T.V. Grayaznova et al. / Journal of Organometallic Chemistry 785 (2015) 68e71
69
sophisticated palladium catalysis. We recently exploited the ad-
vantages of electrochemical syntheses in developing electro-
However the best result was obtained in a reaction with BQ and
sodium acetate or lutidine as a base (entry 7). Replacing H-dieth-
chemical
and
ligand-directed
CeH
acetoxylation
and
ylphosphonate 2 with a-hydroxyethylphosphonate 3 does not
perfluoroalkylation reactions [24e26]. The aim of the present study
is to develop electrocatalytic phosphonations and to obtain
mechanistic insights into the reaction that may aid in future reac-
tion optimizations.
produce the desired product 4 both at room temperature and at
refluxing within the electrolysis (entries 12, 13). However, addition
of a strong base NaOH to the reaction mixture resulted in a mod-
erate yield of 4 (entry 14). In the absence of electricity no phos-
phonation of 2-phenylpyridine was observed.
To get insight into the process, the putative palladacycle inter-
mediate [(PhPy)Pd(EtO)
Pd(BuO) P(O)] complex described by Murakami and co-workers
23], was synthesized, and its reactivity and electrochemical
properties were explored. The stirring of the dimeric acetate pal-
ladacycle 6 [27] and 2 (1:2.4 ratio) for an hour at room temperature
affords the desired complex 5 as a white precipitate in 90% yield
2
P(O)]
2
(5), similar to the [(PhPy)
Results and discussion
2
2
[
Our initial investigations focused on achieving the electro-
oxidative Pd-catalyzed phosphonation of 2-phenylpyridine 1. Both
H-phosphonate HP(O) (OEt) 2 and a-hydroxyphosphonate 3 were
2
examined as phosphorylating agents. For optimization of the re-
action conditions, a set of electrolysis was carried out with various
bases and additives, such as N-methylmaleimide (NMMI), 1,4-
benzoquinone (BQ), and 2,2 -bipyridine (bpy), which are known
reagents for facilitating reductive elimination reactions. The elec-
trolysis results are presented in Table 1.
The joint electrochemical oxidation of 1 and 2 (1.0:1.1 ratio) in
2
the presence of palladium acetate Pd(OAc) (10 mol %) afforded the
desired ortho CeH substitution product 4 in moderate or good
yields in the presence of a base, even in the absence of any other
additives. The target product 4 was formed under electrochemical
(Scheme 1). This procedure, involving a ligand exchange reaction, is
more straightforward than the one described for the synthesis of
[
(PhPy)Pd(BuO)
2
P(O)]
2
complex, which involved reaction of
a
-
0
ꢀ
hydroxybutylphosphonate and complex 6 at 120 C with excess of
K
2
4
HPO [23].
An X-Ray single diffraction study revealed that the structure of
complex 5 (Fig. 1) with diethylphosphonate ligands differs from the
previously described dipalladium complex with dibutylphospho-
nate ligands. The central metal containing cycle of complex 5 is
nearly planar with the dihedral angle between two phenylpyridine
ꢀ
fragments being equal 19 . The complex with dibutylphosphonate
ꢀ
oxidation at room or enhanced temperature (80 С) even in the
ligands [23] has a folded metal containing cycle with a considerably
distorted tricyclic moiety.
A cyclic voltammetry study (Fig. 2) reveals the complex 5 to be
oxidized in two irreversible steps at more positive potentials (1.18
and 1.69 V) compared with the acetate complex 6 (0.62 and 1.60 V).
The Murakami reaction [23] was carried out with complex 5
absence of NMMI, BQ or bpy (entries 1, 4, 6, 10, 14). The base was
found to be the only critical additional component for the CeP
coupling, as the reaction does not occur without it (entries 11, 15).
Table 1
a
Optimization of reaction conditions.
(Scheme 2A). The procedure involved refluxing the reagents in
ꢀ
CD
3
CN in the presence of NMMI (2 equiv.) for 4 h at 120 C. In this
way, only half of the initial complex was transformed into the
product 4. By comparison, the isolated complex 5 was electro-
chemically oxidized (Scheme 2B) in CH
3
CN at room temperature
under air-free conditions at the first oxidation peak potential, the
31
complete conversion giving a single product 4 ( Р NMR spectrum
revealed the only signal with 18 ppm) which was isolated in 90%
d
Р
yield. Thus, the electrochemical oxidation more effectively pro-
moted elimination of product from intermediate complex 5.
Importantly, the phosphonation reaction described in Scheme 2
did not require any additional reagents (such as NMMI, BQ, etc.) to
promote the reductive elimination of product. We speculate that
the AgOAc oxidant in the reported [22, 23] chemical CeH phos-
phonations does not transform the Pd(0) species into Pd(II) in the
catalytic cycle, but rather oxidizes the intermediate phosphonate
palladacycle to release the desired product of CeH substitution.
Comparing the oxidation potentials of the intermediate com-
plexes 5 and 6 of catalytic С-Н phosphonation, it is found, that the
phosphoric complex 5 is more difficult to oxidize. Under the reac-
tion conditions (chemical or electrochemical) the acetate complex
Entry
Phosphonating
agent
Base
Additive
4b, [%]
1
2
3
2
2
2
2
2
2
2
2
2
2
2
3
3
3
2
Na
Na
Na
2
HPO
2
HPO
2
HPO
4
4
e
20
43
42
48
45
15
78
72
48
12
n.r.
n.r.
n.r.
30
n.r.
BQ (2 equiv.)
NMMI (4 equiv.)
e
с
4
4
5
6
(EtO)
(EtO)
(EtO)
NaOAc
Lutidine
Lutidine
Lutidine
e
2
2
2
PONa
PONa
PONa
BQ (2 equiv.)
e
d
7
8
BQ (2 equiv.)
bpy(1 equiv.)
bpy(1 equiv.)
e
e
9
0f
1
1
1
1
1
1
1
2
3
4
bpy(1 equiv.)
bpy(1 equiv.)
BQ (2 equiv.)
e
Lutidine
Na HPO
2 4
NaOH
e
g
5
e
a
Unless otherwise noted, reactions were carried out with 1 (7.0 mmol), Pd(OAc)
CN (25 mL) at room
2
(
0.7 mmol, 10 mol%) and a corresponding base (4 equiv.) in CH
3
temperature. Reagents 2 or 3 (7.7 mmol) were dissolved in 5 ml acetonitrile and
added dropwise to the electrolysis mixture (Q ¼ 4F).
b
Isolated yields.
The reaction was carried out at 80 C.
AmOH was the solvent, the reaction was carried out at 80 C.
An equimolar amount of Pd(OAc) was used.
The reaction was carried out under refluxing conditions.
ꢀ
c
d
e
f
ꢀ
2
g
[PhPyEt][EtOP(O) (H)O] was the main product.
2 2
Scheme 1. Synthesis of [(PhPy)Pd(EtO) P(O)] palladacycle.
Grayaznova, Tatyana Vasilevna
