Catalytic Asymmetric Construction of Spirocycles Containing Pyrrolidine Motifs and Spiro Quaternary Stereogenic Centers via 1,3-Dipolar Cycloaddition of Azomethine Ylides with 2-Alkylidene-Cycloketones

The first catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with various sterically hindered alpha,alpha,beta-trisubstituted 2-alkylidene-cycloketones has been developed successfully with silver acetate/TF-BiphamPhos complex for the construction of spiro heterocyclic compounds containing pyrrolidine motifs and a spiro quaternary stereogenic carbon center. The highly efficient catalytic system exhibited high reactivity, excellent diastereoselectivity, good enantioselectivity and broad substrate scope under mild conditions. Subsequent transformations led to the expedient preparation of synthetically useful spiro[pyrrolidine-tetrahydropyranone] and spiro[pyrrolidine-isochroman-1-one] without loss of the diastereo- and enantiomeric excesses.