Gold‐catalyzed Rapid Construction of Nitrogen‐containing Heterocyclic Compound Library with Scaffold Diversity and Molecular Complexity

Abstract

1,3-unsubstituted 2-(1H-indol-2-yl)ethanamines were employed for the first time to react with alkynoic acids (AAs) to achieve gold-catalyzed highly selective cascade reactions to furnish novel indole-fused skeletons. Furthermore, with this powerful gold catalytic system, a library of indole/pyrrole/thiophene/benzene/naphthalene/ pyridine-based nitrogen-containing heterocyclic compounds (NCHCs) with scaffold diversity and molecular complexity was constructed rapidly using various amine nucleophiles (ANs) and diverse AAs as the building blocks. This general protocol features excellent selectivity, extraordinarily broad substrate scope, readily available inputs, good to high yields, high bond-forming efficiency, and step economy, thus providing a facile and efficient access to a variety of valuable nitrogen-containing heterocycles. LRMS (ESI) m/z: 218 [M + H] + ; HRMS (ESI) m/z calculated for C 12 H 11 NO 3 + H + 218.0812, found: 218.0809. 2 3 4 5 6 7 8

Green and Facile Assembly of Diverse Fused N-Heterocycles Using Gold-Catalyzed Cascade Reactions in Water

“…1 H-NMR (500 MHz, DMSO- d 6 ) δ 1.60 (s, 3H), 1.80–1.68 (m, 2H), 1.97–1.86 (m, 1H), 2.32–2.21 (m, 1H), 2.45–2.32 (m, 2H), 2.61–2.53 (m, 1H), 2.69–2.62 (m, 1H), 2.99–2.87 (m, 1H), 4.90–4.81 (m, 1H), 7.00–6.93 (m, 1H), 7.10–7.02 (m, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 10.92 (s, 1H); 13 C-NMR (125 MHz, DMSO- d 6 ) δ 167.9 (CO), 139.7 (C, Ar), 136.0 (C, Ar), 126.2 (C, Ar), 120.9 (CH, Ar), 118.5 (CH, Ar), 117.9 (CH, Ar), 111.1 (CH, Ar), 105.8 (C, Ar), 56.4 (C), 35.6 (CH 2 ), 34.8 (CH 2 ), 31.8 (CH 2 ), 25.3 (CH 3 ), 21.0 (CH 2 ), 16.3 (CH 2 ); ESI-LRMS m / z : 255 [M + H] + ; ESI-HRMS m / z calcd for M + H + 255.1492, found: 255.1488. The characterization data is in accordance with that reported in [ 43 ].…”

“…1 H-NMR (400 MHz, DMSO- d 6 ) δ 1.84 (s, 3H), 2.72–2.60 (m, 1H), 2.81–2.73 (m, 1H), 3.45–3.35 (m, 1H), 3.73 (s, 3H), 4.57–4.45 (m, 1H), 6.73 (dd, J = 8.7, 2.1 Hz, 1H), 6.89 (d, J = 2.1 Hz, 1H), 7.26 (d, J = 8.7 Hz, 1H), 7.58–7.47 (m, 1H), 7.77–7.67 (m, 2H), 8.29 (d, J = 7.9 Hz, 1H), 11.18 (s, 1H); 13 C-NMR (125 MHz, DMSO- d 6 ) δ 167.2 (CO), 153.3 (C, Ar), 149.4 (C, Ar), 135.8 (C, Ar), 132.2 (CH, Ar), 131.2 (C, Ar), 130.2 (C, Ar), 128.6 (CH, Ar), 126.3 (C, Ar), 123.2 (CH, Ar), 122.8 (CH, Ar), 111.9 (CH, Ar), 111.5 (CH, Ar), 106.2 (C, Ar), 100.3 (CH, Ar), 62.0 (C), 55.4 (OCH 3 ), 35.5 (CH 2 ), 26.0 (CH 3 ), 21.5 (CH 2 ); ESI-LRMS m / z : 319 [M + H] + ; ESI-HRMS m / z calcd for M + H + 319.1441, found: 319.1435. The characterization data is in accordance with that reported in [ 43 ].…”

“…1 H-NMR (400 MHz, DMSO- d 6 ) δ 1.52 (s, 3H), 1.99–1.87 (m, 1H), 2.28–2.16 (m, 1H), 2.64–2.51 (m, 2H), 2.83–2.67 (m, 2H), 3.16–3.01 (m, 1H), 4.28–4.15 (m, 1H), 6.93–6.82 (m, 1H), 7.34–7.21 (m, 2H), 11.00 (s, 1H); 13 C-NMR (100 MHz, DMSO- d 6 ) δ 171.5 (CO), 156.7 (d, J C–F = 231.1 Hz, CF, Ar), 132.9 (C, Ar), 132.5 (C, Ar), 124.0 (d, J C–F = 10.1 Hz, C, Ar), 115.7 (d, J C–F = 4.5 Hz, C, Ar), 111.9 (d, J C–F = 9.9 Hz, CH, Ar), 108.3 (d, J C–F = 25.8 Hz, CH, Ar), 102.9 (d, J C–F = 23.4 Hz, CH, Ar), 59.0 (C), 33.1 (CH 2 ), 32.9 (CH 2 ), 30.1 (CH 2 ), 24.8 (CH 3 ), 22.9 (CH 2 ); ESI-LRMS m / z : 259 [M + H] + ; ESI-HRMS m / z calcd for M + H + 259.1241, found: 259.1238. The characterization data is in accordance with that reported in [ 43 ].…”

“…Dixon and co-workers disclosed linear aliphatic terminal alkynoic acids reacted smoothly with amine nucleophiles bearing a nucleophilic carbon atom in toluene or xylene to produce pyrrole- or indole-based heterocyclic frameworks catalyzed by AuPPh 3 Cl/AgOTf. It should be noted that, based on Dixon’s pioneering work, the reactions of alkynoic acids with amine nucleophiles in aprotic solvents such as toluene, xylene, 1,2-dichloroethane, dichloromethane, etc., have been well studied by Patil’s group as well as our group [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. However, the reactivity of alkynoic acids and amine nucleophiles in the environmentally friendly, abundant, and cheap solvent—water—was seldom explored [ 44 , 45 ], mainly because the ring opening reaction of the activated enol lactone intermediate in water at elevated temperature may lead to the failure of the cascade reaction.…”

Facile Synthesis and Biological Evaluation of New Thieno[2,3‐g]indolizine Derivatives

“…Furthermore, several thienoindolizines has been prepared by solid‐phase synthesis in excellent yield . Finally, one derivative has been prepared by the cascade reaction of 2‐thiophenethylamine with alkylic acid …”