Acid-catalyzed aza-Diels-Alder versus 1,3-dipolar cycloadditions of methyl glyoxylate oxime with cyclopentadiene

Article abstract of DOI:10.1016/j.tetlet.2008.07.110

The acid-catalyzed 1,4- and 1,3-cycloadditions between methyl glyoxylate oxime (1) and cyclopentadiene were investigated using various Lewis and/or Bronsted acids at different temperatures in dichloromethane as solvent. Besides the expected new adducts, (±)-methyl [(3-exo)-2-hydroxy-2-azabicyclo[2.2.1]hept-5-ene]-3-carboxylate (2) and (±)-methyl [(3-endo)-2-hydroxy-2-azabicyclo[2.2.1]hept-5-ene]-3-carboxylate (3), a third adduct, (±)-methyl (1R,4R,5R)-(2-oxa-3-azabicyclo[3.3.0]oct-7-ene)-4-carboxylate (4), whose formation can be explained by a 1,3-dipolar cycloaddition, was obtained. Yields and product ratios were found to be more dependent on the catalyst than on the temperature; these results and the stereochemistry of the adducts, confirmed by spectroscopic data (¹H and ¹³C NMR) and by X-ray crystallography, were used to analyze and propose a mechanistic explanation for both cycloadditions.

Full text of DOI:10.1016/j.tetlet.2008.07.110

Tetrahedron Letters 49 (2008) 5777–5781
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Acid-catalyzed aza-Diels–Alder versus 1,3-dipolar cycloadditions
of methyl glyoxylate oxime with cyclopentadiene
b
Carlos A. D. Sousa a, M. Luísa C. Vale a, José E. Rodríguez-Borges a, , Xerardo Garcia-Mera ,
*
Jesús Rodríguez-Otero c
a CIQ-Departamento de Química, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal
b Departamento de Química Orgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain
c Departamento de Química Física, Facultade de Química, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The acid-catalyzed 1,4- and 1,3-cycloadditions between methyl glyoxylate oxime (1) and cyclo-
pentadiene were investigated using various Lewis and/or Bronsted acids at different temperatures in
dichloromethane as solvent. Besides the expected new adducts, ( )-methyl [(3-exo)-2-hydroxy-2-azabi-
cyclo[2.2.1]hept-5-ene]-3-carboxylate (2) and ( )-methyl [(3-endo)-2-hydroxy-2-azabicyclo[2.2.1]hept-
5-ene]-3-carboxylate (3), a third adduct, ( )-methyl (1R,4R,5R)-(2-oxa-3-azabicyclo[3.3.0]oct-7-ene)-4-
carboxylate (4), whose formation can be explained by a 1,3-dipolar cycloaddition, was obtained. Yields
and product ratios were found to be more dependent on the catalyst than on the temperature; these
results and the stereochemistry of the adducts, confirmed by spectroscopic data (1H and 13C NMR) and
by X-ray crystallography, were used to analyze and propose a mechanistic explanation for both
cycloadditions.
Received 26 May 2008
Revised 17 July 2008
Accepted 21 July 2008
Available online 24 July 2008
Keywords:
Aza-Diels–Alder reaction
1,3-Dipolar cycloaddition
Glyoxylate oxime
Isoxazolidines
Ó 2008 Elsevier Ltd. All rights reserved.
2-Hydroxy-2-azabicyclo[2.2.1]heptenes
The great versatility of cycloadditions, their high stereochemi-
cal control and the fair predictability of their regiochemistry allied
to the rapid accumulation of polyfunctionality in a relatively small
molecular framework have contributed to the popularity of these
reactions.1 Within the diverse transformations comprising cyc-
loadditions, aza-Diels–Alder reactions of imine derivatives and
dienes leading to six-membered aza-heterocycles, monocyclic
and bicyclic molecules, have attracted much interest, especially
those employing cyclopentadiene as starting material.2,3 The imi-
nes, used as aza-dienophiles, generally require activation by an
electron-withdrawing group and a Lewis acid (LA) and/or Bronsted
acid (BA) to participate in these [4+2] cycloaddition reactions.3 It
has been shown that the electronic nature of the substituents at
the diene/dienophile pair may strongly influence the reaction
pathways and determine either a concerted mechanism (synchro-
nous or asynchronous) or a stepwise one.4 In addition, experimen-
talists have always employed catalysts to change the kinetics of
this class of reactions. In particular, a wide range of homogeneous
and heterogeneous Lewis acids have been used to improve the rate
and exo/endo selectivities of these cycloadditions.2,3
iminium cation complex that rapidly undergoes cycloaddition
under mild conditions. The products obtained, 2-azabicyclo-
[2.2.1]hept-5-enes,3 can be used as precursors of a large variety
of compounds of chemical, biological and pharmaceutical interest,
such as proline mimetic structures.5 N-Hydroxylimines (oximes)
bearing electron-withdrawing groups, on both carbon and oxygen,
have been used upon occasion as imino dienophiles.6 Fleury and
co-workers investigated cycloadditions of O-protected oxime
derivatives (XYC = NOR) with cyclopentadiene to afford the corres-
ponding adducts with low to moderate yields.6a–c Nonetheless,
aza-Diels–Alder reactions using non-O-functionalized oximes have
never been reported in the literature, resulting in an unknown
behaviour of the hydroxyl group bound to the nitrogen atom.
The resulting N-hydroxyl-2-azabicycloalkenes would be an impor-
tant and versatile group of synthons useful in the preparation of
new pyrrolidinic derivatives.5
It is well known that LAs often increase not only the rate of the
Diels–Alder reactions but also their selectivity. Thus, we decided to
investigate, in this work, the influence of several LAs and their
advantages/disadvantages relatively to BAs in the aza-Diels–Alder
reaction between cyclopentadiene and methyl glyoxylate oxime
(1) to afford the corresponding exo/endo adducts (Scheme 1).
Methyl glyoxylate oxime (1)8a was obtained by treatment of
methyl 2-hydroxy-2-methoxyacetate (methyl hemiacetal of
methyl glyoxylate)7 with equimolar amounts of hydroxylamine
hydrochloride, triethylamine and a catalytic amount of DMAP, in
Reports on cycloadditions between iminodienophiles of glyoxy-
lates and cyclopentadiene showed these reactions to be highly
accelerated by the addition of a LA, due to the formation of an
* Corresponding author. Tel.: +351 226082864; fax: +351 226082959.
E-mail address: jrborges@fc.up.pt (J. E. Rodríguez-Borges).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.110

5778
C. A. D. Sousa et al. / Tetrahedron Letters 49 (2008) 5777–5781
OH
HO
OH
HO
H
N
N
+
N
CO2Me
cycloadducts
G
CO2Me
OH
pyrrolidinic
derivatives
1
G= CH2OH, CO2H, CO2R
Scheme 1. Retrosynthetic analysis of pyrrolidinic derivatives from cycloadducts of glyoxylate oxime 1 and cyclopentadiene.
dry CH2Cl2 at room temperature.8 The E-configuration of oxime
1 has been unambiguously assigned by X-ray crystallography
(Fig. 1).
Treatment of oxime 1 with freshly distilled cyclopentadiene
(2 equiv) and acid (TFA, BF3ꢀEt2O, AlCl3, ZnI2 or HClO4) in CH2Cl2
under an argon atmosphere at different temperatures (ꢁ78 °C,
ꢁ20 °C and ꢁ12 °C) yielded a mixture of the exo and endo formally
[4+2] aza-Diels–Alder cycloadducts 2 and 3, together with the
formally [3+2] cycloadduct 4 (Scheme 2).
The products were isolated from the reaction mixture by chro-
matographic purification and identified by analytical and spectro-
scopic techniques.9 Thus, the endo-configuration of cycloadduct 3
has been confirmed by X-ray crystallography (Fig. 2).
The structure and stereochemistry of cycloadduct 4 were estab-
lished not only in terms of its spectral data, but also based on the
spectral data and X-ray diffraction studies of the corresponding
3,5-dinitrobenzoate derivative ( )-5 (Fig. 3). Furthermore, the ratio
of adducts obtained, for each reaction, was also confirmed by GC
(Table 1).
On checking the literature for 1,3-dipolar cycloadditions,10
there are some reports on oximes undergoing 1,3-dipolar cycload-
ditions via the nitrone tautomer with alkenes (dipolarophiles) to
afford isoxazolidines.10h–j Nonetheless, 1,3-polar cycloadditions
using non-O-functionalized oximes have never been reported in
literature, resulting in an unknown behaviour of the hydroxyl
group bound to the nitrogen atom. The presence of a nitrogen atom
within the resulting isoxazolidine ring makes this heterocyclic
moiety especially attractive for the synthesis of a number of alka-
loids, and other nitrogen-containing natural products, and many
products of potential interest.10
Concerning the effect of temperature on product ratio and yield,
when Lewis acids were used as catalysts, little or no change was
observed when the temperature was raised from ꢁ78 °C to
ꢁ12 °C. However, with TFA, a significant modification in both ratio
of 2/4 and product yield occurred. When the reaction was per-
formed at ꢁ20 °C during 48 h, and/or using excess of acid (2 equiv),
a decrease in the yield was verified (all these experiments resulted
in the formation of a large amount of a polymer, which may indi-
cate some degradation of the products). The dependence of the
ratios of adducts (mainly 2/4), when using Bronsted acids, on the
experimental conditions is not yet fully understood and is under
further investigation.
In order to confirm whether adduct 4 resulted from Meisenhei-
mer rearrangement11 of 2 or 3, or was formed via an independent
pathway, these adducts (2 and 3) were subjected to the same reac-
tion conditions of the cycloaddition (except Cp) during 5 h. No
trace of 4 was detected in the reaction mixture, thus confirming
the independent pathway hypothesis.
Generally, most oximes undergo the normal Beckmann rear-
rangement in the presence of certain acids, including Lewis acids,
or under neutral conditions to yield an amide or a mixture of
Figure 1. X-ray crystallographic structure of oxime 1.
H
CO2CH3
+
OH
O
O
H
N
NH
LA or BA
N
+
Me
O
N OH
CH2Cl2 , 5 or 48 h
H
CO2CH3
OH
( )-2 - exo
CO2CH3
( )-4
T = -78, -20 or -12 ºC
1
( )-3 - endo
DNB-Cl
Et3N/DMAP
CH2Cl2
H2NOH.HCl
Et3N/DMAP
CH2Cl2
93%
O2N
99%
NO2
H
O
H
O
OH
N
O
Me
O
OMe
H
CO2CH3
hemiacetal of
methyl glyoxylate
( )-5
Scheme 2. Products of cycloaddition between oxime 1 and Cp, and 3,5-dinitrobenzoyl derivative of adduct 4.

C. A. D. Sousa et al. / Tetrahedron Letters 49 (2008) 5777–5781
5779
Table 1
Cycloaddition reactions of cyclopentadiene (2 equiv) with oxime 1
Entry
T (°C)
ꢁ78
Reaction time (h)
5
Acid
Yielda (%)
2/3/4 ratiob,c (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
—
TFA
BF3
AlCl3
ZnI2
TFA
—
—/—/traces
32/15/53
6/14/80
26
44
32
11
65
48
29
12
60
46
24
10
9
0/42/58
27/19/54
25/13/62
5/18/77
ꢁ12
ꢁ20
5
BF3
AlCl3
ZnI2
HClO4
TFA
0/38/62
26/21/53
28/21/51
18/14/68
5/18/77
0/40/60
26/22/52
40/18/42
48
BF3
Figure 2. X-ray crystallographic structure of endo adduct 3.
AlCl3
ZnI2
HClO4
52
Yield (%) and ratio (%) of adducts obtained at different temperatures using different
acids (1 equiv) in CH2Cl2.
a
Isolated yield after aqueous work-up, trituration with methanol and filtration
through a pad of Celite/silica.
b
Adduct ratios determined by yield of pure, isolated compounds (flash chro-
matography), with recovery of oxime 1.
c
Adduct ratios determined by GC (see Supplementary data).
LANL2DZ was used.14 All calculations were carried out with GAUSS-
IAN03 program.15
Recent studies devoted to Diels–Alder and 1,3-dipolar cycload-
dition reactions have shown that the global indexes defined in the
context of DFT theory are a powerful tool to understand the behav-
iour of polar cycloadditions16 or highly asynchronous concerted
cycloadditions.3b The difference of global electrophilicity between
the reagent pair,
of the process and thereby the feasibility of the cycloaddition.
The global electrophilicity index, , has been defined by Parr et
al.17 by the following simple expression: 2/2
= ( ), in terms of
the electronic chemical potential, , and the chemical hardness,
. Both quantities may be approached in terms of the one electron
energies of the frontier molecular orbital HOMO and LUMO, H and
L, as L)/2 and ꢂ (eL
ꢂ (eH
H), respectively.18 Table 2 shows
Dx, can be used to predict the polar character
x
x
l
g
l
g
e
e
l
+
e
g
+ e
Figure 3. X-ray crystallographic structure of compound 5.
the calculated parameters for the reactants 1 and Cp, and for the
intermolecular complexes involved in the cycloadditions catalyzed
by BA and LA; several interesting conclusions can be drawn from
this table. First, it is worth noting that protonation (corresponding
to BA) or coordination (corresponding to LA) to the carbonyl oxy-
gen or oxime nitrogen atoms of 1 gives rise to complexes of similar
electron energies. Therefore, these complexes can be in equilib-
rium, opening the reactive channels for the formation of the for-
mally [4+2] and [3+2] cycloadducts. The low electrophilicity of 1
amides, and a wide variety of examples are listed in reviews.12
When we performed the referred cycloaddition reactions, we were
not able to isolate (or detect) any amide or nitrile, or their adduct
derivatives. This may be due to the syn geometry of the hydrogen
atom (E-oxime), which does not allow the occurrence of the
referred rearrangement; on the other hand, oxime isomerization
is not probable at low temperatures.
(1.77 eV), which leads to a value of only 0.94 eV for Dx, is the rea-
In an attempt to explain the stereochemical outcome of the 1,3-
dipolar and aza-Diels–Alder reactions, we present in Scheme 3
three models for the approach of diene/dienoplile and diene/1,3-
dipole.
son for the high temperature required to perform the uncatalyzed
reaction. In contrast, protonation of 1 or formation of LA complexes
increases considerably the electrophilicity of this reactant, which
increases
Dx values and, therefore, favours the polar character of
Although in this scheme the catalyst (H or M = BF3, AlCl3 and
ZnI2) is arbitrarily coordinated to the nitrogen atom, there is the
possibility of coordination to the oxygen atom. Besides the
cycloadducts 2/3/4, no more isomers have been obtained.
For the interpretation of the experimental results, at least in a
qualitative way, some quantum chemical calculations have been
carried out.
Calculations were carried out with DFT (density functional the-
ory) employing B3LYP functional. B3LYP combines the three-co-
efficient dependent hybrid functional for the exchange energy
proposed by Becke (B3) with the correlation functional proposed
by Lee, Yang and Parr (LYP).13 6-31G(d) Pople’s basis set were used
for all elements except iodine, for which the effective core potential
the process and the feasibility of the cycloaddition. The increment
in electrophilicity is much more noticeable for BA than for LA,
which is in general agreement with the higher yield obtained with
BA.
Regarding the LAs, AlCl3 and ZnI2 are able to form an intermo-
lecular complex in which the metal is coordinated simultaneously
to the carbonyl oxygen and the oxime nitrogen atom; this may be
due to their large size. However, there is a clear difference between
these two LAs: only in the case of ZnI2, this dicoordinated complex
is clearly more favourable than the other two possible monocoor-
dinated complexes. This fact makes it possible that ZnI2 activates
electrophilically the
a and b positions of 1, simultaneously. This
behaviour is in agreement with the ratio of the 1,3-cycloaddition

5780
C. A. D. Sousa et al. / Tetrahedron Letters 49 (2008) 5777–5781
Aza-Diels-Alder
[4+2] cycloaddition
1,3-Dipolar cycloaddition
[3+2] cycloaddition
MeO2C
H
N
H
1
H
H
S
O
H
HO
OH
H
MeO2C
N
N
S
3
S
H
work up
(HCO3 )
CO2Me
H
-
(1R,3endo)
(1S,3exo)
work up
-
(HCO3 )
SI face
SI face
a
exo
approach
LA
O
b
LA
(H/M)
c
(H/M)
endo
approach
H
O
N
O
H
N
O
MeO
MeO
H
H
RE face
RE face
work up
(HCO3 )
work up
(HCO3 )
H
CO2Me
H
-
-
MeO2C
N
HO
H
N
OH
H
MeO2C
H
N
H
H
R
O
R
R
H
(1S,3endo)
(1R,3exo)
Scheme 3. Cycloaddition of oxime 1 and Cp. (a) oxime 1 acts as a dienophile and Cp as diene, affording exo adduct; (b) oxime 1 acts as a dienophile and Cp as diene, affording
endo adduct; (c) oxime 1 is the ‘four-electron component’ and Cp acts as polarophile in the [4+2] cycloaddition reaction. During work-up, deprotonation of the nitrogen atom
takes place.
The analysis of the endo/exo selectivity would require a deeper
Table 2
computational study, which implies that all the transition states
must be optimized for all the possible catalyzed reactions. How-
ever, some conclusions can be inferred from the geometries of
the intermolecular complexes. So, while the bulky AlCl3 catalyst
affords total endo selectivity due to the hindrance of the exo
approach, the smaller BF3 allows obtaining some amount of exo
cycloadduct. On the other hand, the ZnI2 complex yields a reverse
exo selectivity as a consequence of the double coordination (N,O)
that disfavours the endo approach of Cp to the N@C bond. Never-
theless, the energies and geometries of the transition states should
be known in order to better explain the observed selectivities.
In conclusion, we have shown that glyoxylate oximes can act
either as dienophiles or as 1,3-dipoles when reacting with 1,3-
dienes, giving rise to the corresponding cycloadducts by indepen-
dent highly asynchronous concerted mechanisms. Both reactions
occur by acid-mediated catalysis. According to the results
obtained, the 1,3-dipolar cycloaddition seems to be kinetically
more favourable. Further developments of the asymmetric
cycloadditions between glyoxylate oximes and 1,3-dienes are in
progress in our laboratory.
Computed parameters for 1, Cp, protonated 1 and intermolecular complexes formed
between 1 and LA: electron energy (a.u.), HOMO and LUMO energies (a.u.), electronic
chemical potential (a.u.), chemical hardness (a.u.) and electrophilicity (eV)
E
eHOMO
eLUMO
l
g
x
1
Cp
ꢁ397.68341 ꢁ0.27938 ꢁ0.05897 ꢁ0.1692 0.2204
ꢁ194.10106 ꢁ0.21153 ꢁ0.00987 ꢁ0.1107 0.2017
1.77
0.83
1–H+(N)
1–H+(O)
1–BF3(N)
1–BF3(O)
1–AlCl3(N)
1–AlCl3(O)
ꢁ398.01179 ꢁ0.48789 ꢁ0.30242 ꢁ0.3952 0.1855 11.46
ꢁ398.00985 ꢁ0.47199 ꢁ0.28373 ꢁ0.3779 0.1883 10.32
ꢁ722.25781 ꢁ0.30706 ꢁ0.09736 ꢁ0.2022 0.2097
ꢁ722.25220 ꢁ0.30535 ꢁ0.09879 ꢁ0.2021 0.2066
2.65
2.69
3.69
3.57
4.13
4.28
3.36
4.58
ꢁ2020.96315 ꢁ0.30491 ꢁ0.13038 ꢁ0.2176 0.1745
ꢁ2020.96756 ꢁ0.28674 ꢁ0.12511 ꢁ0.2059 0.1616
1–AlCl3(NO)a ꢁ2020.96557 ꢁ0.27980 ꢁ0.13705 ꢁ0.2084 0.1428
1–ZnI2(N)
1–ZnI2(O)
1–ZnI2(NO)a
ꢁ2199.69821 ꢁ0.24201 ꢁ0.13127 ꢁ0.1866 0.1107
ꢁ2199.68703 ꢁ0.24171 ꢁ0.11373 ꢁ0.1777 0.1280
ꢁ2199.70691 ꢁ0.23129 ꢁ0.13284 ꢁ0.1821 0.0985
a
Metal is coordinated simultaneously to the carbonyl oxygen and the oxime
nitrogen atom.
to the aza-Diels–Alder products observed experimentally, as only
with ZnI2 as catalyst, a ratio of approximately 1:1 is obtained for
all the temperatures. For BF3, this ratio is the highest (3–4:1), so
1,3-polar cycloaddition is clearly favoured. Therefore, it seems that
a more favourable coordination with the oxime’s nitrogen atom fa-
vours this cycloaddition. Concerning this ratio of adducts, AlCl3
(where the coordination with the carbonyl oxygen atom is the
most favourable) occupies an intermediate position between the
LAs.
Acknowledgements
This work was supported by Centro de Investigação em Química
of University of Porto. The authors thank the Fundação para a Ciên-
cia e Tecnologia (FCT) for financial support of this work under
project POCTI/QUI/44471/2002 (Pluri-annual and Programmatic
Funding) and for the grant to C.A.D. Sousa (SFRH/BD/31526/2006).

C. A. D. Sousa et al. / Tetrahedron Letters 49 (2008) 5777–5781
5781
Jd1 = 6.6 Hz, Jd2 = 2.2 Hz, 1H, 5-H), 2.49 (dd, J = 18.2 Hz, J = 8.1 Hz, 1H, 6syn-H),
2.09 (dquint, Jd = 18.2 Hz, Jquint = 2.2 Hz, 1H, 6anti-H); 13C NMR (75 MHz, CDCl3):
169.8 (COO), 137.7 (C8), 127.9 (C7), 91.9 (C1), 67.2 (C4), 52.0 (MeO), 45.9 (C5),
34.5 (C6); ESI-MS: calculated for [C8H11NO3+H]+ (M+H+) 170.18, found 170.47.
Anal. Calcd for C8H11NO3: C, 56.80; H, 6.55; N, 8.28. Found: C, 56.75; H, 6.59; N,
Supplementary data
This material contains the synthetic methods and characteriza-
tion data of all compounds (1H NMR, 13C NMR, DEPT, COSY and
HMQC spectra, chromatographic data and X-ray data). Supplemen-
tary data associated with this article can be found, in the online
version, at doi:10.1016/j.tetlet.2008.07.110.
8.25.
( )-Methyl
[(3-exo)-2-hydroxy-2-azabicyclo[2.2.1]hept-5-ene]-3-
carboxylate (2): 1H NMR (300 MHz, CDCl3): 6.66 (br s, 1H, exch. D2O, OH),
6.68–6.64 (m, 1H, 5-H), 6.34 (dd, J = 5.7 Hz, J = 2.1 Hz, 1 H, 6-H), 4.29 (br s, 1H,
1-H), 3.76 (s, 3H, OMe), 3.16 (br s, 1H, 4-H), 2.89 (d, J = 2.1 Hz, 1H, 3endo-H), 1.82
(d, J = 9.3 Hz, 1 H, 7syn-H), 1.50 (dd, J = 9.3 Hz, J = 1.5 Hz, 1 H, 7anti-H). 13C NMR
(75 MHz, CDCl3): 172.9 (COO), 138.1 (C6), 133.1 (C5), 70.4 (C3), 69.5 (C4), 52.2
(C1), 47.6 (OCH3) 45.2 (C7); ESI-MS: calculated for [C8H11NO3+H]+ (M+H+)
170.18, found 170.53. Anal. Calcd for C8H11NO3: C, 56.80; H, 6.55; N, 8.28.
Found: C, 56.76; H, 6.60; N, 8.26. ( )-Methyl [(3-endo)-2-hydroxy-2-
azabicyclo[2.2.1]hept-5-ene]-3-carboxylate (3): Mp 102–105 °C; 1H NMR
(300 MHz, CDCl3): 8.13 (br s, 1H, exch. D2O, OH), 6.24 (br s, 2H, 5-H + 6-H),
4.11 (br s, 1H, 1-H), 3.76 (d, J = 3.6 Hz, 1H, 3exo-H), 3.66 (s, 3H, OMe), 3.33 (br s,
1H, 4-H), 2.22 (d, J = 8.7 Hz, 1H, 7syn-H), 1.74 (d, J = 8.7 Hz, 1H, 7anti-H). 13C NMR
(75 MHz, CDCl3): 172.1 (COO), 139.5 (C5), 134.3 (C6), 72.9 (C1), 71.2 (C3), 51.9
(OCH3), 46.3 (C7), 45.3 (C4); ESI-MS: calculated for [C8H11NO3+H]+ (M+H+)
170.18, found 170.67. Anal. Calcd for C8H11NO3: C, 56.80; H, 6.55; N, 8.28.
Found: C, 56.77; H, 6.57; N, 8.26. ( )-Methyl (1R,4R,5R)-[2-(3,5-dinitrobenzoyl)-
2-ox-3-azabicyclo[3.3.0]oct-7-ene]-4-carboxylate (5): Mp 60–62 °C; 1H NMR
(300 MHz, CDCl3): 9.16 (t, Jmeta = 2.1 Hz, 1H, 40-H), 9.07 (d, Jmeta = 2.1 Hz, 2H,
20-H + 60-H), 6.21–6.17 (m, 1H, 8-H), 5.84 (dt, Jd = 7.8 Hz, Jt = 2.2 Hz, 1H, 7-H),
5.28 (dd, J = 6.7 Hz, J = 1.8 Hz, 1H, 1-H), 5.22 (d, J = 9.9 Hz, 1H, 4-H), 3.84 (s, 3H,
OMe), 3.77–3.66 (m, 1H, 5-H), 2.67 (ddt, Jt = 18.0 Hz, Jd1 = 8.7 Hz, Jd2 = 2.2 Hz,
1H, 6syn-H), 2.44 (ddt, J = 18.0 Hz, J = 2.4 Hz, J = 2.2 Hz, 1H, 6anti-H). Anal. Calcd
for C15H13N3O8: C, 49.59; H, 3.61; N, 11.57. Found: C, 49.53; H, 3.70; N, 11.52.
Methyl glyoxylate oxime (1): see Supplementary data and Ref. 8a.
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