Synthesis of Multisubstituted Allenes via Palladium-Catalyzed Cross-Coupling Reaction of Propargyl Acetates with an Organoaluminum Reagent

Abstract

We describe a convenient method for the synthesis of multisubstituted allenes from cross-coupling of propargyl acetates with ­organoaluminum reagent: The reaction of propargyl acetates with 1.2 equivalents of organoaluminum reagent mediated by Pd(PPh₃)₂Cl₂ (1 mol%)/Ph₃P (2 mol%) and K₂CO₃ in THF may produce tri- or tetrasubstituted allenes in good to excellent yields (83–94%) and high regio­selectivities (up to 99%) at 60 °C in 3–4 hours.

Key words

allenes - palladium - propargyl acetate - organoaluminum reagent - cross-coupling

• References


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• 12 Experimental Section ¹H NMR and ¹³CNMR spectra were recorded on a Varian 400 MHz spectrometer. The chemical shifts are reported relative to TMS. Analytical thin-layer chromatography (TLC) was performed on silica 60F-254 plates. Flash column chromatography was carried out on silica gel (200–400 mesh). All reactions were carried out under nitrogen atmosphere. Chemical reagents and solvents were purchased from Damas-beta and Aldrich, and were used without further purification with the exception of these reagents: THF, Et₂O, hexane, and toluene were distilled from sodium under nitrogen, and CH₂Cl₂ was distilled from CaH₂. Compounds of propargyl acetates 1a–o were prepared according to literature procedures.^5l,13,14 Purification of the reaction products was carried out by flash chromatography. General Procedures for the Synthesis of Propargyl Acetates 1a–o To a solution of the alkyne (16.5 mmol) in anhydrous THF (25 mL) at –78 °C under nitrogen atmosphere was added n-BuLi 1.6 M (16.5 mmol). The reaction was stirred at this temperature for 20 min then at r.t. for 1 h. After cooling to –78 °C, the aldehyde or ketone (15.0 mmol) was added, and the reaction was stirred at r.t. for 1 h. After addition of acetate anhydrous (30.0 mmol) at 0 °C, the reaction mixture was warmed to r.t. and stirred for 2 h before being quenched with a sat. aq NH₄Cl solution. The mixture was extracted with Et₂O (3 × 30 mL). The combined organic layers were washed with brine, dried over MgSO₄, filtered, and evaporated to give the crude products. The crude product was subjected to flash column chromatography on silica gel (hexane or EtOAc and hexane) to afford the corresponding propargylic acetate 1. 1,3-Diphenylprop-2-ynyl Acetate (1a)^{5l 1}H NMR (400 MHz, CDCl₃): δ = 7.62–7.58 (m, 2 H), 7.50–7.46 (m, 2 H), 7.44–7.37 (m, 3 H), 7.36–7.28 (m, 3 H), 6.70 (s, 1 H), 2.14 (s, 3 H) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 169.7, 137.1, 131.8, 128.9, 128.7, 128.6, 128.2, 127.7, 122.0, 87.0, 85.5, 66.0, 21.0 ppm.General Procedures for the Cross-Coupling Reaction of Propargyl Acetates with TrimethylaluminumUnder a dry nitrogen atmosphere, a mixture of Pd(PPh₃)₂Cl₂ (0.0035 g, 0.005 mmol), Ph₃P (0.0026 g, 0.01 mmol), and K₂CO₃ (0.138 g, 1.0 mmol) in a reaction vessel was added AlMe₃ (0.6 mmol) in THF (1 mL) followed by an addition of propargyl acetate (0.50 mmol). The resulted solution was stirred at 60 °C for 3–4 h. After completion the reaction, the mixture was diluted with sat. NH₄Cl solution (5 mL) and extracted with EtOAc (3 × 15 mL). The combined organic layers were dried over anhydrous Na₂SO₄, filtered, and evaporated under vacuum. The residue was subjected to flash column chromatography on silica gel (hexane or EtOAc and hexane) to afford the corresponding allene products 2. 1,3-Diphenylbuta-1,2-diene (2a)^5l Yellow oil; 0.174 g (85%). ¹H NMR (400 MHz, CDCl₃): δ = 7.48–7.44 (m, 2 H), 7.36–7.28 (m, 6 H), 7.25–7.20 (m, 2 H), 6.48 (q, J = 2.8 Hz, 1 H), 2.23 (d, J = 2.8 Hz, 3 H) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 206.8, 136.3, 134.5, 128.7, 128.5, 127.03, 127.02, 126.9, 125.8, 104.5, 96.6, 16.8 ppm.
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