Dirhodium-Catalyzed Chemo- and Site-Selective C–H Amidation of N,N-Dialkylanilines

Abstract

A method for dirhodium-catalyzed C(sp³)–H amidation of N,N-dimethylanilines was developed. Chemoselective C(sp³)–H amidation of N-methyl group proceeded exclusively in the presence of C(sp²)–H bonds of the electron-rich aromatic ring. Site-selective C(sp³)–H amidation proceeded exclusively at the N-methyl group of N-methyl-N-alkylaniline derivatives with secondary, tertiary, and benzylic C(sp³)–H bonds α to a nitrogen atom.

Key words

C–H amidation - dirhodium complex - aniline - nitrene - site selectivity

Publication History

Received: 16 November 2020

Accepted after revision: 10 December 2020

Accepted Manuscript online:
10 December 2020

Article published online:
07 January 2021

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• 19 General Procedure for Dirhodium-Catalyzed C(sp³)–H Amidation of N,N-Dialkylanilines To a suspension of N,N-dialkylanilines (0.5 mmol, 10 equiv), TrocNHOTs (18.1 mg, 0.05 mmol, 1.0 equiv), and K₂CO₃ (10.4 mg, 0.075 mmol, 1.5 equiv) in toluene (0.25 mL) were added Rh₂(oct)₄ (1.9 mg, 0.05 equiv) at room temperature. After being stirred for 12 h, the reaction was quenched by addition of water and extracted with EtOAc. The organic layer was washed with brine and dried over Na₂SO₄, filtered, and concentrated. The yields of the aminated product 2 were determined by ¹H NMR analysis using 1,3-dinitrobenzene as internal standard. The residue was purified by preparative TLC purification to afford the aminated product 2. Trichloroethyl{[methyl(phenyl)amino]methyl}carbamate (2aa) Colorless oil. ¹H NMR (400 MHz, CDCl₃, 323 K): δ = 7.29–7.25 (m, 2 H), 6.84–6.81 (m, 3 H), 5.41 (br s, 1 H), 4.91 (d, J = 6.0 Hz, 2 H), 4.73 (s, 2 H), 3.01 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 154.9, 147.7 129.6, 118.7, 113.6, 95.5, 74.6, 59.6, 37.8. IR (neat): 3326, 2952, 1722, 1598, 1499, 1367, 1220, 1132, 1041, 817, 750 cm^–1. HRMS-ESI⁺: m/z calcd for C₁₁H₁₃Cl₃N₂O₂ [M + H]⁺: 311.0115; found: 311.0115.