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

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.

A Simple and Effective Protocol for the Pechmann Reaction to Obtain 4-Methylcoumarin Derivatives Using a High-Speed Mixer Ball Mill Process

“…As an important novelty of our research, we carried out coumarins synthesis under solvent-free conditions, using a highspeed mixer ball mill process with a milling frequency of 60 Hz, Teflon ball mill jars, and single stainless-steel balls 8 mm in diameter. Considering the above-stated facts and our constant efforts to study the synthesis of new bioactive small heterocyclic molecules under sustainable reaction conditions [52][53][54][55], we developed a simple green procedure for the synthesis of 4-methylcoumarin derivatives, including 7-amino-4-methylcoumarin This molecule has been considered an important molecule and building block in biophysical research as a common fluorescent probe [56,57].…”