F. A. Luzzio et al. / Tetrahedron Letters 48 (2007) 6704–6708
6707
Weinheim, 1990; Rosini, G.; Ballini, R. Synthesis 1988,
833.
3. Conclusion
3. (a) Larock, R. C. Comprehensive Organic Transformations,
2nd ed.; Wiley-VCH: New York, 1999; p 821; March, J.;
Smith, M. B. Advanced Organic Chemistry, 5th ed.; John
Wiley and Sons: New York, 2001; p 1552; Pradhan, P. K.;
Dey, S.; Jaisankar, P.; Giri, V. S. Synth. Commun. 2005,
35, 913–922; Petrini, M.; Ballini, R.; Rosini, G. Synthesis
1987, 8, 713–714; Rotman, A.; Daly, J. W.; Creveling, J.
R. J. Labelled Compd. 1975, 11, 445–452; (b) Ballini, R.;
Petrini, M. Tetrahedron 2004, 60, 1017–1047; Ballini, R.;
Petrini, M. Tetrahedron Lett. 1989, 30, 5329–5332; Aiz-
purua, J. M.; Oiarbide, M.; Palomo, C. Tetrahedron Lett.
1987, 28, 5361–5364; Chickashita, H.; Morita, Y.; Itoh, K.
Synth. Commun. 1987, 17, 577–683; Thominiaux, C.;
Rousse, S.; Desmaele, D.; d’Angelo, J.; Riche, C. Tetra-
hedron: Asymmetry 1999, 10, 2015–2021; Barton, D. H.
R.; Motherwell, W. B.; Simon, E. S.; Zard, S. Z. J. Chem.
Soc., Perkin Trans. 1 1986, 2243–2252; Ono, N.; Kamim-
ura, A.; Miyake, H.; Hamamoto, I.; Kaji, A. J. Org.
Chem. 1985, 50, 3692–3698; Olah, G. A.; Arvanaghi, M.;
Vankar, Y. D.; Prakash, G. J. S. Synthesis 1980, 8, 662–
663; Chung, W. K.; Chiu, P. Synlett 2005, 55–58; (c)
Ballini, R.; Petrini, R.; Polzoneti, V. Synthesis 1992, 355–
In summary, we have described a protocol for direct
conversion of ring-activated b-aryl-b-hydroxynitro
compounds to the corresponding b-arylnitroethanes.
Although the direct ionic reduction of activated benzylic
alcohols with TES/TFA is well-precedented, the appli-
cation of this reaction to benzylic b-nitroalkanols repre-
sents a new and useful extension of this transformation
and thus provides intermediates, which can be easily
transformed to the corresponding amines. Though lim-
ited to aryl rings bearing electron donating substituents,
the reaction is a reasonable alternative to both the
nitroaldol/dehydration/reduction sequence and the
Kornblum reaction, which utilizes b-arylhaloethanes
and nitrite ion.
4. Experimental
4.1. Typical procedure for the TES/TFA reduction of
nitroalcohols
´
357; Balogh-Hergovich, E.; Kaizer, J.; Speier, G. Chem.
Lett. 1996, 573–574; Narayana, C.; Reddy, N. K.;
Kalbalka, G. W. Synth. Commun. 1992, 22, 2587–2592;
Urpi, F.; Vilarrasa, J. Tetrahedron Lett. 1990, 31, 7499–
7500; Aizpurua, J. M.; Oiarbide, M.; Palomo, C.
Tetrahedron Lett. 1987, 28, 5365–5366; (d) Gissot, A.;
N’Gouela, S.; Matt, C.; Wagner, A.; Mioskowski, C. J.
Org. Chem. 2004, 69, 8997–9001; Rossi, E.; Sassano, S.;
Stradi, R. Synthesis 1986, 9, 765–766; Polet, D.; Alexakis,
A. Tetrahedron Lett. 2005, 46, 1529–1532.
4.1.1. 1,2,3-Trimethoxy-5-(2-nitroethyl)benzene (1f,
Table 1). To a stirred suspension containing 1-(3,4,5-
trimethoxy-phenyl)-2-nitroethanol
(2f,
Table
1)
(32.5 mg, 0.13 mmol) and triethylsilane (200 lL,
1.25 mmol) at 0 ꢁC, was added trifluoroacetic acid
(50 lL, 0.67 mmol) dropwise. As the reaction pro-
ceeded, the suspension turned into a clear solution.
The reaction mixture was stirred from 0 ꢁC to room
temperature for 16 h, after which the reaction mixture
was quenched by the slow addition of saturated aqueous
sodium bicarbonate (2 mL). The product was extracted
with dichloromethane (3 · 2 mL) and the combined or-
ganic layers were washed with brine (2 mL), dried over
sodium sulfate and concentrated. The crude oily residue
was purified by flash column chromatography eluting
first with hexane then followed by hexane/diethyl ether
(1:1) to yield the pure arylalkylnitro compound (1f,
Table 1) as an off-white amorphous solid (19.0 mg,
62%): Rf: 0.18 (petroleum ether/diethyl ether, 1:1); mp:
80–81 ꢁC (lit.:15 82–83 ꢁC).
4. (a) Luzzio, F. A. Tetrahedron 2001, 57, 915–945; (b)
Henry, L. C. R. Acad. Sci. Ser. C 1895, 1265; (c) Henry, L.
Bull. Soc. Chim. Fr. 1895, 13, 999; (d) Seebach, D.; Colvin,
E. W.; Leher, F.; Weller, T. Chimia 1979, 33, 1–18.
5. For a recent comprehensive review, see: Ballini, R.;
Bosica, G.; Fiorini, D.; Palmieri, A.; Petrini, M. Chem.
Rev. 2005, 105, 933–971, and references cited therein.
6. For examples of alkaloid syntheses, which utilize b-
arylnitroethyl intermediates and incorporate b-arylethyl-
amino substructures see: Degnan, A. P.; Meyers, A. I. J.
Org. Chem. 2000, 65, 3503–3512; Bagul, T. D.; Lakshma-
iah, G.; Kawabata, T.; Fuji, K. Org. Lett. 2002, 4, 249–
251; McNulty, J.; Larichev, V.; Pandey, S. Biorg. Med.
Chem. Lett. 2005, 15, 5315–5318; McNulty, J.; Mao, J.;
Gibe, R.; Mo, R.; Wolf, S.; Pettit, G. R.; Herald, D. L.;
Boyd, M. R. Bioorg. Med. Chem. Lett. 2001, 11, 169–172;
He, F.; Bo, Y.; Altom, J.; Corey, E. J. J. Am. Chem. Soc.
1999, 121, 6771–6772; Hill, R. K.; Sawada, S.; Bock, M.
G.; Greene, J. R. Heterocycles 1987, 25, 515–520; Seebach,
D.; Ehrig, V.; Leitz, H. F.; Henning, R. Chem. Ber. 1975,
108, 1946–1960.
Acknowledgements
Support of this work by the Molecular Pharmacology
Research Core and the Clinical Pharmacology Section
of the National Cancer Institute is gratefully
acknowledged.
7. (a) Luzzio, F. A.; Ott, J. P.; Franklin, J. M. Abstracts of
Papers of the American Chemical Society, 224th National
Meeting: 515-ORGN Part 2, August 18, 2002; (b) Luzzio,
F. A.; Fitch, R. W. J. Org. Chem. 1999, 64, 5485–5493; (c)
For selective reductions of nitrostyrenes, see Refs. 17 and
20.
References and notes
8. McDonald, E.; Martin, R. T. Tetrahedron Lett. 1977, 15,
1317–1320; Achintya, K.; Sinhababu, K.; Borchardt, R. T.
Tetrahedron Lett. 1983, 24, 227–230.
1. Presented at the 231st National Meeting, American
Chemical Society, Atlanta, GA; March 26–30, 2006.
MEDI 45.
9. Recent references include: (a) Abate, A.; Brenna, E.;
Fuganti, C.; Gatti, F. G.; Giovenzana, T.; Malpezzi, L.;
Serra, S. J. Org. Chem. 2005, 70, 1281; (b) Xu, Y.; Rito, C.
J.; Etgen, G. J.; Ardecky, R. J.; Bean, J. S.; Bensch, W. R.;
Bosley, J. R.; Broderick, C. L.; Brooks, D. A.; Domini-
2. Ono, N. The Nitro Group in Organic Synthesis; Wiley-
VCH: New York, 2001; The Chemistry of Amino, Nitroso,
Nitro and Related Groups; Patai, S., Ed.; Wiley: Chiches-
ter, 1996; Nitro Compounds: Recent Advances in Synthesis
and Chemistry; Feuer, H., Nielsen, A. T., Eds.; VCH: