Solvent-Free, Uncatalyzed Asymmetric “Ene” Reactions of N-tert-Butylsulfinyl-3,3,3-trifluoroacetaldimines: General Approach to Enantiomerically Pure alfa-(Trifluoromethyl)tryptamines.
A novel approach to regioselectively substituted and stereoselectively -trifluoromethylated tryptamines is reported based on the ene reaction of Boc-protected 3-methyleneindolines with optically pure (R)- or (S)-tert-butanesulfinyltrifluoroacetaldimine. Boc- and sulfinylamido-protected -trifluoromethyltryptamines are obtained in 60-70% yield and 85/15 dr by just heating equimolar amounts of the two reaction partners at 80–90 °C for 2-3 h without solvent. The absolute configuration of the amino -carbon has been assigned based on the vibrational circular dichroim (VCD) spectral analysis. The two protecting group can be chemoselectively removed allowing further regio- and stereoselective elaboration of the ene products to various biologically interesting compounds.