Rhodium-Catalyzed Annulative Coupling of Isothiazoles with Alkynes through N–S Bond Cleavage

Abstract

A Rh­(III)-catalyzed annulative coupling of 3,5-diarylisothiazoles and alkynes is reported. The N–S bond in the isothiazole ring acts as an internal oxidant to regenerate the Rh­(III) species in combination with an external Cu­(II) oxidant, and the corresponding 1:2 coupling products are obtained. The remarkable difference in the reaction outcome between isothiazoles and the relevant isoxazoles has been investigated by DFT calculations, revealing that the relative stability of the enolate intermediates dictates the product selectivity.

Harnessing sulfur and nitrogen in the cobalt(iii)-catalyzed unsymmetrical double annulation of thioamides: probing the origin of chemo- and regio-selectivity

“…The additives AgBF 4 , NaSbF 6 , and KPF 6 were evaluated under the conditions of entry 8 (entries 9-11), but only AgBF 4 effectively led to 3a in 55% yield (entry 9). Among the solvents tested DCE, PhMe, DMF, HFIP, CH 3 CN, 1,4-dioxane, or TCE (entries 8, [12][13][14], DCE was clearly the most efficient one (entry 8). The yield of 3a was increased to 76% when the reaction was performed using the Cp*Co(CO)I 2 complex (15 mol%), AgSbF 6 (30 mol%), and Cu(OAc) 2 (1.5 equiv) (entry 15).…”

Transition Metal‐Free Synthesis of Substituted Isothiazoles via Three‐Component Annulation of Alkynones, Xanthate and NH4I

“…a). Forthermore, 3,5‐diphenylisothiazole could undergo Rh(III)‐catalyzed annulative coupling with alkynes smoothly and converted into different isoquinoline‐isothiochromene conjugates ( 4 a and 4 b ) in 89% and 87% yields, respectively [12] . The transformation above was also applicable to 2‐thiophene‐substituted and 3‐thiophene‐substituted alkynones, and their reactions with 1,2‐diphenylethyne furnished compounds ( 4 c and 4 d ) with novel structures in 77% and 81% yields, respectively (eq.…”

“…General procedures for synthesis of 3 a‐3 d : [12] To an oven‐dried Schlenk tube were added isothiazole 2 (0.2 mmol), 1,2‐diphenylethyne (0.4 mmol), [Cp*Rh(MeCN) 3 ] [SbF 6 ] 2 (6.6 mg, 4.0 mol%), and Cu(OAc) 2 (72.6 mg, 0.4 mmol). The tube was flushed with N 2 , and DCE (3.0 mL) was added via syringe.…”

“…(Z)‐1‐((3,4‐diphenyl‐1H‐isothiochromen‐1‐ylidene)methyl)‐3,4‐diphenylisoquinoline (4 a) [12] . Yellow solid (263 mg, 89% yield); R f =0.5 (Hexane /EtOAc=10:1); 1 H NMR (500 MHz, CDCl 3 ) δ 8.45 (d, 1H), 8.06 (d, J =7.0 Hz, 2H), 7.82–7.49 (m, 5H), 7.48–7.26 (m, 9H), 7.24–7.04 (m, 12H); 13 C NMR (125 MHz, CDCl 3 ) δ 152.8, 140.1, 138.4, 137.6, 137.5, 136.6, 135.3, 132.1, 131.5 (2 C), 131.4 (2 C), 130.9 (2 C), 130.8, 130.4, 130.13, 129.9, 129.3 (2 C), 129.1, 128.3 (2 C), 128.2, 128.1 (2 C), 128.0, 127.8 (2 C), 127.4, 127.3, 127.2 (2 C), 127.0, 126.8, 126.7, 126.4, 125.7, 125.6, 124.6, 116.1.…”

“…Z)‐1‐((3,4‐bis(4‐methoxyphenyl)‐1H‐isothiochromen‐1‐ylidene)methyl)‐3,4‐bis(4‐methoxyphenyl)isoquinoline (4 b) [12] . Yellow solid (309 mg, 87% yield); R f =0.5 (hexane/EtOAc=3:1); 1 H NMR (500 MHz, CDCl 3 ) 8.40–8.43 (m, 1H), 8.01–8.05 (m, 2H), 7.71–7.73 (m, 1H), 7.57–7.59 (m, 2H), 7.51 (d, J =9 Hz, 2H), 7.41–7.44 (m, 1H), 7.30–7.33 (m, 1H), 7.18–7.20 (m, 2H), 7.12–7.14 (m, 3H), 7.04 (d, J =8.5 Hz, 2H), 6.93 (d, J =8.5 Hz, 2H), 6.80 (d, J =8.5 Hz, 2H), 6.70 (d, J =8.5 Hz, 2H), 6.64 (d, J =8.5 Hz, 2H), 3.86 (s, 3H), 3.79 (s, 3H), 3.75 (s, 3H), 3.746 (s, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 158.7, 158.6, 158.5, 158.2, 152.5, 137.0, 135.6, 132.5 (2 C), 132.4 (2 C), 132.2 (2 C), 130.9, 130.9, 130.7, 130.7 (2 C), 130.2, 130.1, 129.0, 128.0, 127.9, 127.8, 126.3, 126.27, 125.6, 125.5, 124.7, 115.9, 113.9 (2 C), 113.5 (2 C), 113.2 (2 C), 112.8 (2 C), 55.2, 55.12, 55.09, 55.05.…”