Synthesis of β,γ-Unsaturated Ketones by Allylation of Pentamethylcyclopentadienyl Ketones Followed by Removal of Pentamethylcyclopentadiene

Abstract

A new route to β,γ-unsaturated ketones is disclosed. Aryl pentamethylcyclopentadienyl ketones underwent allylation with allyldimethylaluminum to yield the corresponding alcohols. Heating the alcohols in boiling toluene resulted in removal of pentamethylcyclopentadiene to provide β,γ-unsaturated ketones. The removal would proceed via a retro-carbonyl-ene process. Synthesis of an alkyl allyl ketone is also described.

allylation - cleavage - pentamethylcyclopentadiene - ketones

References and Notes

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<A NAME="RU10906ST-3">3</A> General Procedure (Table 1, Entry 2): BuLi (1.7 M hexane solution, 6.5 mL, 11 mmol) was added to a solution of 1,2,3,4,5-pentamethyl-1,3-cyclopentadiene (1.9 mL, 12 mmol) in THF (30 mL) at 0 °C. The resulting white suspension was stirred for 40 min. p-Trifluoromethyl-benzoyl chloride (1.49 mL, 10.0 mmol) was then added to the suspension at 0 °C. After being stirred for 30 min, the mixture was poured into water and extracted with EtOAc. The organic layer was dried over Na₂SO₄. Evaporation followed by silica gel column chromatographic purification (hexane-EtOAc = 80:1) provided 2b (2.84 g, 9.2 mmol) in 92% yield. Allylmagnesium bromide (0.94 M ethereal solution, 2.4 mL, 2.3 mmol) was placed in a 20-mL reaction flask under argon. Chlorodimethylaluminum (1.04 M hexane solution, 2.2 mL, 2.3 mmol) was added at -20 °C. After the mixture was stirred for 10 min, ketone 2b (0.46 g, 1.5 mmol in 6 mL of THF) was added dropwise. The whole mixture was stirred for 1 h at -20 °C. The reaction was quenched with 1 M HCl. Extractive workup yielded a crude oil. The oil was passed through a pad of silica gel with EtOAc to remove polar impurities. The filtrate was concentrated in vacuo. The resulting oil was dissolved in toluene (13 mL) and heated at reflux for 15 min under an atmosphere of argon. Concentration and purification on silica gel (hexane-EtOAc = 10:1) afforded 4b (0.31 g, 1.4 mmol) in 95% yield. Ketone 2b: colorless oil. IR (neat): 2921, 1674, 1325, 1169, 1130, 1068 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 1.26 (s, 3 H), 1.69 (s, 6 H), 1.83 (s, 6 H), 7.49 (d, J = 8.0 Hz, 2 H), 7.59 (d, J = 8.0 Hz, 2 H). ¹³C NMR (125.7 MHz, CDCl₃): δ = 10.77, 11.61, 18.84, 70.60, 123.91 (q, J = 273 Hz), 125.11 (q, J = 4 Hz), 127.67, 133.29 (q, J = 32 Hz), 139.19, 139.56, 141.30, 201.94. Anal. Calcd for C₁₈H₁₉F₃O: C, 70.12; H, 6.21. Found: C, 69.88; H, 6.33. Ketone 4b showed spectra identical to the reported data: Toy PH. Dhanabalasingam B. Newcomb M. Hanna IH. Hollenberg PF. J. Org. Chem.  1997,  62:  9114