Copper(I) complexes with polymeric 2,2′-biquinoline-containing ligands as electrocatalysts for selective oxidation of the secondary hydroxy group in 3,24-dihydroxy-5β-cholane with oxygen

Article abstract of DOI:10.1134/S1070428011010064

Indirect electrocatalytic selective oxidation of the secondary hydroxy group in 3,24-dihydroxy-5β-cholane was performed using atmospheric oxygen in the presence of copper(I) complex with a polymeric 2,2′-biquinoline- containing ligand as catalyst. The reaction was characterized by a high yield (85%), 100% selectivity, and mild conditions, the Cu^II/Cu^I redox potential being -0.55 V relative to Ag/AgCl/KCl.

Full text of DOI:10.1134/S1070428011010064

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 1, pp. 62–65. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © T.V. Magdesieva, A.V. Dolganov, G.V. Latyshev, A.V. Yakimanskii, M.Ya. Goikhman, I.V. Podeshvo, N.V. Lukashev, 2011,
published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 1, pp. 65–68.
Copper(I) Complexes with Polymeric 2,2′-Biquinoline-
Containing Ligands as Electrocatalysts for Selective Oxidation
of the Secondary Hydroxy Group in 3,24-Dihydroxy-
5β-cholane with Oxygen
T. V. Magdesievaa, A. V. Dolganova, G. V. Latysheva, A. V. Yakimanskiib, M. Ya. Goikhmanb,
I. V. Podeshvob, and N. V. Lukasheva
a Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
e-mail: tvm@org.chem.msu.ru
b Institute of High-Molecular Compounds, Russian Academy Sciences, St. Petersburg, Russia
Received December 17, 2009
Abstract—Indirect electrocatalytic selective oxidation of the secondary hydroxy group in 3,24-dihydroxy-5β-
cholane was performed using atmospheric oxygen in the presence of copper(I) complex with a polymeric
2,2′-biquinoline-containing ligand as catalyst. The reaction was characterized by a high yield (85%),
100% selectivity, and mild conditions, the CuII/CuI redox potential being –0.55 V relative to Ag/AgCl/KCl.
DOI: 10.1134/S1070428011010064
The scope of synthetic application of direct elec-
trochemical oxidation of alcohols at a platinum or
glassy carbon electrode is strongly limited, for this
process occurs at fairly high anode potentials and is
generally characterized by low selectivity [1, 2]. In
a number of cases, the above problems may be solved
by using various mediator or catalytic systems [3–9]
(see also references given therein). The selectivity of
oxidation is determined by many factors; it is espe-
cially important in the synthesis of polyfunctionalized
organic compounds, e.g., pharmaceutical agents, or-
ganic materials with tunable properties, etc. Up to now,
numerous procedures, both electrochemical and purely
chemical, for selective oxidation of secondary and
primary hydroxy groups have been reported [10], each
being characterized by its own advantages and disad-
vantages. Taking into account continuous extension of
the range of problems to be solved by chemists, devel-
opment of new economic methods for selective cata-
lytic oxidation of hydroxy groups of different origins
remains as important as previously.
from their significance from the viewpoints of both
fundamental and applied science, in particular taking
into account wide application of steroids in pharma-
ceutical practice. Considerable difference in the reac-
tivity of primary and secondary hydroxy groups was
observed in reactions performed in the presence of
electrochemically generated nickel hydroxide oxida-
tive systems like NiIII(O)OH. For example, 3α- or
3β-hydroxy group can be selectively oxidized in the
presence of 17β-hydroxy group [11], but the yield is
fairly low (28%). Selective oxidation of cholic acid
at the 3α-hydroxy group was reported, the 7α- and
12α-hydroxy groups remaining unchanged [11]. The
yield of the oxidation product was relatively low
(38%) as a result of side oxidative decomposition at
the C3–C4 bond and subsequent lactonization. Selec-
tive electrocatalytic oxidation of the 3β-hydroxy group
in the presence of 11β- and 20β-hydroxy groups was
reported to provide a yield of 78% [11]. For compar-
ison, it should be noted that the yield in well known
Oppenauer oxidation of the 3β-hydroxy group in
structurally related steroids generally does not exceed
30% [12].
Steroidal alcohol molecules often contain different
kinds of hydroxy groups; therefore, they may be con-
venient models for studying oxidative selectivity of
catalytic systems. Interest in such studies originates
High selectivity observed in electrochemical proc-
ess may be rationalized by preferential adsorption of
62

COPPER(I) COMPLEXES WITH POLYMERIC BIQUINOLINE-CONTAINING LIGANDS
63
X
O
X
O
O
O
N
N
O
O
O
m
N
N
Cu
ClO4
L
L
n
[CuI(PA)L2][ClO4]
O
O
HO
OH
X =
; m:n = 8:2; L is solvent.
N
H
N
H
steroid molecule on the electrode surface at the less
sterically hindered α-side. Therefore, in most cases less
sterically hindered hydroxy groups are oxidized first.
The reactivity of different hydroxy groups over nickel
hydroxide electrode decreases in the following series
[13]: 3β-OH ≈ 3α-OH > 17β-OH >> 20β-OH >
11β-OH. This experimental reactivity series is deter-
mined primarily by spatial accessibility of hydroxy
groups, and 11β-, 17β-, and 20β-hydroxy groups
appear most sterically shielded.
readily than primary hydroxy groups (see table). These
findings prompted us to examine the possibility of
using previously proposed [14, 15] catalytic system for
selective oxidation of secondary hydroxy group in
model steroidal alcohols whose molecules also contain
primary hydroxy groups. As models for studying the
selectivity of electrocatalytic aerobic oxidation in the
presence of polymeric copper(I) complex we selected
steroidal alcohols I and II possessing both primary and
secondary hydroxy groups.
We recently proposed [14, 15] an electrochemical
synthetic approach (using soluble anodes) to new
redox-active catalytic systems on the basis of poly-
(amido acids) (PA) containing biquinoline fragments
capable of coordinating copper(I) ions. These polymer-
ic ligands are especially interesting due to their ability
to stabilize copper(I) complexes which tend to undergo
disproportionation in solution to give Cu(0) and Cu(II)
species.
Me
Me
OH
Me
H
H
H
H
HO
I
Me
OH
H
The polymeric copper(I) complex whose structure
is shown above exhibits a high electrocatalytic activity
in aerobic oxidation of aliphatic and aromatic alcohols
in the presence of atmospheric oxygen [14]. The volt-
ammetric curves observed for [Cu(PA)L2]ClO4 in
an argon atmosphere containing molecular oxygen, re-
action mechanism, and the relative catalytic activities
of polymeric copper complexes having different struc-
tures were discussed in detail in [14–16]. Electrocata-
lytic aerobic oxidation of alcohols leads to the forma-
tion of the corresponding carbonyl compounds in high
yield, while molecular oxygen is reduced to water [14].
No further oxidation of carbonyl compounds (to car-
boxylic acids) is observed.
Me
OH
Me
H
H
H
HO
OH
II
The reactions were carried under mild conditions at
room temperature under an oxygen pressure equal to
atmospheric, and the CuII/CuI redox potential was
equal to –0.55 V relative to silver chloride electrode
(Ag/AgCl/KCl), as was proposed in [14]. The general
Scheme 1.
Analysis of the current density in the oxidation of
simple model primary and secondary alcohols showed
that secondary hydroxy groups are oxidized more
Cu+
+
O2
+
RCH2OH
+
e–
+
2H+
Cu2+
+
RCHO
+
2H2O
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011

MAGDESIEVA et al.
64
Yields of carbonyl compounds and current densities in elec-
trocatalytic aerobic oxidation of alcohols in the presence
of [Cu(PA)L2]ClO4 (0.03 mol %) immobilized on the
surface of a graphite electrode, CH2Cl2, –0.55 V (relative to
Ag/AgCl/KCl), 20°C
The reaction can be carried out in both acetonitrile
and methylene chloride, and the yields of the corre-
sponding carbonyl compounds were fairly high (see
table). Methylene chloride turned out to be the optimal
solvent for the oxidation of steroid I. Unfortunately,
steroid II was poorly soluble in methylene chloride, as
well as in other solvents suitable for electrolysis
(acetonitrile, DMF, DMSO), so that we failed to per-
form electrochemical reaction and identify products.
Current density,
mA/cm2
Oxidation
product
Yield,
%
Initial alcohol
PhCH2OH
BuOH
1.00
1.10
1.25
1.25
1.27
PhCHO
94
93
94
91
85
BuCHO
Catalytic oxidation of compound I under the above
conditions (the amount of electricity passed through
the solution was 2 F/mol), gave 24-hydroxy-5β-cholan-
3-one in 85% yield and 100% selectivity (Scheme 2).
Even traces of oxidation products of both hydroxy
groups or oxidative decomposition products were not
detected in the reaction mixture.
PhCH(OH)Me
cyclo-C6H11OH
I
PhCOMe
Cyclohexanone
III
reaction scheme is illustrated by Scheme 1. The cata-
lyst was polymeric complex [Cu(PA)L2]+ ClO4– (its
preparation was described in [14]) which was immobi-
lized on a graphite electrode. For this purpose, a con-
ductive graphite fabric with a high specific surface
area (12 m2/g) was impregnated with a dilute solution
of the polymer in N-methylpyrrolidin-2-one, and poly-
meric copper(I) complex was obtained using a soluble
copper anode as source of Cu(I) ions. The graphite
fabric treated in such a way was used as working
electrode in the electrocatalytic process which was
performed in the potentiostatic mode at a potential of
–0.55 V. The catalytic surface was examined by cryo-
genic transmission electron microscopy (Cryo-TEM)
to estimate the width of the polymer layer. A section of
the fabric looked like dark graphite fibers with cavities
between them.* The polymer was distributed fairly
uniformly over the fiber surface, and the average width
of the polymer layer was ~10 nm. The catalytic surface
was fairly stable. No appreciable change in the cata-
lytic activity was observed after 20-h electrolysis or
104–105 catalytic cycles. The immobilized catalyst
exhibited high activity even at a fairly low concen-
tration of copper, 0.03 mol % with respect to the
substrate.
Thus the results of our experimental study indicated
that the catalytic system proposed by us previously
[14] on the basis of copper(I) complex with polymeric
2,2′-biquinoline-containing ligand is effective for
selective oxidation of secondary hydroxy groups in the
presence of primary ones. An important advantage of
the proposed approach is electrocatalytic character of
the process. Chemical oxidants inevitably give rise to
by-products resulting from reduction of the oxidant,
whereas in our case electric current acts as additional
reagent.
EXPERIMENTAL
Acetonitrile of pure grade was stirred for 12 h over
calcium hydride, distilled, heated for 2 h under reflux
over phosphoric anhydride, and distilled again; a frac-
tion with bp 81–82°C was collected. N-Methylpyrro-
lidin-2-one (from Aldrich) was dehydrated over cal-
cium hydride and distilled under reduced pressure;
a fraction with bp 35°C (5 mm) was collected. Meth-
ylene chloride of pure grade was distilled over calcium
Scheme 2.
Me
Me
Me
Me
OH
OH
O2, [Cu(PA)L2]ClO4
Me
H
H
Me
H
H
H
H
H
H
HO
O
I
III
* The corresponding image is available from the authors by
e-mail.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011

COPPER(I) COMPLEXES WITH POLYMERIC BIQUINOLINE-CONTAINING LIGANDS
65
hydride, and a fraction with bp 41°C was collected.
The PA polymer was synthesized according to the
procedure reported in [17]. Steroids I and II were
synthesized by standard methods [18, 19]; the other
examined alcohols were commercially available prod-
ucts (from Aldrich).
This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 08-03-00142, 07-03-00619, 07-03-90824).
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