Highly Efficient Cadmium-Catalyzed Three-Component Coupling of an Aldehyde, Alkyne, and Amine via C-H Activation under Microwave Conditions

Abstract

The first use of Cd^²+ as catalyst for a facile three-component coupling of an aldehyde, alkyne, and amine has been demonstrated to synthesize propargylamines under microwave irradiation in chlorobenzene without the use of a co-catalyst or activator in the absence of inert atmosphere. This method has been proved to be applicable to a wide range of substrates.

Key words

transition-metal catalyst - multicomponent reaction - aldehydes - A^³ coupling - propargylamines

References and Notes

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20

General Procedure for the Synthesis of Propargylamines Aldehyde (1 mmol), amine (1.1 mmol), alkyne (1.2 mmol), CdI₂ (7 mol%), and chlorobenzene (2 mL) were placed in a sealed pressure-regulation 10 mL pressurized vial with ‘snap-on’ cap, and the mixture was irradiated in a single-mode microwave synthesis system at 300 W and 130 ˚C for 7-8 min. After completion of the reaction (as monitored by TLC), the solvent was evaporated under vacuum. Water (20 mL) was added to the reaction mixture, and the product was extracted with EtOAc (3 × 10 mL). The combined organic phases were dried over anhyd MgSO₄, filtered, and the solvent was evaporated under vacuum. The residue was purified by column chromatography on silica gel (EtOAc-hexane, 1:9) to afford the pure propargylamines.
Representative Data
4-(1,3-Diphenylprop-2-ynyl)morpholine (4a) FT-IR (KBr): 2935, 2756, 1590, 1490, 1451, 1319, 1152, 757, 694 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.61 (d, J = 7.2 Hz, 2 H), 7.49 (m, 2 H), 7.39-7.25 (m, 6 H), 4.78 (s, 1 H), 3.76-3.72 (m, 4 H), 2.64-2.61 (m, 4 H) ppm. ^¹³C NMR (75 MHz, CDCl₃): δ = 137.7, 131.7, 128.5, 128.2, 128.3, 128.0, 127.7, 122.9, 88.4, 84.9, 67.1, 62.0, 49.8. Anal. Calcd for C₁₉H₁₉NO: C, 82.28; H, 6.90; N, 5.05. Found: C, 82.32; H, 6.82; N, 5.12.