Palladium-Catalyzed Hydroamination Route to 2-Substituted Tetrahydroquinolines

Significance

The palladium-catalyzed intramolecular addition-cyclization of aniline-alkynes (hydroamination) to tetrahydroquinolines using the catalyst system Pd(PPh₃)₄ [20 mol%]/PhCOOH [50 mol%] is reported. In the absence of benzoic acid, no reaction takes place. The reaction tolerates aromatic and aliphatic alkynes and does not require N-protection. The yields of the products range between good to excellent, except in one case (R¹ = H; R² = t-Bu) for which no product was formed. The scope of the reaction was extended to an asymmetric version, using (R,R)-RENORPHOS as the chiral ligand. The synthetic utility of the methodology was demonstrated by the successful synthesis of two alkaloids, (+/-)-angustureine and (+/-)-galipinine.