The A3 Redox-Neutral C1-Alkynylation of Tetrahydroisoquinolines: A Comparative Study between Visible Light Photocatalysis and Transition-Metal Catalysis

Considering the current challenges of the A(3) redox-neutral C1-alkynylation of tetrahydroisoquinolines (THIQs), we studied this synthetic tool under visible light photocatalysis and transition-metal catalysis in order to describe alternative reaction conditions and discuss possible improvements to this process. We demonstrated that 1-alkynylated THIQs can be readily obtained by three different approaches: iridium-based photocatalysis and copper ([CuBr(PPh3)(3)]) and silver (AgNO3) catalysis under mild, selective and accessible reaction conditions. Among these approaches, the copper(I)-based methodology resulted in the most robust, optimal reaction conditions for the synthesis of a series of 18 1-alkynylated THIQs in moderate to excellent yields and with high selectivity for the endo-alkynylated products. Moreover, this reaction can be accelerated by microwave irradiation (120 degrees C, 15 min) affording a novel library of diverse THIQs with alkyne and N-substituent moieties, from unreactive and uncommon substrates, that could be further transformed into new compounds of interest.

Automated summary

Through visible light photocatalysis and transition metal catalysis, we found that iridium-based photocatalysis as well as copper ([CuBr(PPh3)(3)]) and silver (AgNO3) catalysis can easily achieve 1-alkynylated THIQs under mild, selective, and accessible reaction conditions. The copper(I)-based methodology provided the most robust and optimal reaction conditions for synthesizing a series of 18 1-alkynylated THIQs with high selectivity for endo-alkynylated products.