1,4,2-Dioxazol-5-ones as Isocyanate Equivalents: Chemoselective Non-Metal-Catalyzed Carboxamidation of Indoles

Abstract

1,4,2-Dioxazol-5-ones are known to undergo decarboxylation under thermal conditions followed by Lossen’s rearrangement to give isocyanates. Described herein is the in situ trapping of the isocyanates by indoles to give indole-3-carboxamides in good to excellent yields.

Key words

dioxazolones - isocyanates - Lossen rearrangement - indolecarboxamides - metal-free reaction

Publication History

Received: 07 January 2022

Accepted after revision: 15 January 2022

Article published online:
03 February 2022

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• 18 N-Phenyl-1H-indole-3-carboxamide (3aa); Typical Procedure KO ^t Bu (20 mmol) was added in one portion to a stirred solution of 1H-indole (2a; 10 mmol) and 3-phenyl-1,4,2-dioxazol-5-one (1a; 12 mmol) in toluene (20 mL) at r.t., and the mixture was then stirred at 110 °C for 1–2 h until the reaction was complete (TLC). The mixture was cooled to r.t. and H₂O (20 mL) was then added. The resulting mixture was extracted with EtOAc (3 × 50 mL), and the extracts were dried (Na₂SO₄) and then concentrated under reduced pressure. The residue was purified by chromatography [silica gel, hexane–EtOAc (8:2)] to give a pale yellow solid; yield: 58 mg (57%); mp 172–174 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 1.74 (br s, 1 H), 9.71 (br s, 1 H), 8.30 (d, J = 3.0 Hz, 1 H), 8.20 (d, J = 7.9 Hz, 1 H), 7.77 (d, J = 8.0 Hz, 2 H), 7.47 (d, J = 7.9 Hz, 1 H), 7.33 (t, J = 7.7 Hz, 2 H), 7.17 (m, 2 H), 7.04 (t, J = 7.4 Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 163.73, 140.30, 136.69, 129.13, 128.99, 126.90, 123.05, 122.59, 121.56, 121.11, 120.20, 112.41, 110.97. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₁₃N₂O: 237.1028; found: 237.1026.