Electrochemical-Driven Deracemization of Tetrahydroisoquinolines

Tetrahydroisoquinolines (THIQs) alkaloids represent an important class of molecules that exhibit biological properties, making them highly significant in pharmaceutical research and drug development. Different THIQ alkaloids are used as anti-inflammatory, anti-bacterial, anti-viral, anti-fungal, anti-leishmanial, anti-cancer, and anti-malarial agents.1 Despite their importance, the synthesis and preparation of these compounds, especially in an enantioselective manner, is still a challenging task which often requires the use of harsh conditions and toxic reagents.1 On the other hand, the stereoselective reduction of α-substituted Dihydroisoquinolines (DHIQs) is very well known; the main drawback is that the synthesis of DHIQs remains difficult due to the isolation and stability of these compounds. In order to find a valuable methodology for the synthesis of enantiomerically pure α-substituted THIQs, our group decided to study the possibility to directly oxidize these compounds to the corresponding DHIQs by using electrochemistry as a versatile and mild energy source; subsequently the direct stereoselective reduction of the electrogenerated DHIQ intermediate will deliver the desired enantioenriched THIQ.