Cobalt(II)[salen]-Catalyzed Selective Aerobic Oxidative Cross-Coupling between Electron-Rich Phenols and 2-Naphthols

Article abstract of DOI:10.1021/acs.joc.9b00822

A selectivity-driven catalyst design approach was adopted to address chemoselectivity issues in the oxidative coupling of phenols. This approach was utilized for developing a Co(II)[salen]-catalyzed aerobic oxidative cross-coupling of phenols in a recyclable 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) solvent. The waste-free conditions offer a sustainable entry to nonsymmetric biphenols via a mechanistic scheme that involves coupling of a liberated phenoxyl radical with a ligated 2-naphthoxyl radical.

Full text of DOI:10.1021/acs.joc.9b00822

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Article
Cobalt(II)[salen] Catalyzed Selective Aerobic Oxidative Cross-
Coupling between Electron-Rich Phenols and 2-Naphthols
Hagai Reiss, Hadas Shalit, Vlada Vershinin, Nagnath Yadav More, Hagit Forckosh, and Doron Pappo
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00822 • Publication Date (Web): 08 May 2019
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Cobalt(II)[salen] Catalyzed Selective Aerobic Oxidative Cross-Coupling
between Electron-Rich Phenols and 2-Naphthols
Hagai Reiss,a Hadas Shalit,a Vlada Vershinin,a Nagnath Yadav More,a Hagit Forckosha, and Doron Pappoa,*
Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
E-mail: Pappod@bgu.ac.il
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A selectivity-driven catalyst design approach was adopted to address chemoselectivity issues in the oxidative coupling of phenols. This approach
was utilized for developing a Co(II)[salen] catalyzed aerobic oxidative cross-coupling of phenols in a recyclable 1,1,1,3,3,3-hexafluoropropan-2-ol
solvent. The waste-free conditions offer a sustainable entry to non-symmetric biphenols via a mechanistic scheme that involves coupling of a
liberated phenoxyl radical with a ligated 2-naphthoxyl radical.
25
were found to mediate the oxidative cross-coupling of
phenols in accordance with this predictive model. To
overcome the mechanistic restriction that limits the cross-
INTRODUCTION
coupling between phenols with
a
high negative
Metal-catalyzed oxidative phenol coupling reactions offer a
sustainable method to prepare biaryl compounds directly
from unfunctionalized arenes.1-3 This process requires a
redox catalyst that can transfer two electrons and two
protons from the coupling partners to an oxidant, such as
a dioxygen molecule or peroxide, while forging a new biaryl
bond.4 Previous studies have shown that first-row
nucleophilicity difference (N << 0), our group turned to the
Fe[TPP]Cl (TPP = tetraphenylporphyrin) complex, which
has a single available site for phenol ligation. The
Fe[TPP]Cl catalyst proved to be efficient for coupling
phenols of type A with weak nucleophilic phenols of type
B, through postulated outer-sphere coupling between
ligated phenoxyl radical B and liberated phenoxyl radical
A (Scheme 1A).16 The chemoselectivity in these reactions
is obtained by the selective binding of phenol B to the metal
in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP).16 In both
mechanisms, the first requirement for achieving high
cross-coupling selectivity is that the oxidation of phenol A
in the presence of phenol B (EoxA < EoxB) will be selective.
Indeed, achieving chemoselectivity when both phenolic
reactants have relatively low oxidation potentials (EoxA ≈
EoxB) is a challenge. For example, the oxidative coupling
between readily oxidized 2-methoxy-4-methylphenol (2a,
Eox = 0.46V [HFIP, Ag vs AgNO3) and 3-carbomethoxy-2-
naphthol (3a, Eox = 0.80V) by FeCl3 [10 mol %, t-BuOOt-
Bu, HFIP, rt] exhibited high cross-coupling selectivity,
affording the desired cross-coupling product 6a in 82%
yield (Scheme 1B).21 However, under the same conditions,
the coupling of phenol 2a and 3-methoxy-2-naphthol (3b),
which has a relatively low oxidation potential (Eox(3b) =
0.56V), was not selective, affording a complex mixture of
homo-, cross-coupling, and dehydrogenation products
(vide infra). To overcome the mechanistic constraints that
limit the selectivity in coupling two readily oxidized phenols,
a selectivity-driven catalyst design approach was adopted.
The Kozlowski group reported the aerobic oxidative
homo- and cross-coupling of phenols by different M[salen]
and M[salan] complexes (M = Cr, Cu, Fe, Mn, Ru or V),
which is an important attempt to deal with the selectivity
issues of the reaction.14 In contrast to the attention devoted
to the latter metals, previous studies have only rarely
vanadium(V)5-13
chromium(III),14
manganese(III),14
iron(III),15-25 cobalt(II)26, 27, and copper(II)28-31 complexes
are effective catalysts for oxidative homo- and cross-
coupling of phenols.32, 33 Consequently, biaryl compounds
that are important for natural products synthesis and that
play a valuable role as catalysts and ligands in asymmetric
transformations are easily prepared in a single step from
simple phenols. Recent mechanistic studies revealed that
the selectivity in these reactions is catalyst dependent.34
Therefore, in order to take this chemistry one step further
and establish it as a benign method to complement
traditional cross-coupling reactions, new catalytic
conditions should be developed.
One possible approach to identify efficient catalytic
systems is to map the reactivity of complexes as catalysts
in the oxidative coupling of two phenols (A and B). This
reaction can afford either biphenol AA, biphenol BB, or
the cross-coupling product, biphenol AB, depending on
the identity of the catalyst and the reaction mechanism
(Scheme 1A). In 2015, our group introduced a model for
predicting the chemoselectivity outcome of oxidative
21
coupling reactions between two different phenols.4,
According to the suggested model, the formation of
biphenol AB via a radical-anion/nucleophile coupling
mechanism is favorable when ligated phenolate A is
selectively oxidized to phenoxyl radical A in the presence
of a stronger nucleophilic phenol(ate) B (EoxA < EoxB and
N > 0, N = NB - NA, N = theoretical global nucleophilicity,
Scheme 1A).21 However, when phenolate A is the superior
focused on the ability of cobalt(II) complexes to mediate
nucleophile (N
predominates.
Fe[phosphate]3,17, 19 and Katsuki’s Fe[salen] complexes23-
<
The
0), biphenol AA formation
multi-coordinated
FeCl3,21
27
oxidative phenolic coupling.26,
The few available
examples include the Co[salen] catalyzed aerobic
oxidative polymerization of 2,3-dihydroxynaphthalene35, 36
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and Guo’s aerobic Co[TPP] 1a, catalyzed oxidative
dimerization of readily oxidized phenols.37 Other related Catalyst-controlled chemoselectivity in oxidative
studies focused on the activity of Co[salen] complexes as phenol coupling. We initiated this study by screening
atmospheric dioxygen carriers38 and as aerobic catalysts different redox catalytic systems that will enable the
in the dehydrogenation of phenols to quinones.39-47 To the oxidative coupling between phenols with relatively close
best of our knowledge, suitable conditions for the aerobic oxidation potentials. For that purpose, 2-methoxy-4-
oxidative cross-coupling of phenols by Co(II) complexes methylphenol (2a, 1 equiv) and 3-methoxy-2-naphthol (3b,
have never been reported.
1 equiv) were chosen (Scheme 2).
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Here we describe a selectivity-driven catalyst design
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study that resulted in the development of highly selective Scheme 2. Catalyst-controlled chemoselectivity in the
and sustainable cobalt[salen]-catalyzed aerobic oxidative oxidative coupling of phenols. a,b,c
cross-coupling between readily oxidized phenols and 2-
naphthols (EoxA ≈ EoxB). This sustainable reaction can be
performed on a multi-gram scale in HFIP as a recyclable
solvent under air atmosphere (open flask); H2O is
produced as the only waste product. On the basis of our
mechanistic investigation a catalytic cycle that involves
coupling between ligated naphthoxyl radical with a
liberated phenoxyl radical is postulated.
Scheme 1. Selective oxidative cross-coupling of
phenols by iron catalysis.
aConditions: [A] FeCl3 (10 mol %), t-BuOO-tBu (1.5 equiv),
HFIP, rt, 16 h; [B] Fe[TPP]Cl (1b, 1 mol %), t-BuOOH (1.1
equiv), HFIP, rt, 16 h; [C] Cu(OH)Cl-TMEDA (1c, 1 mol %),
O2, CH2Cl2, rt, 19 h; [D] Co[TPP] (1a, 0.2 mol %), O2,
Na2CO3, MeOH-H2O, 60 °C, 16 h; [E] Co[salen] (1d, 1 mol
RESULTS AND DICUSSION
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%), air, HFIP, rt, 16 h; b=230 nm; cSee Scheme S2 in the
Co[TPP]/O2/Na2CO3/MeOH-H2O catalytic system.
2
3
The conditions developed by Guo for aerobic oxidative
homocoupling of phenols using Co[TPP] 1a [(0.2 mol %),
O2 (1 atm), and Na2CO3, MeOH-H2O, 60 °C] exhibited
unique selectivity. Under his reported conditions, the
phenol 2a underwent oxidative dimerization while naphthol
3b was left almost unreacted (Scheme 2D). Guo
SI for the exact conditions.
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FeCl3/t-BuOOt-Bu/HFIP catalytic system. The
oxidative coupling reaction between phenol 2a and 2-
naphthol 3b was first carried out using the multi-
coordinated FeCl3 catalyst under previously developed
conditions by our group [FeCl3 (10 mol %), t-BuOOt-Bu,
and HFIP at room temperature].15, 18, 20, 21, 48 HPLC analysis
of the reaction crude revealed the formation of all three
possible coupling products 4, 5, and 6, together with other
undefined over-oxidation compounds (Scheme 2A). As
mentioned above, under these conditions, FeCl3 mediates
the coupling of two phenols via an inner-sphere oxidative
postulated
an
oxidative
radical-radical
coupling
mechanism between two phenoxyl radicals. However, the
factors that lead to the selective formation of biphenol 5
remain in the dark.37 Nevertheless, it is reasonable to
assume that Co[TPP] mediates the reaction by a
mechanism that differs from that of the above copper and
iron catalysts.
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Co[salen] catalytic system. Encouraged by the
finding that Co[TPP] can selectively oxidize phenol 2a in
the presence of naphthol 3b, we examined the reactivity of
cobalt(II) salen complexes, which are known as superior
oxygen carriers.44, 45, 53-55 Therefore, they offer excellent
opportunities for developing sustainable catalytic systems
based on free air as the terminal oxidant. First, phenol 2a
(1 equiv) and naphthol 3b (1 equiv) were mixed with
Co[salen] 1d (1 mol %) in MeOH under air atmosphere at
room temperature. Yet, under these conditions no reaction
took place. However, when the reaction performed in HFIP
(Scheme 2E) a high degree of cross-coupling selectivity
was observed affording unsymmetrical biphenol 6 in an
excellent 86% isolated yield (see Figure 1). The fact that
atmospheric air serves as the terminal oxidant in this
reaction, makes this method to be highly attractive for
large-scale production of biaryl products.
radical-anion
coupling
mechanism.21
The
poor
chemoselectivity here is attributed to the inability of the
catalyst to distinguish between the two ligated phenolic
partners.
Fe[TPP]Cl/t-BuOOH/HFIP catalytic system. The
oxidative cross-coupling between phenol 2a and 2-
naphthol 3b by Fe[TPP]Cl catalyst 1b [(1 mol %), t-
BuOOH, and HFIP, rt] exhibited excellent cross-coupling
selectivity, affording unsymmetrical biphenol 6 as a single
product (Scheme 2B). On the basis of previously reported
competitive NMR studies,16 phenol 2a was found to be a
weak ligand for iron in HFIP, whereas 2-naphthol 3b binds
strongly to complex 1b in the presence of HFIP (see the
supporting information, Figure S1-S4). As a result,
selective binding of 2-naphthol 3b to the iron porphyrin
complex is assumed to be the origin of the
chemoselectivity.16 The postulated mechanism proceeds
with the formation of a high valence [3b][TPP]FeIVO
porphyryl radical intermediate that selectively oxidizes
phenol 2a to a phenoxyl radical 2a [Eox2a < Eox3b]. This
transient radical species reacts with a persistent ligated
naphthoxyl radical [3b][TPP]FeIII-OH intermediate (see
Scheme 1A) via an intermolecular radical−radical coupling
mechanism.16 The fact that two structurally distinctive iron
complexes (FeCl3 and Fe[TPP]Cl) mediate the same
reaction with different selectivities emphasizes the tight
relation between the catalysts’ structural properties and the
mechanism.
Cu(OH)Cl-TMEDA/air/CH2Cl2 catalytic system. The
aerobic oxidative coupling of phenol 2a and 2-naphthol 3b
using Nakajima and Koga’s Cu(OH)Cl-TMEDA (1c)
catalytic system49,
Roithová has shown – with the aid of infrared multiphoton
dissociation (IRMPD) spectroscopy and DFT calculations
– that the mechanism underlying this reaction involves the
coupling of 2-naphthoxyl radicals bound in a binuclear
copper cluster.51,
oxidative dimerization to afford BINOL 4, phenol 2a was
too reactive under the reaction conditions, affording a
mixture of dehydrogenation products. Interestingly, the
cross-coupling product 6 was almost not formed under
these conditions.
Scope and limitation. The scope of the newly
established catalytic system was examined. The general
conditions include mixing the phenol (1 equiv) and the 2-
naphthol (1 equiv) reactants with Co[salen] (1 mol %) in
HFIP at room temperature in an open flask. Under these
conditions, different unsymmetrical biphenols 6-25 were
isolated in moderate to high yields (Figure 1). In general,
readily oxidized phenols with either ortho- or para-methoxy
groups and 2-naphthols substituted with electron-donating
groups (such as alkyl, aryl, hydroxy, or methoxy) or weak
electron-withdrawing groups (e.g. Br) are suitable coupling
partners. In addition, oxidizable functional groups, such as
primary alcohol (see 15) and allyl (see 25) groups were
stable under the mild reaction conditions. 6-methoxy-2-
naphthol has oxidation potential comparable to its phenolic
partners, and as a result, only moderate selectivity was
observed under the general conditions. To improve the
yield of the cross-coupling products, 1.5 equiv of the
phenolic reactant was used and the reactions were
performed at 4 C (see 7, 17, 19, 23 and 24). The reaction
between phenol 2a and 3-(CO2Me)-2-naphthol (3a) or 6-
(CO2Me)-2-naphthol, which are the preferred coupling
partners in the FeCl3/t-BuOOt-Bu/HFIP catalytic system
(vide-supra),21 failed to afford the corresponding biaryl
coupling products 6a and 26.
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was not selective (Scheme 2C).
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Whereas 2-naphthol 3b underwent
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Figure 1. The reaction scope.
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Conditions: A solution of phenol (1 equiv), 2-naphthol (1 equiv) and Co[salen] 1d (1 mol %) was stirred at room temperature
up to 24 hours in HFIP (0.1 M). aIsolated yields of pure products; bCo[salen] 1e was used instead of 1d; cThe Reaction was
performed with 1.5 equiv of the phenol at 4 °C.
Several other Co[salen] complexes that differ in their
electronic properties were also tested. These readily
available complexes mediate the reaction with similar
catalytic activity, implying that in this reaction electronic
and steric changes have only minor influence over the
catalytic activity. For example, under similar conditions
cobalt salen 1e (Scheme 2, R = t-Bu), which differs from
complex 1d (R = Br) in its electronic nature, successfully
mediated the oxidative coupling of phenol 2a and 3b
affording biphenol 6 in an improved 92% yield.
Co[salen] 1e (0.4 mol %), HFIP, air, rt, 48 h]. This simple-
setting reaction afforded the desired coupling product 6 in
78% yield (2.43 g). Since H2O is the only side product
formed in this process, the expensive fluorinated alcohol
solvent was successfully recovered by simple distillation
(90% yield).56 This experiment demonstrates that this
technology is suitable for benign preparative applications.
The scalability of the process was illustrated by
performing the coupling of phenol 2a with 2-naphthol 3b
(1:1 ratio, 10 mmol) on a multi-gram scale [Scheme 3,
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naphthol 3b were revealed (Scheme 4C).73,
This
supports the premise that coordination of the 2-naphthol to
the metal occurs prior to the oxidation of the phenol, which
is probably the rate determining step.
The Co[salen] and the Fe[TPP]Cl catalytic systems
exhibited similar cross-coupling selectivity for the oxidative
coupling of phenol 2a and naphthol 3b (Scheme 2). Since
selectivity is closely related to the coupling mechanism, it
is reasonable to assume that the two catalytic systems
would mediate the reaction by closely related outer-sphere
radical-radical coupling mechanisms.16
Scheme 3. Large-scale aerobic oxidative coupling of
phenols 2a and 3b by Co[salen] catalyst.
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Scheme 4. Mechanistic studies
To clarify the observed selectivity and reactivity of the
reaction, we performed a mechanistic investigation. In
recent years, HFIP has become the solvent of choice in
oxidation processes57-64 as it stabilizes cationic radical
species.61, 65 In oxidative phenol coupling reactions, HFIP
forms strong hydrogen-bonds with the oxidant,64, 66, 67 the
phenoxyl radicals,16, 21 and the redox catalysts.16, 68 As a
result it significantly enhances the reaction rate and the
20
selectivity.4,
Cobalt(II) salen complexes reversibly
uptake dioxygen molecules in strong coordination
solvents, such as pyridine, DMSO, and DMF,69-71 forming
monomeric cobalt(III)-superoxide complexes that exist in
equilibrium with -peroxocobalt(III) dimer complexes
(Scheme 4A). 39, 42, 43, 45, 53, 72 A similar trend was observed
when complexes 1d or 1e dissolved in HFIP under air
atmosphere. The UV spectra of these complexes revealed
a rapid change in the oxidation state of complex 1e in HFIP
and the formation of cobalt(III) species (see Supporting
Information, Figure S5), whereas the absorbance change
for complex 1d took a longer time (several hours).
Furthermore, the initial red-orange color of the complexes
in HFIP turned black for complex 1e (R = t-Bu) and upon
solvent removal, a black solid69 with a molecular weight
compatible with a -peroxocobalt(III) dimer was detected
by mass-spectroscopy. The elemental analysis of this solid
afforded mass fractions of carbon, nitrogen, oxygen,
fluorine, and hydrogen, which support a molecular formula
of a -peroxocobalt(III) dimer bound to HFIP and H2O
molecules ([(HFIP)2(H2O)6(1e)O]2) (1f, eq. 3, see the
64
Supporting Information, Table S1).62,
This dimeric
complex disassembled to complex 1e when dissolved in
CDCl3 or methanol.
A series of control experiments and kinetic studies were
carried out to uncover the coupling mechanism. When
16
phenol 2a alone, which is a weak ligand in HFIP, was
mixed with the cobalt catalyst 1d in HFIP no oxidation
processes took place (Scheme 4B, eq.1). On the other
hand, under similar conditions, 2-naphthol 3b was not
stable affording a mixture of dehydrogenation products
(Scheme 4B, eq.2). However, a highly chemoselective
cross-coupling reaction occurred when phenol 2a and 2-
napthol 3b were mixed together with the catalyst, affording
unsymmetrical biphenol 6 in 86% isolated yield (eq.3
indicating that 2-naphthol 3b probably act as a fifth ligand
and activates the Co[salen] catalyst. This assumption was
confirmed by initial-rate kinetic studies. A first-order
behavior for phenol 2a and a zero-order behavior for 2-
A] Dimerization of cobalt(II) salen complexes in the
presence of O2. B] Control experiments for studying the
role of the fifth ligand of the Co[salen] 1d catalyst. C]
Dependence of the initial rate on 2-methoxy-4-
methylphenol (2a) and 3-methoxy-2-naphthol (3b)
concentrations.
Based on these findings, a mechanism for the oxidative
coupling of electron-rich phenols with 2-naphthol
derivatives is postulated (Scheme 5). The catalytic cycle
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amounts of hydrogen peroxide urea complex (UHP; 1, 2.5,
begins with the formation of -peroxocobalt(III) dimer
complex Ia, which is found in equilibrium with cobalt(III)-
superoxide complex Ib. Conversion of these complexes to
intermediate II takes place upon 2-naphthol 3b ligation.
The abstraction of a hydrogen atom from phenol 2a, by the
cobalt-superoxide complex II, generates complex III and a
liberated phenoxyl radical 2a with a relatively long lifetime
in HFIP. Although the subsequent steps in the catalytic
cycle are kinetically invisible, it is suggested, based on the
independent EPR studies of Bolzacchini et al.54 and
Tkáč,75 that complex III undergoes a rapid consecutive
proton-coupled-electron transfer (PCET) process to form a
cobalt-ligated naphthoxyl radical species (complex IV).54
The ligated naphthoxyl radical in IV and the liberated
phenoxyl radical [2a] can then couple, undergo coupling
to afford biphenol 6 and complex V. Thus, the observed
chemoselectivity can be explained in terms of the different
roles played by the two coupling partners during the
catalytic cycle.
and 5 equiv, green circles, blue triangles and red squares,
solid lines, respectively) under Ar atmosphere. This part of
the study revealed that in methanol the oxidative
dimerization of phenol 2a is H2O2 dependent (solid lines)
and that the reaction proceeds significantly faster with UHP
rather than under aerobic conditions (compare the red
squares with the gray diamonds). This suggests that in
methanol, hydrogen peroxide serves as a terminal oxidant
in the oxidative coupling reaction. These results are in
agreement with the findings of the Stahl group,77, 78 who
reported that in methanol the aerobic oxidation of
hydroquinone (HQ) to benzoquinone (BQ) by Co[salophen]
catalyst involves a slow HQ to BQ oxidation step (O2 
H2O2), followed by an extremely rapid second oxidation
step (HQ to BQ and H2O2  2H2O). In contrast, the
oxidative coupling of phenol 2a in HFIP under aerobic
conditions (dashed gray line, Figure 2B) exhibited
reactivity similar to that in the presence of UHP (solid lines,
Figure 2B), indicating that the oxidative coupling using
hydrogen peroxide as the terminal oxidant is a slow
process in HFIP and that H2O2 disproportionation is a
competitive process that terminates the catalytic cycle,
while regenerating complex Ib. The latter complex could
re-enter the aerobic catalytic cycle; hence, O2 alone serves
as the terminal oxidant in this oxidative coupling reaction.
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Figure 2. Comparison between terminal oxidants (O2 and
H2O2) in the Co[salen]-catalyzed oxidative coupling of 2a
in methanol or in HFIP.
Scheme 5. Postulated mechanism for the Co[salen]-
catalyzed aerobic oxidative cross-coupling of phenols in
HFIP.
Complex V (Scheme 5) can mediate either: 1) the
formation of a second biaryl bond, while utilizing hydrogen
peroxide as the oxidant,76, 77 and/or 2) the co-catalyzed
disproportionation of two molecules of H2O2 into two
molecules of H2O and a single O2 molecule, which in turn,
enters the aerobic catalytic cycle (Figure 2A). To
distinguish between the two possible routes, we studied
the oxidative homocoupling reactions of phenol 2a (1
equiv) by catalyst 1d (1 mol %) in the presence of
triethylamine (TEA, 0.5 equiv). As mentioned above,
phenol 2a is stable under our reaction conditions in the
absence of a fifth ligand (Scheme 4B, eq. 1), therefore,
TEA was needed to promote the homocoupling. The
dimerization of 2a was succesfully carried out in methanol
or in HFIP (Figure 2B) either under air (open flask, gray
diamonds, dashed line) or in the presence of different
Conditions: 'H2O2' conditions = phenol 2a (0.05 mmol), 1d
(1 mol %), Et3N (0.025 mmol), hydrogen peroxide urea
complex [1 equiv (green circles), 2.5 equiv (blue triangles)
and 5 equiv (red squares)] in MeOH or HFIP (1 mL), Ar
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atm, rt; 'aerobic' conditions = phenol 2a (0.05 mmol), 1d (1 according to the general method. The crude residue was
2
3
4
mol %), Et3N (0.025 mmol) in MeOH or HFIP (1 mL), under purified by column chromatography (ethyl acetate/hexane
air (open flask), rt.
20:80) to afford compound 6 (67 mg, 86% yield) as an
amorphous light pink solid. H NMR (400 MHz, CDCl3) δ 7.74
1
5
6
7
(d, J = 8.0 Hz, 1H), 7.43 (d, J = 8.2 Hz, 1H), 7.34 (t, J = 7.2 Hz,
1H), 7.27 (t, J = 7.3 Hz, 1H), 7.20 (s, 1H), 6.82 (s, 1H), 6.72 (s,
1H), 5.99 (s, 1H, OH), 5.49 (s, 1H, OH), 4.05 (s, 3H), 3.95 (s,
3H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 147.2, 146.9,
142.9, 141.5, 129.4, 129.0, 128.8, 126.8, 124.9, 124.3, 124.2,
124.0, 120.8, 117.4, 111.6, 105.9, 56.0 (2XC), 21.3.
8
9
Conclusions
In summary, a selectivity-driven catalyst design
approach was successfully applied to develop an efficient,
highly selective aerobic oxidative cross-coupling of
phenols. The catalytic reaction, which relies on the readily
available Co[salen] catalysts 1d and 1e, is both scalable
and sustainable. The latter advantage was conferred by
the recyclability of the HFIP solvent and the mild waste-
free conditions (an open flask at room temperature). The
postulated mechanism involves coupling between a
liberated phenoxyl radical and a ligated naphthoxyl radical,
whereas the selectivity is attributed to the difference in the
binding ability of the two phenols to the catalyst in HFIP.
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1-(2-hydroxy-3-methoxy-5-methylphenyl)-6-methoxynaphthal-
en-2-ol (7). 2-methoxy-4-methylphenol (47 µL, 0.375 mmol) and
6-methoxy-2-naphthol (44 mg, 0.25 mmol) were reacted
according to the general method at 4 °C. The crude residue was
purified by column chromatography (ethyl acetate/hexane
20:80) to afford compound 7 (47.4 mg, 61% yield) as an
amorphous light yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.71
(d, J = 8.8 Hz, 1H), 7.37 (d, J = 9.2 Hz, 1H), 7.25 (d, J = 8.8 Hz,
1H), 7.14 (d, J = 2.6 Hz, 1H), 7.04 (dd, J = 9.2, 2.6 Hz, 1H), 6.82
(d, J = 1.8 Hz, 1H), 6.70 (broad multiplet, J = 1.8, 0.9 Hz, 1H),
5.59 (s, 1H, OH), 5.26 (s, 1H, OH), 3.97 (s, 3H), 3.90 (s, 3H),
2.35 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 155.9, 149.3, 147.2,
141.6, 130.3, 130.1, 128.5, 126.4, 124.4, 119.8, 119.5, 118.9,
118.2, 116.9, 112.0, 106.5, 56.1, 55.4, 21.2. HRMS (ESI): m/z
[M+H]+ calcd for C19H19O4 311.1278, found 311.1278.
Experimental Section
General Methods. All reagents were of reagent grade quality,
purchased commercially from Sigma-Aldrich, Alfa-Aesar, or
Fluka, and used without further purification. Purification by
column chromatography was performed on Sigma-Aldrich
chromatographic silica gel (40-60 μm). TLC analyses were
performed using Merck silica gel glass plates 60 F254. NMR
spectra were recorded on Bruker DPX400 or DMX500
instruments; chemical shifts, given in ppm, are relative to Me4Si
as an internal standard or to the residual solvent peak. HR-MS
data were obtained using a LTQ Orbitrap XL ETD (Thermo
Fisher Scientific, Germany & USA) high resolution mass
spectrometer. HPLC analysis was carried out on Agilent 1260
instrument equipped with a G4212-60008 photodiode array
detector. Gas chromatography measurements were carried out
in an Agilent 7820A GC equipped with a FID detector working
under standard conditions and an Agilent HP-5 column.
Spectrophotometer measurements were carried out in Thermo
Scientific UV-vis Helios Omega.
General procedure for aerobic oxidative coupling of
phenols by Co[salen] 1d catalyst. A solution of phenol (0.25
mmol), 2-naphthol (0.25 mmol) and Co[salen] 1d (1.8 mg, 1 mol
%) in HFIP (0.1 M, 2.5 mL) was stirred at room temperaturea.
After complete consumption of the starting materials (indicated
by TLC or HPLC within 24 h) the reaction was quenched by
addition of CH2Cl2 and HCl 1 M. The organic phase was
separated and dried over MgSO4. The volatiles were removed
under reduced pressure and the crude residue was purified by
column chromatography (silica gel 40-60 m), affording the
biphenol cross-coupling product.
1-(2-hydroxy-3-methoxy-5-methylphenyl)naphthalen-2-ol (8).20
2-methoxy-4-methylphenol (32 µL, 0.25 mmol) and 2-naphthol
(36 mg, 0.25 mmol) were reacted according to the general
method. The crude residue was purified by column
chromatography (ethyl acetate/hexane 20:80) to afford
compound 8 (54.8 mg, 78% yield) as an amorphous a light
brown solid. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.9 Hz,
2H), 7.42 (dd, J = 8.0, 1.1 Hz, 1H), 7.35 – 7.26 (m, 2H), 7.26 –
7.19 (m, 1H), 6.79 (d, J = 1.4 Hz, 1H), 6.67 (d, J = 0.9 Hz, 1H),
5.56 (s, 1H, OH), 5.37 (s, 1H, OH), 3.92 (s, 3H), 2.32 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 150.8, 147.2, 141.7, 133.1, 130.4,
129.8, 129.2, 128.1, 126.5, 124.8, 124.4, 123.3, 119.3, 117.8,
116.6, 112.1, 56.1, 21.2.
1-(2-hydroxy-3-methoxy-5-methylphenyl)-6-(2,4,6-triisopropyl-
phenyl)naphthalen-2-ol (9). 2-methoxy-4-methylphenol (41 µL,
0.325 mmol due to low solubility of the naphthol) and 6-(1,3,5-
tri-i-propyl-phenyl)-2-naphthol (87 mg, 0.25 mmol) were reacted
according to the general method. The crude residue was
purified by column chromatography (ethyl acetate/hexane
25:75) to afford compound 9 (64.4 mg, 53% yield) as an
amorphous yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.81 (d,
J = 8.8 Hz, 1H), 7.63 (d, J = 1.6 Hz, 1H), 7.50 (d, J = 8.6 Hz,
1H), 7.33 (d, J = 8.9 Hz, 1H), 7.23 (dd, J = 8.6, 1.7 Hz, 1H), 7.10
(s, 2H), 6.87 (d, J = 1.8 Hz, 1H), 6.82 (d, J = 1.6 Hz, 1H), 5.68
(s, 1H, OH), 5.44 (s, 1H, OH), 3.99 (s, 3H), 2.98 (hept, J = 6.9
Hz, 1H), 2.68 (m, 2H), 2.41 (s, 3H), 1.34 (d, J = 6.9 Hz, 6H),
1.17 – 0.99 (m, 12H). 13C NMR (100 MHz, CDCl3) δ 150.8,
147.9, 147.3, 147.0, 146.9, 141.7, 137.0, 135.8, 131.8, 130.5,
129.9, 129.2, 128.9, 128.4, 124.5, 124.4, 120.6, 120.5, 119.3,
117.9, 116.4, 112.1, 56.1, 34.3, 30.3 (2XC), 24.4, 24.2 (2XC),
aExcept for reactions with 6-methoxy-2-naphthol that were
performed at 4 °C with 1.5 equiv of the phenol.
1-(2-hydroxy-3-methoxy-5-methylphenyl)-3-methoxynaphthal-
en-2-ol (6).79 2-methoxy-4-methylphenol (32 µL, 0.25 mmol)
and 3-methoxy-2-naphthol (44 mg, 0.25 mmol) were reacted
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24.1, 21.3. HRMS (ESI): m/z [M+H]+ calcd for C33H39O3 5.67 (s, 1H, OH), 5.46 (s, 1H, OH), 3.97 (s, 3H), 2.37 (s, 3H).
483.2894, found 483.2892.
13C NMR (100 MHz, CDCl3) δ 151.6, 147.2, 141.7, 134.5, 130.6,
129.8, 129.7, 127.5, 127.0, 126.7, 124.2, 121.0, 118.4, 118.2,
116.2, 112.3, 56.1, 21.2. HRMS (ESI): m/z [M+Na]+ calcd for
6-(4-(tert-butyl)phenyl)-1-(2-hydroxy-3-methoxy-5-ethylphen-
yl)naphthalen-2-ol (10). 2-methoxy-4-methylphenol (32 µL, C18H15BrO3Na 381.0097, 383.0076 found 381.0092, 383.0070.
0.25 mmol) and 6-t-butyl-phenyl-2-naphthol (69 mg, 0.25 mmol) 3-bromo-1-(2-hydroxy-3-methoxy-5-methylphenyl)naphthalen-
were reacted according to the general method. The crude 2-ol (14).20 2-methoxy-4-methylphenol (32 µL, 0.25 mmol) and
residue was purified by column chromatography (ethyl 3-bromo-2-naphthol (55.8 mg, 0.25 mmol) were reacted
acetate/hexane 20:80) to afford compound 10 (92 mg, 89% according to the general method. The crude residue was
yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J purified by column chromatography (ethyl acetate/hexane
= 1.9 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.70 – 7.67 (m, 3H), 20:80) to afford compound 14 (65 mg, 72% yield) as a yellow
7.59 (d, J = 8.8 Hz, 1H), 7.56 – 7.52 (m, 2H), 7.35 (d, J = 8.9 liquid. 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.73 (d, J =
Hz, 1H), 6.88 (d, J = 1.8 Hz, 1H), 6.79 (dd, J = 1.9 Hz, 0.8 Hz, 7.4 Hz, 1H), 7.44 (d, J = 7.7 Hz, 1H), 7.43 – 7.28 (m, 2H), 6.85
1H), 5.73 (s, 1H, OH), 5.56 (s, 1H, OH), 3.98 (s, 3H), 2.41 (s, (s, 1H), 6.70 (s, 1H), 5.77 (s, 1H, OH), 5.62 (s, 1H, OH), 3.96
3H), 1.43 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 150.9, 150.1, (s, 3H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 147.1 (2XC),
147.3, 141.8, 138.3, 136.0, 132.3, 130.4, 130.1, 129.5, 126.9, 141.6, 132.6, 131.8, 130.2, 129.6, 127.2, 126.7, 125.2, 124.3,
126.2, 125.9, 125.8, 125.4, 124.5, 119.4, 118.3, 116.7, 112.1, 124.1, 119.6, 118.6, 112.2, 112.1, 56.1, 21.2.
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56.1, 34.6, 31.5, 21.3. HRMS (ESI): m/z [M+H]+ calcd for
C28H29O3 413.2111, found 413.2104.
1-(2-hydroxy-3-methoxy-5-methylphenyl)-6-(3-hydroxypropyl)-
naphthalen-2-ol (15). 2-methoxy-4-methylphenol (32 µL, 0.25
mmol) and 6-(3-hydroxypropyl)-2-naphthol (50.5 mg, 0.25
1-(2-hydroxy-3-methoxy-5-methylphenyl)naphthalene-2,3-diol
(11). 2-methoxy-4-methylphenol (32 µL, 0.25 mmol) and 2,3 mmol) were reacted according to the general method. The
dihydroxynaphthalene (40 mg, 0.25 mmol) were reacted crude residue was purified by column chromatography (ethyl
according to the general method. The crude residue was acetate/hexane 20:80) to afford compound 15 (64 mg, 76%
purified by column chromatography (ethyl acetate/hexane yield) as an amorphous yellow solid. 1H NMR (400 MHz, CDCl3)
30:70) to afford compound 11 (43 mg, 58% yield) as a white δ 7.76 (d, J = 8.8 Hz, 1H), 7.62 (d, J = 1.4 Hz, 1H), 7.42 (d, J =
1
solid. H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 7.6 Hz, 1H), 8.6 Hz, 1H), 7.27 (d, J = 8.8 Hz, 1H), 7.22 (dd, J = 8.7, 1.8 Hz,
7.50 (d, J = 8.3 Hz, 1H), 7.37 – 7.28 (m, 2H), 7.24 (ddd, J = 8.2, 1H), 6.84 (d, J = 1.7 Hz, 1H), 6.72 (dd, J = 1.9, 0.8 Hz, 1H), 5.61
6.8, 1.4 Hz, 1H), 6.83 (d, J = 1.7 Hz, 1H), 6.76 (d, J = 1.0 Hz, (s, 1H, OH), 5.38 (s, 1H, OH), 3.97 (s, 3H), 3.42 (t, J = 6.6 Hz,
1H), 5.95 (s, 3H, OH), 3.97 (s, 3H), 2.36 (s, 3H). 13C NMR (100 2H), 2.90 (t, J = 7.3 Hz, 2H), 2.37 (s, 3H), 2.23 (quin., J = 6.7
MHz, CDCl3) δ 147.0, 145.1, 141.0, 140.9, 130.3 (2XC), 127.9, Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 150.6, 147.3, 141.8,
126.8, 125.0, 124.6, 124.2, 123.9, 119.6, 118.2, 111.8, 109.9, 135.4, 131.8, 130.5, 129.4 (2XC), 127.9, 127.2, 125.2, 124.5,
56.1, 21.2. HRMS (ESI): m/z [M+H]+ calcd for C18H17O4 119.4, 118.1, 116.6, 112.1, 56.2, 34.2, 33.9, 33.3, 21.3. HRMS
297.1121, found 297.1119.
(ESI): m/z [M+H]+ calcd for C21H23O4 339.1591, found
339.1589.
6-bromo-1-(2-hydroxy-3-methoxy-5-methylphenyl)naphthalen-
2-ol (12).20 2-methoxy-4-methylphenol (32 µL, 0.25 mmol) and 1-(2-hydroxy-3-methoxy-5-methylphenyl)-6-isopropylnaphthal-
6-bromo-2-naphthol (55.8 mg, 0.25 mmol) were reacted en-2-ol (16). 2-methoxy-4-methylphenol (32 µL, 0.25 mmol) and
according to the general method. The crude residue was 6-i-propyl-2-naphthol (47 mg, 0.25 mmol) were reacted
purified by column chromatography (ethyl acetate/hexane according to the general method. The crude residue was
20:80) to afford compound 12 (72 mg, 80% yield) as an purified by column chromatography (ethyl acetate/hexane
amorphous yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.95 (d, 20:80) to afford compound 16 (54 mg, 67% yield) as a yellow
J = 2.0 Hz, 1H), 7.71 (d, J = 8.9 Hz, 1H), 7.40 (dd, J = 9.0, 2.0 oil. 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.8 Hz, 1H), 7.63
Hz, 1H), 7.33 (d, J = 9.0 Hz, 1H), 7.29 (d, J = 8.9 Hz, 1H), 6.84 (d, J = 1.6 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 7.29 (dd, J = 8.7
(d, J = 1.7 Hz, 1H), 6.68 (d, J = 1.8 Hz, J = 0.8 Hz, 1H), 5.64 (s, Hz, J = 1.9 Hz, 1H), 7.27 (d, J = 8.7 Hz, 1H), 6.84 (d, J = 1.8
1H, OH), 5.43 (s, 1H, OH), 3.97 (s, 3H), 2.36 (s, 3H). 13C NMR Hz, 1H), 6.73 (d, J = 1.8 Hz, 1H), 5.63 (s, 1H, OH), 5.41 (s, 1H,
(100 MHz, CDCl3) δ 151.1, 147.2, 141.7, 131.7, 130.5, 130.3, OH), 3.96 (s, 3H), 3.04 (hept, J = 6.9 Hz, 1H), 2.37 (s, 3H), 1.33
130.0, 129.6, 128.8, 126.8, 124.2, 118.9, 118.7, 117.1, 117.0, (d, J = 6.9 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 150.3, 147.2,
112.2, 56.1, 21.2.
143.7, 141.7, 131.6, 130.3, 129.5, 129.3, 126.4, 124.8, 124.5,
124.4, 119.6, 117.7, 116.4, 112.0, 56.1, 33.9, 24.0, 24.0 (2XC),
21.2. HRMS (ESI): m/z [M+H]+ calcd for C21H23O3 323.1642,
found 323.1637.
7-bromo-1-(2-hydroxy-3-methoxy-5-methylphenyl)naphthalen-
2-ol (13). 2-methoxy-4-methylphenol (32 µL, 0.25 mmol) and 7-
bromo-2-naphthol (55.8 mg, 0.25 mmol) were reacted
according to the general method. The crude residue was
purified by column chromatography (ethyl acetate/hexane
20:80) to afford compound 13 (38 mg, 42% yield) as a yellow
oil. 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 9.0 Hz, 1H), 7.66
(d, J = 8.7 Hz, 1H), 7.59 (d, J = 1.8 Hz, 1H), 7.39 (dd, J = 8.7,
1.8 Hz, 1H), 7.28 (d, J = 9.0 Hz, 1H), 6.85 (s, 1H), 6.67 (s, 1H),
1-(2-hydroxy-5-methoxy-3-methylphenyl)-6-methoxynaphthal-
en-2-ol (17). 2-methyl-4-methoxy phenol (51.8 mg, 0.375 mmol)
and 6-methoxy-2-naphthol (44 mg, 0.25 mmol) were reacted
according to the general method at 4 °C. The crude residue was
purified by column chromatography (ethyl acetate/hexane
20:80) to afford compound 17 (50.5 mg, 65% yield) an
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amorphous pale brown solid. 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.9 Hz, 1H), 6.97 (dd, J = 8.9, 3.1 Hz, 1H), 6.79 (d, J =
(d, J = 8.9 Hz, 1H), 7.31 (d, J = 9.1 Hz, 1H), 7.26 (d, J = 8.9 Hz, 3.0 Hz, 1H), 5.41 (s, 1H, OH), 4.62 (s, 1H, OH), 3.76 (s, 3H).
1H), 7.16 (d, J = 2.4 Hz, 1H), 7.08 (dd, J = 9.1, 2.4 Hz, 1H), 6.87 13C NMR (100 MHz, CDCl3) δ 154.2, 151.8, 148.3, 133.0, 131.0,
(d, J = 2.8 Hz, 1H), 6.61 (d, J = 2.8 Hz, 1H), 3.90 (s, 3H), 3.76 129.3, 128.4, 127.5, 124.3, 124.0, 119.7, 117.9, 117.6, 116.9,
(s, 3H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 156.3, 116.2, 114.3, 55.9.
153.5, 150.0, 146.5, 130.1, 129.4, 128.1, 127.0, 125.8, 119.7,
118.8, 118.3, 118.1, 114.6, 112.9, 106.7, 55.7, 55.4, 16.6. 1-(4-hydroxy-3,5-dimethoxyphenyl)naphthalen-2-ol (22).80 2,6-
HRMS (ESI): m/z [M+H]+ calcd for C19H19O4 310.1278, found dimethoxyphenol (38.5 mg, 0.25 mmol) and 2-naphthol (36 mg,
9
310.1273.
0.25 mmol) were reacted according to the general method. The
crude residue was purified by column chromatography (ethyl
acetate/hexane 25:75) to afford compound 22 (66.3 mg, 89%
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1-(2-hydroxy-5-methoxy-3-methylphenyl)naphthalen-2-ol
(18).79 2-methyl-4-methoxyphenol (34.5 mg, 0.25 mmol) and 2- yield) as an amorphous brown solid. 1H NMR (400 MHz, CDCl3)
naphthol (36 mg, 0.25 mmol) were reacted according to the δ 7.84 – 7.78 (m, 2H), 7.51 – 7.46 (m, 1H), 7.41 – 7.32 (m, 3H),
general method. The crude residue was purified by column 7.28 (d, J = 8.9 Hz, 1H), 6.65 (s, 2H), 5.78 (s, 1H, OH), 5.43 (s,
chromatography (ethyl acetate/hexane 20:80) to afford 1H, OH), 3.89 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 150.4,
compound 18 (32 mg, 46% yield) as an amorphous yellow solid. 148.0, 134.8, 133.6, 129.5, 128.9, 128.1, 126.6, 124.7 (2XC),
1H NMR (400 MHz, CDCl3) δ 7.85 (t, J = 8.9 Hz, 2H), 7.39 (m, 123.4, 121.1, 117.3, 107.5, 56.5.
Hz, 3H), 7.29 (d, J = 8.9 Hz, 1H), 6.89 (s, 1H), 6.63 (s, 1H), 5.38
(s, 1H, OH), 4.57 (s, 1H, OH), 3.76 (s, 3H), 2.35 (s, 3H). 13C 1-(4-hydroxy-3,5-dimethoxyphenyl)-6-methoxynaphthalen-2-ol
NMR (100 MHz, CDCl3) δ 153.6, 151.7, 146.6, 133.0, 130.8, (23). 2,6-dimethoxyphenol (58 mg, 0.375 mmol) and 6-
129.2, 128.3, 127.3, 127.1, 124.3, 123.9, 118.7, 118.4, 117.7, methoxy-2-naphthol (44 mg, 0.25 mmol) were reacted
114.4, 113.0, 55.7, 16.6.
according to the general method at 4 °C. The crude residue was
purified by column chromatography (ethyl acetate/hexane
25:75) to afford compound 23 (38.6 mg, 47% yield) as a brown
1-(2-hydroxy-3,5-dimethoxyphenyl)-6-methoxynaphthalen-2-ol
(19). 2,4-dimethoxyphenol (58 mg, 0.375 mmol) and 6- liquid. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.9 Hz, 1H),
methoxy-2-naphthol (44 mg, 0.25 mmol) were reacted 7.39 (d, J = 9.2 Hz, 1H), 7.24 (d, J = 8.9 Hz, 1H), 7.14 (d, J =
according to the general method at 4 °C. The crude residue was 2.6 Hz, 1H), 7.05 (dd, J = 9.2, 2.6 Hz, 1H), 6.62 (s, 2H), 5.73 (s,
purified by column chromatography (ethyl acetate/hexane 1H, OH), 5.21 (s, 1H, OH), 3.91 (s, 3H), 3.88 (s, 6H). 13C NMR
10:90) to afford compound 19 (46.7 mg, 57% yield) as a pale (100 MHz, CDCl3) δ 155.9, 148.8, 148.0, 134.8, 129.8, 128.8,
brown solid. 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.8 Hz, 128.2, 126.3, 124.9, 121.4, 119.1, 117.7, 107.4, 106.4, 56.5,
1H), 7.41 (d, J = 9.2 Hz, 1H), 7.26 (d, J = 8.8 Hz, 1H), 7.15 (d, 55.5. HRMS (ESI): m/z [M+H]+ calcd for C19H19O5 327.1227,
J = 2.6 Hz, 1H), 7.05 (dd, J = 9.2, 2.6 Hz, 1H), 6.63 (d, J = 2.8 found 327.1221.
Hz, 1H), 6.40 (d, J = 2.8 Hz, 1H), 5.41 (s, 1H, OH), 5.36 (s, 1H,
OH), 3.95 (s, 3H), 3.90 (s, 3H), 3.76 (s, 3H). 13C NMR (100 1-(4-hydroxy-5-methoxy-2-methylphenyl)-6-methoxynaphthal-
MHz, CDCl3) δ 156.0, 153.7, 149.3, 148.1, 138.0, 130.1, 128.6, en-2-ol (24). 2-methoxy-5-methylphenol (52 mg, 0.375 mmol)
128.2, 126.4, 119.5, 119.0, 118.3, 116.9, 106.5 (2XC), 100.1, and 6-methoxy-2-naphthol (44 mg, 0.25 mmol) were reacted
56.1, 55.8, 55.4. HRMS (ESI): m/z [M+H]+ calcd for C19H19O5 according to the general method at 4 °C. The crude residue was
327.1227, found 327.1234.
purified by column chromatography (ethyl acetate/hexane
25:75) to afford compound 24 (30.8 mg, 40% yield) as a white
1-(2-hydroxy-3,5-dimethoxyphenyl)naphthalen-2-ol (20).21 2,4- solid. 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.9 Hz, 1H), 7.25
dimethoxyphenol (38.6 mg, 0.25 mmol) and 2-naphthol (36 mg, (d, J = 8.9 Hz, 1H), 7.17 (dd, J = 6.8, 6.1 Hz, 2H), 7.04 (dd, J =
0.25 mmol) were reacted according to the general method. The 9.1, 2.7 Hz, 1H), 6.99 (s, 1H), 6.74 (s, 1H), 5.75 (s, 1H, OH),
crude residue was purified by column chromatography (ethyl 4.95 (s, 1H, OH), 3.91 (s, 3H), 3.83 (s, 3H), 1.93 (s, 3H). 13C
acetate/hexane 15:85) to afford compound 20 (56.4 mg, 76% NMR (100 MHz, CDCl3) δ 156.0, 149.0, 146.0, 145.5, 132.0,
yield) as a yellow-orange liquid. 1H NMR (400 MHz, CDCl3) δ 129.9, 128.8, 128.1, 126.2, 124.0, 120.6, 119.1, 117.7, 117.0,
7.85 – 7.81 (m, 2H), 7.52 – 7.50 (m, 1H), 7.40 – 7.31 (m, 2H), 113.6, 106.6, 56.2, 55.5, 18.9. HRMS (ESI): m/z [M+H]+ calcd
7.30 (d, J = 8.9 Hz, 1H), 6.65 (d, J = 2.8 Hz, 1H), 6.42 (d, J = for C19H19O4 311.1278, found 311.1276.
2.8 Hz, 1H), 5.49 (s, 1H, OH), 5.42 (s, 1H, OH), 3.95 (s, 3H),
3.76 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 153.8, 150.9, 148.3, 1-(5-allyl-2-hydroxy-3-methoxyphenyl)naphthalen-2-ol
(25).
138.2, 133.1, 130.1, 129.3, 128.3, 126.7, 124.9, 123.5, 119.4, Eugenol (38.5 µL, 0.25 mmol) and 2-naphthol (36 mg, 0.25
118.0, 116.6, 106.6, 100.3, 56.2, 55.9.
mmol) were reacted according to the general method. The
crude residue was purified by column chromatography (ethyl
acetate/hexane 10:90) to afford compound 25 (54 mg, 70%
yield) as an amorphous brown solid. 1H NMR (400 MHz, CDCl3)
δ 7.83 (d, J = 8.7 Hz, 2H), 7.47 (d, J = 8.1 Hz, 1H), 7.40 – 7.31
(m, 2H), 7.30 (d, J = 8.7 Hz, 1H), 6.86 (s, 1H), 6.76 (s, 1H), 6.00
(m, 1H), 5.67 (s, 1H, OH), 5.41 (s, 1H, OH), 5.12 (m, 2H), 3.98
(s, 3H), 3.40 (d, J = 6.6 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ
150.9, 147.4, 142.3, 137.4, 133.1, 132.7, 129.9, 129.2, 128.2,
1-(2-hydroxy-5-methoxyphenyl)naphthalen-2-ol
(21).16
4-
metho-xyphenol (31.1 mg, 0.25 mmol) and 2-naphthol (36 mg,
0.25 mmol) were reacted according to the general method. The
crude residue was purified by column chromatography (ethyl
acetate/hexane 10:90) to afford compound 21 (48.4 mg, 73%
yield) as a yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.86 –
7.82 (m, 2H), 7.41 – 7.35 (m, 3H), 7.28 (d, J = 8.9 Hz, 1H), 7.06
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126.5, 124.8, 124.1, 123.4, 119.5, 117.8, 116.5, 116.1, 111.4, highly enantioselective oxidative coupling of 2-naphthols. Angew.
56.1, 39.9. HRMS (ESI): m/z [M+H]+ calcd for C20H19O3
307.1334, found 307.1324.
Chem. Int. Ed. 2002, 41 (23), 4532-4535.
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ASSOCIATED CONTENT
Supporting Information
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The Supporting Information is available free of charge on the
ACS Publications website at DOI:
13. Somei, H.; Asano, Y.; Yoshida, T.; Takizawa, S.; Yamataka, H.;
Sasai, H., Dual activation in a homolytic coupling reaction promoted
by an enantioselective dinuclear vanadium(IV) catalyst. Tetrahedron
Lett. 2004, 45 (9), 1841-1844.
Kinetic data and mechanistic studies as well as full
spectroscopic data for all compounds,
14. Lee, Y. E.; Cao, T.; Torruellas, C.; Kozlowski, M. C., Selective
Oxidative Homo- and Cross-Coupling of Phenols with Aerobic
Catalysts. J. Am. Chem. Soc. 2014, 136 (19), 6782-6785.
15. Vershinin, V.; Dyadyuk, A.; Pappo, D., Iron-catalyzed selective
oxidative arylation of phenols and biphenols. Tetrahedron 2017, 73
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Conflicts of interest
There are no conflicts to declare.
Acknowledgments
16. Shalit, H.; Libman, A.; Pappo, D., meso-Tetraphenylporphyrin
Iron Chloride Catalyzed Selective Oxidative Cross-Coupling of
Phenols. J. Am. Chem. Soc. 2017, 139 (38), 13404-13413.
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This work was supported by the Israel Science Foundation
(grant number 164/16). The authors would like to thank the
COST-CHAOS organization for funding the participation in
the conference.
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946-953.
Mechanistic Characterization of Low-Overpotential, H2O2-Selective
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Page 13 of 13
The Journal of Organic Chemistry
1
TOC:
2
3
4
5
6
7
Ph
N
Ph
N
Co II
R
O
O
R
EDG
t-Bu
t-Bu
8
9
Co[salen]
[1 mol %]
OH
OH
EDG
1 equiv
+
air
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[open flask]
OH
OH
+ H2O
HFIP [recyclable]
room temperature
MeO
MeO
1 equiv
 High selectivity  Scalable  No waste
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