Base-free two-step synthesis of 1,3-diketones and β-ketoesters from α-diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes (original) (raw)

2011, Organic & Biomolecular Chemistry

Experimental Methods General. All reagents and solvents were obtained from Aldrich and Fluka. Tetrahydrofuran was freshly distilled from sodium/benzophenone, Melting points were determined on a Fisher apparatus and are uncorrected. All reactions were performed under a dry Ar atmosphere unless otherwise specified. Reaction progress was monitored by analytical thinlayer chromatography using GF silica plates purchased from Merck. Visualization was achieved by shortwave UV light (254 nm). 1 H and 13 C NMR spectra were recorded on both a Varian Gemini-200 and JEOL Eclipse-300 model spectrometers using CDCl 3 as solvent. Chemical shifts are reported as parts per million downfield from an internal tetramethylsilane standard (δ = 0.0 for 1 H) or from solvent references. NMR coupling constants are reported in hertz (Hz). IR spectra were obtained with a Nicolet Magna 750 FT-IR spectrometer. Low-and high-resolution electron impact mass spectra were obtained on JEOL JMS-AX505HA spectrometer. General procedure for the synthesis of aldols. (5a-k) To a stirred solution of aldehyde (1 eq), and trialkylborane or triphenylborane 1 M (3 eq.), in THF under argon, a solution of diazoketone(1 eq.) in THF was added dropwise. Then, the reaction mixture was stirred at room temperature until disappearance of diketone as evident by TLC analysis (~1h). The solvent was removed under reduced pressure and the crude oil obtained was purified by flash chromatography eluting with a hexane/ethyl acetate (9:1) solvent system. General procedure for the oxidation of aldols to 1,3 diketones. To a stirred solution of the corresponding aldol 5a-f (1 eq) in CH 2 Cl 2 (20 ml) and 1g of molecular sieves 4 Å, PCC (5 eq.) was added at 0 °C. The reaction mixture was stirred for 4 h, and then diluted with Et 2 O and pass through a short celite plug. The solvent was removed under reduced pressure and the residue was subjected to flash chromatography eluting with a hexane/ethyl acetate (9:1) solvent system. 2-Ethyl-1,3-Bisphenylpropane-1,3-dione (6a). 2-Diazo-1-phenyletanone 1a (0.15g, 1 mmol) was reacted with triethylborane 1M in THF 2a (3 mmol) and benzaldehyde 4a (0.11 g, 1 mmol) according to the general procedure to provide 5a (0.1 g, 41%). Then, 5a was oxidized with PCC to afford 6a as a white solid (0.06 g, 58%) Mp: 81-85 °C.