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DOI: 10.1055/s-2003-36226
3-Chloro-propenyl Esters in Organic Synthesis: A New Chromium-Catalysed Homoaldol Reaction
Publication History
Publication Date:
18 December 2002 (online)
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
- 1
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6a
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6c
Takai K.Kataoka Y.Utimoto K. Tetrahedron Lett. 1989, 30: 4389 -
7a 3-Halo-1-propenyl
esters 4a-d were
prepared according to Neuenschwander procedure:
Neuenschwander M.Bigler P.Christen K.Iseli R.Kyburz R.Mühle H. Helv. Chim. Acta 1978, 61: 2047 -
7b The new compounds 4c and 4d have
the following NMR spectra: (Z)-4c 1H NMR (200 MHz,
CDCl3) δ = 3.49 (s, 3 H, OCH3),
4.10 (dd, 2 H, 3
J
H-H = 8.1 Hz, 4
J
H-H = 1.2 Hz, H-3), 4.18
(s, 2 H, CH2O), 5.23 (dt, 1 H, 3
J
H-H = 8.1 Hz, 3
J
H-H = 6.5 Hz, H-2), 7.26
(dt, 1 H, 3
J
H-H = 6.5 Hz, 4
J
H-H = 1.2 Hz, H-1); 13 C
NMR (75 MHz, CDCl3) δ = 36.2 (C-3),
59.3 (CH3O), 69.0 (CH2O), 110.1 (C-2), 135.8
(C-1), 166.6 (C=O). (E)-4c 1H NMR (300 MHz,
CDCl3) δ = 3.48 (s, 3 H, OCH3),
4.10 (dd, 2 H,
3
J
H-H = 7.5 Hz, 4
J
H-H = 1.2 Hz, H-3), 4.13
(s, 2 H, CH2O), 5.68 (dt, 1 H, 3
J
H-H = 7.5 Hz, 3
J
H-H = 12.1 Hz, H-2), 7.46
(dt, 1 H, 3
J
H-H = 12.1 Hz, 4
J
H-H = 1.2 Hz, H-1); 13C
NMR (75 MHz, CDCl3) δ = 40.7 (C-3), 59.2 (CH3O),
69.0 (CH2O), 111.7 (C-2), 138.2 (C-1), 166.9 (C=O).(Z)-4d 1 H
NMR (200 MHz, CDCl3) δ = 1.29 [s,
9 H, (CH3)3], 4.21 (dd, 2 H, 3
J
H-H = 8.0 Hz, 4
J
H-H = 1.1 Hz, H-3), 5.18
(dt, 1 H, 3
J
H-H = 8.0 Hz, 3
J
H-H = 6.5 Hz, H-2), 7.22
(dt, 1 H, 3
J
H-H = 6.5 Hz, 4
J
H-H = 1.1 Hz, H-1); 13C
NMR (75 MHz, CDCl3) δ = 36.2 (C-3),
59.3 (CH3O), 69.0 (CH2O), 110.1 (C-2), 135.8
(C-1), 166.6 (C=O). (E)-4d 1H NMR (200 MHz,
CDCl3) δ = 1.26 [s, 9 H, (CH3)3],
4.11 (dd, 2 H,
3
J
H-H = 8.0 Hz, 4
J
H-H = 1.1 Hz, H-3), 5.64
(dt, 1 H, 3
J
H-H = 8.0 Hz, 3
J
H-H = 12.7 Hz, H-2), 7.43
(dt, 1 H, 3
J
H-H = 12.7 Hz, 4
J
H-H = 1.1 Hz, H-1); 13C
NMR (75 MHz, CDCl3) δ = 40.7 (C-3),
59.2 (CH3O), 69.0 (CH2O), 111.7 (C-2), 138.2 (C-1),
166.9 (C=O)
- 8
Fürstner A.Shi N. J. Am. Chem. Soc. 1996, 118: 12349 - 9
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Hiyama T.Kimura K.Nozaki H. Tetrahedron Lett. 1981, 22: 1037 -
12a
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12b
Hoppe D.Thomas H. Angew. Chem., Int. Ed. Engl. 1997, 36: 2282 -
12c
Hoppe D. Angew. Chem., Int. Ed. Engl. 1984, 23: 932
References
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).