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

Abstract

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*RhCl 2 ] 2 -catalyzed reaction, TIPS-EBX is acted as the Brønsted base to go through the self-assisted deprotonation mechanism to produce the C8alkynylation 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.

Directing‐Group‐mediated C−H‐Alkynylations

“…Furthermore, current DFT‐calculations suggest that a fourth, concerted mechanism may be operational, that does not include a single of the reactive intermediates I1‐3 mentioned above …”

Combined Approach of Hypervalent Iodine Reagents and Transition Metals in Organic Reactions

“…Further, TIPS‐EBX adds to the complex; then acetylene group inserts into Rh−C bond. Finally, C‐8 alkynylated product is formed with elimination of 2‐iodobenzoic acid and catalyst is regenerated [83] …”

“…Further, on addition of N ‐methylisoquinoline gives vinyl‐gold complex. Finally, α or β ‐elimination generates C‐4 alkynylated product along with 2‐iodobenzoic acid and regenerated catalyst [131] …”

Gold and hypervalent iodine(iii): liaisons over a decade for electrophilic functional group transfer reactions

“…As usual, the intrinsic electronic bias of the isoquinolones/2-pyridone rings allowed the alkynylation at the most electron-rich C4 site. A theoretical investigation on the operating mechanism in this reaction by the Yu and Liu group 35 Ariafard's proposal 25 that the iodine(III) centre, instead of the Au(I)-centre, acts as a strong Lewis acid to activate the alkyne moiety efficiently (cf. 11).…”