Asymmetric Organocatalytic Cascade Reaction For The Synthesis Of Substituted Oxazolidine, Oxazine Derivatives

In this assay, we have realized the efficient and highly stereoselective synthesis of a series of substituted multicyclic fused oxazolidine and oxazine derivatives bearing multiple chiral centres based on the development of asymmetric organocatalytic cascade reactions.In the first part of our research work we studied the researching methodology of the asymmetric organocatalytic cascade reactions of the rationally designed bifunctional nucleophiles of methyl 3-(2-hydroxyphenylamino)-3-oxopropanoate withα,β-unsaturated aldehydes. Based on the optimizations of catalysts, reaction temperature, solvent, and acidic additives, as well as the final expansion of the scope of different subjects, a seires of substituted multicyclic fused oxazolidine derivatives have been successfully prepared in good yields and highly stereoselective manner through a one-pot operation. The final products could be afforded in up to 93% yield and up to 96:4 dr values, and the ee values of them were generally>90%.Then we studied the cascade reactions of cinnamaldehyde with different nucleophiles of methyl 3-(2-carbamoylphenylamino)-3-oxopropanoate and methyl 3-(2-(hydroxymethyl) phenylamino)-3-oxopropanoate respectively, and succeeded in the preparations of a series of substituted oxazine derivatives. The enantioselectivities were excellent and all the ee values were>92%. The final products could be afforded in up to 99% yield and 1:1 to 5:1 dr values.Based on previous works, we have finally prepared a series of substituted multicyclic fused oxazolidine and oxazine derivatives bearing a quaternary chiral carbon centre by using multifunctional catalysts in the asymmetric cascade reactions of the above bifunctional nucleophiles with different vinyl ketones. The corresponding final products could be afforded in up to>99% yield, up to>98% ee values and most of them>8:1 dr values.