Solvent-free, uncatalyzed asymmetric ene reactions of N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines: a general approach to enantiomerically pure α-(trifluoromethyl) tryptamines

A novel approach to regioselectively substituted and stereoselectively alpha-trifluoromethylated tryptamines is reported based on the ene reaction of Boc-protected 3-methyleneindolines with optically pure (R)- or (5)-tert-butanesuEfinyEtrifluoroacetaEdimine. Boc- and sulfinylamido-protected alpha-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 a solvent. The absolute configuration of the amino alpha-carbon has been assigned based on the vibrational circular dichroism (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.