Abstract
Considering the current challenges of the A3 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 °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.
Key words A
3 coupling reaction - C1-alkynylation - tetrahydroisoquinolines - photocatalysis - transition-metal catalysis
