Brønsted Acid Mediated Cyclization of Enaminones. Rapid and Efficient Access to the Tetracyclic Framework of the Strychnos Alkaloids

The development of an efficient diastereoselective method that permits rapid construction of the tetracyclic core 17 of the Strychnos-Aspidosperma alkaloids is described. Enaminone 16, synthesized in high yield, has been cyclized under the influence of a Brønsted acid to provide the core tetracyclic framework 17 of the Strychnos alkaloids in optically active form or alternatively to the β-ketoester tetrahydro-β-carboline (THBC) unit 18, by varying the equivalents of acid and the molar concentration. Attempts to utilize 18 to form the C(7)–C(16) bond of the akuammiline related alkaloids represented by strictamine (22), using metal-carbenoid chemistry, are also described.