Rhodium(III) Iodide Catalyzed Carboamination of Alkynes through C–N Bond Activation

Abstract

Here, we report a RhI₃-catalyzed intramolecular carboamination reaction to access polysubstituted indoles. The protocol features a broad substrate scope (>20 examples), good functional-group compatibility, and a low catalyst loading (5 mol% Rh). Good to excellent yields (up to 98%) were obtained. An unprecedented C–N bond-cleavage mode via a six-membered transition state σ-bond metathesis mechanism was proposed based on control experiments. A series of C3-allylated indole derivatives were accessed, proving that the system provides an alternative catalytic route to polysubstituted indoles.

Key words

rhodium catalysis - carboamination - alkynes - indoles - C–N bond cleavage - allylindoles

Publication History

Received: 21 November 2022

Accepted after revision: 13 January 2023

Accepted Manuscript online:
13 January 2023

Article published online:
09 February 2023

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• 14 1-Methyl-3-(2-methylprop-2-en-1-yl)-2-phenyl-1H-indole (2a); Typical Procedure In a nitrogen-filled glove box, an oven-dried 4 mL vial was charged with amine 1a (23.7 mg, 0.091 mmol) and RhI₃ (2.3 mg, 0.005 mmol). Toluene (1 mL) was added, and the mixture was stirred at rt for 5 minutes until the solids fully dissolved. The vial was then sealed with a PTFE-lined cap and the mixture was stirred for 12 h on a pie-block preheated to 120 °C. The mixture was then directly filtered through Celite and silica gel, which were washed with EtOAc (20 mL). The solvent was removed under reduced pressure, and the crude residue was purified by flash column chromatography (silica gel) to give a yellow oil; yield: 22.9 mg (98%). IR (FTIR): 3056, 2907, 1647, 1466, 1361, 1014, 890 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.64 (d, J = 7.8 Hz, 1 H), 7.53–7.47 (m, 2 H), 7.47–7.40 (m, 3 H), 7.37 (d, J = 8.2 Hz, 1 H), 7.30–7.24 (m, 1 H), 7.15 (ddd, J = 7.9, 6.9, 1.0 Hz, 1 H), 4.78 (s, 1 H), 4.70 (s, 1 H), 3.64 (s, 3 H), 3.40 (s, 2 H), 1.73 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 145.5, 138.7, 137.4, 132.1, 130.6, 128.4, 128.2, 128.1, 121.7, 119.7, 119.3, 110.8, 110.8, 109.4, 33.4, 31.1, 22.9. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₉H₁₉NNa: 284.1410; found: 284.1409.