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DOI: 10.1055/s-2008-1042920
Organocatalyzed Asymmetric Inverse-Electron-Demand Hetero-Diels-Alder Reaction of α,β-Unsaturated Trifluoromethyl Ketones and Aldehydes
Publikationsverlauf
Publikationsdatum:
17. März 2008 (online)
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Abstract
The inverse-electron-demand hetero-Diels-Alder reaction of aldehydes and α,β-unsaturated trifluoromethyl ketones occurred under mild conditions using a chiral diphenylprolinol silyl ether as the catalyst. After subsequent chemical transformations, the corresponding 6-trifluoromethyl-3,4-dihydropyan-2-ones were obtained in good enantioselectivities.
Key words
organocatalyzed - hetero-Diels-Alder reaction - unsaturated trifluoromethyl ketone - aldehyde - dihydropyranone
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References and Notes
General Experimental Procedure
To a stirred solution of aldehyde 1 (1.2 mmol), catalyst 11 (0.20 mmol), p-fluorophenol (0.20 mmol), and SiO2 (100 mg) in CH2Cl2 (10 ml) was added α,β-unsaturated trifluoromethyl ketones (1.0 mmol) at r.t. and the reaction mixture was stirred for the time as specified in Table
[2]
(monitored by TLC). The resulted mixture was directly purified by column chromatography on silica gel to give product 3. Jones reagent was added to the solution of 3 (0.8 mmol) in acetone (15 mL) at r.t. until the salmon pink of the solution did not disappear in one minute. The mixture was stirred at r.t. for 2 h and then quenched by MeOH (1 mL) and H2O (2 ml). The resulted mixture was extracted with Et2O
(3 ¥ 10 ml) and dried over Na2SO4. After removal of the solvent, the crude product of
7
was obtained and used in the next step directly without further purification. The solution of 7 (0.5 mmol) and Et3N (1.4 mmol) in dry CH2Cl2 (5 ml) was stirred at -20 °C under nitrogen atmosphere for 5 min. Then, methanesulfonyl chloride (0.8 mmol) was added with a microsyringe and the resulted mixture was stirred at this temperature for 2 h. After the reaction was complete, the mixture was poured into 5 mL of 10% HCl. The solution was extracted with CH2Cl2 (3 × 10 mL), washed with sat. aq NaHCO3 and NaCl solutions, and dried over Na2SO4. After removal of the solvent, the residue was subjected to fast column chromatography on silica gel to give product 8.
trans-3-Methyl-4-phenyl-6-trifluoromethyl-3,4-dihydro-
pyane-2-one (8a): colorless oil; [α]D
20 +69.9 (c 1.67, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.33-7.08 (m, 5 H), 5.88 (d, J = 2.7 Hz, 1 H), 3.46-3.41 (m, 1 H), 2.74-2.65 (dq, J
1
= 11.4 Hz, J
2
= 7.8 Hz, 1 H), 1.09 (d, J = 7.8 Hz, 3 H). 19F NMR (282 MHz, CDCl3): δ = -72.20 (s, 3 F). 13C NMR (75 MHz, CDCl3): δ = 168.10, 140.45 (q, J = 37.9 Hz), 139.46, 129.32, 128.16, 127.57, 118.50 (q, J = 269.7 Hz), 111.49, 43.81, 40.42, 13.91. IR (film): 3032, 1787, 1197
cm-1. MS (70 eV): m/z (%) = 256 (16.53) [M+], 56 (100). HRMS: m/z calcd for C13H11F3O2: 256.0711; found: 256.0720. The chiral HPLC analytical data: Chiralpak OD column, detected at λ = 214 nm, eluent: n-hexane-i-PrOH (95:5), 0.3 mL/min, t
R(minor) = 24.1 min, t
R(major) = 26.4 min.