A Novel Indium-Catalyzed Three-Component Reaction: General and Efficient One-Pot Synthesis of Substituted Pyrroles

Abstract

A convenient and general approach towards the synthesis of substituted pyrroles from propargylic acetates, silyl enol ethers, and primary amines was described. This novel transformation was catalyzed by indium trichloride in a one-pot synthesis, and high yields of various pyrrole derivatives were obtained.

Key words

pyrrole - indium - one-pot reaction - propargylic acetate - enoxysilane

References and Notes

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7

General Experimental Methods
Propargylic acetates 1 and enoxysilanes 2 were prepared according to published procedures. All other compounds are commercially available and were used without further purification. Infrared spectra were recorded on a Nicolet AVATER FTIR360 spectrometer. NMR spectra were recorded on a Bruker AVANCE DPX-400 instrument at 400 MHz (^¹H) or 100 MHz (^¹³C). The chemical shift values (δ) are given in parts per million(ppm) and are referred to the residual peak of the deuterated solvent (CDCl₃). MS measurements were performed on Bruker Reflex III mass spectrometer. Elemental analyses were performed with a PerkinElmer 2400 microanalyser. Flash chromatography was performed with QingDao silica gel (300-400 mesh).

8

A Representative Procedure for the Synthesis of Substituted Pyrrole 2-Benzyl-1,3,5-triphenyl-1 H -pyrrole (6aa)
To a 10 mL flask, propargylic acetate 1a (0.5 mmol), enoxysilane 2a (1.0 mmol), chlorobenzene (2.0 mL), and InCl₃ (0.05 mmol) were successively added. The reaction was allowed to stir at 75 ˚C for 0.5 h, followed by adding primary amines 7a (1.0 mmol). The reaction mixture was heated to keep refluxing for an additional 1 h until completion (monitored by TLC). Upon cooling to r.t., the reaction mixture was then quenched with 1 M HCl (2 mL). The organic and aqueous layers were separated, and the latter was extracted with Et₂O (3 × 5 mL). The combined organic layers were dried over MgSO₄ and filtered. The filtrate was concentrated in vacuo, and then the residue was purified by silica gel column chromatography (EtOAc-hexane, 1:100) to afford the corresponding substituted pyrroles. A yellow solid, mp 146-147 ˚C; yield 87% (0.167 g). ^¹H NMR (400 MHz, CDCl₃): δ = 7.50-7.52 (m, 2 H), 7.33-7.37 (m, 2 H), 7.07-7.24 (m, 12 H), 6.95-6.97 (m, 2 H), 6.88-6.90 (m, 2 H), 6.66 (s, 1 H), 4.04 (s, 2 H) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 140.5, 139.1, 136.9, 134.8, 133.2, 130.2, 129.0, 128.8, 128.7, 128.3, 128.2, 128.1, 128.0, 127.7, 126.1, 125.9 (3), 124.4, 109.6, 31.5 ppm. IR (film): 1493, 1599, 3024 cm^-¹. ESI-MS: m/z (%) = 386 (100) [M + H⁺]. Anal. Calcd (%) for C₂₉H₂₃N: C, 90.35; H, 6.01; N, 3.63. Found: C, 90.38; H, 6.00, N, 3.63.