Hydrogen-Bond-Promoted Metal-Free Hydroamination of Alkynes

Abstract

An original metal-free regio- and stereoselective intermolecular hydroamination of alkynes is described. Various (E)-enamines were obtained from arylacetylenes and aliphatic secondary amines in the presence of ethylene glycol as a solvent. The latter is assumed to play a major role in the mechanism through hydrogen bonding and proton exchange.

Key words

hydroamination - alkynes - amines - metal-free - enamines - green chemistry

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• 22 Hydroamination of Alkynes with Amines; General Procedure Under an atmosphere of argon, a screw-cap vial was charged with ethylene glycol (250 μL, 8.9 equiv) and the appropriate alkyne (0.5 mmol, 1 equiv) and amine (2.5 mmol) at r.t. The tube was sealed under a positive pressure of argon and the mixture was stirred and heated to 150 °C for 8 h. The mixture was cooled to r.t., diluted with EtOAc (5 mL), and washed with H₂O (3 × 2 mL) and brine (1 × 2 mL). The organic phase was dried (MgSO₄), filtered, and concentrated under reduced pressure (rotary evaporator). Excess amine was then removed from the residue under high vacuum to give the desired enamine without any need for further purification. In the case of amines with high boiling points, such as dibutylamine or dipentylamine, the residues were dried by heating to 50 °C under high vacuum. (E)-N,N-Dipentyl-2-phenylethylenamine (3b) Solid; yield: 97 mg (75%). ¹H NMR (400 MHz, CDCl₃): δ = 7.20–7.14 (m, 4 H), 6.95–6.92 (m, 1 H), 6.76 (d, J = 14 Hz, 1 H), 5.07 (d, J = 14 Hz, 1 H), 3.07 (t, J = 7.1 Hz, 4 H), 1.60–1.54 (m, 4 H), 1.39–1.33 (m, 4 H), 1.33–1.28 (m, 4 H), 0.92 (t, J = 7.2 Hz, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 140.4, 138.5, 128.5, 123, 122.5, 96.3, 51.7, 29.2, 27.6, 22.5, 14.1. HRMS (ESI-TOF): m/z [M + H]⁺ Calcd for C₁₈H₃₀N: 260.2300; found: 260.2301.