in the strained structure.Currently,the reported approaches for the preparation of1,2-oxazetidines are rare.In particular,the asymmetric methods towards this class of heterocycles are even rare.Therefore,development of efficent methods for the synthesis of chiral 1,2-oxazetidines and application of these strained molecules for the development of new reactions will be highly desirable.In this thesis,we have designed a general and practical method to access a series of structurally diverse chiral 1,2-oxazetidines from readily available chiral epoxides and?-bromo esters,both of which in turn could be readily prepared from amino acids as cheap chiral sources,in 3-4 steps by using mild Mitsunobu reactions as an efficient ring-closure approach to form the highly strained four-membered rings.The new method is operationally simple,and a range of N-nosyl-protected 3-and 4-substituted as well as 3,4-disubstituted chiral 1,2-oxazetidines could be conveniently prepared in gram-scale with excellent enantioselectivities(93–99% ee)and good overall yields for the first time.After establishing the new method for the synthesis of chiral 1,2-oxazetidines,we next carried out the synthetic utility research of these molecules.We found that oxygen atom in the 1,2-oxazetidine ring demonstrated unique electrophilic reactivity.Under alkaline conditions,methyl 2-cyano-2-phenylacetate could function as carbon nucleophilie to react with chiral 1,2-oxazetidines,providing the amino-tethered ether product via umpolung C-O bond-forming reaction.Subsequently,this intermediate compound could undergo intramolecular cyclization to generate the morpholine heterocycles in 51% yield and 1.3:1 dr.These preliminary results from current research proved the great values of 1,2-oxazetidines,which makes a good starting point for our future research.