Synthesis of unusual oxime ethers by reaction of tetranitromethane with B-alkylcatecholboranes

Article abstract of DOI:10.1002/chem.201000680

The reaction of tetranitromethane with B-alkylcatecholboranes leads to the formation of unusual dinitrooxime ethers. A tentative mechanism is provided, which suggests the involvement of extremely fast addition of alkyl radicals to tetranitromethane. The substitution of one of the nitro groups in the oxime ethers by nucleophiles (such as secondary amines, halogens and styrene) and by radicals generated from B-alkylcatecholboranes is reported.

Full text of DOI:10.1002/chem.201000680

FULL PAPER
DOI: 10.1002/chem.201000680
Synthesis of Unusual Oxime Ethers by Reaction of Tetranitromethane
with B-Alkylcatecholboranes
Monique Lꢀthy,[a] Kurt Schenk,[b] and Philippe Renaud*[a]
Abstract: The reaction of tetranitromethane with B-alkylcatecholboranes leads to
the formation of unusual dinitrooxime ethers. A tentative mechanism is provided,
Keywords: boranes · nitroalkanes ·
which suggests the involvement of extremely fast addition of alkyl radicals to tet-
oxime ethers · radical reactions ·
ranitromethane. The substitution of one of the nitro groups in the oxime ethers by
radical traps
nucleophiles (such as secondary amines, halogens and styrene) and by radicals gen-
erated from B-alkylcatecholboranes is reported.
Introduction
also described in the literature but oxime ethers 1 substitut-
ed with two halides (X,Y=F, Cl or Br) are extremely
rare.[10] The formation of nitrolate ethers 1 (X=NO2, Y=C)
was achieved by self-condensation of 1,1-dinitroalkanes,[11]
alkylation of nitrolate salts[12] and methylation of nitrolic
acids with diazomethane.[13] To the best of our knowledge,
dinitro-substituted oxime ethers of type 2 have not been re-
ported in the literature. Over the last decade, we have dem-
onstrated that B-alkylcatecholboranes (RBCat), easily avail-
able by hydroboration of alkenes, are remarkable precursors
for primary, secondary and tertiary alkyl radicals.[14] During
our study on the reactivity of B-alkylcatecholboranes, we
discovered that they react spontaneously with tetranitrome-
thane to afford dinitrooxime ethers 2. Herein, we report a
detailed study of this unexpected reaction as well as some
further transformations of dinitrooxime ethers 2.
Oxime ethers are important sub-structures of biologically
active compounds used extensively by the pharmaceutical
and agrochemical industries.[1] They are useful motifs with
which to introduce diversity and create large libraries of
compounds (for example, in parallel combinatorial chemis-
try,[2] in dynamic combinatorial chemistry with mixed libra-
ries,[3] in libraries that use chemical-domain shuffling[4] and
in combinatorial chemistry in the agrosciences).[5] In organic
synthesis, oxime ethers are also interesting building blocks
because of the electrophilic oxime moiety and for the poten-
tial to undergo rearrangement.[6] The chemistry of oxime
ethers of the general structure 1 is widely known when R, X
and Y are alkyl or aryl substituents.[7] Compounds with the
structure 1 that have two heteroatoms bonded to the oxime
function (X,Y=heteroatoms) are, in contrast, much less
documented in the literature. Sulfur-substituted oxime
ethers 1 (X,Y=S) were reported by Kim and Yoon and
used in a free-radical acylation reaction.[8] Amino-substitut-
ed 1 (X,Y=N,N or N,S) can be easily derived from guani-
dine or thiourea precursors.[9] N-Alkoxyimidoyl halides are
Results and Discussion
[a] M. Lꢀthy, Prof. P. Renaud
Department of Chemistry and Biochemistry, University of Bern
Freiestrasse 3, 3012 Bern (Switzerland)
Fax : (+41)31-631-3426
The reaction of tetranitromethane with B-cyclohexylcate-
cholborane (3a), prepared in situ from cyclohexene and cat-
echolborane (CatBH), was investigated first. It was antici-
pated that this reaction should afford cyclohexanol 7 after
hydrolysis of one or more of the intermediates 4–6. Indeed,
addition of a radical to the oxygen atom of a nitro group
(additions that involve tin,[15] silyl[16] and alkyl[17] radicals are
well documented in the literature) should afford the inter-
E-mail: philippe.renaud@ioc.unibe.ch
[b] Dr. K. Schenk
ꢁcole Polytechnique Fꢂdꢂrale de Lausanne
Laboratoire de Cristallographie
Le Cubotron, Dorigny, 1015 Lausanne (Switzerland)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201000680.
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mediate radical 8a, which was expected to give either 4, 5
or 6 (or a mixture thereof) after fragmentation. Aqueous
workup should produce cyclohexanol 7 in all three cases
(Scheme 1).
coupling interaction was observed. A small amount of a side
product, unambiguously identified as the mononitrooxime
ether 9a (5%), was also isolated. Attempts to optimize the
reaction conditions by the use of an excess of tetranitrome-
thane were unsuccessful and led to lower yield and several
unidentified side reactions. The use of an excess of 3a re-
sulted in enhanced formation of the side-product 9a (see
below).
The scope of the reaction was examined (Scheme 3a). To
avoid problems associated with the in situ formation of the
boronate, pure boronates 3a–c were prepared and distilled
Scheme 1. Expected reactions between B-cyclohexylcatecholborane and
tetranitromethane.
To test our hypothesis, cyclohexene was hydroborated
with catecholborane (2 equiv) and catalytic N,N-dimethyla-
cetamide in dichloromethane at reflux temperature.[18] The
excess of catecholborane was solvolysed with tert-butanol
and the solution of organoborane 3a was cooled to ꢀ788C
before a dilute solution of tetranitromethane was slowly
added. Without addition of any radical initiator, a spontane-
ous, highly exothermic reaction took place. The solution was
stirred at room temperature before aqueous workup. Analy-
sis of the crude product by GC did not show the presence of
cyclohexanol, instead the oxime ether 2a was isolated in
48% yield by column chromatography (Scheme 2). The
Scheme 3. Reaction of B-alkylcatecholboranes 3 with tetranitromethane.
under inert atmosphere prior to use.[19] The reaction of pure
3a with tetranitromethane (1 equiv) gave 2a in 60–75%
yield (GC). Due to product contamination by traces of 9a,
the dinitrooxime ether 2a must be chromatographed twice,
which results in a decreased isolated yield (58%). We next
studied the reaction with boronates 3b and 3c, which have a
tertiary and primary alkyl group, respectively. Whereas the
tertiary alkylcatecholborane 3b was as efficient as 3a (2b,
61%), the primary alkylboronate 3c afforded 2c only in low
yield (19%). With this latter substrate, side products are
formed but none of them could be clearly identified. For in-
stance, a double-addition product similar to 9a was not ob-
served. Similar results were obtained with B-n-propyl- and
B-n-octylcatecholboranes. Nevertheless, the preparation of
secondary and tertiary O-alkyl dinitro methanone oximes is
possible and a one-pot procedure from hindered tri- or
tetra-substituted olefins can be envisaged. For example,
when 3b was generated in situ by hydroboration of 2,4-di-
methyl-2-butene with borane dimethyl sulfide complex[20]
followed by subsequent esterification with catechol, the re-
action with tetranitromethane afforded 2b in 65% isolated
yield from the alkene (Scheme 3b).
Scheme 2. Reaction of tetranitromethane with B-cyclohexylcatecholbor-
ane generated in situ from cyclohexene.
structure of 2a was determined by multinuclear NMR spec-
troscopy. The 14N NMR spectra revealed the three nitrogen
atoms as two strong singlets (d=ꢀ32.9 and ꢀ40.9 ppm rela-
tive to CH3NO2) for the nitro groups and a broad flat peak
(d=ꢀ18.8 ppm). According to this data, rotation around the
1
C=N double bond is prevented. Furthermore, H/15N HMBC
ꢀ ꢀ
analysis suggested a C O N connectivity of the alkyl group
From our past experience of B-alkylcatecholborane-medi-
ated reactions, it was expected that alkyl radicals were in-
ꢀ
and excluded a direct C N connection because only one
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Synthesis of Unusual Oxime Ethers
FULL PAPER
volved in the process. To substantiate this assumption, the
boronate 3d, generated from (+)-carene, was used as a radi-
cal probe (Scheme 4 and Figure 1). The boronate 3d was
Scheme 4. Radical probe experiment with B-alkylcatecholborane 3d, de-
rived from (+)-carene.
Scheme 5. Tentative mechanism for the reaction of B-alkylcatecholbor-
anes 3 with tetranitromethane.
product. The radical process involves fast addition of the
alkyl radical to tetranitromethane to afford the aminoxyl
radical 8.[17] This type of radical are known to decompose
slowly when R=methoxymethyl to afford the methoxy-
methyl cation, NO2 and the nitroform anion (NO2)3Cꢀ (k=
1.1ꢄ104 sꢀ1 at 28C).[17a] When a B-alkylcatecholborane 3 is
present, fast reaction with 8 should overcome the radical-
fragmentation process and lead to the borate ester 11, ac-
companied by regeneration of the starting alkyl radical. This
step is closely related to the fast reaction observed between
nitroxides, such as 2,2,6,6-tetramethylpiperidine N-oxide
(TEMPO), and B-alkylcatecholboranes.[21,22] The radical
process may be initiated by traces of oxygen or by a single-
electron-transfer process between tetranitromethane and the
B-alkylcatecholborane, which leads to an alkyl radical, a
boron nitronate of nitroform and nitrogen dioxide.[23] The
relative inefficiency of the reaction observed with primary
B-alkylcatecholboranes may be explained by the fact that
the reaction between 8 and organoborane 3, a two-step pro-
cess that involves the reversible formation of a complex fol-
lowed by an irreversible fragmentation process, is not taking
place efficiently. This increases the lifetime of 8, which final-
ly decomposes, probably by b-fragmentation of the trinitro-
methyl radical, and leads to a range of unidentified side
products. The second part of the mechanism represents a re-
arrangement of the borate 11. Borate 11 is probably in equi-
librium with the ate complex 12, which may decompose to
give 13 and, after a final rearrangement, lead to the dini-
trooxime ether 2 and the nitrate boronate 14.
Figure 1. Influence of the concentration of tetranitromethane on the reac-
tion of 3d depicted in Scheme 4.
previously used as a successful probe to demonstrate the
presence of radical intermediates in reactions that involve
B-alkylcatecholboranes.[21] Reaction of 3d with tetranitro-
methane gives a mixture of the bicyclic compound 2d and
monocyclic compound 10. The ratio of 2d/10 was deter-
mined by GC analysis. The GC yields were only moderate
(cumulative yields of 2d and 10 ranged between 26 and
34%), however, this was sufficient to identify a clear trend
in the results. It was found that the ratio 2d/10 varies sub-
stantially upon changes of tetranitromethane concentration
(Figure 1). Under the standard conditions used in Scheme 3
([C
ACHTUNGTRENNUNG
ranged 2d. At lower concentration ([CAHCUTNGTRENNUNG
product 10, a result of cyclopropane ring opening, becomes
the major product. This behaviour suggests that a very fast
reaction takes place between the alkyl radical and tetrani-
tromethane. The modest yield of the process did not allow
for a precise kinetic study, but it is evident that tetranitro-
methane is one of the fastest radical traps described to date.
This is in accordance with the work of Steenken et al. who
reported that addition of the methoxymethyl radical to tet-
ranitromethane occurs with
a
rate constant of 6ꢄ
109 mꢀ1 sꢀ1.[17a]
On the basis of these results, a tentative mechanism is
proposed in Scheme 5. This mechanism involves an efficient
radical-chain process followed by a rearrangement to the
The following two observations are in accordance with
the proposed mechanism. Firstly, reaction of tricyclohexyl-
borane[24] with tetranitromethane requires initiation with air
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10173

P. Renaud et al.
and only affords traces of the oxime 2a. It is to be expected
that the radical steps, in particular the reaction of the ami-
noxyl radical 8 with tricyclohexylborane, will be less effi-
cient because trialkylboranes are far less reactive in radical-
chain processes than B-alkylcatecholboranes. Secondly, an
attempt was made to use 1,1-dinitrocyclohexane[25] instead
of tetranitromethane. Under the standard conditions, no
oxime formation was observed; under initiation with air,
partial decomposition of 3a was observed and 1,1-dinitrocy-
clohexane was partly recovered. This could be explained by
the lower reactivity of 1,1-dinitrocyclohexane relative to tet-
ranitromethane as a radical trap, by the absence of an effi-
cient initiation mechanism based on a single-electron-trans-
fer process or by the inefficiency of the rearrangement de-
picted in Scheme 5 (11!2) when the gem-dinitro groups are
replaced by alkyl residues.
gous to the derivatisation of nitrolate methyl ethers present-
ed by Walser and Fryer,[13] a variety of amines displaced one
of the nitro groups in 2a (Scheme 7). The reaction of 2a
The reaction of the dinitrooxime ether 2a with B-alkylca-
techolborane 3a was examined to determine the origin of
the side-product 9a. The reaction affords 9a as a 1:1 E/Z
mixture in 56% yield (GC). A similar yield of 9a was ob-
tained from the reaction of tetranitromethane with an
excess of boronate 3a (Scheme 6). Interestingly, the analo-
Scheme 7. Reaction of dinitrooxime ether 2a with secondary amines.
with piperidine in dichloromethane at room temperature af-
forded 16 in 82% yield as a single stereoisomer. When an
excess of piperidine is used only one nitro group is substitut-
ed.[26] Similar results were obtained with dibenzylamine,
bis(4-bromobenzyl)amine and bis(naphth-2-ylmethyl)amine;
compounds 17–19 were obtained in 39–50% unoptimised
yield. Compound 19 afforded single crystals suitable for X-
ray analysis, which confirmed the E geometry of the oxime
moiety (see Figure 2 and the Supporting Information).[27] It
is very likely that 16–18 also possess the E geometry. Indi-
rectly, the X-ray crystal structure of 19 confirmed the postu-
lated structure of the dinitrooxime ether 2a.
Scheme 6. The reaction of 2a with B-alkylcatecholborane 3a.
gous side reaction of tetranitromethane with 2b was not ob-
served, presumably due to increased steric hindrance. We
assume that the formation of 9a involves addition of the cy-
clohexyl radical to the oxime moiety to afford the radical
adduct 15, followed by b-fragmentation of nitrogen dioxide.
The radical mechanism of this process was further supported
by the fact that no reaction takes place between 2a and cy-
clohexylpinacolborane under similar reaction conditions.
Indeed, it is well established that alkylpinacolboranes are
very poor radical precursors.
Figure 2. X-ray crystal structure of 19.
The substitution of one nitro group by piperidine could
also be performed in a sequential manner. Reaction of B-al-
kylcatecholboranes 3a and 3b with tetranitromethane, fol-
lowed by treatment with piperidine directly afforded the
mono-nitro derivatives 16 and 20 in 61 and 55% yield, re-
spectively (Scheme 8).
The displacement of the nitro group in nitrolate ethers by
a solution of hydrogen chloride in alcohol was observed in
1955.[11b] An identical derivatisation of 2a with chloride or
bromide was achieved upon treatment with aqueous HCl or
The reactivity of the unusual oxime ether 2a was also in-
vestigated. It was found that one of the nitro groups could
be easily displaced by weakly nucleophilic species. Analo-
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Synthesis of Unusual Oxime Ethers
FULL PAPER
reaction is slow at ambient temperature (several days) but
24 was isolated in 45% yield after reaction in hot benzene
for 15 h. A plausible mechanism involves electrophilic addi-
tion of 2a to styrene, nitrite elimination and formation of
the cyclic intermediate 25 or the nitrite ester 26, both of
which can undergo hydrolysis to give 24 (Scheme 10).
Scheme 8. Sequential one-pot reaction of tetranitromethane with B-alkyl-
catecholboranes 3 and piperidine.
Conclusion
HBr, respectively. The acid-catalysed reaction in ether at
room temperature afforded the chloro and bromo deriva-
tives 21 and 22 in good yields as single isomers (Scheme 9).
The two remaining nitrogen atoms were visualised by
The reaction of tetranitromethane with B-alkylcatecholbor-
anes leads to the formation of unusual dinitrooxime ethers.
A radical mechanism that involves extremely fast addition
of alkyl radicals to tetranitromethane is proposed. Further-
more, we have demonstrated that substitution of one of the
nitro groups by nucleophiles or alkyl radicals generated
from B-alkylcatecholboranes is possible.
1
14N NMR and H/15N HMBC spectroscopic analysis. The rel-
ative configurations of 21 and 22 were not determined.
Under similar conditions, ether 23 was generated from 16 in
moderate yield. The single isomer 23 showed a slow isomeri-
sation upon standing for several months to give a mixture of
E and Z isomers.
Experimental Section
Preparation of reagents
Tetranitromethane: Prepared according to the literature procedure.[28] The
isolated tetranitromethane (9.36 g, 38%), a colourless crystalline solid,
was stored at 48C. M.p. 148C; 13C NMR (75 MHz, CDCl3): d=118.6 ppm
(nonet, JACHTUNTRGNEU(GN C,N)=9.4 Hz). Spectral data are in accordance with the litera-
ture.[29] Caution! Tetranitromethane is a weak but highly sensitive explo-
sive. Conditions contributing to instability: heat, sparks and open flames.
In the presence of impurities tetranitromethane may be highly explosive.
Mild shocks can ignite combustible organic matter that is wet with tetra-
nitromethane.
Scheme 9. Reaction of 2a and 16 with HX (X=Cl, Br).
2-Cyclohexylbenzo[d]ACTHNUTRGNE[UNG 1,3,2]dioxaborole (3a): A mixture of cyclohexene
(5.1 mL, 50 mmol) and catecholborane (6.4 mL, 60 mmol) was stirred at
1008C for 16 h. The disappearance of the olefinic protons was followed
by 1H NMR spectroscopy in degassed C6D6 under nitrogen atmosphere.
The mixture was transferred by cannula to a distillation apparatus and
the excess of catecholborane was removed (p=25 mbar, T=458C). The
crude product was distilled under vacuum (p=10ꢀ1 mbar, T=908C) to
afford 3a as a colourless liquid. 1H NMR (300 MHz, C6D6): d=7.07–7.01
(m, 2H), 6.83–6.77 (m, 2H), 1.90–1.80 (m, 2H), 1.65–1.47 (m, 5H), 1.39–
1.23 ppm (m, 4H); 13C NMR (75 MHz, C6D6): d=148.9, 122.7, 112.6,
The reaction of 2a with different olefins was examined.
With most alkenes, including tetramethylethylene, 3,3-dime-
thylbut-1-ene and methyl acrylate, no reaction was ob-
served. With allylsilane the disappearance of 2a was ob-
served but no product could be identified. Interestingly, it
was found that styrene added to the oxime moiety and sub-
stituted a nitro group to give product 24 (Scheme 10). The
28.2, 27.3, 27.0, 22.0 ppm (br; C B); 11B NMR (160 MHz, C6D6): d=
ꢀ
35.8 ppm.
2-(2,3-Dimethylbutan-2-yl)benzo[d]ACTHNUTRGNEUGN[1,3,2]dioxaborole (3b): A mixture of
2,3-dimethyl-2-butene (1.2 mL, 10 mmol) and borane dimethyl sulfide
(90% in SMe2, 1.1 mL, 10 mmol) was stirred at 08C for 2.5 h. CH2Cl2
(8 mL) was added and the mixture was transferred by cannula to a sus-
pension of catechol (1.1 g, 10 mmol) in CH2Cl2 (5 mL) at 08C. Hydrogen
evolution was observed. The mixture was stirred at 08C for 3 h and then
at RT for 1 h. The solvents and dimethyl sulfide were removed in vacuo.
The crude product was filtered under inert atmosphere (glove box) to
afford 3b as a colourless liquid. 1H NMR (300 MHz, C6D6): d=7.08–7.01
(m, 2H), 6.81–6.76 (m, 2H), 1.77 (sept, J=6.9 Hz, 1H), 1.14 (s, 6H),
0.90 ppm (d, J=6.9 Hz, 6H); 13C NMR (75 MHz, C6D6): d=148.8, 122.8,
112.7, 35.9, 22.1, 19.0 ppm.
Radical addition to tetranitromethane
Method a: Synthesis of dinitromethanone O-alkyl oximes from B-alkylca-
techolboranes (2a): A solution of tetranitromethane (4 mmol) in CH2Cl2
(6 mL) was cautiously added to a solution of B-alkylcatecholborane 3a
(808 mg, 4 mmol) in CH2Cl2 (12 mL) over a period of 10 min at ꢀ788C.
After complete addition, more CH2Cl2 (2 mL) was added. During the ad-
dition the solution turned yellow and finally into a dark-brown mixture.
The mixture was stirred overnight and allowed to warm up slowly from
Scheme 10. Reaction of 2a with styrene.
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P. Renaud et al.
ꢀ788C to RT. Filtration of the crude reaction mixture over a pad of silica
gel then short flash chromatography on silica gel (100:0, 98:2, 90:10 pen-
tane/Et2O) gave crude 2a contaminated by side-product 9a (4%) (GC
evaluation). Purification by a second flash chromatography (pentane/0–
1% Et2O) afforded 2a (511 mg, 58%) as a pale-yellow liquid.
lution immediately turned a dark-yellow colour. The reaction mixture
was stirred at 08C for 1 h and then at RT for 3.5 h. The mixture was ex-
tracted with Et2O. The combined organic layers were washed with water
and brine then dried over anhydrous Na2SO4, filtered and the solvents
were removed under reduced pressure. Purification by flash chromatog-
raphy (98:2 pentane/Et2O) afforded 16 (59 mg, 82%) as a dark-yellow
liquid.
Method b: One-pot procedure from cyclohexene (1–8 mmol scale): Cate-
cholborane (1.7 mL, 16 mmol) was added to a solution of cyclohexene
(0.81 mL, 8 mmol) and N,N-dimethylacetamide (0.11 mL, 1.2 mmol) in
CH2Cl2 (16 mL). The mixture was stirred at 408C for 5 h. After cooling
to 08C, tert-butanol (0.75 mL, 8 mmol) was added to solvolyse the excess
of catecholborane. Hydrogen evolution was observed. The solution was
stirred at RT for 30 min and then further diluted with CH2Cl2 (9 mL).
The reaction mixture was cooled to ꢀ788C and a solution of tetranitro-
methane (1.57 g, 8 mmol) in CH2Cl2 (10 mL) was cautiously added
through a dropping funnel over a period of 25 min. A yellow colouration
of the reaction mixture was observed after addition of the first few drops.
With further addition the reaction mixture turned a dark-brown colour
and some brown vapour was observed. After complete addition, more
CH2Cl2 (3 mL) was added and the reaction was stirred at ꢀ788C for
5 min. The cooling bath was removed and the mixture allowed to warm
to RT. The reaction mixture turned black immediately and was stirred
overnight at RT. The mixture was purified by flash chromatography on
silica gel (99:1, 95:5, 90:10 cyclohexane/tert-butyl methyl ether) afforded
2a (839 mg, 48%) as a pale yellow liquid (contaminated by traces of
side-product 9a). 1H NMR (400 MHz, CDCl3): d=4.56–4.48 (m, 1H),
2.04–1.97 (m, 2H), 1.81–1.71 (m, 2H), 1.68–1.51 (m, 3H), 1.45–1.26 ppm
(m, 3H); 13C NMR (100 MHz, CDCl3): d=146.6 (br), 89.8, 30.9, 25.0,
23.3 ppm; 14N NMR (36 MHz, CDCl3): d=ꢀ18.8 (br, 1N; oxime N, exact
value taken from the 15N-trace of the 1H/15N-HMBC spectra), ꢀ32.9 (s,
1N; NO2), ꢀ40.9 ppm (s, 1N; NO2); IR (film): n˜ =2942, 2863, 1557, 1451,
1322, 1050, 1004 cmꢀ1; MS (EI, 70 eV): m/z (%): 171 [M+ꢀNO2] (2), 98
(10), 83 (99), 67 (30), 55 (100); elemental analysis calcd (%) for
C7H11N3O5: C 38.71, H 5.10, N 19.35; found: C 38.85, H 5.04, N 19.47.
Method b: One-pot synthesis from 3a: A solution of tetranitromethane
(1 mmol) in CH2Cl2 (1.5 mL) was added cautiously to a solution of 3a
(213 mg, 1.05 mmol) in CH2Cl2 (3.2 mL) at ꢀ788C over a period of
10 min. After complete addition, more CH2Cl2 (0.5 mL) was added. The
reaction mixture was stirred overnight and allowed to warm up slowly
from ꢀ788C to RT. At 08C, piperidine (4 mmol) was slowly added. Some
brown vapour was observed. The mixture was stirred at 08C for 1 h and
then at RT for 4 h. The dark mixture was purified by flash chromatogra-
phy on silica gel (98:2, 96:4 pentane/Et2O) to afford 16 (162 mg, 61%) as
1
a dark-yellow liquid. H NMR (400 MHz, CDCl3): d=4.08–4.02 (m, 1H),
3.17–3.15 (m, 4H), 1.96–1.92 (m, 2H), 1.73–1.61 (m, 8H), 1.55–1.44 (m,
3H), 1.40–1.25 ppm (m, 3H); 13C NMR (100 MHz, CDCl3): d=82.8, 48.6,
31.3, 25.7, 25.6, 23.9, 23.6 ppm; IR (film): n˜ =2933, 2856, 1656, 1543,
1450, 1200, 993 cmꢀ1; MS (EI, 70 eV): m/z (%): 255 [M]+ (3), 209 (20),
127 (35), 111 (77), 99 (9), 81 (41), 69 (34), 55 (100), 41 (58); elemental
analysis calcd (%) for C12H21N3O3: C 56.45, H 8.29, N 16.46; found: C
56.48, H 8.37, N 16.44.
Acknowledgements
This work was supported by the Swiss National Science Foundation
(grant numbers 21-67106.01 and 7SUPJ062348). We thank BASF Corpo-
ration for a donation of chemicals and Dr. Kandhasamy Sarkunam for
running preliminary experiments that triggered our study.
CyclohexylACHTUNGTRENNUNG(nitro)methanone O-cyclohexyl oxime (9a): Compound 3a
(96 mg, 0.475 mmol) was added to a solution of 2a (87 mg, 0.4 mmol) in
CH2Cl2 (1 mL) at 08C. The solution turned yellow, then brown and final-
ly black. The reaction mixture was stirred at 08C for 3 h and then at RT
for 4 h. The black mixture was purified by flash chromatography on silica
gel (100:0, 98:2 pentane/Et2O). Residual starting material was removed
by a second flash chromatography (pentane/0–1% Et2O) to afford 9a
(30 mg, 30%, E/Zꢁ1:1) as a yellow liquid. 1H NMR (300 MHz, CDCl3):
d=4.24–4.15 (m, 1H), 4.12–4.03 (m, 1H), 3.21–3.11 (m, 1H), 2.64–2.54
(m, 1H), 1.99–1.64 (m, 20H), 1.57–1.20 ppm (m, 20H); 13C NMR
(75 MHz, CDCl3): d=164.7, 156.1, 84.2, 82.8, 38.7, 37.0, 31.3, 31.1, 29.3,
27.7, 26.1, 25.63, 25.61, 25.60, 25.55, 25.4, 23.6, 23.5 ppm; IR (film): n˜ =
2933, 2856, 1539, 1450, 1046, 983 cmꢀ1; MS (EI, GC-MS, 70 eV): m/z
(%): first isomer: 208 [M+ꢀNO2] (3), 126 (100), 98 (8), 93 (18), 83 (43),
67 (27), 55 (52), 41 (38); second isomer: 208 [M+ꢀNO2] (2), 126 (32), 98
(4), 93 (8), 83 (100), 67 (14), 55 (54), 41 (29).
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Chem. Eur. J. 2010, 16, 10171 – 10177

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Received: March 17, 2010
Revised: May 14, 2010
Published online: July 19, 2010
Chem. Eur. J. 2010, 16, 10171 – 10177
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10177