Zn(OTf)₂-Mediated Expeditious and Solvent-Free Synthesis of Propargylamines via C–H Activation of Phenylacetylene

Abstract

Zn(OTf)₂-mediated expeditious and solvent-free synthesis of propargylamines via A³ coupling of aldehydes, amines, and phenylacetylene has been described. The described protocol proceeds effectively with variety of substituted benzaldehydes, enolizable aldehyde, and formaldehyde. Recyclability of the catalyst, low catalyst loading, and use of inexpensive catalyst are the key features of the present protocol.

Key words

Zn(OTf)₂ - solvent-free synthesis - C–H activation - A³ coupling - propargylamine

• References and Notes

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• 20 Typical Experimental Procedure: Preparation of 1-(1,3-Diphenylprop-2-yn-1-yl)piperidine (4a) To a 25 mL flask were added aldehyde 1a (0.110 mL, 1.0 mmol), amine 2a (0.130 mL, 1.2 mmol), alkyne 3a (0.165 mL, 1.5 mmol), and Zn(OTf)₂ (0.02 g, 0.05 mmol). The reaction mixture was stirred at 100 °C until complete consumption of starting aldehyde (TLC monitoring). The reaction mixture was cooled to room temperature, diluted with EtOAc, and then washed with cold H₂O (2 × 5 mL). The organic phase was separated, and the aqueous layer was extracted further with EtOAc (2 × 5 mL). Concentration of the combined organic layers afforded the crude product, which was further purified by column chromatography on 100–200 silica gel (hexane–EtOAc, 20:1) to afford propargylamine 4a as a pale yellow oil; yield 0.284g, 96%; R_f = 0.8 (5% EtOAc–hexane). ¹H NMR (500 MHz, CDCl₃): δ = 7.65–7.63 (m, 2 H), 7.55–7.51 (m, 2 H), 7.38–7.29 (m, 6 H), 4.81 (s, 1 H), 2.62–2.55 (m, 4 H), 1.63–1.57 (m, 4 H), 1.47–1.45 (m, 2 H). The catalyst was recovered from the aqueous layer via evaporation under reduced pressure and dried at 120 °C for 2 h to obtain pure Zn(OTf)₂. The recovered catalyst was reused for the next reaction in the same way.