A Simple and Efficient Protocol to 1,2,4-Substituted Pyrroles via a Sonogashira Coupling-Acid-Catalyzed Cyclization

Abstract

A facile and efficient protocol for the synthesis of 1,2,4-substituted pyrrole derivatives was developed. As a result of the ready availability of materials and the simple operation, this type of reaction should have potential utility in organic synthesis.

Key words

pyrroles - Sonogashira reaction - gallium triflate - cyclization - 2-bromoallylamine

References and Notes

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6

General Procedure for the Synthesis of 3a
To a solution of 1a (0.5 mmol) and 2a (0.6 mmol) in 5 mL of THF was charged CuI (2 mg. 0.01 mmol) and PdCl₂(PPh₃)₂ (7 mg, 0.01 mmol), then charged 1 mL of Et₃N under an N₂ atmosphere at r.t. The reaction was monitored by TLC until it went to completion (4 h). The reaction mixture was quenched with H₂O, extracted with Et₂O (30 mL), and dried over anhyd Na₂SO₄. After evaporation of the Et₂O, chromatography on silica gel (PE) of the crude product afforded 3a. ^¹H NMR (400 MHz, CDCl₃): δ = 7.35-7.32 (m, 4 H), 7.27-7.23 (m, 1 H), 6.52-6.52 (d, J = 0.8 Hz, 1 H), 6.01-6.00 (d, J = 2.0 Hz, 1 H), 3.84-3.81 (t, J = 7.4 Hz, 2 H), 2.12 (s, 3 H), 1.64-1.56 (m, 2 H), 1.23-1.17 (q, J = 7.5 Hz, 2 H), 0.83-0.79 (t, J = 7.4 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 134.6, 134.2, 129.1, 128.6, 126.9, 120.4, 118.7, 110.3, 47.0, 34.0, 20.2, 14.0, 12.2. IR (neat): 1491, 1342 cm^-¹. HRMS: m/z calcd for C₁₅H₁₉N: 213.1517; found: 213.1518.