Enantioselective Synthesis of 1-Aryl Tetrahydroisoquinolines by the Rhodium-Catalyzed Reaction of 3,4-Dihydroisoquinolinium Tetraarylborates

The 1-aryl tetrahydroisoquinolines (1-aryl THIQs) are omnipresent in biologically active molecules. Here we report on the direct asymmetric synthesis of these valuable compounds via the reaction of 3,4-dihydroisoquinolinium tetraarylborates. The dual roles of anionic tetraarylborates, which function as both prenucleophiles and stabilizers of 3,4-dihydroisoquinolinium cations, enable this rhodium(I)-catalyzed protocol to convergently provide enantioenriched 1-aryl THIQs in good yields (<= 95%) with <= 97% ee, as demonstrated by the formal synthesis of (-)-solifenacin and the facile synthesis of (-)-Cryptostyline I.

Automated summary

The direct asymmetric synthesis of 1-aryl tetrahydroisoquinolines utilizing 3,4-dihydroisoquinolinium tetraarylborates is reported in this study. The dual roles of anionic tetraarylborates enable the convergent synthesis of enantioenriched 1-aryl THIQs in good yields with high enantioselectivity, as demonstrated by the formal synthesis of (-)-solifenacin and (-)-Cryptostyline I.