Arylation, Vinylation, and Alkynylation of Electron-Deficient (Hetero)arenes Using Iodonium Salts

Abstract

Arylation, vinylation, and alkynylation of electron-deficient arenes and heteroarenes have been achieved by chemoselective C-H zincation followed by copper-catalyzed coupling reactions using iodonium salts. This approach offers a direct and general access to a wide scope of (hetero)biaryls as well as alkenylated and alkynylated heteroarenes under mild conditions. It is particularly useful and valuable for the rapid and modular synthesis of diverse (hetero)aryl compounds, as demonstrated in the synthesis of transient receptor potential vanilloid 1 (TRPV1) antagonists and angiotensin II receptor type 1 (AT1 receptor) antagonists.

Diaryliodoniums Salts as Coupling Partners for Transition-Metal Catalyzed C- and N-Arylation of Heteroarenes

“…The reaction was successfully extended to the synthesis of various 2-arylbenzoxazoles as attractive synthetic targets displaying potent biological activities. Applying these optimized conditions to benzothiazole failed to produce the desired arylated product [96]. After the screening of the reaction conditions, the promoting effect of microwave activation was demonstrated by the successful C2-H arylation of benzothiazole at 130 • C in dioxane (Scheme 24).…”

Copper-Catalyzed Arylation with Diaryliodonium Salts

“…Recently, Liu and Wang reported a one-pot methodology for the arylation of electron-deficient heteroarenes 34 that involves the formation of a heteroarylzinc chloride 35 through a selective C-H zincation and a subsequent coppercatalyzed arylation with diaryliodonium salts. 22 A range of (hetero)biaryls 36 can be obtained under mild conditions and with a good functional group tolerance (Scheme 13). The authors also extended this strategy to the vinylation and alkynylation of heteroarenes and applied the arylation methodology to the synthesis of some pharmaceuticals.…”

N-Heterocyclic Carbene (NHC)-Catalyzed One-Pot Aerobic Oxidative Synthesis of 2-Substituted Benzo[d]oxazoles, Benzo[d]thiazoles and 1,2-Disubstituted Benzo[d]imidazoles

“…[29] Following general procedure A on a 1 mmol scale with NHC Precursor I as the catalyst, 5g was afforded as white solid 210mg (75%); Rf =0. [29] Following general procedure A on a 1 mmol scale, 5h was afforded as white solid 100mg (43%); Rf = 0.5 (Pe/EtOAc=50/1); FT-IR (KBr) 3058, 1602, 1520, 1479, 1437, 1228, 1152, 970, 835, 807, 758, 732, 700, 623, 497 cm -1 ; 1 H NMR (400 MHz, CDCl3) δ 8.09 (t, J = 7.1 Hz, 3H), 7.90 (d, J = 7.9 Hz, 1H), 7.51 (dd, J = 8.0, 7.4 Hz, 1H) [31] Following general procedure A on a 1 mmol scale, 5i was afforded as light yellow solid 196 mg (90%); Rf =0.4 (Pe/EtOAc=100/1); FT-IR (KBr) 3100, 3055, 1540, 1475, 1434, 1415, 1311, 1231, 1222, 1078, 911, 851, 825, 713, 701, 623 [32] Following general procedure A on a 1 mmol scale, white solid was afforded; the product need to be furthur purified by recrystallized from cold methanol, totally 150 mg white crystal solid was afforded [33] Following general procedure A on a 1 mmol scale, 5l was afforded as colorless oil 160 mg (75%); Rf = 0.35(Pe/EtOAc=100/1); FT-IR (KBr) 3429, 3071, 2926, 2851, 1514, 1448, 1436, 1313, 1244, 1146, 1124, 1094, 1014, 992, 757, 728 cm -1 ; 1 H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.0 Hz, 1H), 7.81 (dd, J = 7.9, 0.4 Hz, 1H), 7.48 -7.36 (m, 1H), 7.29 (dt, J = 12.5, 2.7 Hz, 1H), 3.08 (tt, J = 11.7, 3.6 Hz, 1H), 2.19 (dd, J = 13.3, 2.1 Hz, 2H), 1.93 -1.80 (m, 2H), 1.79 -1.70 (m, 1H), 1.62 (qt, J = 12. [34] Following general procedure A on a 1 mmol scale, 5m was afforded as colorless oil 80 mg (45%); Rf =0.3 (Pe/EtOAc =100/1); FT-IR (KBr) 3436, 2966,2936,2869,1518,1456,1437,1094,1037,1013,758, 729 cm -1 ; 1 H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 7.9 Hz, 1H), 7.84 (dd, J = 8.0, 0.5 Hz, 1H), 7.49 -7.38 (m, 1H), 7.38 -7.29 (m, 1H), 3.43 (hept, J = 6.9 Hz, 1H), 1.49 (d, J = 6.9 Hz, 6H); 13 C NMR (101 MHz, CDCl3) δ 178.6, 153.1, 134.7, 125.8, 124.5, 122.6, 121.5, 34.1, 22.9; MS m/z (relative intensity, %): 177 (32), 162(100).…”