Expedient Synthesis of N-Fused Indoles through an Intramolecular [3+2]-Cycloaddition Approach

Abstract

A variety of N-fused indolo pyrrolo-pyrroles and pyrrolo-pyrrolizidines were synthesized by intramolecular 1,3-dipolar cycloaddition reaction of azomethine ylide generated from N-alkenylindole carbaldehyde which were prepared by the N-alkylation of indole 2-aldehyde with Baylis-Hillman bromides.

Key words

N-fused indoles - indolo pyrrolo-pyrroles - pyrrolo-­pyrrolizidines 1,3-dipolar cycloaddition - azomethine ylides - ­Baylis-Hillman adducts

References and Notes

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17

Synthesis of N-Fused Indole 3a - Typical Procedure
A solution of 1a (1 mmol) and sarcosine 2 (1.5 mmol) in toluene (10 mL) was stirred and heated at reflux for 6 h. After evoperation of the solvent under reduced pressure, the crude product was purified by short column chromatography on silica gel (hexane-EtOAc, 5:95) to provide the product in 78% yield as viscous colorless oil. ^¹H NMR (300 MHz, CDCl₃): δ = 1.84 (s, 3 H), 2.36 (s, 3 H), 2.60 (s, 2 H), 3.25-3.38 (m, 1 H), 3.71-3.81 (m, 1 H), 3.74 (s, 3 H), 4.07-4.15 (m, 1 H), 4.81 (s, 1 H), 7.03-7.53 (m, 9 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 21.04, 39.66, 47.49, 49.65, 53.02, 59.33, 67.95, 104.52, 109.70, 118.91, 119.12, 121.26, 127.36, 128.51, 128.72, 132.08, 137.01, 138.46, 174.93. MS: m/z = 346.85 [M⁺]. Anal. Calcd for C₂₂H₂₄N₂O₂: C, 76.08; H, 6.62; N, 8.06. Found: C, 76.00; H, 6.57; N, 8.14.