Approach to Trisubstituted 1H-Pyrroles from Alkynoates and Amines Mediated by tert-Butyl Perbenzoate

Abstract

A simple and concise tandem cyclization of alkynoates with amines in the presence of tert-butyl perbenzoate (TBPB) leads to 1,2,4-trisubstituted 1H-pyrroles. A variety of aromatic amines and aliphatic amines can be used in this approach, and a wide range of functionalized 1,2,4-trisubstituted 1H-pyrroles are obtained in good to excellent yields. This protocol not only corresponds to the construction of a pyrrole fragment, but also provides a new way to form C–C and C–N bonds.

Key words

1H-pyrroles - oxidation - cyclization - alkynoates - amines

• References and Notes

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• 29 Synthesis of Dimethyl 1-p-Tolyl-1H-pyrrole-2,4-dicarboxylate (3aa); Typical Procedure: A mixture of 1a (284 mg, 2.0 mmol), p-toluidine (107 mg, 1.0 mmol), TBPB (446 mg, 2.3 mmol) and dioxane (2.0 mL) was added successively to a Schlenk tube. After stirring for 3 h at 100 °C, the solution was directly subjected to isolation by PTLC (GF₂₅₄; PE–EtOAc, 10:2) to afford the desired product 3aa (243 mg, 89%). Yellow oil; IR (KBr): 2951, 2857, 1717, 1640, 1516, 1475, 1443, 1257, 1160, 1044, 978, 912, 167, 740 cm^–1; ¹H NMR (CDCl₃, 400 Hz): δ = 7.21–7.14 (q, J = 8.4 Hz, 4 H), 6.77–6.76 (d, J = 3.2 Hz, 1 H), 6.22–6.22 (d, J = 3.2 Hz, 1 H), 3.81 (s, 3 H), 3.71 (s, 3 H), 2.37 (s, 3 H); ¹³C NMR (CDCl₃, 100 Hz): δ = 164.4, 162.1, 138.3, 136.7, 129.7, 127.0, 125.0, 124.9, 119.1, 110.8, 52.3, 51.6, 21.0; MS (EI): m/z (%) = 242.05 (100.00), 273.05 (86.88); Anal. Calcd for C₁₅H₁₅NO₄: C, 65.92; H, 5.53; N, 5.13. Found: C, 66.07; H, 5.45; N, 5.30.