Communications
Table 2: One-pot transformation of chiral nitroalkanes into nitriles.[a]
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Entry
Substrate
Reagent
Product
Yield [%]
1
2
TFAA
SOCl2
62
66
3
4
TFAA
SOCl2
63
69
[3] a) H. Sasai, T. Suzuki, S. Arai, T. Arai, M. Shibasaki, J. Am.
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5
6
TFAA
SOCl2
73
72
[a] Typical reaction conditions: BnBr (1.1 equiv), KOH (1.05 equiv),
nBu4NI (5 mol%) in THF, room temperature, 3 h; then TFAA (trifluoro-
acetic anhydride) or SOCl2 (4.5 equiv), NEt3 (9 equiv), À208C, 12 h.
verified by chiral HPLC assays. The overall protocol provides
access to a class of compounds that are otherwise not easily
accessed by known methods in catalytic asymmetric syn-
thesis.[12]
[4] a) J. von Braun, W. Sobecki, Ber. Dtsch. Chem. Ges. 1911, 44,
2526; b) J. von Braun, E. Danziger, Ber. Dtsch. Chem. Ges. 1913,
46, 103; c) M. Bartra, P. Romea, F. Urpꢁ, J. Vilarasa, Tetrahedron
1990, 46, 587; d) D. Edmont, D. M. Williams, Tetrahedron Lett.
2000, 41, 8581; e) C. C. Hughes, D. Trauner, Angew. Chem. 2002,
114, 4738; Angew. Chem. Int. Ed. 2002, 41, 4556; f) D. H. R.
Barton, I. Fernandez, C. S. Richard, S. Z. Zard, Tetrahedron
1987, 43, 551; g) D. Albanese, D. Landini, M. Peno, G. Pozzi,
Synth. Commun. 1990, 20, 965; h) D. Albanese, D. Landini, M.
Penseo, Synthesis 1990, 333.
In summary, we have documented a convenient protocol
for the synthesis of optically active aldoximes and nitriles
starting from chiral nitroalkanes. The salient features of the
method include: 1) the reaction can be performed at room
temperature under ambient atmosphere, 2) inexpensive
reagents are employed (BnBr, KOH, nBu4NI), and 3) the
use of heavy metals is precluded. This provides an environ-
mentally friendly reaction that excludes the potential con-
tamination of the products by metal impurities. Given the
ongoing advances in catalytic asymmetric synthesis that
involve nitro compounds, the methodology described herein
expands their possibilities for conversion into valuable
synthetic targets.
[5] For other metal-mediated reductions of nitroalkanes to oximes,
´
see: a) M. Hudlicky, Reductions in Organic Chemistry, Ellis
Horwood, Chichester, 1984; b) K. Johnson, E. F. Degering, J.
Am. Chem. Soc. 1939, 61, 3194; c) J. E. McMurry, J. Melton, J.
Org. Chem. 1973, 38, 4367; d) Y. Akita, M. Inaba, H. Uchida, A.
Ohta, Synthesis 1977, 792.
[6] a) H. B. Hass, M. L. Bender, J. Am. Chem. Soc. 1949, 71, 1767;
b) H. B. Hass, M. L. Bender, J. Am. Chem. Soc. 1949, 71, 3482;
c) C. D. Nenitzescu, D. A. Isacescu, Ber. Dtsch. Chem. Ges. B.
1930, 63, 2484; d) R. Filler, H. Novar, J. Org. Chem. 1960, 25,
733; e) C. F. Bigge, J. T. Drummond, G. Johnson, T. Malone,
A. W. Probert, Jr., F. W. Marcoux, L. L. Coughenour, L. J.
Brahce, J. Mol. Chem. 1989, 32, 1580; f) T. C. Bedard, J. Y.
Corey, L. D. Lange, N. P. Rath, J. Organomet. Chem. 1991, 401,
261; g) W. Kirmse, W. Konrad, D. Schnitzler, J. Org. Chem. 1994,
59, 3821.
Received: September 3, 2004
Published online: December 21, 2004
Keywords: chirality · nitro compounds · oximes · reduction ·
[7] For the transformation of phenylnitromethane into benzalde-
hyde oxime, see: L. Weisler, R. W. Helmkamp, J. Am. Chem.
Soc. 1945, 67, 1167.
.
synthetic methods
[8] No reaction was observed by 1H NMR spectroscopy when
nitrobenzene was treated with benzyl bromide (1.1 equiv), KOH
(1.05 equiv), and nBu4NI (5 mol%) in THFat room temperature
for 6 h.
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