Photoinitiated ambient temperature copper-catalyzed atom transfer radical addition (ATRA) and cyclization (ATRC) reactions in the presence of free-radical diazo initiator (AIBN)

Article abstract of DOI:10.1039/c0dt01764g

The use of UV light in copper-catalyzed atom transfer radical addition (ATRA) and cyclization (ATRC) reactions of various (poly)halogenated compounds to highly active alkenes in the presence of AIBN is reported. Radicals generated from photodecomposition of AIBN efficiently regenerated the copper(i) complex at ambient temperature enabling ATRA of CCl₄ and CBr₄ with catalyst loadings as low as 0.05 mol-%. The desired monoadduct was obtained in lower yields in the ATRA of less active halogenated compounds, which was mostly due to incomplete alkene conversions. Ambient temperature ATRA of CCl ₄ to various 1,6-dienes followed by sequential ATRC was also performed in the presence of UV light using [Cu^II(TPMA)Cl][Cl] complex and AIBN. High yields of the 5-exo-trig cyclic product were obtained for all dienes with preferential formation of the cis isomer. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c0dt01764g

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PAPER
Photoinitiated ambient temperature copper-catalyzed atom transfer radical
addition (ATRA) and cyclization (ATRC) reactions in the presence of
free-radical diazo initiator (AIBN)
Marielle Nicole C. Balili and Tomislav Pintauer*
Received 14th December 2010, Accepted 13th January 2011
DOI: 10.1039/c0dt01764g
The use of UV light in copper-catalyzed atom transfer radical addition (ATRA) and cyclization
(ATRC) reactions of various (poly)halogenated compounds to highly active alkenes in the presence of
AIBN is reported. Radicals generated from photodecomposition of AIBN efficiently regenerated the
copper(I) complex at ambient temperature enabling ATRA of CCl4 and CBr4 with catalyst loadings as
low as 0.05 mol-%. The desired monoadduct was obtained in lower yields in the ATRA of less active
halogenated compounds, which was mostly due to incomplete alkene conversions. Ambient
temperature ATRA of CCl4 to various 1,6-dienes followed by sequential ATRC was also performed in
the presence of UV light using [CuII(TPMA)Cl][Cl] complex and AIBN. High yields of the 5-exo-trig
cyclic product were obtained for all dienes with preferential formation of the cis isomer.
Introduction and background
Transition metal catalyzed Kharasch addition or atom transfer
radical addition (TMC ATRA) is an effective tool for carbon–
carbon bond formation and has gained considerable interest in
organic synthesis.1–8 The reaction is typically catalyzed by tran-
sition metal complexes of Cu, Ru, Fe, or Ni.5,8–12 However, until
recently, the large amounts of metal catalyst needed to achieve high
selectivity towards the desired monoadduct made TMC ATRA an
expensive and environmentally unfriendly process. The principal
reason for the need of high catalyst concentration in TMC ATRA
under standard reaction conditions ([MtnLm]0 : [RX]0 : [alkene]0 =
((5–30) : 400 : 100) is the fact that radical termination reactions
lead to the irreversible accumulation of the persistent radical or
deactivator (transition metal complex in the higher oxidation
state, Mtn+1LmX, Scheme 1). Consequently, lowering catalyst
concentration in the system relative to alkyl halide will result in
only limited conversions of alkene and small yields of the desired
monoadduct.
The most effective solution towards lowering catalyst con-
centration in ATRA systems involves regeneration techniques
originally developed for mechanistically similar atom transfer
radical polymerization (ATRP).7,13–16 In all of these processes, the
activator (transition metal complex in the lower oxidation state,
Mtn+1LmX, Scheme 1) is continuously regenerated from the deacti-
vator in the presence of reducing agents such as phenols, glucose,
ascorbic acid, hydrazine, tin(II) 2-ethylhexanoate, magnesium and
free radical initiators (Scheme 1). Such regeneration compensates
Scheme 1 Proposed mechanism for catalyst regeneration in ATRA in the
presence of reducing agents.
for unavoidable radical–radical termination reactions, enabling a
significant decrease in the amount of metal catalyst. In particular,
our research group has focused on the use of free radical diazo ini-
tiators such as 2,2¢-azobis(2-methylpropionitrile) or AIBN,4,7,17–24
Department of Chemistry and Biochemistry, Duquesne University, 600
Forbes Avenue, 308 Mellon Hall, Pittsburgh, PA, 15282, USA. E-mail:
pintauert@duq.edu; Fax: +1 412 396 5683; Tel: +1 412 396 1626
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Table 1 Propagation rate constants (M-1s-1) of highly active alkenes in
In spite of the promising results with V-70, the use of this
low temperature free radical initiator is not practical on a large
scale because of the high cost of production and shipment.
Therefore, we explored other ways to perform the reactions
at lower temperature using cheaper and readily available free
radical diazo initiators, such as AIBN. One possible alternative to
generate the isobutyronitrile radicals from AIBN without the use
of heat is through UV irradiation. Commonly used thermal radical
initiators, including azo and peroxide compounds, are also known
to be capable of photoinitiation. The light-induced decomposition
of AIBN is established to be first-order with a rate constant of k =
free radical polymerization.26,27
Alkene
kp (60 ◦C)
kp (25 ◦C)
methyl acrylate
butyl acrylate
vinyl acetate
styrene
methyl methacrylate
2.8 ¥ 104
3.1 ¥ 104
7.9 ¥ 103
3.6 ¥ 103
8.2 ¥ 102
1.4 ¥ 104
1.5 ¥ 104
3.4 ¥ 103
87
3.2 ¥ 102
as well as ascorbic acid.25 We have shown that radicals generated
from thermal decomposition of AIBN were very effective reducing
agents in ATRA reactions utilizing simple a-olefins (1-hexene, 1-
octene and 1-decene) in the presence of as low as 5.0 ppm of
copper catalyst.19 However, significantly higher catalyst loadings
were required for more active alkenes such as styrene and
methyl acrylate. The elevated temperatures used in these ATRA
reactions, which were necessary for faster decomposition of AIBN
(rate determining step), increased the propagation rate constants
and, as a result, the target monoadducts were contaminated by
oligomers/polymers formed by direct initiation from free radical
initiator. The potential solution to this problem is to lower the
reaction temperature or use reducing agents that do not generate
free radicals such as ascorbic acid25 or magnesium.28–32
In our recent work, we reported copper catalyzed ATRA
reactions of various alkyl halides to alkenes using a free radical di-
azo initiator 2,2¢-azobis(4-methoxy-2,4-dimethylvaleronitrile) or
V-70, which readily decomposes at room temperature.23 The use
of a low temperature radical initiator allowed the reactions to
be performed at ambient temperature, which also lowered the
propagation rate constants of highly active alkenes (Table 1).
Impressive results were obtained in the addition of CCl4 and
CBr4 to various alkenes, with TONs as high as 12 500. Indeed,
a lower reaction temperature enabled more selective formation of
the single addition adducts, as opposed to reactions performed at
60 ◦C using AIBN (Table 2).
◦
1.2◦¥ 10-5 s-1 at 25 C,33 which is similar to the thermal one at
60 C (1.5 ¥ 10-5 s-1).18 Additionally, alkyl halides with weak C–
X bonds (where X = Br-, Cl- or I-) can also undergo photolysis.
Alkyl chlorides typically absorb between 10 and 200 nm, whereas
alkyl bromides and iodides absorb at longer wavelengths (l =
200–350 nm).34 Indeed, light was successfully used by Kharasch
in the 1940s in the addition of polyhalogenated alkanes (CBr4,
CCl4, CBr3Cl, CCl3Br) to alkenes.35–37 Thus, the advantages of
employing UV irradiation in ATRA reactions utilizing free radical
diazo initiators are two-fold. Firstly, ATRA reactions could
be carried out at lower temperatures, which will consequently
lower the propagation rate constants of highly polymerizable
alkenes and allow selective formation of the desired monoadduct.
Secondly, UV irradiation could increase the yield of monoadduct
as a result of the contribution of non-metal catalyzed Kharasch
addition.
In this article, ambient temperature photoinitiated ATRA
reactions of poly- and monohalogenated compounds to highly
active alkenes in free radical polymerization, such as methyl
acrylate, methyl methacrylate, vinyl acetate, acrylonitrile and
styrene, catalyzed by [CuII(TPMA)X][X] (X = Br- or Cl-, TPMA =
tris(2-pyridylmethyl)amine) complexes in the presence of AIBN
are presented. Furthermore, the methodology is also extended
to synthetically more useful ATRA followed by sequential ATRC
reactions, resulting in the formation of interesting 5-exo-trig cyclic
compounds.
Table 2 ATRA of CCl4 to highly active alkenes at 60 and 25 ◦C catalyzed
by [CuII(TPMA)Cl][Cl] complex
Alkenea
styrene
[Alk]0 : [CuII]0
500 : 1
T/◦C
Init.
Yield (%)
Experimental section
60
25
60
25
60
25
60
25
60
25
60
25
60
25
60
25
60
25
60
25
AIBN
V-70
AIBN
V-70
AIBN
V-70
AIBN
V-70
66
94
61
94
60
~100
47
80
30
62
General procedures
1000 : 1
2000 : 1
1000 : 1
2000 : 1
1000 : 1
1000 : 1
000 : 1
All reagents were obtained from commercial sources. 2,2¢-
Azobis(2-methylpropionitrile) (AIBN) was recrystallized from
cold methanol and dried at room temperature under vac-
uum. Solvents (acetonitrile and toluene) were degassed and
deoxygenated using Innovative Technology solvent purifier.
Tris(2-pyridylmethyl)amine (TPMA)38 and copper(II) complexes
[CuII(TPMA)Cl][Cl]20 and [CuII(TPMA)Br][Br]19 were synthesized
according to published procedures. All other reagents were used
as received. UV-irradiation was carried out using a high-intensity
UV curing lamp (Spectroline model SB-100PC, Spectronics Cor-
poration, Westbury, NY, long wave UV (365 nm)), which was
equipped with a 2F100C clear filter that reduces transmission of
medium wave (UV-B) and short wave (UV-C) radiation to safe
levels, while emitting a UV intensity of 27 000 mW cm-2 at 6 inches
(15 cm). The UV-lamp was typically placed approximately 15 cm
from the reaction mixture. 1H NMR spectra were obtained at room
temperature using a Bruker Avance 400 MHz spectrometer with
methyl acrylate
AIBN
V-70
methyl methacrylate
vinyl acetate
AIBNb 46
V-70
AIBNb 90
V-70 98
AIBNb 78
V-70 88
AIBNb 53
V-70b
68
AIBNb 38
V-70b
62
66
acrylonitrile
1000 : 1
2000 : 1
a Data for AIBN and V-70 were taken from references 20 and 23,
respectively. b This work.
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Table 3 Photoinitiated Kharasch addition of (poly)halogenated com-
pounds to alkenes at ambient temperature in the presence of AIBN
chemical shifts given in ppm relative to the residual solvent peak
(CDCl3, 7.26 ppm).
Entrya Alkene
1
RX
—
[Alk.]0 : [RX]0 Conv. (%) Yield (%)b
Kharasch addition of halogenated compounds to alkenes
1 : 0
86
0
A stock solution containing an alkene, AIBN, and an internal
standard (toluene or p-dimethoxybenzene for methyl acrylate and
methyl methacrylate; anisole for vinyl acetate, acrylonitrile and
styrene) was prepared ([alkene]0 : [AIBN]0 = 1 : 0.05). The desired
amount of alkyl halide was added to 0.3 ml of the stock solution.
The total volume was adjusted by adding acetonitrile to obtain
constant alkene concentration in each reaction system ([alkene]0 =
0.75 M). The resulting solution was then placed in the NMR tube,
purged with argon for 30 s, capped and sealed with Teflon tape.
The NMR tubes were then placed under a UV lamp for 24 h. A
water bath was used to maintain the reaction temperature at 23
2 ◦C.
2
3
4
5
6
7
8
9
CCl4
CBr4
1 : 1.25
1 : 1.25
1 : 1.25
1 : 1.25
93
95
79
48
84
87
88
80
2
38
0
30
0
0
CHCl3
CHBr3
CCl3CO2Et 1 : 1.25
BzCl
BzBr
—
1 : 4
1 : 4
1 : 0
0
0
10
11
12
13
14
15
16
17
CCl4
CBr4
1 : 1.25
1 : 1.25
1 : 1.25
1 : 1.25
85
93
83
84
85
83
86
33
4
9
0
3
0
0
0
0
Copper-catalyzed ATRA of halogenated compounds to alkenes
CHCl3
CHBr3
CCl3CO2Et 1 : 1.25
BzCl
BzBr
—
The corresponding alkene, alkyl halide, AIBN (for CCl4, CBr4,
CHCl3, CHBr3, and CCl3CO2Et : [alkene]0 : [RX]0 : [AIBN]0
1 : 4
1 : 4
1 : 0
=
1 : 1.25 : 0.05; for benzyl chloride (BzCl) and benzyl bromide
(BzBr) : [alkene]0 : [RX]0 : [AIBN]0 = 1 : 4 : 0.05) and an internal
standard (toluene or p-dimethoxybenzene for methyl acrylate
and methyl methacrylate; anisole for vinyl acetate, acrylonitrile,
and styrene) were dissolved in acetonitrile to make up a stock
solution of 1.1 M in alkene. The desired amount of CuII complex
([CuII(TPMA)Cl][Cl] for alkyl chlorides, or [CuII(TPMA)Br][Br]
for alkyl bromides) from 0.025 M solution was added to 0.3 ml
of the reaction mixture in the NMR tube. The total concentration
of alkene was adjusted to 0.75 M by the addition of acetonitrile.
After purging the solution with argon for 30 s, the NMR tube was
capped, sealed with Teflon tape, and placed under a UV lamp for
24 h. A water bath was used to maintain the reaction temperature
at 23 2 ◦C.
18
19
20
21
22
23
24
25
CCl4
CBr4
1 : 1.25
1 : 1.25
1 : 1.25
1 : 1.25
38
42
34
36
34
33
33
0
0
11
0
0
0
0
0
0
CHCl3
CHBr3
CCl3CO2Et 1 : 1.25
BzCl
BzBr
—
1 : 4
1 : 4
1 : 0
26
27
28
29
30
31
32
33
CCl4
CBr4
1 : 1.25
1 : 1.25
1 : 1.25
1 : 1.25
26
32
9
14
7
20
28
0
1
0
CHCl3
CHBr3
CCl3CO2Et 1 : 1.25
BzCl
BzBr
—
1 : 4
1 : 4
1 : 0
0
2
10
0
0
0
Results and discussion
Kharasch addition of halogenated compounds to highly active
alkenes
In the first set of experiments, the non-metal catalyzed Kharasch
addition of halogenated alkanes to alkenes that are highly active in
free radical polymerization was initiated by free radicals generated
from the photodecomposition of AIBN. As shown in Table 3
(entries 3 and 5), addition of polybrominated compounds (CBr4
and CHBr3) to methyl acrylate at ambient temperature resulted in
low yields of the monoadduct (30–38%). Discrepancy between
the conversion and the yield can be attributed to free radical
polymerization. Addition of CCl4 (entry 2) resulted in much
lower monoadduct yield (2%) with a high percent conversion,
again indicating the formation of AIBN-initiated polymers. Nearly
quantitative conversions of methyl acrylate were also observed for
other less active alkyl halides with no apparent formation of the
monoadduct (entries 4, 6, 7, and 8). These results were consistent
with the early work of Kharasch et al.35,36
34
35
36
37
38
39
40
CCl4
Br4
1 : 1.25
1 : 1.25
1 : 1.25
1 : 1.25
12
27
11
26
10
11
10
0
11
0
0
0
0
0
CHCl3
CHBr3
CCl3CO2Et 1 : 1.25
BzCl
BzBr
1 : 4
1 : 4
a All reactions were performed in CH3CN in the presence of UV
light for 24 h. Reaction temperature was maintained at 23
2
◦C,
[alkene]0 : [AIBN]0 = 1 : 0.05, [alkene]0 = 0.75 M. b Yield is based on
the formation of monoadduct and was determined using 1H NMR
spectroscopy (relative errors are 10%).
cases was also low, suggesting insignificant polymer formation.
The selective formation of the monoadduct is expected with vinyl
acetate because it has a high chain transfer constant (ktr/kp =
1.04 for CCl4).27 The desired monoadduct was not obtained in the
addition of other halogenated compounds (entries 28–32).
Similarly, low yields of the monoadduct were obtained in the
addition of CCl4 (20%, entry 26) and CBr4 (28%, entry 27) to vinyl
acetate. However, the percent conversion of vinyl acetate in both
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Table 4 Photoinitiated copper catalyzed ATRA of CCl4 and CBr4 to
Kharasch addition of halogenated compounds to other highly
active alkenes such as methyl methacrylate (entries 10–16),
acrylonitrile (entries 18–24), and styrene (entries 34–40) was also
conducted without a copper catalyst. Very low yields of the
monoadduct were obtained only in the case of CBr4 (entries 11, 19,
and 35). The results presented in Table 3 clearly indicate that the
investigated (poly)halogenated compounds are ineffective chain
transfer agents in photoinitiated Kharasch addition for alkenes
that are highly active in free radical polymerization.
highly active alkenes at ambient temperature in the presence of AIBN
Entrya Alkene
1
RX
[Alk.]0 : [CuII]0 Conv. (%) Yield (%)b
c
CCl4
1000 : 1
100
47
2
3
4
5
6
7
8
CCl4
CCl4
CCl4
CCl4
CBr4
CBr4
CCl4
100 : 1
500 : 1
1000 : 1
2000 : 1
500 : 1
10 000 : 1
1000 : 1
100
100
100
100
100
100
100
100
99
84
85
100
76
d
d
c
Photoinitiated copper catalyzed ATRA of CCl4 and CBr4 to highly
active alkenes in the presence of AIBN
46
Photoinitiated ambient temperature non-metal catalyzed Kha-
rasch addition in the presence of AIBN was clearly ineffective
in generating the desired monoadduct for a series of alkyl halides
and alkenes (Table 3). Our focus therefore shifted towards the
use of metal catalysts, which have been shown to be more
effective halogen atom transfer agents.4,14,22 In particular, we
concentrated on copper complexes with tetradentate nitrogen
based ligand tris(2-pyridylmethyl)amine (TPMA) because they
have been shown to be very active in a variety of ATRA/ATRC
reactions.7,17–20,23–25 The results for the addition of CCl4 and CBr4
are summarized in Table 4. Experiments conducted in the presence
of copper(II) complex but in the absence of AIBN did not yield any
monoadduct. As evident from Table 4, total conversion of methyl
acrylate to the desired monoadduct was observed in the presence
of 1 mol-% of the [CuII(TPMA)Cl][Cl] catalyst (entry 2). Nearly
quantitative yields were also obtained using even lower catalyst
loadings (~0.05 mol-%, entries 3–5). Even more impressive results
were obtained in the ATRA of CBr4 using as low as 0.01 mol-% of
the [CuII(TPMA)Br][Br] catalyst (entry 7). Generally, decreasing
the reaction temperature does indeed increase the selectivity
towards monoadduct formation. For example, when the reaction
9
CCl4
CCl4
CCl4
CCl4
CBr4
CBr4
CCl4
100 : 1
500 : 1
1000 : 1
2000 : 1
500 : 1
10 000 : 1
1000 : 1
100
100
95
100
99
91
81
100
73
10
11
12
13
14
15
90
d
d
c
100
100
100
48
16
17
18
19
20
21
22
CCl4
CCl4
CCl4
CCl4
CBr4
CBr4
CCl4
100 : 1
500 : 1
1000 : 1
2000 : 1
500 : 1
10 000 : 1
1000 : 1
100
100
100
96
100
95
98
84
75
65
96
87
88
d
d
c
99
23
24
25
26
27
28
29
CCl4
CCl4
CCl4
CCl4
CBr4
CBr4
CCl4
100 : 1
500 : 1
1000 : 1
2000 : 1
500 : 1
10 000 : 1
1000 : 1
99
98
96
95
99
78
65
99
98
95
92
99
74
38
d
d
c
◦
in entry 2 was repeated at 60 C in the absence of UV light, the
monoadduct was obtained in only 47% yield (entry 1).
The results for ATRA of CCl4 and CBr4 to methyl methacrylate
(entries 8–14) also show drastic improvements in the presence
of copper(II)/TPMA catalysts. The CCl4–methyl methacrylate
monoadduct was formed in excellent yields using between 1
and 0.05 mol-% of [CuII(TPMA)Cl][Cl] (entries 9–12). In the
ATRA of CBr4 to methyl methacrylate (entries 13–14), high
yields of the monoadduct were obtained at even lower catalyst
loadings (0.01 mol-% relative to the alkene). At an alkene-to-
copper(II) ratio of 1000 : 1, the amount of monoadduct formed at
ambient temperature (entry 11) was again approximately two times
higher than at 60 ◦C (entry 8). The ATRA of CCl4 and CBr4
to acrylonitrile (entries 16–21), vinyl acetate (entries 23–28)
and styrene (entries 30–35) also showed high selectivity towards
monoadduct formation. However, the conversion of styrene was
significantly lower than for other alkenes, which was due to the
slower rate of addition at ambient temperature (vide infra).
The results presented in Table 4 are very similar to our
previous findings using low temperature free radical initiator V-
70.23 Therefore, they indicate that the generation of free radicals
from the photolysis of AIBN is as efficient as in thermal
decomposition of V-70 at room temperature. Hence, photolysis
of AIBN can be successfully applied in catalyst regeneration for
ambient temperature ATRA reactions.
30
31
32
33
34
35
CCl4
CCl4
CCl4
CCl4
CBr4
CBr4
100 : 1
500 : 1
1000 : 1
2000 : 1
500 : 1
99
50
32
27
77
60
96
46
29
22
75
51
d
d
10 000 : 1
a All reactions were performed in CH3CN in the presence of UV
light for 24 h. Reaction temperature was maintained at 23
2
◦C, [alkene]0 : [AIBN]0 = 1 : 0.05, [alkene]0 = 0.75 M, catalyst =
[CuII(TPMA)Cl][Cl]. b Yield is based on the formation of monoadduct
and was determined using 1H NMR spectroscopy (relative errors
are 10%). c AIBN decomposition by heating at 60 ◦C. d Catalyst =
[CuII(TPMA)Br][Br].
Photoinitiated copper catalyzed ATRA of CHCl3, CHBr3,
CCl3CO2Et, BzBr and BzCl to highly active alkenes in the
presence of AIBN
Encouraged by the results obtained in the addition of CCl4
and CBr4 (Table 4), photoinitiated copper catalyzed ATRA
reactions in the presence of AIBN were investigated with
less active alkyl halides, including CHCl3, CHBr3, ethyl
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Table 5 Photoinitiated copper catalyzed ATRA of less active
(poly)halogenated compounds to alkenes at ambient temperature in the
presence of AIBN
trichloroacetate (CCl3CO2Et), benzyl bromide (BzBr) and benzyl
chloride (BzCl). Alkyl halides with a smaller number of halogen
atoms on the carboradical center typically have lower activation
rate constants,39 and are thus less reactive towards addition.
Such ATRA reactions often require elevated temperatures, high
catalyst loadings, and/or large excess of alkyl halide in order
to achieve reasonable yields of the monoadduct. For instance,
Snapper et al. reported quantitative yields of the monoadduct in
ATRA of CHCl3 to styrene using as high as 10 equivalents of alkyl
halide relative to alkene and as much as 5 mol-% of ruthenium
catalyst.40 Reactions involving monohalogenated compounds are
expected to be even less active, and such substrates are by far the
least common in transition metal catalyzed ATRA. Nonetheless,
they are particularly attractive from the point of view of further
synthetic modifications of the resulting monoadduct.
The effect of the presence of UV light in our system is two-fold.
On the one hand, UV irradiation promotes photodecomposition
of AIBN, which is a necessary step for catalyst regeneration. On
the other, it might weaken the carbon–halogen bond making it
more susceptible to homolysis. As indicated in Table 5 (entries 1–
3), addition of polyhalogenated compounds CHBr3, CHCl3 and
CCl3CO2Et to methyl acrylate proceeded with reasonable yields
using 1 mol-% of copper catalyst. However, monoadduct was
formed in much lower yields in the case of monohalogenated alkyl
halides BzBr (entry 4) and BzCl (entry 5) even when 4.0 eq. were
used. For both alkyl halides, the selectivity was relatively high and
therefore the low yield can be attributed to incomplete conversions.
For methyl methacrylate (entries 6–10), acrylonitrile (entries 11–
15) and vinyl acetate (entries 16–18), monoadducts were obtained
in significantly lower yields than with methyl acrylate. In the
case of methyl methacrylate, the low yields were not mainly
due to incomplete alkene conversions, but rather free radical
polymerization initiated by AIBN. Additional possibilities could
include monoadduct re-activation. BzBr and BzCl were quite
inactive alkyl halides in copper-catalyzed ATRA involving vinyl
acetate (entries 19 and 20). Lastly, ATRA reactions in the case of
styrene proceeded quite efficiently with trihalogenated compounds
(entries 21–23), and were also moderate for monohalogenated ones
(entries 24–25).
Entrya Alkene
1
RX
[Alk.]0 : [RX]0 Conv. (%) Yield (%)b
CHCl3
1 : 1.25
70
63
2
3
4
5
6
CHBr3
CCl3CO2Et 1 : 1.25
BzBr
BzCl
CHCl3
1 : 1.25
51
55
42
35
98
46
49
33
26
31
1 : 4
1 : 4
1 : 1.25
7
8
9
10
11
CHBr3
CCl3CO2Et 1 : 1.25
BzBr
BzCl
CHCl3
1 : 1.25
80
86
70
59
69
20
28
12
7
1 : 4
1 : 4
1 : 1.25
48
12
13
14
15
16
CHBr3
CCl3CO2Et 1 : 1.25
BzBr
BzCl
CHCl3
1 : 1.25
55
50
49
47
10
35
40
21
16
9
1 : 4
1 : 4
1 : 1.25
17
18
19
20
21
CHBr3
CCl3CO2Et 1 : 1.25
BzBr
BzCl
CHCl3
1 : 1.25
5
10
3
0
89
5
10
0
0
78
1 : 4
1 : 4
1 : 1.25
22
23
24
25
CHBr3
CCl3CO2Et 1 : 1.25
BzBr
BzCl
1 : 1.25
61
68
40
29
49
61
34
23
1 : 4
1 : 4
a All reactions were performed in CH3CN in the presence of UV
light for 24 h. Reaction temperature was maintained at 23
2
◦C,
[alkene]0 : [CuII]0 : [AIBN]0 = 100 : 1 : 5, [alkene]0 = 0.75 M, catalyst =
Despite the unfavorable yields obtained in copper-catalyzed
ATRA of BzBr and BzCl to alkenes, to the best of our knowledge,
these are the first ever reported ATRA reactions involving
monohalogenated benzyl halides. Although detailed optimization
studies are needed, the monoadduct yields could be improved by
increasing reaction times, performing reactions neat, increasing
the concentrations of the catalyst and/or alkyl halide relative
to alkene, or using a more active copper(II) complex. These
possibilities are currently being investigated in our laboratories.
[CuII(TPMA)Cl][Cl] for R–Cl and [CuII(TPMA)Br][Br] for R–Br. b Yield
is based on the formation of monoadduct and was determined using H
1
NMR spectroscopy (relative errors are 10%).
the formation of functionalized cyclic compounds. This type of
cyclization reaction is particularly attractive since the nature and
number of functional groups in the final cyclic product can be
controlled by using the appropriate alkyl halide and 1,6-diene.
Furthermore, the reaction is very chemoselective with almost
exclusive formation of a 5-exo-trig cyclic product because of large
differences in the rates of ring closures (kexo-trig/kendo-trig = 100).41
As indicated in Table 6, cyclizations did not occur in the absence
of a copper catalyst (entries 1, 4, 7, and 10). In contrast, excellent
results were obtained when [CuII(TPMA)Cl][Cl] complex was used
in conjunction with AIBN. Nearly quantitative yields of the 5-
exo-trig products were obtained even at catalyst loadings as low as
0.05mol-%, relativeto1,6-diene(entries 3, 6, 9, and12). Formation
of 6-endo-trig and linear addition products (monoadduct and
diadduct) was not observed with any substrate. Interestingly, the
Photoinitiated copper catalyzed ATRA followed by sequential
ATRC in the presence of AIBN
In order to expand the synthetic applications of copper(I) regen-
eration in the presence of radicals generated from photodecom-
position of AIBN, ATRA reactions of various 1,6-dienes were
conducted followed by sequential cyclizations (ATRC). In this
domino type reaction, the sequential addition of alkyl halide
to diene and subsequent ring closure via intramolecular attack
of the generated radical to the second double bond leads to
3064 | Dalton Trans., 2011, 40, 3060–3066
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Table 6 Ambient temperature photoinitiated ATRA of CCl4 to 1,6-dienes followed by sequential ATRC catalyzed by [CuII(TPMA)Cl][Cl] in the presence
of AIBN
Entrya
1,6-Diene
Product
[Diene]0 : [CuII]0
Conv. (%)
Yield (%)b
cis : trans
1
2
3
4
5
6
7
8
1
1a
100 : 0
100 : 1
2000 : 1
100 : 0
100 : 1
2000 : 1
100 : 0
100 : 1
2000 : 1
100 : 0
100 : 1
2000 : 1
0
0
0
100
100
0
100
100
0
88
92
0
87
90
85
96
0
92
97
0
86
93
0
84
90
82 : 18
80 : 20
0
80 : 20
79 : 21
0
85 : 15
83 : 17
0
85 : 15
85 : 15
2
3
4
2a
3a
4a
9
10
11
12
a All reactions were performed in methanol in the presence of UV light for 24 h. Reaction temperature was maintained at 23
2
◦C,
[diene]0 : [CCl4]0 : [AIBN]0 = 1 : 1.25 : 0.05, catalyst = [CuII(TPMA)Cl][Cl]. b Yield is based on the formation of 5-exo-trig product and was determined by
1H NMR spectroscopy using p-dimethoxybenzene or anisole as internal standard (relative errors are 10%).
diastereoselectivity of the cyclization reactions was independent
of the nature of the substituents present in 1,6-diene. For all four
substrates, 5-exo-trig cyclopentane derivatives were formed with
a cis : trans ratio of approximately 83 : 17. Additionally, results
presented in Table 6 show similar diastereoselectivities regardless
of the catalyst loading. These findings are in good agreement
with previous studies and indicate that copper complex is not
involved in the cyclization steps, but rather only in the formation
and trapping of radicals.24,25,42 The results for ATRA reactions
followed by sequential ATRC show that higher catalyst loadings
are required for a photoinitiated AIBN system, as compared to a
thermal one.24 This is most likely induced as a result of a decrease
in radical ring closure and/or activation rate constant, which slows
down the overall rate of consumption of 1,6-diene.
active tri- and monohalogenated compounds, which was mostly
due to incomplete alkene conversions. Ambient temperature
ATRA of CCl4 to various 1,6-dienes followed by sequential
ATRC were also performed in the presence of UV light using
[CuII(TPMA)Cl][Cl] complex and AIBN. High yields of the 5-exo-
trig cyclic product were obtained for all dienes with preferential
formation of the cis isomer. Addition products (monoadduct and
diadduct) and the 6-endo-trig cyclohexane derivatives were not
observed. The ratio of cis : trans cyclic isomers was found to be
independent of the catalyst loading, indicating that the copper
complex was not involved in the cyclization steps, but rather only
in the formation and trapping of radicals.
Acknowledgements
Financial support through a National Science Foundation CA-
REER Award (CHE-0844131) is greatly acknowledged.
Conclusions
In conclusion, we have described the use of UV light in copper-
catalyzed atom transfer radical addition (ATRA) and cyclization
(ATRC) reactions of various (poly)halogenated compounds to
highly active alkenes in the presence of AIBN. Radicals generated
from photodecomposition of AIBN efficiently regenerated the
copper(I) complex at ambient temperature enabling ATRA of CCl4
and CBr4 with catalyst loadings as low as 0.05 mol-%. The desired
monoadduct was obtained in lower yields in the ATRA of less
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