Cu(I) complexes with diethoxyphosphoryl-1,10-phenanthrolines in catalysis of C-C and C-heteroatom bonds formation

Article abstract of DOI:10.1016/j.ica.2015.04.004

Diethoxyphosphoryl substituted 1,10-phenanthroline copper(I) complexes were tested as catalysts in the Sonogashira-type reaction, α-arylation of phosphoryl-stabilized C-H acids, C-N, C-P bond forming reactions (substitution reactions) and in the reaction of phenylacetylene and bis(pinacolato)diboron (addition reaction). The complexes demonstrate fairly high catalytic activity and in some cases their efficiency is superior to that of the parent Cu(phen)(PPh₃)Br (phen = phenanthroline).

Full text of DOI:10.1016/j.ica.2015.04.004

Accepted Manuscript
Cu(I) complexes with diethoxyphosphoryl-1,10-phenanthrolines in catalysis of
C–C and C–heteroatom bonds formation
A.Yu. Mitrofanov, A.G. Bessmertnykh-Lemeune, I.P. Beletskaya
PII:
S0020-1693(15)00187-5
http://dx.doi.org/10.1016/j.ica.2015.04.004
ICA 16492
DOI:
Reference:
To appear in:
Inorganica Chimica Acta
Received Date:
Accepted Date:
30 March 2015
9 April 2015
Please cite this article as: A.Yu. Mitrofanov, A.G. Bessmertnykh-Lemeune, I.P. Beletskaya, Cu(I) complexes with
diethoxyphosphoryl-1,10-phenanthrolines in catalysis of C–C and C–heteroatom bonds formation, Inorganica
Chimica Acta (2015), doi: http://dx.doi.org/10.1016/j.ica.2015.04.004
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Cu(I) complexes with diethoxyphosphoryl-1,10-phenanthrolines in catalysis
of C–C and C–heteroatom bonds formation
a,b
A.Yu. Mitrofanov , A.G. Bessmertnykh-Lemeune , I.P. Beletskaya
b
a*
a
Department of Chemistry, Moscow State University, Leninskie Gory, GSP-1, Moscow 119991, Russia
Institut de Chimie Moleculaire de l’Université de Bourgogne (ICMUB), Université de Bourgogne, UMR CNRS
b
6
302, 9, avenue Alain Savary, BP 47870, 21078 Dijon, Cedex, France
Abstract
Diethoxyphosphoryl substituted 1,10-phenanthroline copper(I) complexes were tested
as catalysts in the Sonogashira-type reaction, α-arylation of phosphoryl-stabilized C-H acids,
C–N, C–P bond forming reactions (substitution reactions) and in the reaction of
phenylacetylene and bis(pinacolato)diboron (addition reaction). The complexes demonstrate
fairly high catalytic activity and in some cases their efficiency is superior to that of the parent
3
Cu(phen)(PPh )Br (phen = phenanthroline).
Keywords: Cu-catalysis, formation of C–C and C–heteroatom bonds, phosphorylated
phenanthrolines.
1
. Introduction
Copper(I) complexes with 1,10-phenanthroline ligands are well-established catalysts
for various C–C and C–heteroatom bond forming reactions [1, 2]. However, functionalized
,10-phenanthrolines are still rarely used in these reactions though some of them demonstrate
1
a higher efficiency than the parent ligand [3-6]. The introduction of the diethoxyphosphoryl
substituent at different positions of the phenanthroline scaffold described by us [7] was made
with the aim to design recyclable heterogeneous catalysts according to grafting of their
copper(I) complexes on metal oxide supports. Indeed, phosphonic acids are known to form
the most robust organic-inorganic hybrid materials with an increased resistance to desorption
as compared to those prepared from organosilanes or carboxylic acids [8-12]. But first we
need to know the catalytic efficiency of these complexes which could be influenced by the
electronic effects of the substituent as well as the ability of the phosphoryl group to
coordinate the copper ion that could interfere with desired catalytic cycles. Another important
point for design of heterogeneous hybrid catalysts is to elucidate the most appropriate position
of the phosphonate group at the phen backbone.
*
Corresponding author. Tel.: +7 495 939 36 18; fax: +7 495 932 36 18.
E-mail address: beletska@org.chem.msu.ru (I.P. Beletskaya).
1

Recently we reported the synthesis of copper(I) complexes 1a-d and 2a-c (Figure)
13]. In this work these complexes were tested as catalysts in cross-coupling reactions
substitution reactions) and in the synthesis of β-styreneboronic acids in the reaction of
[
(
alkynes and bis(pinacolato)diboron (an addition reaction).
Figure. Structures of diethoxyphosphoryl-1,10-phenanthrolines (Pphen) and their copper(I)
complexes.
2
. Experimental section
2
.1. Generals
All chemicals exсept phenanthroline phosphonates were of commercial quality
Aldrich, Acros) and used as received. Phenanthroline phosphonates and their copper
(
complexes were obtained according to our previous reports [7, 13]. Complex 1e was prepared
using a literature procedure [3]. Testing of the catalytic properties was carried out using
1
31
Carousel 12 Plus equipment for parallel synthesis (Radleys). H, P NMR spectra were
recorded at 300 MHz on a Bruker Avance-300. Gas Chromatography (GC) analyses were
carried out using Thermo Scientific Trace GS Ultra DSQ II System fitted with a Thermo-TR-
2

5
MS capillary column (length - 30 m, ID - 0.25 mm, film thickness - 0.25 µm). The
measurements were made at the "Pôle Chimie Moléculaire", the technological platform for
chemical analysis and molecular synthesis (http://www.wpcm.fr) which relies on the Institute
of the Molecular Chemistry of University of Burgundy and WelienceTM, a Burgundy
University private subsidiary.
2
.2. Cu(I)-catalyzed coupling of phenylacetylene with 4-iodoanisole
A Pyrex glass tube (2 cm in diameter) from Carousel system equipped with a Teflon
stir bar, was charged with 4-iodoanisole (234 mg, 1 mmol), potassium carbonate (276 mg, 2
mmol), Cu(Pphen)(PPh )Br (1a-1e) or [Cu(Pphen) ]PF (2a-2c) (10 mol% with respect to 4-
iodoanisole) was sealed with rubber septum. The tube was evacuated and purged with N
3
2
6
2
three times. Subsequently, toluene (4 ml) and phenylacetylene (121 µl, 1.1 mmol) were added
through a syringe into the tube. The reaction mixture was stirred at reflux and periodically
1
analyzed using H NMR spectroscopy.
2
.3. Cu(I)-catalyzed α-arylation of diethylcyanomethylphosphonate
A Pyrex glass tube equipped with a Teflon stir bar, was charged with 1-iodo-4-
nitrobenzene (150 mg, 0.6 mmol), cesium carbonate (489 mg, 1.5 mmol), CuI (9.5 mg, 0.05
mmol) and Pphen (2-Pphen, 3-Pphen or 4-Pphen) (15.8 mg, 0.05 mmol) was sealed with
2
rubber septum. The tube was evacuated and purged with N three times. Subsequently,
acetonitrile (2 ml) and diethylcyanomethylphosphonate (81 µl, 0.5 mmol) were added through
a syringe into the tube. The reaction mixture was stirred at 60 ˚C and periodically analyzed
3
using P NMR spectroscopy.
1
2
.4. Cu(I)-catalyzed coupling of diphenylamine with iodobenzene
A Pyrex glass tube from Carousel system equipped with a Teflon stir bar, was charged
with diphenylamine (84.6 mg, 0.5 mmol), potassium tert-butoxide (112 mg, 1 mmol) and
Cu(Pphen)(PPh )Br (1a-1e) (10 mol% with respect to the diphenylamine) was sealed with
rubber septum. The tube was evacuated and purged with N three times. Subsequently,
3
2
toluene (4 ml) and iodobenzene (61 µl, 0.55 mmol) were introduced into the tube through the
septum using a syringe. The reaction mixture was stirred at reflux and periodically analyzed
using GC chromatography. The yields of the target product were determined using dodecane
as an internal standard.
3

2
.5. Cu(I)-catalyzed coupling of di-n-butyl phosphite with 4-iodoanisole
A Pyrex glass tube equipped with a Teflon stir bar, was charged with 4-iodoanisole
(
117 mg, 0.5 mmol), cesium carbonate (195 mg, 0.6 mmol) and Cu(Pphen)(PPh
3
)Br (1a-1c,
1
e) was sealed with rubber septum. The tube was evacuated and purged with N three times.
2
Subsequently, toluene (2 ml) and di-n-butyl phosphite (233 µl, 1.2 mmol) were added through
a syringe into the tube. The reaction mixture was stirred at reflux and periodically analyzed
1
using H NMR spectroscopy.
2
.6. Cu(I)-catalyzed boration of phenylacetylene
A Pyrex glass tube equipped with a Teflon stir bar, was charged with bis(pinacolato)diboron
(
(
127 mg, 0.5 mmol), potassium tert-butoxide (3.4 mg, 0.03 mmol) and Cu(Pphen)(PPh
1a-1c, 1e) (3 mol% with respect to phenylacetylene) was sealed with rubber septum. The
three times. Subsequently, THF (2 ml), methanol (40
3
)Br
tube was evacuated and purged with N
2
µl, 1 mmol) and phenylacetylene (55 µl, 0.5 mmol) were added through a syringe into the
1
tube. The reaction mixture was stirred at room temperature and analyzed using H NMR
spectroscopy.
3
. Results and discussion
Firstly, catalytic properties of copper(I) complexes 1a-d and 2a-c were investigated in
cross-coupling reactions of aryl halides with various nucleophiles. To ensure an accurate
comparison of the complexes, the molar ratio of reagents and the catalyst as well as the
dilution of the reaction mixtures were the same for each reaction series and relevant control
experiments using copper(I) complexes 1e and 2d with unsubstituted 1,10-phenanthroline
were performed.
Palladium-free Sonogashira-type reaction was investigated using the reaction of
phenylacetylene and 4-iodoanisole in the presence of cesium carbonate in toluene at 110°C
[
3]. The results are summarized in Table 1. According to these data, the full conversion was
observed after 48 h for all studied complexes (entries 1, 2, 4 and 5), except for 1b (entry 3).
The functionalization of the phenanthroline ligand did not significantly increase the catalytic
efficiency of the studied complexes with the only one exception that being the sterically bulky
2
-phosphonate 2-Pphen (entry 5). Detailed studies of this reaction using an increased loading
of the reagents confirmed this preliminary result and indicated that the reaction proceeded
smoothly giving the product in 61% yield only after 2 h which was increased up to 76 and
1
00% after 3 and 5 hours, respectively.
4

Table 1. Cross-coupling of phenylacetylene with 4-iodoanisole catalyzed by
a
3
Cu(Pphen)(PPh )Br.
b
Yield (%)
Entry
Catalyst
8
h
24 h
67
-
48 h
100
-
1
2
3
4
5
Cu(phen)(PPh
Cu(2-Pphen)(PPh
Cu(3-Pphen)(PPh
Cu(4-Pphen)(PPh
Cu(5-Pphen)(PPh
3
)Br (1e)
28
100
19
3
)Br (1a)
3
)Br(1b)
)Br (1c)
)Br (1d)
40
76
82
60
3
23
100
3
26
100
a
Reaction conditions: 1 mmol of 4-iodoanisole, 1.1 mmol of phenylacetylene, 2 mmol of K
2
CO
3
and 10 mol%
b
1
2
of the catalyst in toluene (4 ml) at reflux under N . Yield was determined by H NMR.
This reaction proceeded even with homoleptic bis-chelates [Cu(Pphen)
2 6
]PF (2-Pphen,
3
-Pphen, 2,9-Pphen) but more slowly as compared to the complexes discussed above. Indeed,
the full conversion of 4-iodoanisole was not achieved in the presence of 10 mol% of 2a-2c
even after 48 h (Table 2). This difference is simple to explain because the catalytic reaction
3
occurs after a reversible dissociation of one phenanthroline ligand from 2 and PPh from 1.
The ligand dissociation reactions are favored in the mixed ligand copper(I) complexes 1a-e
compared to the corresponding bis-chelates 2a-2c and this can influence their catalytic
activity [13]. Interestingly that 2a and 2c demonstrate a similar efficiency showing that a
more simple ligand dissociation in complex 2c is compensated by unfavourable steric effects
of bulky 2,9-Pphen in the catalytic cycle.
Table 2. Cross-coupling of phenylacetylene with 4-iodoanisole catalyzed by
a
[
2 6
Cu(Pphen) ]PF .
b
Yield (%)
Entry
Catalyst
8
h
24 h
68
48 h
68
c
1
2
3
[Cu(2-Pphen) ]PF (2a)
-
2
6
[Cu(3-Pphen)
2
]PF
6
(2b)
(2c)
29
23
42
50
[Cu(2,9-Pphen)
2
]PF
6
52
73
a
Reaction conditions: 1 mmol of 4-iodoanisole, 1.1 mmol of phenylacetylene, 2 mmol of K
2
CO
3
and 10 mol%
b
1
c
2
of the catalyst in toluene (4 ml) at reflux under N . Yield was determined by H NMR. Not determine.
5

In the reaction of α-arylation of diethylcyanomethylphosphonate by 1-iodo-4-
nitrobenzene performed with Cs CO in MeCN at 60 °С (Scheme), the complex obtained in
2
3
situ from CuI and 1,10-phenanthroline gives the best results affording the product in
quantitative yield after 4 h. When phenanthroline was replaced by 3-Pphen and 4-Pphen, the
product was obtained after 4 h in 85% and 89% yields, respectively, whereas the sterically
hindered 2-Pphen afforded the product in 66% yield only after 16 hours of the reaction. It
should however be noted, that the selectivity of the reaction was about 100% for all studied
catalysts.
Scheme. Cu-catalyzed α-arylation of diethylcyanomethylphosphonate by 1-iodo-4-
nitrobenzene.
Copper complexes are known as excellent catalysts for the C–N bond forming
reactions and particularly for the synthesis of arylamines [1]. A comparison of
3
Cu(Pphen)(PPh )Br complexes with that of unsubstituted phenanthroline was performed
using a model reaction of iodobenzene with diphenylamine in the presence of t-BuOK in
toluene at reflux [3].
The results are summarized in Table 3. Prolonged reaction time (7 h) was needed for
the reaction performed with Cu(I) complexes bearing the diethoxyphosphoryl substituent on
the phenanthroline ligand compared to that of unsubstituted Cu(phen)(PPh
3
)Br which
afforded the product after 3 hours. Nevertheless, complexes 1b-1d give the product almost
quantitatively. Sterically hindered complex Cu(2-Pphen)(PPh
3
)Br (1a) was inefficient for this
reaction.
a
Table 3. Cross-coupling of iodobenzene with diphenylamine.
6

b
Yield (%)
Entry
Catalyst
3
h
5 h
7 h
1
2
3
4
5
Cu(phen)(PPh
Cu(2-Pphen)(PPh
Cu(3-Pphen)(PPh
Cu(4-Pphen)(PPh
Cu(5-Pphen)(PPh
3
)Br (1e)
97
3
3
)Br (1a)
4
5
3
)Br(1b)
)Br (1c)
)Br (1d)
79
67
41
82
89
57
93
95
92
3
3
a
Reaction conditions: 0.55 mmol of iodobenzene, 0.5 mmol of diphenylamine, 1 mmol of t-BuOK and 10 mol%
b
. Yield was determined by GC.
of the catalyst in toluene (4 ml) at reflux under N
2
The reaction of 4-iodoanisole with di-n-butyl phosphite catalyzed by Cu(I) complexes
under the same conditions (toluene, reflux) in the presence of Cs CO required 20 mol% of
2
3
the catalyst (Table 4). This reaction afforded the product in quantitative yields after 24 h of
the reaction for all studied complexes. However, the most rapid reaction was observed for the
complex with unsubstituted ligand Cu(phen)(PPh
3
)Br and Cu(4-Pphen)(PPh
3
)Br. Using the
last complex, the catalyst loading can be decreased up to 10 mol%.
a
Table 4. Cu-catalyzed coupling of di-n-butyl phosphite with 4-iodoanisole.
b
Yield (%)
Entry
Catalyst (mol%)
4
h
8 h
82
25
23
68
24 h
100
100
100
100
100
1
2
3
4
5
Cu(phen)(PPh
3
)Br (1e) (20)
64
Cu(2-Pphen)(PPh
3
)Br (1a) (20)
3
)Br (1b) (20)
10
10
42
Cu(3-Pphen)(PPh
Cu(4-Pphen)(PPh
3
)Br (1c) (20)
)Br (1c) (10)
c
c
Cu(4-Pphen)(PPh
3
-
-
a
Reaction conditions: 0.5 mmol of 4-iodoanisole, 1.2 mmol di-n-butylphosphite, 0.6 mmol Cs CO
2
3
and the
b
. Yield was determined by H and P NMR. Not determine.
1
31
c
catalyst in toluene (2 ml) at reflux under N
2
Recently it was shown that the copper complexes catalyzed the reaction of
bis(pinacolato)diboron with alkynes with high efficiency and regiospecificity [14, 15].
Although catalytic systems for this reaction are generally composed of copper(I) salts and
phosphine ligands, we have shown that copper phenanthroline complexes 1a-1c and 1e are
also active in the reaction of bis(pinacolato)diboron with phenylacetylene and even more
7

efficient than known catalytic systems [14, 16]. Using 1 equiv. of bis(pinacolato)diboron and
Cu(phen)(PPh )Br (1e) the reaction was completed after 4 hours affording pinacol ester of
Z)-β-styreneboronic acid in 75% yield (Table 5, entry 1). Interestingly that Cu(I) complexes
with 1a-1c were more active and almost quantitative yields of the product were observed after
hours (entries 2-4). When 1.5 equiv. of bis(pinacolato)diboron were used under the same
3
(
4
conditions, quantitative yields of the ester were obtained with all studied complexes. The
reaction proceeded regiospecifically affording only (Z)-β-styreneboronate as product.
Table 5. Cu-catalyzed boration of phenylacetylene.
b
Yield (%)
Entry
Catalyst
Cu(phen)(PPh )Br (1e)
Cu(2-Pphen)(PPh
Cu(3-Pphen)(PPh
3
Cu(4-Pphen)(PPh )Br (1c)
1
2
3
3
75
98
94
90
3
)Br (1a)
3
)Br (1b)
4
a
Reaction conditions: 0.5 mmol of phenylacetylene, 0.5 mmol of bis(pinakolato)diboron, 0.03 mmol of
b
. Yield was
t-BuOK, 1 mmol MeOH and 3 mol% of the catalyst in THF (2 ml) at room temperature under N
2
1
determined by H NMR.
In summary, the catalytic efficiency of diethoxyphosphoryl-1,10-phenanthroline
copper(I) complexes is quite unusual regarding the dependence of their efficiency on the
location of the diethoxyphosphoryl substituent at the phenanthroline backbone. Taking into
account a possible difference in the rate-determining step of these reactions, it is difficult to
reach conclusions about the electronic and steric factors that influence their course. We
2
cannot exclude that a coordination of P(O)(OEt) substituent to the copper ion also influences
the catalytic properties of these complexes. Indeed, copper ions in higher oxidation states are
more oxophylic and should better bind to the oxygen of a phosphoryl group than Cu(I) ions.
4
. Conclusions
Diethoxyphosphoryl substituted 1,10-phenanthroline copper(I) complexes are efficient
catalysts for different C–C and C–heteroatom bond forming reactions and for the synthesis of
β-styreneboronic acids according to the reaction of alkynes and bis(pinacolato)diboron.
8

3
Sometimes their efficiency is even superior to that of Cu(phen)(PPh )Br. These readily
available air-stable complexes are useful for a search of efficient catalytic systems for Cu-
catalyzed reactions. Currently, efforts are underway to immobilize these catalysts on a titania
support and to prepare an efficient recyclable Cu-catalyst.
Acknowledgments
We would like to thank Ministry of Science and Education of the Russian Federation (grant
No. RI ME FI61314X0012), the Russian Foundation for Basic Research (grant No. 12-03-
9
3114) and CNRS (the International Associated French–Russian Laboratory of Macrocycle
Systems and Related Materials (LAMREM) of CNRS and RAS) for their financial support.
A.Yu. Mitrofanov is grateful to the French government for PhD fellowship.
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