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DOI: 10.1055/s-2008-1078028
Observations on the Synthesis and Carbocyclisation Reactions of 6-Oxohexa-2,3-dienoates
Publikationsverlauf
Publikationsdatum:
05. August 2008 (online)
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Abstract
6-Oxohexa-2,3-dienoates can be readily prepared via an atom economical Claisen rearrangement of propargyl vinyl ethers formed in situ by the reaction of propargylic alcohols with acetals. Preliminary experiments have demonstrated that these functionalised allenic esters undergo a facile amine-induced carbocyclisation under mild reaction conditions, yielding densely functionalised cyclopentanones containing chiral quaternary carbon centres.
Key words
acetals - alcohols - allenes - cyclisation - rearrangements
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1a
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6a
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Saucy G.Marbet R. Helv. Chim. Acta 1967, 50: 1158 - For a metal-catalysed synthesis of allenes from propargylic alcohols, see:
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References and Notes
All pyruvic acid esters were purchased from the Aldrich chemical company.
8General Experimental Procedure for the Synthesis of Allenic Esters 8a-g: A solution of the propargylic alcohol (7.00 mmol), acetal (7.70 mmol) and PTSA (30 mg) in anhyd toluene (30 mL) in a flask fitted with a Dean and Stark separator was heated to a vigorous reflux for 24 h. The cooled solution was concentrated at reduced pressure and the crude oils were purified by flash column chromatography, eluting with PE-EtOAc (20:1) to give the described allenes 8a-g as pale yellow oils. Data for 8f: IR (thin film): 2933 (CH), 2804 (CH), 1957 (s, C=C=C), 1716 (C=O), 1450 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 1.50-1.80 (m, 10 H, CH2), 1.87 (d, J = 2.9 Hz, 3 H, Me), 3.72 (s, 3 H, OMe), 5.27 (q, J = 2.9 Hz, 1 H, CH), 9.32 (s, 1 H, CHO). ¹³C NMR (75 MHz, CDCl3): δ = 210.7, 201.4, 167.7, 98.2, 95.7, 52.3, 51.5, 30.7, 30.6, 25.5, 22.0, 22.0, 15.0. HRMS: m/z [M + H] calcd for C16H18O3: 223.13341; found: 223.13276.
10General Experimental Procedure for the Preparation of Cyclopentanones 20a-c: Pyrrolidine (0.45 mmol) was added to a solution of the allenic ester (0.45 mmol) in MeCN (8 mL) at r.t. The solution was stirred at r.t. for 12 h and then concentrated at reduced pressure. The crude oil was dissolved in THF (10 mL) and 10% aq AcOH (10 mL) was added. The acidic solution was stirred at r.t. for 12 h and then the mixture was poured into sat. aq NaHCO3 solution (10 mL). The aqueous phase was separated and extracted with EtOAc (3 × 20 mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4), filtered and concentrated at reduced pressure. The crude oils were purified by flash column chromatography, eluting with PE-EtOAc (5:1) to give the title cyclopentanones 20a-c. Data for 20c: mp 34-36 ˚C. IR (Nujol): 3496 (br s, OH), 2929, 2856 (CH), 1747 (C=O, ketone), 1728 (C=O, ester), 1452 cm-¹. Diastereoisomer 1: ¹H NMR (300 MHz, CDCl3): δ = 1.30-1.74 [m, 10 H, (CH2)5], 1.47 (s, 3 H, Me), 2.27 (d, J = 18.4 Hz, 1 H, CH2CO), 2.53 (br s, 1 H, OH), 2.82 (d, J = 18.4 Hz, 1 H, CH2CO), 3.11 [s, 1 H, CH(OH)], 3.70 (s, 3 H, OMe). ¹³C NMR (75 MHz, CDCl3): δ = 213.7, 173.6, 77.9, 62.3, 54.2, 49.6, 42.5, 39.0, 29.4, 25.7, 24.3, 22.8, 22.3, 16.4. Diastereoisomer 2: ¹H NMR (300 MHz, CDCl3): δ = 1.20-1.75 [m, 10 H, (CH2)5], 1.33 (s, 3 H, Me), 2.18 (d, J = 5.6 Hz, 1 H, OH), 2.22 (d, J = 17.4 Hz, 1 H, CH2CO), 2.59 (d, J = 17.4 Hz, 1 H, CH2CO), 3.69 (s, 3 H, OMe), 4.39 [d, J = 5.4 Hz, 1 H, CH(OH)]. ¹³C NMR (75 MHz, CDCl3): δ = 212.3, 172.9, 85.9, 60.0, 52.8, 47.3, 42.2, 36.7, 29.0, 25.6, 23.3, 22.1, 15.6. HRMS: m/z [M + H] calcd for C13H20O4: 241.14398; found: 241.14411.