An Efficient One-Pot Synthesis of Novel Fused Pyrroles and Indoles by Dipolar Cycloaddition under Microwave and Conventional Conditions

Abstract

The straightforward synthesis of families of novel tri­cyclic and tetracyclic pyrrolino and indolino heterocycles in a one-pot [3+2]-cycloaddition reaction is described. The process enables the synthesis of diversified pyrroles or pyrrolines in high yields in a single step. Microwave and conventional thermal conditions were explored, with remarkable acceleration observed under the microwave conditions.

Key words

cycloadditions - azomethine ylides - indoles - pyrroles - fused-ring systems

References and Notes

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7

Typical Thermal Procedure: To propargylformylpyrrole (2 mmol) in xylene (10 mL), was added methyl sarcosinate (4 mmol). The reaction mixture was refluxed with stirring for 2 h under nitrogen atmosphere. Then sulfur (8 mmol) was added and the refluxing was continued for another hour. After cooling, the solvent was removed under reduced pressure, and the crude product was purified by flash chromatography on silica gel eluting with heptane-EtOAc (4:1) to give product 8a (71% yield). IR (film): 3106, 3020, 1693, 1215, 1095 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 6.95 (dd, J = 0.5, 2.7 Hz, 1 H), 6.89 (s, 1 H), 6.27 (dd, J = 2.7, 3.5 Hz, 1 H), 6.12 (dd, J = 0.5, 3.5 Hz, 1 H), 4.67 (s, 2 H), 4.03 (s, 3 H), 3.82 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 161.9, 138.7, 129.5, 123.4, 123.2, 118.7, 112.2, 111.9, 96.7, 50.9, 46.8, 35.1.

8

Typical Microwave Irradiation Procedure: To propargyl-formylpyrrole (1.25 mmol) and methyl sarcosinate
(2.25 mmol) placed in a test tube (Ø = 10 mm), were added sulfur (5 mmol) and xylene (0.5 mL) and mixed thoroughly on a vortex mixer. The mixture was irradiated at a final temperature of 130 °C at a maximum power of 100 W. After cooling and removal of the solvent under reduced pressure, followed by filtration through a short silica gel column using heptane-EtOAc (4:1) as eluent, the desired product 8a was obtained in 85% yield.