Asymmetric catalytic alkylation of vinyl azides with 3-bromo oxindoles: water-assisted chemo- and enantiocontrol

A highly chemo- and enantioselective alkylation of vinyl azides with 3-bromo-3-substituted oxindoles was achieved through a chiral N,N & PRIME;-dioxide/Ni(OTf)(2)-mediated conjugate addition/water addition/elimination tandem process. Water was critical to the chemo- and enantioselectivity. The hydrated Na3PO4 acted as both a base and a reservoir to regulate the amount of water in solution. A wide range of enantioenriched oxindoles having alpha-carbonyl-substituted all-carbon quaternary stereocenters were achieved in good yields and good ee values (51 examples, up to 90% yield, 97% ee). Easy transformations of products to analogues of (+)-physovenine and (+)-desoxyeseroline enhanced the synthetic value. Mechanistic studies including control experiments, kinetic studies, and density functional theory (DFT) calculations, enabled a proposition of a possible catalytic cycle along with transition states to elucidate the reaction process and chiral induction.

Automated summary

A highly chemo- and enantioselective alkylation of vinyl azides with 3-bromo-3-substituted oxindoles was achieved using a chiral N,N'-dioxide/Ni(OTf)2-mediated tandem process. Water played a critical role in the chemo- and enantioselectivity, and hydrated Na3PO4 served as both a base and a water reservoir. The reaction produced a wide range of enantioenriched oxindoles with alpha-carbonyl-substituted all-carbon quaternary stereocenters, and the products could be easily transformed into valuable analogues.