r-Nitro Ketone Synthesis Using N-Acylbenzotriazoles
Alan R. Katritzky,*,‡ Ashraf A. A. Abdel-Fattah,‡ Anna V. Gromova,‡ Rachel Witek,‡ and
Peter J. Steel§
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200, and Department of Chemistry, University of Canterbury,
Christchurch, New Zealand
Received June 15, 2005
Readily available N-acylbenzotriazoles 2a-l (derived from a variety of aliphatic, (hetero)aromatic,
and N-protected R-amino carboxylic acids) smoothly convert primary 3a-c and R-functionalized
primary nitroalkanes 3d into the corresponding R-nitro ketones 5a-p in yields of 39-86% (average
63%).
Introduction
Recent interest in R-nitro ketones has been directed
toward their reductive conversion into diastereomerically
enriched vicinal nitro alcohols.11 The nitro group in these
versatile building blocks can readily be reduced with
retention of configuration,12 and the resulting amino
alcohols are key intermediates in the construction of
numerous pharmacologically important compounds3,13
and chiral auxiliaries.14 Additionally, R-nitro ketones are
valuable precursors for the syntheses of many classes of
natural products including jasmonoids and prostaglandin
intermediates1a and pheromones.15
Available methods for the synthesis of R-nitro ketones
include four main approaches (Scheme 1): (i) nitrations
of (a) enol acetates with trifluoroacetic anhydride and
ammonium nitrate,16 (b) potassium enolates with pentyl
nitrate,17 or (c) enol silyl ethers with tetranitromethane;18
(ii) oxidations of (a) olefins using trimethylsilyl nitrate-
chromium trioxide19 or (b) â-nitrostyrenes using lithium
tert-butyl peroxide;20 (iii) Henry reactions followed by
Over the years, R-nitro ketones have gained much
attention due to their great versatility.1 The juxtaposition
of the carbonyl carbon and the carbon bearing the nitro
group offers flexible reactivity patterns that are particu-
lar to this class of compound providing viable and often
superior means to various functionalized materials.2
R-Nitro ketone intermediates are extensively utilized for
the syntheses of diverse classes of compounds, including
oxazolidinones,3 isoxazoles,4 pyrroles,5 furoxans,6 amides,7
ketones,1a,8 R-deuterated ketones,1a,9 R-aminoketones,10
and tosyl hydrazones.1a
* To whom correspondence should be addressed. Fax: (352) 392-
9199.
‡ University of Florida.
§ University of Canterbury.
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1990, 709. (c) Ballini, R. Synlett 1999, 1009.
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Petrini, M. Synlett 1992, 64. (c) Ballini, R.; Fiorini, D.; Gil, M. V.;
Palmieri, A Green Chem. 2003, 5, 475. (d) Zhang, N.; Tomizawa, M.;
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10.1021/jo051231x CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/20/2005
J. Org. Chem. 2005, 70, 9211-9214
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