Diamino Alcohol Catalyzed Enantioselective Crossed Aldol Reaction of Acetaldehyde with Isatins - A Concise Total Synthesis of Antitumor Agents

Enantioselective crossed aldol reactions of isatin derivatives and acetaldehyde have been developed with a series of simple diamino alcohol catalysts to afford 3-substituted 3-hydroxyindolin- 2-ones in high chemical yields (up to 95 %) and optical purities (up to 92 % ee). The synthetic potential of the present protocol has been demonstrated by concise, enantioselective, protecting-group-free, and transition metal-free total syntheses of antitumor and antiviral agents with the tryptanthrin architecture, that is, phaitanthrin B and cephalanthrin A, along with the biologically active indolidine alkaloids chimonamidine and donaxaridine as well as the formal synthesis of CPC-1. The highly enantioselective outcome of this catalytic crossed aldol reaction was evaluated by calculating the Gibbs free energies of the possible transition states.