Electrochemically Driven Deracemization of Tetrahydroisoquinolines

Tetrahydroisoquinolines (THIQs) 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. Despite their importance, the synthesis and preparation of these compounds, is still a challenging task which often requires the use of harsh conditions and toxic reagents.1 Nowadays, the advent of radical chemistry allowed to open new opportunities to explore the reactivity of the different functional groups, especially electrochemistry emerged as a powerful technique for organic chemistry, allowing to improve selectivity and scalability of processes.2 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. This protocol has been also developed under flow conditions in order to both increase the scalability and the productivity of the overall process. References: [1] B. K. Kumar, K. V. G. C. Sekhar, S. Chander, S. Kunjiappan and S. Murugesan. RSC Adv., 2021, 11, 12254–12287. [2] M. Yan, Y. Kawamata & P.S. Baran. Chem. Rev. 2017, 117, 13230–13319