Catalyst-/Additive-Free One-Pot Synthesis of Oxazolidines in Water via Regioselective and Stereoselective C-H Functionalization Approach

A catalyst-free approach for the synthesis of oxazolidine derivatives is developed here. Though the synthesized oxazolidines contain three stereogenic centers, single diastereomer of the product is obtained. Single crystal X-ray analysis of the product confirmed the stereochemistry. The reaction is performed by taking tetrahydroisoquinoline/cyclic benzylic amine (1 equivalent) and aromatic aldehyde (2 equivalent) in water under refluxing condition which produces excellent yield (87-96 %). With pyrrolidine as amine substrate, the reaction gives alpha,beta-unsaturated cyclic imines which is an example of beta-C-H functionalization of secondary amine. The proposed mechanism shows that the reaction proceeds through the formation of azomethine ylide which undergoes [3+2]-cycloaddition reaction providing the oxazolidine product.