Azodioxy-carbonyl compounds by oxidation of cyclic imines with m-CPBA

Article abstract of DOI:10.1016/j.tet.2011.01.054

This article reports a simple and efficient synthesis of C-nitroso compounds (azodioxy esters or ketones and oximes) through a double oxidation of cyclic imines (4,5-dihydrooxazoles and 3,4-dihydro-2H-pyrroles) with m-CPBA. C-Nitroso derivatives seem to b

Full text of DOI:10.1016/j.tet.2011.01.054

Tetrahedron 67 (2011) 2090e2095
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Azodioxy-carbonyl compounds by oxidation of cyclic imines with m-CPBA
,
Serena Perrone a, Tullio Pilati b, Francesca Rosato a, Antonio Salomone a, Valeria Videtta a, Luigino Troisi a
*
a Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy
b C.N.R. ‘Institute of Molecular science and Technology’, Via C. Golgi 19, 20133 Milano, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 October 2010
Received in revised form 20 December 2010
Accepted 18 January 2011
Available online 25 January 2011
This article reports a simple and efficient synthesis of C-nitroso compounds (azodioxy esters or ketones
and oximes) through a double oxidation of cyclic imines (4,5-dihydrooxazoles and 3,4-dihydro-2H-
pyrroles) with m-CPBA. C-Nitroso derivatives seem to be potential donors of nitric oxide, one of the most
powerful biological messenger.
Published by Elsevier Ltd.
Keywords:
Imines
Oxaziridines
Azodioxy
Oximes
C-Nitroso compounds
O
1. Introduction
O
O
N
R
m-CPBA
silica gel
R
R
O
N
N
O
C-Nitroso compounds (RN¼O; R¼alkyl or aryl group) are an
interesting family of molecules that have an important role in or-
ganic chemistry and biochemistry. Recently, it was reported that
appropriately substituted C-nitroso compounds act solely as donors
of neutral nitric oxide (NO) through a first-order homolytic CeN
bond scission.1 The nitric oxide, considered a very pollutant gas for
decades, also co-responsible of the atmospheric ozone layer de-
pletion, was lately identified as one of the most powerful endoge-
nous signalling molecule. This messenger is produced in living
organisms for controlling many of their biological functions.2e8
Methods for the preparation of C-nitroso compounds have been
recently reviewed.9 Lee and Keana10 showed that oxazoline oxi-
dation with 3-chloroperoxybenzoic acid (m-CPBA) gave the con-
densed oxaziridine (A) (Scheme 1), which upon further
manipulation converted into the nitroso ester 1 as the final product.
According toTaylor et al.11 oxaziridines, prepared by oxidation of
an imine (1.0 mmol) with peracetic acid (1.0 mmol), were oxidized
with a second mole of peroxy acid giving nitrosoalkane dimers 2
(Scheme 2).
A
O
H2O
O
O
O
m-CPBA
R
R
N
NH
OH
O
1
Scheme 1. C-nitroso compounds through oxazoline oxidation.
R
O
R
O
R
O
CH3CO3H
CH3CO3H
PhCO2H
N
N
N
N
R
Ph
Ph
2
Analogously, Emmons12 observed that oxaziridines reacted
smoothly with 1 equiv of peracetic acid affording good yields of
nitrosoalkanes that rapidly dimerized (Scheme 3).
R = CH3; C2H5; i-C3H7; C6H11
Scheme 2. Azodioxy compounds from imines.
Yields: 36% - 50%
The stability of nitrosoalkane dimers has been commented on
previously by Gowenlock.13
Recently, we synthesized several chiral and achiral oxaziridines
that have been successively used in the [3þ2] cycloaddition
* Corresponding author. Fax: þ39 0832 298626; e-mail address: luigino.troisi@
unisalento.it (L. Troisi).
0040-4020/$ e see front matter Published by Elsevier Ltd.
doi:10.1016/j.tet.2011.01.054

S. Perrone et al. / Tetrahedron 67 (2011) 2090e2095
2091
through reduction of enantiomerically pure or racemic
a-amino
O
R
acids to the corresponding amino alcohols,19 which were sub-
O
R
R
R'
O
O
R
N
O
sequently condensed with ortho esters20 (Scheme 5).
O
N N
R'
R
N
R'
R
R'
O
O
COOH
CH2OH
NaBH4
(CH3O)3CR
R''
R'
R''
R'
3
R
R''
R'
NH2
NH2
N
R = alkyl groups
R'= alkyl or aryl groups
Yields: 33% - 87%
Scheme 5. Oxazolines synthesis from amino acids.
Scheme 3. Azodioxy compounds from oxaziridines.
From the previous literature we expected that 7aei would be
converted into the corresponding 8aei (or 9aei), but surprisingly
we got new and unexpected results that we report in this work.
Particularly, when to an ice-cooled solution of 7a in CH2Cl2 was
added m-CPBA (1.1 equiv), aftera 10 h period, GCand GCeMSshowed
the formation of a new product, together with the 50% of unreacted
starting material. The same reaction carried out with 2.2 equiv of
m-CPBA instead produced the total conversion of the starting 2-
phenyloxazoline into the new product. The reaction work-up was
conducted in a non-aqueous way, according to a modified Emmons’s
procedure: the crude mixture was stirred with excess powdered an-
hydrous sodium carbonate (with neutralization of the acidic reaction
mixture) until carbon dioxide evolution ceased. After filtration, the
mixturewasconcentrated invacuoatroom temperature and afterthe
addition of diethyl ether a white solid (99% yield) was obtained. The
1H,13C NMR, GCeMS and the X-ray diffraction analysis of this product
were in agreement with the structure of the trans dimer 12a (Fig.1).21
reactions with alkenes,14,15 alkynes16 and nitriles,17 to generate
stable isoxazolidines 4, isoxazolines 5 and 2,3-dihydro-1,2,4-oxa-
diazoles 6, respectively (Scheme 4).
O
R
Ar
N
Ar
4
Ar'
O
O
R
R
Ar
Ar
Ar
N
N
Ar'
R
5
Ar'
O
Ar
N
N
N
Ar'
6
Scheme 4. [3þ2] Cycloaddition between oxaziridines and dipolarophiles.
The oxaziridines have been prepared from the respective imines
according to Emmons’s methodology,18 which is based on the ad-
dition of the m-CPBA (1.1 mmol) to an imine (1.0 mmol) in CH2Cl2
(20 mL) at 0 ꢀC. No nitrosoalkane was ever isolated or observed in
the various synthesis reactions.
Fig. 1. Projection of compound 12a at 93 K. The molecule lies on a crystallographic
centre of symmetry; only the asymmetric unit was labelled. ADPs at 50% probability
level; H atoms not to scale.
2. Results and discussion
We hypothesize that the starting oxazoline 7a, oxidized with
m-CPBA, is initially converted into the corresponding unstable
condensed 2,3-oxaziridine 8a, which in the presence of the peroxy
acid, quickly is further oxygenated generating 10a as a transient
intermediate (Scheme 6).
N-Oxide 10a rearranges to monomeric C-nitroso compound 11a
that rapidly dimerizes to trans azodioxy ester 12a. This last product
was isolated and characterized. The dimer 12a, dissolved in toluene
and heated at reflux, after a few minutes underwent a thermal
conversion into oxime 13a, giving the Z and E isomeric forms (Z/E
ratio 58:42, Scheme 6). Such rearrangement probably occurs via
azodioxide monomerization to nitroso compounds, which sub-
sequently undergo 1,3 hydrogen migration to form oximes.22 The
slight prevalence of the Z isomer respect to the E one was probably
due to the possible formation of hydrogen bond between hydroxyl
and carbonyl group in Z isomer. Indeed, calculations performed at
With the aim of synthesizing more reactive oxaziridines for
cycloaddition reactions with various dipolarophiles, we turned our
attention to the preparation of more strained oxaziridines (for ex-
ample, condensed to other heterocycles), through the oxidation of
cyclic imines, such as 4,5-dihydrooxazoles 7aeh and 5-methyl-3,4-
dihydro-2H-pyrrole 7i (Table 1). Oxazolines 7aeh were prepared
Table 1
Condensed oxaziridines synthesis
the 6-31G /B3LYP level (in the gas phase) showed only a small
*
Entry Starting material
R
R0
R00
X
Product Total yield (%)
energy difference (0.47 kcal/mol) between the two isomers, that
justified the result. NOESY measurements were in agreement with
the assigned structures.
1
2
3
4
5
6
7
8
9
7a
7b
7c
7d
7e
7f
7g
7h
7i
Ph
Ph
Et
Me
Et
H
H
H
H
H
H
H
Bn
i-Pr
i-Pr
Bn
O
O
O
O
O
O
O
O
8aa
8ba
8ca
8da
8ea
8fa
8g
d
d
d
d
d
d
97
97
98
The same trend was found in a similar reaction carried out on
the known (þ)-(4S)-oxazoline 7b;23e25 the (ꢁ)-(S, S)-trans dimeric
azodioxy ester 12b ([
a
]
24.0 ꢁ104.6, c 0.1, CHCl3) was obtained in 50%
D
Et
Et
i-Bu
yield using 1.1 equiv of m-CPBA and in quantitative yield using
2.2 equiv of m-CPBA, respectively (Table 2, entry 2). The dimer 12b,
isolated and heated at reflux in toluene, was converted into Z and E
isomer of the oxime 13b (Z/E ratio 70/30; Table 3, entry 2).
Me Me
Me Me Me
Me
8h
H
H
CH2 8i
a
Not isolated product.

2092
S. Perrone et al. / Tetrahedron 67 (2011) 2090e2095
The (ꢁ)-(4S)-oxazolines 7c26, 7d27 and 7e20 also produced
O
N
O
Ph
similar results affording at first the trans dimers 12c (Table 2, entry
3), 12d28 (Table 2, entry 4) and 12e (Table 2, entry 5), which then,
after the reflux, were transformed into 13c (Z/E ratio 50:50), 13d (Z/
E ratio 50:50) and 13e (Z/E ratio 66:33), respectively (Table 3, en-
tries 3e5). Previously, Aitken et al., oxidizing the chiral oxazoline
7d using 1.6 equiv of m-CPBA, isolated the dimer 12d together with
the E/Z mixture of the isomeric oximes 13d.28
O
N
O
N
Ph
m-CPBA
m-CPBA
Ph
O
O
7a
8a
10a
An equimolar mixture of cis/trans azodioxy-carbonyl dimer 12f
was instead obtained when the oxazoline 7f29 reacted under the
same conditions described above (Table 2, entry 6). Both the trans
and cis dimer, refluxed in toluene separately, provided a mixture of
Z/E oxime 13f with a diastereomeric ratio of 66:33 (Table 3, entry 6).
Oxazolines lacking hydrogen atoms at the 4 position produced
different results. For instance, the 2-ethyl-4,4-dimethyl-4,5-dihy-
dro-oxazole 7g oxidized with m-CPBA (1.1 equiv) at 0 ꢀC, after 3 h,
afforded the stable condensed 2,3-oxaziridine 8g, which did not
need further purification (yield¼97%; Table 1, entry 7). Therefore,
we previously used 8g in the [3þ2] cycloaddition reactions with
alkenes, alkynes and nitriles.30 The stability of this condensed
oxaziridine is probably caused by two alkyl groups in 4 position
that, of course, provide an improved thermal stability to the mol-
ecule compared to previous cases. The 2,4,4-trimethyl-4,5-dihydro-
oxazole 7h, treated under the same conditions, led to stable
oxaziridine 8h,31 too (Table 1, entry 8). However, 7 and 7h treated
with an excess of m-CPBA (2.2 equiv), produced the dimeric azo-
dioxy esters 12 and 12h in high yields, both in the two cis/trans
isomeric forms with a diastereomeric ratio of 20:80 and of 33:66,
respectively (Table 2, entries 7 and 8). The oxaziridines 8 and 8
oxidized with 1.1 equiv of m-CPBA, also gave the azodioxides 12 and
12, respectively, with the same yield and ratio. Moreover, 12 and
12h, when heated at reflux for few hours in toluene, retained the
dimeric structure but the cis isomeric form showed a tendency to
interconvert into the trans isomer. After about 1 h of reflux, the cis/
trans ratio became 4:96 for 12 and 8:92 for 12h. Furthermore,
theoretical studies on the cis/trans-isomerization of azodioxy
compounds have shown that, in a thermal reaction, the fragmen-
tation of the cis form into two nitrosomonomers and their re-
combination to the trans form take place via the symmetry-allowed
‘from step to step’ mechanism (Fig. 2).32 For the azodioxides 12g
and 12h, oxime formation is precluded because their respective
O
O
N
N
Ph
O
Ph
O
OH
O
13a
11a
O
O
N
O
Ph
Ph
O
N
O
O
12a
Scheme 6. Suggested mechanism for azodioxide and oxime synthesis.
Table 2
Azodioxy compounds synthesis
Entry Starting
material
R
R0
R00
X
Product Ratio trans/cis Total yield
(%)
1
2
3
4
5
6
7
8
9
7a
7b
7c
7d
7e
7f
7g
7h
7i
Ph
Ph
Et
Me
Et
H
H
H
H
H
H
H
Bn
i-Pr
i-Pr
Bn
O
O
O
O
O
O
O
O
12a
12b
12c
12d
12e
12f
100/0
100/0
100/0
100/0
100/0
50/50
80/20
66/33
100/0
99
96
99
97
98
97
98
97
98
monomeric C-nitroso compounds contain no hydrogen
a to nitro-
Et
Et
i-Bu
gen for migration.22
Me Me
12g
12h
Me Me Me
Me
Finally, even the cyclic imine 7i, 5-methyl-3,4-dihydro-2H-pyr-
role, behaved similarly. The stable condensed oxaziridine 8i and the
trans azodioxy ketone 12i were formed through oxidation of 7i
with 1.1 equiv and 2.2 equiv of m-CPBA, respectively (Table 1, entry
9; Table 2, entry 9). The trans dimer heated in toluene at 80 ꢀC, after
10 min, gave the Z and E oxime 13i (diastereomeric ratio 66:33;
Table 3, entry 9).
H
H
CH2 12i
Table 3
Rearrangement of azodioxides to oximes
O
R
R
R
O
R
N
N
N
N
O
O
Entry Starting material
R
R0 R00
X
Product Ratio Z/E Total yield (%)
1
2
3
4
5
6
7
8
9
12a
12b
12c
12d
12e
12f
12g
12h
12i
Ph
Ph
Et
Me
Et
H
H
H
H
H
H
H
Bn
i-Pr
i-Pr
Bn
O
O
O
O
O
O
O
O
13a
13b
13c
13d
13e
13f
d
58/42
70/30
50/50
50/50
66/33
66/33
d
99
96
98
97
99
99
d
R
O
O
N
N
Et
i-Bu
Et Me Me
Me Me Me
Me
R
d
d
d
H
H
CH2 13i
66/33
98
Fig. 2. cis/trans Interconversion of azodioxy dimer through the monomeric form.

S. Perrone et al. / Tetrahedron 67 (2011) 2090e2095
2093
3. Conclusions
4.2.1. 5-Methyl-6-oxa-1-aza-bicyclo[3.1.0]hexane (8i). Yield: 97 mg
(98%), yellow oil. 1H NMR (400.13 MHz, CDCl3):
d¼1.50 (3H, s, CH3),
In summary, we have carried out an efficient and simple syn-
thesis of C-nitroso derivatives from enantiomerically pure or ra-
cemic a-amino acids.
1.50e1.59 (2H, m, CH2CH2CH2), 1.69e1.75 (1H, m, CH2CHHCO), 2.20
(1H, ddd, J¼2.0 , 7.0 , 8.6 Hz, CH2CHHCO), 2.82e2.89 (1H, m,
NeCHH), 3.33 (1H, ddd, J¼2.0 , 7.0 , 8.6 Hz, NeCHH) ppm; 13C NMR
(100.62 MHz, CDCl3):
d
¼18.5, 19.9, 30.5, 55.4, 87.7 ppm; FTIR
(CHCl3): 2993, 2932 and 2862 (CeH aliph.), 1372 (CeO),1221 (NeO)
cmꢁ1; GCeMS (70 eV): m/z (%)¼99 (100) [M]þ, 98 (63), 80 (10), 69
(39); HRMS (ESI): calcd for C5H10NO: (100.0762) [MþH]þ; found:
(100.0760).
4. Experimental section
4.1. General experimental methods
All reactions involving air-sensitive reagents were performed
under an atmosphere of nitrogen in oven-dried glassware by using
syringe/septum cap techniques. Et2O, THF and toluene were pu-
rified by distillation from sodium before use. CH2Cl2 was distilled
from calcium hydride before use. Petroleum ether refers to the
40e60 ꢀC boiling fraction. Cyclic imines, 7a and 7gei, and m-
chloroperbenzoic acid (m-CPBA) were of commercial grade
(Aldrich) and used without further purification. 2-Oxazolines,
7b,23e25 7c,26 7d27 and 7e20, 7f were prepared according to the
general literature procedure,20 which involved condensation of
ortho esters, as received commercially (Aldrich) and without fur-
ther purification, with 2-amino alcohols in the presence of a cat-
alyst (CF3COOH). Amino alcohols were synthesized by reduction
4.3. General procedure for the synthesis of azodioxy-carbonyl
dimers 12aei28
A solution of m-CPBA (540 mg, 2.2 mmol, 70%) in CH2Cl2
(10 mL), previously cooled in an ice bath, was added dropwise to
an ice cooled solution of the cyclic imines 7aei (1.0 mmol) in
CH2Cl2 (10 mL) The mixture was allowed to gradually warm to
room temperature (with stirring) over a 12-h period. After further
dilution with CH2Cl2 (10 mL), the solution was stirred with excess
powdered anhydrous sodium carbonate until carbon dioxide
evolution ceased. After filtration, the solvent was evaporated in
vacuo at room temperature giving the dimers 12aei as pure
compounds.
of the corresponding commercially available a-amino acids, fol-
lowing reported synthetic protocols.19 The 1H and the 13C NMR
spectra were recorded with a Bruker Avance 400 apparatus
(400.13 and 100.62 MHz, for 1H and 13C, respectively) with CDCl3
4.3.1. trans-Benzoic acid 2-nitrosoethyl ester dimer (12a). Yield:
177 mg (99%), bright white needle-like crystals with mp 74e75 ꢀC
(diethyl ether). 1H NMR (400.13 MHz, CDCl3):
d¼4.72 (2H, t,
as the solvent and TMS as an internal standard (
d
¼7.26 ppm for 1H
J¼5.1 Hz, OeCH2), 4.81 (2H, t, J¼5.1 Hz, NeCH2), 7.39 (2H, t,
spectra;
d
¼77.0 ppm for 13C spectra). The IR spectra were recorded
J¼7.6 Hz, Ph), 7.54 (1H, t, J¼7.6 Hz, Ph.), 7.98 (2H, d, J¼7.6 Hz, Ph)
with an FTIR spectrophotometer Digilab Scimitar Series FTS 2000.
Polarimetric measurements were performed by a Jasco P-120
polarimeter. GCeMS analyses were performed with an Agilent
Technologies 6850 series II gas chromatograph (5% phenyl-
polymethylsiloxane capillary column, 30 m, 0.25 mm i.d.), equip-
ped with a 5973 Network mass-selective detector operating at
70 eV. The electrospray ionization [HRMS (ESI)] experiments were
carried out in a hybrid QqTOF mass spectrometer (PE SCIEXeQ-
STAR) equipped with an ion-spray ionisation source. MS (þ)
ppm; 13C NMR (100.62 MHz, CDCl3):
d
¼57.7, 58.8, 128.4, 129.3,
129.7, 133.3, 166.1 ppm; FTIR (CHCl3): 3028 (CeH arom.), 2981 and
2950 (CeH aliph.), 1722 (C]O), 1219 (NeO) cmꢁ1; GCeMS (70 eV):
m/z (%)¼358 (<1) [M]þ, 179 (5), 161 (10), 123 (12), 105 (100), 77
(65), 57 (30); HRMS (ESI): calcd for C18H19N2O6: (359.1243)
[MþH]þ; found: (359.1245).
4.3.2. trans-(S)-Benzoic acid 2-nitroso-3-phenypropyl ester dimer
(12b). Yield: 258 mg (96%), bright white needle-like crystals with
mp 110e111 ꢀC (diethyl ether). 1H NMR (400.13 MHz, CDCl3):
spectra were acquired by direct infusion (5
containing the appropriate sample (10 pmol
m
L minꢁ1) of a solution
ꢁ1) dissolved in
m
L
d
¼2.94 (2H, dd, J¼5.3 , 7.2 Hz, PhCH2), 4.52 (1H, dd, J¼3.4 , 11.7 Hz,
a solution 0.1% acetic acid, methanol/water (50:50) at the opti-
mum ion voltage of 4800 V. The nitrogen gas flow was set at 30 psi
(pounds per square inch) and the potentials of the orifice, the
focussing ring and the skimmer were kept at 30, 50 and 25 V
relative to ground, respectively. Melting points were determined
with an Electrothermal melting point apparatus and are un-
corrected. TLC was performed on Merck silica gel plates with
F-254 indicator; viewing was by UV light (254 nm). Column
chromatographies were performed on silica gel (63e200 mm)
using petroleum ether/diethyl ether (Et2O) or petroleum ether/
ethyl acetate (AcOEt) mixtures as eluents.
OCHH), 4.61 (1H, dd, J¼8.6 , 11.7 Hz, OeCHH), 6.02e6.09 (1H, m,
NeCH), 7.19e7.30 (7H, m, Ph), 7.41 (1H, t, J¼7.5 Hz, Ph), 7.80 (2H, d,
J¼7.9 Hz, Ph) ppm; 13C NMR (100.62 MHz, CDCl3):
¼34.5, 62.8,
d
66.1, 127.3, 128.2, 128.8, 129.2 (2C), 129.6, 133.1, 135.1, 165.8 ppm;
FTIR (CHCl3): 3031 (CeH arom.), 2958 and 2850 (CeH aliph.), 1722
(C]O), 1273 (NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼538 (<1) [M]þ,
24
269 (6), 147 (43), 130 (72), 117 (31), 105 (100), 91 (51), 77 (72). [a]
D
ꢁ104.6 (c 0.1, CHCl3); HRMS (ESI): calcd for C32H31N2O6: (539.2182)
[MþH]þ; found: (539.2185).
4.3.3. trans-(S)-Propionic acid 3-methyl-2-nitrosobutyl ester dimer
(12c). Yield: 171 mg (99%), pale yellow oil. 1H NMR (400.13 MHz,
4.2. General procedure for the synthesis of condensed
oxaziridines 8g,30 8h31 and 8i
CDCl3):
d
¼0.98 (3H, d, J¼6.8 Hz, CHCH3), 1.05 (3H, d, J¼6.8 Hz,
CHCH3), 1.12 (3H, t, J¼7.5 Hz, CH2CH3), 2.21e2.33 (3H, m, CH2CH3
and CHCH3), 4.34 (1H,dd, J¼9.5 , 11.7 Hz, OeCHH), 4.57 (1H, dd,
J¼3.0 , 11.7 Hz, OeCHH), 5.44 (1H, td, J¼3.0 , 9.5 Hz, NeHC) ppm;
To an ice cooled solution of the oxazolines 7geh or 2-methyl-1-
pyrroline 7i(1.0 mmol)inCH2Cl2 (10 mL)wasadded dropwisea small
excessofm-CPBA(270 mg,1.1 mmol, 70%)inCH2Cl2 (5 mL)previously
cooled in an ice bath. The reaction was taken under stirring and
cooling (0e5 ꢀC) for about 3 h and monitored by gas-chromatogra-
phy. When the reaction was completed, the organic mixture was
washed once with a dilute cooled solution of Na2S2O3 (5%, 10 mL),
then three time with 10 mL of a cooled solution of Na2CO3 (5%). After
drying over anhydrous Na2SO4, the mixture was concentrated in
vacuo affording the condensed oxaziridine as pure compound.
13C NMR (100.62 MHz, CDCl3):
d
¼8.7, 18.3, 19.4, 27.0, 28.0, 61.3,
70.7, 173.8 ppm; FTIR (CHCl3): 2974 and 2885 (CeH aliph.), 1738
(C]O), 1211 (NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼346 (<1)
24
[M]þ,173 (3), 156 (4), 99 (27), 69 (89), 57 (100); [
a
]
þ1.9 (c 0.1,
D
CHCl3); HRMS (ESI): calcd for C16H31N2O6: (347.2182) [MþH]þ;
found: (347.2181).
4.3.4. trans-(S)-Propionic acid 2-nitroso-3-phenylpropyl ester dimer
(12e). Yield: 217 mg (99%), green oil. 1H NMR (400.13 MHz,

2094
S. Perrone et al. / Tetrahedron 67 (2011) 2090e2095
CDCl3):
d
¼1.10 (3H, t, J¼7.5 Hz, CH2CH3), 2.26 (2H, q, J¼7.5 Hz,
m/z (%)¼230 (<1) [M]þ, 98 (55), 85 (10), 72 (100); HRMS (ESI): calcd
for C10H19N2O4: (231.1345) [MþH]þ; found: (231.1343).
CH2CH3), 2.78 (1H, dd, J¼7.5 , 14.0 Hz, HHCePh), 2.88 (1H, dd,
J¼7.5 , 14.0 Hz, HHCePh), 4.32 (1H, dd, J¼8.9 , 11.8 Hz, OeCHH),
4.39 (1H, dd, J¼3.6 , 11.8 Hz, OeCHH), 5.81e5.87 (1H, m, NeCH),
4.4. General procedure for the synthesis of oximes 13aef28
and 13i
7.14e7.27 (5H, m, Ph) ppm; 13C NMR (100.62 MHz, CDCl3):
d
¼8.8,
27.1, 34.2, 61.8, 66.1, 127.2, 128.6, 129.0, 129.7, 135.0, 173.6 ppm;
FTIR (CHCl3): 3027 (CeH arom.), 2945 (CeH aliph.), 1742 (C]O),
1181 (NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼442 (<1) [M]þ, 221
A solution of the azodioxy-carbonyl dimers 12aef,i (1.0 mmol)
in toluene (5 mL) was heated at reflux under magnetic stirring for
10e50 min. After this time, TLC was used to monitor reaction
progress. The solution was cooled to room temperature and evap-
orated to dryness to give a crude material. The reaction mixture was
purified by chromatography on silica gel (petroleum ether/ethyl
acetate¼70:30 for entries 1 and 5 of Table 3; petroleum ether/
diethyl ether¼70:30 for entries 3 and 6 of Table 3).
(8), 147 (62), 130 (100), 117 (89), 91 (82), 57 (63); [
a
]
24 ꢁ55.0 (c 0.1,
D
CHCl3); HRMS (ESI): calcd for C24H31N2O6: (443.2182) [MþH]þ;
found: (443.2180).
4.3.5. cis/trans Propionic acid 4-methyl-2-nitrosopentyl ester dimer
mixture (12f). Yield: 181 mg (97%), colourless oil. cis/trans Ratio
50:50 calculated by 1H NMR. 1H NMR (400.13 MHz, CDCl3):
d
¼0.92e0.96 (12H, m, CHCH3),1.07e1.16 (6H, m, CH2CH3),1.30e1.42
4.4.1. Benzoic acid 2-hydroxyiminoethyl ester (13a). Total yield:
177 mg (99%). Z-Isomer: yield: 102 mg (57%), white solid with mp
62e63 ꢀC (hexane). Rf (petroleum ether/ethyl acetate¼70:30):
(2H, m, CHCH2CH), 1.49e1.52 (2H, m, CHCH2CH), 1.84e1.91 (2H, m,
CH3CHCH3), 2.23e2.32 (4H, m, CH2CH3), 4.20e4.26 (2H, m, OeCH2),
4.39e4.44 (2H, m, OeCH2), 5.76e5.89 (2H, m, NeCH) ppm; 13C NMR
0.53; 1H NMR (400.13 MHz, CDCl3):
d
¼4.93 (2H, d, J¼5.6 Hz,
(100.62 MHz, CDCl3):
d¼8.8, 21.7, 21.9, 22.7, 24.7, 24.8, 27.1, 36.9, 37.3,
OeCH2), 7.45 (2H, t, J¼7.5 Hz, Ph), 7.58 (1H, t, J¼7.4 Hz, Ph), 8.07
(2H, t, J¼7.5 Hz, Ph), 7.65 (1H, t, J¼5.6 Hz, HC]N), 9.24 (1H, s,
broad, OH, exchanges with D2O) ppm; 13C NMR (100.62 MHz,
63.1, 63.2, 63.7,173.6,173.8 ppm; FTIR (CHCl3): 2962 and 2870 (CeH
aliph.), 1742 (C]O), 1453 and 1385 (NeO cis), 1199 (NeO trans)
cmꢁ1; GCeMS (70 eV): m/z (%)¼374 (<1) [M]þ, 187 (1), 145 (10), 113
(21), 75 (35), 57 (100); HRMS (ESI): calcd for C18H35N2O6: (375.2495)
[MþH]þ; found: (375.2491).
CDCl3):
d¼61.4, 128.4, 129.4, 129.8, 133.3, 146.4, 166.1 ppm; FTIR
(CHCl3): 3579 (free OH), 1722 (C]O), 1269 (CeO), 1113 (C]N),
920 (NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼179 (5) [M]þ, 161 (9),
123 (11), 105 (100), 77 (5), 57 (25); HRMS (ESI): calcd for
C9H10NO3: (180.0660) [MþH]þ; found: (180.0661). E-Isomer:
yield: 75 mg (42%), white solid with mp 65e66 ꢀC (hexane). Rf
(petroleum ether/ethyl acetate¼70:30): 0.59; 1H NMR
4.3.6. Propionic acid 2-methyl-2-nitrosopropyl ester dimer
(12g). Total yield: 156 mg (98%). trans-Isomer: yield: 124 mg (78%),
blue oil. 1H NMR (400.13 MHz, CDCl3):
d
¼1.13 (3H, t, J¼7.6 Hz,
CH2CH3), 1.60 [6H, s, C(CH3)2], 2.32 (2H, q, J¼7.6 Hz, CH2CH3), 4.39
(2H, s, OeCH2) ppm; 13C NMR (100.62 MHz, CDCl3):
(400.13 MHz, CDCl3):
d
¼5.18 (2H, d, J¼3.9 Hz, OeCH2), 6.99 (1H, t,
d
¼8.9, 23.1,
J¼3.9 Hz, HC]N), 7.48 (2H, t, J¼7.5 Hz, Ph), 7.58 (1H, t, J¼7.4 Hz,
27.3, 68.1, 86.1, 173.5 ppm; FTIR (film): 2983 and 2944 and 2884
(CeH aliph.), 1745 (C]O), 1181 (NeO) cmꢁ1; GCeMS (70 eV): m/z
(%)¼318 (<1) [M]þ, 159 (1), 129 (10), 57 (100); HRMS (ESI): calcd for
C14H27N2O6: (319.1869) [MþH]þ; found: (319.1871). cis-Isomer:
Ph), 8.07 (2H, t, J¼7.5 Hz, Ph), 9.50 (1H, s, broad, OH, exchanges
with D2O) ppm; 13C NMR (100.62 MHz, CDCl3):
d
¼58.8, 128.5,
129.4, 129.7, 133.4, 148.4, 166.2 ppm; FTIR (CHCl3): 3683 (free OH),
1723 (C]O), 1266 (CeO), 1117 (C]N), 920 (NeO) cmꢁ1; GCeMS
(70 eV): m/z (%)¼179 (5) [M]þ, 161 (9), 123 (11), 105 (100), 77 (5),
57 (25); HRMS (ESI): calcd for C9H10NO3: (180.0660) [MþH]þ;
found: (180.0662).
yield: 32 mg (20%), blue oil. 1H NMR (400.13 MHz, CDCl3):
d¼1.13
(3H, t, J¼7.6 Hz, CH2CH3), 1.15 [6H, s, C(CH3)2], 2.23 (2H, q, J¼7.6 Hz,
CH2CH3), 4.80 (2H, s, OeCH2) ppm; 13C NMR (100.62 MHz, CDCl3):
d
¼8.9, 23.5, 27.5, 68.7, 97.3, 173.8 ppm; FTIR (film): 2983 and 2944
and 2884 (CeH aliph.), 1743 (C]O), 1375 and 1348 (NeO) cmꢁ1
;
4.4.2. Z/E Benzoic acid 2-hydroxyimino-3-phenylpropyl ester mixture
(13b). Total yield: 258 mg (96%), white low melting solid. Rf
(petroleum ether/ethyl acetate¼70:30): 0.55; 1H NMR
GCeMS (70 eV): m/z (%)¼318 (<1) [M]þ, 159 (1), 129 (10), 57 (100);
HRMS (ESI): calcd for C14H27N2O6: (319.1869) [MþH]þ; found:
(319.1870).
(400.13 MHz, CDCl3):
d
¼3.69 (2H, s, PhCH2, E isomer), 3.88 (2H, s,
PhCH2, Z isomer), 4.84 (2H, s, OeCH2, Z isomer), 5.20 (2H, s,
OeCH2, E isomer), 7.18e7.27 (10H, m, Ph), 7.38e7.45 (4H, m, Ph),
7.55 (2H, t, J¼7.5 Hz, Ph), 7.92 (4H, d, J¼8.2 Hz, Ph), 8.60 (2H, s,
broad, OH, exchanges with D2O) ppm; 13C NMR (100.62 MHz,
4.3.7. Acetic acid 2-methyl-2-nitrosopropyl ester dimer (12h). Total
yield: 141 mg (97%). trans-Isomer: Yield: 93 mg (64%), green oil. 1H
NMR (400.13 MHz, CDCl3):
d
¼1.60 [6H, s, C(CH3)2], 2.05 (3H, s,
CH3CO), 4.38 (2H, s, OeCH2) ppm; 13C NMR (100.62 MHz, CDCl3):
CDCl3):
d
¼31.9, 37.4, 58.8, 64.2, 126.7, 126.8, 128.3, 128.6, 128.7,
d
¼20.4, 23.1, 68.2, 86.0, 170.1; FTIR (CHCl3): 2986 and 2850 (CeH
128.8, 129.1, 129.5, 129.7, 133.2, 135.8, 136.0, 155.0, 156.6,
165.9 ppm; FTIR (CHCl3): 3681 (free OH), 3309 (broad OH), 1722
aliph.), 1746 (C]O), 1213 (NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼
290 (<1) [M]þ, 115 (12), 55 (20), 43 (100); HRMS (ESI): calcd for
C12H23N2O6: (291.1556) [MþH]þ; found: (291.1554). cis-Isomer:
(C]O), 1271 (CeO), 1113 (C]N), 940 (NeO) cmꢁ1
; GCeMS
(70 eV): m/z (%)¼269 (7) [M]þ, 147 (43), 130 (72), 117 (76), 105
(100), 91 (51), 77 (80); HRMS (ESI): calcd for C16H16NO3:
(270.1130) [MþH]þ; found: (270.1128).
Yield: 48 mg (33%), green oil. 1H NMR (400.13 MHz, CDCl3):
d¼1.12
[6H, s, C(CH3)2], 1.94 (3H, s, CH3CO), 4.77 (2H, s, OeCH2) ppm; 13C
NMR (100.62 MHz, CDCl3):
d
¼18.1, 24.7, 66.7, 97.2, 170.2; FTIR
(CHCl3): 2986 and 2850 (CeH aliph.), 1746 (C]O), 1377 and 1350
(NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼290 (<1) [M]þ, 115 (12), 55
(20), 43 (100); HRMS (ESI): calcd for C12H23N2O6: (291.1556)
[MþH]þ; found: (291.1555).
4.4.3. Propionic acid 2-hydroxyimino-3-methylbutyl ester (13c).
Total yield 169 mg (98%). Z-Isomer: Yield: 84 mg (49%), pale yel-
low oil. Rf (petroleum ether/diethyl ether¼70:30): 0.52; 1H NMR
(400.13 MHz, CDCl3):
d
¼1.11 [6H, d, J¼7.0 Hz, CH(CH3)2], 1.12 (3H,
t, J¼7.6 Hz, CH2CH3), 2.36 (2H, q, J¼7.6 Hz, CH2CH3), 3.37 [1H,
eptet, J¼7.0 Hz, CH(CH3)2], 4.66 (2H, s, OeCH2), 8.75 (1H, s, broad,
OH, exchanges with D2O) ppm; 13C NMR (100.62 MHz, CDCl3):
4.3.8. trans-5-Nitrosopentan-2-one dimer (12i). Yield: 112 mg
(98%), orange oil. 1H NMR (400.13 MHz, CDCl3):
d
¼2.14 (2H, quintet,
J¼6.7 Hz, CH2CH2CH2), 2.16 (3H, s, CH3CO), 2.60 (2H, t, J¼6.7 Hz,
d
¼8.9, 18.5, 25.9, 27.4, 62.2, 64.3, 159.9, 173.9 ppm; FTIR (CHCl3):
CH2CO), 4.27 (2H, t, J¼6.7 Hz, NeCH2) ppm; 13C NMR (100.62 MHz,
3582 (free OH), 3305 (broad OH), 2975, 2941 and 2885 (CeH
aliph.), 1737 (C]O), 1266 (CeO), 1182 and 1082 (C]N), 920
(NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼173 (2) [M]þ, 156 (4), 99
CDCl3):
d
¼19.0, 29.9, 40.0, 58.1, 206.8 ppm; FTIR (CHCl3): 2960 and
2862 (CeH aliph.), 1716 (C]O), 1213 (NeO) cmꢁ1; GCeMS (70 eV):

S. Perrone et al. / Tetrahedron 67 (2011) 2090e2095
2095
(28), 69 (91), 57 (100); HRMS (ESI): calcd for C8H16NO3: (174.1130)
[MþH]þ; found: (174.1130). E-Isomer: Yield: 84 mg (49%), pale
yellow oil. Rf (petroleum ether/diethyl ether¼70:30): 0.59; 1H
(NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼187 (<1) [M]þ, 145 (9), 113
(21), 75 (33), 57 (100); HRMS (ESI): calcd for C9H18NO3: (188.1286)
[MþH]þ; found: (188.1283).
NMR (400.13 MHz, CDCl3):
d
¼1.11 [6H, d, J¼6.9 Hz, CH(CH3)2], 1.16
(3H,t, J¼7.6 Hz, CH2CH3), 2.38 (2H, q, J¼7.6 Hz, CH2CH3), 2.64 [1H,
eptet, J¼6.9 Hz, CH(CH3)2], 4.98 (2H, s, OeCH2), 8.75 (1H, s, broad,
OH, exchanges with D2O) ppm; 13C NMR (100.62 MHz, CDCl3):
Acknowledgements
Thanks are due to the University of Salento and C.I.N.M.P.I.S.
(Consorzio Interuniversitario Nazionale Metodologie e Processi
Innovativi di Sintesi) for financial support.
d
¼9.0, 19.8, 27.5, 30.5, 57.8, 160.7, 173.8 ppm; FTIR (CHCl3): 3587
(free OH), 3283 (broad OH), 2974, 2939 and 2886 (CeH aliph.),
1738 (C]O), 1266 (CeO), 1182 and 1082 (C]N), 920 (NeO) cmꢁ1
;
GCeMS (70 eV): m/z (%)¼173 (2) [M]þ, 156 (4), 99 (28), 69 (91), 57
(100); HRMS (ESI): calcd for C8H16NO3: (174.1130) [MþH]þ; found:
(174.1132).
Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2011.01.054.
4.4.4. Propionic acid 2-hydroxyimino-3-phenylpropyl ester (13e).
Total yield: 219 mg (99%). Z-Isomer: yield: 146 mg (66%), yellow oil.
Rf (petroleum ether/ethyl acetate¼70:30): 0.51; 1H NMR
References and notes
(400.13 MHz, CDCl3):
d¼1.10 (3H, t, J¼7.5 Hz, CH2CH3), 2.29 (2H, q,
1. Chakrapani, H.; Bartberger, M. D.; Toone, E. J. Org. Chem. 2009, 74, 1450e1453.
2. Brennan, P. A.; Moncada, S. Ann. R. Coll. Surg. Engl. 2002, 84, 75e78.
3. Snyder, S. H. Science 1992, 257, 494e496.
J¼7.5 Hz, CH2CH3), 3.80 (2H, s, PhCH2), 4.60 (2H, s, OeCH2), 7.16e7.32
(5H, m, Ph), 8.75 (1H, s, broad, OH, exchanges with D2O) ppm; 13C
€
4. Forstermann, U.; Boissel, J.-P.; Kleinert, H. FASEB J. 1998, 12, 773e790.
NMR (100.62 MHz, CDCl3):
d
¼8.9, 27.2, 31.8, 63.4, 126.7, 128.6, 129.0,
5. Channon, K. M.; Qian, H. S.; George, S. E. Arterioscler., Thromb., Vasc. Biol. 2000,
20, 1873e1881.
6. Fujiwara, N.; Osanai, T.; Kamada, T.; Katoh, T.; Takahashi, K.; Okumura, K. Cir-
culation 2000, 101, 856e861.
7. Ignarro, L. J.; Napoli, C.; Loscalzo, J. Circ. Res. 2002, 90, 21e28.
8. Lee, J.; Chen, L.; West, A. H.; Richter-Addo, G. B. Chem. Rev. 2002, 102,
1019e1065.
9. Gowenlock, B. G.; Richter-Addo, G. B. Chem. Rev. 2004, 104, 3315e3340.
10. Lee, T. D.; Keana, J. F. W. J. Org. Chem. 1976, 41, 3237e3241.
11. Taylor, K. G.; Chi, M. S.; Clark, M. S. J. Org. Chem. 1976, 41, 1131e1135.
12. Emmons, W. D. J. Am. Chem. Soc. 1957, 79, 6522e6524.
13. Chilton, H. T. J.; Gowenlock, B. G. J. Chem. Soc. 1954, 3174e3178.
14. Fabio, M.; Ronzini, L.; Troisi, L. Tetrahedron 2007, 63, 12896e12902.
15. Troisi, L.; De Lorenzis, S.; Fabio, M.; Rosato, F.; Granito, C. Tetrahedron: Asym-
metry 2008, 19, 2246e2251.
16. Fabio, M.; Ronzini, L.; Troisi, L. Tetrahedron 2008, 64, 4979e4984.
17. Troisi, L.; Ronzini, L.; Rosato, F.; Videtta, V. Synlett 2009, 1806e1808.
18. Emmons, W. D. J. Am. Chem. Soc. 1956, 78, 6208e6209; Widmer, J.; Keller-
Schierlein, W. Helv. Chim. Acta 1974, 57, 657e664.
135.5, 154.9, 173.8 ppm; FTIR (CHCl3): 3579 (free OH), 3295 (broad
OH), 3028 (CeH arom.), 2941 (CeH aliph.), 1739 (C]O), 1266 (CeO),
1177 and 1083 (C]N), 920 (NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼
221 (8) [M]þ, 147 (78), 130 (100), 117 (85), 91 (83), 57 (73); HRMS
(ESI): calcd for C12H16NO3: (222.1130) [MþH]þ; found: (222.1130); E-
Isomer: yield: 73 mg (33%), yellow oil. Rf (petroleum ether/ethyl
acetate¼70:30): 0.56; 1H NMR (400.13 MHz, CDCl3):
¼1.09 (3H, t,
d
J¼7.5 Hz, CH2CH3), 2.27 (2H, q, J¼7.5 Hz, CH2CH3), 3.61 (2H, s,
PhCH2), 4.95 (2H, s, OeCH2), 7.16e7.32 (5H, m, Ph), 8.75 (1H, s, broad,
OH, exchanges with D2O) ppm; 13C NMR (100.62 MHz, CDCl3):
d
¼8.9, 29.7, 37.4, 58.2, 126.8, 128.8, 129.0, 136.1, 156.6, 173.7 ppm;
FTIR (CHCl3): 3582 (free OH), 3289 (broad OH), 3028 (CeH arom.),
2941 (CeH aliph.), 1738 (C]O), 1266 (CeO), 1177 and 1084 (C]N),
920 (NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼221 (8) [M]þ, 147 (78),
130 (100),117 (85), 91 (83), 57 (73); HRMS (ESI): calcd for C12H16NO3:
(222.1130) [MþH]þ; found: (222.1129).
19. McKennon, M. J.; Meyers, A. I.; Drauz, K.; Schwarm, M. J. Org. Chem. 1993, 58,
3568e3571.
20. Kamata, K.; Agata, I.; Meyers, A. I. J. Org. Chem. 1998, 63, 3113e3116.
21. Crystal data for compound 12a: C18
H
18N2O6, Fw¼358.34, T¼93 K, monoclinic,
ꢀ
space group P21/c, a¼5.5243 (4), b¼8.6318 (8), c¼17.6998 (16) A,
b
¼94.366 (3),
4.4.5. Propionic acid 2-hydroxyimino-4-methylpentyl ester (13f).
Total yield: 185 mg (99%). Z-Isomer: yield: 123 mg (66%), pale green
oil. Rf (petroleum ether/diethyl ether¼70:30): 0.56; 1H NMR
ꢀ
V¼841.56 (12) A3, Z¼2, Dx¼1.414 Mg mꢁ3,
dimensions 0.44ꢂ0.24ꢂ0.14 mm3, ¼0.71073 A (Mo K
monochromator, Bruker SMART-APEX CCD diffractometer, equipped with
m
(Mo K
a
)¼0.108 mmꢁ1; crystal
ꢀ
l
a
) radiation, graphite
a Bruker KRYOFLEX low temperature device. Data collection:
u and 4 scan mode,
(400.13 MHz, CDCl3):
d
¼0.87 [6H, d, J¼6.7 Hz, CH(CH3)2],1.08 (3H, t,
2
q
<60ꢀ; 9958 collected reflections, 3072 unique, merging R¼0.0223. The struc-
J¼7.7 Hz, CH2CH3), 1.93e2.03 [m, 1H, CH(CH3)2], 2.22 (2H, d,
J¼7.5 Hz, CHCH2), 2.31 (2H, q, J¼7.7 Hz, CH2CH3), 4.56 (2H, s,
OeCH2), 8.70 (1H, s, broad, OH, exchanges with D2O) ppm; 13C NMR
ture was solved by SIR2002 ( Burla, M. C.; Camalli, M.; Carrozzini, B.; Cascarano, G.
L.; Giacovazzo, C.; Polidori, G.; Spagna, R. J. Appl. Crystallogr. 2003, 36, 1103 ) and
refined by full-matrix least-squaresbased on Fo2, using SHELXL97 (Sheldrick, G.M.,
Acta Cryst, 2008, A64, 112e122). H atoms were refined isotropically. The final
consistency index were R¼0.0458 and wR¼0.1028 [0.0367 and 0.0967, re-
(100.62 MHz, CDCl3):
d¼8.86, 22.6, 25.6, 27.3, 34.6, 64.1, 155.8,
spectively for 2552 reflections with Io>2.
s
(Io)]; goodness-of-fit¼1.065. Detailed
173.9 ppm; FTIR (CHCl3): 3583 (free OH), 3286 (broad OH), 2960
(CeH aliph.), 1730 (C]O), 1266 (CeO), 1183 and 1083 (C]N), 920
(NeO) cmꢁ1; GCeMS (70 eV): m/z (%)¼187 (<1) [M]þ, 145 (9), 113
(21), 75 (33), 57 (100); HRMS (ESI): calcd for C9H18NO3: (188.1286)
[MþH]þ; found: (188.1285). E-Isomer: yield: 62 mg (33%), pale
green oil. Rf (petroleum ether/diethyl ether¼70:30): 0.61; 1H NMR
crystallographic data were deposited as CCDC 782701 with the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.
22. Greer, M. L.; Sarker, H.; Mendicino, M. E.; Blackstock, S. C. J. Am. Chem. Soc. 1995,
117, 10460e10467.
23. Xu, Q.; Li, Z. Tetrahedron Lett. 2009, 50, 6838e6840.
24. May, A. E.; Willoughby, P. H. J. Org. Chem. 2008, 73, 3292e3294.
25. Schwekendiek, K.; Glorius, F. Synthesis 2006, 18, 2996e3002.
26. Kurth, M. J.; Decker, O. H. W.; Hope, H.; Yanuck, M. D. J. Am. Chem. Soc. 1985, 107,
443e448.
27. Kurth, M. J.; Decker, O. H. W. J. Org. Chem. 1985, 50, 5769e5775.
28. Aitken, R. A.; Armstrong, D. P. Arkivoc 2000, iii, 186e192.
29. Zhou, A.; Njogu, M. N.; Pittman, C. U. Tetrahedron 2006, 62, 4093e4102.
30. Videtta, V.; Perrone, S.; Rosato, F.; Alifano, P.; Tredici, M. S.; Troisi, L. Synlett
2010, 18, 2781e2783.
(400.13 MHz, CDCl3):
d
¼0.84 [6H, d, J¼6.6 Hz, CH(CH3)2], 1.10 (3H, t,
J¼7.7 Hz, CH2CH3), 1.78e1.85 [1H, m, CH(CH3)2], 2.05 (2H, d,
J¼7.2 Hz, CHCH2), 2.32 (2H, q, J¼7.7 Hz, CH2CH3), 4.90 (2H, s,
OeCH2), 8.70 (1H, s, broad, OH, exchanges with D2O) ppm; 13C NMR
(100.62 MHz, CDCl3):
173.7 ppm; FTIR (CHCl3): 3586 (free OH), 3286 (broad OH), 2960
d
¼8.86, 22.3, 25.9, 27.3, 39.6, 58.8, 156.5,
31. Ashburn, S. P.; Coates, R. M. J. Org. Chem. 1984, 49, 3127e3133.
(CeH aliph.), 1738 (C]O), 1260 (CeO), 1183 and 1084 (C]N), 922
32. Minato, T.; Yamabe, S.; Oda, H. Can. J. Chem. 1982, 60, 2740e2748.