Synthesis of novel chiral dispiro pyrrolidines/pyrrolizidines via 1,3-dipolarcycloaddition and evaluation of their mechanism by DFT calculation

Optically active spirooxindoles containing pyrrolidine and pyrrolizidines framework have been proven to have broad spectrum of considerable bioactivity and curative applications.1 In this regard, spirooxindoles have received extensive attention in the last years and among all the developed synthetic methodologies, 1,3-dipolar cycloaddition has been found to be one of the most efficient and straightforward pathways, leading to rapid assembly of pyrrolidine and pyrrolizidine spirooxindole skeletons.2 In continuation of previous our works3, a variety of chiral dispiro pyrrolidines/pyrrolizidines have been synthesized in three and four contiguous and two quaternary stereogenic centers in generally high yields and excellent diastereo- and enantioselectivities (up to 99%). This new scaffold has been established via asymmetric 1,3-dipolar cycloadditions of acenaphthoquinone azomethine ylides with dipolarophiles which are generated from (S)-camphorsultam, as chiral auxiliary, with isatin-derived under optimized reaction conditions (Fig. 1). The structures of the products, after purification, were assigned and approved using NMR, mass, IR and single-crystal X-ray analysis. The reaction mechanism was discussed by quantum mechanical calculations.

Keywords:

1 , 3-Dipolar cycloaddition reaction , Azomethine ylide , Dispiropyrrolidines , Dispiro pyrrolizidines