An efficient, selective, and reducing agent-free copper catalyst for the atom-transfer radical addition of halo compounds to activated olefins

Article abstract of DOI:10.1021/ic901942p

Efficient and selective ATRA reactions of CCl₄, CBr₄, TsCl (Ts = tosyl), or Cl₃CCO₂Et with activated olefins (styrene, methyl methacrylate, n-butyl methacrylate, ferf-butyl methacrylate) using the Tp^tBuCu(NCMe) complex as a catalyst have been achieved In the absence of any reductant and with low catalyst loadings.

Full text of DOI:10.1021/ic901942p

642 Inorg. Chem. 2010, 49, 642–645
DOI: 10.1021/ic901942p
An Efficient, Selective, and Reducing Agent-Free Copper Catalyst for the
Atom-Transfer Radical Addition of Halo Compounds to Activated Olefins
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Jose Marıa Munoz-Molina, Tomas R. Belderraın,* and Pedro J. Perez*
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Laboratorio de Catalisis Homogenea, Departamento de Quımica y Ciencia de los Materiales, Unidad Asociada
al CSIC, Campus de El Carmen, Universidad de Huelva, 21007-Huelva, Spain
Received October 2, 2009
Efficient and selective ATRA reactions of CCl4, CBr4, TsCl (Ts = tosyl), or Cl3CCO2Et with activated olefins (styrene,
methyl methacrylate, n-butyl methacrylate, tert-butyl methacrylate) using the TptBuCu(NCMe) complex as a catalyst
have been achieved in the absence of any reductant and with low catalyst loadings.
Introduction
(Scheme 1a).7 The commonly accepted mechanism for this
radical process is shown in Scheme 1b. The metal complex
reacts with an R-X (X = halide) bond to generate the
The transition-metal-catalyzed Kharasch reaction,1 so-called
atom-transfer radical addition (ATRA),2 constitutes a pro-
mising synthetic tool in organic synthesis. Several metals such
as Fe,3 Ru,4 Ni,5 or Cu6 are known to promote this trans-
formation either in the inter- or intramolecular version
radical R and a metal halide complex. The former radical
3
species may react with the olefin to give radical R0 (addition
step) or, alternatively, with another radical ( R or R0) in
3
3
nonproductive side reactions (termination steps). Following
the addition, the resulting radical recovers the halide from the
metal in the deactivation step, the metal center being reduced
to the initial oxidation state to be ready to restart the catalytic
*To whom correspondence should be addressed. Tel.: 34959219956.
Fax: 34959219942. E-mail: perez@dqcm.uhu.es (P.J.P.), trodri@dqcm.uhu.es
(T.R.B.).
(1) Kharasch, M. S.; Engelmann, H.; Mayo, F. R. J. Org. Chem. 1938, 2,
288.
(2) (a) Kharasch, M. S.; Jensen, E. V.; Urry, W. H. Science 1945, 102, 128.
(b) Kharasch, M. S.; Jensen, E. V.; Urry, W. H. J. Am. Chem. Soc. 1945, 67, 1626.
(3) (a) De Malde, M.; Minisci, F.; Pallini, U.; Volterra, E.; Quilico, A.
Chim. Ind. 1956, 38, 371. (b) Minisci, F.; Galli, R. Chim. Ind. 1963, 45, 1400.
(4) (a) Quebatte, L.; Solari, E.; Scopelliti, R.; Severin, K. Organometallics
2005, 24, 1404. (b) Quebatte, L.; Scopelliti, R.; Severin, K. Angew. Chem., Int.
Ed. 2004, 43, 1520. (c) Tutusaus, O.; Delfosse, S.; Demonceau, A.; Noels, A. F.;
cycle. It is worth mentioning that radical R0 can also react
3
with another olefin molecule to start a polymerization route.
The main drawback of the metal-catalyzed ATRA reactions
is the formation of the side products, which not only decrease
the yield in the desired addition products but also induce the
accumulation of Mnþ1, affecting the [Mnþ]/[Mnþ1] ratio and,
finally, bringing the catalytic reaction to the end. A methodol-
ogy envisaged to solve this problem was introduced by Severin
and co-workers with Ru-based catalysts and consisted of the
addition of a reducing agent (magnesium powder) to con-
tinuously regenerate the lower oxidation state of the metal at
room temperature ([LmMnþ] in Scheme 1b).8 The main
advantage of this strategy is that magnesium does not generate
free radicals; however, the total metal concentration increases
in the system.9 Also, the groups of Severin10 and Pintauer11
~
~
Vinas, C.; Teixidor, F. Tetrahedron Lett. 2003, 44, 8421. (d) Tutusaus, O.; Vinas,
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C.; Nꢀunez, R.; Teixidor, F.; Demonceau, A.; Delfosse, S.; Noels, A. F.; Mata, I.;
Molins, E. J. Am. Chem. Soc. 2003, 125, 11830. (e) Opstal, T.; Verpoort, F. New
J. Chem. 2003, 27, 257. (f) De Clercq, B.; Verpoort, F. J. Organomet. Chem.
2003, 672, 11. (g) Simal, F.; Wlodarczak, L.; Demonceau, A.; Noels, A. F. Eur. J.
Org. Chem. 2001, 14, 2689. (h) Tallarico, J. A.; Malnick, L. M.; Snapper, M. L.
J. Org. Chem. 1999, 64, 344. (i) Simal, F.; Wlodarczak, L.; Demonceau, A.;
Noels, A. F. Tetrahedron Lett. 2000, 41, 6071.
(5) (a) Gossage, R. A.; van de Kuil, L. A.; van Koten, G. Acc. Chem. Res.
1998, 31, 423. (b) van de Kuil, L. A.; Grove, D. M.; Gossage, R. A.; Zwikker,
J. W.; Jenneskens, L. W.; Drenth, W.; van Koten, G. Organometallics 1997, 16,
4985. (c) Kleij, A. W.; Gossage, R. A.; Klein Gebbink, R. J. M.; Brinkmann, N.;
Reijerse, E. J.; Kragl, U.; Lutz, M.; Spek, A. L.; van Koten, G. J. Am. Chem. Soc.
2000, 122, 12112.
(6) (a) Hajek, M.; Kotora, M.; Davis, R.; Fischer, C.; Joshu, W. A. C.
Collect. Czech. Chem. Commun. 1996, 61, 774. (b) Davies, R.; Stephens, K.;
Hajek, M. J. Mol. Catal. A 1994, 92, 269. (c) Villemin, D.; Sauvaget, F.; Hajek,
M. Tetrahedron Lett. 1994, 35, 3537. (d) Kotora, M.; Hajek, M. J. Fluorine
Chem. 1993, 64, 101. (e) Kotora, M.; Hajek, M.; Dobler, C. Collect. Czech.
Chem. Commun. 1992, 57, 2622. (f) Kotora, M.; Hajek, M. J. Mol. Catal. A
1992, 77, 51. (g) Hajek, M.; Silhavy, P. Collect. Czech. Chem. Commun. 1980,
48, 1710. (h) Hajek, M.; Silhavy, P.; Malek, J. Collect. Czech. Chem. Commun.
(7) (a) Clark, A. J. Chem. Soc. Rev. 2002, 31, 1. (b) de Campo, F.;
Lastecoueres, D.; Verlhac, J.-B. J. Chem. Soc., Perkin Trans. 1 2000, 575.
~
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(c) Munoz-Molina, J. M.; Belderraín, T. R.; Perez, P. J. Adv. Synth. Catal. 2008,
350, 2365. (d) Ricardo, C.; Pintauer, T. Chem. Commun. 2009, 3029.
(8) Thommes, K.; Icli, B.; Scopelliti, R.; Severin, K. Chem. Eur. J. 2007,
13, 6899.
(9) (a) Pintauer, T.; Matyjaszewski, K. Chem. Soc. Rev. 2008, 37, 1087.
(b) Pintauer, T.; Eckenhoff, W. T.; Ricardo, C.; Balili, M. N. C.; Biernesser, A. B.;
Noonan, S. J.; Taylor, M. J. W. Chem. Eur. J. 2009, 15, 38.
(10) Quebatte, L.; Thommes, K.; Severin, K. J. Am. Chem. Soc. 2006, 128,
7440.
(11) (a) Eckenhoff, W. T.; Pintauer, T. Inorg. Chem. 2007, 46, 5844.
(b) Eckenhoff, W. T.; Garrity, S. T.; Pintauer, T. Eur. J. Inorg. Chem. 2008, 563.
(c) Nicole, M.; Balili, C.; Pintauer, T. Inorg. Chem. 2009, 48, 18.
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1980, 45, 3502. (i) Munoz-Molina, J. M.; Caballero, A.; Díaz-Requejo, M. M.;
Trofimenko, S.; Belderraín, T. R.; Perez, P. J. Inorg. Chem. 2007, 46, 7725.
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pubs.acs.org/IC
Published on Web 12/11/2009
2009 American Chemical Society

Article
Inorganic Chemistry, Vol. 49, No. 2, 2010 643
Scheme 1. (a) Atom-Transfer Radical Addition Reaction and (b) the
CommonlyAccepted Mechanism for the ATRA Reaction Also Showing
Nondesired Byproducts
Figure 1. Kinetic monitoring (1H NMR, 30 °C, C6D6) of the consump-
tion of styrene in the reaction with CCl4 using complexes 1 or 2 as the
catalysts. Reactions performed at 30 °C; [Cu]/[styrene]/[CCl4] = 1:500:
2000. Rate constants: (a) 1 as catalyst, kobs = 2.01 ꢀ 10-4 s-1; (b) 2 as
catalyst, kobs = 1.76 ꢀ 10-4 s-1
.
related TptBuCu(NCMe)13 (2) complex, which only differs
from our previous report in the methyl group located at R1
(eq 1). As a probe reaction, we carried out the experiment
with styrene, CCl4 in C6D6 at 30 °C, monitoring the disap-
pearance of the olefin with 1 and 2 in separate experiments.
As shown in Figure 1, complex 2 providednearlyquantitative
conversions into the addition product, whereas in the case of
1 the reaction was not completed.
have independently reported azobis(isobutyronitrile) (AIBN)
as the reducing agent in ATRA catalyzed by ruthenium and
copper complexes. These reactions needed heating at 60 °C in
order to make AIBN an efficient radical source.
As an alternative to the above methods, Pintauer and co-
workers have very recently described the use of 2,20-azobis(4-
methoxy-2,4-dimethyl valeronitrile), a room-temperature ra-
dical initiator known as V-70, as the reducing agent.9 Such
an additive has provided efficient ATRA reactions with
R-olefins with 0.005 mol % of catalyst loading. However, it
was not that efficient with the more reactive monomers such
as styrene, methyl acrylate, or methyl methacrylate probably
due to their low kdeact/kp ratio (Scheme 1).12 In the above
cases, AIBN or V-70 also promote the generation of free
radicals, which would lead to competing termination or free-
radical polymerization due to their known ability to function
as efficient chain-transfer agents, against the atom economy
of the ATRA reactions. Therefore, the current state of the art
indicates that the best catalytic systems reported require an
additive as a reducing agent, and that for the most reactive
olefins this strategy is not yet very efficient.
After that finding, we also studied the effect of added
acetonitrile on the reaction rate. Such a study is based in our
previous mechanistic proposal6i (Scheme 2) in which the
presence of a coordinating substrate, that is, MeCN, would
reduce the amount of the TpxCu species and therefore would
Results and Discussion
control the free-radical concentration ( R), slowing down the
3
We have previously reported that Cu(I) complexes con-
taining trispyrazolylborate ligands (TpxCu) catalyze the
ATRA of polyhalogenated alkanes to various olefins under
mild conditions,6i the best catalyst being the complex TptBu,
MeCu(NCMe) (1). With the idea in mind of avoiding the use
of such additives and the functionalization of the more
reactive olefins, we checked the catalytic capabilities of the
radical homocoupling side reaction. Furthermore, MeCN is
also proposed6i to favor the formation of a pentacoordinated
Cu(II) species that would prevent the accumulation of the
TpxCuCl species and the subsequent formation of (Tpx)2Cu
species that would suppose a dead-end in the catalytic cycle.
Consequently, the addition of acetonitrile should slow down
reaction rates but wouldlead to an enhancement of yields and
selectivity. Three experiments with 0, 20, and 40 equiv of
MeCN with respect to the initial amount of complex 2 were
carried out to evaluate the reaction rate. As shown in Figure 2,
the reaction inthe presenceof20 equivofMeCN yielded90%
of the product after 24 h (entry 2), whereas only 69% or 80%
yield were obtained when no or 40 equiv were added,
respectively, as the result of catalyst deactivation.
(12) (a) Odian, G. Principles of Polymerization, 4th ed.; John Wiley & Sons:
Hoboken, NJ, 2004. (b) Beranek, I.; Fischer, H. Polar Effects on Radical Addition
Reactions: An Ambiphilic Radical. In Free Radicals in Synthesis and Biology;
Minisci, F., Ed.; Kluwer: Dordrecht, The Netherlands, 2004 (Nato ASI series C,
vol 260, p 303).
(13) Carrier, S. M.; Ruggiero, C. E.; Houser, R. P.; Tolman, W. B. Inorg.
Chem. 1993, 32, 4889.

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Munoz-Molina et al.
644 Inorganic Chemistry, Vol. 49, No. 2, 2010
Table 1. Atom Transfer Radical Addition (ATRA) of CCl4 to Various Olefins
Catalyzed by TptBuCu(NCMe)a
entry
alkene
R-X [Cu]/[Olefin] time (h) conv/yield (%)b
1
2
3
4
5
6
7
8
styrene
CCl4
1:2000
1:2000
1:5000
1:2000
1:2000
1:5000
1:2000
1:5000
1:2000
1:2000
1:5000
1:2000
1:2000
1:2000
1:2000
1:2000
1:2000
1:2000
24
48
24
24
48
24
24
24
24
48
24
24
24
48
48
48
24
24
90/90
>99/>99
38/38
84/83
94/92
68/66
98/95
33/33
47/45
60/57
37/33
>99/>99
>99/97
42/42
40/40
38/38
36/22
35/17
CBr4
MMA
CCl4
CBr4
9
10
11
12
13
14
15
16
17
18
BuMA
tBuMA
1-hexene CCl4
1-octene CCl4
1-decene CCl4
CCl4
CCl4
Figure 2. Consumption of styrene with time in the ATRA reaction of
CCl4 to styrene catalyzed by complex 2, in the presence of different
amounts of MeCN. Reactions performed at 30 °C with a [Cu]/
[styrene]/[CCl4] ratio of1:2000:4000. Rate constants:(a)noMeCNadded,
kobs = 7.79 ꢀ 10-5 s-1; (b) 20 equiv of MeCN added, kobs = 4.97 ꢀ
MA
BA
CCl4
CCl4
a All reactions were performed in the presence of 20 equiv of MeCN;
temperature = 30 °C; [Olefin]/[R-X] = 1:2, except entries 3, 6, 8, and
11, [Olefin]/[R-X] = 1:1.2. Solvent is benzene-d6. b The conversions and
yields were determined by 1H NMR spectroscopy after the desired times.
10-5 s-1; 40 equiv of MeCN added, kobs = 1.38 ꢀ 10-5 s-1
.
Scheme 2. Mechanistic Proposal for ATRA Reactions Catalysed by
TpxCu Complexes
Table 2. ATRA Reaction of Polychlorinated Esters and Sulfonyl Chlorides to
Olefins Catalyzed by Complex 2a
entry alkene
R-X
[Cu]/[Olefin] time (h) conv/ yield (%)b
1
2
3
4
Styrene TsCl
1:300
24
24
24
48
>99/>99
>99/>99
99/98
Cl3CCO2Et
MMA TsCl
Cl3CCO2Et
1:1000
1:300
1:1000
68/65
a All reactions were performed in the presence of 20 equiv of MeCN;
temperature = 30 °C; [Olefin]/[R-X] = 1:2 for entries 2 and 4;
[Olefin]/[R-X] = 1:1.2 for entries 1 and 3. Solvent is benzene-d6. b The
conversions and yields were determined by 1H NMR spectroscopy after
the desired times.
(L = olefin). On the other hand, this catalytic system was
not very successful with less activated R-olefins (entries
14-16). The use of CBr4 did not induce significant changes
in the conversion when styrene was used (entries 4 and 5),
although in the case of methyl methacrylate a decrease in the
activity was observed (entries 9-11). In addition, low selec-
tivity was obtained with acrylates (entries 17 and 18),
probably due to their well-known high propagation rate
Once the ability of complex 2 to induce the ATRA of CCl4
to styrene was established, we carried out a study of its use in
ATRA reactions of CCl4 and CBr4 to various olefins14 in the
presence of 20 equiv of MeCN. In a typical procedure,
a solution (C6D6) of 2, containing 20 equiv of MeCN,
2000 equiv of the olefin, and 4000 equiv of CCl4 or CBr4,
was heated at 30 °C and the conversion monitored with time
by 1H NMR. As shown in Table 1, remarkable results were
obtained for the more reactive olefins. Thus, the addition of
CCl4 to styrene (entries 1 and 2) proceeded with excellent
yield and selectivity for the addition product, using 0.05 mol %
of the copper catalyst. Similarly, nearly quantitative yields
were observed for the addition of CCl4 to methacrylates
(entries 7, 12, and 13) with that catalyst loading. The results
shown in Table 1 exceed those reported with other copper-
based catalysts that, in addition, required the presence of a
reducing agent, in contrast with the lackof such an additive in
the system reported herein. The decrease in conversion when
1:5000 [catalyst]/[olefin] was used can be explained in terms
of a decrease in the concentration of the active species TpxCu
due to the formation of significant amounts of TpxCuL
constant (MA: kp,25 = 5.8 ꢀ 102 M-1 s-1; MMA: kp,25
=
1.9 ꢀ 102 M-1 s-1).12
In order to extend the use of our catalytic system to
synthetically interesting reactions, we decided to use other
halide compounds instead of carbon tetrahalides, employing
sulfonyl chloride or ethyl trichloroacetate. The radical addi-
tion of sulfonyl chlorides to olefins catalyzed by copper
catalysts was previously, and independently, reported by
the groups of Suzuki and Percec.15 Typically, these reactions
were carried out with CuCl (1-2 mol %) in the presence of
Et3NHCl at 80-100 °C. In a similar manner, Severin and
co-workers used Ru-based catalysts8 for this transformation
(0.1 mol %, 48 h, room temperature, Mg as the reducing
agent). In our case, when complex 2 was used as a catalyst,
p-toluenesulfonyl chloride (TsCl) was efficiently added to
(14) Olefins used: styrene (Sty), methyl methacrylate (MMA), n-butyl
methacrylate (BMA), tert-butyl methacrylate (tBMA), methyl acrylate
(MA), butyl acrylate (BA), 1-hexene, 1-octene, and 1-decene.
(15) (a) Percec, V.; Barboiu, B.; Kim, H.-J. J. Am. Chem. Soc. 1998, 120,
305. (b) Lim, J.-C.; Kotani, J.; Suzuki, M.; Saegusa, T. Macromolecules 1991, 24,
2698.

Article
Inorganic Chemistry, Vol. 49, No. 2, 2010 645
styrene or methyl methacrylate at 30 °C (eq 2, Table 2). The
use of an olefin/Cu ratio of 300:1 led to the addition products
in quantitative yieldsafter 24 h at 30 °C (Table 2, entries 1 and
3). It should be noted that, for example, the 1:1 addition
product between p-toluenesulfonyl chloride (TsCl) and styr-
ene (1-[(2-chloro-2-phenylethyl)sulfonyl]-4-methylbenzene)
can be easily transformed into (E)-β-(p-toluenesulfonyl)styr-
ene in the presence of NBu3.
from Aldrich. Olefins (styrene, methyl methacrylate, n-butyl
methacrylate, tert-butyl methacrylate, methyl acrylate, butyl
acrylate, 1-decene, 1-octene, and 1-hexene) were filtered on
alumina columns prior to use. The homoscorpionate ligand
was prepared according to literature methods as well as the
complexes TptBu,MeCu(NCMe) (1) and TptBuCu(NCMe) (2).
NMR experiments were run on a Varian Mercury 400-MHz
spectrometer.
General Procedure for the ATRA of CCl4 to Olefins. The
desired amount of a stock solution of the copper complex in
benzene-d6, an appropriate amount of MeCN, and the corre-
sponding amount of the olefin and CCl4 were dissolved in
the required amount of C6D6 to arrive at a total volume of
1.1 mL. The initial concentrations were [catalyst] = 0.94 mM,
[MeCN] = 18.8 mM, [olefin] = 1.88 M, and [CCl4] = 3.76 M.
The solution was transferred into a NMR pressure tube
and sealed with a Teflon screw cap. The tube was removed
from the glovebox and placed in an oil bath at 30 °C. The
On the other hand, the ATRA reactions of polychlorinated
esters to olefins (eq 3) are synthetically interesting since the
resulting products are precursors of lactones.16 As shown in
Table 2 (entries 2 and 4), complex 2 (0.1 mol %) catalyzes the
addition of Cl3CCO2Et to olefins at 30 °C. After 24 h, the
monoadducts were obtained in good yields without the
assistance of reducing agents. These results are, at least, as
good as those reported for others catalytic systems. For
example, the addition of Cl3CCO2Et to styrene at room
temperature gave 94% yield with the Ru/Mg system,8 in
good agreement with similar conversions obtained with 2 as a
catalyst. However, it is worth mentioning that this copper-
based system does not require the use of a reducing agent to
achieve the conversions described with other systems that do
need such an additive.
1
conversions were monitored by H NMR spectroscopy at the
desired times.
General Procedure for the ATRA of CBr4 to Olefins. The
procedure was identical to that described above for CCl4. All
reactions were performed with an appropriate amount of a stock
solution of the copper complex, MeCN, olefin, CBr4, and C6D6
to reach a final volume of 1.5 mL. The initial concentrations
were [catalyst] = 0.69 mM, [MeCN] = 13.8 mM, [olefin] = 1.38
M, and [CBr4] = 1.66 M.
General Procedure for the ATRA of TsCl to Olefins. The
procedure was identical to that described above for CCl4. All
reactions were performed with an appropriate amount of a stock
solution of the copper complex, MeCN, olefin, TsCl, and C6D6
to reach a final volume of 1.5 mL. The initial concentrations
were[catalyst] =4.33mM,[MeCN] =86.6mM,[olefin] =1.30M,
and [TsCl] = 1.56 M.
General Procedure for the ATRA of Cl3CCO2Et to Olefins.
The procedure was identical to that described above for CCl4.
All reactions were performed with an appropriate amount of a
stock solution of the copper complex, MeCN, olefin,
Cl3CCO2Et, and C6D6 to reach a final volume of 1.5 mL. The
initial concentrations were [catalyst] = 1.38 mM, [MeCN] =
27.6 mM, [olefin] = 1.38 M, and [Cl3CCO2Et] = 2.76 M.
In conclusion, we have described a catalytic system for the
ATRA reactions of halo compounds to olefins that does not
need the presence of reducing agents and takes place with
high efficiency and selectivity under mild conditions. Experi-
mentaland theoretical studies aiming to understand the effect
of the Tpx ligand are currently underway in our laboratory.
Acknowledgment. We thank the MEC (Proyecto
CTQ2008-00042BQU) and the Junta de Andalucıa (Proyecto
P07-FQM-02794) for financial support.
Experimental Section
General Information. All preparations were carried out in
a glovebox. Starting materials and reagents were purchased
Supporting Information Available: NMR data for the pro-
ducts, NMR spectra of reaction mixtures, and kinetic plots. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(16) (a) Pirrung, F. O. H.; Hiemstra, H.; Speckamp, W. N. Tetrahedron
1994, 50, 12415. (b) Pirrung, F. O. H.; Steeman, W. J. M.; Hiemstra, H.;
Speckamp, W. N. Tetrahedron Lett. 1992, 33, 5141.