Carbonyl oxide chemistry. 5. Nucleophilic trapping reaction with aldo and keto oximes. Synthesis of hydroperoxynitrones

Full text of DOI:10.1021/jo961375z

J . Org. Chem. 1996, 61, 8677-8680
8677
Ca r bon yl Oxid e Ch em istr y. 5.1
Nu cleop h ilic Tr a p p in g Rea ction w ith Ald o
a n d Keto Oxim es. Syn th esis of
Hyd r op er oxyn itr on es
Sch em e 1. Sin glet Oxygen Oxygen a tion of
2-Meth oxyfu r a n (1) In th e P r esen ce of Ald o a n d
Keto Oxim es 4
M. Rosaria Iesce,*,† Flavio Cermola,† Antonio Guitto,†
Federico Giordano,‡ and Rachele Scarpati†
Dipartimento di Chimica Organica e Biologica
dell’Universita` di Napoli Federico II, via Mezzocannone 16,
I-80134 Napoli, Italy, and Dipartimento di Chimica
dell'Universita` di Napoli Federico II, via Mezzocannone 4,
I-80134 Napoli, Italy
Received J uly 22, 1996
Recently, we reported that 1-methoxy-2,3,7-trioxabicyclo-
[2.2.1]hept-5-ene (2), obtained by dye-sensitized photo-
oxygenation at -78 °C of the furan 1, in participating
solvents leads to cyclic or acyclic adducts via carbonyl
oxide 3.1 We have now investigated the behavior of endo-
peroxide 2 with aldo and keto oximes in order to verify
if, toward carbonyl oxide 3, the nucleophilic character of
the oxime oxygen2 prevailed over the dipolarophilic
character of the oxime carbon-nitrogen double bond.4
The research was also part of a program on the prepara-
tion and use of organic peroxides.5,7
Unexpectedly, hydroperoxynitrones 5 were obtained
that were generally isolated and characterized. These
results were especially surprising in light of the fact that
the only previously reported hydroperoxynitrones were
obtained by singlet oxygen oxygenation of some nitrones
1
at -78 °C. The latter were characterized by H NMR
spectra recorded at -60 °C, since upon warming to room
temperature they led to complex mixtures of compounds
via cyclic peroxides.8
of the reaction mixture were recorded at -60 °C and, in
addition to unreacted 4a , showed the presence of a single
compound. Upon triphenylphosphine reduction at -60
°C the latter led to the known1 (Z) unsaturated aldehyde
9. In addition to the ester signal (δ 165.2 ppm), the 13C
NMR spectrum of the reaction product showed a CdN
resonance (δ 163.2 ppm) similar to that of the starting
oxime (δ 160.5 ppm). A single signal (δ 88.4 ppm) in the
typical δ range for carbons bearing two heteroatoms was
also present. These data are in agreement with the
structure of R-oxime ether hydroperoxide 7a ,11 and
therefore, the 1,2,4-dioxazolidine structure 8a must be
excluded13 (Scheme 1). It follows that the carbon-
nitrogen double bond of oxime 4a is unable to give [3 +
2] cycloaddition to the carbonyl oxide 3, and an oxygen
nucleophilic trapping reaction takes place. The fact that
both cyclohexanone O-methyl and O-acetyl oxime under
the same conditions were recovered unchanged provides
strong evidence for the suggested mechanism. At -20
°C compound 7a is converted to the hydroperoxynitrone
5a . To our knowledge, a rearrangement of this type has
never been observed. Here it occurred through certain
Resu lts a n d Discu ssion
We carried out the tetraphenylporphyrin-sensitized
photooxygenation of 2-methoxyfuran (1) in CDCl3-CFCl3
at -60 °C in the presence of an excess of cyclohexanone
1
oxime (4a ).9 After 90 min the H and 13C NMR spectra
† Dipartimento di Chimica Organica e Biologica.
‡ Dipartimento di Chimica.
(1) Iesce, M. R.; Cermola, F.; Guitto, A.; Scarpati, R.; Graziano, M.
L. J . Org. Chem. 1995, 60, 5324.
(2) The nucleophile trapping reaction of carbonyl oxides with
methanol has been extensively used to verify the production of the
dipolar species, but the behavior of these elusive entities toward
nucleophiles other than alcohols has not yet been well defined.3
(3) Bunnelle, W. H. Chem. Rev. 1991, 91, 335.
(4) As 1,3-dipoles, carbonyl oxides participate in the cycloaddition
chemistry characteristic of this class of reactive intermediates, and a
number of π-bonded systems have been found to be suitable dipolaro-
philic partners.3,5 Hence, the reaction with imines is quite efficient,
and 1,2,4-dioxazolidines are obtained generally in high yields.6
(5) Reference 1 and references therein.
(6) McCullough, K. J .; Mori, M.; Tabuchi, T.; Yamakoshi, H.;
Kusabayashi, M.; Nojima, M. J . Chem. Soc., Perkin Trans. 1 1995, 41
and references therein.
(7) (a) Iesce, M. R.; Cermola, F.; Guitto, A.; Scarpati, R.; Graziano,
M. L. Synlett 1995, 1161 and references therein. (b) Iesce, M. R.;
Cermola, F.; Graziano, M. L.; Cimminiello, G.; Scarpati, R. J . Chem.
Soc., Perkin Trans. 1 1992, 1855. (c) Iesce, M. R.; Graziano, M. L.;
Cermola, F.; Scarpati, R. J . Chem. Soc., Chem. Commun. 1991, 1061.
(8) Erden, I.; Griffin, A.; Keeffe, J . R.; Brinck-Kohn, V. Tetrahedron
Lett. 1993, 793. Cf. also: Ching, T. Y.; Foote, C. S. Tetrahedron Lett.
1975, 3771.
(9) Control experiments showed that oximes are unreactive at -20
°C with both singlet oxygen and with dimethyl 1-methoxy-4-phenyl-
2,3,7-trioxabicyclo[2.2.1]hept-5-ene-5,6-dicarboxylate; the latter is an
endo-peroxide that does not open into the corresponding carbonyl oxide
and was stable at the temperature of the experimental conditions
used.7b,10
(10) Graziano, M. L.; Iesce, M. R.; Cimminiello, G.; Scarpati, R. J .
Chem. Soc., Perkin Trans. 1 1989, 241.
(11) In the 1H NMR spectrum the broad singlet at δ 14.11 ppm is
unusually low for a OOH group that ordinarily absorbs at ca. δ 8-9
ppm. This observed shift can be attributed to intramolacular H-bonding
to the unsaturated nitrogen.12
(12) Richardson, W. H. In The Chemistry of Peroxides; Patai, S., Ed.;
J . Wiley and Sons: New York, 1983; Chapter 5, p 152.
(13) 13C NMR data also exclude the structure of nitrone derived from
the nitrogen trapping of 3 by the oxime since the 13C nitronyl chemical
shift appears in the range δ 125-150 ppm.14
(14) Dopp, D.; Dopp, H. In Houben-Weyl; Klamann, D., Hagemann,
H., Eds.; Thieme: Stuttgart, 1990; Band E14b/2, p 1379.
S0022-3263(96)01375-8 CCC: $12.00 © 1996 American Chemical Society

8678 J . Org. Chem., Vol. 61, No. 24, 1996
Notes
Sch em e 2. Ch em ica l P r op er ties of
Hyd r op er oxyn itr on e 5a
F igu r e 1.
1
short-lived intermediates evidenced by recording the H
and 13C NMR spectra of the reaction mixture at regular
time intervals at -40 °C. At this temperature, it was
found that the signals of 7a decreased, while new signals
appeared that collapsed into those of the nitrone 5a . In
particular, in addition to two singlets at δ 3.78 ppm and
δ 3.79 ppm, two sets of 1H signals due to two CHCHdCH
systems were present in the range δ 6.0-6.5 ppm as well
as four carbon signals at δ 92.1, 98.5, 102.6, and 104.6
ppm in the 13C NMR spectrum. These data would
suggest that the intermediates are two conformational
isomers of dihydro-1,2,4,5-trioxazine 6a . No further
intermediate was observed in the rearrangement of 6a
to 5a .15
showed a complex mixture that, upon warming to room
temperature, led to hydroperoxynitrone 5e and large
amounts of unidentified compounds.
In conclusion, the reported results show that the
carbon-nitrogen double bond of oximes is unable to give
[3 + 2] cycloaddition to carbonyl oxide 3 and an oxygen
nucleophilic trapping reaction takes place. The reaction,
which is the first ever reported addition of an oxime to a
carbonyl oxide,3 provides a useful one-pot synthesis of
hydroperoxynitrones 5. The latter, owing to the presence
of both nitrone and hydroperoxy functions, may exhibit
interesting biological properties and serve as useful
materials in various industrial processes.19,20 Finally, the
high yield together with the mild reaction conditions
make the conversion of hydroperoxynitrone 5a into
hydroperoxy-2,3-dihydroisoxazole 11 a convenient entry
to the synthesis of this compound class. Isoxazoline 11
shows an unusual stability for this ring system21 and
represents the first example of derivatives bearing a
hydroperoxy substituted carbon on nitrogen.
When the sensitized photooxygenation of 1 in the
presence of 4a was carried out in CH2Cl2 at -20 °C, in
addition to unreacted 4a , only the nitrone 5a was
observed. Silica gel chromatography led to the isolation
of 5a , whose structure was assigned on the basis of
elemental analyses and spectral data and was confirmed
by X-ray crystallography (Figure 1).16
In addition to cyclohexanone (12), treatment of the
hydroperoxynitrone 5a with Et2S led to (Z)-syn-oxime 13
(85%), which slowly converted into (Z)-anti-isomer 15
(Scheme 2). Under acid conditions the latter isomerized
to (E)-anti-oxime 14, which was directly obtained by acid
hydrolysis of the hydroperoxynitrone 5a . The function-
alized nitrone 5a reacted with dimethyl acetylenedicar-
boxylate (DMAD) at room temperature and, by 1,3-
dipolar cycloaddition, led to the hydroperoxy-2,3-
dihydroisoxazole 11 in 90% yield. In refluxing C6H6
compound 5a gave a mixture of products [9 (32%), 10
(33%), 12 (6%), and 13 + 15 (22%)] that were structurally
similar to those previously obtained from thermally
unstable hydroperoxynitrones.8
Exp er im en ta l Section
Gen er a l. Melting points are uncorrected. IR spectra were
recorded with chloroform as solvent. 1H and 13C NMR spectra
were run in CDCl3 at 400 and 100.6 MHz, unless otherwise
stated. Chemical shifts are reported in ppm referenced to the
TMS. DEPT techniques were employed to determine the
multiplicity in the 13C spectra. The solvents used for the
reactions were anhydrous. 2-Methoxyfuran (Aldrich), tetra-
phenylporphyrin (TPP) (Fluka), cyclohexanone oxime (Fluka),
Similar results were obtained when the photooxygen-
ation of 1 was carried out in the presence of oximes 4b-e
(Scheme 1).17 However, it should be noted that (1) in
contrast to nitrones 5a ,b,d ,e, compound 5c was stable
only below -15 °C and at room temperature decomposed
to the oxime 13, acetophenone and ketone-related un-
identified peroxides;18 (2) for series e, the 1H NMR
spectrum of the photooxygenation reaction at -60 °C
(18) This mixture was also obtained when the reaction was carried
out in CH2Cl2 at -20 °C. The low stability of 5c can be related to that
observed for nitrones similarly substituted on the hydroperoxidic
carbon.8
(19) For nitrone applications see among others: Kato, K.; Nakano,
M.; Richaado, G. K. J pn. Patent 06239737, 1994; Chem. Abstr. 1995,
122, 1096k. Krimer, M. Z.;, Styngin, E. P.; Rekhten, M. A.; Grush-
etskaya, G. N.; Uzhavka, Z. N.; Panasenko, A. A.; Molchanov, O. Yu.;
Abelentsev, V. I. Zh. Org. Chim. 1993, 29, 1859. Sandler, S. R.; Karo,
W. Organic Functional Group Preparations; Academic Press: New
York, 1986; Vol. III, p 355.
(20) For hydroperoxide applications see among others: Oda, K.;
Takei, K. J pn. Patent 0710709, 1995; Chem. Abstr. 1995, 122, 207776r.
Inoi, T. J pn. Patent 0211501, 1990; Chem. Abstr. 1990, 113, 120874m.
Organic Peroxides; Ando, W., Ed.; Wiley: Chichester, 1992. Sheldon,
R. A. In The Chemistry of Peroxides; Patai, S., Ed.; Wiley: Chichester,
1983; p 161. Kropf, H.; Torkler, F. In Houben-Weyl; Kropf, H., Ed.;
Thieme: Stuttgart, 1990; Band E14b/2; p 39.
(15) The hypothesis that the rearrangement occurs through the
intermediacy of an undetected oxaziridine is to be ruled out since
methyl (Z)-3-[2-(1-hydroperoxycyclohexyl)oxaziridin-3-yl]propenoate,
casually obtained by prolonged irradiation of the photooxygenation
mixture (see Experimental Section), was a stable compound and under
no conditions gave the nitrone 5a .
(16) The authors have deposited X-ray data for this structure with
the Cambridge Crystallographic Data Center. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Center, 12 Union Road, Cambridge, CB2 1EZ, UK.
(17) The stereochemistry of the carbon-nitrogen double bond of
7c,d , derived from the asymmetric oximes 4c,d , was not assigned.
(21) Freeman, J . P. Chem. Rev. 1983, 83, 241.

Notes
J . Org. Chem., Vol. 61, No. 24, 1996 8679
(Z)-3-(d ih yd r o-6-m et h yl-6-p h en yl-1,2,4,5-t r i-
acetone oxime (Fluka), acetaldehyde oxime (mixture of syn and
anti) (Fluka), benzaldehyde oxime (Fluka) and dimethyl acetyl-
enedicarboxylate (DMAD) (Aldrich) were used without purifica-
tion. Acetophenone oxime22 was prepared according to the
literature procedure. Silica gel (0.063-0.2 mm Macherey-Nagel)
and light petroleum (bp 40-60 °C) were used for column
chromatography. CAUTION: since organic peroxides are po-
tentially hazardous compounds, they must be handled with care.
No particular difficulties were experienced in handling any of
the new peroxides reported in this work.
Met h yl
oxa zin -3-yl)p r op en oa te (6c) (one isomer): 1H NMR (CFCl3/
CDCl3) δ 1.80 (s, 3 H), 3.63 (s, 3 H), 6.00 (d, J ) 6.3 Hz, 1 H),
6.10 (d, J ) 11.9 Hz), 6.42 (dd, J ) 11.9, 6.3 Hz, 1 H), 8.49 (br
s, 1 H); 13C NMR (CFCl3/CDCl3) δ 21.2 (q), 53.4 (q), 92.5 (s),
105.2 (d), 165.7 (s).
Met h yl (Z)-3-(d ih yd r o-6-m et h yl-1,2,4,5-t r ioxa zin -3-yl)-
p r op en oa te (6d ) (two isomers): 1H NMR (CFCl3/CDCl3) δ 1.39
and 1.54 (2 × d, J ) 5.3 Hz, 6 H), 4.78 and 4.95 (2 × q, J ) 5.3
Hz, 2 H), 8.24 and 8.31 (2 × br s).
(Z)-1-Hydr oper oxy-1-ph en yl-N-[(Z)-3-(m eth oxycar bon yl)-
2-p r op en ylid en e]eth yla m in e N-oxid e (5c): 1H NMR (CFCl3/
CDCl3) δ 2.22 (s, 3 H), 3.77 (s, 3 H), 6.21 (d, J ) 11.3 Hz, 1 H),
9.19 (d, J ) 10.1 Hz, 1 H) and 12.91 (br s, 1 H); 13C NMR (CFCl3/
CDCl3) δ 23.5 (q), 52.1 (q), 106.2 (s), 166.3 (s).
Gen er a l P r oced u r e for th e TP P -Sen sitized P h otooxy-
gen a tion of 2-Meth oxyfu r a n (1) in th e P r esen ce of Oxim es
4 in CF Cl3/CDCl3. Each solution (5 × 10-2 M) of the furan 1
(0.5 mmol) and the oxime 4 (2.5 mmol) in CFCl3/CDCl3 (1:2 v/v),
after the addition of the sensitizer (1.8 × 10-4 mmol), was
irradiated at -60 °C with a halogen-superphot lamp (Osram,
650 W). During irradiation, dry oxygen was bubbled through
the solution, which was kept at this temperature. When the
reaction was complete (90 min), the 1H and 13C NMR spectra
recorded at -60 °C showed the presence of 7, in addition to the
unreacted oxime 4, except for entry e. Compounds 7a -d
converted slowly at -40 °C and rapidly at -20 °C into inter-
mediates 6a -d (1H NMR), which in turn rearranged into the
corresponding hydroperoxynitrones 5a -d . For entry e, the 1H
NMR of the irradiation reaction at -60 °C showed a complex
mixture which evolved continuously upon heating, leading to
the hydroperoxynitrone 5e and large amounts of unidentified
products at rt. Nitrones 5a ,b,d ,e were stable at rt, while 5c
decomposed to a mixture of oxime 13, acetophenone, and ketone-
related unidentified peroxidic compounds.23 Selected spectral
data of compounds 7a -d , 6a -d , and 5c were deduced by a
careful analysis of the 13C and/or 1H NMR spectra of the related
reaction mixtures, recorded at -60, -40, and -20 °C, respec-
tively, after the signals of the other products were subtracted.
It was not possible to run satisfactory 13C NMR spectra for 6b
and 6d owing to their low concentration in the reaction mixtures.
Cycloh exa n on e oxim e O-[(Z)-1-h yd r op er oxy-3-(m eth -
oxyca r bon yl)-2-p r op en yl] eth er (7a ): 1H NMR (CFCl3/CDCl3)
δ 3.77 (s, 3 H), 6.19 (d, J ) 11.7 Hz, 1 H), 6.51 (dd, J ) 11.7, 7.0
Hz, 1 H), 7.54 (d, J ) 7.0 Hz, 1 H) and 14.11 (br s, 1 H); 13C
NMR (CFCl3/CDCl3) δ 52.2 (q), 88.4 (d), 124.9 (d), 137.0 (d), 163.2
(s), 165.2 (s).
Tr ip h en ylp h osp h in e Red u ction of th e Eth er s 7a -d . To
0.5 mL of the solution of 7a -d in CFCl3/CDCl3 at -60 °C was
added a solution of triphenylphosphine (10 mg, 0.037 mmol) in
1
CDCl3 (0.2 mL) precooled at this temperature. After 4 h the H
NMR, recorded at -60 °C, showed, in addition to the oximes
4a -d , only the presence of the (Z)-unsaturated aldehyde 9.1
Gen er a l P r oced u r e for th e TP P -Sen sitized P h otooxy-
gen a tion of 2-Meth oxyfu r a n (1) in th e P r esen ce of Oxim es
4 in CH2Cl2. Each 2 × 10-2 M solution of the furan (1 mmol)
in CH2Cl2 and the oxime (5 mmol), after the addition of the
sensitizer (3.6 × 10-4 mmol), was photooxygenated at -20 °C.
When each reaction was complete (90 min) the solvent was
removed under reduced pressure at rt and the residue analyzed
1
by H NMR. In addition to the unreacted oximes 4, the spectra
for entries a ,b,d showed the presence of only 5a ,b,d , and for
entry e, a mixture of 5e and unidentified compounds. Chroma-
tography on a short column of silica gel, eluting with light
petroleum/ether (8:2, 1:1), gave successively the oxime 4 and the
hydroperoxynitrones 5a ,b,d ,e. For series c no nitrone 5c was
detected spectroscopically and silica gel chromatography, using
light petroleum/ether (8:2) as eluent, gave the oxime 4c as well
as complex mixtures of 13 and 15 along with acetophenone and
ketone-related peroxidic unidentified products.
(Z)-1-H yd r op er oxy-N-[(Z)-3-(m et h oxyca r b on yl)-2-p r o-
p en ylid en e]cycloh exyla m in e N-oxid e (5a ): 65% yield; mp
76-78 °C (from diethyl ether/hexane); IR 3530, 3161, 1713, 1606,
1074 cm-1; H NMR δ 1.50-2.30 (m, 10 H), 3.77 (s, 3 H), 6.05
1
(dd, J ) 11.7, 1.4 Hz, 1 H), 7.35 (dd, J ) 11.7, 10.5 Hz, 1 H),
8.97 (dd, J ) 10.5, 1.4 Hz, 1 H) and 10.58 (br s, 1 H); 13C NMR
δ 22.2 (t), 24.6 (t), 31.6 (t), 51.7 (q), 105.6 (s), 123.4 (d), 131.0
(d), 131.6 (d), 166.3 (s). Anal. Calcd for C11H17NO5: C, 54.31;
H, 7.04; N, 5.76. Found: C, 54.1; H, 6.8; N, 5.6.
(Z)-2-H yd r op er oxy-N-[(Z)-3-(m et h oxyca r b on yl)-2-p r o-
p en ylid en e]-2-p r op yla m in e N-oxid e (5b): 80% yield; mp 77-
78 °C (from tert-butyl methyl ether/hexane); IR 3526, 3160, 1713,
1606, 1078 cm-1; 1H NMR δ 1.77 (s, 6 H), 3.78 (s, 3 H), 6.06 (dd,
J ) 11.7, 1.0 Hz, 1 H), 7.35 (dd, J ) 11.7, 10.2 Hz, 1 H), 8.89
(dd, J ) 10.2, 1.0 Hz, 1 H), 9.82 (br s, 1 H); 13C NMR δ 22.4 (q),
51.1 (q), 103.7 (s), 123.0 (d), 130.5 (d), 131.1 (d), 165.7 (s). Anal.
Calcd for C8H13NO5: C, 47.29; H, 6.45; N, 6.89. Found: C, 47.1;
H, 6.3; N, 6.6.
Acet on e oxim e O-[(Z)-1-h yd r op er oxy-3-(m et h oxyca r -
bon yl)-2-p r op en yl] eth er (7b): 1H NMR (CFCl3/CDCl3) δ 2.39
and 2.57 (2 × s, 6 H), 3.79 (s, 3 H), 6.21 (d, J ) 11.5 Hz, 1 H),
6.47 (dd, J ) 11.5, 7.9 Hz, 1 H), 7.48 (d, J ) 7.9 Hz, 1 H), 14.04
(br s, 1 H); 13C NMR (CFCl3/CDCl3) δ 20.9 (q), 21.4 (q), 52.3 (q),
88.7 (d), 125.4 (d), 136.3 (d), 157.6 (s), 165.2 (s).
Acetop h en on e oxim e O-[(Z)-1-h yd r op er oxy-3-(m eth oxy-
ca r bon yl)-2-p r op en yl] eth er (7c):17 1H NMR (CFCl3/CDCl3)
δ 2.70 (s, 3 H), 3.53 (s, 3 H), 6.17 (d, J ) 11.3 Hz, 1 H), 6.68 (dd,
J ) 11.3, 8.1 Hz, 1 H), 7.33 (d, J ) 8.1 Hz, partially overlapping
to phenyl hydrogens), 13.74 (br s, 1 H); 13C NMR (CFCl3/CDCl3)
δ 21.9 (q), 52.0 (q), 91.2 (d), 157.7 (s), 164.3 (s).
Aceta ld eh yd e oxim e O-[(Z)-1-h yd r op er oxy-3-(m eth oxy-
ca r bon yl)-2-p r op en yl] eth er (7d ):17 1H NMR (CFCl3/CDCl3)
δ 2.21 (d, J ) 6.2 Hz, 3 H), 3.78 (s, 3 H), 6.20 (d, J ) 11.5 Hz,
1 H), 6.42 (dd, J ) 11.5, 7.9 Hz, 1 H), 6.84 (d, J ) 7.9 Hz) and
7.53 (q, J ) 6.2 Hz) partially overlapping to the two quartet
signals of the unreacted syn- and anti-oximes 4d , 13.5 (br s, 1
H); 13C NMR (CFCl3/CDCl3) δ 13.0 (q), 52.2 (q), 97.0 (d), 125.7
(d), 136.5 (d), 144.3 (d), 165.3 (s).
Meth yl (Z)-3-(1,2,4-tr iox-5-a za sp ir o[5.5]u n d ec-3-yl)p r o-
p en oa te (6a ) (two isomers): 1H NMR (CFCl3/CDCl3) δ 3.78 and
3.79 (2 × s), 6.00-6.60 (m), 8.28 and 8.45 (2 × br s); 13C NMR
δ 92.1 (s), 98.5 (s), 102.6 (d), 104.6 (d).
(Z)-1-H yd r op er oxy-N-[(Z)-3-(m et h oxyca r b on yl)-2-p r o-
p en ylid en e]eth yla m in e N-oxid e (5d ): 80% yield; oil; IR 3522,
1
3120, 1715, 1609, 1081 cm-1; H NMR δ 1.60 (d, J ) 5.9 Hz, 3
H), 3.78 (s, 3 H), 5.46 (q, J ) 5.9 Hz, 1 H), 6.14 (dd, J ) 11.7,
1.0 Hz, 1 H), 7.37 (dd, J ) 11.7, 10.3 Hz, 1 H), 8.77 (dd, J )
10.3, 1.0 Hz, 1 H), 11.59 (br s, 1 H); 13C NMR δ 16.8 (q), 51.8
(q), 101.2 (d), 124.3 (d), 130.5 (d), 132.4 (d), 166.1 (s). Anal. Calcd
for C7H11NO5: C, 44.44; H, 5.86; N, 7.41. Found: C, 44.2; H,
5.6; N, 7.3.
(Z)-1-H yd r op er oxy-N-[(Z)-3-(m et h oxyca r b on yl)-2-p r o-
p en ylid en e]ben zyla m in e N-oxid e (5e): 20% yield; oil; IR
3520, 3113, 1715, 1604, 1078 cm-1; 1H NMR δ 3.77 (s, 3 H), 6.08
(dd, J ) 11.8, 1.1 Hz, 1 H), 6.28 (s, 1 H), 7.35 (dd, J ) 11.8, 10.3
Hz) and 7.30-7.55 (m) together 6 H, 8.91 (dd, J ) 10.3, 1.1 Hz,
1 H), 11.47 (br s, 1 H); 13C NMR δ 51.8 (q), 104.3 (d), 124.4 (d),
127.1 (d), 128.7 (d), 130.4 (d), 130.5 (d), 131.4 (s), 132.6 (d), 166.1
(s). Anal. Calcd for C12H13NO5: C, 57.37; H, 5.22; N, 5.58.
Found: C, 57.2; H, 5.1; N, 5.4.
Met h yl (Z)-3-(d ih yd r o-6,6-d im et h yl-1,2,4,5-t r ioxa zin -3-
yl)p r op en oa te (6b) (two isomers): 1H NMR (CFCl3/CDCl3) δ
1.43 (s), 1.60 (two overlapping s) and 1.65 (s) (together 12 H),
3.81 and 3.82 (2 × s, 6 H), 6.10-6.70 (m), 8.41 and 8.75 (2 × br
s).
(22) Campbell, K. N.; Campbell, B.; Chaput, E. P. J . Org. Chem.
1943, 8, 99.
(23) When a sample of this mixture was treated with Et2S, aceto-
phenone was formed in addition to Et2SO, and after completion of the
reduction, the oxime 13 and the ketone were present in ca. 1:1 molar
ratio (1H NMR).
syn -Meth yl (Z)-4-(Hyd r oxyim in o)-2-bu ten oa te (13).
A
solution of 5a (243 mg, 1 mmol) in CCl4 (20 mL) was treated
with Et2S (135 mg, 1.5 mmol). When the reduction was complete
1
(30 min) the H NMR showed the presence of the (Z)-syn-oxime

8680 J . Org. Chem., Vol. 61, No. 24, 1996
Notes
13 in addition to Et2S and Et2SO. Removal of the solvent and
of the unreacted Et2S gave a residue that was rapidly chromato-
graphed on a short column of silica gel using light petroleum/
ether (8:2) as eluent to give 108 mg (84%) of 13: mp 40-42 °C
3.69, 3.77 and 3.90 (3 × s, 9 H), 5.84 (d, J ) 11.7 Hz, 1 H), 6.15
(dd, J ) 11.7, 9.3 Hz, 1 H), 6.87 (d, J ) 9.3 Hz, 1 H), 7.90 (br s,
1 H); 13C NMR δ 21.8 (t), 21.9 (t), 25.3 (t), 29.7 (t), 30.0 (t), 51.5
(q), 51.8 (q), 53.3 (q), 59.4 (d), 98.7 (s), 108.5 (s), 119.9 (d), 143.8
(d), 152.7 (s), 159.0 (s), 162.1 (s), 166.1 (s). Anal. Calcd for
1
(from hexane); IR 3579, 3316, 1719, 1631, 1601 cm-1; H NMR
δ 3.79 (s, 3 H), 6.05 (dd, J ) 11.7, 1.0 Hz, 1 H), 7.30 (dd, J )
11.7, 9.8 Hz, 1 H), 8.38 (dd, J ) 9.8, 1.0 Hz, 1 H), 9.30 (br s, 1
H); 13C NMR δ 51.8 (q), 124.4 (d), 128.4 (d), 143.8 (d), 165.7 (s).
Anal. Calcd for C5H7NO3: C, 46.51; H, 5.47; N, 10.85. Found:
C, 46.4; H, 5.3; N, 10.7.
C
17H23NO9: C, 52.98; H, 6.02; N, 3.64. Found: C, 52.7; H, 5.9;
N, 3.5.
Th er m olysis of Hyd r op er oxyn itr on e 5a . A solution of 5a
(243 mg, 1 mmol) in dry C6H6 (10 mL) was kept on reflux. After
30 min the 1H NMR spectrum showed a mixture composed of
the aldehyde 9,1 the hydroxamic acid 10,24 the ketone 12, the
(Z)-syn-oxime 13, and the (Z)-anti-oxime 15. After removal of
the solvent, the residue was chromatographed on silica gel with
light petroleum/ether (9:1, 8:2, 1:1, 1:19) to give successively 12
(6%), 9 (32%), a mixture of 13 and 15 (together 22%), and 10
(33%).
Compound 13 slowly converted into (Z)-anti-isomer 15: mp
74-75 °C (from diethyl ether/hexane); IR 3572, 3346, 1719, 1629,
1
1603 cm-1; H NMR δ 3.77 (s, 3 H), 6.03 (d, J ) 11.5 Hz, 1 H),
6.64 (dd, J ) 11.5, 9.7 Hz, 1 H), 7.60 (br s, 1 H), 8.91 (d, J ) 9.7
Hz, 1 H); 13C NMR δ 51.7 (q), 123.2 (d), 136.8 (d), 148.9 (d), 165.8
(s). Anal. Calcd for C5H7NO3: C, 46.51; H, 5.47; N, 10.85.
Found: C, 46.4; H, 5.3; N, 10.8.
Met h yl (Z)-3-[2-(1-Hyd r op er oxycycloh exyl)oxa zir id in -
3-yl]p r op en oa te. A solution of the photooxygenation mixture
of 1 (98 mg, 1 mmol) with the oxime 4a (565 mg, 5 mmol) and
TPP in CH2Cl2 at -20 °C was allowed to irradiate for a long
time (6 h). The 1H NMR spectrum of a sample showed the
presence of a small amount of the hydroperoxyoxaziridine in
addition to the hydroperoxynitrone 5a and unreacted oxime 4a .
Removal of the solvent gave a residue that was chromatographed
on silica gel with light petroleum/ether (9:1, 8:2, 1:1) to give
successively the oxime 4a , the oxaziridine [(20 mg, 8%), mp 45-
a n ti-Meth yl (E)-4-(Hyd r oxyim in o)-2-bu ten oa te (14). A
solution of 5a (243 mg, 1 mmol) in acetone (25 mL) was treated
with 2 M HCl (0.05 mL) and kept at rt. After 1 h, the acetone
was removed in vacuo, and the residue was treated with H2O
and extracted three times with CHCl3. The organic layers were
dried over MgSO4 and evaporated to a residue that was
chromatographed on silica gel with light petroleum/ether (17:3)
to give 103 mg (80%) of 14: mp 90-93 °C (from tert-butyl methyl
1
ether/hexane); IR 3569, 3346, 1718, 1647, 1600 cm-1; H NMR
1
δ 3.80 (s, 3 H), 6.18 (d, J ) 16.1 Hz, 1 H), 7.34 (dd, J ) 16.1,
10.2 Hz, 1 H), 7.89 (d, J ) 10.2 Hz, 1 H), 9.39 (br s, 1 H); 13C
NMR δ 52.1 (q), 126.8 (d), 137.6 (d), 149.4 (d), 166.5 (s). Anal.
Calcd for C5H7NO3: C, 46.51; H, 5.47; N, 10.85. Found: C, 46.4;
H, 5.4; N, 10.6. Control experiments showed that, under the
conditions used for 5a , both (Z)-syn-oxime 13 and (Z)-anti-oxime
15 isomerized to (E)-anti-oxime 14.
47 °C (from C6H6/hexane); IR 3543, 3434, 1723, 1661 cm-1; H
NMR δ 1.30-2.30 (m, 10 H), 3.80 (s, 3 H), 5.87 (m, 2 H) and
6.21 (m, 1 H), 9.08 (br s, 1 H); 13C NMR δ 21.5 (t), 21.9 (t), 25.1
(t), 30.1 (t), 31.1 (t), 51.9 (q), 68.9 (d), 95.9 (s), 127.5 (d), 142.8
(d), 165.7 (s). Anal. Calcd for C11H17NO5: C, 54.31; H, 7.04; N,
5.76. Found: C, 54.2; H, 6.9; N, 5.6.], and the nitrone 5a (110
mg, 45%).
Dim eth yl 2-(1-Hyd r op er oxycycloh exyl)-3-[(Z)-2-(m eth -
oxyca r b on yl)vin yl]-2,3-d ih yd r oisoxa zole -4,5-d ica r b ox-
yla te (11). A solution of 5a (243 mg, 1 mmol) in dry Et2O (50
mL) was treated with DMAD (710 mg, 5 mmol), and the
resulting mixture was stirred at rt. The 1H NMR spectrum,
recorded after 1 h, showed the presence of the hydroperoxy-2,3-
dihydroisoxazole 11 in addition to the unreacted DMAD. After
removal of the solvent, the residue was chromatographed on a
short column of silica gel using light petroleum/ether (9:1, 3:2)
as eluent to give successively the unreacted DMAD and the
hydroperoxy-2,3-dihydroisoxazole 11 in 90% yield: mp 59-61
°C dec (from tert-butyl methyl ether/hexane); IR 3532, 3420,
Ack n ow led gm en t. This work was financially sup-
ported by the CNR (Rome) and the Ministero
dell’Universita` e della Ricerca Scientifica e Tecnologica
(MURST). The NMR spectra were run and the crystal-
lographic work was undertaken at the Centro di Metod-
ologie Chimico-Fisiche, Universita` di Napoli Federico
II.
J O961375Z
(24) Matlin, S. A.; Sammes, P. G.; Upton, R. M. J . Chem. Soc., Perkin
Trans. 1 1979, 2481.
1753, 1719, 1658, 1603 cm-1 1H NMR δ 1.30-2.20 (m, 10 H),
;