1,2-Bis(trifluoromethyl)ethene-1,2-dicarbonitrile: (2+2) cycloadditions with vinyl ethers

Article abstract of DOI:10.1002/hlca.201100449

The title compound (short version: BTE) occurs in (E)- and (Z)-isomers (both with b.p. of ca. 100°) which equilibrate with nucleophilic catalysts. Both undergo (2+2) cycloadditions with methyl vinyl ether at 25°. Three stereogenic centers in the cyclobutanes led to four rac-diastereoisomers, which were obtained in pure and crystalline state. The structures were elucidated by ¹⁹F-NMR spectroscopy and confirmed by two X-ray analyses. The cycloadditions were not stereospecific: e.g., (E)-BTE furnished 73% trans-adducts (with respect to the CF₃ groups) and 27% cis-adducts. The loss of stereochemical integrity occurs in the intermediate gauche-zwitterions which can cyclize or rotate, but not dissociate. Under extreme conditions (2M LiClO₄ in Et₂O, 70°, 3months), the thermodynamic equilibrium of the four cyclobutanes was achieved. Considerations of Coulombic attraction and conformational strain in the zwitterionic intermediates allow us to rationalize the observed proportions of diastereoisomeric cyclobutanes. Ethyl vinyl ether and butyl vinyl ether furnished cyclobutanes in similar diastereoisomer ratios. Copyright

Full text of DOI:10.1002/hlca.201100449

Helvetica Chimica Acta – Vol. 95 (2012)
1
1,2-Bis(trifluoromethyl)ethene-1,2-dicarbonitrile: (2 þ 2) Cycloadditions with
Vinyl Ethers
by Gonzalo Urrutia-Desmaison1), Rolf Huisgen*, and Heinrich Nçth2)
Department Chemie der Ludwig-Maximilians-Universitꢀt, Butenandt-Strasse 5 – 13, D-81377 Mꢁnchen
Dedicated to the Memory of Jꢀrgen Sauer
The title compound (short version: BTE) occurs in (E)- and (Z)-isomers (both with b.p. of ca. 1008)
which equilibrate with nucleophilic catalysts. Both undergo (2 þ 2) cycloadditions with methyl vinyl ether
at 258. Three stereogenic centers in the cyclobutanes led to four rac-diastereoisomers, which were
obtained in pure and crystalline state. The structures were elucidated by 19F-NMR spectroscopy and
confirmed by two X-ray analyses. The cycloadditions were not stereospecific: e.g., (E)-BTE furnished
73% trans-adducts (with respect to the CF3 groups) and 27% cis-adducts. The loss of stereochemical
integrity occurs in the intermediate gauche-zwitterions which can cyclize or rotate, but not dissociate.
Under extreme conditions (2m LiClO4 in Et2O, 708, 3 months), the thermodynamic equilibrium of the
four cyclobutanes was achieved. Considerations of Coulombic attraction and conformational strain in the
zwitterionic intermediates allow us to rationalize the observed proportions of diastereoisomeric
cyclobutanes. Ethyl vinyl ether and butyl vinyl ether furnished cyclobutanes in similar diastereoisomer
ratios.
1. Introduction. – 1.1. (2 þ 2) Cycloadditions of Electrophilic and Nucleophilic C¼C
Bonds. The dimerization of ethene to give cyclobutane is an equilibrium reaction in
which cyclobutane dominates at 258. However, high temperature is required to surpass
the activation barrier, i.e., E ꢀ 44 kcal molꢁ1, but at 5008 the equilibrium shifts to the
side of ethene. The process involves the 1,4-tetramethylene biradical as an intermedi-
ate.
When electrophilic and nucleophilic C¼C bonds are chosen as reactants, the
formation of cyclobutanes proceeds at room temperature, as discovered by Williams
et al. [1] in the du Pont Laboratories. The (2 þ 2) cycloaddition of ethenetetracarboni-
trile (TCNE) with enol ethers serves as an example (Scheme 1). Here, a tetra-
methylene-type 1,4-zwitterion 1 is an attractive intermediate bearing a carboxonium
ion at one terminus, and two CN groups stabilizing the anionic charge at the other
end.
The intermediacy of the zwitterion has been established by plenty of mechanistic
criteria in the Munich Laboratory in the 1970s (for a review, see [2]): low stereo-
1
)
)
Present address: Institut fꢁr Chemie und Biochemie der Freien Universitꢀt Berlin, Takustrasse 3, D-
14195 Berlin.
Department Chemie der Ludwig-Maximilians-Universitꢀt Mꢁnchen, Butenandt-Strasse 5 – 13, D-
81377 Mꢁnchen.
2
ꢂ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 1
specifity of ring closure, reversibility of zwitterion formation, high influence of solvent
polarity on the rate constant, structureꢁrate relationships. Furthermore, various
methods of interception were successful (for a review, see [3]).
A rapid evolution of the (2 þ 2) cycloaddition chemistry took place in the light of a
new concept, the WoodwardꢁHoffmann rules for conservation of orbital symmetry (for
a review, see [4]). The p2s þ p2s cycloaddition is forbidden to be concerted. In the two-
step process, 1,4-biradicals and 1,4-zwitterions occur which are not alternatives, but
rather extremes on a continuous scale. It depends on the substitution pattern where a
specific tetramethylene has to be located on that scale.
When methyl (Z)-prop-1-enyl ether (2) was reacted with TCNE, the (Z)-geometry
of substituents is retained in the main cycloadduct cis-5. The minor product, trans-5,
goes back to a rotation in the zwitterionic intermediate, 3 > 4 (Scheme 2). In benzene,
the cyclobutanes with retention and inversion occurred in a 95 :5 ratio. The fraction of
trans-5 rose with solvent polarity, and reached a cis/trans ratio of 84 :16 in MeCN [5].
Scheme 2
An eventual rotation about the former C¼C bond of the acceptor olefin, TCNE,
remains hidden, since the pattern of substitution does not give rise to stereogenic
centers. We set out to learn about acceptor rotation and to broaden the basis of the
project.
1.2. (E)- and (Z)-1,2-Bis(trifluoromethyl)ethene-1,2-dicarbonitrile ((E)- and (Z)-9,
resp.) as an Acceptor-Substituted Ethylene. The pioneering work on this (E)/(Z) pair
also came from the du Pont Laboratories. The synthesis, described by Cairns and co-

Helvetica Chimica Acta – Vol. 95 (2012)
3
workers [6][7] and outlined in Scheme 3, is not a convenient, but a reproducible
procedure. In the last step, the chlorosulfite 8 undergoes eliminattion of SO2 and HCl in
refluxing sulfur at 4408; the ingenuity of the authors is baffling. The assignment of (E)-
and (Z)-9 mainly rested on the 19F-NMR spectra of the DielsꢁAlder adducts with
cyclohexa-1,3-diene.
Scheme 3
Cairns and co-workers studied the (2 þ 2) cycloadditions of (E)- and (Z)-BTE (i.e.,
(E)- and (Z)-9, resp.) with ethyl vinyl ether and tert-butyl vinyl sulfide, and obtained
pairs of cycloadducts; the 19F-NMR analysis indicated high stereospecificity [6]. It was
only in the slower reactions with (Z)-prop-1-enyl propyl ether that signals of a minor
third adduct appeared in the 19F-NMR spectrum. The slow isomerization of (Z)-
BTE ! (E)-BTE in certain solvents was recognized as a complicating factor.
In our hands, all the studied cyclobutane formations from (E)- and (Z)-BTE with
vinyl ethers turned out to be of moderate stereospecificity; e.g., the reaction with ethyl
vinyl ether gave rise to 21 and 13%, respectively, of inversion products. How did the
errors about the steric course come about? Probably, the quality of 19F-NMR analysis
in 1963 was not comparable with modern high-resolution technique.
2. Results and Discussion. – 2.1. Preparation of BTE, and of the (E)- and (Z)-
Isomers. The elimination of SO2 and HCl from 1-cyano-2,2,2-trifluoroethyl chlorosul-
fite (8; Scheme 3) formally generates a carbene which dimerizes; the mechanism is
unknown. The thermolysis of 8 in sulfur at 4408 described by Cairns and co-workers [6]
was repeated on a 0.5-mol scale and gave up to 57% of BTE (62% [6]) with an (E)/(Z)
ratio of 55 :45. The isomer separation succeeded by vapor-phase chromatography
(VPC) on trisiloxane 704 (Dow Corning) as a stationary phase.
The elegant (E)/(Z)-assignment of the BTE isomers via the DielsꢁAlder adducts
[6] is supplemented here by analysis of the 19F,13C coupling in the NMR spectrum:
1J(C,F) ¼ 280 Hz was observed for (E)- and (Z)-BTE; only the latter shows an
additional F,F coupling between the non-equivalent 13CF3 (natural abundance) and
5
12CF3: two quadruplets with J(F,F) ¼ 11.1 Hz.
On handling BTE, the volatility (b.p. 1018) and the propensity of isomerization
must be considered. The equilibrium (E)-BTE > (Z)-BTE, established by nucleo-
philes, is solvent-dependent and contains the (Z)-form as minor fraction: 3.2% in
cyclohexane, 4.9% in CH2Cl2, and 6.6% in MeCN (slow without catalysis). Previously,

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Helvetica Chimica Acta – Vol. 95 (2012)
we described a mild catalysis by cyclic azo compounds which allowed the measurement
of isomerization rates [8].
A desirable additional access to (Z)-BTE was provided by a triplet-sensitized
photoisomerization of (E)-BTE. Direct irradiation into the UV-absorption band
initiated polymerization, but triplet sensitizers established photostationary equilibria
which reached nearly a 1:1 ratio of (E)- and (Z)-BTE. The data compiled in Table 1
reveal a relation with triplet energies [9].
Table 1. Triplet-Sensitized Photoisomerization of (E)-BTE (0.20m) in a Photoreactor of DURAN 70
Glass
Sensitizer (concentration)
Triplet energy
Solvent
Photostationary
equilibrium (Z) > (E)
[kcal molꢁ1
]
Diacetyl (0.046m)
56
61
62
66
69
69
74
Pentane
Pentane
Pentane
Benzene
Pentane
Benzene
Benzene
32 : 68
33 : 67
36 : 64
43 : 57
44 : 56
49 : 51
46 : 54
Naphthalene (0.055m)
Anthraquinonea)
Pyruvic acid (0.045m)
Benzophenone (0.033m)
Benzophenone (0.020m)
Xanthone (0.051m)
a) Saturated solution.
2.2. BTE and Alkyl Vinyl Ethers. 2.2.1. Procedure and Cycloadducts. The reactions
of (E)- and (Z)-BTE with methyl vinyl ether in CH2Cl2 proceeded at 208, and the
yellow color of the charge-transfer (CT) complex disappeared in 3 – 4 days. Thus, BTE
is substantially less active than TCNE, where the orange-red CT color fades within
30 min [10]. The cycloadducts 12 of BTE were distilled in vacuo and obtained in 90%
yield.
Three stereogenic centers in cyclobutane 12 allow four racemic diastereoisomers.
All four were present, though in rather different ratios, starting from (E)- or (Z)-BTE
(Table 2). The (1S)-enantiomers of 12 are chosen as illustrations in Scheme 4; trans and
cis refer to the relative positions of CF3 groups. The two major cycloadducts, 12(trans-1)
(52%) from (E)-BTE and 12(cis-1) (66%) from (Z)-BTE, show retention of acceptor
structure. By coincidence, adducts with acceptor inversion amount to 27% in both
reactions.
The major isomers of 12 crystallized from the distilled cycloadducts. The separation
of the others succeeded by preparative VPC on dinonyl phthalate as stationary phase.
All four rac-diastereoisomers of 12 were obtained in pure and crystalline state.
Analogous cycloadditions of (E)- and (Z)-BTE with ethyl vinyl ether and butyl
vinyl ether furnished adducts 13 and 14, respectively. In Table 2, relative yields of the
four diastereoisomers are collected. Thus, ethyl vinyl ether does not produce two
cycloadducts [6], but rather four rac-diastereoisomers with (E)- or (Z)-BTE.
According to the (R,S) convention, 12(cis-1) is (1RS,2SR,3SR)-3-methoxy-1,2-bis(tri-
fluoromethyl)cyclobutane-1,2-dicarbonitrile.
The loss of stereochemical integrity occurs on the level of the zwitterions 10 and 11
(Scheme 4) by rotation about the former C¼C bond of BTE. Our system is unsuitable

Helvetica Chimica Acta – Vol. 95 (2012)
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Table 2. Cycloadditions of (E)- and (Z)-BTE with Alkyl Vinyl Ethers in CH2Cl2 at 208: 19F-NMR
Analysis of Cycloadducts
Cycloadduct
Ratio of diastereoisomeric cyclobutanes [%]
Compound No.
R
Yield [%]
trans-1
trans-2
cis-1
cis-2
Reactions of (E)-BTE
12
13
14
Me
Et
Bu
89
89
98
52
56
59
21
23
21
1
2
2
26
19
18
Reactions of (Z)-BTE
12
13
14
Me
Et
Bu
90
90
99
2
1
2
25
12
14
66
81
79
7
5
3
Equilibrium of cyclobutanes (LiClO4)
12 Me
23
57
2
18
Scheme 4
for diagnosing donor rotation (former C¼C bond of vinyl ether). The occurrence of two
trans- and two cis-structures goes back to the initial orientation in the CT complex and
the formation of the first s-bond.
2.2.2. Structure Elucidation by 19F-NMR Spectroscopy. F,F Spin coupling through
five bonds is weak (0 – 2 Hz), but the lone electron pairs at the F-atoms mediate
ꢃcoupling through spaceꢄ. This term was used by Petrakis and Sederholm [11] and even
applied to cis-vicinal and trans-vicinal CF3 groups in cyclobutanes [12]. All the
cyclobutanes of Table 2 with cis-CF3 groups gave rise to two quadruplets with 5J(F,F) ¼
1
11.0 – 11.5 Hz in the H-decoupled 19F-NMR spectrum; trans-CF3 groups appear as
singlets, and only higher resolution reveals quadruplets with 5J(F,F) ¼ 1.0 – 1.5 Hz.
Furthermore, in compounds 12 – 14 the ensemble of 19F-chemical shifts allows us to

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Helvetica Chimica Acta – Vol. 95 (2012)
evaluate the contributions of mutual deshielding by substituents (Sect. 4.4) and to
allocate the structures to all four diastereoisomers. Two X-ray analyses served as
pivotal points.
2.2.3. X-Ray Structures of Two Cyclobutanes. The ring of cyclobutane is puckered
according to electron diffraction in the gas phase; the folding angle f amounts to 288,
and the inversion barrier is 1.45 kcal molꢁ1 [13][14]. Numerous X-ray analyses of
cyclobutane derivatives brought to light planar structures as well as puckered rings with
a variety of angles f [15]. The puckering angle – also the intracyclic torsion angle is
often quoted – is a compromise of angle strain (Baeyer) and conformational strain
(Pitzer).
Crystals of 12(trans-1) and 12(cis-1) were chosen for the X-ray analyses. The ball-
and-stick models shown in Fig. 1 illustrate the dominant influence of the voluminous
CF3 groups on the ring conformation. In 12(trans-1), the CF3 substituents approach
diaxial positions with a torsion angle of 1478 at the C(1)ꢁC(2) bond. The puckering
angle f is 228.
Fig. 1. X-Ray crystal structures of compounds 12(trans-1) and 12(cis-1)
In 12(cis-1), the cis-located CF3 groups enclose a torsion angle of 308 at the
C(1)ꢁC(2) bond. The shortest distance of F-atoms in neighboring CF3 groups amounts
to 267 pm. With a Van der Waals radius of 135 pm for the F-atom [16], the F ··· F
distance indicates close contact. This repulsive interaction of the CF3 groups increases
the puckering angle f to 318. Another consequence of the ring folding: the sum of the
intracyclic angles falls short of 3608 by 4.48 for 12(trans-1) and 8.38 for 12(cis-1).
The lengths of the CꢁC bonds – 155 pm in the cyclobutane parent [13][14] – are
increased by number and size of substituents. The tetrasubstituted C(1)ꢁC(2) bond of
157.7 pm in 12(trans-1) and of 158.4 pm in 12(cis-1) (Table 3) is substantially longer
than C(3)ꢁC(4) bond of 153.5 and 152.4 pm, respectively. The even longer C(2)ꢁC(3)
bond, with 158.4 pm for 12(trans-1) and 160.0 pm for 12(cis-1), suggests the
participation of a hyperconjugated structure with zwitterionic character.
2.2.4. The Role of the Zwitterions as Intermediates. The different diastereoisomer
mixtures of 12 – 14, obtained with (E)- and (Z)-BTE, do not change composition on
distillation or storage of solutions. This is in accordance with kinetic control of
cycloadditions. An observation of mechanistic significance: when (E)- or (Z)-BTE
were used in excess over the vinyl ether, the 19F-NMR spectra of the unconsumed BTE
after the end of the reaction did not show isomerization. A numerical example: ethyl
vinyl ether was reacted in CH2Cl2 with 1.2 equiv. of (Z)-BTE (isomer purity 99.4%), in

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Table 3. X-Ray Analysis of Cyclobutanes 12(trans-1) and 12(cis-1); Selected Bond Lengths and Angles
(standard deviations in parentheses)
12(trans-1)
12(cis-1)
Bond lengths [pm]
C(1)ꢁC(2)
157.7(5)
158.4(5)
153.5(6)
156.1(5)
153.1(5)
153.3(5)
147.7(6)
149.0(5)
158.4(4)
160.0(4)
152.4(4)
155.7(4)
151.9(4)
153.3(4)
148.3(4)
147.5(4)
C(2)ꢁC(3)
C(3)ꢁC(4)
C(4)ꢁC(1)
C(1)ꢁCF 3
C(2)ꢁCF 3
C(1)ꢁCN
C(2)ꢁCN
Bond angles [8]
C(4)ꢁC(1)ꢁC(2)
C(1)ꢁC(2)ꢁC(3)
C(2)ꢁC(3)ꢁC(4)
C(3)ꢁC(4)ꢁC(1)
89.2(3)
87.1(3)
89.9(3)
89.4(3)
88.4(2)
85.2(2)
89.2(2)
88.9(2)
the course of which 14% trans- and 86% cis-adducts were formed; however, the (E)-
content (0.6%) of the excess BTE was virtually undiminished. We must conclude that
the zwitterions, once formed, do not dissociate back to the reactants. This is in marked
contrast with the behavior of TCNE: after the interaction with 1.1 equiv. of (Z)-but-2-
enyl ethyl ether, the unconsumed 0.1 equiv. of the enol ether showed a (Z)/(E) ratio of
82 :18 and – by coincidence – also a 82 :18 ratio for cis/trans-cycloadduct [17].
Concentrated solutions of LiClO4 in Et2O resemble a salt melt and belong to the
most polar media known [18][19]. In 2m LiClO4 at 708, the cyclobutane ring of 12
appears to entertain an equilibrium with a small concentration of the zwitterionic
rotamers, which, in turn, mediate the equilibration of the four diastereoisomers.
Various mixtures of diastereoisomers were heated with ethereal 2m LiClO4 at 708 in
sealed NMR tubes for 3 months; the slow isomerizations were followed up by 19F-NMR
spectroscopy, as exemplified by Fig. 2; the plunge of 12(cis-1) from 52 to 2% is
dramatic.
The equilibrium system, established in a medium of high ionic strength, contains
80% 12(trans) and 20% 12(cis), corresponding to DG ¼ 0.94 kcal molꢁ1; the relative
shares of the four diastereoisomers are included in Table 2. Within the trans- and cis-
pair, the ortho-effect between 3-MeO and the bulky cis-vic-2-CF3 is disadvantageous,
as 23 vs. 57% (trans), and 2% vs. 18% (cis) testify. The high space demand of the CF3
substituent finds a numerical base in the conformational energies (kcal molꢁ1): CN,
0.17; MeO, 0.60; CF3, 2.1 [20][21].
2.2.5. Which Forces Determine the Steric Pathways? Our zwitterionic intermediates
are substituted tetramethylenes. The parent is a 1,4-biradical, a high-energy inter-
mediate in the thermolysis of cyclobutane; according to calculations [22], it prefers the
anti-conformation (zig-zag). The introduction of substituents (CN, CF3, OR) stabilizes
the tetramethylene, and the electrostatic attraction of the charge centers favors the
gauche-conformation, as shown in 10 and 11; the distance of the termini is roughly half
that of the anti-zwitterion.

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Helvetica Chimica Acta – Vol. 95 (2012)
Fig. 2. Equilibration of the four rac-diastereoisomers of 12 with 2m LiClO4 in Et2O at 708
The Newman projection with the bond C(2)ꢁC(3) as axis allows us to recognize the
torsion angle between the bond C(1)ꢁC(2), the former C¼C bond of the acceptor, and
C(3)ꢁC(4), which comes from the vinyl group (Fig. 3). Two different configurations of
the zwitterion, 15 and 16 (both racemic), emerge from the interaction of (E)-BTE and
methyl vinyl ether; the p-bonds are omitted in the formulae for the sake of clarity. Due
to the Coulombic potential, the torsion angle will be less than 608 (staggered). The
cationic charge is placed on the O-atom of the carboxonium ion. The CN and CF3
groups stabilize the carbanion, but to a different extent. In the resonance parameters of
Taft and co-workers [23], CN (0.49) ranks higher than CF3 (0.27). Consequently, the
center of anionic charge moves below (in 15) or above (in 16) the bisector of the
acceptor angle, and the torsion angle in 16 comes closer to the eclipsed conformation
than that in 15.
Fig. 3. BTE and methyl vinyl ether: putative conformations of zwitterionic intermediates 15 and 16
Prelog and Helmchen introduced the descriptors of two-dimensional chirality, Re
and Si [24]. When the positions are numbered as in the corresponding cyclobutanes,
(1R,2Si,3Si) would describe the configuration of 15, and (1S,2Re,3Si) that of 16. On 1,4-

Helvetica Chimica Acta – Vol. 95 (2012)
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cyclization, the more favorable zwitterion 15 furnishes the more hindered cyclobutane
and vice versa with 16. This model allows a rationalization of the steric course.
Four zwitterions are shown in Fig. 4, all based on the (S)-configuration of the
initially formed stereogenic center at C(1). The horizontal double arrows indicate
rotations about the acceptor bond, the vertical ones are reserved to donor rotations.
The rotamers (1S,2Re,3Re)-15 and (1S,2Si,3Si)-15 have greater torsion angles than
(1S,2Re,3Si)-16 and (1S,2Si,3Re)-16, and offer a more favorable compromise of Pitzer
strain and Coulombic potential. It is plausible that type 15, due to its energetic
advantage, enjoys a preference over type 16 in the formation from (E)- and (Z)-BTE
with methyl vinyl ether.
Fig. 4. Formation of four rac-diastereoisomers of 12 by (2 þ 2) cycloaddition of (E)- and (Z)-BTE with
methyl vinyl ether: proposed steric course
The zwitterion (1S,2Re,3Re)-15 produces 53% of 12(trans-1) by direct cyclization
and 26% of 12(cis-2) via (1S,2Si,3Re)-16 by rotation about the acceptor bond, i.e.,
together 79%. The selectivity in the formation of zwitterion (1S,2Si,3Si)-15 (and its
enantiomer) from (Z)-BTE appears to be even higher: 66% retention (!12(cis-1))
and 25% with acceptor rotation (!12(trans-2)) add up to 91% of the product.
The double arrows between the zwitterions do not indicate established rotamer
equilibria. Most of the zwitterions cyclize without rotation (Table 2).
2.2.6. Solvent Polarity and Diastereoisomer Ratios. The rate-determining step of the
cycloaddition is the formation of the zwitterion. The transition state (TS) of
establishing this first bond is certainly accompanied by an increase of charge separation

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Helvetica Chimica Acta – Vol. 95 (2012)
and should respond to solvent polarity. The Reichardt parameter ET is based on
solvatochromism and has been proved to be a useful measure of solvent polarity [25].
The influence of solvents on the ratio of diastereoisomeric cyclobutanes was studied
for the cycloadditions of (E)- and (Z)-BTE with ethyl vinyl ether (Table 4). The
diastereoisomers of 13 (Scheme 4) were generated via the same set of zwitterions
shown in Fig. 4, but now with MeO replaced by EtO. We tentatively concluded above
that the favored conformations (1S,2Re,3Re) and (1S,2Si,3Si) are the entrance gates to
the collection of zwitterions for the reactions of (E)- and (Z)-BTE, respectively.
Table 4. (2 þ 2) Cycloadditions of BTE with Ethyl Vinyl Ether: Influence of Solvent Polarity on the Ratio
of Diastereoisomeric Cyclobutanes 13 [%]
Solvent
ET [kcal molꢁ1
]
13(trans-1)
13(trans-2)
13(cis-1)
13(cis-2)
(E)-BTE as Reactant
without
C6D6
CH2Cl2
SO2
MeCN
60
64
56
51
46
20
21
23
20
14
1
1
2
3
2
19
14
19
26
38
34.3
40.7
)
a
45.6
(Z)-BTE as Reactant
without
C6D12
C6D6
CH2Cl2
MeCN
1
1
1
1
3
10
11
14
13
7
83
85
81
81
78
6
3
4
5
12
30.9
34.3
40.7
45.6
a) Not known.
In the interaction of (E)-BTE, direct ring closure of zwitterion (1S,2Re,3Re)-15 to
give 13(trans-1) remains the major pathway, although diminishing with increasing
polarity of the solvent from 64% in C6D6 to 46% in MeCN; 13(cis-2) profits with a rise
from 14 to 38%. In terms of Fig. 4, a rotation of the acceptor bond, i.e., (1S,2Re,3Re)-
15 ! (1S,2Si,3Re)-16, must precede the formation of 13(cis-2). The growth of solvation
energy increases the lifetime of the zwitterions as well as the chance of rotation.
Among the diastereoisomers of 13 obtained with (Z)-BTE, the direct cyclization of
zwitterion, (1S,2Si,3Si)-15 ! 13(cis-1), participates with 85% in C6D6 and with 78% in
MeCN.
The values compiled in Table 4 reflect relative rates and are based on substantial
ratios of rate constants: k(MeCN)/k(C6D6) ¼ 170 for (E)-BTE and 121 for (Z)-BTE,
both at 258 [26].
The diastereoisomer ratio did not change during the reaction. As a precaution, 19F-
NMR spectra were recorded from minute to minute (30 – 100% reaction) for BTE þ
ethyl vinyl ether in MeCN. Thus, even in the polar MeCN, kinetic control remains
undisturbed. The zwitterions, once formed, do not dissociate back to the reactants, as
described (Sect. 2.2.4) for experiments in CH2Cl2. When ethyl vinyl ether was reacted
with 1.7 equiv. of (Z)-BTE (purity 99.7%) in MeCN, the 19F-NMR analysis of the
unconsumed (Z)-BTE showed 99.2% purity, i.e., virtually no dissociation of zwitterions
either.

Helvetica Chimica Acta – Vol. 95 (2012)
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Experimental Part
1. General. See [8]. Prep. VPC was carried out with an instrument APG 402, Fa. Hupe & Busch, with
inserted evaporation chamber; for stationary phases, see below. A Varian Aerograph 1440 instrument
served anal. VPC (injection of sample directly on column), combined with Varian CDS 111 Integrator
(high sensitivity for purity of (E)- and (Z)-BTE). IR Spectra: The C ꢂ N str. frequency of the
cycloadducts is either missing or tiny; this is an old experience for nitriles with adjacent electron-
1
attracting substituents. H-NMR Spectra were recorded with Varian XL 100 (100 MHz) or Bruker WP
200 (200 MHz), and 13C-NMR spectra with Bruker WP 80 DS (20.15 MHz) or Bruker WP 200
1
(50.29 MHz); for 19F-NMR spectra, usually H-decoupled, Varian XL 100 (94.1 MHz) or Jeol FX 90
(84.29 MHz) were used with FCCl3 as internal standard (negative sign for CF3 in cycloadducts).
2. Materials. Methyl vinyl ether (Baker, 99.9%) was distilled over LiAlH4. Ethyl vinyl ether (Merck)
and butyl vinyl ether (EGA), likewise distilled over solid LiAlH4, were fractionated with a Vigreux
column (20 cm). Org. solvents were usually p.a. or Uvasol quality (mostly Merck); for purification, see
[27]. Standards for quant. 19F-NMR analysis: fluorobenzene (Fluka) and trifluoromethylbenzene
(Merck), passed through a column of basic Al2O3, were dried over molecular sieves, and rectified under
Ar; 1,1-dichloro-2,2,2-trifluoroethylbenzene [28], b.p. 918/37 Torr, was stored under Ar at 08.
3. 1,2-Bis(trifluoromethyl)ethene-1,2-dicarbonitrile (¼2,3-Bis(trifluoromethyl)but-2-enedinitrile;
BTE; 9). 3.1. Trifluoroacetaldehyde Hydrate (¼2,2,2-Trifluoroethane-1,1-diol; 6) [29]. Trifluoroacetic
acid (4.2 mol) in abs. Et2O (1 l) was cooled to ꢁ 788, and a suspension of LiAlH4 (1.25 mol) in Et2O (1 l)
was slowly added; fract. distillation gave 6 (83%); b.p. 101 – 1048 (103 – 1058 [29]).
3.2. Trifluoroacetaldehyde Cyanohydrin (¼ 3,3,3-Trifluoro-2-hydroxypropanenitrile; 7). The con-
version of 6 ! 7 according to [30] gave 76% of 7 with b.p. 53 – 548/12 Torr; with a drop of conc. H2SO4
added, 7 could be stored at 08.
3.3. 1-Cyano-2,2,2-trifluoroethyl Chlorosulfite (8). For the reaction with SOCl2, the presence of some
NH4Cl [6] is mandatory, though its function is unclear. SOCl2 (3.6 mol, Merck, freshly distilled) and
NH4Cl (1.3 g) were refluxed for 15 min. Compound 7 (0.99 mol) was dropwise introduced into the ice-
cooled, stirred SOCl2. After refluxing (bath 908) for 12 h, distillation over a Vigreux column (60 cm)
removed the excess of SOCl2, and the yellow 8 followed at 458/14 Torr (50%): 76%. B.p. 41 – 428/10 Torr
[6]). Compound 8 is of limited storability.
3.4. Thermolysis of 8 at 4408. A failed experiment of pyrolysis of 8 in an Ar stream suggests a
protective role of sulfur. The apparatus described in [6] was only slightly modified. The elemental sulfur
(230 g) was refluxed in a double-necked flask in a salt bath regulated at 460 – 4658. Two vertical tubes
(60 cm, 3-cm-wide) acted as air coolers for the sulfur vapor, one bearing a jacketed, water-cooled
dropping funnel, the other leading to the cooled (CO2/acetone) trap. The chlorosulfite 8 (0.496 mol) was
introduced into the boiling sulfur with a rate of ca. 1 drop/s. After evaporation of the condensed SO2, 9
was twice distilled (the second time over a 20-cm column) and obtained as a colorless liquid, b.p. 101 –
1028, which consisted of (E)-9/(Z)-9 55 :45. Yield variable, up to 57% ([6]: 62%).
3.5. Separation of (E)- and (Z)-BTE. Cairns et al. [6] used VPC with a ꢃsilicone fluidꢄ on
diatomaceous earth at 538. We found Dow Corning 704 (1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisilox-
ane) suitable. Acid-washed kieselgur (Merck 9697; 250 g) was mixed with DC 704 (45 g) in pentane (1 l).
The solvent was removed in the rotatory evaporator (208), the material was dried at 208/10 Torr, filled
into a U-shaped column (2 m, ˘ 3 cm), and fit into the VPC instrument APG 402. BTE was injected in
300 ml portions into the column kept at 358, inlet and outlet at 908, and with N2 stream 400 ml/min.
Retention times (tR): 15 min for (E)-BTE and 27 min for (Z)-BTE; base line was reached in between. A
total of 6.8 g of isomer mixture furnished 2.8 g of (E)-BTE and 2.3 g of (Z)-BTE (75%); purity control
was conducted by 19F-NMR or anal. VPC. For storage and reactions of BTE, acid-washed glassware was
employed, and the experimenter should be aware of the fact that BTE (mol. mass 214) has virtually the
same volatility as H2O.
3.6. Photostationary Equilibrium of (E)- and (Z)-BTE (Table 1). a) The soln. of (E)-BTE (2.14 g,
10.0 mmol) and benzophenone (0.91 g, 5.0 mmol) in pentane (150 ml) was irradiated in a water-cooled
reactor made of DURAN 50 glass (non-transparent in the absorption range of BTE) with a Hg high-
pressure arc (HANAU Q700, 500 W) for 8 h under Ar; the 19F-NMR singlets indicated an (E)/(Z) ratio

12
Helvetica Chimica Acta – Vol. 95 (2012)
of 51:49. On cooling the soln. to ꢁ 788, BTE and benzophenone crystallized, and they were isolated by
suction; distillation provided the BTE mixture þ little pentane.
b) The soln. (1.0 ml) of (E)-BTE (0.20m) and benzophenone (0.049m) in benzene was irradiated in a
NMR tube, and periodically 19F-NMR spectra were recorded. Hours (fraction of (Z)-9): 1.5 (9%), 4
(20%), 10 (37%), 40 (49%). For workup, benzene as solvent is unsuitable.
3.7. Characterization of BTE. a) (E)-BTE ((E)-9) crystallized in colorless thin leaflets (recryst. from
pentane or sublimation at 258/12 Torr). M.p. 60.5 – 61.58 (closed cap.). UV (CH2Cl2): lmax (log e) 227
(4.10). 13C-NMR (CDCl3, 20.2 MHz, 1H-decoupled): 107.3 (s, slightly broadened, 2 C ꢂ N); 117.6 (q,
2
1J(C,F) ¼ 280, 2 CF3); 123.9 (q, J(C,F) ¼ 40.3, 2 olefin. C). 19F-NMR (CH2Cl2, 94.1 MHz): ꢁ 62.1 (s,
1
2 CF3); ꢁ 60.8, ꢁ 63.8 (2s, 13C-satellites, J(C,F) ¼ 280). MS (70 eV, 308): 214 (31, Mþ), 195 (11, [M ꢁ
F]þ), 145 (36, [M ꢁ CF3]þ), 69 (100, CF3).
b) (Z)-BTE ((Z)-9). Purity by anal. VPC: 99.27% (Z), 0.73% (E). UV (CH2Cl2): lmax (log e) 232
(3.98). 13C-NMR (CDCl3, 20.2 MHz): 109.2 (s, 2 C ꢂ N); 117.1 (q, 1J(C,F) ¼ 279, 2 CF3); 123.9 (q,
2J(C,F) ¼ 40, 2 olefin. C). 19F-NMR (CH2Cl2, 94.1 MHz): ꢁ 59.1 (s, 2 CF3); ꢁ 57.7, ꢁ 60.7 (2q, 13C-
satellites, 1J(C,F) ¼ 280, 5J(C,F) ¼ 11.1, 2 CF3). Anal. calc. for C6F6N2 (214.08): C 33.66, N 13.09; found:
C 33.81, N 13.12.
4. (2 þ 2) Cycloadditions of BTE and Methyl Vinyl Ether. 4.1. (E)-9. Methyl vinyl ether (68 mg,
1.17 mmol) was condensed into a NMR tube at ꢁ 788, closed with a septum, and weighed. After injection
of the soln. of (E)-9 (221 mg, isomer purity > 99.9%) in CH2Cl2 (0.5 ml) at ꢁ 788, the tube was cooled
with liquid N2 and melted off at the tapered position.
The yellow soln. (CT complex color) at r.t. became colorless in 4 d. A 19F-NMR spectrum was
recorded, before the content of the tube was transferred into a microflask and distilled at 608/0.02 Torr:
12 as a colorless, partially crystalline oil (248 mg, 89%); a weighed amount of standard – 1,1-dichloro-
2,2,2-trifluoroethylbenzene (d ꢁ 78.2) – was added for the quant. 19F-NMR analysis in CH2Cl2. The
diastereoisomer ratios of 12 remained constant in weeks at r.t. and were determined by the following 19F-
NMR signals: ꢁ 62.6 (q, 2-CF3, cis-1); ꢁ 66.3, ꢁ 71.6 (2s, trans-1); ꢁ 67.7 (q, 2-CF3, cis-2); ꢁ 70.3 (s, 2-
CF3, trans-2). The integrals were added up, and the relative amounts are collected in Table 2. Anal. calc.
for C9H6F6N2O (272.15): C 39.72, H 2.22, N 10.29; found for isomer mixture: C 40.00, H 2.37, N 10.26.
Besides 12, the 19F-NMR spectrum before distillation indicated 7% of 1:2 adducts [31]. In another
experiment with 1.79 mmol of methyl vinyl ether and 0.96 mmol of (E)-9 in CH2Cl2 (0.5 ml), 11% of 1:2
adducts and 89% of 1:1 adducts (unchanged isomer ratio) were formed (rel. yields). An experiment
without solvent gave a slightly varied isomer composition (Table 4).
4.2. (Z)-9. A specimen (1.17 mmol) with 99.2% (Z)- and 0.8% (E)-content was reacted with methyl
vinyl ether (1.10 mmol) in CH2Cl2 (0.5 ml), as described above. The distillation at 608/0.05 Torr furnished
oil and crystals (270 mg, 90%). The 19F-NMR spectrum (CH2Cl2) was unchanged after 4 weeks at r.t. and
confirmed kinetic control of the cycloaddition. The ratios of the diastereoisomers listed in Table 2 do not
include the 0.8% admixture of (E)-9. The weight standard for the 19F-NMR analysis was fluorobenzene
with d ꢁ 113.7. Anal. of diastereoisomer mixture: calc. for C9H6F6N2O (272.15): C 39.72, H 2.22, N 10.29;
found: C 39.84, H 2.16, N 10.47.
4.3. Separation of Cyclobutanes 12. The column (8 m, ˘ 1 cm) for the prep. VPC was filled with acid-
washed kieselgur (Anakrom A; 0.15 – 0.18 mm; Fa. Antechnika) and charged with 10% of dinonyl
phthalate (Fa. Merck); column temp., 608; inlet temp., 958; detector temp., 1158; N2 pressure, 1.1 atm. tR:
22.0 h for cis-1, 22.4 h for cis-2, 19.0 h for trans-2, and 20.1 h for trans-1; 5 portions of 30 – 60 mg of the
mixture, obtained from (E)-9, were used for the isolation of trans-1, trans-2, and cis-2, whereas the cryst.
product from (Z)-9 was an ample source of cis-1.
4.4. Note on Structural Assignment by 19F-NMR Spectroscopy. The F,F coupling is limited to cis-
located CF3 groups (J(F,F) ꢀ 11). A second criterion of differentiation comes from a net of mutual
deshielding effects by substituents. The size of this effect on d(F) varies and allows a consistent
attribution:
cis-vic-MeO > trans-vic-MeO > cis-vic-CF3 > trans-vic-CF3 > 1,3-cis-MeO > 1,3-trans-MeO

Helvetica Chimica Acta – Vol. 95 (2012)
13
4.5. (1RS,2RS,3RS)-3-Methoxy-1,2-bis(trifluoromethyl)cyclobutane-1,2-dicarbonitrile (12(trans-1)).
This is the main constituent (52%) of the oil and crystals from (E)-9 and the unsaturated ether. The oil
was adsorbed by filter paper; repeated recrystallization of the solid from CH2Cl2/pentane and subsequent
sublimation at 358/0.05 Torr gave colorless prisms. M.p. 78.5 – 798 (sealed cap.). IR (KBr): 714s, 810w,
996m, 1077m, 1089m; 1136s, 1143s, 1198vs þ 1210vs (br.), 1285s (CꢁF, CꢁO str.), no C ꢂ N str. visible;
2845w (MeO), 2920w, 2950w (CꢁH, sharp). 1H-NMR (100 MHz, CDCl3, F-decoupled): 3.85 (s, MeO);
the ABX system of ring-H was simulated with the program LAME [32]: 3.32, 3.40 (AB, CH2(4)); 4.81 (X,
HꢁC(3)); 2JAB ¼ 13.8, 3JAX ¼ 9.1, 3JBX ¼ 8.9. 13C-NMR (50.3 MHz, 1H-decoupled): 36.6 (s, C(4)); 39.9 (q,
2
2J(C,F) ¼ 34, C(1)); 51.6 (q, J(C,F) ¼ 29, C(2)); 60.0 (s, MeO); 77 (C(3), overlap with CDCl3); 111.0,
111.3 (2s, 2 CN); 121.6 (q, 1J(C,F) ¼ 284, CF3); 122.4 (q, 1J(C,F) ¼ 283, CF3). 19F-NMR (CDCl3,
94.1 MHz): ꢁ 66.5 (br. s, 2-CF3); ꢁ 71.2 (br. s, 1-CF3); on 1H-decoupling 2 sharp s).
4.6. (1RS,2RS,3SR)-Isomer (12(trans-2)). The fraction of VPC was distilled at 608/0.1 Torr and
crystallized at 08. M.p. ca. 208. IR: 726m (sharp), 921m, 985m; 1057s (CꢁO); 1202vs þ 1262vs (br. (CꢁF,
CꢁO)), no C ꢂ N; 2850w, 2950w (CꢁH). 1H-NMR (CDCl3, 100 MHz, F-decoupled): 3.54 (s, MeO), ABX
2
system calc. with the method of effective Larmor frequencies [33]: 2.90, 3.06 (AB part, JAB ¼ 13.4,
HAꢁC(4), HBꢁC(4)); 4.49 (X, 3JAX ¼ 8.1, 3JBX ¼ 7.9, HꢁC(3)). 19F-NMR (CH2Cl2, 94.1 Hz): ꢁ 68.9 (br. s,
2-CF3), ꢁ 71.6 (s, structured, 1-CF3); (CDCl3): ꢁ 69.0 (br. s, 2-CF3), ꢁ 70.5 (d, partially resolved,
5J(F,F) ¼ 1.5, 1-CF3).
4.7. (1RS,2SR,3SR)-Isomer (12(cis-1)). The colorless leaflets, obtained by VPC, were sublimed at
408/0.05 Torr. M.p. 78.0 – 78.58 (pentane). IR: 731m, 747m, 993m, 1030m, 1043m (all sharp); 1174s,
1183m, 1193s, 1202s, 1238m, 1261s, 1303s (all CꢁO, CꢁF str.); 2255vw (C ꢂ N non-conjug.), 2840vw (CꢁH
1
of MeO); 2950w, 2980w, 3035w (CꢁH, sharp). H-NMR (CDCl3, 100 MHz, F-decoupled): 3.02 (br. d,
3
4
3J(3,4) ¼ 9.0, CH2(4)); 3.60 (s, MeO); 4.69 (t, J(3,4) ¼ 9.0, HꢁC(3)); (F-coupled): 3.02 (dq, J(H,F) ¼
0.9, CH2(4)); 4.69 (tq, 4J(H,F) ¼ 1.9, HꢁC(3)). 13C-NMR (CDCl3, 50.3 MHz, 1H-decoupled): 36.2 (s,
2
2
C(4)); 42.3 (q, J(C,F) ¼ 30, C(1)); 53.6 (q, J(C,F) ¼ 31, C(2)); 59.9 (s, MeO); 77 (below CꢁD signals,
C(3)); 112.4 (q, 3J(C,F) ¼ 3.5, CN); 113.4 (q, 3J(C,F) ¼ 1.5, CN); 120.6 (q, 1J(C,F) ¼ 281, CF3); 121.1 (q,
1J(C,F) ¼ 284, CF3). 19F-NMR (CDCl3, H-decoupled): ꢁ 62.9 (br. q, J(F,F) ¼ 11.0, 2-CF3); ꢁ 68.9 (q,
1
5
5J(F,F) ¼ 11.4, 1-CF3).
4.8. (1RS,2SR,3RS)-Isomer (12(cis-2)). Distillation of the product (288 mg), which was obtained
from (E)-9 and methyl vinyl ether in MeCN, furnished oil and crystals, which were separated by filter
paper. Colorless needles (23 mg) were obtained from pentane. M.p. 77.5 – 78.08. IR: 720m, 743m, 985s,
1043m (all sharp); 1109s, 1179vs þ 1220vs (br.), 1290s (br., CꢁO, CꢁF), 2255vw (C ꢂ N, uncertain).
1H-NMR (CDCl3, 100 MHz, 19F-decoupled): 3.82 (s, MeO); ABX calc. with effective Larmor frequencies
[33]: 3.26, 3.35 (AB, JAB ¼ 13.4, CH2(4)); 4.73 (X, 3J(3,4A) ¼ 8.8, 3J(3,4B) ¼ 7.7, HꢁC(3)); (fully
6
coupled): 33.0, 33.2 (2 apparent dqq, J(H,F) ¼ 0.8 and 0.6, CH2(4)); 3.82 (q, J(H,F) ¼ 0.3, MeO); 4.74
(apparent tq, 4J(H,F) ¼ 0.8, HꢁC(3)). 13C-NMR (CDCl3, 50.3 MHz, 1H-decoupled): 35.4 (s, C(4)); 41.4
2
2
(q, J(C,F) ¼ 37, C(1)); 57.3 (q, J(C,F) ¼ 37, C(2)); 58.7 (s, MeO); 73.1 (s, C(3)); 109.9, 112.1 (br. 2s,
2 CN); 120.3 (q, 1J(C,F) ¼ 276, CF3); 121.9 (q, 2J(C,F) ¼ 281, CF3). 19F-NMR (CDCl3, 50.3 MHz, H-
decoupled): ꢁ 67.9, ꢁ 68.8 (2q, 5J(F,F) ¼ 11.4, further split, 2 CF3); (CH2Cl2): ꢁ 67.8, ꢁ 68.8 (2q,
5J(F,F) ¼ 11.2, 2 CF3).
4.9. Equilibration of Cyclobutanes 12. LiClO4 (p.a.) was dried at 1608/0.3 Torr for 4 h and dissolved in
abs. Et2O. The 2m soln. (0.5 ml) and the diastereoisomers of 12 (114 mg, ca. 0.40 mmol, obtained with
(E)-9), in a sealed NMR tube, were heated in a thermostat at 708; in a second tube, a specimen of 12,
prepared from (Z)-9, was treated correspondingly with 2m LiClO4. Fig. 2 shows the slow isomerization;
after 143 d, the two isomer mixtures have become identical within the limits of the 19F-NMR analysis. No
BTE signals were observed. Beginning decomposition was noticed after 160 d.
5. (2 þ 2) Cycloadditions of BTE (9) with Ethyl Vinyl Ether. 5.1 (E)-9. The procedure was similar to
that described above; a brief description of one example would be sufficient. Ethyl vinyl ether (70 mg,
0.97 mmol) and (E)-9 (246 mg, 1.15 mmol) in CH2Cl2 (4 ml) showed a light-yellow CT complex color
which slowly faded. After 8 d at r.t., the solvent was removed, and distillation at 558/0.3 Torr furnished 13
as a colorless oil (248 mg, 89%); Table 2 shows the ratio of the four diastereoisomers. The quant. 19F-
NMR analysis was based on the following signals: ꢁ 71.6, ꢁ 66.4 (2s) for 13(trans-1), ꢁ 70.3 (s) for
13(trans-2), ꢁ 62.7 (q) for 13(cis-1), and ꢁ 67.7 (q) for 13(cis-2). As described above, the elemental

14
Helvetica Chimica Acta – Vol. 95 (2012)
analysis was carried out for the isomer mixture. Anal. calc. for C10H8F6N2O (286.18): C 41.97, H 2.82, N
9.79; found: C 41.94, H 2.92, N 9.75.
Further cycloaddition experiments were carried out in other solvents. The fast reaction in MeCN was
virtually complete for (E)-9 after 13 min and for (Z)-BTE after 4.5 min.
In the reaction of (Z)-9 without solvent, the deep-yellow color disappeared in 20 min; the 19F-NMR
analysis (Table 2) was performed with fluorobenzene (ꢁ113.7 in CH2Cl2) as a weight standard. The
distilled oil (65%/0.02 Torr) showed the same isomer composition as before. Anal. calc. for C10H8F6N2O
(286.18): C 41.97, H 2.82, N 9.79; found: C 42.03, H 2.82, N 9.89.
5.2. Separation of the Isomers of Cyclobutanes 13 and Assignment. Only partial separation was
achieved with VPC on dinonyl phthalate or bis(2-ethylhexyl) sebacate as stationary phases. The major
products were 13(trans-1) (52%) from (E)-9 and 13(cis-1) (66%) from (Z)-9. Besides the F,F-coupling of
cis-located CF3 groups, the mutual deshielding effects of substituents (Sect. 4.4) established the
structures.
5.3. (1RS,2RS,3RS)-3-Ethoxy-1,2-bis(trifluoromethyl)cyclobutane-1,2-dicarbonitrile (13(trans-1)).
The compound partially crystallized from the distilled mixture, obtained with (E)-9. Oily constituents
were removed by pressing between filter papers. Colorless prisms crystallized from pentane. M.p. 28.5 –
29.58. IR: 714m (sharp, CF3 deform.), 1200vs and 1282s (very br., CꢁO, CꢁF str.); no clear C ꢂ N vibr.
1H-NMR (CDCl3, 100 MHz, F-decoupled): 1.25 (t, 3J ¼ 7.0, Me of EtO); 3.5 – 3.9 (m, CH2 of EtO); 3.03,
3.08 (AB from Larmor frequencies, 2J(4A,4B) ¼ 13.8, HAꢁC(4), HBꢁC(4)); 4.58 (X of ABX, 3J(3,4A) ¼
3
1
10.2, J(3,4B) ¼ 7.8, HꢁC(3)). 19F-NMR (CDCl3, 94.1 MHz, H-decoupled): ꢁ 71.9, ꢁ 66.7 (2s, 2 CF3);
in CH2Cl2: ꢁ 71.6, ꢁ 66.4.
5.4. (1RS,2SR,3SR)-Isomer (13(cis-1)). This compound crystallized from the dist. material (experi-
ment with (Z)-9). M.p. 35.0 – 35.58 (pentane). IR: 732m, 749w (both sharp); 1031m, 1045m, 1167s,
Table 5. X-Ray Crystallographic Data of Compounds 12(trans-1) and 12(cis-1)
12(trans-1)
12(cis-1)
CCDC
856014
856015
Molecular formula
Molecular mass
Temp. [K]
C9H6F6N2O
272.15
153
C9H6F6N2O
272.15
153
Space group, Z
Crystal size [mm]
Unit cell dimensions:
a [ꢅ]
b [ꢅ]
c [ꢅ]
b [8]
Volume [ꢅ3]
Density calc. [g/cm3]
Wave number (MoKa) [mmꢁ1
2q Range [8]
C2/c, 8
0.30 ꢃ 0.24 ꢃ 0.35
P21/c, 4
0.30 ꢃ 0.28 ꢃ 0.42
20.047(6)
7.754(3)
14.106(4)
98.54(2)
2232.7(18)
1.619
7.091(2)
15.378(4)
10.238(3)
103.69(3)
2168.3(13)
1.667
]
1.72
2 – 40
1.72
2 – 50
Reflex width [8]
Measurement speed [8/min]
Reflections collected
Control reflections
1.0
1.3 – 29.3
1284
1.2
1.5 – 29.3
2269
52
108
Reflections unique with I > 3s(I)
1109
1902
930
1563
Parameters refined
Final R
wR2
181
0.069
0.057
186
0.058
0.058

Helvetica Chimica Acta – Vol. 95 (2012)
15
1206vs (br.), 1236s (br.), 1273s (br., CꢁO, CꢁF str.); no distinct CN band. 1H-NMR (CDCl3, 100 MHz,
F-decoupled): 1.27 (t, 3J ¼ 7.0, Me of EtO); 3.02 (2 d, 3J ¼ 9.0, CH2(4)); 3.3 – 3.9 (m, diastereotopic CH2 of
3
4
EtO); 4.74 (t, J(3,4) ¼ 9.0, HꢁC(3)); (fully coupled): 3.02 (dq, J(H,F) ¼ 1.0, only partially resolved,
CH2(4)); 4.74 (tq, J(H,F) ¼ 1.7, HꢁC(3)). 19F-NMR (CDCl3, 94.1 MHz, H-decoupled): ꢁ 63.0 (br. q,
4
1
5J(F,F) ¼ 11.4, 2-CF3); ꢁ 69.1 (q, J(F,F) ¼ 11.4, 1-CF3).
5
6. 3-Butoxy-1,2-bis(trifluoromethyl)cyclobutane-1,2-dicarbonitrile (14). The cycloaddition of (E)-9
to butyl vinyl ether in CH2Cl2 at r.t. was complete after 3 d; the solvent was removed, and
(trifluoromethyl)benzene (19F-NMR, d ꢁ 63.1) was added in a weighed amount. The yield of the four
diastereomeric adducts 14 was 99% (for composition, see Table 2). Distillation at 658/0.3 Torr gave a
colorless oil. The separation was not attempted. Anal. calc. for C12H12F6N2O (314.23): C 45.86, H 3.85, N
8.92; found: C 46.00, H 3.92, N 9.15.
The color of the deep-yellow soln. of (Z)-9 (0.59 mmol) and butyl vinyl ether (0.51 mmol) in CH2Cl2
(0.5 ml) faded in 16 h. Evaporation of the solvent left 14 as a colorless oil (158 mg, 99%). The elemental
analysis confirmed the purity. Anal. calc. for C12H12F6N2O (314.23): C 45.86, H 3.85, N 8.92; found: C
46.12, H 3.87, N 9.00.
Without separation of the diastereoisomers of 14, the close relation of the 19F-NMR spectrum with
those of 12 and 13 allowed the structural assignments. 19F-NMR (CH2Cl2, 94.1 MHz, H-decoupled):
ꢁ 66.2 (s) and ꢁ 71.6 (s) for 14(trans-1), ꢁ 68.8 (s) and ꢁ 70.3 (s) for 14(trans-2), ꢁ 62.6 (q, J ¼ 11.5) and
ꢁ 68.9 (q, J ¼ 11.5) for 14(cis-1), and ꢁ 67.6 and ꢁ 68.6 (2q, J ¼ 11.0) for 14(cis-2).
7. X-Ray Analyses of 12(trans-1) and 12(cis-1). For details, see Table 5. Crystallographic data have
been deposited with the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 IEZ,
UK, with deposition numbers CCDC-856014 for 12(trans-1) and 856015 for 12(cis-1).
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Received November 16, 2011