Green H₂O-Promoted Solvent-Free Synthesis of Enaminocarbonyl Compounds with High Stereoselectivity from Electron-Deficient Terminal Alkynes

Abstract

A green H₂O-promoted solvent-free hydroamination of electron-deficient terminal alkynes with amines has been developed. All secondary amines, including aliphatic and aromatic amines, gave the corresponding (E)-enamines in good to excellent yields, whereas primary aromatic amines afforded Z-configured products in moderate yields. Propiolates, propyn-1-ones, propynamides, and 1-(ethynylsulfonyl)-4-methylbenzene were explored in this Michael addition.

Key words

green chemistry - water catalysis - hydroamination - alkynes - enamines

• References and Notes

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• 10 When D₂O was used as additive in the reaction instead of H₂O, the ¹H NMR spectrum of the product (Figure S3; Supporting Information) showed that about half the double-bond protons were replaced by deuterium. However, as hydrogen exchange between both substrates and D₂O was found to occur, the degree of participation of H₂O/D₂O in protonation/deuteration could not be conclusively demonstrated by this experiment.
• 11 Ethyl (2E)-3-[Methyl(phenyl)amino]acrylate (3a); Typical Procedure Ethyl propiolate (0.5 mmol) was slowly added with stirring to a mixture of N-methylaniline (0.6 mmol) and distilled H₂O (0.1 mL) in a 2 mL vial, and the vial then sealed. The mixture was heated at 80 °C with stirring for 1 h. The reaction was then quenched with sat. brine (0.5 mL), and the mixture was cooled to r.t. and extracted with EtOAc (3 × 1 mL) by pipette in the same vial. The combined organic layers were dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, PE–EtOAc (8:1)] to give a pale yellow oil; yield: 96.7 mg (94%). ¹H NMR (400 MHz, CDCl₃): δ = 7.94 (d, J = 13.2 Hz, 1 H), 7.38–7.31 (m, 2 H), 7.15–7.08 (m, 3 H), 4.94 (d, J = 13.2 Hz, 1 H), 4.18 (q, J = 7.1 Hz, 2 H), 3.24 (s, 3 H), 1.28 (t, J = 7.1 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 169.3, 148.6, 146.7, 129.6, 124.3, 120.0, 90.5, 59.44, 36.7, 14.7. MS (ESI): m/z [M + H]⁺ calcd for ­C₁₂H₁₆NO₂: 206.1; found: 206.1.