CuCl-catalyzed isomerization of gem-Chlorofluoro-cyclopropanes into chlorofluoroalkenes

Article abstract of DOI:10.1016/j.mencom.2013.01.006

CuCl-catalyzed isomerization of gem-chlorofluorocyclopropanes into chlorofluoroalkenes occurs as a result of the ring opening accompanied by the migration of chlorine atom. In the case of vinyl- or cyclopropyl-containing substrates, chlorofluoroalkadienes

Full text of DOI:10.1016/j.mencom.2013.01.006

Mendeleev
Communications
Mendeleev Commun., 2013, 23, 19–21
CuCl-catalyzed isomerization of gem-chlorofluoro-
cyclopropanes into chlorofluoroalkenes
Nikolai V. Volchkov,* Maksim A. Novikov, Mariya B. Lipkind and Oleg M. Nefedov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 6390; e-mail: volchkov@ioc.ac.ru
DOI: 10.1016/j.mencom.2013.01.006
CuCl-catalyzed isomerization of gem-chlorofluorocyclopropanes into chlorofluoroalkenes occurs as a result of the ring opening accom-
panied by the migration of chlorine atom. In the case of vinyl- or cyclopropyl-containing substrates, chlorofluoroalkadienes are formed.
CuCl/
A common feature of gem-dihalogenocyclopropanes is their ability
to undergo solvolytic and thermal cyclopropyl-allylic type ring-
opening of the three-membered cycle.1–3 Such reactions are induced
by stoichiometric amounts of silver salts1–3,4 or some other electro-
philic reagents3 or by heating1–3,5 and lead to 2-haloallylic deriva-
tives or 2-halo-1,3-dienes. gem-Dihalogenocyclopropanes can also
thermally isomerize into 2,3-dihaloalkenes1–3,6 via the cleavage of
a C–C bond opposite to the dihalomethylene group and the migra-
tion of a halogen atom to the adjacent carbon atom. At the same
time, reported examples of similar reactions for gem-chlorofluoro
analogues are limited to the thermal rearrangements of strained
bicyclic gem-chorofluorocyclopropanes7–9 in high-boiling solvents
and the isomerizations of gem-chlorofluoro(vinyl)cyclopropanes under
gas-phase pyrolysis.10 To the best of our knowledge no catalytic
version of such processes has been published to date. Herein, we
report the general procedure for CuCl-catalyzed transformation of
gem-chlorofluorocyclopropanes† in aprotic solvents leading to cor-
responding chlorofluoroalkenes in 60–98% overall yields.
F
Cl
CH2Cl
F
MeCN
Ph
Ph
F
+
80°C
F
CH2Cl
Ph
1
Z-2
E-2
Cl
+
Ph
3
Scheme 1
In fact, heating of 1-chloro-1-fluoro-2-phenylcyclopropane 1
(syn: anti = 58:42) in acetonitrile in the presence of 0.1–1.0 equiv.
CuCl at 80°C leads mainly to stereoisomeric (Z)- and (E)-3-chloro-
2-fluoro-1-phenylpropenes 2 and small amounts of 3-chloro-
2-fluoro-3-phenylpropene 3 (Scheme 1, Table 1).‡ Note that in
the absence of CuCl no isomerization of 1 was observed even
after prolonged heating.
The conversion of 1 and the ratio between the resulting
isomeric products depend on reaction time and the amount of
CuCl used (see Table 1). In this case, the syn and anti-isomers
of 1 exhibited noticeably different reactivity. For example, with
the use of 0.2–0.5 equiv. of CuCl the conversion of syn-1 after
†
General procedure for the synthesis of gem-chlorofluorocyclopropanes.
The starting gem-chlorofluorocyclopropanes were synthesized as reported10
by the addition of chlorofluorocarbene, which was generated from dichloro-
fluoromethane under the action of KOH under the conditions of phase-
transfer catalysis, to corresponding alkenes. Typically, 130 g of a 50%
aqueous solution of KOH (1.2 mol) were added to a solution of 0.5 mol of
an alkene, 0.7 mol of CHCl2F and 1.0 g of BnEt3NCl in 100 ml of CH2Cl2
cooled to –5°C with intense stirring for 1 h keeping the temperature of
the reaction mixture in a range of 0–5°C. Thereafter, the reaction mixture
was additionally stirred for 8 h and diluted with water. The organic layer
was washed with water and dried with CaCl2, and gem-chlorofluorocyclo-
propanes were separated by distillation.
‡
General procedure for the isomerization of gem-chlorofluorocyclopropanes.
Method A. A mixture of 2–4 mmol of gem-chlorofluorocyclopropane
and 0.1–2 mmol of CuCl in 2 ml of MeCN was stirred under argon at
80°C for 7–90 h depending on the experiment (GLC control). After com-
pletion of the reaction, the mixture was diluted with 20 ml of CH2Cl2,
washed with water (3×50 ml) and dried with Na2SO4. The solvent was
distilled off, and the residue was analyzed by GLC, NMR spectroscopy,
and GS/MS.
Table 1 Isomerization of 1 (syn:anti = 58:42) in the presence of CuCl or CuCl/LiCl depending on reaction time, catalyst amount, and solvent.
Composition (mol%, GLC)
Amount
of 1/mmol
Amount of
CuCl/mmol
Amount of
LiCl/mmol
Entry
Solvent
T/°C
Time/h
syn-1
anti-1
Z-2
E-2
3
1
2
3
4
2.0
2.0
4.0
2.0
0.0
0.4
0.8
1.0
MeCN
MeCN
MeCN
MeCN
80
80
80
80
0.0
0.0
0.0
0.0
48
7
24
7
50
58
28
1
18
0
42
3
0
0
0
0
51
68
56
65
0
18
30
25
33
0
1
1
1
1
5
6
2.0
2.0
2.0
1.0
MeCN
MeCN
80
80
0.0
2.0
7
80
7
50
0
0
4
0
0
0
0
0
64
89
64
79
33
8
31
19
3
3
1
1
7
8
9
4.0
2.0
2.0
0.4
1.0
1.0
MeCN
diglyme
dioxane
80
120
110
0.4
2.0
2.0
20
4
6
0
0
0
0
0
0
84
86
66
15
9
29
1
2
4
© 2013 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2013, 23, 19–21
7 h was 52–69% at the almost complete conversion of anti-1,
whereas prolongation of the processing to 20–50 h or the use of
1.0 equiv. of CuCl for 7 h resulted in the quantitative conversion
of both of the isomers. Entry 5 (Table 1) demonstrates that further
prolongation after achievement of the complete conversion of 1
leads to the rise of the fraction of the more thermodynamically
stable (Z)-isomer 2, whose concentration grew from 64 to 89%
with a drop of (E)-isomer 2 from 33 to 8%. In all cases, the
relative concentration of isomer 3 did not exceed 1–4%. It is
likely that the reversible isomerization of chlorofluorophenyl-
propenes Z-2, E-2 and 3 occurs in the course of reaction through
the 1,3-chlorine shift.
With the use of diglyme or dioxane as a solvent in the presence
of 0.5 equiv. of CuCl, no noticeable transformations of 1 were
observed even at 110–120°C for 24 h; this was likely due to the
insolubility of CuCl in these solvents. However, the addition of
lithium chloride to CuCl caused its dissolution and consequently,
full isomerization of 1 within 4–6 h (entries 8,9). Note that, for
analogous reactions in acetonitrile, which dissolves CuCl relatively
well, the addition of LiCl also accelerated the reaction, although
the effect of LiCl in this case was not so pronounced (cf. entries
4 and 6).
Table 2 Isomerization of 7 (syn: anti = 68:32) in the presence of 0.05 equiv.
of CuCl, 0.05 equiv. of LiCl in MeCN at 80°C.
Composition, mol% (GLC)
Time/h
syn-7
anti-7
Z-8
E-8
20
46
70
90
26
13
5
0
0
0
0
61
73
85
86
11
10
8
1
7
bicyclo[4.1.0]heptanes 9. Thus, endo-Cl isomer was completely
converted into chlorofluorocycloheptene 10 and a small amount
of fluorocycloheptadiene 11 (the product of its dehydrochlorina-
tion) upon the heating of a mixture of 65% endo-Cl-9 and 34%
exo-Cl-9 in acetonitrile in the presence of 0.1 equiv. of CuCl and
0.1 equiv. of LiCl for 24 h (Scheme 4). Under these conditions,
exo-Cl-9 remained essentially intact.
Cl
F
F
Cl
CuCl, LiCl
+
MeCN, 80°C
The developed catalytic isomerization turned to be a general
method, which can be used for analogous transformations of
methyl-, vinyl- and cyclopropyl-substituted gem-chlorofluoro-
cyclopropanes. Thus, heating of 1-chloro-1-fluoro-2,2-dimethyl-
cyclopropane 4 in acetonitrile in the presence of 0.05 equiv. of
CuCl and 0.05 equiv. of LiCl at 80°C for 30 h yielded almost
quantitatively a mixture of 1-chloro-2-fluoro-3-methylbut-2-ene
5 and 3-chloro-2-fluoro-3-methylbut-1-ene 6 in a ratio of 3:1
(Scheme 2).
endo-Cl-9, 65%
exo-Cl-9, 34%
Cl
+
+
exo-Cl-9
F
F
10, 63%
11, 2%
34%
Scheme 4
Note that the previously described7 thermal transformations
of endo-Cl-9 in quinoline at 200°C occurred with the formation of
only cycloheptatriene, and the isomerization products that were
formed in our catalytic reactions were not observed.
F
F
CuCl,
LiCl
F
Cl
Me
Me
Me
Cl
Cl
+
MeCN,
80°C
Me Me
Me
It is known10 that the gas-phase thermal rearrangements of
2-chloro-2-fluoro-1-vinylcyclopropanes 12a,b occur nonselec-
tively because of the competitive processes of vinylcyclopropane-
cyclopentene and cyclopropyl-allyl transformations.10 On the
contrary, we found that catalytic isomerization of 12a,b in the
presence of 0.1–0.4 equiv. CuCl proceeds with the formation of
only acyclic chlorofluorodienes 13 and 14 (Scheme 5).
4
5
6
Scheme 2
U
nder analogous conditions, 1-chloro-1-fluoro-cis-2,3-dimethyl-
cyclopropane 7 (syn:anti = 68:32) underwent isomerization
with the formation of (Z)- and (E)-4-chloro-3-fluoropent-2-enes 8
(Scheme 3, Table 2).
ClH2C
C
F
C
R
CH CH2
F
F
F
Cl
F
Cl
CuCl,
LiCl
Me
Me
Me
+
+
13a Z/E = 8:1, 17%
13b Z/E = 1:1, 14%
MeCN,
80°C
F
Cl
Me
Me Me
Me
Cl
Me Cl
CuCl/MeCN
80°C
+
R
syn-7
anti-7
Z-8
E-8
H2C
C
F
C
R
CH CH2Cl
Scheme 3
12a,b
a R = H
14a Z/E = 1:40, 81%
14b Z/E = 1:16, 86%
In this case, as can be seen in Table 2, the rate of conversion
of anti-7 was much higher than that of syn-7. Thus, the complete
conversion of anti-7 at 80°C was achieved within 20 h, whereas
the complete conversion of syn-7 required 90 h.
b R = Me
Scheme 5
Differences in reactivity were even more pronounced in the
case of the rearrangements of stereoisomeric 7-chloro-7-fluoro-
In this case, the expected typical products of cyclopropyl-allyl
isomerization, corresponding chlorofluorodienes 13a,b, were
obtained in small amounts (14–17%), and the main products
were 5-chloro-2-fluoropenta-1,3-dienes 14a,b (81–86%). The
latter may be formed in the course of the isomerization of 12a,b
through cyclopropane ring opening with the migration of chlorine
atom to the terminal carbon atom of the vinyl group or as a result
of the isomerization of chlorofluorodienes 13a,b through the
1,5-chlorine shift.
Method B. A mixture of 40–80 mmol of cyclopropane, 4–8 mmol of
CuCl, 4–8 mmol of LiCl and 20 ml of MeCN was heated under argon in
a glass liner in a steel autoclave at 80°C for 24–96 h (GLC control). After
completion of the reaction, the mixture was diluted with 50 ml of CH2Cl2,
washed with water (3×50 ml) and dried with Na2SO4. The solvent was
distilled off using a rotary evaporator or by fraction distillation at atmo-
spheric pressure, and the residue was distilled.
Interesting results were obtained in the case of 2-chloro-
2-fluoro-1,1'-bi(cyclopropyl) 15 (syn: anti = 48:52, 0.5 equiv. of
For full experimental details and characterization data for all com-
pounds, see Online Supplementary Materials.
– 20 –

Mendeleev Commun., 2013, 23, 19–21
4 (a) T. N. Grant and F. G. West, J. Am. Chem. Soc., 2006, 128, 9348;
F
Cl
F
CuCl/MeCN
80°C
(b) T. N. Grant and F. G. West, Org. Lett., 2007, 9, 3789; (c) L. Wu and
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Cl
15
16
Scheme 6
CuCl, 80°C, 6 h), affording (3E)-6-chloro-2-fluorohexa-1,3-diene
16 in 60% yield as the only product (Scheme 6).
In summary, the catalytic isomerization of phenyl-, alkyl-,
vinyl- and cyclopropyl-substituted gem-chlorofluorocyclopropanes
can be readily performed in the presence of CuCl. In this case,
the resulting chlorofluoroalkenes or chlorofluoroalkadienes con-
taining a reactive allylic chlorine atom along with fluorine-con-
taining 1,3-diene fragments can be further used for the prepara-
tion of various fluorine-containing functional alkenes and also
for the diene synthesis of carbocyclic organofluorine compounds.
6 (a) M. Christl, M. Schreck, T. Fischer, M. Rudolph, D. Moigno, H. Fisher,
S. Deuerlein and D. Stalke, Chem. Eur. J., 2009, 15, 11256; (b) M. Ceylan
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7 T. Ando, H. Hosaka, H. Yamanaka and W. Funasaka, Bull. Chem. Soc.
Jpn., 1969, 42, 2013.
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9 A. P. Molchanov and R. R. Kostikov, Zh. Org. Khim., 2001, 37, 832
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10 N. V. Volchkov, M. B. Lipkind, A. V. Zabolotskikh, A. V. Ignatenko and
This work was supported by the President of the Russian
Federation (Program for the support of leading schools, grant
no. NSh-604.2012.3), the Federal Target Program ‘Scientific and
Scientific Pedagogic Personnel of the Innovative Russia’ (grant
no. 8431) and the RussianAcademy of Sciences (grant nos. OKh-01
and P-08).
O. M. Nefedov, Mendeleev Commun., 2006, 153.
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2013.01.006.
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Received: 19th October 2012; Com. 12/4000
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