Highly Enantioselective Construction of Polycyclic Spirooxindoles by Organocatalytic 1,3‐Dipolar Cycloaddition of 2‐Cyclohexenone Catalyzed by Proline‐Sulfonamide

Abstract

The enantioselective 1,3‐dipolar cycloaddition of 2‐cyclohexene‐1‐one and azomethine ylides generated in situ from isatins and amino esters was developed by employing prolinosulfonamides as the catalyst. Consequently, novel polycyclic spirooxindole scaffolds with three contiguous stereocenters were prepared in high yield (up to 95 %) with excellent diastereo‐ (>20:1 dr) and enantioselectivity (up to 99 % ee).

Recent Advances of Catalytic Asymmetric 1,3-Dipolar Cycloadditions

“…179 The [3+2] cycloaddition using cyclohexenone as electrophile was developed by Yang and co-workers (Scheme 124). 180 By using proline 4-dodecylbenzenesulfonamide 279 as catalyst, the reaction of azomethine ylides generated from isatins and αaminomalonate provided spirooxindoles 280 stereoselectively.…”

Decade Advance of Isatin in Three‐component Reactions

“…The hydrogen‐bonding interaction among phosphoric acid 22.1 , phenols and imines 22.2 .This kind of transient intermediates was helpful for the generation of 22.3 . The Yang group [22b] reported the organic catalyzed‐enantioselective construction of polycyclic spirooxindoles 22.4 (Scheme 22).…”

Bifunctional Sulfonamide as Hydrogen Bonding Catalyst in Catalytic Asymmetric Reactions: Concept and Application in the Past Decade

“…Asymmetric synthesis of spirooxindoles was successfully overcome by Yang and coworkers through 1,3‐dipolar cycloaddition of cyclic enones with azomethine ylides which produced in situ from isatins and aminomalonate diesters (Scheme 37). [91] With powerful ‘Hua Cat’ 5 , highly enantio‐ and diastereoselective spiro products were afforded in good yield from various 5‐ or 6‐substituted isatins and different aminomalonic acid substrates. However, 7‐substituted isatins gave declined dr ratio and ee value in 5 catalysis for the reason that substituted group on C 7 position of isatins hindered the formation of H‐bond between 5 and N−H moiety on isatins.…”