Direct synthesis of polysubstituted 2-aminothiophenes by Cu(ii)-catalyzed addition/oxidative cyclization of alkynoates with thioamides

Abstract

A facile and direct synthetic method was developed for the construction of structurally important 2-aminothiophenes in moderate to excellent yields (up to 91%), via Cu(II)-catalyzed addition/oxidative cyclization of readily available thioamides with alkynoates under an air atmosphere.

Formation of Highly Substituted Indenes through Acid Promoted Cyclodehydration with Nucleophile Incorporation

“…(Z)-2-Benzoyl-3-(3,5-dimethoxyphenyl)-N,N-dimethyl acrylamide (5e). To a RBF was added N,N-dimethyl-3-oxo-3-phenylpropanamide 12 (300 mg, 1.56 mmol), 3,5-dimethoxybenzaldehyde (200 mg, 1.20 mmol), acetic acid (0.2 mL), piperidine (0.25 mL) and dry DCE (2.5 mL). Powdered molecular sieves (∼300 mg, 4Å) were added, the reaction mixture heated to 60 °C and allowed to stir for 18 h. The reaction was then cooled to 40 °C and allowed to stir for a further 24 h. The reaction was then diluted with EtOAc (10 mL) and washed successively with distilled H 2 O (10 mL), 2.0 M NaOH (10 mL), 1.0 M HCl (10 mL) and brine (2 × 15 mL).…”

“…1 H NMR (400 MHz, CDCl 3 ) δ 7.84 (dd, J = 8.3, 1.3 Hz, 2H), 7.59 (tt, J = 7.4, 1.3 Hz, 1H), 7.51−7.46 (m, 2H), 7.13 (s, 1H), 6.65 (d, J = 2.2 Hz, 2H), 6.50 (t, J = 2.2 Hz, 1H), 3.78 (s, 6H), 3.09 (s, 3H), 2.88 (s, 3H); 13 (Z)-2-Benzoyl-3-(3,4-dimethoxyphenyl)-N,N-dimethyl acrylamide (5f). To a RBF under N 2(g) was added N,N-dimethyl-3-oxo-3-phenylpropanamide 12 (930 mg, 4.86 mmol), 3,4-dimethoxybenzaldehyde (1.21 g, 7.29 mmol), acetic acid (0.4 mL), piperidine (0.5 mL) and dry DCE (5 mL). Powdered molecular sieves (∼300 mg, 4Å) were added, and the reaction was heated to 60 °C and allowed to stir for 2 d. The reaction was then heated to 80 °C for 4 h before being cooled to 50 °C and allowed to stir for 2.5 d. The reaction was then diluted with EtOAc (10 mL) and washed successively with distilled H 2 O (10 mL), 2.0 M NaOH (10 mL), 1.0 M HCl (10 mL) and brine (2 × 15 mL).…”

“…(Z)-2-Benzoyl-3-(4-methoxyphenyl)-N,N-dimethyl acrylamide (5g). To a RBF under N 2(g) was added N,N-dimethyl-3-oxo-3phenylpropanamide 12 (1.50 g, 7.84 mmol), p-anisaldehyde (0.73 mL, 6.0 mmol), acetic acid (0.6 mL), piperidine (0.75 mL) and dry DCE (7.5 mL). Powdered molecular sieves (∼300 mg, 4Å) were added, and the reaction was heated to 60 °C and allowed to stir for 2 d. The reaction was then cooled to 40 °C and allowed to stir for 3 d before being again warmed to 60 °C and allowed to stir for 24 h. The reaction was then diluted with EtOAc (10 mL) and washed (Z)-2-Benzoyl-3-(3-methoxyphenyl)-N,N-dimethyl acrylamide (5h).…”

“…Powdered molecular sieves (∼300 mg, 4Å) were added, and the reaction was heated to 60 °C and allowed to stir for 2 d. The reaction was then cooled to 40 °C and allowed to stir for 3 d before being again warmed to 60 °C and allowed to stir for 24 h. The reaction was then diluted with EtOAc (10 mL) and washed (Z)-2-Benzoyl-3-(3-methoxyphenyl)-N,N-dimethyl acrylamide (5h). To a RBF under N 2(g) was added N,N-dimethyl-3-oxo-3phenylpropanamide 12 (500 mg, 2.61 mmol), 3-methoxybenzaldehyde (889 mg, 6.53 mmol), acetic acid (0.4 mL), piperidine (0.5 mL) and dry DCE (5 mL). Powdered molecular sieves (∼300 mg, 4Å) were then added, and the reaction allowed to reflux for 16 h. The reaction was then diluted with EtOAc (10 mL) and washed successively with distilled H 2 O (10 mL), 2.0 M NaOH (10 mL), 1.0 M HCl (10 mL) and brine (2 × 15 mL).…”

1,2‐Diaza‐1,3‐diene‐Based Multicomponent Reactions in Sequential Protocols to Synthesize Arylamino‐5‐hydrazonothiophene‐3‐carboxylates

“…In this latter class, the most common synthetic route is the Gewald reaction, a MCR between carbonyl derivatives, activated nitriles and sulfur under basic conditions . Other reactions of this type use activated thioamides as building block that can react with carbonyl derivatives bearing a leaving group in α position, or with DDQ, or with alkynoates . Recently, we have proposed a new sequential multicomponent reaction between primary amines, β‐keto esters, isothiocyanates and 1,2‐diaza‐1,3‐butadienes (DDs) that produces 2,5‐dihydrothiophenes (DHT) .…”