Enantioselective Synthesis of 8-Hydroxytetrahydroisoquinolines

Significance

The synthesis of 8-hydroxytetra­hydroisoquinolines by electrophilic aromatic substitution is a challenging problem. Indeed, due to steric hindrance around the hydroxy group, the competitive formation of a second constitutional isomer occurs. An alternative appears to be the gold-catalyzed phenol synthesis starting from furans via an arene oxide intermediate with intra­molecular migration of the oxygen (A. S. K. Hashmi et al. J. Am. Chem. Soc. 2000, 122, 11553-11554; Angew. Chem. Int. Ed. 2005, 44, 2798-2801). The starting substrate could be accessed in high enantiomeric purity by rhodium-catalyzed hydrogenation of furyl-substituted dehydroamino acids.