Unexpected Synthesis of N-Acyl Indolines via a Consecutive Cyclization of Iminophosphorane

Abstract

N-Acyl indolines were obtained unexpectedly from a consecutive cyclization of iminophosphorane in refluxing xylene or 1,2-dichlorobenzene in good yields. This new approach provides an efficient and direct access to the biologically important indolines which are further oxidizable to indoles and oxindoles.

Key words

N-acyl indoline - iminophosphorane - cyclization - Staudinger reaction

References and Notes

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9

Iminophosphorane 2 To a stirred solution of 2-(2-azidophenyl)ethanol (0.33 g, 2.0 mmol) and Et₃N (0.60 g, 6.0 mmol) in CH₂Cl₂ (15 mL) was added a solution of acyl chloride (2.0 mmol) in CH₂Cl₂ (10 mL) at r.t. The reaction mixture was stirred for 30 min. It was then pour into H₂O to remove the Et₃NHCl, and extracted with CH₂Cl₂ three times. The organic phase was combined and dried with anhyd Na₂SO₄. The crude product was purified by flash chromatography (PE-Et₂O, 15:1) to yield azide 1. To a stirred solution of azide 1 (2 mmol) in CH₂Cl₂ (15 mL) was added a solution of Ph₃P (0.52 g, 2 mmol) in dry CH₂Cl₂ (10 mL). After the reaction mixture was stirred for 1 h, the solvent was removed under reduced pressure, and the residue was recrystallized from Et₂O and CH₂Cl₂ (2:1;
v/v) to give the iminophosphorane 2.
Spectral Data for the Unreported Compounds
Compound 2a: yield 93%, white solid, mp 140-141 ˚C. ^¹H NMR (600 MHz, CDCl₃): δ = 8.07 (d, 2 H, J = 7.8 Hz, ArH), 7.78-6.46 (m, 22 H, ArH), 4.68 (t, 2 H, J = 6.6 Hz, OCH₂), 3.39 (t, 2 H, J = 6.6 Hz, CH₂). MS: m/z (%) = 501 (8) [M⁺], 396 (38), 380 (29), 262 (42), 183 (100), 108 (36), 105 (45), 77 (48). Anal. Calcd for C₃₃H₂₈NO₂P: C, 79.02; H, 5.63; N, 2.79. Found: C, 79.24; H, 5.74; N, 2.61.

10

N-Acyl Indolines 4 and 5 The solution of iminophosphorane 2 (2 mmol) in xylene or 1,2-dichlorobenzene was heated to reflux for 1-24 h under N₂. The crude product was purified by flash chromatography to yield N-acyl indolines 4 and 5. Spectral data for com-pounds 4 and 5 are identical with the literature reports.
Compound 4a: white solid, mp 121-123 ˚C. ^¹H NMR (600 MHz, CDCl₃): δ = 8.31-7.03 (m, 9 H), 4.06 (br, 2 H), 3.12 (t, J = 8.4 Hz, 2 H). ^¹³C NMR (150 MHz, CDCl₃): δ = 168.8, 142.4, 136.8, 132.1, 130.1, 128.4, 126.9, 124.7, 123.9, 123.8, 117.3, 50.7, 28.1. MS: m/z (%) = 223 (66) [M⁺], 105 (100), 77 (33). Anal. Calcd for C₁₅H₁₃NO: C, 80.69; H, 5.87; N, 6.27. Found: C, 80.53; H, 5.85; N, 6.42.