Diethylzinc-Promoted Synthesis of Trifluromethyl-Containing Tryptamine Analogues from Indoles and 2-Trifluromethyl-N-(4-Toluenesulfonyl)-Aziridine

Abstract

Incorporation of fluorine atoms into biologically active organic molecules often causes enhancement of activity, stability, and solubility, as well as reduction of toxicity. Tryptamine derivatives are known for important medicines concerning our mental health. Therefore, fluorinated tryptamine derivatives could be promising medicinal candidates for pharmaceutical chemistry. We have already reported the regioselective ring-opening reaction of 2-CF3-N-Ts-aziridine (Ts=4-toluenesulfonyl) with some nucleophiles. If this ring-opening reaction proceeds smoothly at the C3 position of indoles, it could provide a solution for the synthesis of CF3-containing tryptamine analogues. We examined the diethylzinc-promoted direct C3 alkylation of indoles with 2-CF3-N-Ts-aziridine under basic conditions. We have developed the synthesis of CF3-tryptamine from 2-CF3-N-Ts-aziridines and indoles by using diethylzinc as a base with excellent yields and complete regioselectivity.