The Journal of Organic Chemistry
Article
The above-described procedure was adapted for the following
experiments [(i) and (ii)]: (i) Reactions Using Bicarbonate
Phosphonium Salt (1b) as the Catalyst. With all the other conditions
ACKNOWLEDGMENTS
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MIUR (Italian Ministry of University and Research, Research
Grant PRIN 2008) is gratefully acknowledged for financial
support.
−2
unaltered, catalyst 1b (6.7 mg; 1.5 × 10 mmol) was used in place of
a. The results, not reported here, did not showed appreciable
1
differences between the two catalytic systems. (ii) Reactions on Larger
Scale Carried out Using Substrates 2c and 2d. A 25-mL glass flask was
charged with the aldehyde (30 mmol; 2c: 1.74 g; 2d: 4.68 g), methyl
carbonate phosphonium salt (1a, 0.3 mmol, 148 mg) and nitroethane
REFERENCES
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(
6
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(
36 mmol; 2.7 g). Under these conditions, the molar ratio
(
2
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the nitroaldol products were purified through a filtration on silica gel
(
(
5 g of silica gel, 200 mL of diethylether). Products were obtained with
(
high purity (95%): 3c (3.67 g) and 3d (6.72 g) were isolated in 92 and
Ed.; Pergamon: Oxford, 1999; Vol. 1. (b) Ono, N. In The Nitro Group
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97% yields, respectively.
Addition of Nitroethane to Cyclic Ketones in the Presence of CILs
(
as Catalyst. A 7-mL glass reactor shaped as a test tube was charged
with the ketone (5: 5.0 mmol; 5a: 490 mg; 5b: 420 mg),
phosphonium salt (1a: 246, 492, 1230 mg; 0.5, 1, 2.5 mmol), and
nitroethane (450 mg and 1875 mg; 6.0 and 25.0 mmol). Molar ratios
nitroethane/ketone and 1a/ketones were in the range of 1.2−5.0 and
(
2
0.1−0.5, respectively. The mixture was kept under magnetic stirring at
room temperature for 20 h. Then, the reaction was quenched by
adding a 5% HCl aqueous solution (3.0 mL). The resulting mixture
was extracted with diethylether (2.0 mL) from which products 6a and
2
(
6
b were isolated. These compounds were purified by column
chromatography (eluant: ethylacetate/petroleum ether mixture, 30/
0 v/v) yielding pure 1-(1-nitroethyl)cyclohexanol (6a, 248 mg, yield
Org. Chem. 2004, 1, 137−139.
(
(
6) Italian Ministry Research Grant (PRIN 2008) 200895XNPL_004
7) Fabris, M.; Lucchini, V.; Noe,
M.; Perosa, A.; Selva, M. Chem.
7
̀
=
57%) and 1-(1-nitroethyl)cyclopentanol (6b, 69 mg, yield = 17%).
Eur. J. 2009, 15, 12273−12282.
Addition of Nitromethane to Cyclic Ketones in the Presence of
(
(
9
(
8) Selva, M.; Tundo, P. Acc. Chem. Res. 2002, 35 (9), 706−716.
9) Cunningham, I. D.; Woolfall, M. J. Org. Chem. 2005, 70, 9248−
CILs as Catalyst. Reactions of Table 2 were carried out according to
the following procedure. A 7-mL glass reactor shaped as a test tube,
was charged with the ketone (5: 5.0 mmol; 5a: 490 mg; 5b: 420 mg),
phosphonium salt (1a: 246, 492, 1230 mg; 0.5, 1, 2.5 mmol) and
nitromethane (366 mg and 1525 mg; 6.0, 25.0 mmol). Molar ratios
nitroethane/ketone and 1a/ketones were in the range of 1.2−5.0 and
256.
10) Aliphatic aldehydeswere convenient substrates for preliminary
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S. Eng. Sci. Rep. Kyushu Univ. 2008, 1, 25−28.
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(12) Under a 0.01 CIL/substrate ratio, the aldol formation rapidly
decreased. A plausible reason was the contamination of the reacting
aldehyde with trace levels of the corresponding (carboxylic) acid, able
to neutralize the basic salt. For this reason, freshly distilled aldehydes
were always used.
0.1−1.0, respectively.
The reactor was heated at the desired temperature (25−50 °C, see
Table 2 for details), and the mixture was kept under magnetic stirring
throughout the reaction. After 20 h, the reaction was quenched by
adding a 5% HCl aqueous solution (3.0 mL).
At the end of reactions of entries 1, 3, 4, and 6 of Table 2, diethyl
ether (3 mL) was added to the reaction mixtures and the aqueous
phase was separated. Products were purified by column chromatog-
raphy (eluant: ethyl acetate/petroleum ether mixture, 30/70 v/v)
yielding 1-(nitromethyl)cyclohexanol (7a, 461 mg, yield = 58%), 1-
(13) The syn/anti ratio was determined according to NMR analyses
reported in the literature, in which usually, Janti < Jsyn: (a) Seebach, D.;
Beck, A. K.; Mukhopadhyay, T.; Thomas, E. Helv. Chim. Acta 1982,
65, 1101−1133. (b) Ballini, R.; Bosica, G.; Marcantoni, E.; Vita, P. J.
Org. Chem. 2000, 65, 5854−5857.
(
(
(
nitromethyl)cyclopentanol (7b, 200 mg, yield =25%), 1,1-bis-
nitromethyl)cyclohexane (8a, 410 mg, yield = 81%), 1,1-bis-
nitromethyl)cyclopentane (8b, 426 mg, yield = 91%). The structures
(
14) Crugeiras, J.; Rios, A.; Riveiros, E.; Richard, J. P. J. Am. Chem.
Soc. 2009, 131, 15815−15824.
(15) (a) Simoni, D.; Invidiata, F. P.; Manfrenidi, S.; Ferroni, R.;
Lampronti, I.; Roberti, M.; Pollini, G. P. Tetrahedron Lett. 1997, 38,
1
13
of all products were confirmed by H and C NMR.
2
390.
749. (b) Gan, C.; Chen, X.; Lai, G.; Wang, Z. Synlett 2006, 3, 387−
ASSOCIATED CONTENT
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(
16) Additional experiments showed that even the increase of the
*
S
Supporting Information
temperature from 25 to 50 °C, was not of help since the reaction
selectivity dropped due to the onset of side processes. The structures
of the corresponding products were not assigned.
(17) (a) Fraser, H. B.; Kon, G. A. R. J. Chem. Soc. 1934, 604−610.
Characterization data and NMR spectra of compound 6b. This
(
b) Buehler, C. A.; Pruett, R. L. J. Am. Chem.. Soc. 1951, 73, 5504−
5
4
506. (c) Kisanga, P. B.; Verkade, J. G. J. Org. Chem. 1999, 64, 4298−
303. (d) Simoni, D.; Rondanin, R.; Morini, M.; Baruchello, R.;
AUTHOR INFORMATION
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Invidiata, F. P. Tetrahedron Lett. 2000, 41, 1607−1610.
18) Gattow, G.; Behrendt, W. Angew. Chem., Int. Ed. Engl. 1972, 11,
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Mikkola, J.-P. Catal. Lett. 2011, 141, 1254−1261.
(
5
(
Notes
The authors declare no competing financial interest.
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dx.doi.org/10.1021/jo202294k | J. Org. Chem. 2012, 77, 1805−1811