Direct Catalytic Decarboxylative C1-Alkylation of Unprotected Tetrahydroisoquinolines via Photoredox Catalysis

The direct catalytic functionalization at the C1-position of unprotected tetrahydroisoquinolines (THIQs) remains a challenging task in synthetic chemistry. In this study, we have developed a photocatalytic strategy that utilizes readily available alkyl carboxylic acids as alkylating agents. Under the catalysis of 9-phenylacridine and visible-light irradiation, direct decarboxylative alkylation of unprotected THIQs has been achieved. This method requires no prefunctionalization of substrates and exhibits excellent substrate compatibility with a wide range of carboxylic acids and THIQ derivatives, providing an efficient and versatile approach for the rapid assembly of pharmaceutically active C1-alkylated 3,4-dihydroisoquinoline (DHIQ) skeletons.