Metal nitrite: A powerful oxidizing reagent

Article abstract of DOI:10.1021/ja206736q

An efficient and simple source of nitroso reagents and their oxidation reactions are described. The combination of a Lewis acid and a metal nitrite was applied to the oxidation of silyl enol ethers. Amino acid and peptide derivatives were easily accessed through in situ C-C bond cleavage of fully substituted silyl enol ethers upon oxidation.

Full text of DOI:10.1021/ja206736q

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Metal Nitrite: A Powerful Oxidizing Reagent
Mahiuddin Baidya and Hisashi Yamamoto*
Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, United States
S Supporting Information
b
Chart 1. Oxidation of Silyl Enol Ethers with Metal
Nitritesaꢀd
ABSTRACT: An efficient and simple source of nitroso
reagents and their oxidation reactions are described. The
combination of a Lewis acid and a metal nitrite was applied
to the oxidation of silyl enol ethers. Amino acid and peptide
derivatives were easily accessed through in situ CꢀC bond
cleavage of fully substituted silyl enol ethers upon oxidation.
uring the last three decades, new classes of nitroso com-
D
pounds have emerged and found numerous applications in
organic synthesis.1ꢀ4 Since most of these compounds are toxic
and explosive and require several steps to prepare, their scopes of
application are limited. The development of new practical, safe
sources of nitroso compounds for oxidation reactions remains a
challenge.
The combination of metal nitrite and Lewis acid could be a
convenient route: triisopropylsilylchloride (TIPSCl) was ex-
posed to silver nitrite in acetonitrile to generate silyl nitrite
(eq 1).5 A pale-green color immediately appeared with the
precipitation of silver chloride, clearly indicating the generation
of the nitroso compound.6a Indeed, addition of silyl enol ether 1a
into the reaction mixture exclusively afforded keto oxime 2a in
71% isolated yield.
aSi = TMS for 2bꢀk, 2u, and 2v; TIPS for 2lꢀo; TBS for 2t; and
Si(TMS)3 for 2pꢀs [(Z)-silyl enol ethers were used]. b Instead of silyl
enol ethers, sodium enolates were used for 2w and 2x. cIsolated yields are
reported. dDMF was used as the solvent for 2lꢀo.
The reaction seemed to be general, and several Lewis acids
could be used with silver nitrite: TiCl4 (40%), InCl3 (41%),
FeCl3 (47%), and AlCl3 (45%). Furthermore, other commer-
cially available nitrite salts, including NaNO2/15-crown-5 (74%)
and nBu4NNO2 (60%), could also be employed. Thus, this route
appears to be a simple, easily accessible, and relatively safe source
of nitroso reagents.6b
The oxygen bridge between the Lewisacid(LA) and the nitroso
moiety (LAꢀOꢀNO) plays a crucial role. The activation of the
oxophilic Lewis acid overcompensates for the resonance stabiliza-
tion of the nitroso moiety.
Experiments that probed the scope of this process under the
optimized conditions are summarized in Chart 1. A broad
spectrum of silyl enol ethers, both cyclic and acyclic, were
employed to afford the desired products in good to excellent
yields. Generally, (E)-oximes were observed, except for the
seven- and eight-membered rings (2d and 2e). The scaleup was
also compatible: the reaction of the silyl enol ether derived from R-
tetralone was performed on a gram scale, and the desired product
was isolatedin90% yield(2j). Oxidation proceededsmoothlywith
silyl dienol ether to generate the 1,4-adduct (2k) exclusively.
When triisopropyl silyl enol ethers were used, the desired oximes
were TIPS-protected upon isolation (2lꢀo). Acid-sensitive het-
erocyclic furan substitution was also tolerated (2n).
While the reactions of silyl nitrite with aldehyde-derived silyl
enol ethers were sluggish under the optimized conditions,
oxidation with aluminum nitrite proceeded cleanly, and R-
hydroxyimino aldehydes 2pꢀs were obtained in high yields. In
contrast, conventional procedures for preparing these com-
pounds require multistep transformations. Exposure of silyl
ketene acetals to the sodium enolates of active methylene
derivatives furnished the desired products in good yields (2tꢀx).
Received: July 19, 2011
Published: August 10, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/ja206736q J. Am. Chem. Soc. 2011, 133, 13880–13882
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Chart 2. Double Oxidation of Silyl Enol Ethers 1
Scheme 1. Plausible Mechanism for the Formation of 3
Chart 3. Oxidation of Quaternary Silyl Enol Ethers and One-
Pot CꢀC Bond Cleavage Reactionsa
aIsolated yields. bNot observed.
When excess aluminum nitrite derived from AlCl3 and
(nBu)4NNO2 was used, the silyl enol ethers 1 produced the
doubly oxidized products 3 as the major products (Chart 2). On
the other hand, mixtures of 2 and 3 were isolated for 1e and 1g
(entries 4 and 6). The 2/3 ratio did not change even when the
reaction time was prolonged. Surprisingly, no double oxidation
product was observed for 12-membered ring 1f (entry 5).
On the basis of these observations, a possible path for the
formation of 3 is depicted in Scheme 1. After the first mono-
oxidation, oxime 2 complexes with the Lewis acid, which induces
further enolization of the ketone. The enol thus obtained is further
oxidized to generate dioxime 3. We hypothesize that a syn
alignment of the CdO and CdN bonds in 2 is required for double
coordination with the aluminum ion. Such a preferred alignment,
which was observed in the crystal structure of 2b (five-membered
ring A in Scheme 1), induced the enolization process required for
further oxidation. In contrast, the anti alignment of the CdO and
CdN bonds of the 12-membered ring 2f (B in Scheme 1) impedes
the required coordination with aluminum, and thus, no further
oxidation proceeds. A mixed situation can be considered for the
formation of mixtures of 2 and 3 from eight-membered-ring and
acyclic silyl enol ethers (1e and 1g, respectively).
When fully substituted silyl enol ethers were used, clean
formation of the nitroso derivative was observed (eq 2). How-
ever, the nitroso compound easily dimerized (for the crystal
structure, see p S26 in the Supporting Information) and pre-
cipitated from the reaction mixture.
aIsolated yields are given.
methyl esters gave the expected peptides in good yields (6mꢀr).
Various derivatives containing heteroatoms such as oxygen,
sulfur, and nitrogen were also effective for this cleavage process.
It should be emphasized that secondary amines can also be
reacted with high efficiency under very mild reaction conditions
to generate tertiary amides, for which amide synthesis methods
are relatively rare.
These substituted oximes 5 and 6 were chemoselectively
reduced with indium metal to access protected amino acids
and dipeptides 7 in excellent yields (Scheme 2).8 The synthetic
utility of this new oxidation/cleavage strategy was further verified
Gratifyingly, switching the solvent from CH3CN to N,N-
dimethylformamide (DMF) retarded the dimerization process
significantly, and subsequent treatment with external nucleo-
philes caused the carbonꢀcarbon bond cleavage reaction (eq 2).7
Sodium methoxide produced the expected carbonꢀcarbon bond
cleavage products in high yields (5aꢀc in Chart 3). Amazingly,
both primary and secondary amines could also efficiently cleave
the CꢀC bond to render amides (6aꢀl). Importantly, free amino
acid esters were also effective. L-Valine, L-alanine, and L-proline
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dx.doi.org/10.1021/ja206736q |J. Am. Chem. Soc. 2011, 133, 13880–13882

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Scheme 2. Synthesis of Protected Amino Acids and Dipep-
tides by Indium-Mediated Reduction of Oximes
(2) Cyanonitroso compounds: (a) Horsewood, P.; Kirby, G. W.
Chem. Commun. 1971, 1139. R-Halonitroso compounds:(b) Wichterle,
O. Collect. Czech. Chem. Commun. 1947, 12, 292. (c) Oppolzer, W.;
Tamura, O. Tetrahedron Lett. 1990, 31, 991. (d) Oppolzer, W.; Tamura,
O.; Sundarababu, G.; Signer, M. J. Am. Chem. Soc. 1992, 114, 5900.
(e) Zhang, D.; Suling, C.; Miller, M. J. J. Org. Chem. 1998, 63, 885. Vinyl
nitroso compounds:(f) Faragher, R.; Gilchrist, T. L. Chem. Commun.
1976, 581. (g) Gilchrist, T. L.; Roberts, T. G. J. Chem. Soc., Perkin Trans.
1 1983, 1283. Nitrosoimines:(h) Gilchrist, T. L.; Peek, M. E.; Rees,
C. W. Chem. Commun. 1975, 913. (i) Gilchrist, T. L.; Harris, C. J.;
Hawkins, D. G.; Moody, C. J.; Rees, C. W. J. Chem. Soc., Perkin Trans. 1
1976, 2166. Nitrosoamidines:(j) Miller, C. A.; Batey, R. A. Org. Lett.
2004, 6, 699. N-Phosphinoylnitroso compounds:(k) Ware, R. W., Jr.;
King, S. B. J. Am. Chem. Soc. 1999, 121, 6769. (l) Ware, R. W., Jr.; King,
S. B. J. Org. Chem. 2000, 65, 8725. (m) Ware, R. W., Jr.; Day, C. S.; King,
S. B. J. Org. Chem. 2002, 67, 6174. Nitroso formate esters:(n) Kirby,
G. W.; McGuigan, H.; Mackinnon, J. W. M.; Mclean, D.; Sharma, R. P.
J. Chem. Soc., Perkin Trans 1 1985, 1437.
Scheme 3. Synthesis of a Protected Peptidoglycan Mimetic
Peptide Analogue
(3) Nitroso benzene and pyridylnitroso compounds: (a) Merino, P.;
Tejero, T. Angew. Chem., Int. Ed. 2004, 43, 2995. (b) Yamamoto, H.;
Momiyama, N. Chem. Commun. 2005, 3514. (c) Yamamoto, H.;
Kawasaki, M. Bull. Chem. Soc. Jpn. 2007, 80, 595. (d) Labaziewicz, H.;
Lindfors, K. R.; Kejonen, T, H. Heterocycles 1989, 29, 2327.
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Lallemand, J.-Y.; Ricard, L. Tetrahedron: Asymmetry 1999, 10, 2165. (d)
Blakemore, P. R.; Kim, S.-K.; White, J. D.; Yokochi, A. F. T. J. Chem. Soc.,
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(5) Weidenbruch, M.; Sabeit, F. Z. Naturforsch. 1976, 31B, 1212.
(6) (a) More intense color was observed for the reaction with Ph3SiCl
and (EtO)3SiCl. (b) (iPr)3SiONO is not volatile. Its boiling point is
40.5ꢀ41.5 °C at 1.9 mbar (see ref 5), which is much higher than that of
commonly used isobutyl nitrite (bp = 66 °C at atmospheric pressure).
(7) CꢀC bond cleavage reactions using nitrosobenzene and ketones:
(a) Payetee, J. N.; Yamamoto, H. J. Am. Chem. Soc. 2008, 130, 12276.
(b) Delgado, A.; Garcia, J. M.; Mauleon, D.; Minguillon, C.; Subirats,
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by the short synthesis of a peptidoglycan mimetic peptide
analogue.9 Scheme 3 demonstrates the power of this process
by the remarkably short synthesis of aminopimelyl-L-alanyl-L-
alanine (9), a biologically important peptide analogue.
In conclusion, we have developed a new and flexible route to
metal nitrite that is useful for R- and/or R,R0-oxidation of
carbonyl compounds under very mild conditions. For R,R-
disubstituted ketones, the resultant nitroso compounds can be
smoothly cleaved by treatment with O- and N-nucleophiles to
generate polyfunctional amides. This methodology can be used
for the rapid synthesis of amino acid and peptide derivatives.
(8) (a) Harrison, J. R.; Moody, C. J.; Pitts, M. R. Synlett 2000, 1601.
(b) Pitts, M. R.; Harrison, J. R.; Moody, C. J.; Pitts, M. R. J. Chem. Soc.,
Perkin Trans. 1 2001, 955.
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Disteche, M.; Frere, J.-M.; Nicholas, R. A.; Pratt, R. F. Biochem. J.
2003, 373, 949. (b) Macheboeuf, P.; Contreras-Martel, C.; Job, V.;
Dideberg, O.; Dessen, A. FEMS Microbiol. Rev. 2006, 30, 673.
(c) Sauvage, E.; Duez, C.; Herman, R.; Kerff, F.; Petrella, S.; Anderson,
J. W.; Adediran, S. A.; Pratt, R. F.; Frere, J.-M.; Charlier, P. J. Mol. Biol.
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’ ASSOCIATED CONTENT
S
Supporting Information. Complete experimental proce-
b
dures, characterization data for prepared compounds, and crys-
tallographic data (CIF). This material is available free of charge
via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
yamamoto@uchicago.edu
’ ACKNOWLEDGMENT
We gratefully acknowledge NIH for a grant supporting this
research (Asymmetric Oxidation: 2R01GM068433-05). We also
thank Dr. Antoni Jurkiewicz, Dr. Ian Steele, and Dr. Jin Qin for
sharing their expertise in NMR spectroscopy, X-ray crystal-
lography, and mass spectrometry, respectively.
’ REFERENCES
(1) Reviews: (a) Kirby, G. W. Chem. Soc. Rev. 1977, 6, 1. (b) Iwasa,
S.; Fakhruddin, A.; Nishiyama, H. Mini-Rev. Org. Chem. 2005, 2, 157.
(c) Bodnar, B. S.; Miller, M. J. Angew. Chem., Int. Ed. 2011, 50, 5630.
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dx.doi.org/10.1021/ja206736q |J. Am. Chem. Soc. 2011, 133, 13880–13882