Construction of Indole‐Fused Heterocycles Starting from 2‐Thioxoindolines, Iminoindolines, and Their Derivatives

Abstract

Indole-based heterocycles containing sulfur or nitrogen atoms are important frameworks that occur widely in biological active natural products and drugs. Consequently, several novel chemical transformations and new catalytic strategies have been developed for the preparation of these skeletons in a highly efficient and selective manner. This review focuses on recent advancements in the construction of indole-fused heterocyclic compounds by using iminoindolines, 3-diazoindol-2-imines, 2-thioxoindolines, and their derivatives as starting materials.

Synthesis of Indole-Fused Dihydrothiopyrano Scaffolds via (3 + 3)-Annulations of Donor–Acceptor Cyclopropanes with Indoline-2-Thiones

“…1 H NMR (400 MHz, DMSO-d 6 ) δ 7.76 (d,J = 7.3 Hz,1H),4H),5H),5.30 (dd,J = 8.1,5.9 Hz,1H),4H),3.77 (dd,J = 10.6,7.3 Hz,1H),3.62 (dd,J = 10.8,7.1 Hz,1H),2H), 1.18 (t, J = 7.1 Hz, 3H), 1.05 (t, J = 7.1 Hz, 3H); 13 C{ 1 H} NMR (101 MHz, DMSO-d 6 ) δ 177. 4, 165.7, 164.7, 149.1, 138.4, 137.9, 132.5, 128.9, 128.6, 128.5, 128.5, 128.4, 128.1, 127.7, 127.6, 127.1, 123.2, 119.8, 81.2, 69.2, 63.3, 62.9, 45.5, 41.8, 13.6, 13.4; HRMS: m/z calculated for C 23 H 22 NO 4 SCl [M + H] + 444.1037, found 444.1036; IR (neat) (v): 2924, 2853, 1741, 1501, 1446, 1366, 1254, 1227, 1023, 736, 698 cm −1. Diethyl-2- (2-((1-methyl-1H-indol-2-yl)thio)-2-phenylethyl)malonate (4). In a Schlenk tube, indoline-2-thione 1a (3 mmol, 0.447 g, 1 equiv), donor−acceptor cyclopropane 2c (3 mmol, 0.829 g, 1 equiv), and Sc(OTf) 3 (0.3 mmol, 0.147 g, 0.1 equiv) were dissolved in anhydrous DCE (6 mL) under N 2 atmosphere.…”

“…In Figure , several indole-fused tricyclic heterocyclic natural products or drugs are shown, having antitumor, antifungal, antibacterial, and analgesic activities . To the best of our knowledge, handful numbers of methodologies for accessing the indole-fused thiopyrano derivatives are known; however, there is no strategy that involves donor–acceptor cyclopropanes (DACs). DACs received much attention in recent decades due to their outstanding strained arrangement and immense synthetic application .…”

Organocatalytic asymmetric synthesis of multifunctionalized α-carboline-spirooxindole hybrids that suppressed proliferation in colorectal cancer cells

“…Recently, [3 + 3] annulations with isatin-derived MBH carbonates as dielectrophiles have been reported based on N -sulfonyl ketimines 13 a or enolizable cyclic carbonyl derivatives 13 b in the presence of achiral Lewis-bases (Scheme 1b). On the other hand, indolin-2-imines 14 have been proved to be useful C , N -dinucleophiles for the asymmetric construction of α-carboline derivatives, while reacting with bromoenals, 15 a α,β-unsaturated esters, 15 b and α,β-unsaturated N -acylated succinimide 15 c in different organocatalytic systems. These achievements, coupled with our persistent interest in constructing pharmacologically relevant molecules as lead compounds for drug discovery, 16 led us to ask whether indolin-2-imines could react with isatin-derived MBH carbonates as C , N -dinucleophiles in the presence of chiral Lewis-bases (Scheme 1c).…”

One‐Pot Regio‐ and Diastereoselective Synthesis of Tetrahydro‐α‐carbolines via Cascade Reactions of Iminoindolines with Morita‐Baylis‐Hillman Bromides of Nitroalkenes

“…[8][9][10][11][12][13][14][15][16] Substrates for the synthesis of tetrahydro-α-carbolines via various intra-and intermolecular cyclizations include 3-substituted indoles, [8] 2-substituted indoles, [9] tosyliminoindolines [10][11][12][13][14] and others such as nitropyridine [15] and o-iodobenzamide. [16] While tosyliminoindoline and its derivatives have been employed for the synthesis of a wide variety of heterocycles, [17] they react in a [4 + 2] [10][11] or [3 + 3] [12][13][14] fashion in the synthesis of tetrahydro-α-carbolines (Scheme 1a). Although α,β-unsaturated carbonyl compounds participate in the [3 + 3] annulation of tetrahydro-α-carbolines, [12][13][14] nitroalkene derivatives have not been employed in such capacity as 3-carbon components.…”