Organocatalytic approach for the syntheses of corynantheidol, dihydrocorynantheol, protoemetinol, protoemetine, and mitragynine.

O-Trimethylsilyl (TMS)-protected diphenylprolinol-catalyzed Michael addition of a functionalized alkylidene malonate and n-butanal affords an aldehyde. This adduct can serve as the common intermediate for the assembly of secologanin tryptamine and dopamine alkaloids; this is demonstrated by the total syntheses of corynantheidol, dihydrocorynantheol, protoemetinol, and protoemetine, and the formal synthesis of mitragynine. The key steps include reductive amination of this aldehyde with tryptamine, condensation of this aldehyde with 4-methoxytryptamine, condensation of dimethoxyphenethylamine with a lactone derived from this aldehyde, and subsequent Bischler-Napieralski cyclization and reduction.