An efficient, one-pot reductive alkylation of indoles with N-protected aminoethyl acetals in the presence of TES/TFA is reported. It represents the first general method for the direct synthesis of tryptamine derivatives from indoles and nitrogen-functionalized acetals. This convergent and versatile approach employs safe and inexpensive reagents, proceeds under mild conditions, and tolerates several functional groups. The new procedure was efficiently applied to a gram-scale synthesis of both luzindole, a reference MT2-selective melatonin receptor antagonist, and melatonin.

Synthesis of Tryptamine Derivatives via a Direct, One-Pot Reductive Alkylation of Indoles. -The method can be used to synthesize melatonin (VIII) and luzindole (IIIe), an MT2 melatonin receptor antagonist. -(RIGHI, M.; TOPI, F.; BARTOLUCCI, S.; BEDINI, A.; PIERSANTI*, G.; SPADONI, G.; J. Org. Chem. 77 (2012) 14, 6351-6357, http://dx.