Regiodivergent Metal-Controlled Synthesis of Multiply Substituted Quinolin-2-yl- and Quinolin-3-ylphosphonates

Abstract

In this study, we developed a selective method for synthesis of multi-substituted quinoline-2-ylphosphonates and quinoline-3-ylphosphonates by copper-or gold-catalyzed reactions of phosphoryl-substituted conjugated ynones with 2′-amino-2,2,2-trifluoroacetophenones. The approach proposed makes it possible to obtain various substituted quinolines in good yields. It is also shown that (4,4,4-trifluoro-3-oxobut-1-yn-1-yl)phosphonate reacts with 2-aminoaryl ketones under non-catalytic conditions with formation of 4-substituted quinoline-2-ylphosphonates in high yields.

Switchable Selectivity in the Annulation of o‐Trifluoroacetylanilines and Activated Terminal Alkynes Based on Transition Metal and Phosphine Catalysis

“…In addition, they are quite promising compounds for switchable synthesis of various trifluoromethyl substituted compounds. In particular, there are known works on divergent synthesis of various heterocyclic compounds based on phosphine [8i,l] or metal‐complex catalysis [8c,e] . However so far there are no studies in literature to combine both approaches in syntheses via o ‐trifluoroacetylanilines.…”

Non-Friedländer Route to Diversely 3-Substituted Quinolines through Au(III)-Catalyzed Annulation Involving Electron-Deficient Alkynes

“…In the case of propiolonitrile 6, the addition of AlCl 3 as a cocatalyst was beneficial, and we obtained, although in a low yield, 3-cyanoquinoline 7. Relevant gold(I)-catalyzed routes for the preparation of quinoline-3carboxylates 43 and quinoline-3-phosphonates 44,45 2-aminobenzaldehyde 2a, we also tested the catalytic system of Mitrofanov and Beletskaya, 45 namely IPrAuCl/AgSbF 6 ; however, it turned out to be ineffective (Table S1, entry 14). Thus, in contrast to the previously proposed gold(I)-catalyzed approaches, 43−45 our gold(III)-catalyzed method, employing sulfonylalkynes and other electron-deficient alkynes, represents a general synthetic route to diversely 3-substituted quinolines.…”

“…In the case of propiolonitrile 6 , the addition of AlCl 3 as a cocatalyst was beneficial, and we obtained, although in a low yield, 3-cyanoquinoline 7 . Relevant gold­(I)-catalyzed routes for the preparation of quinoline-3-carboxylates and quinoline-3-phosphonates , starting from alkynylcarbonyls and alkynylphosphonates have been previously reported. For our model reaction between alkynylsulfone 1a and 2-aminobenzaldehyde 2a , we also tested the catalytic system of Mitrofanov and Beletskaya, namely IPrAuCl/AgSbF 6 ; however, it turned out to be ineffective (Table S1, entry 14).…”

“…Relevant gold­(I)-catalyzed routes for the preparation of quinoline-3-carboxylates and quinoline-3-phosphonates , starting from alkynylcarbonyls and alkynylphosphonates have been previously reported. For our model reaction between alkynylsulfone 1a and 2-aminobenzaldehyde 2a , we also tested the catalytic system of Mitrofanov and Beletskaya, namely IPrAuCl/AgSbF 6 ; however, it turned out to be ineffective (Table S1, entry 14). Thus, in contrast to the previously proposed gold­(I)-catalyzed approaches, − our gold­(III)-catalyzed method, employing sulfonylalkynes and other electron-deficient alkynes, represents a general synthetic route to diversely 3-substituted quinolines.…”

“…The principal difference between our general approach and the previously reported annulations of alkynylcarbonyls/alkynylphosphonates − is associated with the different chemical nature of the employed gold species. While gold­(I) catalysts have been used previously, we employed gold­(III)-based complex PicAuCl 2 .…”