Domino CN Coupling/Annulation versus CN Coupling/ Hydroamination of 2‐Alkynyl‐3‐bromobenzothiophenes and 2‐Alkynyl‐3‐bromothiophenes. Highly Efficient Synthesis of Benzothieno[3,2‐b]quinolines and Thieno[3,2‐b]pyrroles

Abstract

While the palladium‐catalyzed reaction of 2‐alkynyl‐3‐bromothiophenes with anilines afforded thienopyrroles by a domino CN coupling/hydroamination process, the reaction of 2‐alkynyl‐3‐bromobenzothiophenes with anilines resulted, under identical conditions, in the formation of benzothienoquinolines by a domino CN coupling/annulation process. The electronic character of the aniline also has an influence on the product distribution.

Efficient synthesis of novel thieno[3,2-b]-, [2,3-c]- and [3,2-c]pyridones by Sonogashira coupling of bromothiophenes with terminal alkynes and subsequent intramolecular C–N bond-forming reaction

“…Based on the retrosynthetic analysis and on previous experience of Iaroshenko's group related to the development of new coupling reactions of alkynyl thiophenes 11 and alkynyl pyridines, 12 we envisaged that 1-(3-bromothiophen-2-yl)-3-arylprop-2-yn-1-ones 1 are suitable substrates for the synthesis of thieno [3,2-b]pyridin-7-one derivatives 3. The requisite starting material, 3-bromothiophene-2-carbonyl chloride, was prepared by the deaminative bromination of commercially available methyl 3-aminothiophene-2-carboxylate with tert-butyl nitrite and CuBr 2 in acetonitrile, 13 followed by alkaline hydrolysis and subsequent treatment with thionyl chloride according to the described procedures (see the Experimental part).…”

Efficient synthesis of novel benzo[b][1,8]naphthyridin-4(1H)-ones and pyrido[2,3-b]quinoxalin-4(1H)-ones from alkynones and primary amines

“…Based on previous experience of the Iaroshenko's group related to the development of new coupling reactions of pyridinyl alkynones 5 and alkynyl thiophenes, 7 we envisaged that 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-one (2), which can be prepared by allowing a lithium acetylide to react with 2-chloro-3-formylquinoline, followed by oxidation of the resulting 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-ol (1) 8 is suitable substrate for the synthesis of benzo [b] [1,8]naphthyridin-4(1H)-one derivatives 3 (Scheme 1). The requisite starting material, 2-chloro-3-formylquinoline, was obtained by treatment of acetanilide with the Vilsmeier reagent (DMF/POCl 3 ) according to the described procedure.…”

“…Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-one 2 (170 mg, 0.58 mmol), cyclopropylamine (40 mg, 0.7 mmol), potassium carbonate (162 mg, 1.17 mmol), Pd(PPh 3 ) 4 (5 mol %), and DMF (10 ml) were refluxed at 170 C for 3 h, 3f was isolated after column chromatography (silica gel, n-heptane/EtOAc¼2:1) as a yellow solid (61 mg, 57%), mp 193 C. 1 7,32.2,111.6,120.8,125.4,125.6,128.2,128.4,128.5,129.3,129.4,132.1,136.8,137.1,148.9,151.7,158.2,179.3;IR (KBr,cm Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-one 2 (170 mg, 0.58 mmol), allylamine (40 mg, 0.7 mmol), potassium carbonate (162 mg, 1.17 mmol), Pd(PPh 3 ) 4 (5 mol %), and DMF (10 ml) were refluxed at 170 C for 3 h, 3g was isolated after column chromatography (silica gel, n-heptane/EtOAc¼2:1) as a yellow solid (141 mg, 90%), mp 286e288 C. d¼106.2, 119.3, 125.2, 126.7, 127.7, 127.7, 128.7, 128.8, 129.8, 130.8, 132.5, 133.6, 136.6, 148.7, 149.0, 150.2, 153.1, 178 Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-one 2 (170 mg, 0.58 mmol), 3-(4-morpholino)propylamine (101 mg, 0.7 mmol), potassium carbonate (162 mg, 1.17 mmol), Pd(PPh 3 ) 4 (5 mol %), and DMF (10 ml) were reflux at 170 C for 3 h, 3h was isolated after column chromatography (silica gel, n-heptane/EtOAc¼2:1) as a solid (200 1, 53.4, 53.4, 55.9, 66.8, 66.9, 111.2, 120.9, 125.4, 125.6, 128.1, 128.2, 128.2, 128.7, 128.7, 129.4, 129.5, 132.2, 135.8, 137.6, 149.1, 149.3, 157.0, 178.6 …”

Recent progress on the chemistry of thieno[3,2‐b]quinoline derivatives (part III)

“…Salman et al [ 20 ] carried out the reaction of 2,3‐dibromobenzothiophene 40 with alkynes 57 , in the presence of Pd(PPh 3 ) 2 Cl 2 (5 mol%), afforded the 2‐alkynyl‐3‐bromo‐benzo‐ thiophenes 58a‐c , which reacted with anilines 59a‐m in toluene in the presence of palladium acetate, P(t‐Bu) 3 ·HBF 4 , KO‐t‐Bu, and CuI formed the benzothienoquinolines 60a‐m (Scheme 9).…”

“…On the other hand, the reaction of 2‐alkynyl‐3‐bromobenzothiophenes 58b,c with anilines 59a,n‐p in the presence of palladium catalyst gave a mixture of benzothienoquinolines 60n‐q and benzothienopyrroles 61a‐d in 50‐60% and 30‐40% yields, respectively (Scheme 10). [ 20 ]…”