Atom transfer radical addition (ATRA) catalyzed by copper complexes with N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) ligand

Article abstract of DOI:10.1016/j.polymer.2015.02.021

Synthesis, characterization, electrochemical studies and ATRA activity of copper complexes with N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) ligand in the presence of ascorbic acid as a reducing agent were reported. [Cu^II(TPEN′)Br][Br] (TPEN′ denotes tetracoordinated ligand) catalyst showed a very low activity in ATRA of CBr₄ to 1-octene, methyl methacrylate, methyl acrylate and styrene in methanol, which is a typical solvent used for ATRA reactions employing ascorbic acid. On the contrary, the yields and stereoselectivity towards monoadduct formation were dramatically increased in slightly polar but aprotic acetone. Based on molecular structures of isolated [Cu^II(TPEN)][BPh₄] and [Cu^II(TPEN′)Br][Br] complexes, as well as UV-Vis and cyclic voltammetry studies, an equilibrium was proposed involving inactive [Cu^II(TPEN)]²⁺ and ATRP active [Cu^II(TPEN′)Br]⁺ cations The halidophilicity of the bromide-based deactivating complex ([Cu^II(TPEN′)Br][Br]) decreased approximately 750 times upon changing the solvent from acetone (K_Br = 3000 ± 230) to methanol (K_Br = 4.1 ± 0.1), explaining poor catalytic activity in methanol. In acetone, [Cu^II(TPEN′)Br][Br] complex was nearly as active in ATRA reactions employing ascorbic acid as previously reported [Cu^II(TPMA)Br][Br].

Full text of DOI:10.1016/j.polymer.2015.02.021

Accepted Manuscript
Atom Transfer Radical Addition (ATRA) Catalyzed by Copper Complexes with
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) Ligand
Aman Kaur, Erin E. Gorse, Thomas G. Ribelli, Callista C. Jerman, Tomislav Pintauer
PII:
S0032-3861(15)00172-X
10.1016/j.polymer.2015.02.021
JPOL 17634
DOI:
Reference:
To appear in: Polymer
Received Date: 19 December 2014
Revised Date: 2 February 2015
Accepted Date: 14 February 2015
Please cite this article as: Kaur, A, Gorse, EE, Ribelli, TG, Jerman CC, Pintauer T, Atom
Transfer Radical Addition (ATRA) Catalyzed by Copper Complexes with N,N,N’,N’-tetrakis(2-
pyridylmethyl)ethylenediamine (TPEN) Ligand, Polymer (2015), doi: 10.1016/j.polymer.2015.02.021.
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ACCEPTED MANUSCRIPT
Atom Transfer Radical Addition (ATRA) Catalyzed by Copper
Complexes with N,N,N’,N’-tetrakis(2-
pyridylmethyl)ethylenediamine (TPEN) Ligand
Aman Kaur,a Erin E. Gorse,a Thomas G. Ribelli,b Callista C. Jermanb and Tomislav Pintauera*
a*Department of Chemistry and Biochemistry, Duquesne University, 600 Forbes Avenue, 308
Mellon Hall, Pittsburgh, Pennsylvania, 15282, USA. Tel: 412-396-1626, Fax: 412-396-5683, E-
mail: pintauert@duq.edu
bDepartment of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh,
Pennsylvania, 15213, USA.
KEYWORDS. Tris(2-pyridyl)methyl amine, copper, homogeneous catalysis, multidentate N-
donor ligand, ATRA.
ABSTRACT. Synthesis, characterization, electrochemical studies and ATRA activity of copper
complexes with N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) ligand in the
presence of ascorbic acid as a reducing agent were reported. [CuII(TPEN’)Br][Br] (TPEN’
denotes tetracoordinated ligand) catalyst showed a very low activity in ATRA of CBr4 to 1-
octene, methyl methacrylate, methyl acrylate and styrene in methanol, which is a typical solvent
used for ATRA reactions employing ascorbic acid. On the contrary, the yields and
stereoselectivity towards monoadduct formation were dramatically increased in slightly polar but
aprotic acetone.
Based on molecular structures of isolated [CuII(TPEN)][BPh4] and
[CuII(TPEN’)Br][Br] complexes, as well as UV-Vis and cyclic voltammetry studies, an
equilibrium was proposed involving inactive [CuII(TPEN)]2+ and ATRP active [CuII(TPEN’)Br]+
cations The halidophilicity of the bromide-based deactivating complex ([CuII(TPEN’)Br][Br])
decreased approximately 750 times upon changing the solvent from acetone (KBr =3000±230) to
methanol (KBr =4.1±0.1), explaining poor catalytic activity in methanol. In acetone,
[CuII(TPEN’)Br][Br] complex was nearly as active in ATRA reactions employing ascorbic acid
as previously reported [CuII(TPMA)Br][Br].
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INTRODUCTION AND BACKGROUND
Over the past several decades, copper complexes have attracted a considerable interest as
catalysts for carbon-carbon bond forming reactions, in particular atom transfer radical addition
(ATRA)1-5 and polymerization (ATRP).6-12 Mechanistically, in both processes, the copper(I)
complex homolytically cleaves a carbon halogen bond from alkyl halide to generate the
corresponding radical and copper(II) halide (Scheme 1). The radical then adds across a carbon-
carbon double bond of an alkene or monomer to generate the secondary radical, which is rapidly
trapped by copper(II) halide to form the desired monoadduct (ATRA). This step also regenerates
the activator or copper(I) complex. ATRP is mechanistically very similar to ATRA with the
[Insert Scheme 1]
exception that the activation-addition-deactivation cycles are repeated many times resulting in
polymers with well-defined molecular weights and narrow molecular weight distributions
(Ð=Mw/Mn).
Recent advances in the area of catalyst regeneration in transition metal catalyzed ATRA and
ATRP reactions not only enable the approach of the equilibrium from the right-hand side
(Scheme 1), but also a significant decrease in the catalyst concentration.1,3,6,13-27 In such
processes, the activator (transition metal complex in the lower oxidation state) that is responsible
for homolytic
cleavage of carbon-halogen bond is continuously regenerated from the deactivator (transition
metal complex in the higher oxidation state) in the presence of reducing agents such as free-
radical diazo initiators, tin(II) 2-ethylhexanoate, glucose, phenols, ascorbic acid, magnesium and
metallic copper.1,2,6,13-21,23,28,29 Transition metal complexes in the higher oxidation states are
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typically air stable and therefore their use surpasses otherwise necessary deoxygenation
techniques.
Electrochemical measurements are commonly used to predict the activity of copper complexes
in atom transfer radical processes, namely ATRA and ATRP.30-37 Generally, for a given alkyl
halide, the equilibrium constant for atom transfer (KATRP=ka/kd) can be directly correlated with
E1/2
values
provided
that
the
halidophilicity
of
the
copper
complex
-
II
2+
[CuIILmX]+
(
, KX, X=Br or Cl) remains constant. As a result, for copper
X +[Cu Lm ]
complexes with neutral nitrogen based ligands commonly used in ATRA and ATRP, a linear
correlation between ln(KATRP) and E1/2 values is typically observed.34,38,39 Another method of
predicting the activity of copper catalysts in ATRP is to directly compare the stability constants
of CuII and CuI complexes with the particular ligand
[CumLn ]
β m
II and
=
; m=I or II, n=1 or 2
[1]
[Cum ][L]n
(
β
β
I, respectively, Eq [1]). Both
β
II and I should be large in order to eliminate or suppress
β
possible concurrent reactions such as coordination of monomer and/or polymer, which are
typically present in large excess relative to the catalyst. Generally, a copper complex with a low
reduction potential should be more stable in its oxidized form (i.e. CuII should be more stable
than CuI) in order to achieve high catalytic activity.35,36
With the recent discovery indicating that the reducing agents can significantly reduce the
amount of copper complexes in ATRA and ATRP,14 a significant effort has been devoted
towards development of more active catalysts that could be used at even lower concentrations,
and potentially enable controlled radical polymerization of
α-olefins. The research in this area is
significantly focused on ligand design, which can be used to tailor electronic properties of the
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copper(I) center. Currently, tetradentate neutral nitrogen based ligands tris(2-pyridyl)methyl
amine (TPMA) and tris[2-(dimethylamino)ethyl]amine (Me6TREN) are among the most active
[Insert Scheme 2]
ligands in copper catalyzed ATRA and ATRP (Scheme 2). They form very stable copper(I and
II) complexes and more importantly are very reducing (-0.25 mV<E1/2<-0.30 mV, v.s. SCE,
Scheme 3).39 Recently, a new class of multidentate nitrogen based ligands such as
N,N,N’,N’-
tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) have been shown to be quite promising in
copper catalyzed ATRP of acrylic, methacrylic, and styrenic monomers at very low
concentrations and in the absence of a reducing agent.40 For example, CuIBr/TPEN catalyst
mediated ATRP at a catalyst/initiator molar ratio of 0.005 and produced polymers with well-
controlled molecular weights and low polydispersities. ATRP also occurred even at a
catalyst/initiator molar ratio as low as 0.001 with copper concentration in the produced polymers
as low as 6-8 ppm (catalyst/ monomer molar ratio = 10-5). Inspired by these results, we reverted
our attention to potential use of TPEN ligand in copper catalyzed ATRA.
In this article, we report on the synthesis, characterization, electrochemical studies and ATRA
activity of copper complexes with TPEN ligand in the presence of ascorbic acid as a reducing
agent.
EXPERIMENTAL SECTION
General. All chemicals were purchased from commercial sources, and used as received unless
otherwise
stated.
N
,N
,
N’
,N
’-tetrakis(2-pyridylmethyl)ethylenediamine
(TPEN)
and
[CuII(TPEN)Br][Br] were synthesized according to previously published literature procedures.38
Cyclic voltammetry experiments were performed under argon. Copper(II) complexes were
synthesized under ambient conditions.
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Instrumentation and Equipment. 1H NMR spectra were obtained using Bruker 400 MHz
spectrometer and chemical shifts are given in ppm relative to residual solvent peaks [CDCl3
δ
7.26 ppm; (CD3)CO δ2.05 ppm; CD3CN δ1.96 ppm]. IR spectra were recorded in the solid state
using Nicolet Smart Orbit 380 FT-IR spectrometer (Thermo Electron Corporation). Elemental
analyses for C, H, and N were obtained from Roberston Microlabs, NJ. UV-Vis spectra were
recorded using a Beckman DU-530 spectrometer in 1.0 cm path-length airtight quartz cuvettes.
All cyclic voltammograms were measured at 25°C with a NuVant potentiostat. Solutions of
CuIIBr2 and CuII(BPh4)2 complexes with TPEN ligand (1.0 mM) were prepared in the mixture of
acetonitrile (4.9 mL) and DMF (0.1 mL) containing 0.1 M NBu4Br or NBu4BPh4 as the
supporting electrolyte. Measurements were carried out under argon atmosphere at a scanning
rate (ν
) of 0.1 Vs-1, using a platinum disk and platinum mesh as the working and counter
electrode, respectively. An Ag|AgI|I- reference electrode was used and potentials were measured
relative to a ferrocenium/ferrocene couple, which was used as an internal standard.
X-ray Crystal Structure Determination. The X-ray intensity data were collected at 150 K
using graphite-monochromated Mo-K radiation (0.71073 Å) with a Bruker Smart Apex II CCD
diffractometer. Data reduction included absorption corrections by the multi-scan method using
SADABS.41 Crystal data and experimental conditions are given in Table 1. Structures were
solved
[Insert Table 1]
by direct methods and refined by full matrix least squares using SHELXTL 6.1 bundled software
package.42 The H-atoms were positioned geometrically (aromatic C-H 0.93, methylene C-H
0.97, and methyl C-H 0.96) and treated as riding atoms during subsequent refinement, with
Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C). The methyl groups were allowed to rotate about their
6

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local threefold axes. Crystal Maker 8.3 was used to generate molecular graphics. CCDC-
1039735 (for [(CuIIBr2)2TPEN]) and CCDC-1039736 [CuII(TPEN)][BPh4]2 contain the
supplementary crystallographic data for this paper. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/ data_request/cif.
Synthesis of Copper Complexes.
[(CuIIBr2)2(TPEN)]. A solution of TPEN (724 mg, 1.7 mmol) in 2.0 mL of dichloromethane
was added to a suspension of CuIIBr (763 mg, 3.4 mmol) in 1.0 mL of dichloromethane, resulting
in the formation of a green solution. After stirring for 5 min at ambient temperature,
[(CuIIBr2)2(TPEN)] was precipitated as green powder (yield=1.22 g, 82%). X-ray quality crystals
were obtained by crystallization in DMF via slow diffusion of diethyl ether. FT-IR (solid):ν
(cm-
1) = 2944(m), 1600(m), 1570(s), 1466(m), 1461 (s), 1261(m), 1262(m), 1062(s), 863(m),
670(m), 619(m). Anal. Calcd. for C26H28Br4Cu2N6 (871.24): C, 34.84; H, 3.24; N, 9.65. Found:
C, 35.50; H, 3.31; N, 8.82.
[CuII(TPEN)][BPh4]2. [(CuII(TPEN’)Br][Br] (131.0 mg, 0.203 mmol) was dissolved in solution
of methanol and DMF (95/5), and NaBPh4 (138.0 mg, 0.406 mmol) was added. Green powder
which precipitated immediately was washed with methanol, collected by filtration, and dried
under vacuum to yield (139 mg, 61%) of [(CuII(TPEN)][BPh4]2.
[CuII(TPEN)][BPh4]2 suitable for X-ray analysis were obtained in acetone by slow diffusion of
(cm-1) = 3054(s), 2998(s), 2923(s), 1694(m), 1580(m), 1477(m),
Crystals of
diethyl ether. FT-IR (solid):
ν
1427 (m), 1398(m), 1291(m), 1062 (m), 733(s), 702(s), 611(m). Anal. Calcd. for C74H68B2CuN6
(1126.53): C, 78.90; H, 6.08; N, 7.46. Found: C, 79.16; H, 6.13; N, 7.99.
General Procedure for ATRA reactions. ATRA reactions were performed in 5.0 mm air
tight J. Young NMR tubes. In a typical experiment, alkene (1.11 x 10-3 mol, V(methyl
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acrylate)=100
ꢀ
L, V(1-octene)=174
ꢀL, V(methyl methacrylate)=120 ꢀL and V(styrene)=127
ꢀ
L) was dissolved in 400
ꢀ
L of methanol or acetone. Carbon tetrabromide (CBr4) was then
added to the solution (1.25 eq, 0.455 g), followed by addition of 0.2 mL of ascorbic acid solution
(0.25M) in methanol as a reducing agent and 1,4-dimethoxybenzene as internal standard. After
the desired amount of copper(II) was added (for 0.01 M [CuII(TPEN)Br][Br] in methanol or
mixture of acetone and methanol (9:1): 1000:1 (V=80
ꢀL), 5000:1 (V=16 ꢀL), 10000:1 (V=8.06
ꢀ
L) and 20000:1 (V=4.03 L)), the NMR tube was sealed and placed in an oil bath thermostated
ꢀ
at 60 ºC for 24 hours. The conversion of alkene and the percent yield of monoadduct were
determined using 1H NMR spectroscopy.
Determination of Halidophilicity Constants (KBr)
The equilibrium constant (KBr) for association of Br- anions to [CuII(TPEN)]2+ cations was
determined according to previously published literature procedure.43 Solutions containing
[CuII(TPEN)][(OTf)2], (2.5 mM, OTf- = trifluoromethanesulfonate) were titrated with different
amounts of tetrabutylammonium bromide (TBABr) in a given solvent (several methanol-acetone
mixtures, as well as pure methanol and acetone). Spectra of the original solution containing no
bromide anions and of solutions containing
n
equivalents of Br- v.s. CuII were then collected.
TBABr was added to the solution until no further changes in the spectra were observed (i.e. all of
[CuII(TPEN)][BPh4]2 was converted to [CuII(TPEN)’Br][Br]).
[Insert Table 1]
RESULTS AND DISCUSSION
Copper catalyzed ATRA reactions in the presence of non-radical generating reducing agent
such as ascorbic acid are typically conducted in polar protic and aprotic solvents such as MeOH,
EtOH and acetone.44-47 The solubility of ascorbic acid in such solvents is relatively high, as
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opposed to conventional non-polar ATRA solvents like anisole or toluene. Shown in Table 2 are
the results for ATRA of CBr4 to various alkenes catalyzed by CuIIBr2/TPEN complex in the
presence of
[Insert Table 2]
ascorbic acid as a reducing agent. The results for previously reported [CuII(TPMA)Br][Br]
complex are included for comparison.44 Interestingly, for all alkenes investigated, the activity of
CuIIBr2/TPEN was much lower than that of [CuII(TPMA)Br][Br]. The differences are
particularly noticeable for more active alkenes such as methyl methacrylate and methyl acrylate.
It is important to observe that relatively high conversions were achieved for both alkenes at low
catalyst loadings. However, the yield of the monoadduct was dramatically decreased. This
clearly points to inefficient deactivation, which is not consistent with previously conducted
ATRP studies.40 Hence, our attention shifted towards examining the structures of the deactivator
or CuIIBr2/TPEN complex in both the solid state and solution.
In addition to [CuII(TPEN’)Br][Br] (TPEN’ denotes tetracoordinated ligand) which was
previously isolated directly from ATRP reaction mixture, we were able to isolate and structurally
characterize two new complexes, namely [(CuIIBr2)2(TPEN)] (Figure 1) and [CuII(TPEN)][BPh4]
(Figure 2). Both complexes indicated that TPEN ligand can also coordinate to the copper(II)
center
[Insert Figure 1]
[Insert Figure 2]
in a tridentate and hexadentate fashion, respectively.
In previously characterized
[CuII(TPEN’)Br][Br]40 the molar ratio of CuIIBr2 to TPEN was 1:1. The TPEN ligand was
coordinated to the copper(II) center using four of its six donor nitrogen atoms from pyridine
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rings. The fifth nitrogen atom was only weekly coordinated to the Cu2+ ion (CuII-N=2.525(5) Å),
resulting in a highly distorted octahedral geometry. The structure of the complex was similar to
previously characterized [CuII(TPEN)][ClO4]2 in which the metal center was also coordinated by
four nitrogen atoms with one pyridyl nitrogen atom involved only in partial coordination.48 In
the molecular structure of [(CuIIBr2)2(TPEN)], the stoichiometric ratio between CuIIBr2 and
TPEN was found to be 2:1. The hexadentate TPEN ligand was coordinated to two copper(II)
centers through two sets of bis(2-pyridylmethyl)amino units. The molecule also contained a
two-fold symmetry. Each copper(II) cation was coordinated by two nitrogen atoms from
pyridine rings (CuII-N=1.979(2) Å and 1.989(2) Å), one tertiary amine nitrogen (CuII-
N=1.979(2) Å), and two bromide anions (CuII-Br=2.4755(4) Å and 2.4844(4) Å) in a highly
distorted trigonal bipyramidal geometry (τ=0.67; τ values range between 0 (ideal square
pyramidal geometry) and 1 (ideal trigonal bipyramidal geometry)). The structure of
[(CuIIBr2)2(TPEN)] shared many similar structural features with other ATRA/ATRP active
CuIIBr2 complexes containing neutral tridentate nitrogen based ligand such as
49
CuII(PMDETA)Br2
(PMDETA=
N
,N
,
N’,N”,N”-pentamethyldiethylenetriamine)
or
50
CuII(terpy)Br2 (terpy=2,2’:6’,2”-terpyridine). Lastly, crystals of [CuII(TPEN)][BPh4]2 suitable
for X-ray analysis were obtained in acetone by slow diffusion of diethylether. The
corresponding molecular structure is shown in Figure 2. The Cu(II) center adopted distorted
octahedral geometry and was coordinated by six nitrogen donor atoms from TPEN ligand. The
axial Cu-Nax bond distances (Cu-Nax=2.475(4) Å and 2.210(3) Å) were found to be longer than
the equatorial ones (average Cu-Neq= 2.050(6) Å). In a structurally related [CuII(TPEN)][PF6]2
complex, the coordination sphere around Cu2+ cation was occupied by only five nitrogen atoms
from TPEN ligand due to the dissociation of one of the pyridine arms (Cu-Npy=5.008Å).
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Furthermore, contrary to the octahedral [CuII(TPEN)][BPh4]2 complex, the axial bond distances
48
in [CuII(TPEN)][PF6]2 (Cu-Nax=2.005Å and 1.972Å) were found to be shorter than the
equatorial ones (Cu-Neq=2.148Å, 2.029Å and 2.084Å). Apart from [CuII(TPEN)][BPh4]2,
hexacoordination of TPEN based ligands was also observed in some FeII and ZnII complexes.51-53
With these transition metals, TPEN appears to be more strongly coordinating to the metal center
as indicated by shorter and nearly equal MtII-N bond distances (average FeII-N=1.981 Å and
ZnII-N=2.160 Å).
So far, based on the isolation of copper(II)/TPEN complexes discussed above, it appears that
the only two possible deactivators in the system include [(CuIIBr2)2(TPEN)] and
[CuII(TPEN’)Br][Br]. Hexacoordinated [CuII(TPEN)]2+ cation can be clearly ruled out since it
does not contain coordinated bromide anions. Furthermore, the presence of [(CuIIBr2)2(TPEN)]
can also be ruled out due to three important experimental observations. Firstly, the ratio of
CuIIBr2 to TPEN in [(CuIIBr2)2(TPEN)] is 2:1, as opposed to 1:1, which was used
experimentally. Secondly, [(CuIIBr2)2(TPEN)] complex was virtually insoluble in solvents used
for ATRA studies, namely MeOH and acetone. It was only slightly soluble in DMSO and DMF.
Also, most importantly, based on cyclic voltammetry studies, [(CuIIBr2)2(TPEN)] (E1/2=-641 mV
v.s. Fc/Fc+ couple,
[CuII(TPEN’)Br][Br] (E1/2=-689 mV v.s. Fc/Fc+ couple,
∆Ep=124 mV, ipa/ipc= 0.98) was found to be less reducing than
∆
Ep=100 mV, ipa/ipc= 0.98). Hence, our
attention focused on the possibility for the existence of an equilibrium between inactive
[CuII(TPEN)][Br]2 and active ATRA deactivator [CuII(TPEN’)Br][Br]. The position of this
equilibrium should be very dependent on solvent polarity, with [CuII(TPEN)]2+ cations being
more favored in polar protic medium such as MeOH, due to its ability to effectively stabilize Br-
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anions via intermolecular interactions. To further examine this equilibrium, solution studies
were conducted using UV-Vis spectroscopy.
Shown in Figure 3 are UV-Vis spectra of [CuII(TPEN)][OTf]2 complex in acetone and
methanol in the absence and presence of externally added tetrabutylammonium bromine (2.0 eq.
relative to CuII complex). In methanol and acetone, the UV-Vis spectra of [CuII(TPEN)][OTf]2
are nearly identical, with strong absorption band and shoulder appearing at 684 and 960 nm,
respectively. The addition of 2.0 eq. of TBABr in acetone gives rise to a completely different
UV-Vis spectrum with an absorption band centered around 744 nm. Interestingly, only slight
changes were observed in methanol indicating that the predominant species in solution were still
[CuII(TPEN)]2+ cations.
[Insert Figure 3]
Furthermore, very small changes were also observed in methanol solution containing as much as
100 eq. of TBABr relative to starting [CuII(TPEN)][OTf]2 complex. This experimental results
clearly confirm that the predominant species in methanol include hexacoordinated
[CuII(TPEN)]2+ cations. In acetone, on the other hand, bromide anions readily displace one of
the coordinated pyridine arms to form active deactivator or [CuII(TPEN’)Br]+ species. The
equilibrium constant for association of Br- anions to [CuII(TPEN)]2+ cations was further
quantified in different mixtures of acetone and methanol using UV-Vis spectroscopy. Data were
analyzed using previously published procedures.43 The halidophilicity (KBr) values in different
MeOH/acetone mixtures are listed in Table 3. The halidophilicity of the bromide-based
deactivating complex ([CuII(TPEN’)Br][Br]) approximately decreased 750 times upon changing
the solvent from
[Insert Table 3]
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acetone (KBr =3000±230) to methanol (KBr =4.1±0.1), clearly indicating that a predominant
species in methanol were deactivation inactive [CuII(TPEN)]2+ cations, which clearly explains
very poor results for ATRA studies summarized in Table 1. The results in methanol could be
improved by externally adding the source of Br- anions. However, as indicated in Table 3, under
normal ATRA conditions, as much as 2400 equivalents would be needed to insure quantitative
formation of the deactivator or [CuII(TPEN’)Br][Br]. Alternatively, a much more useful
solution would be to conduct experiments in slightly polar but aprotic acetone. Indeed, as
indicated in Table 4, a dramatic improvement in catalytic performance was observed. For 1-
octene (entries 1 and 2), the
[Insert Table 4]
desired monoadduct was formed in very high yields using catalyst loadings as low as 0.01 mol-%
(relative to alkene). Furthermore, at catalyst loadings between 0.02 and 0.1 mol-% relative to
alkene high yields of the monoadduct were also observed in the case of more active methyl
methacrylate (entries 3 and 4), methyl acrylate (entries 6 and 7) and styrene (entries 9 and 10).
The yields slightly decreased at lower ratios of alkene to copper catalyst (10000:1, entries 5, 8
and 11). What is even more important to notice, particularly in the case of MMA, MA and
styrene, is that the stereoselectivity towards monoadduct formation was dramatically increased in
acetone when compared to methanol due to an increase in deactivation efficiency. Based on the
results presented in Table 4, the activity of [CuII(TPEN’)Br][Br] complex in ATRA reactions in
the presence of ascorbic acid as a reducing agent was nearly as high as the one obtained
previously with [CuII(TPMA)Br][Br].44
CONCLUSIONS
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In summary, synthesis, characterization, electrochemical studies and ATRA activity of copper
complexes with TPEN ligand in the presence of ascorbic acid as a reducing agent were reported.
[CuII(TPEN’Br][Br] (TPEN’ denotes tetracoordinated ligand) catalyst showed a very poor
performance in ATRA of CBr4 to 1-octene, methyl methacrylate, methyl acrylate and styrene in
MeOH, which is a typical solvent used for ATRA reactions employing ascorbic acid. On the
contrary, the yields and stereoselectivity towards monoadduct formation were dramatically
increased in slightly polar but aprotic acetone. Based on molecular structures of isolated
[CuII(TPEN)][BPh4] and [CuII(TPEN’)Br][Br] complexes, as well as UV-Vis and cyclic
voltammetry studies, an equilibrium was proposed involving inactive [CuII(TPEN)]2+ and
deactivation active [CuII(TPEN’Br]+ cations The halidophilicity of the bromide-based
deactivating complex ([CuII(TPEN’)Br][Br]) approximately decreased 750 times upon changing
the solvent from acetone (KBr =3000±230) to methanol (KBr =4.1±0.1), explaining poor catalytic
activity in methanol. In acetone, the activity of [CuII(TPEN’)Br][Br] complex in ATRA
reactions that utilize ascorbic acid as a reducing agent was nearly as high as the one obtained
previously with [CuII(TPMA)Br][Br].
ACKNOWLEDGMENT
Financial support from the National Science Foundation (CHE-0844131 and CHE-1360886) is
greatly acknowledged. Part of the data reported in this manuscript were obtained in the
Department of Chemistry at Carnegie Mellon University while the corresponding author was on
a sabbatical leave. TP wishes to express his gratitude to Prof. Krzysztof Matyjaszewski and his
group members for their hospitality.
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Graphical Abstract
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Captions for Schemes, Figures and Tables
Scheme 1. Proposed mechanism for copper catalyzed ATRA and ATRP.
Scheme 2. Highly active ligands for copper catalyzed ATRA and ATRP.
Scheme 3. Proposed equilibrium between [CuII(TPEN)]2+ and [CuII(TPEN’]Br+ species in
ATRA (TPEN’ denotes tetracoordinated ligand).
Figure 1. Molecular structure of [(CuIIBr2)2(TPEN)] at 150 K shown with 30% probability
displacement ellipsoids. H-atoms have been omitted for clarity. Symmetry codes used to
generate equivalent atoms: (1) -x+2,-y+1, -z+2. Selected bond distances [Å] and angles (o): Cu1-
N1 2.119(2), Cu1-N2 1.979(2), Cu1-N3 1.989(2), Cu1-Br1 2.4755(4), Cu1-Br2 2.4844(4), N1-
Cu1-N2 82.16(8), N1-Cu1-N3 81.42(9), N2-Cu1-N3 163.15(9), N2-Cu1-Br1 94.73(6), N1-Cu1-
Br1 118.43(6), N2-Cu1-Br1 94.73(6), N3-Cu1-Br1 96.39(7), N1-Cu1-Br2 118.81(6), N2-Cu1-
Br2 93.37(6), N3-Cu1-Br2 91.22(6).
Figure 2. Molecular structure of [CuII(TPEN)][BPh4]2 at 150 K shown with 30% probability
-
displacement ellipsoids. H-atoms, counterion BPh4 and solvent molecule (acetone) have been
omitted for clarity. Selected bond distances [Å] and angles (o): Cu1-N1 2.050(3), Cu1-N2
2.024(3), Cu1-N3 2.210(3), Cu1-N4 2.063(3), Cu1-N5 2.475(4), Cu1-N6 2.067(3), N1-Cu1-N2
112.72(12), N1-Cu1-N4 81.27(11), N1-Cu1-N6 165.61(11), N2-Cu1-N3 96.71(11), N2-Cu1-
N4,159.08(12), N2-Cu1-N5 87.48(12), N2-Cu1-N5 87.48(12), N3-Cu1-N6 80.83(11), N4-Cu1-
N6 85.36(11), N4-Cu1-N5 78.00(11).
20

ACCEPTED MANUSCRIPT
Figure 3. UV-Vis spectra of [CuII(TPEN)][OTf]2 complexes in acetone and methanol in the
absence and presence of externally added tetrabutylammonium bromide (TBABr).
Table 1.
Crystallographic data and experimental details for [(CuIIBr2)2(TPEN)] and
[CuII(TPEN)][BPh4]2.
Table 2. ATRA of CBr4 to alkenes catalyzed by [CuII(TPEN’)Br][Br] and [CuII(TPMA)Br][Br]
complexes in methanol in the presence of ascorbic acid as a reducing agent.a
Table 3. Association constants (KBr) for [CuII(TPEN)]2+ with Br- Anions in Acetone/Methanol
Solutions Determined Spectrophotometrically at Ambient Temperature.
Table 4. ATRA of CBr4 to alkenes catalyzed by [CuII(TPEN’)Br][Br] in acetone in the presence
of ascorbic acid as a reducing agent.a
21

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Scheme 1. Proposed mechanism for copper catalyzed ATRA and ATRP.
22

ACCEPTED MANUSCRIPT
Scheme 2. Highly active ligands for copper catalyzed ATRA and ATRP.
23

ACCEPTED MANUSCRIPT
Scheme 3. Proposed equilibrium between [CuII(TPEN)]2+ and [CuII(TPEN’]Br+ species in
ATRA (TPEN’ denotes tetracoordinated ligand).
24

ACCEPTED MANUSCRIPT
Table 1.
Crystallographic data and experimental details for [(CuIIBr2)2(TPEN)] and
[CuII(TPEN)][BPh4]2.
Name
[(CuIIBr2)2(TPEN)]
[CuII(TPEN)][(BPh4]2
Formula
Color
Shape
C26H28Br4Cu2N6·2(C3H7NO) C26H28CuN6·2(C24H20B)·(C3H6O)
Green
Cubic
1017.44
Triclinic
P-1
Green
Cubic
1184.59
Triclinic
P-1
Formula Weight
Crystal System
Space Group
Temp (K)
Cell Constants
a, Å
150
150
8.2417(1)
10.5925(1)
12.0617(1)
95.074(1)
107.344(1)
101.917(1)
970.68(2)
1
11.586(1)
13.581(1)
23.002(2)
75.197(2)
78.967(2)
67.586(2)
3217.2(6)
2
b, Å
c, Å
α
, deg
, deg
β
γ
, deg
V, Å3
Formula units/unit cell
Dcal'd, gcm-3
Absorption coefficient, mm-1 5.25
1.74
1.223
0.39
F(000)
504
1564
Diffractometer
Bruker Smart ApexII
Bruker Smart ApexII
Radiation, graphite monochr. Mo Kʎ (
Crystal size, mm 0.28 × 0.14 × 0.09
range, deg 2.3< <27.4
Range of h,k,l ±12, ±15, ±18
Reflections collected/unique 17444/4815
ʎ
=0.71073 Å)
Mo Kʎ (
0.50 × 0.29 × 0.18
0.9< <23.1
±12, ±15, ±25
22249/9092
0.04
ʎ =0.71073 Å)
θ
θ
θ
Rint
0.02
Refinement Method
Data/Restraints/Parameters
GOF on F2
multi-scan
6513/0/219
0.9
multi-scan
9058/0/786
1.02
Final R indices [I>2
R indices (all data)
σ
(I)]
0.034
0.05
0.132
0.157
Max. Resid. Peaks (e*Å-3)
1.26 and -1.10
0.59 and -0.35
25

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Table 2. ATRA of CBr4 to alkenes catalyzed by [CuII(TPEN’)Br][Br] and [CuII(TPMA)Br][Br]
complexes in methanol in the presence of ascorbic acid as a reducing agent.a
Entry
Ligand
Alkene
[Alk]0:[CuII]0 Conv.[%]/Yield[%]b TONc
Solvent=Methanol
1
TPEN
TPMAd
TPEN
TPMA
TPEN
TPMA
TPEN
TPMA
TPEN
TPMA
TPEN
TPMA
TPEN
TPMA
TPEN
TPMA
TPEN
TPEN
TPEN
1-octene
5000:1
10000:1
1000:1
5000:1
10000:1
1000:1
5000:1
10000:1
45/45
2250
4500
3900
8500
290
2
90/90
3
39/39
4
85/85
5
MMA
90/29
6
100/ 100
78/28
1000
1400
4300
3200
5700
150
7
8
100/86
67/32
9
10
11
12
13
14
15
16
17
18
19
99/57
MA
100/15
100/ 100
100/12
98/85
1000
600
4250
2600
6400
610
100/26
99/64
Styrene
1000:1
5000:1
10000:1
97/61
90/60
3000
1800
76/18
aAll reactions were performed in methanol 60 ºC for 24h with [alkene]0:[CBr4]0:[ascorbic
acid]0=1:1.25:0.07, [alkene]=1.34M. bThe yield is based on the formation of monoadduct and
1
was determined using H NMR spectroscopy (relative errors ±10%). cTONs for all reactions
were calculated taking into account the percent yield of monoadduct.
dData for
[CuII(TPMA)Br][Br] complex were taken from Ref. 44.
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Table 3. Association constants (KBr) for [CuII(TPEN)]2+ with Br- Anions in Acetone/Methanol
Solutions Determined Spectrophotometrically at Ambient Temperature.
MeOH/ACTN.
(% v/v)
[MeOH]
(M)
KBr
Equiv. of TBABr for complete
(99.999%) association of Br-
0/100
0
3000±230 (3)a
450±50 (6)
45±8 (5)
33
20/80
40/60
60/40
80/20
100/0
4.9
220
9.9
2200
3600
6400
2400
14.8
19.8
24.7
28±6 (5)
16±2 (6)
4.1±0.1 (5)
aThe number in parentheses after each value of KBr indicates the number of spectra used for the
calculation of the association constant (halidophilicity).
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Table 4. ATRA of CBr4 to alkenes catalyzed by [CuII(TPEN’)Br][Br] in acetone in the presence
of ascorbic acid as a reducing agent.a
Entry
Alkene
[Alk]0:[CuII]0 Conv.[%]/Yield[%]b TONc
Solvent=Acetone
1
1-octene
MMA
5000:1
10000:1
1000:1
5000:1
10000:1
1000:1
5000:1
10000:1
1000:1
5000:1
10000:1
84/84
4200
7300
730
2
73/73
3
98/73
4
71/62
3100
4400
1000
4100
6400
870
5
63/44
6
MA
100/ 100
98/82
7
8
82/64
9
Styrene
100/87
100/78
82/47
10
11
3900
4700
aAll reactions were performed in acetone 60 ºC for 24h with [alkene]0:[CBr4]0:[ascorbic
acid]0=1:1.25:0.07, [alkene]=1.34M. bThe yield is based on the formation of monoadduct and
1
was determined using H NMR spectroscopy (relative errors ±10%). cTONs for all reactions
were calculated taking into account the percent yield of monoadduct.
28

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Figure 1. Molecular structure of [(CuIIBr2)2(TPEN)] at 150 K shown with 30% probability
displacement ellipsoids. H-atoms have been omitted for clarity. Symmetry codes used to
generate equivalent atoms: (1) -x+2,-y+1, -z+2. Selected bond distances [Å] and angles (o): Cu1-
N1 2.119(2), Cu1-N2 1.979(2), Cu1-N3 1.989(2), Cu1-Br1 2.4755(4), Cu1-Br2 2.4844(4), N1-
Cu1-N2 82.16(8), N1-Cu1-N3 81.42(9), N2-Cu1-N3 163.15(9), N2-Cu1-Br1 94.73(6), N1-Cu1-
Br1 118.43(6), N2-Cu1-Br1 94.73(6), N3-Cu1-Br1 96.39(7), N1-Cu1-Br2 118.81(6), N2-Cu1-
Br2 93.37(6), N3-Cu1-Br2 91.22(6).
29

ACCEPTED MANUSCRIPT
Figure 2. Molecular structure of [CuII(TPEN)][BPh4]2 at 150 K shown with 30% probability
-
displacement ellipsoids. H-atoms, counterion BPh4 and solvent molecule (acetone) have been
omitted for clarity. Selected bond distances [Å] and angles (o): Cu1-N1 2.050(3), Cu1-N2
2.024(3), Cu1-N3 2.210(3), Cu1-N4 2.063(3), Cu1-N5 2.475(4), Cu1-N6 2.067(3), N1-Cu1-N2
112.72(12), N1-Cu1-N4 81.27(11), N1-Cu1-N6 165.61(11), N2-Cu1-N3 96.71(11), N2-Cu1-
N4,159.08(12), N2-Cu1-N5 87.48(12), N2-Cu1-N5 87.48(12), N3-Cu1-N6 80.83(11), N4-Cu1-
N6 85.36(11), N4-Cu1-N5 78.00(11).
30