Expedient Access to Indolyl-Substituted Tri- and Diarylmethanes and (±)-Colletotryptin E by Silica Sulfuric Acid Catalyzed Transindolylation

Abstract

An expedient access to a series of nonsymmetrical bis(indolyl)methanes (BIMs) through transindolylation of readily available symmetrical 3,3′-BIMs with various indoles catalyzed by silica-supported sulfuric acid has been established. This approach not only provides a useful strategy for the synthesis of structurally diverse BIMs, but also provides examples of nucleophilic substitution of BIMs with aromatic and nonaromatic π-systems, leading to a library of indolyl-substituted tri- and diarylmethanes. Moreover, this method was successfully applied in the first total synthesis of the 2,3′-BIM alkaloid (±)-colletotryptin E in three steps with an overall yield of 46%. The features of this procedure include a metal-free process, an inexpensive and environmentally friendly catalyst, mild reaction conditions, broad functional-group tolerance, good yields, and gram-scalable preparations.

Key words

silica sulfuric acid - bisindolylmethanes - triarylmethanes - transindolylation - colletotryptin E - indoles

Publication History

Received: 13 February 2022

Accepted after revision: 08 March 2022

Article published online:
01 April 2022

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• 14 Silica Sulfuric Acid^13f A slurry of silica gel (230–400 mesh, pore size 60 Å; 10 g) in anhyd Et₂O (50 mL) was treated with concd H₂SO₄ (>95%, 3 mL) with vigorous stirring at 0 °C for 30 min. The solvent was then removed under reduced pressure to give a free-flowing SSA that was dried in vacuo for 24 h and heated at 120 °C for 3 h using a hot plate and a sand bath to give the solid catalyst SSA, which was stored in a desiccator.
• 15 BIMs 9; General ProcedureThe appropriate symmetrical BIM 7 (0.5 mmol) and indole 8 (0.5 mmol) were dissolved in MeCN (10 mL). The SSA (0.25 mmol) was added and the mixture was stirred at r.t. until the starting material was consumed (TLC). The reaction was then quenched with aq NaHCO₃, and the catalyst was collected by filtration and rinsed with CH₂Cl₂. The filtrate was extracted with EtOAc (2 × 10 mL), dried (Na₂SO₄), filtered, and concentrated in vacuo. The crude product was purified by radial chromatography (silica gel, 100% hexane to 70% EtOAc–hexane) to afford a pure racemic mixture of nonsymmetrical BIM 9. In some cases, the symmetrical BIM 10 was detected as a minor product.3-[1H-Indol-3-yl(phenyl)methyl]-1-methyl-2-phenyl-1H-indole (9a)¹¹ Orange solid; yield: 180.1 mg (87%); mp 98–100 °C. IR (ATR): 3412, 3050, 2926, 1604, 1451, 1420, 1362, 1331, 1094, 1013, 735, 717, 695 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.92 (s, 1 H), 7.45–7.43 (m, 3 H), 7.39–7.34 (m, 5 H), 7.28 (br s, 1 H), 7.26–7.14 (m, 7 H), 7.11–6.92 (m, 2 H), 6.87 (dd, J = 2.3, 1.2 Hz, 1 H), 5.76 (s, 1 H), 3.65 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 144.6, 138.3, 137.8, 136.6, 132.1, 130.8, 128.9, 128.4, 128.3, 128.0, 127.9, 127.5, 125.8, 124.0, 121.8, 121.5, 121.3, 120.0, 119.5, 119.2, 115.7, 111.0, 109.4, 40.0, 30.9.
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• 17 O-Benzyl-(±)-colletotryptin E (16)BIM 14 (0.5 mmol) and 3-(2-hydroxyethyl)indole (15) (0.5 mmol) were dissolved in MeCN (10 mL). SSA (0.25 mmol) was added and the resultant mixture was stirred at r.t. until the starting material was consumed (TLC). The reaction was quenched with aq NaHCO₃ and the catalyst was collected by filtration and rinsed with CH₂Cl₂. The filtrate was extracted with EtOAc (2 × 10 mL), dried (Na₂SO₄), and filtered. The filtrate was evaporated in vacuo to afford a crude product that was purified by radial chromatography (silica gel, 100% hexane to 60% EtOAc–hexane) to give a red solid; yield: 95.2 mg (46%); mp 92–94 °C.IR (ATR): 3399, 2923, 2853, 1706, 1458, 1364, 1298, 1100, 743 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.39 (s, 1 H), 8.15 (s, 1 H), 7.63 (d, J = 7.1 Hz, 1 H), 7.45 (d, J = 7.9 Hz, 1 H), 7.35–7.27 (m, 4 H), 7.26–7.24 (m, 1 H), 7.23–7.12 (m, 5 H), 7.04 (t, J = 7.1 Hz, 1 H), 6.99 (s, 1 H), 4.93–4.90 (m, 1 H), 4.56 (s, 2 H), 4.17–7.09 (m, 2 H), 3.89–8.85 (m, 2 H), 3.15–3.12 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 137.7, 136.9, 136.3, 135.5, 128.5, 127.8, 127.8, 126.5, 122.4, 122.1, 121.4, 119.8, 119.2, 119.0, 118.4, 115.1, 111.2, 110.8, 108.4, 73.0, 72.4, 62.7, 34.6, 29.7, 28.0. HRMS (ESI-TOF): m/z: [M + H]⁺ calcd for C₂₇H₂₇N₂O₂: 411.2073; found: 411.2074.