gem-Dihalocyclopropane formation by iron/copper activation of tetrahalomethanes in the presence of nucleophilic olefins. Evidence for a carbene pathway

Article abstract of DOI:10.1016/j.tetlet.2004.01.124

The activation of CBr₄ and CCl₄ by a bimetallic iron/copper couple in acetonitrile is a new, inexpensive, nontoxic and efficient procedure for gem-dibromo- and gem-dichloromethylenation of nucleophilic alkenes. This new route to gem-dihalocyclopropanes involves dihalocarbene species.

Full text of DOI:10.1016/j.tetlet.2004.01.124

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2635–2638
gem-Dihalocyclopropane formation by iron/copper activation of
tetrahalomethanes in the presence of nucleophilic olefins.
Evidence for a carbene pathway
*
Eric L ꢀe onel, Michael Lejaye, Sylvain Oudeyer, Jean Paul Paugam and Jean-Yves N ꢀe d ꢀe lec
Laboratoire d’Electrochimie, Catalyse et Synth ꢁe se Organique, UMR 7582, CNRS-Universit ꢀe Paris XII, 2, Rue Henri Dunant,
B.P. 28, F-94320 Thiais, France
Received 9 December 2003; revised 23 January 2004; accepted 26 January 2004
4 4
Abstract—The activation of CBr and CCl by a bimetallic iron/copper couple in acetonitrile is a new, inexpensive, nontoxic and
efficient procedure for gem-dibromo- and gem-dichloromethylenation of nucleophilic alkenes. This new route to gem-dihalo-
cyclopropanes involves dihalocarbene species.
Ó 2004 Elsevier Ltd. All rights reserved.
The formation of gem-dihalocyclopropanes is already
well documented, and most methods involve the addi-
tion of dihalocarbenes to an appropriate alkene.
gem-dichlorocyclopropanes. Finally, another route to
gem-dichlorocyclopropanes is the reductive cyclization
of b-chlorotrichloromethyl radical adducts, which
1
;2
10
Many routes have been reported for the generation of
dibromo- and dichlorocarbenes. They are easily
obtained by a-elimination of hydrogen halides from
bromoform or chloroform under basic reaction condi-
tions. The reaction of sodium methylate with ethyl
occurs, however, with poor selectivity.
We have previously described a simple and efficient way
for the activation of CBr or CCl by bimetallic iron/
copper or nickel/copper systems in dimethylform-
4
4
3
4
11;12
dibromomalonate or ethyl trichloroacetate also gives
dibromo or dichlorocarbene, respectively. Alternatively,
the reduction of carbon tetrachloride either by TiCl /
amide.
primary alcohols into the corresponding alkyl bromides
This was used for the efficient conversion of
11
or chlorides, and in the conversion of arylaldehydes
12
into benzal bromides or chlorides. The key step in
4
5
LiAlH4 or electrochemically at a lead cathode in a
6
divided cell has also been described. Other reported
methods are less frequently used because of either the
4
these reactions is the reduction of CX into the corre-
sponding dihalocarbene, which reacts with DMF to
produce a Vilsmeier type intermediate, which is the
7
high cost (iron porphyrinate complexes ) or the toxicity
(thermal decomposition of mercury complexes ) of the
carbene precursors. The thermal decomposition of
2;8
11–13
actual halogenating reagent
(Scheme 1).
9
sodium trichloroacetate, or of trichloro or trifluoro-
1
On the basis of the possible formation of such a
dihalocarbene, we thought it possible to use this method
(
trichloromethyl)silane is also used in the synthesis of
reduction
reduction
ROH
+
H
RX
Fe/Cu or Ni/Cu
DMF
CO
(CH3)2N
,
X
CX4
CX3
CX3
CX2
DMF
X
ArCHX2
X
ArCHO
Scheme 1.
Keywords: Dihalocarbenes; Radicals; Cyclopropanes; Bimetallic reduction.
*
Corresponding author. Tel.: +33-149781127; fax: +33-149781148; e-mail: leonel@glvt-cnrs.fr
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.01.124

2636
E. L ꢀe onel et al. / Tetrahedron Letters 45 (2004) 2635–2638
of activation for accessing dihalocyclopropanes starting
with nucleophilic olefins if, on the one hand, the reaction
could be conducted in a solvent other than DMF to
prevent the formation of the Vilsmeier species and, on
the other hand, the generated carbene or carbenoid is
sufficiently electrophilic. The mechanism given in
Scheme 1 raises, however, a complex question, since the
CCl3
CCl3
CCl4
CCl3
CCl3
+
fast
Cl
Scheme 4.
reduction of CX
well known that this radical readily adds to olefins. In
4 3
first produces a CX radical, and it is
14
15
addition, copper as well as iron are known to, inde-
pendently, generate alkyl radicals from organic halides.
What, therefore, would be the behaviour of the mixed
1, entries 1 and 2). However, only the cyclopropanes 6
and 7 were isolated; no traces of 4,4-dichlorobut-3-en-2-
one (Scheme 3) were found. The fragmentation in the
case of isopropenyl acetate (Scheme 3) may, however,
not be fast enough and may thus not provide clear-cut
evidence for one way or the other. With b-pinene,
cyclopropanes 8 and 9 were formed in good yields
(Table 1, entries 3 and 4) and only traces of the radical
adduct such as the one shown in Scheme 4 were
detected.
copper/iron system in the presence of olefin/CX cou-
4
ples?
With all these questions in mind, we started this inves-
tigation with cyclohexene as substrate and CBr
CCl , according to the reaction conditions indicated in
4
or
4
16
Scheme 2. Dibromo- and dichloronorcaranes 1 and 2
were formed in moderate yields, along with small
amounts of the corresponding adducts 3 and 4, which
result from a free-radical chain reaction. Thus, we can
not rule out the formation of 1 and 2 by reduction of,
respectively, 3 and 4. It was important to ascertain the
extent such a free-radical pathway contributes, if at all,
to the formation of the dihalocyclopropane products.
In order to definitely rule out any involvement of a
radical pathway, we conducted the following additional
experiment. We prepared an authentic free-radical
15
adduct according to the method reported by Ghelfi,
that is the reduction of CCl by iron in DMF in the
4
presence of styrene. The adduct 1,1,1,3-tetrachloro-3-
phenylpropane was isolated and then allowed to react
with the copper/iron system in acetonitrile. The only
product was the dimer of 1,1,1,3-tetrachloro-3-phenyl-
propane, as characterized by GC–MS. So, it is clear that
There are typical processes, which can be used to check
the possible occurrence of free-radical intermediates. We
selected two unsaturated compounds, isopropenyl ace-
tate and b-pinene, which should rearrange after the
addition of a radical onto the olefinic bond, thus
diverting the process from the formation of a cyclo-
under our reaction conditions, the reduction of CX
only leads to the carbene species, perhaps under the
guise of a metallocarbene.
4
15
15;17
propyl ring (Schemes 3 and 4
).
16
Our process was applied to the synthesis of dihalocy-
clopropanes from various alkenes using either CBr or
CCl . The results are reported in Table 2. The yield of
The reactions were carried out according to the condi-
tions reported in Scheme 2. The results given in Table 1
clearly indicate that the major products are the cyclo-
propyl adducts.
4
4
cyclopropyl compounds range from poor to high in the
case of nucleophilic olefins, and compare favourably
with those given in most published procedures. Yields
With isopropenyl acetate, yields are poor, probably
because of the formation of telomers or polymers (Table
4
obtained with CBr are generally of the same order as
with CCl
4
. In contrast, no cyclopropane was formed
Cu: 15 mmol (1g)
Fe: 27 mmol (1.5g)
X
X
+
X
X
X
X
X
+
+
CX4
CH CN 30 mL
CX3
3
X = Br, Cl
30 mmol
1
0 mmol
1: X = Br, 25%
: X = Cl, 20%
3 traces
4 traces
5: for X = Br, 40%
not detected for X = Cl
2
Scheme 2.
O
O
O
O
O
CCl4
+
Cl C
3
Cl3C
CCl3
+
O
Cl
O
-
HCl
Cl
Cl
O
Scheme 3.

E. L ꢀe onel et al. / Tetrahedron Letters 45 (2004) 2635–2638
2637
a
Table 1. Reaction of CBr
4
or CCl
4
with isopropenyl acetate and b-pinene
Entry
Olefin
Polyhalomethane
Product
Number
Isolated yield (%)
15
O
O
O
Br
Br
1
CBr
4
6
O
O
O
O
O
Cl
Cl
2
3
4
CCl
4
7
8
9
11
50
53
Br
Br
CBr
4
Cl
Cl
CCl
4
a
Experimental conditions, see Ref. 16.
a
Table 2. gem-Dibromo- or dichlorocyclopropane formation by iron/copper activation of CBr
4
or CCl
4
and olefins
Entry
Olefin
Tetrahalomethane
Product
Number
Isolated yield (%)
26
Br
Br
1
CBr
4
10
11
12
Cl
Br
Cl
2
3
CCl
4
36
35
Br
CBr
4
Cl
Cl
4
CCl
4
13
44
Br
Cl
Br
5
6
CBr
4
14
15
70
88
Cl
CCl
4
Br
Br
Br
Br
7
8
CBr
4
4
16
17
55
26
Br
Br
CBr
Br
Br
9
CBr
4
1
2
25
20
Cl
Cl
10
CCl
4
Br
Br
1
1
1
2
CBr
4
8
9
50
53
Cl
Cl
CCl
4
(continued on next page)

2638
E. L ꢀe onel et al. / Tetrahedron Letters 45 (2004) 2635–2638
Table 2 (continued)
Entry
Olefin
Tetrahalomethane
CBr
Product
Number
Isolated yield (%)
57
Br
Br
1
3
4
4
18
Cl
Cl
1
CCl
4
19
6
50
15
11
––
O
O
O
Br
Br
15
16
17
CBr
4
O
O
O
O
Cl
Cl
CCl
4
7
O
CO
CO
CO
CO
2
CH
3
3
3
3
CBr
4
––
––
2
CH
CH
CH
2
CCl
4
––
––
––
––
––
––
––
––
––
1
1
2
8
9
0
2
CO CH3
2
H
H
CO
C
2
CBr
4
3
CO CH3
2
CO
C
2
3
CCl
4
a
Experimental conditions, see Ref. 16.
with electrophilic olefins (Table 2, entries 17–20). This
clearly indicates that the generated carbenoid species are
electrophilic.
(b) Freidlina, R. K.; Kamyshova, A. A.; Posldova, N. N.;
Chukovskaya, E. Izv. Akad. Nauk SSSR 1979, 7, 1610–
1
612.
1. L ꢀe onel, E.; Paugam, J. P.; N ꢀe d ꢀe lec, J.-Y. J. Org. Chem.
997, 62, 7061–7064.
1
1
1
1
In conclusion, we have reported in this paper a new,
inexpensive, nontoxic and efficient procedure for gem-
dibromo- or gem-dichloromethylenation of nucleophilic
alkenes. We have notably demonstrated that the key
species is indeed a carbenoid.
2. L ꢀe onel, E.; Paugam, J. P.; Heintz, M.; N ꢀe d ꢀe lec, J.-Y.
Synth. Commun. 1999, 29, 4015–4024.
3. Newman, M. S.; Sujeeth, P. K. J. Org. Chem. 1978, 43,
4
367–4369.
14. L ꢀe onel, E.; Dolhem, E.; Devaud, M.; Paugam, J. P.;
N ꢀe d ꢀe lec, J.-Y. Electrochim. Acta 1997, 42, 2125–2132.
1
5. Bellesia, F.; Forti, L.; Ghelfi, F.; Pagnomi, U. M. Synth.
Commun. 1997, 27, 961–971.
1
6. A solution of CX
5
4 4 4
(CBr or CCl , (30 mmol)) diluted in
mL of acetonitrile was added to a well-stirred mixture of
References and notes
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9
1