Intramolecular cycloaddition of fluorinated 1,3,4-oxadiazoles to dienes

Article abstract of DOI:10.1016/j.jfluchem.2007.02.020

Cycloaddition reactions of fluorinated 1,3,4-oxadiazoles with conjugated and unconjugated dienes was studied. The reactions resulted in the formation of products of double cycloaddition (7-oxabicycloheptane type compounds), along with products of intramolecular cycloaddition (oxatricyclic and oxatetracyclic compounds). The structure of 4-(trifluoromethyl)-2-ethoxycarbonyl-1,6-dimethyl-3-oxatricyclo [2.2.1.0^2,6]heptane was confirmed by single crystal X-ray diffraction analysis.

Full text of DOI:10.1016/j.jfluchem.2007.02.020

Journal of Fluorine Chemistry 128 (2007) 740–747
www.elsevier.com/locate/fluor
Intramolecular cycloaddition of fluorinated 1,3,4-oxadiazoles to dienes
d,3
N.V. Vasil’ev
a,b,*
b,1
, D.V. Romanov , A.A. Bazhenov , K.A. Lyssenko , G.V. Zatonsky
b,1
c,2
a
Moscow State Regional University, 107005 Moscow, Russian Federation
b
4
State Scientific Center ‘‘State Research Institute of Biological Engineering’’, 123424, Volocolamskoe sh. 75/1, Moscow, Russian Federation
c
A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova str. 28, 117813 Moscow, Russian Federation
d
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 117913 Moscow, Russian Federation
Received 28 January 2007; received in revised form 27 February 2007; accepted 27 February 2007
Available online 3 March 2007
Abstract
Cycloaddition reactions of fluorinated 1,3,4-oxadiazoles with conjugated and unconjugated dienes was studied. The reactions resulted in the
formation of products of double cycloaddition (7-oxabicycloheptane type compounds), along with products of intramolecular cycloaddition
2
,6
(
oxatricyclic and oxatetracyclic compounds). The structure of 4-(trifluoromethyl)-2-ethoxycarbonyl-1,6-dimethyl-3-oxatricyclo[2.2.1.0 ]hep-
tane was confirmed by single crystal X-ray diffraction analysis.
2007 Published by Elsevier B.V.
#
Keywords: Fluorinated 1,3,4-oxadiazoles; Diene; [2 + 4]-Cycloaddition; [2 + 3]-Cycloaddition
1
. Introduction
The reactions are controlled by the LUMO of oxadiazoles
and the HOMO of dienophiles. This statement agrees well with
experimental data (low ionization potentials of fluorinated
oxadiazoles [8]) and quantum-chemical calculation [6]. The
donor properties of involved dienophiles also provide support
for the inverted mechanism of oxadiazole cycloaddition;
acceptor-type dienophiles (the derivatives of maleic acid,
fumaric acid, acetylenedicarboxylic acid, etc.) do not enter
cycloaddition. Steric factors also have considerable effect on
cycloaddition—the yields of cycloadducts decrease going from
ethylene to propylene, and isobutylene, despite substantial
increase of electron density of double bond. Strained multiple
bonds in cyclic alkenes are of crucial importance; and increase
in the bond strain facilitates the occurrence of cycloaddition
processes [4].
Previously [1–3], the cycloaddition of 1,3,4-oxadiazoles to
alkenes was studied using 2,5-bis(trifluoromethyl)oxadiazole
1a) as an example. More recently, this reaction was extended
(
to other oxa,diazoles, such as 2,5-bis(polyfluoroalkyl)-1,3,4-
oxadiazoles (1b–d) [4–6], as well as 2,5-bis(methoxycarbo-
nyl)-1,3,4-oxadiazole (1e) [3].
The first step of the process, involves [2 + 4]-cycloaddition
with the formation of intermediate 2,3-diaza-7-oxabicy-
clo[2.2.1]hept-2-ene (2) intermediate (Scheme 1), which under
reaction conditions (ꢀ100 8C) undergoes retro [2 + 3]-cycload-
dition with the elimination of nitrogen and the formation of
carbonyl ylide (3, Scheme 1)—the most probable intermediate
in this process, although the formation of a biradical and an
oxirane intermediates was also considered [2,7].
Donor 1,3,4-oxadiazoles are not prone to cycloaddition with
the use of an endo-diene fragment. Thus, 2,5-dimethyl-1,3,4-
oxadiazole reacts with perfluorobutyne-2 to form only
condensed cycloadduct (5), which is the product of an initial
ene reaction followed by the [4 + 2]-cycloaddition of per-
fluorobutyne-2 to the resulting exo-diene component (Scheme
*
Corresponding author at: Moscow State Regional University, 107005
Moscow, Russian Federation. Tel.: +7 9263447837; fax: +7 495 2293014.
E-mail addresses: nikolai-vasilev@mail.ru (N.V. Vasil’ev),
kostya@xrlab.ineos.ac.ru (K.A. Lyssenko), Zatonsk@cacr.ioc.ac.ru
2
) [9].
Thus, the applicability of the double cycloaddition processes
(
G.V. Zatonsky).
1
Fax: +7 495 4905704.
2
of 1,3,4-oxadiazoles with the participation of two alkene
molecules to the synthesis of compounds from the 7-
oxabicycloheptane series has been determined to date. The
Fax: +7 495 135 5085.
3
Fax: +7 495 135 5328.
4
E-mail: 79262047229@megawap.ru.
0022-1139/$ – see front matter # 2007 Published by Elsevier B.V.
doi:10.1016/j.jfluchem.2007.02.020

N.V. Vasil’ev et al. / Journal of Fluorine Chemistry 128 (2007) 740–747
741
Scheme 1. Mechanism of reaction of fluorinated oxadiazoles with alkenes.
regioselectivity and stereoselectivity of the processes and the
donor, acceptor, and steric requirements imposed on the
formation of a transition state have been found.
heteroatoms (divinyl ether, divinyl sulfide, and diallyl ether),
and other compounds with two multiple bonds were studied in
cycloaddition reactions.
Intramolecular cycloaddition reactions as the tool for
synthesis of various cage compounds are of considerable
interest. Zeitz and Gerninghans [10] were the first to study this
Oxadiazole 1a reacted with butadiene under relatively mild
conditions to form mixture of compounds 9 and 10 isolated in
25 and 24%, respectively. Because compound 10 is much more
volatile than compound 9, these products can be easily
separated by fractional distillation. The mechanism of
formation compounds 9 and 10 involves of a carbonyl ylide
9a as common intermediate (Scheme 5). Compound 9 resulted
from the interaction of 9a with the second butadiene molecule,
but oxatricycloheptane 10 forms as the result of intramolecular
reaction.
2
-ethylsulfonyl-5-trifluoromethyl-1,3,4-oxadiazole (1f) in
cycloaddition with cyclooctadiene-1,5. This reaction resulted
in the formation of a tetracyclic compound (6) (Scheme 3). The
cycloaddition reaction of 2,5-bis(trifluoromethyl)oxadiazole 1a
with 7-tert-butoxynorbornadiene resulted in the formation of
oxabishomocubane (7) by the intramolecular cycloaddition
mechanism [7], although norbornadiene reacted by different
cycloaddition mechanism to form a cycloadduct (8) [2,4].
2,3-Dimethylbutadiene reacted with oxadiazole 1a in a more
complicated manner. In this case, we failed to isolate a double
cycloaddition product. At the same time, an intramolecular
cycloaddition product (11), as well as trifluoroacetamide (12)
and 2-trifluoromethyl-4,5-dimethylpyridine (13), which unex-
pectedly resulted from this interaction, were isolated (Scheme
6). The formation of compounds 12 and 13 can be explained by
an relative reactivity of 2,3-dimethylbutadiene, which is able to
undergo [4 + 2]-cycloaddition to the C N bond of oxadiazole
2
. Results and discussion
In order to determine the scope and limitations of the
intramolecular cycloaddition of fluorinated 1,3,4-oxadiazoles
we studied bis(trifluoromethyl)-1,3,4-oxadiazole (1a) and 2,5-
bis(perfluoropropyl)-1,3,4-oxadiazole (1c) in reaction with
dienes. Both 1a and 1b [11,12], readily prepared using
improved published procedure [6,8]. Unsymmetrical 2-tri-
fluoromethyl-5-ethoxycarbonyl-1,3,4-oxadiazole (1g) and
2
-trifluoromethyl-5-methoxycarbonyl-1,3,4-oxadiazole (1h)
were prepared using standard procedure depicted by Scheme 4.
Butadiene-1,3,2,3-dimethylbutadiene-1,3 (representatives
of acyclic dienes), along with unconjugated dienes containing
Scheme 3. Cycloaddition reactions of fluorinated oxadiazoles 1a and 1f.
Scheme 2. Interaction of 2,5-dimethyl-1,3,4-oxadiazole with perfluorobutyne-2.
Scheme 4. Synthesis of 2-trifluoromethyl-5-alkoxycarbonyl-1,3,4-oxadiazoles 1g and 1h.

742
N.V. Vasil’ev et al. / Journal of Fluorine Chemistry 128 (2007) 740–747
Scheme 5. Interaction of oxadiazole 1a with butadiene.
Scheme 6. Interaction of oxadiazole 1a with 2,3-dimethylbutadiene.
1
a forming an unstable cycloadduct (12a). Pyridine 13 resulted
of oxatricycloheptane 14 was observed in this process (Scheme
7). However interaction is realized oppositely to charged
distribution in molecules of 1g and 2,3-dimethylbutadiene. As
judged from the formation of compounds 12 and 13, the [4 + 2]-
cycloaddition of 2,3-dimethylbutadiene with oxadiazole 1g
occurred non-specifically. At the same time, urethane (12a) and
2-ethoxycarbonyl-4,5-dimethylpyridine (13a), which might be
formed in this reaction, were not detected.
from the subsequent ionic transformations of cycloadduct 12a
involving ring opening of oxadiazoline and elimination of
trifluoroacetamide 12 (Scheme 6).
Both processes occurred at comparable rates; it is likely that
they are characteristic of the interaction of oxadiazoles with
2
,3-dimethylbutadiene. This was supported by the reaction of
oxadiazole 1g with 2,3-dimethylbutadiene, which lead to a
similar result: the formation of intramolecular cycloaddition
product 14, trifluoroacetamide 12, and pyridine 13, which were
detected in reaction mixture by GC–MS and NMR spectro-
scopy. The intramolecular cycloaddition of compound 1g is
likely be a regiospecific, since the formation of only one isomer
The structure of 14 was confirmed by single crystal X-ray
diffraction (Fig. 1) and is in a good agreement with NMR data.
According to XRD 14 crystallize with two independent
molecules, which are almost identical with small variation of
ester group conformation. The bond lengths in 14 are close to
Scheme 7. Interaction of oxadiazole 1g with 2,3-dimethylbutadiene.

N.V. Vasil’ev et al. / Journal of Fluorine Chemistry 128 (2007) 740–747
743
Scheme 8. Interactions of oxadiazole 1a with divinyl ether, divinyl sulfide, and
diallyl ether.
Fig. 1. The general view of one of the independent molecules 14. The second
position of the disordered ester group is omitted for clarity. Selected bond
˚
lengths (A): O(1)–C(4) 1.422 (1), O(1)–C(1) 1.440 (2), O(2)–C(10) 1.204 (2),
C(1)–C(2) 1.525 (2), C(1)–C(6) 1.527 (2), C(2)–C(3) 1.514 (2), C(3)–C(8)
Scheme 9. Interactions of oxadiazoles 1a,c with cyclopentadiene, furan, and N-
ethylpyrrole.
1
.4975 (19), C(3)–C(5) 1.5194 (19), C(3)–C(4) 1.5301 (18), C(4)–C(5) 1.5320
19), C(5)–C(6) 1.518 (2) and angles (8): C(4)–O(1)–C(1) 98.00 (9), O(1)–
C(1)–C(2) 103.57 (10), C(7)–C(1)–C(2) 118.09 (12), O(1)–C(1)–C(6) 103.50
10), C(7)–C(1)–C(6) 118.05 (12), C(2)–C(1)–C(6) 102.96 (10), C(3)–C(2)–
(
(
Attempt to involve diallyl phthalate and diallyl acetal in
reactions with oxadiazoles 1a,c at elevated temperature (130–
C(1) 95.75 (10), C(8)–C(3)–C(2) 121.26 (12), C(8)–C(3)–C(5) 124.98 (13),
C(2)–C(3)–C(5) 106.47 (11), C(8)–C(3)–C(4) 125.09 (12), C(2)–C(3)–C(4)
150 8C) resulted in the formation of polymer products only.
1
02.93 (10), C(5)–C(3)–C(4) 60.31 (9), O(1)–C(4)–C(3) 108.77 (10), C(10)–
C(4)–C(3) 125.66 (12), O(1)–C(4)–C(5) 108.60 (10), C(10)–C(4)–C(5) 124.06
12), C(3)–C(4)–C(5) 59.50 (9), C(9)–C(5)–C(6) 121.64 (13), C(9)–C(5)–C(3)
24.47 (13), C(6)–C(5)–C(3) 106.82 (11), C(9)–C(5)–C(4) 124.63 (13), C(6)–
The interaction of cyclopentadiene with oxadiazole 1a
occurred under relatively mild conditions (90–100 8C, etc.), but
resulted in the selective formation of cycloadduct (19) (Scheme
(
1
C(5)–C(4) 103.01 (11), C(3)–C(5)–C(4) 60.19 (9), C(5)–C(6)–C(1) 95.41 (10).
9
) and the product of intramolecular cycloaddition was not
detected, even when the reaction was carried out at a high
degree of dilution. In reaction of furan or N-ethylpyrrole with
oxadiazoles 1a,c at temperatures higher than 200 8C only
decomposition products were found.
expected. The conformation of five-membered rings
O(1)C(1)C(2)C(3)C(4), O(1)C(1)C(6)C(5)C(4) and C(1)C(2)
C(3)C(5)C(6) is envelope one with the deviation of C(1) atom by
˚
Cyclohexadiene-1,3 reacted with oxadiazole 1a at 125 8C
forming mainly a cycloaddition product 20, along with smaller
amount of 21. Cyclohexadiene-1,4 was essentially different
from the above isomer; it reacted only at 200 8C to form a
mixture of compounds 22a,b (Scheme 10).
0
.76–0.80 A. The C O bond of ester group is characterized by
antiperiplanar conformation with torsion angles O(2)C
10)C(4)O(1) in twin independent molecules vary in the range
(
of 177.6–178.18.
The interaction of oxadiazole 1a with divinyl ether occurred
only at high temperature leading product (15) isolated in a low
yield. Divinyl sulfide reacted with oxadiazole 1a under milder
conditions to form compounds 16 and 17. On the other hand, he
reaction of oxadiazole 1a with diallyl ether rapidly proceeds at
The reaction of oxadiazole 1a with cycloheptatriene slowly
occurred at elevated temperature, but surprisingly resulted in a
moderate yield formation of an intramolecular cycloaddition
product (23) (Scheme 11). After first distillation, tetracyclo-
decene 23 contained ꢁ20% impurities of four unidentified
isomers of the same molecular weight (GC–MS). Pure product
1
30 8C with high yield formation cycloadduct 18 (Scheme 8).
Scheme 10. Interactions of oxadiazole 1a with cyclohexadiene-1,3 and cyclohexadiene-1,4.

744
N.V. Vasil’ev et al. / Journal of Fluorine Chemistry 128 (2007) 740–747
spectra were recorded in CDCl on a Bruker AC-300
3
1
spectrometer at 300.1 MHz. F NMR spectra (CDCl ) were
9
3
recorded on ‘‘Bruker WP-200 SY’’ spectrometer at
19
1
1
88.31 MHz. H F NMR spectra were recorded in CDCl3
on a Bruker DRX-500 spectrometer at 500.1 and 470.6 MHz for
1
19
H and F, respectively; TMS and CFCl was an internal
3
1
19
standard for H and F, respectively. IR spectra recorded on a
Hitachi 127-30 instrument (KBr or liquid film). The mass-
spectra were recorded on an HP 5890 II Series gas
chromatograph equipped with an HP 5972A MSD mass-
selective detector. Melting points were determined in open
capillaries and are uncorrected.
Scheme 11. Interactions of fluorinated oxadiazoles with cycloheptatriene and
cyclooctadiene-1,5.
2
3 was separated by repeated vacuum fractionation, and its
structure was confirmed by NMR spectroscopy and single
crystal X-ray diffraction analysis [13]. It should be also pointed
out, that oxadiazole 1c did not react with cycloheptatriene
under analogous conditions.
3.1. Crystallographic data
Crystals of 14 (C H F O , M = 264.24) are monoclinic,
1
2 15 3 3
The interaction of oxadiazoles 1a,c,g with cyclooctadiene-
space group P2 /n, at 100 K: a = 16.6738 (11), b = 12.0893 (8),
1
3
˚
˚
1
,5 resulted in exclusive formation of intramolecular cycload-
ducts; 24a,c,g: 58, 61, and 42% yield, respectively (Scheme
1). Cycloaddition of oxadiazoles 1g and 1a occurred relatively
c = 12.3106 (9) A, b = 90.116 (6)8, V = 2481.5 (3) A , Z = 8
0
ꢂ3
ꢂ1
(Z = 2), dcalc = 1.415 g cm
F(0 0 0) = 1104. Intensities of 19,028 reflections were mea-
,
m(Mo Ka) = 1.29 cm ,
1
fast (6 h at 140 8C; and 25 h at 150 8C, respectively), but the
reaction of oxadiazole 1c was slow even at 160 8C (80 h).
These differences in the reactivity of oxadiazoles 1a,c,g are
not explained by Frontier Orbital Method under consideration
of the orbital characteristics of their molecules. The LUMO and
HOMO energies calculated by the G 6-31* method are 2.53 and
ꢂ12.33 eV (1a); 2.25 and ꢂ12.28 eV (1c); 1.98 and ꢂ11.76 eV
sured with a Bruker SMART APEX2 CCD diffractometer
˚
[l(Mo Ka) = 0.71072 A, v-scans, 2u < 588] and 6531 inde-
pendent reflections [Rint = 0.0401] were used in further
refinement. The structure was solved by direct method and
2
refined by the full-matrix least-squares technique against F in
the anisotropic–isotropic approximation. The positions of
hydrogen atoms were calculated geometrically. For 14 the
refinement converged to wR2 = 0.1316 and GOF = 1.054 for all
independent reflections (R1 = 0.0510 was calculated against F
for 4353 observed reflections with I > 2s(I)). All calculations
were performed using SHELXTL PLUS 5.0.
(
1g), respectively. Reactivity of oxadiazoles have to change
as 1a ! 1c ! 1g, but we observe another sequences:
1
c ! 1a ! 1g.
In conclusion, the cycloaddition of fluorinated 1,3,4-
oxadiazoles to dienes offers interesting and relatively simple
approach to the preparation of oxatricyclic and oxatetracyclic
compounds. In general, we failed to find a direct relationship
between the structures of parent dienes or oxadiazoles and the
predominant formation of intramolecular cycloaddition or
double cycloaddition products in of our experiments. It seemed
likely the stereochemistry of approaching reactants, that is, the
initial exo or endo addition of a multiple bond to an oxadiazole
ring, wasresponsiblefortheresultingstructure. Atthesametime,
based on the experimental data available, we can conclude that
the formation of intramolecular cycloaddition or double cyclo-
addition products is almost independent of process temperature;
this is inconsistent with the effect of the stereozchemistry above.
Moreover, the structure of flattened carbonyl ylide intermediate
The crystallographic data have been deposited with the
Cambridge Crystallographic Data Center, CCDC 634037.
Copies of this information may be obtained free of charge from:
The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ,
UK (Fax: +44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk
or http://www.ccdc.cam.ac.uk).
3.2. 2-Trifluoromethyl-5-ethoxycarbonyl-1,3,4-oxadiazole
(1g)
7.5 g (0.074 mol) of dry triethylamine was added with
stirring to suspension of 10 g (0.075 mol) of C H OC(O)-
2
5
C(O)NHNH [15] in 150 ml of dry ether and then at ꢂ10 8C
2
12.0 g (0.09 mol) of trifluoroacetylchloride was slowly added
as a gas over the reaction mixture (ꢁ1 h). The reaction mixture
was brought to room temperature, was hold for another 30 min,
filtrated, the precipitate was washed 3ꢃ 30 ml of dry ether, the
solvent was removed under vacuum and the residue 15.2 g
(without additional cleaning) was mixed with 38.0 g (0.26 mol)
of P O and slowly heated the reaction mixture in vacuum
9
a, which is formed in the reactions of acyclic dienes, suggests
that the stereochemistry of initially approaching reactants does
not play a crucial role because rapid conformational conversion
into intermediate 9b comes into play. It is likely that spatial
correspondence in the resulting carbonyl ylide intermediate is a
crucial stereochemical factor for the occurrence of intramole-
cular cycloaddition in the interaction of cyclic dienes.
2
5
(30 mmHg) up to 150–170 8C collecting liquid fractions. After
consecutive distillation gave 8.42 g of oxadiazole 1g (54%)
2
0
3
. Experimental
with b.p. 88–90 8C (12 mmHg), n
1
1.3940. IR (KBr): n 2990,
740, 1620 cm ; H NMR (CDCl ): d 1.45 (t, J = 7.0 Hz, 3H,
D
ꢂ1
1
3
1
9
Commercial reagents and solvents used in the study were
1
prepared according to known recommendations [14]. H NMR
–CH ), 4.55 (q, J = 7.0 Hz, H, –CH ); F NMR (CDCl ): d
3 2 3
+
ꢂ65.5 (s, CF ); MS, 70 eV, m/z (%): 209 [M ꢂ 1] (2), 195 (4),
3

N.V. Vasil’ev et al. / Journal of Fluorine Chemistry 128 (2007) 740–747
745
1
2CH), 5.1, 5.3 and 5.6 (m, 6H, 6CH ); F NMR (CDCl ): d
9
1
91 (4), 183 (45), 169 (6), 165 (40), 139 (12), 137 (43), 69
100); Anal. Calcd. for C H F N O : C, 34.30; H, 2.40; N,
3
(
ꢂ78.0 (s, CF ), ꢂ76.5 (s, CF ), ꢂ76.1 (s, CF ), ꢂ72.8 (s, CF ),
6
5
3
2
3
3
3
3
3
1
3.33. Found: C, 34.51; H, 2.49; N, 13.07.
ꢂ70.7 (s, CF ); Anal. Calcd. for C H F O: C, 50.35; H, 4.20;
3
12 12 6
N, 0.00. Found: C, 49.93; H, 4.05.
3.3. 2-Trifluoromethyl-5-methoxycarbonyl-1,3,4-
oxadiazole (1h)
3.4.2. 2,4-Bis(trifluoromethyl)-3-
oxatricyclo[2.2.1.0 ]heptane (10) [13]
2
,6
5
.0 g (0.024 mol) of anhydride of trifluoroacetic acid was
20
1
B.p. 43 8C (18 mmHg) nD 1.3565; H NMR (CDCl ): d 1.7
3
added at 0 8C to 2.0 g (0.017 mol) of CH OC(O)C(O)NHNH
see Section 3.2 [15]), then reaction mixture was slowly heated
3
2
(
d, JAB = 23.5 Hz, 2H, 2CH ), 1.8 (d, J = 23.5 Hz, 2H,
19
2
AB
(
2
CH ), 2.15 (s, 2H, 2CH); F NMR (CDCl ): d ꢂ69.6 (s, 3F,
2
3
to boiling and hold while boiling for 2 h. Reaction mixture was
brought to room temperature another 5.0 g (0.026 mol) of
anhydride of trifluoroacetic acid and 0.2 g of dry pyridine was
added and it was heated for another 3 h periodically (three
times) cooling in order to add 0.1 g of pyridine. Mixture was
fractioned twice in vacuum, after second distillation formed
CF ), ꢂ74.6 (s, 3F, CF ); Anal. Calcd. for C H F O: C, 41.38;
3 3 8 6 6
H, 2,59. Found: C, 41.55; H, 2.63.
3
3
.4.3. 4-(Trifluoromethyl)-2-ethoxycarbonyl-1,6-dimethyl-
2
,6
-oxatricyclo[2.2.1.0 ]heptane (11)
2
0
1
2
0
B.p. 60 8C (17 mmHg), nD 1.3740; H NMR (CDCl ): d
3
1
.2 g of oxadiazole 1h (36%) with b.p. 80 8C (15 mmHg), nD
ꢂ1 1
1.75 (br s, 6H, 2CH ), 1.7 (d, J = 24.0 Hz, 2H, 2CH ), 1.8 (d,
3 AB 2
1
.3830. IR (KBr): n 2995, 1750, 1630 cm ; H NMR (CDCl3):
1
1
9
9
JAB = 24.0 Hz, 2H, 2CH2); F NMR (CDCl ): d ꢂ65.4 (s, 3F,
3
d 4.10 (s, –CH3); F NMR (CDCl ): d ꢂ65.4 (s, CF ); Anal.
3
3
CF ), ꢂ75.3 (s, 3F, CF ); Anal. Calcd. for C H F O: C, 46.15;
3
3
10 10 6
Calcd. for C H F N O : C, 30.61; H, 1.53; N, 14.29. Found: C,
3 3 2 3
5
H, 3.85. Found: C, 46.34; H, 4.03.
3
0.70; H, 1.49; N, 14.17.
3.4. A general procedure for cycloaddition reactions of
oxadiazoles. Preparation of compounds 9–24
3.4.4. Trifluoracetamide (12)
1
B.p. 75 8C (17 mmHg), m.p. 75 8C, corresponding [16]; H
NMR (DMSO-d ): d 8.5 (br s, 1H, NH ), 8.8 (br s, 1H, NH );
6
2
2
1
9
A mixture of oxadiazoles 1a,c,g (0.019 mol) and a
corresponding diene (0.019 mol) was heated in a sealed Pyrex
tube and then fractionated or sublimed in a vacuum. IR-spectra
F NMR (DMSO-d
6
): d ꢂ75.4 (s, CF
3
); Anal. Calcd. for
C H F NO: C, 21.24; H, 1.77; N, 12.39. Found: C, 21.52; H,
2 2 3
1.92; N, 12.15.
ꢂ1
of all cycloadducts exhibit a band at 2950–2980 cm and the
spectra of compounds 9, 15, 16, 19, 20, 22, 23 exhibit a low-
3
.4.5. 2-(Trifluoromethyl)-4,5-dimethylpyridine (13)
1
ꢂ1
intensity band at 1620–1650 cm ; in the spectra of compounds
20
B.p. 85 8C (17 mmHg), nD 1.4340; H NMR (CDCl ): d
3
ꢂ1
1
2
3
4, 24g was present a high-intensity band at 1680–1700 cm
The reaction conditions and yields of compounds 9–21, 23,
4 are shown in Table 1.
.
2
.28 (s, 3H, CH ), 2.35 (s, 3H, CH ), 7.43 (s, 1H, Ar CH), 8.42
3
19
3
(
(
(
(
s, 1H, Ar CH); F NMR (CDCl ): d ꢂ68.0 (s, 3F, CF ), ꢂ75.3
3
3
+
s, 3F, CF ); MS, 70 eV, m/z (%): 175 [M] (2), 160 (3), 148
3
34), 131 (5), 119 (100), 113 (2), 107 (60), 91 (46), 77 (25), 69
7); Anal. Calcd. for C H F N: C, 54.86; H, 4.57; N, 8.00.
.4.1. 1,4-Bis(trifluoromethyl)-2,5(6)-divinyl-7-
8
8 3
oxabicyclo[2.2.1]heptane (9) [13]
Found: C, 52.31; H, 4.83; N, 8.19.
1
Mixture of three isomers: b.p. 82–84 8C (18 mmHg). H
NMR (CDCl ): d 1.7–2.5 (m, 4H, 2CH ), 2.8 and 3.3 (m, 2H,
3
2
3.4.6. 4-(Trifluoromethyl)-2-ethoxycarbonyl-1,6-dimethyl-
3-oxatricyclo[2.2.1.0 ]-heptane (14)
2
,6
Table 1
Cycloaddition conditions and yield of compounds 9–24
1
B.p. 78 8C (2 mmHg), m.p. 60–62 8C; H NMR (CDCl ): d
3
a
Yield (%)
Entry
Compounds
Temperature (8C)
Time (h)
1.30 (t, J = 7.0 Hz, 3H, CH ), d 1.40 (s, 6H, 2CH ), 1.82 (d,
3
3
JAB = 20.0 Hz, 2H, 2CH ), 1.94 (d, J = 20.0 Hz, 2H, 2CH2),
2
BA
1
2
9, 10
11, 12, 13
150
150
20
18
25 (9), 24 (10)
32 (11), 15 (12),
1
9
4
.32 (q, J = 7.0 Hz, 2H, CH O,); F NMR (CDCl ): ꢂ75.0 (s,
2
3
3
0 (13)
CF ); Anal. Calcd. for C H F O : C, 54.55; H, 5.68. Found:
3
12 15
3 3
3
4
5
6
7
8
9
14
15
16, 17
18
19
20, 21
22a,b
23
24a
24c
24g
150
14
25
5
27 (14)
15 (15)
20 (16), 25 (17)
84 (18)
50 (19)
C, 54.81; H, 5.74.
180–190
175
130
30
4
3.4.7. 1,4-Bis(trifluoromethyl)-2-vinyloxy-5(6)-vinyloxy-7-
oxabicyclo[2.2.1]heptane (15)
90
125
30
70
80
25
80
6
45 (20), 16 (21)
–
1
Mixture of three isomers: b.p. 98 8C (13 mmHg); H NMR
200
(
CDCl ): d 1.5, 1.75, 2.02, 2.15, 2.50, 2.7, 3.1 (m, CH ), 4.15,
3 2
1
.2, 4.4, 4.55, 4.65 (m, CH), 5.1, 6.35 (m, CH ); F NMR
1
1
1
1
0
1
2
3
160–180
150
62 (23)
9
4
58 (24a)
61 (24c)
42 (24g)
160
(CDCl ): d ꢂ78.4 (s, CF ), ꢂ78.15 (s, CF ), ꢂ76.4 (s, CF ),
3 3 3
3
3
3
3
140
ꢂ75.6 (s, CF ), ꢂ72.85 (s, CF ) ꢂ71.25 (s, CF ); Anal.
a
Calcd. for C H F O : C, 45.28; H, 3.77. Found: C, 45.57;
12 12 6 3
The ratio of addends was 1:1; the yields were calculated based on the
amount of diene.
H, 3.44.

746
N.V. Vasil’ev et al. / Journal of Fluorine Chemistry 128 (2007) 740–747
3.4.8. 1,4-Bis(trifluoromethyl)-2-vinylsulfanyl-5(6)-
vinylsulfanyl-7-oxabicyclo[2.2.1]heptane (16)
3.4.14. 1,5,12,16-Tetrakis(trifluoromethyl)-23,24-dioxa-
5
heptacyclo[14.6.1.1 .0 .0 .0 .0
,12 2,15 4,13 6,11 17,22
]tetracosa-
2
0
Mixture of two isomers: b.p. 88–90 8C (3 mmHg), nD
8,19-diene (22a) and 1,5,12,16,20,27-hexakis-
(trifluoromethyl)-31,32,33-trioxadecacyclo-
1
.4660; H NMR (CDCl ): d 1.13–1.3, 1.5–1.75, 2.1–2.3, 2.4–
1
2
3
5
[14.14.1.1 .1
,12 20,27 2,15 4,13 6,11 17,30 19,28 21,26
.0
.6 (m, CH ), 3.8–3.9, 4.1–4.2 (m, CH), 5.25–5.40, 6.2–6.5 (m,
2
.0 .0 .0 .0
tritriaconta-8,23-diene (22b) [13]
.0
]
1
9
CH ); F NMR (CDCl ): d ꢂ69.85 (s, CF ), ꢂ73.96 (s, CF ),
3
3
3
ꢂ78.66 (s, CF ); Anal. Calcd. for C H F OS : C, 41.14; H,
Product 22a was sublimated at 2 mmHg and
110 ! 130 8C, m.p. 192–213 8C, contained ꢁ70% main
3
12 12
6
2
3
.43. Found: C, 40.82; H, 3.20.
1
compound with n = 1; H NMR (CDCl ) main compound: d
3
3
thiatetracyclo[3.3.0.0 .0 ]octane (17)
.4.9. 2,4-Bis(trifluoromethyl)-3-oxa-8-
,7 4,6
1.6, 1.8, 2.0–2.3 (m, CH ); 2.95 (br s, CH); 5.95 (s); 6.0 (br
2
2
19
s); F NMR (CDCl ): d ꢂ70.5 (br s, CF ); MS, 70 eV, m/z
3
3
1
+
B.p. 64 8C (15 mmHg), m.p. 64 8C; H NMR (CDCl ): d
(%): 338 [M] (2), 266 (3), 256 (100), 215 (15), 197 (16), 185
(7), 159 (22), 141 (15), 127 (5), 109 (4), 91 (20), 79 (60), 69
(6), 67 (32).
3
1
9
2
.55 (m, 4H, 2CH ), 3.85 (br d, J = 7.7 Hz, 2H, 2CH);
F
2
NMR (CDCl ): d ꢂ75.5 (s, 3F, CF ), ꢂ78.5 (s, 3F, CF ); Anal.
3
3
3
Calcd. for C H F OS: C, 36.36; H, 2.27. Found: C, 36.94; H,
8
Product 22b was sublimed at 2 mmHg and 130 ! 160 8C,
6 6
2
.53.
m.p. 280–310 8C (decom.), contains main compound with
1
n = 2, and n = 1, and n > 2; H NMR (CDCl ): d 1.5, 1.7, 2.0,
3
1
2.3 (m, CH ); 2.8–3.0 (m, CH); 5.9 (br s); 6.0 (m); F NMR
9
3.4.10. 6,8-Bis(trifluoromethyl)-3,7-
dioxatetracyclo[4.4.0.0 .0 ]decane (18)
2
5,9 8,10
(CDCl ): d ꢂ71.0 (br s, CF ); MS, 70 eV, m/z (%): 527
3
3
1
+
+
B.p. 81 8C (13 mmHg), m.p. 76 8C; H NMR (CDCl ): d 2.0
[M ꢂ 69] (2), 515 [M ꢂ 80 ꢂ 1] (3), 159 (6), 141 (4), 127 (3),
3
(dd, JXA = 16.0 Hz, JXB = 5.0 Hz, 2H, 2CH), 2.4 (dd,
JAB = 18.5 Hz, JAX = 16.0 Hz, 2H, 2CH2), 2.55 (dd,
82 (100), 69 (2), 67 (25).
JBA = 18.5 Hz, JBX = 5.0 Hz, 2H, 2CH ), 3.6 (dd, J
2
0 0
=
F
3.4.15. 5,7-Bis(trifluoromethyl)-6-
2,5 4,8
oxatetracyclo[5.3.0.0 .0 ]dec-9-ene (23) [13]
A B
1
9
2
0.5 Hz, 2H, 2CH ), 3.9 (dd, 2H, 2CH , J = 20.5 Hz);
0 0
B A
2
2
1
NMR (CDCl ): d ꢂ79.38 (s, 3F, CF ), ꢂ82.10 (s, 3F, CF );
B.p. 77 8C (10 mmHg), m.p. 45–47 8C; H NMR (CDCl ): d
3
3
3
3
Anal. Calcd. for C H F O : C, 43.48; H, 3.62. Found: C,
1
1.35 (d, J = 12.1, 1H, CH ); 2.15 (d.t, J = 12.1, J = 7.3, 1H,
CH ); 2.66 (dd, J = 7.3, J = 6.8, 2H, 2CH); 2.98 (br.d, 2H, 2CH,
0
10
6
2
2
4
3.81; H, 3.83.
2
1
9
J = 6.8); 6.08 (br.s, 2H, CH CH); F NMR (CDCl ): d ꢂ75.4
3
1
3
3
oxatetracyclo[5.5.1.0 .0 ]trideca-3,9(10)-diene (19)
.4.11. 1,7-Bis(trifluoromethyl)-13-
2
(s, 3F, CF ); ꢂ74.2 (s, 3F, CF ); C NMR (CDCl ): d 130.5 (s,
3
3
3
,6 8,12
C ); 130.5 (s, C ); 123.1 (q, J = 1077.5, CF ); 122.8 (q,
3
2
0
Mixture of two isomers: b.p. 118–120 8C (13 mmHg), nD
J = 1100.5, CF ); 102.3 (q, J = 120.0, CCF ); 91.9 (q,
3
3
1
.4520; H NMR (CDCl ): d 2.4–2.5, 2.8, 2.85, 3.2–3.4, 3.7–3.9
1
J = 120.0, CCF ); 49.4 (s, CH); 41.1 (s, CH); 21.1 (s, CH ).
3 2
3
1
m, CH , CH), 5.5–5.6, 5.8 (m, CH ); F NMR (CDCl ): d
9
(
Anal. Calcd. for C H F O: C, 48.89; H, 2.96. Found: C, 48.55;
11 8 6
2
3
ꢂ70.1 (s, CF ), ꢂ71.47 (s, CF ), ꢂ71.85 (s, CF ) ꢂ72.85 (s,
H, 3.17.
3
3
3
CF ); Anal. Calcd. for C H F O: C, 54.19; H, 3.87. Found: C,
3
14 12 6
5
3.82; H, 3.45.
3.4.16. 6,8-Bis(trifluoromethyl)-7-
2
oxatetracyclo[6.3.0.0 .0 ]undecane (24a) [13]
,6 5,9
1
3
oxatetracyclo[6.6.1.0 .0 ]pentadeca-3,10(12)-diene
.4.12. 1,8-Bis(trifluoromethyl)-15-
2
B.p. 101 8C (17 mmHg), m.p. 83–85 8C; H NMR (CDCl ):
3
,7 9,14
19
d 1.85 (s, 8H, 4CH ); 2.53 (s, 4H, 4CH); F NMR ꢂ75.1 (s,
2
(
20)
Mixture of two isomers: b.p. 138 8C (13 mmHg), m.p. 38–
CF ); Anal. Calcd. for C H F O: C, 50.35; H, 4.20. Found: C,
3
12 12 6
50.61; H, 4.63.
1
4
1 8C. H NMR (CDCl ): d 1.3, 1.55–2.3 (m, 8H, 4CH ), 2.75–
3
2
19
3
.10 (m, 4H, 4CH), 5.65–5.70, 6.0–6.2 (m, 4H, 4CH );
F
3.4.17. 6,8-Bis(n-heptafluoropropyl)-7-
2
,6 5,9
oxatetracyclo[6.3.0.0 .0 ]undecane(24c) [13]
NMR (CDCl ): d ꢂ70.58 (s, CF ), ꢂ70.91 (s, CF ), ꢂ71.36 (s,
3
3
3
1
CF ), ꢂ71.54 (s, CF ); Anal. Calcd. for C H F O: C, 56.80;
B.p. 78 8C (2 mmHg), m.p. 45 8C; H NMR (CDCl ): d 1.85
3
3
16 16
6
3
1
9
H, 4.73. Found: C, 57.11; H, 4.98.
(s, 8H, 4CH ); 2.65 (s, 4H, 4CH); F NMR ꢂ81.0 (br s, 6F,
2
2
CF ); ꢂ117.3 (br s, 4F, 2CF ); ꢂ125.6 (br s, 4F, 2CF ). Anal.
3 2 2
3
oxatetracyclo[4.3.0.0 .0 ]nonane (21)
.4.13. 4,6-Bis(trifluoromethyl)-5-
,4 3,7
Calcd. for C H F O: C, 39.51; H, 2.47. Found: C, 39.76; H,
16 12 14
2
2.25.
1
B.p. 71 8C (14 mmHg), m.p. 73 8C; H NMR (CDCl ): d
3
1
JBA = 12.5 Hz), 2.05 (br s, 2H, 2CH), 2.51 (br s, 2H, 2CH);
.94 (br d, 2H, 2CH , J = 12.5 Hz), 2.00 (d, 2H, 2CH ,
1
3.4.18. 6-Trifluoromethyl-8-ethoxycarbonyl-7-
2,6 5,9
oxatetracyclo[6.3.0.0 .0 ]undecane (24g)
2
AB
2
9
F
2
0
1
NMR (CDCl ): d ꢂ69.38 (s, 3F, CF ), ꢂ72.05 (s, 3F, CF ); MS,
B.p. 98 8C (1 mmHg), nD 1.4630; H NMR (CDCl ):
3
3
3
3
+
7
0 eV, m/z (%): 258 [M] (25), 239 (7), 230 (8), 189 (25), 161
100), 146 (7), 141 (75), 133 (25), 114 (15), 91 (45), 69 (52);
Anal. Calcd. for C H F O: C, 46.51; H, 3.10. Found: C, 46.78;
d 1.3 (t, 3H, CH ); 1.83 (br s, 8H, 4CH ), 2.45 (s, 4H,
1
3
2
9
(
4CH), 4.3 (q, 2H, CH O); F NMR ꢂ74.84 (s, CF ); Anal.
2
3
Calcd. for C H F O : C, 57.93; H, 5.86. Found: C, 58.23;
14 17 3 3
1
0
8
6
H, 3.44.
H, 5.51.

N.V. Vasil’ev et al. / Journal of Fluorine Chemistry 128 (2007) 740–747
747
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