C–H Alkynylation of N‑Methylisoquinolone by Rhodium or Gold Catalysis: Theoretical Studies on the Mechanism, Regioselectivity, and Role of TIPS-EBX

The Rh/Au-catalyzed regioselective C-8/C-4 alkynylation of N-methylisoquinolone has been theoretically investigated with the aid of density functional theory (DFT) calculations. The versatile function of substrate 1-[(triisopropylsilyl)­ethynyl]-1,2-benziodoxol-3­(1H)-one (TIPS-EBX) is explored in this study. In the [Cp*RhCl2]2-catalyzed reaction, TIPS-EBX is acted as the Brønsted base to go through the self-assisted deprotonation mechanism to produce the C8-alkynylation product solely. The obvious regioselectivity could be attributed to the electron effects. In contrast, due to the steric effects, the C4-alkynylation product becomes the major product by employing AuCl as the catalyst. In this reaction, the iodine­(III) center in the TIPS-EBX moiety could be employed as a strong Lewis acid to activate the alkyne moiety efficiently.