Thiourea-Catalyzed Domino Michael–Mannich [3+2] Cycloadditions: A Strategy for the Asymmetric Synthesis of 3,3′-Pyrrolidinyl-dispirooxindolesFinancial support from the European Research Council (ERC Advanced Grant 320493 ‘DOMINOCAT’) is gratefully acknowledged.
Received: 22 May 2017
Accepted after revision: 08 June 2017
13 July 2017 (eFirst)
Dedicated to Professor Victor Snieckus on the occasion of his 80th birthday
The asymmetric synthesis of trifluoromethylated 3,3′-pyrrolidinyl-dispirooxindole derivatives with four contiguous stereogenic centers, including two vicinal spiro-stereocenters, is described. Employing a bifunctional thiourea catalyst, a domino Michael–Mannich [3+2] cycloaddition occurs readily between isatin ketimines and isatin-derived enoates with good yields and very high stereoselectivities, providing a direct entry to the title compounds of potential medical value.