An unprecedented Ag-catalyzed exo'-selective [3 + 2] cycloaddition of imino esters with 4-benzylidene-2,3dioxopyrrolidines is described. The reaction was efficiently catalyzed by Ag/(R, S p )-ThioClickFerrophos (TCF) leading to the construction of the corresponding spirobipyrrolidine scaffolds in excellent enantio-and diastereoselectivities. This reaction is the first example of a silver-catalyzed exo'-selective asymmetric [3 + 2] cycloaddition, as well as the first exo'selective spirobipyrrolidine construction via a [3 + 2] cyclo-addition process using imino esters. The wide substrate scope of this reaction enabled the preparation of structurally diverse spirobipyrrolidine derivatives, which are attracting attention as targets for drug discovery. Mechanistic studies suggested that the unusual exo'-selectivity of this reaction is not due to epimerization following the common exo-or endo-selective cycloaddition, but instead is due to a stepwise Michael addition/Mannich sequence with bond rotation.

The asymmetric 1,3-dipolar cycloaddition of glycine imino esters to 1-propene-1,3-sultone or sulfocoumarins is described. The reaction was efficiently catalyzed by Cu­(MeCN)4BF4/DTBM-Segphos or Cu­(MeCN)4BF4/tBu-FcPhox at room temperature to afford fused pyrrolidines as single regioisomers with excellent diastereoselectivity and enantioselectivity. The broad substrate scope of this reaction provides convenient access to structurally diverse multisubstituted pyrrolidines in an optically pure fashion.

The 1,3‐dipolar cycloaddition of glycine imino esters (azomethine ylide precursors) with 1‐propene‐1,3‐sultone proceeded smoothly by using copper phosphine complexes at room temperature to give the bicyclic sultone‐fused pyrrolidines as single regio‐ and stereoisomers in good yields. A preliminary asymmetric reaction with a chiral copper complex gave the fused sultone‐pyrrolidine with excellent enantioselectivity.

The conjugated addition reaction of 1-pyrroline-5-carbonitrile to α-enones was effectively catalyzed by AgF/ThioClickFerrophos (TCF) in diethyl ether in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and nearly single diastereomers of adducts with good enantiomeric excesses (up to 97% ee) were obtained in high yields. The reduction of the nitrile group with H2/Raney Ni in ethanol successfully transformed the conjugate adduct to the corresponding spirocyclic piperidine (60% yield) as a single stereoisomer.