An Efficient, Solvent-Free and Green One-Pot Protocol for the Rapid Access to Polyfunctionalized Carbazoles

Abstract

The solvent-free one-pot p-extension reaction of indole to carbazole has been carried out very efficiently on the surface of a basic alumina as an inexpensive reusable solid support by involving several 2-(3-formyl-1H-indol-2-yl)acetophenones/acetates and a wide range of 2-aryl/hetero-aryl/alkyl-substituted nitroolefins (or in situ generated nitroolefins from aldehydes and nitromethane)/nitrodienes/chalcones/cinnamyl esters as acceptors under aerobic conditions. This oxidant-free one-shot protocol delivers high to excellent yields (76-92 %) of a novel series of 3-nitro/benzoyl/carboxylate carbazole derivatives in eco-friendly and economical manners and allows a variety of sensitive functional groups on aromatic rings. Moreover, the synthesized 3-nitrocarbazoles are valuable synthons for the easy access to tetra cyclic pyrido[3,2-c]carbazoles, 3-iodo/ arylacetylenyl-substituted carbazoles and (Z)-N-carbazole-substituted nitroenamine (Z/E = 99:1).

Multicomponent Reaction for Diastereoselective Synthesis of Spiro[carbazole-3,4′-pyrazoles] and Spiro[carbazole-3,4′-thiazoles]

“…For explanation of the formation of the various spiro compounds, a plausible reaction mechanism was proposed in Scheme on the basis of the previous works , and the present experiments. First, alkylation of indole with aldehyde in the presence of Lewis acid CuSO 4 resulted in a 3-substituted indole ( A ), which in turn converted to indole-2,3-quinodimethane ( B ) by Lewis acid CuSO 4 catalyzed dehydration.…”

“…Ethyl acetate and petroleum ether (v/v = 1:6) as the eluent, yellow solid, 0.244 g, 42%, mp 188−190 °C; 1 H NMR (400 MHz, CDCl 3 ) δ δ 8.31 (s, 1H), 7.38−7.34 (m, 3H), 7.26−7.25 (m, 1H), 7.21−7.17 (m, 3H), 7.17−7.13 (m, 3H), 7.05−7.02 (m, 4H), 7.00−6.98 (m, 3H), 4.87 (d, J = 10.8 Hz, 1H), 4.67 (s, 1H), 4.47 (d, J = 10.8 Hz, 1H), 4.20 (q, J = 7.2 Hz, 2H), 2.30 (s, 3H), 2.25 (s, 3H), 2.10 (s, 3H), 1.23 (t, J = 7.2 Hz, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 172. 6, 170.8, 160.9, 137.0, 136.3, 135.5, 134.6, 132.0, 130.4, 129.3, 129.1, 128.5, 128.0, 127.6, 126.7, 126.2, 125.4, 121.8, 119.7, 119.5, 119.0, 111.0, 107.9, 63.0, 61.7, 44.2, 42.2, 15.6, 13.9;IR (KBr) υ 3398, 3102, 2958, 1707, 1532, 1324, 1311, 1165, 1113 Ethyl rel-(1S,2S,3S,4R)-3′-methyl-5′-oxo-1′-phenyl-2,4-di-o-tolyl-1,1′,2,4,5′,9-hexahydrospiro[carbazole-3,4′-pyrazole]-1-carboxylate (1m′). Ethyl acetate and petroleum ether (v/v = 1:6) as the eluent, yellow solid, 0.081 g, 14%, mp 192−194 °C; 1 H NMR (400 MHz, CDCl 3 ) δ δ 8.25 (s, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.46 (t, J = 7.2 Hz, 1H), 7.36 (t, J = 7.2 Hz, 2H), 7.26−7.22 (m, 3H), 7.19−7.17 (m, 3H), 7.07−7.06 (m, 3H), 6.96 (d, J = 7.2 Hz, 1H), 6.90 (t, J = 7.2 Hz, 2H), 5.01 (d, J = 10.8 Hz, 1H), 4.99 (s, 1H), 4.75 (d, J = 10.8 Hz, 1H), 4.13 (q, J = 6.8 Hz, 2H), 2.46 (s, 3H), 2.36 (s, 3H), 1.13 (t, J = 6.8 Hz, 3H), 1.02 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 170.…”

“… Levy reported copper catalyzed reaction of aromatic aldehydes and indole-2-acetate to generate indolo-2,3-quinodimethane intermediate (b in Scheme ). Chen also developed in situ generation of active indole-2,3-quinodimethane from 2-methyl-3-indolylmethanols by using secondary chiral amine as iminium activation catalyst (c in Scheme ). Melchiorre and co-workers successfully provided the amine-catalyzed asymmetric Diels–Alder reaction of β-indolyl unsaturated aldehydes, from which indole-2,3-quinodimethanes were generated as the active dienes (d in Scheme ).…”

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

“…On the other hand, the Diels-Alder reaction of the in situ generated indole-2,3-quinodimethanes with various dienophiles is also a powerful method for rapid construction of functionalized tetrahydrocarbazoles [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68]. In this respect, Lévy reported a copper-catalyzed three-component reaction of aromatic aldehydes, ethyl indole-2-acetate and N-alkylmaleimides for the efficient construction of polycyclic tetrahydrocarbazoles, in which indolo-2,3-quinodimethane intermediate was initially generated and sequentially underwent a [4 + 2] cycloaddition reaction (reaction 1 in Scheme 1) [69][70][71][72][73][74]. This metal-catalyzed one-pot reaction not only combined the advantages of a traditional Diels-Alder reaction and the recently developed multicomponent reactions, but also meets the goal of green and sustainable chemistry.…”