Microwave-enhanced ruthenium-catalysed atom transfer radical additions

Article abstract of DOI:10.1016/j.tetlet.2007.07.029

The first monomode microwave-assisted atom transfer radical additions (ATRA) of carbon tetrachloride to various olefins were successfully performed, affording the adducts with almost quantitative yields in less than 10 min at 160 °C.

Full text of DOI:10.1016/j.tetlet.2007.07.029

Tetrahedron Letters 48 (2007) 6334–6338
Microwave-enhanced ruthenium-catalysed atom transfer
radical additions
´
Yannick Borguet, Aurore Richel, Sebastien Delfosse, Alain Leclerc, Lionel Delaude and
Albert Demonceau*
` `
Laboratory of Macromolecular Chemistry and Organic Catalysis, University of Liege, Sart-Tilman (B.6a), B-4000 Liege, Belgium
Received 29 May 2007; revised 1 July 2007; accepted 4 July 2007
Available online 30 July 2007
Abstract—The first monomode microwave-assisted atom transfer radical additions (ATRA) of carbon tetrachloride to various
olefins were successfully performed, affording the adducts with almost quantitative yields in less than 10 min at 160 °C.
Ó 2007 Elsevier Ltd. All rights reserved.
Known for more than half a century, the Kharasch
reaction is an effective method for the formation of
carbon–carbon bonds.1 This process consists in adding
a polyhalogenated alkane to an alkene and requires
either a radical initiator—as in the original Kharasch
reaction—or a transition metal catalyst. The latter really
emerged in the mid-1990s when it was extended to olefin
polymerisation, the so-called atom transfer radical poly-
merisation (ATRP), discovered by Sawamoto2 and Mat-
yjaszewski.3 Because of the similarities between both
transformations (Scheme 1), the metal-catalysed Khar-
asch reaction was then named as atom transfer radical
addition (ATRA). ATRP is currently an area of utmost
interest in polymer chemistry4 and it is well established
that knowledge from ATRA should be especially useful
for understanding ATRP.
R
X
+
Mtn
ATRA
Mtn
R• Mtn+1
X
R'
R'
R'
R
R
•
+
Mtn+1
X
X
n
ATRP
Mtn
R'
R'
R'
R'
R'
•
R
R
+
Mtn+1
X
X
n
n
Scheme 1. Commonly accepted mechanism for ATRA and ATRP
reactions.
Several transition metal complexes have been described
to catalyse both processes. Amongst them, copper- and
ruthenium-based catalysts are nowadays the most popu-
lar ones.4 In particular, we have reported in recent years
that [RuCl(Cp#)(PR3)2] (Cp# is the cyclopentadienyl
ligand or a derivative thereof),5 [RuCl2(@CHPh)L2]6
and [RuCl2(p-cymene)L]7 complexes displayed high cat-
alytic performance.8
syntheses in household microwave ovens, there has been
a steadily growing interest in this research field.11 In
recent years, indeed, a plethora of publications have
shown that microwave heating is an efficient tool in
organic synthesis to enhance the effectiveness of the
reactions, but surprisingly enough only a limited
number of examples of radical reactions has been
reported.12 In particular, to the best of our knowledge,
there is only one paper on Kharasch additions acceler-
ated by microwaves. Thus, using a domestic microwave
oven for the copper-catalysed addition reactions of
tetrachloromethane and ethyl trichloroacetate with
styrene, a 3 to 21-fold increase of the reaction rate was
observed compared to classical heating.13 As part of
our ongoing research programme on microwave-assisted
On the other hand, since 1986, when Gedye9 and Gigu-
ere10 published their first articles on microwave-assisted
Keywords: Catalysis; Microwave; Olefins; Radicals and radical reac-
tions; Ruthenium and compounds.
*
Corresponding author. Tel.: +32 4 366 3495; fax: +32 4 366 3497;
e-mail: A.Demonceau@ulg.ac.be
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.029

Y. Borguet et al. / Tetrahedron Letters 48 (2007) 6334–6338
6335
Table 1. Addition of carbon tetrachloride to 1-decene catalysed by
Cl
CCl4
[Ru]
various ruthenium complexesa
CCl3
1-Decene conversionb (%)/
Kharasch additionb (%)
R
R
Microwave
135 or 160 ºC, 10 - 30 min
D,c,d
85 °C
30 h
MW,c,e
135 °C
30 min
MW,c,e
160 °C
10 min
Scheme 2. Kharasch addition of carbon tetrachloride to olefins.
transformations,14,15 we now wish to report that the
Kharasch addition can be dramatically accelerated
under single-mode microwave irradiation (Scheme 2).
No catalyst
<1/<1
<1/<1
1/<1
[RuCl2(p-cymene)(PAr3)]
Ar: p-C6H4OCH3
p-C6H4CH3
C6H5
89/89
79/78
67/66
59/58
45/44
64/63
91/83
88/87
90/90
88/87
90/87
79/77
54/54
67/65
92/92
95/95
92/91
96/96
95/95
85/84
70/61
The study began with the more challenging, non-acti-
vated case of 1-decene, a sluggish substrate in Kharasch
chemistry, together with carbon tetrachloride as a reac-
tion partner. [RuCl2(p-cymene)(PAr3)] complexes were
elected as (pre)catalysts, because they proved to be
moderately active in this field. Previous experiments7f
demonstrated that very long reaction times (at least
200–300 h) were necessary for complete conversion of
the substrate at 60 °C, using a thermostated oil bath as
the heating source (Supplementary Fig. S1). As
expected, when the same experiments were conducted
at 85 °C, the conversions were faster, yet relatively slow
since 50–150 h were still required for the reaction to
proceed to completion.
p-C6H4F
p-C6H4Cl
p-C6H4CF3
[RuCl2(PPh3)3]
a Reaction conditions: Prior to use, the reagents, the solvent (toluene)
and the internal standard (dodecane) were dried using well estab-
lished procedures, distilled and kept under nitrogen at À20 °C.
b Conversions and yields based on GC using dodecane as internal
standard.
c The catalyst (0.03 mmol) was dissolved in toluene (1 mL) and sub-
sequently added through a septum to the solution of 1-decene
(9 mmol), CCl4 (13 mmol), dodecane (0.25 mL) in toluene (3 mL).
d The reaction was performed using a thermostated oil bath.
e The reaction mixture (2 mL) was introduced in a 10 mL microwave
reaction vial and irradiated in a microwave reactor CEM Discover at
a maximum power of 150 W.
In a typical microwave experiment, a mixture of
[RuCl2(p-cymene)(PAr3)] complex, 1-decene and carbon
tetrachloride in toluene was irradiated using a CEM
Discover reactor at a maximum power of 150 W, and
monitored by GC using dodecane as internal standard.
Two reaction conditions were chosen, either 135 °C for
30 min, or 160 °C for 10 min.
100
80
60
40
20
0
Examination of the results summarised in Table 1
clearly demonstrates that microwave irradiation at
160 °C for 10 min is a highly efficient protocol for the
Kharasch addition. Excellent yields were indeed
obtained with most of the [RuCl2(p-cymene)(PAr3)]
complexes under investigation. Microwave irradiation
at 135 °C for 30 min was, however, slightly less efficient
and more time was required to complete each reaction.
Under both conditions, all [RuCl2(p-cymene)(PAr3)]
complexes proved to be—almost—equipotent catalysts
for the test reaction, with the exception of the elec-
tron-poor [RuCl2(p-cymene)(P(p-C6H4CF3)3)] com-
plex,7f which displayed a significantly lower activity.
Additional experiments indicated that [RuCl2(PPh3)3]
catalysed reactions, first reported by Nagai et al.16 and
then applied to a variety of synthetically useful reac-
tions,17 were also dramatically accelerated under micro-
wave irradiation, albeit to a lesser extent than in the
presence of [RuCl2(p-cymene)(PAr3)] complexes (Table
1). On the other hand, several control experiments were
conducted to assess the actual role of the catalyst, in
particular, given the high temperatures employed. As
expected, no reaction occurred in the absence of a
catalyst, even under extended reaction times with heat-
ing to 160 °C.
100
120
140
160
180
Temperature, °C
Figure 1. Optimisation of reaction conditions: time and temperature
effects on the microwave-assisted addition of CCl4 to 1-decene
catalysed by [RuCl2(p-cymene)(PPh3)]; 10 min runtime (j, h) or
30 min runtime (d, s); 1-decene (j, d), Kharasch adduct (h, s). The
reaction conditions are the same as in Table 1.
Below 160 °C, the reaction was incomplete with signifi-
cant amounts of 1-decene remaining (Fig. 1). At
135 °C, increasing the run time from 10 to 30 min
improved the conversion from 68% to 87%, and at
145 °C the conversion increased from 85% to 94%. At
160 °C and above, the products were greater than 97%
pure as judged by GC. Thus, the optimal combination
of yield and conversion was determined to be 160 °C,
for 30 min. At 135 °C, however, the conversion never
reached completion (Fig. 2), seemingly because of the
competitive decomposition of the catalyst. Indeed,
although in the beginning [RuCl2(p-cymene)(PPh3)]
was completely soluble in the reaction mixture at ambi-
ent temperature, a brownish solid appeared on the wall
of the reaction vial after microwave irradiation and
cooling to room temperature.
To optimise the conditions, we next studied the com-
bined effects of temperature and reaction time (Figs. 1
and 2).

6336
Y. Borguet et al. / Tetrahedron Letters 48 (2007) 6334–6338
tion temperature.15,18 We found that the conversions
100
80
60
40
20
0
were negligible at temperatures lower than 120 °C after
a reaction time of 0 min, so that the reactions performed
at 135 and 160 °C for 0 min, in fact, were exposed to
longer reaction times above 120 °C. These times (as ob-
tained from the data of the experimental set-up) were 25
and 115 s for the reaction temperatures of 135 and
160 °C, respectively (Supplementary Fig. S7). On the
other hand, when the Kharasch additions were per-
formed under conventional heating, the reactions
started with the immersion of the sealed tube in the oil
bath. The conversion was obviously zero at time t = 0.
In addition, a short induction period was observed
(Fig. 3 and Supplementary Figs. S4 and S5), which
can be simply explained by the time needed for the heat
to be transferred to the reaction medium. In light of
these results and taking into account the temperature
problems inherent to both methods, it is likely that
microwave irradiation and conventional heating are
equipotent protocols, thereby ruling out the so-called
‘microwave effect’. However, compared to conventional
heating, microwave irradiation is much more conve-
nient, providing a fast and direct heating of the reactants
at the desired temperature.
0
1
2
Time, h
Figure 2. Optimisation of reaction conditions: time and temperature
effects on the microwave-assisted addition of CCl4 to 1-decene
catalysed by [RuCl2(p-cymene)(PPh3)]; temperature: 135 (j, h) or
160 °C (d, s); 1-decene (j, d), Kharasch adduct (h, s). The reaction
conditions are the same as in Table 1.
For comparison, Kharasch addition of CCl4 to decene
was also conducted using a thermostated oil bath under
otherwise identical conditions (concentration, tempera-
ture, etc.), except that the reactions were performed in
sealed tubes, which were immersed in the oil bath at
160 °C. Examination of Figure 3 clearly demonstrates
that microwave irradiation is superior to conventional
heating. Indeed, under microwave conditions, decene
conversions were as follows: 92%, 95% and 99% for run-
times of 10, 20 and 30 min, respectively, against 37%,
70% and 85% for conventionally heated reactions.
It is also worth noting that our results do not confirm
previous works. In a comparable study, indeed, using
a domestic multimodal microwave oven instead of a
´
monomodal microwave reactor, Adamek reported quite
significant microwave acceleration with respect to that
achievable under conventional heating protocols.13
Interestingly, as stated very recently by Rannard and
co-workers20 in all atom transfer radical reactions
(ATRA and ATRP) reported to date, ‘rate enhance-
ments have only been observed when employing labora-
tory-modified domestic multimodal microwave ovens,
where the heating rate and profile are inconsistent and
irreproducible. In the case of reactions performed in
monomodal microwave reactors, for which the micro-
wave power is more focused and the temperature is
accurately monitored, no, or very little, rate enhance-
ment is observed’.20
In Figure 3, it is also observed that the origin is not
intercepted in the plot of substrate conversion against
time (see also Supplementary Fig. S4 for the ln([S]0/
[S]t) vs time plot). Thus, experiments performed for
0 min revealed already 1-decene conversions of 10%
and 85% for the reaction temperatures of 135 and
160 °C, respectively (Supplementary Fig. S6). This effect
was confirmed for other substrates, such as 1-hexene
(Supplementary Fig. S5). For the sake of understanding,
it is worth mentioning first that the CEM Discover
microwave instrument is programmed so as t = 0 when
the desired temperature is attained and not—as
expected—when irradiation starts. The phenomenon
described above is therefore related to the time that
the microwave reactor takes to reach the desired reac-
The microwave conditions from Figures 1–3 were iden-
tified as the preferred reaction conditions and were then
utilised for the Kharasch addition of CCl4 to a diverse
set of olefins using two readily available catalysts,
[RuCl2(p-cymene)(PPh3)] (1) and [RuCl2(PPh3)3] (2)
(Table 2).
100
80
60
40
20
0
1-Hexene was first employed and, surprisingly enough,
this substrate proved to be less reactive than 1-decene
whatever the heating system may be. Again, microwave
irradiation at 160 °C for 10 min was clearly superior to
conventional heating at 85 °C for 30 h (Supplementary
Figs. S5 and S8). The most striking results, however,
were found with highly polymerisable alkenes, such as
styrene and methyl methacrylate. Thus, with
[RuCl2(PPh3)3] as the catalyst, the standard conditions
furnished full conversion of styrene together with low
yield of the Kharasch adduct (34%). On the contrary,
when the same reaction was performed under micro-
waves, complete conversions were accomplished within
0
1
2
Time, h
Figure 3. Comparison between microwave heating and conventional
heating for the addition of CCl4 to 1-decene catalysed by [RuCl2(p-
cymene)(PPh3)] at 160 °C; microwave heating (d, s), conventional
heating in an oil bath (j, h); 1-decene (d, j), Kharasch adduct (s,
h). The reaction conditions are the same as in Table 1.

Y. Borguet et al. / Tetrahedron Letters 48 (2007) 6334–6338
6337
Table 2. Addition of carbon tetrachloride to representative olefins
catalysed by [RuCl2(p-cymene)(PPh3)] (1) and [RuCl2(PPh3)3] (2)a
Table 3. Addition of chloroform to 1-decene catalysed by [RuCl2(p-
cymene)(PPh3)] (1) and [RuCl2(PPh3)3] (2)a
Substrate
Catalyst
Substrate conversionb (%)/
Kharasch additionb (%)
Reaction conditions
Substrate conversionb
(%)/Kharasch
additionb (%)
D,c,d
85 °C
30 h
MW,c,e
135 °C
30 min
MW,c,e
160 °C
10 min
(1)
(2)
D, 85 °Cc,d
100 h
300 h
1 h
5 h
1 h
13/12
22/21
13/13
26/26
39/38
59/59
10/10
21/20
5/4
14/13
10/9
1-Hexene
1
2
1
2
1
2
1
2
40/23
74/74
54/53
100/92
100/96
99/92
93/81
100/58
95/50
81/81
56/56
99/85
69/63
62/58f
100/34f
87/43
100/52
96/54
MW, 135 °Cc,e
MW, 160 °Cc,e
Styrene
99/83
Methyl methacrylate
Butyl acrylate
100/80
100/77
100/51
98/52
5 h
28/26
a–e The reaction conditions are the same as in Table 1.
99/46
a–e The reaction conditions are the same as in Table 1.
of the Kharasch addition and the applied conditions
(high temperature, high pressure), however, are un-
known due to the opaqueness of the reaction chamber
of the microwave reactor.
f 60 °C, 30 h.
a short time and the product was formed in high yields
(85–95%). It is also noteworthy that the yields were
higher at 135 °C than at 160 °C, revealing thereby the
occurrence of side reactions. The latter were identified
as mainly oligomerisation/polymerisation of the sub-
strate, as indicated by the GPC trace of the reaction
mixture.
In summary, we have developed an efficient method for
the ruthenium-catalysed Kharasch reaction using micro-
wave irradiation. This procedure is straightforward and
high yielding, even with some highly polymerisable sub-
strates, such as styrene and methyl methacrylate, an
advantage over conventional protocols.
A similar phenomenon was evidenced with methyl meth-
acrylate (Supplementary Fig. S9). Under conventional
heating, indeed, the yields culminated at 50% at com-
plete conversion of the substrate, whereas under micro-
wave heating at 135 °C the Kharasch addition reached
90%, confirming thereby the beneficial effect of micro-
waves both on the rate19 and the outcome of the reac-
tion. On the contrary, with n-butyl acrylate—another
highly polymerisable substrate—recourse to microwaves
did not improve the process compared to conventional
heating.
Acknowledgements
The authors are grateful to the ‘Fonds National de la
Recherche Scientifique’ (F.N.R.S.), Brussels, for the
purchase of major instrumentations. We also thank
BRS, Drogenbos, Belgium, for helpful discussions and
technical support.
Supplementary data
With the encouraging results obtained, our next goal
was to extend this protocol to the reaction between
two very sluggish partners in Kharasch chemistry, that
is, chloroform and 1-decene (Scheme 3).
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/
j.tetlet.2007.07.029.
As expected, the Kharasch addition was extremely slow
under conventional heating at 85 °C. The yield, indeed,
did not exceed 20% after 300 h of reaction (Table 3 and
Supplementary Fig. S11). By contrast, the reaction was
much faster under microwave irradiation at 160 °C and
around 60% conversion was reached after 5 h when
[RuCl2(p-cymene)(PPh3)] was used as catalyst (Supple-
mentary Fig. S12). [RuCl2(PPh3)3], on the other hand,
was less active, affording the desired adduct in 26% yield
under the same experimental conditions, presumably be-
cause of the low solubility of the complex in the reaction
medium. Details of the complex’ solubility in the course
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