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Synlett 2003(1): 0043-0046
DOI: 10.1055/s-2003-36226
LETTER
© Georg Thieme Verlag Stuttgart · New York

3-Chloro-propenyl Esters in Organic Synthesis: A New Chromium-Catalysed Homoaldol Reaction

Marco Lombardo*, Stefano Morganti, Sebastiano Licciulli, Claudio Trombini*
Università di Bologna, Dipartimento di Chimica ‘G. Ciamician’, via Selmi 2, 40126 Bologna, Italy
Fax: +39(51)2099456; e-Mail: trombini@ciam.unibo.it;
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Publication History

Received 18 September 2002
Publication Date:
18 December 2002 (online)

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Abstract

Chromium(II) oxidatively adds to 3-halo-propenyl esters affording heterosubstituted allylchromium(III) reagents exploitable in the Nozaki-Hiyama-Kishi reaction. A catalytic cycle based on the Cr(III)-Mn(0) redox couple was applied, affording protected homoaldols as the major products, at 65 °C in acetonitrile as solvent.

Key words

3-halo-propenyl esters - catalytic Nozaki-Hiyama-Kishi reaction - heterosubstituted allylchromium complexes - homo­aldol reaction - regioselectivity

    References

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11

Typical Experimental Procedure (Table [2] , Run 1).
(Z)-4-Cyclohexyl-4-trimethylsilyloxy-but-1-en-1-yl acetate (11, R = c-C6H11). A flame dried 10 mL flask is charged under argon with freshly distilled CH3CN (2.5 mL), manganese powder (0.164 g, 3 mmol, ˜50 mesh, 99.9% purity, Aldrich)and chromium(III) chloride (0.016 g, 0.1 mmol, 99% purity, Aldrich). The heterogeneous mixture is left unstirred for 15 min, then vigorously stirred for 30 min until the solution turns light blue, an evidence of chromium(II) chloride formation. 3-Chloro-propenyl acetate 4a (0.175 mL, 1.5 mmol), cyclohexanecarboxaldehyde (0.120 mL, 1 mmol), trimethylsilyl chloride (0.150 mL, 1.2 mmol, purified immediately before use by elution through a short column of basic alumina) and tetrabutylammonium iodide (0.075 g, 0.2 mmol) are sequentially added to the reaction mixture. The temperature is raised to 65 °C and stirring is continued vigorously for 2 h at 65 °C. The reaction mixture is cooled to room temperature and finally quenched with 5 mL of water. Inorganic salts are removed by filtration through Celite, the organic solvent is evaporated at reduced pressure and the aqueous layer is extracted with diethyl ether (3 × 10 mL). The combined organic layers are dried (Na2SO4) and evaporated at reduced pressure. Flash-chromatography (cyclohexane-diethyl ether 95:5) of the residue furnishes a fraction containing (Z)-4-cyclohexyl-4-trimethylsilyloxy-but-1-en-1-yl acetate and its regioadduct, 4-cyclohexyl-4-trimethylsilyloxy-but-1-en-3-yl acetate (0.187 g, 0.66 mmol, 66%), in a 9:1 ratio. Title compound: 1H NMR (300 MHz, CDCl3): δ = 0.11 [s, 9 H, (CH3)3Si], 0.85-1.40 (m, 6 H), 1.57-1.88 (m, 5 H), 2.15 (s, 3 H, CH3CO), 2.32 (br dd, 1 H, 3 J H-H = 7.5 Hz, 3 J H-H = 5.8 Hz, H-3), 3.44 (dt, 1 H, 3 J H-H = 3 J H-H = 5.8 Hz, H-4), 4.95 (dt, 1 H, 3 J H-H = 6.5 Hz, 3 J H-H = 7.5 Hz, H-2), 7.08 (dt, 1 H, 3 J H-H = 6.5 Hz, 4 J H-H = 1.4 Hz, H-1); 13C NMR (50 MHz, CDCl3): δ = 0.36, (Me3Si), 20.6 (CH3CO), 26.2, 26.3, 26.5, 28.2, 29.4, 29.5, 42.7 (C-3), 76.1 (C-4), 110.4 (C-2), 135.0 (C-1), 167.8 (C=O); MS (EI): m/z (%) = 185(100), 172(7), 158(3), 129(9), 117(10), 103(67), 95(69), 75(25), 73(78), 55(8). HRMS: m/z calcd for C15H28O3Si 284.1808; found 284.1811.
5-Cyclohexyl-tetrahydrofuran-2-ol (12, R = cC6H11). Potassium carbonate (0.210 g, 1.5 mmol) is added to the previously reported 9:1 mixture of regioadducts (0.140 g,
0.5 mmol) dissolved in CH3OH-H2O (5 mL, 9:1) and the heterogeneous reaction mixture is vigorously stirred at room temperature for 8 h. Water is added (5 mL), CH3OH is evaporated at reduced pressure and the aqueous layer is extracted with diethyl ether (3 × 15 mL). The combined organic layers are dried (Na2SO4) and evaporated at reduced pressure. Purification by flash-chromatography (cyclohexane-diethyl ether 8:2) allows separation of the corresponding γ-lactol (0.076 g, 0.44 mmol, 99%), present as a 3:2 mixture of anomers, and 4-cyclohexyl-1-buten-3,4-diol (0.009 g, 0.05 mmol, 100%), identical to an authentic specimen obtained in previous work. [1] [2] Title compound:
1H NMR (300 MHz, CDCl3): δ = 0.80-2.10 (m, 30 H), 2.44
(d, 1 H, J = 3.0 Hz, OH), 2.62 (d, 1 H, J = 3.0 Hz, OH), 3.69 (br q, 1 H, J ˜ 7.5 Hz, H-5), 3.94 (br q, 1 H, J = ca. 6.85 Hz,
H-5), 5.44-5.48 (m, 1H, H-2), 5.52-5.57 (m, 1 H, H-2).
13C NMR (50 MHz, CDCl3): δ = 25.8, 25.9, 26.0, 26.5, 26.9, 27.0, 28.9, 29.0, 29.5, 29.7, 30.2, 33.1, 33.9, 42.7, 44.1, 82.7 (C-5), 85.7 (C-5), 97.9 (C-2), 98.3 (C-2).