1,3-Dipolar cycloadditions of nonstabilized azomethine ylides to planar chalcones via regio-and stereoselective route: A three-component strategy

Article abstract of DOI:10.1080/00397911.2015.1135954

Simple and efficient strategies toward the synthesis of trisubstituted pyrrolizidines and disubstituted oxazolidine systems by 1,3-dipolar cycloaddition reactions using arylaldehydes and α-amino acids have been developed, followed by a one-pot, three-comp

Full text of DOI:10.1080/00397911.2015.1135954

Synthetic Communications
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1,3-Dipolar Cycloadditions of Nonstabilized
Azomethine Ylides to Planar Chalcones via Regio-
and Stereoselective Route: A Three Component
Strategy
Biswajit Gayen, Avijit Banerji & Kaliprasanna Dhara
To cite this article: Biswajit Gayen, Avijit Banerji & Kaliprasanna Dhara (2016): 1,3-Dipolar
Cycloadditions of Nonstabilized Azomethine Ylides to Planar Chalcones via Regio- and
Stereoselective Route: A Three Component Strategy, Synthetic Communications, DOI:
10.1080/00397911.2015.1135954
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Date: 17 January 2016, At: 22:23

1,3-Dipolar Cycloadditions of Nonstabilized Azomethine Ylides to Planar Chalcones
via Regio- and Stereoselective Route: A Three Component Strategy
Biswajit Gayen1, Avijit Banerji2, Kaliprasanna Dhara2
1Budge Budge Institute of Technology, Kolkata, India, 2Centre of Advanced Studies on
Natural Products including Organic Synthesis, Department of Chemistry, University
College of Science and Technology, University of Calcutta, Kolkata, India
Corresponding author. Avijit Banerji, Email: ablabcu@yahoo.co.uk
Supplemental data for this article can be accessed on the publisher’s website.
Abstract
Simple and efficient strategies towards the synthesis of tri-substituted pyrrolizidines and
di-substituted oxazolidine systems by 1,3-dipolar cycloaddition reactions utilising
arylaldehydes and -amino acids have been developed, followed by one-pot three
component strategy. Electron-deficient dipolarophile, chalcones were reacted with
nonstabilized azomethine ylides derived from arylaldehyde and L-proline in dry dimethyl
formamide leading to substituted pyrrolizidines. The route to substituted oxazolidines
involved cycloaddition to the C=O bond of a second molecule of the aldehyde. The
structures and stereochemistry of the cycloadducts were established by infrared, NMR
spectroscopy, and single-crystal X-ray crystallographic analyses.
Condensed Fukui functions and local electrophilicity indices have been computed to
characterize the reactive sites and predict the preferred interactions of azomethine ylides
to planar chalcones. The softness matching indices have been evaluated to determine the
regioselectivity of the cycloaddition reactions. The theoretical predictions were found to
be in complete agreement with the experimental results implying that the DFT based
1

reactivity indices correctly predict the regioselectivities of 1,3-dipolar cycloadditions of
azomethine ylides to planar chalcones. The FMO energies, electronic chemical potentials,
chemical hardness, chemical softness and global electrophilicity indices of azomethine
ylides have been calculated at DFT/B3LYP/6-31+G (d, p) level of theory.
Graphical Abstract:
KEYWORDS: azomethine ylide, chalcones, multi-component reaction, regio- and
stereoselectivity, cycloaddition.
INTRODUCTION
Substituted Pyrrolidine[1] and Pyrrolizidine[2] alkaloids constitute classes of compounds
with significant biological and pharmaceutical importance.[3] Synthesis and
characterization of such biologically active compound is crucial from the view point of
human health care. Hence, in recent years methods for synthesizing biologically active
compounds are receiving increasing attention. Solution phase synthesis[4] of small
molecules, planar electron deficient -electronic system (chalcones) offers certain
2

advantage over solid phase methodology[5] and is getting increasing recognition in the
pharmaceutical industries.[6]
Multi-component reactions[7] has great importance in Synthetic Organic Chemistry as
three or more molecular units can be combined in single reaction vessel. However, many
multi-component assembly of molecules result in degrees of conformational freedom, so
that it may sometimes be difficult to accomplish stereo- and regio-control reaction in
multi-component reaction strategy. However, by utilizing proper reaction conditions and
starting materials regio- and stereo-control can be established.
RESULT AND DISCUSSION
For synthesizing substituted pyrrolizidine ring systems the methodology which we
employed is 1,3-dipolar cycloaddition[8] between azomethine ylide[9] and
dipolarophile:[10] this follows the (3+2) cycloaddition pathway.[11] The azomethine ylides
are generated in situ in the reaction medium and reacted with the dipolarophile, chalcone
or its derivatives resulting in the formation of substituted pyrrolizidine cycloadducts. The
chalcones are planar molecules, hence the regio-and stereoselectivity would largely be
directed by electronic factors – this was of interest to us. The stereo-structures and X-ray
packing patterns of the cycloadducts were also of interest to us. In this work, we utilized
the decarboxylation[12] route to generate azomethine ylides. There are several possible
configurations of the azomethine ylides,[13] viz. U, W and S-shaped. The U-configuration
can be ruled out on ground of instability due its excessive steric interactions:[14] hence
only the other two possibilities remain. Practically, it was established that only one type
3

of ylide participated in the cycloaddition, viz. the S-shaped ylide. It is possible that both
of ylides were formed and W-shaped ylide converted to S-shaped ylide as all the three
possible ylides are interconvertable[15] among themselves. The mechanistic details for
generate azomethine ylides from aromatic aldehydes and L-proline are given in Scheme
1.
Solution phase preparation of azomethine ylides[16] results from the condensation product
of L-proline and arylaldehyde, subsequent cycloaddition with the dipolarophile chalcone
generated tri-substituted pyrrolizidine moiety in dry DMF solvent at 90oC. The reactions
occurred regio- and stereoselectively, only one cycloadduct (8) with unchanged
stereochemistry was furnished in each entry of the reactions (Table 1, Scheme 2).
A series of reaction was studied to track any stereo- and regiochemical change in the
cycloaddition mode with variation of aldehyde part in azomethine ylide and also variation
with dipolarophile (7) part. The results showed that no significant change was observed
on stereochemical mode in the cycloaddition reaction. The detailed results of the study
are given in Table 1.
During the cycloaddition reaction between dipolarophile (7) and azomethine ylide (6) an
interesting side reaction[17] was noticed, the side reaction was motivating as it was
another cycloaddition reaction and led to the synthesis of another important class of
heterocyclic compound, viz. substituted oxazolidine.[18] Substituted oxazolidine ring
system was generated as a result of cycloaddition between azomethine ylide and
4

arylaldehyde,[19] the carbon-oxygen (C=O) double bond acting as an alternative to
carbon-carbon (C=C) double bond for the cycloaddition. Ylides generated from amino
acids followed by decarboxylation route is generally not so much stable;[20] hence, they
are extremely reactive and reacted with aldehyde carbon-oxygen (C=O) double bond[21]
as initially concentration of aldehyde in the reaction mixture was very high. The
mechanistic details are given in the Scheme 3.
The characterization of the cycloadducts were done by 1H NMR, 13C NMR, IR
spectroscopy and finally the stereochemistry of the cycloadduct was confirmed by solid
state single X-ray spectroscopy.
The 300 MHz 1H NMR spectrum of 8a (Scheme 2) showed a characteristic peak as
doublet at 4 .20 (J = 9.7 Hz) [H-3], a multiplet at 3 .94 [H-7a] and two triplets at
4

.29 (J = 9.8 HZ) [H-2] and 3.47 (J = 9.5 Hz) [H-1]. The 75.5 MHz 13C NMR
spectrum of 8a showed the expected signals to satisfy the structure of cycloadduct 8a.
13C-NMR peak for carbonyl (C=O) appeared at 2

00.7. Assignments were confirmed
from two dimensional 1H-1H COSY experiments. This showed the sequence of
conectivities of protons from H-1 to the others-continuing to the H-7 methylene protons.
Four non-aromatic methane carbons appeared at 7
methylenes -CH2- appeared at 25.1, 31.8 and 5
indicating that it was adjacent to nitrogen.

2.1, 7
 4.7, 6 4.2 and 5 6.8. Three


 3.6, the low-field value of which
5

It was important to know the relative stereochemistry of the cycloadduct 8a-k but it was
not possible from the spectroscopic analyses. To get the accurate relative configuration of
the cycloadduct 8a, it was crystallized in single crystal form and single crystal XRD-
study was carried out on cycloadduct 8a - the detailed results of that study is given below
(Figure 1, 2). Crystallographic data (excluding structural factors) for the structure of
compound 8a have been deposited at the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 822415.
For the side reaction, it was seen that in some cases the yield of the side product was too
low for isolation. However, in some cases it could be isolated and characterized by NMR,
IR and MS- spectroscopy. In a particular cycloadduct, where m-nitrobenzaldehyde was
used as a precursor the cycloadduct was isolated in pure state and characterized well by
different spectroscopic methods. Two sharp doublet peaks at 4 .70 (J = 8.0, H-2), 3 .85
(J = 8.0, H-3) and a broad peak at highly deshielded field, δ 5.35 (H-7a), these were the
most valuable three characteristic peaks that appeared for the cycloadduct 9f.
Stereochemistry of oxazolidine moiety (9f) has been established by single crystal XRD
analysis (Figure 3, 4). Crystallographic data (excluding structural factors) for the
structure of compound 9f have been deposited at the Cambridge Crystallographic Data
Centre as supplementary publication nos. CCDC 828391.
The structures and stereochemistries of compounds 8a and 9f were settled from X-ray
crystallographic analysis. Close similarity of spectroscopical properties of similar series
of compounds to 8a and 9f, indicated similar sterochemistries for them.
6

Sustman[22] classified 1,3-dipolar cycloadditions reactions into three categories on the
basis of FMO interaction between dipole and dipolarophile. The reactions reported in
this paper belongs the category-I,[23] in which the reactions were controlled by the
interaction of HOMOdipole-LUMOdipolarophile. In category-I dipolarophile will be electron
deficient and 1,3-dipole will be electron rich, this is also called NED (Normal Electron
Demand) reactions.[24] The preferred regioselectivity of the reaction reported in Scheme
2, were investigated by theoretical method. From Scheme 2, it is apparent that
azomethine ylides are electron-rich and dipolarophiles are electron-deficient, therefore
our carried out reactions should be controlled by the HOMOdipole-LUMOdipolarophile
interaction. The theoretically computed HOMO-LUMO energy gaps (Table 3) suggested
that HOMOdipole-LUMOdipolarophile interaction leads the reaction course rather than
HOMOdipole-LUMOdipolarophile; as the energy gap for the latter is high. Calculated HOMO
and LUMO energies of dipoles and dipolarophiles are presented in Table 2.
From Table 3 and Figure 5 it is cleared that minimum energy gap between
LUMOdipolarophile- HOMOdipole for the pair of (6a+7a) and maximum energy gap for the
pair of (6f+7a) that was reflected on the experimental results also (Table 1). Therefore,
electron-donating group attached with dipole facilitated the cycloaddition reaction and
electron-withdrawing group retarded[25] the reaction rate. As a result for the first entry, it
was fastest reaction reported in the series of reaction (Table 1) and its yield was
maximum; on the other hand for the couple (6f+7a), it was the slowest reaction on the
series and its yield was very poor and consequently parallel side reaction occurred
prominently i.e. formation of substituted oxazolidine moieties.
7

To predict the regioselectivity, we calculated two local properties, one was local
electrophilicity index[26] (ωk) and another was condensed Fukui function (fk).[27] DFT
based reactivity indices like Fukui functions and local electrophilicity indices are very
helpful to predict the regioselectivity of 1,3-dipolar cycloaddition reactions.[28]
For the 1,3-dipolar cycloaddition most favorable regioselectivity will be correspond to
the “most prominent interaction between electrophilic and nucleophilic sites of
unsymmetrical components”.
In recent few years DFT based calculation on organic chemistry flourish very fast due to
its powerful capability to explain reaction kinetics and thermodynamics,[29] especially in
the field of 1,3-dipolar cycloaddition reactions.[30] A short summary of DFT based local
and global indices is given below.
The local electrophilicity[26] indices is defined as
+
ωk= ωfk
(1)
+
Where, ω is the global electrophilicity and fk is the Fukui function for the nuceophilic
attack. According to Koopman’s theorem[31] electronic chemical potential is defined as
µ=(εH+εL)/2
(2)
(εH, εL are the energy of HOMO and LUMO energy states of the reactive species). It
measures the extent of charge transfer (CT) within the ground state of the reactive
species.
8

Chemical hardness[32] (η) is defined as
=(εL-εH)
(3)
It measures the stability of a system.
Global softness[33] (S) defined as
S=1/2


Global electrophilicity index[26] (ω) defined as
=µ2/2
It measures the stabilization in energy when system requires additional electronic charge
from the environment.
These all are the about global properties. For local properties, the Fukui function can be
written in terms of NPA[34] [Natural Population (electrons) Analysis] as
+
For Nucleophilic attack, fk =qk(N+1)- qk(N)
(6)
(7)
-
For Electrophilic attack, fk =qk(N)- qk(N-1)
qk(N+1), qk(N-1) and qk(N) are the population of electron at kth site.
-
For the dipole 6a, C37 carries higher fk value than C44 (Table 4, Figure 6, 7), again for
dipolarophile 7a, C carries higher local electrophilicity index (ωk) value than C.
Therefore most favorable regioselectivity will be maintained by the interaction of C37 of
dipole 6a with C of dipolarophile 7a and other of course C44 of dipole 6a with C of
dipolarophile (Figure 6, 7).
9

From the outcome of our study it was showed that most favorable regioselectivity will be
-
shown in the Figure 6 & 7 where maximum interaction of fk of azomethine ylide with ωk
of dipolarophile were taken place.
Similarly that of reaction kinetics, DFT based theoretical calculation results matched with
experimental obtaining result of perfect regiochemistry of cycloadducts, where
regiochemistry of the cycloadduct was confirmed by single crystal-XRD study.
From Table 6, it is cleared that cycloaddition between azomethine ylides and aldehydes
are directed by the interaction of LUMOcarbonyl- HOMOdipole. It is also proved from the
comparison of Table 5 and 6, cycloaddition of azomethine ylides and dipolarophile is
more favorable than that of cycloaddition of azomethine ylides with the aldehyde
carbonyl double bond. Only one exception was found when the aldehyde taken is m-
nitrobenzaldehyde, possibly caused by the strong electron-withdrawing effect of nitro
group. The theoretically expected results are exactly reflected in the experimental result
in the formation of two different kinds of cycloadducts.
Two exceptions were observed in case of azomethine ylide corresponding to m-
nitrobenzaldehyde (6f), another when p-nitrobenzaldehyde in the dipolarophile (7c). This
may be due to the strong electronic effect of nitro which may not correctly incorporate in
local electronic effect by DFT based calculation.
10

EXPERIMENTAL SECTION
General Procedure For Cycloaddition Reaction
A reaction mixture of L-Proline 1 (2 mmol), Arylaldehyde 2 (2 mmol) and Chalcone 7 (2
mmol) in equimolar ratio was heated in 10 mL. dry DMF solvent at a temperature 90oC.
The completion of reaction was monitored by TLC. The reaction mixture was worked up
as follows; firstly high boiling solvent DMF was removed by dilution with excess
chloroform and washed with cold water, the resulting DMF free reaction mixture was
allowed to stand for overnight in presence of dry sodium sulphate (Na2SO4). The
chloroform was evaporated by using rotor evaporator under reduced pressure. The crude
product was column chromatographed over silica gel in different proportion of petroleum
ether (60-80oC) and ethyl acetate as eluent.
Computational Methods
All calculations were carried out using the Gaussian 03[35] computational programme.
The geometries were optimized by DFT with Becke’s[36] three-parameter hybrid
exchange functional in combination with the gradient-corrected correlation functional
DFT analysis augmented by X-ray and NMR studies of Lee et al.;[37] B3LYP hybrid
functional and 6-31G++ (d, p) basis set. The electronic populations were computed from
Natural Population Analysis (NPA)[26] at DFT/BYLYP/ 6-31G basis set. All the
optimized structures were checked by existence of none imaginary frequency.
11

Characterized Data Of Compounds 8a And 9f
Compound (8a): ((1S,2R, 3R,7aS)-Hexahydro-3-(4-methoxyphenyl)-1-p-tolyl-1H-
pyrrolizin-2-yl)(phenyl)methanone; (C28H29NO2); Isolated from 5% ethyl t in petroleum
ether (60-80°C); Colourless crystal; m.p.: 106-108oC; IR (KBr): 2942, 1668, 1603, 1509,
1448, 1244, 1032, 804, 703 cm-1; 1H NMR (300 MHz, CDCl3) 4.20 (1H, d, J = 9.8 Hz),
4.29 (1H, t, J = 9.8 Hz), 3.47 (1H, t, J = 8.3 Hz), 3.94 (1H, m), 2.80 & 2.90 (2H, m),
1.78-2.10 (4H, m), 3.73 (3H, s, -OMe), 2.25 (3H, s, -CH3), 6.75 (2H, d, J = 7.6 Hz), 7.02
(2H, d, J = 7.8 Hz), 7.40 (2H, dd, J = 8.1, 2.6 Hz), 7.15-7.35 (7H, m, Ar-H); 13C NMR
(75 MHz, CDCl3)  20.9 (-CH3), 25.1, 31.8, 53.6, 55.1 (-OMe), 56.8, 64.2, 72.1, 74.7,
113.8, 127.4, 128.0, 128.2, 129.3, 132.58, 134.5, 136.3, 137.6, 137.7, 159, 200.7 (C=O);
EI-MS m/z 411 [M]+; Anal.: Calcd for (C28H29NO2): C, 81.72; H, 7.10; N, 3.40%. Found:
C, 82.56; H, 6.78; N, 3.12%.
Compound (9f): (2R,3R,7aS)-Hexahydro-2,3-bis(3-nitrophenyl)pyrrolo[2,1-b]oxazole;
(C18H17N3O5); Colourless crystals; Isolated from 10% ethyl acetate in petroleum ether
(60-80°C); m.p.: 108-110oC; IR (KBr): 1525, 1347, 1081, 1032, 683 cm-1; 1H NMR (300
MHz, CDCl3) δ 5.35 (1H, b), 4.70 (1H, d, J = 8.0 Hz), 3.85 (1H, d, J = 8.0 Hz), 3.15 &
2.85 (2H, m each), 1.80-2.30 (4H, m), 7.40-7.60 (4H, m, Ar-H), 8.10- 8.30 (4H, m, Ar-
H); 13C-NMR (75 MHz, CDCl3) δ 24.1, 31.6, 55.8, 78.1, 87.4, 99.1, 121.2, 122.1, 122.8,
123.4, 129.5, 132.5, 133.2, 140.5, 142.9, 148.6; EI-MS m/z 355 [M]+; HR-MS m/z calcd.
for [MH]+:356.1246; found: 356.1273; Anal. calcd. for (C18H17N3O5): C, 60.84; H, 4.82;
N, 11.83. Found: C, 60.80; H, 4.84; N, 11.78.
12

Crystallographic Data
Crystallographic data (excluding structural factors) for the structures in this article have
been deposited at the Cambridge Crystallographic Data Centre as supplementary
publications. CCDC 821707 (compound 8a): Crystal data for 8a. C28 H29 N O2,
Monoclinic, space group P21/n; a 20.096(3)Å, b 5

.9223(8)Å, c 2

0.685(3)Å,
9

0.0000, 109.080(2)0, 90.0000, V 2326.6(6)Å3, Z 4



, R 0.0411. CCDC

828391 (compound 9f): Crystal data for 9f. C18 H17 N3 O5, Monoclinic, space group
00, 117.485(3) 0,
C2/c; a 2 8.425(3)Å, b 8 .5119(10)Å, c 1 5.7044(18)Å, 9
0
9 0 , V 3370.8(7) Å3, Z 8 , R 0 .0813.
Please view the supplementary material, available online, for complete experimental
details.
ACKNOWEDGMENT
The authors thank the University of Calcutta for providing laboratory and spectroscopic
facilities. B. Gayen thanks the Council of Scientific and Industrial Research (CSIR), New
Delhi, India for the award of Senior Research Fellowship.
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18

Table 1. Regioselective cycloaddition reaction of azomethine ylides (6) with dipolarophile (7)
Entry Aldehyde
Reaction Cycloadduct 8
Cycloadduct 9
% Ratioa of Yielda
cycloadduct (%)
8 and 9
time (m)
1
4-OMe-
40
45
8a:9a
87
C6H4CHO
=97:03
2
3
4
4-Me-
8b:9b
83
69
72
C6H4CHO
=90:10
C6H5CHO 50
8c:9c
=78:22
4-Cl-
52
8d:9d
C6H4CHO
=55:45
5
6
3-Cl-
55
55
8e:9e
71
65
C6H4CHO
=63:37
3-NO2-
8f:9f
C6H4CHO
=56:44
19

7
8
4-OMe-
25
20
8g:9g/a
89
75
C6H4CHO
=96:04
4-Cl-
8h:9h/d
C6H4CHO
=79:21
9
4-Me-
30
70
8i:9i/b
84
72
C6H4CHO
=88:12
10
3-NO2-
8j:9j/f
C6H4CHO
=42:58
11
12
4-OMe-
170
85
8k:9k/a
85
04
C6H4CHO
=96:04
4-OMe-
8l:9l
C6H4CHO
=……..
a Calculated from 1H NMR spectrum analyses of crude reaction mixture.
20

Table 2. Calculated global and local properties of Azomethine ylides and Dipolarophiles
SX102 (eV) (eV)
System Eopt(a.m.u) HOMO(eV) LUMO(eV) µ(eV)
η(eV)
−596.26
−521.05
−481.73
−941.33
−941.32
−686.24
−693.40
−654.08
−858.59
−3.998
−4.134
−4.243
−4.433
−4.488
-4.814
-6.392
-6.582
-7.262
−0.734
−0.843
−0.952
−1.142
−1.197
−2.448
−2.394
−2.475
−3.400
−2.435 3.299
−2.366 3.264
−2.598 3.291
−2.788 3.291
−1.650 3.291
−3.631 2.366
−4.393 3.998
−4.529 4.107
−5.331 3.862
15.19
15.31
15.19
15.20
15.16
21.13
12.50
12.17
12.95
0.901
0.857
1.230
1.180
0.413
2.790
2.412
2.496
3.680
6a
6b
6c
6d
6e
6f
7a
7b
7c
21

Table 3. HOMO- LUMO Energy differences
Reaction
7a +6a
7a +6b
7a +6c
7a+6d
7a+6e
7a +6f
7b+6a
7b+6b
7b+Yd
7b+6f
LUMOdipole − HOMOdipolarophile
LUMOdipolarophile − HOMOdipole
5.658
5.549
5.340
4.250
5.195
3.944
5.848
5.739
5.440
4.134
6.528
1.604
1.740
1.849
2.039
2.054
2.420
1.523
1.659
1.958
2.339
0.598
7c+6a
22

Table 4. Local Fukui function and electrophilicity indices values
Entry
k
f +
f -

C37
C44
C37
C44
C37
C44
C37
C44
C37
C44
C37
C44
C1
0.001
0.055
0.026
0.027
0.037
0.030
0.073
0.032
0.029
0.030
0.117
−0.022
0.034
0.135
0.037
0.136
0.072
0.051
0.262
0.223
0.259
0.242
0.263
0.250
0.251
0.245
0.243
0.232
0.252
0.254
0.189
-0.001
0.182
0.014
0.124
0.042
0.262
0.223
0.259
0.242
0.263
0.250
0.251
0.245
0.248
0.236
0.252
0.254
0.082
0.326
0.092
0.340
0.265
0.188
6a
6b
6c
6d
6e
6f
7a
7b
7c
C2
C1
C2
C1
C2
23

Table 5. Calculated value of HOMO-LUMO of arylaldehydes
System Eopt(a.m.u) HOMO(eV) LUMO(eV)
−459.97
−384.90
−345.48
−805.18
−805.18
−550.10
−6.446
−6.827
−6.963
−7.126
−7.126
−7.861
−1.632
−1.605
−1.877
−1.986
−2.040
−3.318
2a
2b
2c
2d
2e
2f
24

Table 6. HOMO- LUMO Energy differences of Azomethine ylides and arylaldehydes
Reaction
6a + 2a
6b + 2b
6c + 2c
6d + 2d
6e + 2e
6f + 2f
LUMOdipole − HOMOcarbonyl
LUMOcarbonyl − HOMOdipole
5.712
5.984
6.011
5.984
5.929
5.413
2.366
2.502
2.366
2.447
2.448
1.496
25

Scheme 1. General mechanism for the generation azomethine ylide.
26

Scheme 2. General mechanism for the regioselective cycloaddition reactions.
27

Scheme 3. Generation of regioselective substituted oxazolidines.
28

Figure 1. Crystal structure of cycloadduct 8a
29