Meso-Tetraphenylporphyrin Iron Chloride Catalyzed Selective Oxidative Cross-Coupling of Phenols

Article abstract of DOI:10.1021/jacs.7b05898

A novel catalytic system for oxidative cross-coupling of readily oxidized phenols with poor nucleophilic phenolic partners based on an iron meso-tetraphenylporphyrin chloride (Fe[TPP]Cl) complex in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) was developed. The unique chemoselectivity of this reaction is attributed to the coupling between a liberated phenoxyl radical with an iron-ligated phenolic coupling partner. The conditions are scalable for preparing a long list of unsymmetrical biphenols assembled from a less reactive phenolic unit substituted with alkyl or halide groups.

Full text of DOI:10.1021/jacs.7b05898

Subscriber access provided by Grand Valley State | University
Article
meso-Tetraphenylporphyrin Iron Chloride Catalyzed
Selective Oxidative Cross-Coupling of Phenols
Hadas Shalit, Anna Libman, and Doron Pappo
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 01 Sep 2017
Downloaded from http://pubs.acs.org on September 1, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 12
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
meso-Tetraphenylporphyrin Iron Chloride Catalyzed Selective
Oxidative Cross-Coupling of Phenols
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Hadas Shalit,‡ Anna Libman‡ and Doron Pappo*
Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
Supporting Information Placeholder
symmetrical biphenols that are not accessible in an efficient
manner by any other direct methods.
ABSTRACT: A novel catalytic system for oxidative cross-
coupling of readily oxidized phenols with poor nucleophilic
phenolic partners based on an iron meso-
Oxidative homocoupling of phenols is an important reaction
that produces symmetrical dimeric,1b,6 oligomeric and poly-
meric phenolic materials7 that are essential for a wide range
of advanced applications.8 The selectivity and efficiency
problems inherent in these transformations have already
been successfully addressed.9 In contrast, suitable conditions
for the cross-coupling of two phenols, which are much more
challenging transformations that demand a high degree of
chemoselectivity (cross-coupling vs. homocoupling), are
limited in number.4a-c,9c,10 Early work on these transfor-
mations focused on the stoichiometric Cu(II)/amine-
mediated system for the cross-coupling of substituted 2-
naphthols, first studied by Hovorka and Zavada10i-k and later
by Kočovský.10h Other studies included the aerobic oxidative
cross-coupling of dialkylphenols by a Cr[salen] complex,
investigated by the Kozlowski group10f, and our group's4b
efficient synthesis of unsymmetrical biphenols with an FeCl3
catalyst in HFIP. In addition, enantio-enriched C1- and C2-
symmetric BINOLs have been synthesized with chiral
iron[salan] (the Katsuki group4c,9c) and iron[phosphate]3
complexes (the Pappo group4a). Finally, other methods for
coupling phenols with nucleophilic arenes have also been
developed for preparing biaryls10c,11 and polyarenes.12
Recently,4b we postulated that the above oxidative cross-
coupling reactions between two phenols (A and B) follow a
radical-anion coupling mechanism. Such mechanism pro-
ceeds with the selective oxidation of phenol A (EoxA < EoxB,
where Eox is the oxidation potential) by a redox catalyst,
which generates an electrophilic phenoxyl A• radical that
reacts with a nucleophilic phenol(ate) B. The degree of
chemoselectivity relies on the difference in nucleophilicity
between the two phenols (ꢀN = NB – NA, N is the theoretical
global nucleophilicity13). Pairs of phenols with a complemen-
tary relationship (positive ꢀN values) will favor the formation
of an unsymmetrical biphenol A−B, while negative ꢀN values
will be indicative of the low chemoselectivity that favors the
homocoupling biphenol A−A product.4b Thus, when we initi-
ated the current study, only powerful phenolic nucleophiles,
such as 2-naphthol derivatives or phenols with at least a sin-
gle methoxy group, could serve as efficient type B phenols in
oxidative cross-coupling reactions.4b For example, the FeCl3-
catalyzed reaction of 2,6-dimethoxyphenol (2a, Eox2a = 0.40
V, in HFIP vs. Ag/AgNO34b,11a) with 3,4,5-trimethoxyphenol
tetraphenylporphyrin chloride (Fe[TPP]Cl) complex in
1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) was developed. The
unique chemoselectivity of this reaction is attributed to the
coupling between a liberated phenoxyl radical with an iron-
ligated phenolic coupling partner. The conditions are scala-
ble for preparing a long list of unsymmetrical biphenols as-
sembled from a less reactive phenolic unit substituted with
alkyl or halide groups.
INTRODUCTION
Unsymmetrical biaryls, an important class of structural mo-
tifs found in natural products and bioactive compounds, also
serve as ligands in asymmetric catalysis and in various syn-
thetic applications.1 Current protocols for syntheses of biaryl
compounds rely on transition-metal-catalyzed cross-
coupling between two activated arenes (Ar−X and Ar−M).2 In
general, each coupling step is accompanied by number of
selectivity-determining steps, which are essential to set the
regioselectivity (site selection) and the chemoselectivity
(cross-coupling vs. homocoupling) of the coupling reaction.
These burdensome steps impinge on both the atom economy
and step economy of the entire process.3 In contrast, the
biomimetic metal-catalyzed oxidative phenol coupling reac-
tion offers a superior alternative for synthesizing biaryl
bonds directly from two un-functionalized phenolic compo-
nents. In such a reaction, the absence of activated centers
enforces induction of the regio-, chemo- and stereoselectivity
(axial chirality) during the C−C bond forming step.4 There-
fore, to enable precise control of the selectivity, it is neces-
sary to develop variety of metal complexes that mediate oxi-
dative coupling through different mechanisms.5 To achieve
this challenging goal, our group has initiated a project that
aims to address the selectivity problems inherent in the met-
al-catalyzed oxidative coupling of phenols through mecha-
nistically driven catalyst design. Here, we report a novel cata-
lytic system based on a meso-tetraphenylporphyrin iron
chloride (Fe[TPP]Cl) complex and t-BuOOH in 1,1,1,3,3,3-
hexafluoropropano-2-ol (HFIP). The particular mechanism
involved in this reaction makes it suitable for preparing un-
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 12
(2b, Eox2b = 0.46 V), which is relatively a better nucleophile
than its coupling partner 2a (ꢀN = +0.49 eV), favored oxida-
tive cross-coupling (product 3, Scheme 1).4b In contrast, un-
der similar conditions, the coupling between 2,6-
dimethoxyphenol 2a and phenol [2c (3 equiv), Eox2c = 0.63
V], which have a non-complementary relationship (ꢀN = -
0.70 eV), afforded the homocoupling product 4 in 40% yield,
while the desired cross-coupling product 5 was obtained only
in 23% yield (Scheme 1). The development of methods for
1
2
3
4
5
6
7
coupling pairs of phenols with a non-complementary rela-
tionship thus became an urgent scientific goal that we
sought to address. We envisioned that the solution to this
selectivity problem would involve a redox catalyst that would
mediate oxidative cross-coupling via a mechanism that does
not depend on the relative nucleophilicities of the two cou-
pling partners.
8
9
Scheme 1. Chemoselectivity in oxidative coupling of phenols with complementary and non-complementary relationships by a
radical-anion coupling mechanism.4b
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Mechanistic studies that involve kinetic investigations and
electrochemical methods for the oxidative coupling of phe-
nols have been carried out by both the Katsuki group4c,9c and
our group.4a,4b Based on these experiments, a correlation
between the number of coordination sites available for bind-
ing phenolic ligands and the coupling modes has been estab-
lished. The oxidative coupling of phenols by the multi-
coordinated FeCl3 catalyst showed zero-order kinetics for the
phenols, suggesting that the coupling takes place between an
associated phenoxyl radical and a phenol(ate) ligand (intra-
molecular radical-anion/nucleophile coupling, Figure 1A). In
contrast, first-order kinetics was found for 2-naphthols when
the oxidative homocoupling was catalyzed by Fe[salan]4c or
Fe[phosphate]3 complexes.4a These catalysts have one or two
coordination sites available in cis-orientation,14 and therefore
an intermolecular coupling between an associated naphthox-
yl radical and a second liberated naphthol(ate) was proposed
(intermolecular radical-anion coupling, Figure 1B).4c To fur-
ther investigate the relationship between the catalyst struc-
ture and the mode of coupling, the commercially available
Fe[TPP]Cl complex (1a), which has only a single axial posi-
tion available for binding, was examined as a catalyst in oxi-
dative cross-coupling reactions of phenols.
ases), histidine (for peroxidases) or tyrosine (for catalases),18
leaving the other axial position available for binding and
activation of dioxygen or peroxides.19 Iron(IV) oxide bound
to the porphyryl radical20 is responsible for the homolytic
cleavage of an R−H bond in the relevant substrate.21 The oxi-
dized short-lived R• species is not in direct contact with the
metal center and can either recombine with the iron-bound
hydroxyl radical to form an alcohol R−OH (oxygen rebound
mechanism)22 or react with a second radical species to afford
the coupling product R−R through a free radical-radical cou-
pling mechanism.20b It has been shown that by donating spin
density to the redox iron center the axial ligand plays an es-
sential role in controlling the function and reactivity of the
catalyst (‘push effect’).16f,23 Despite the promise of this cata-
lytic pathway, attempts to develop biomimetic oxidative
coupling reactions of phenols that involve iron porphyrin
catalysts has met with only limited success,24 probably as a
result of the formation of the catalytically inactive
bis[(5,10,15,20-tetraphenylporphyrinato)iron(III)]
ꢁ-oxo-
[(Fe[TPP])2O (1d)] and the destruction of the porphyrin lig-
and by highly reactive radical species.25
Here, we report a novel Fe[TPP]Cl/t-BuOOH/HFIP system
for preparing unsymmetrical biphenols from two non-
complementary phenolic units. The power of this scalable
catalytic system lies in the access that it offers to a class of
biphenol products that cannot be synthesized with adequate
efficiency by any other direct methods.9m,9n,11b,26 On the basis
of our mechanistic studies, a unique catalytic cycle that in-
cludes selective oxidation of a readily oxidized phenol A to a
phenoxyl radical A•, which couples with an iron ligated phe-
noxyl radical B•, was postulated (Figure 1C).
The current study relies on previous comprehensive studies
by Groves and others on the relationship between the struc-
tural and electronic environment of iron porphyrins and
their catalytic functions—studies that facilitated investiga-
tions of the mode of action of heme enzymes.15 The added
value of these studies lies in the new pathways that they offer
for the design of biomimetic catalysts with improved syn-
thetic capabilities and unique selectivity.16,17 In heme en-
zymes, the iron porphyrin cofactor attaches to the protein
backbone by coordination of an axial cysteine (for hydroxyl-
ACS Paragon Plus Environment

Page 3 of 12
Journal of the American Chemical Society
tween two liberated para-phenoxyl radicals of 2a.4b In con-
1
2
3
4
5
6
7
8
trast, the oxidative homocoupling of 2a by the FeCl3 catalyst
through a radical-anion coupling mechanism afforded un-
symmetrical biphenol 4 as the sole product (Table 1, entry
4).4b The site specificity in this transformation may be ex-
plained in terms of the coupling between the para-phenoxyl
radical of 2a with the most nucleophilic meta-position of the
second – phenol(ate) 2a – molecule.4b The formation of the
symmetrical biphenol 6 rather than biphenol 4 by catalyst 1a
implies that the two complexes mediate the homocoupling
by different mechanisms. The observed regiospecificity em-
phasizes the power of oxidative coupling as a synthetic strat-
egy for preparing constitutional biaryl isomers in a direct and
efficient manner from (a) single un-functionalized phenolic
unit(s).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Oxidative homocoupling of phenol 2a by iron
catalysts
yield
of 4
yield
of 6
entry
conditions
[%]a
[%]a
Figure 1. Different oxidative coupling mechanisms by vari-
ous iron complexes.
Fe[TPP]Cl [1 mol %], t-
BuOOH
1
--
--
20b
12b
2
t-BuOOH
RESULTS AND DISCUSSION
Fe[TPP]Cl [1 mol %], 4-
Method development
3
nitrophenol (2d, 10 mol %), t- --
BuOOH
60
--
The study commenced with the establishment of suitable
conditions
for
oxidative
homocoupling
of
2,6-
4c
FeCl3 [10 mol %], t-BuOOt-Bu 62
dimethoxyphenol (2a) with the commercially available
Fe[TPP]Cl (1a) complex. At this point in the research, the
true oxidation capability of the catalyst had to be explored;
therefore, after the consumption of phenol 2a, NaBH4 was
added to the reaction mixture to reduce any over-oxidation
by-products. Our first attempt to catalyze the homocoupling
of phenol 2a by catalyst 1a [1 mol %, t-BuOOH (2 equiv)] in
HFIP was not successful; it afforded symmetrical biphenol 6
in poor 20% yield (Table 1, entry 1). A control experiment
without the iron catalyst afforded product 6 in 12% yield (Ta-
ble 1, entry 2), thereby indicating that iron porphyrin was not
an efficient catalyst under those particular reaction condi-
tions. The oxidative coupling of phenol 2a in other solvents,
such as chloroform or 2,2,2-trifluoroethanol (TFE), was also
not successful, and the reaction under elevated temperatures
furnished only oxygenation products.
Conditions: phenol 2a (0.5 mmol), [Fe] catalyst, t-BuOOH
(2 equiv) in two portions every 24 h, HFIP, rt; then NaBH4 (1
equiv) for 2 h aIsolated yields after complete consumption of
b
c
4b
phenol 2a. Low conversion after 48 h. See reference
for
exact conditions.
Next, other electron-deficient phenols were examined as
axial ligands for the oxidative homocoupling of phenol 2a (1
equiv). The addition of phenol 2c, first in catalytic amounts
and later in excess (3 equiv, Table 2, entry 2), afforded the
unsymmetrical biphenol 5 in 65% yield (mixture of para and
ortho isomers, 2.5:1). Since phenol 2c is less nucleophilic than
2,6-dimethoxyphenol 2a, the formation of cross-coupling
product
5 as a major product by the Fe[TPP]Cl/t-
BuOOH/HFIP catalytic system implies that this reaction
probably does not follow a radical-anion coupling mecha-
nism (compare entries 1 and 2 in Table 2). The formation of a
significant amount of homocoupling product 6 (29% yield,
entry 2) may be explained in terms of a competitive free radi-
cal-radical coupling mechanism (vide supra). Other commer-
cially available iron porphyrin catalysts, such as 5,10,15,20-
tetrakis(2,4,6-trimethylphenyl)porphyrin (Fe[TMPP]Cl, 1b)
We thus looked to previous studies showing that electron-
deficient phenols have a strong axial ligand effect that signif-
icantly improves the catalytic activity of iron porphyrins in
oxygenation reactions.27 Indeed, addition of 4-nitrophenol
(2d, 10 mol %, Table 1, entry 3) to the above reaction led to a
significant improvement in the coupling efficiency; under
these conditions, symmetrical biphenol 6 was obtained in
60% yield. It has been suggested that 2d serves as a strong
axial ligand that leaves zero coordination sites for substrate
binding and, therefore, induces outer-sphere coupling be-
and
5,10,15,20-tetrakis(pentafluorophenyl)porphyrin
(Fe[TFPP]Cl, 1c), which differ from catalyst 1a in their elec-
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 12
tronic and structural properties (Figure 1C), were found to be
less effective (Table 2, entries 3 and 4).
2a. b10 mol % of catalyst and t-BuOOt-Bu (2 equiv), then
NaBH4. Compound 4 was formed instead of compound 6.
TMPP = 5,10,15,20-tetrakis (2,4,6-trimethylphenyl)porphyrin,
TFPP = 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin.
c
1
2
3
4
Table 2. Oxidative cross-coupling of phenol 2a with
phenol 2c by iron catalysts
5
6
Reaction scope
The power of the Fe[TPP]Cl/t-BuOOH/HFIP catalytic system
in mediating oxidative cross-coupling reactions between
readily oxidized phenols that have at least (a) single ortho- or
para-methoxy group(s) with less nucleophilic phenols that
possess either alkyl or ortho-halide(s) substituents is demon-
strated in Figure 2. The reaction was found to be general, and
a long list of unsymmetrical biphenols 7−30 that are not ac-
cessible in an efficient manner by other oxidative coupling
methods were obtained in moderate to good yields. While
ortho-halophenols with bond-dissociation energy (BDE) val-
ues28 similar to those of phenol 2c were found to be suitable
coupling partners (biphenols 7−9), the less activated para-
halophenols failed to react under our novel conditions. Phe-
nols with mono ortho-substituents afforded a mixture of two
constitutional isomers in various ratios (7−8, 10−13, 17, 23 and
25). The ability to perform the coupling on a gram scale was
proven by reacting 1 g of 2-t-butyl-4-methoxyphenol (2e)
with 2,4-dimethylphenol (2f, 3 equiv) to afford unsymmet-
rical biphenol 24 in 72% yield (1.22 g).
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
en-
try
1b
yield of
yield of
ratio
(p:o)
conditions
5 [%]a
6 [%]a
FeCl3, t-BuOOt-Bu
23
40 (4)c
1:1
2
Fe[TPP]Cl, t-BuOOH 65
29
2.5:1
Fe[TMPP]Cl (1b),
t-BuOOH
3
11
12
2.2:1
1.7:1
Fe[TFPP]Cl (1c),
17
4
27
t-BuOOH
Conditions: 2,6-dimethoxyphenol (2a, 1 equiv), phenol (2c,
3 equiv), Fe porphyrin catalyst (1 mol%), t-BuOOH (2 equiv)
in two portions every 24 h, HFIP, rt, then NaBH4 (1 equiv) for
a
4 h. Isolated yields after complete consumption of phenol
ACS Paragon Plus Environment

Page 5 of 12
Journal of the American Chemical Society
Fe[TPP]Cl (1 mol %)
PhOH A + PhOH B
unsymmetrical biphenols A B
1
2
3
4
5
6
7
8
9
t-BuOOH (1.1 equiv)
HFIP, rt
OH
OH
OH
OH
OH
OH
OH
MeO
OMe
MeO
OMe
Br
MeO
OMe
MeO
OMe
MeO
iPr
OMe
MeO
OMe
Cl
Cl
Cl
t-Bu
Et
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
OH
OH
OH
OH
OH
7a, 14%
8a, 10%
9, 15%
10a, 50%
10b, 8%b
11a, 28%
12a, 46%
7b, 21%a
8b, 15%b
11b, 26%b
12b, 23%b
OH
OH
OH
OH
OH
OH
MeO
Me
OMe
MeO
OMe
OH
MeO
Me
OMe
OH
MeO
Me
OMe
MeO
OMe
MeO
Me
OMe
OH
OH
Me
Me
t-Bu
OH
Me
Me
17a, 21%
OH
13a, 56%
14, 79%
15, 77%
16, 64%
18, 73%
13b, 20%b
17b, 49%b
OH
MeO
Me
OMe
MeO
Me
t-Bu
MeO
Me
t-Bu
MeO
Me
t-Bu
MeO
t-Bu
OH
MeO
Me
t-Bu
OH
OH
OH
Me
OH
OH
OH
OH
Me
Me
Me
Me
OH
OH
Me
OH
19, 62% [58%]c
20, 46%
21, 77%
22, 72%
23a, 36%
23b, 33%b
24, 72%d
OH
OH
MeO
Me
t-Bu
MeO
Me
Me
OH
MeO
Me
Me
Me
Me
OMe
Me
OMe
Me
Me
OMe
OH
Me
OH
OH
OH
OH
OH
OH
OH
Me
Me
OH
Me
Me
Me
Me
25a, 44%
26, 45%
27, 51%
28, 30%
29, 47%
30, 31%
25b, 37%b
Figure 2. Scope and yields of oxidative coupling reactions of phenols by catalyst 1a in HFIP. General conditions: phenol A (1
equiv), phenol B (2-3 equiv), Fe[TPP]Cl (1a, 1 mol %), t-BuOOH (1.1 equiv), HFIP, rt, 24 h. (a) Yields of isolated products. (b) or-
tho-isomer product. (c) (Fe[TPP])2O (0.5 mol %) was used instead of catalyst 1a. (d) Isolated yield for reaction that was carried
out on a gram scale.
Mechanistic studies
Isotropically shifted signals, sufficiently narrow to be ob-
served in wide-range H-NMR spectra (ca 250 ppm), consti-
1
To probe the mechanism of the Fe[TPP]Cl/t-BuOOH/HFIP
catalytic system and thereby to reveal some of the factors
that control the chemoselectivity of the reaction, a compre-
tute a powerful tool for determining the identity of the axial
ligand in paramagnetic iron porphyrin complexes.27b,29 In this
work, a number of iron porphyrin complexes were prepared
in an NMR tube by mixing Fe[TPP]Cl with different ligands
and Ag2CO3 in CDCl3. The Fe[TPP][phenolate] complexes
were characterized by proton NMR (see SI-II file, sections 3-
4) and the collected data was applied for studying ligand
1
hensive H-NMR study of paramagnetic iron porphyrin com-
plexes and iron-mediated BINOL racemization was under-
taken.
1H-NMR spectroscopy of iron porphyrin complexes
exchange
processes
with
and
without
HFIP.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 12
1
2
3
4
5
A) 1H-NMR spectrum of 1d.
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
B) 1H-NMR spectrum of 1e.
1
1
Figure 3. A) H-NMR spectrum of (Fe[TPP])2O (1d) in CDCl3 and B) H-NMR spectrum of Fe[TPP][OCH(CF3)2] (1e) after
the addition of HFIP. Pyr = pyrrole hydrogen atoms of the TPP ligand, m-Ph = meta-hydrogen atoms of the phenyl
groups in the TPP ligand.
A) 1H-NMR spectrum of 1f and 1g (1:1 ratio).
B) 1H-NMR spectrum of 1e and 1g (1:2 ratio) that formed after the addition of HFIP.
1
Figure 4. H-NMR spectrum of (A) complexes 1f and 1g in CDCl3 and (B) complexes 1e and 1g after the addition of HFIP. Pyr =
pyrrole hydrogen atoms of the TPP ligand. m-Ph = meta-hydrogen atoms of the phenyl groups in the TPP ligand
As mentioned above, the oxidative coupling of phenol 2a is
highly efficient in HFIP. Indeed, in recent years, HFIP has
become the solvent of choice in oxidative coupling reactions
of phenols.4a,4b,10c,10d,11a,11c,12,30 It is a mildly acidic (pKa = 9.3)
ACS Paragon Plus Environment

Page 7 of 12
Journal of the American Chemical Society
and highly polar solvent that forms strong hydrogen-bond
anionic ligands in HFIP (see SI-II file, section 5). The equilib-
1
2
3
4
5
6
7
8
pairs with hydrogen-bond acceptor groups, such as ethers,
peroxides, and carbonyl compounds.10d,30a,31 Furthermore, the
fluorinated alcohol molecules seem to interact with charged
and polar intermediates, such as phenoxyl radicals, leading
to a significant enhancement in the rate and the selectivity of
the radical process.10d,11a,31a
rium constants (K, Figure 5) for the ligand-exchange process
between HFIP and a number of phenols were evaluated by
NMR spectroscopy. The results are displayed in a reactivity
map (N vs. Eox, Figure 5) of the type that was introduced by
us in a previous study, in which the position of each phenol
reflects its relative reactivity in cross-coupling reactions.4b
On the basis of our NMR study, the phenols in the reactivity
map were classified into two groups: a) phenols that dissoci-
ate from the iron porphyrin complex in the presence of HFIP
(colored red, K < ~0.1), and b) phenols that do form detecta-
ble Fe[TPP][phenolate] complexes (colored blue, K > ~0.1).
This part of the study revealed that, in general, electron-rich
phenols with low oxidation potentials (phenols of type A)
and at least one methoxy group at either the ortho or the
para position belong to the first group.The second group is
made up of phenols that have meta-methoxy, alkyl or halide
substituents. These phenols have high oxidation potentials
(phenols of type B) and are considered to be poor nucleo-
philes. It is therefore suggested that the origin of selectivity
in this novel catalytic system is attributed to a selective oxi-
dation of phenol A to a transient phenoxyl radical by Fe-
ligated phenol B complex.
In this study, we reveal yet another role for HFIP—as an ani-
onic ligand for iron complexes. When Fe[TPP]Cl and Ag2CO3
(9 equiv) were mixed in CDCl3 for 8 h, a ligand-exchange
process took place, affording the thermodynamically stable
(Fe[TPP])2O (1d) complex (Figure 3A).32 However, the use of
HFIP (18 equiv) as an additive in the NMR tube, shifted the
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
equilibrium
away
from
complex
1d,
affording
Fe[TPP][OCH(CF3)2] (1e) as the sole detectable complex
(Figure 3B, see SI-II, section 6, Figures S2 and S3). Under
similar conditions, other less acidic fluorinated alcohols,
such as TFE, 1,1,1-trifluoropropan-2-ol and 2,2,2-trifluoro-1-
phenylethanol, were found to be inferior ligands, and com-
plex 1d was formed in various ratios (see SI-II, section 7, Fig-
ure S4). Furthermore, the oxidative cross-coupling between
phenol 2a and 2,6-dimethylphenol (2g) catalyzed by
Fe[TPP]2O (0.5 mol %) afforded biphenol 19 in 58% yield.
These experiments provide spectroscopic and experimental
evidence that (Fe[TPP])2O, which lacks catalytic activity, is
not stable in HFIP, and therefore the catalytic activity of the
iron porphyrin is retained throughout the reaction.
In general, the Hortho and Hpara protons of the phenolic axial
ligand resonate at around -100 ppm (relative to TMS, Figure
4), while the Hmeta signals are located in the low-field region,
from 80 to 120 ppm. The chemical shifts of the phenol sub-
stituents vary according to their location on the ring [for
example, the chemical shifts of 2-Me (7’) and 5-Me (8’) in
complex Fe[TPP][2h] (1g) are 91 and -36 ppm, respectively,
Figure 4A]. In light of this valuable observation [obtained via
NMR studies of a long list of phenols (see SI-II file, section
4)], competitive binding experiments for determining the
phenols' relative association strength to the axial vacant site
of iron porphyrin were performed. For example, a mixture of
complexes Fe[TPP][2e] (1f) and Fe[TPP][2h] was identified
1
by H-NMR when 2-t-butyl-4-methoxyphenol (2e, 7 equiv)
and 2,5-dimethylphenol (2h, 7 equiv) were mixed with
Fe[TPP]Cl (1 equiv) and Ag2CO3 in CDCl3 (Figure 4A). A 1:1
molar ratio was determined for the two complexes based on
the integration of the area of porphyrin's Ph-Hmeta peaks
(10−12 ppm). The addition of HFIP (18 equiv) to that solution
initiated a ligand-exchange process that selectively dissociat-
ed phenol 2e from the complex to afford complex 1g and
Fe[TPP][OCH(CF3)2] (1e) in an approximately 2:1 ratio (Fig-
ure 4B). The weak binding strength of phenol 2e to the iron
in the presence of HFIP is associated with the strong hydro-
gen bonds between the fluorinated alcohol and its para-
methoxy group as demonstrated by Lucarini, Pedulli and
Guerra.33 Indeed, the selective binding of phenol 2h to the
iron porphyrin in preference to the readily oxidized 2e may
explain the cross-coupling selectivity obtained when these
two phenols were reacted by the Fe[TPP]Cl/t-BuOOH/HFIP
catalytic system to afford unsymmetrical biphenol 21 in 77%
yield (Figure 2).
Figure 5. Modified reactivity map for phenols in HFIP based
on their global nucleophilicity N values and their oxidation
potentials (Eox).4b The colors refer to the ability of each phe-
nol to bind to complex 1a in the presence of the competitive
1
HFIP ligand, as determined by H-NMR; red is used for phe-
nols that do not form detectable Fe[TPP][phenolate] com-
plexes and blue for phenols that do form detectable
Fe[TPP][phenolate] complexes.
Consecutive oxidative coupling is a competitive side reaction
that takes place when a biphenol product further reacts un-
der oxidation conditions.12 If the biphenol product has a low
oxidation potential, it can act as a phenol A competitor. In
contrast, if it binds strongly to the catalyst, it serves as a type
B phenol. To investigate the ligand exchange process be-
tween phenols and their corresponding biphenol coupling
1
products, H-NMR spectra of 2,6-dimethylphenol (2g), bi-
The ligand-exchange process was further investigated using
Fe[TPP]Cl as a probe to discriminate between phenols that
associate to iron and phenols that generate weakly basic
phenol 19 (Figure 2) and Fe[TPP]Cl (Ag2CO3, CDCl3) with
and without HFIP, were measured (See SI-II file, section 8,
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 12
additive ArXH
(X = O or S, 50 mol %)
Figure S5). In CDCl3 both phenol 2g and biphenol 19 were
1
bound to the iron porphyrin complex, but the addition of
HFIP led to complete liberation of biphenol 19, which has
methoxy groups at the remote phenolic unit. This finding
supports our experimental results showing that consecutive
reactions are less favorable under our reaction conditions
that involve a limited amount of terminal oxidant and an
excess of phenol B.
1a
cat.
(1 mol %)
31
31
2
(R)-BINOL (
)
(R/ S)-
Ag2CO3 (9 mol %)
HFIP:DCE (1:1)
Ar atm, rt
3
4
5
6
7
8
Ph
Ph
N
N
III
Fe
II
Ph
Ph
Ph
N
N
N
N
Fe
N
N
Ph
SET
Ph
Ph
O
O
OH
OH
BINOL Racemization
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The fact that the Fe[TPP]Cl complex efficiently catalyzes
cross-coupling of phenolic pairs with non-complementary
relationships (ꢀN << 0, Figure 1) implies that the coupling
does not follow a radical-anion coupling mechanism (be-
tween phenoxyl radical A• and ligated anionic phenolate B).
We therefore posited a reaction between an associated phe-
noxyl radical B• and a liberated phenoxyl radical A•. To sup-
port this premise, it was necessary to confirm the existence
of spin transfer from the axial phenolic ligand to the iron
center (‘push effect’).27b
1h
Recently, our group revealed that optically pure 1,1'-bi-2-
naphthol (BINOL, 31, Figure 6) undergoes rapid racemization
in the presence of catalytic amounts of redox Fe(III) or Cu
(II) complexes and that this process is accelerated in the
presence of a terminal oxidant, such as t-BuOOt-Bu.4a It was
postulated that a single electron transfer (SET) process be-
tween an associated binaphtholate ligand and the metal gen-
erates an optically unstable binaphthoxyl radical that yields
racemic BINOL. This process (which is undesired in enanti-
oselective oxidative coupling of 2-napthols) becomes a pow-
erful tool for studying the structural and electronic proper-
ties of metal phenolate complexes.4a Indeed, when (R)-31 was
mixed with Fe[TPP]Cl (1 mol %) and Ag2CO3 (9 mol %)
[HFIP:DCE (1:1), argon atmosphere, room temperature],
complete racemization occurred within 3 h (green diamonds,
Figure 6). The existence of the Fe[TPP][BINOL] (1h) complex
Figure 6. Racemization of (R)-BINOL by Fe[TPP]Cl in the
presence of competitive ligands. Conditions: BINOL (0.25
mmol), additive ArXH (X = O or S, 0% or 50 mol %),
Fe[TPP]Cl (1a, 1 mol%), Ag2CO3 (9 mol %), HFIP:DCE (1:1,
0.25 M), Ar atmosphere, room temperature, 4 h.
1
was confirmed by H-NMR; in contrast, BINOL failed to co-
ordinate to Fe[TMPP]Cl (1b) and Fe[TFPP]Cl (1c) under iden-
tical conditions, probably as a result of steric hindrance or
electronic considerations. Indeed, there was no loss in opti-
cal purity, when (R)-BINOL was mixed with complexes 1b
and 1c. Next, the racemization of (R)-31 by complex 1a in the
presence of competitive axial ligands (50 mol %) was studied.
While phenol (2c, red circles) and 4-nitrophenol (2d, blue
triangles, see SI-II file, sections 9-10, figure S6) decelerated
the racemization rates, 4-nitrothiophenol 32, which is a
much stronger anionic ligand than 31 (see SI-II file, section 11,
Figures S7) led to complete suspension of the racemization
process (black squares). These experiments provide direct
evidence for electron transfer between phenolic ligands and
the iron porphyrin complex, which, in turn, supports the
existence of two main isoelectronic structures, namely, III
and IV (Scheme 2). On the basis of the above studies, it is
most likely that a persistent iron–phenoxyl B• radical com-
plex reacts with a transient liberated phenoxyl radical A•,
Based on the above findings and Groves’ mechanistic studies
of related bioinspired metal porphyrin based C−H function-
alization reactions,17 a mechanistic scheme for the selective
oxidative cross-coupling of phenols by the Fe[TPP]Cl/t-
BuOOH/HFIP catalytic system was postulated (Scheme 2). A
reversible ligand-exchange process between HFIP and phenol
B generates complex Fe[TPP][OCH(CF3)2] (1e). This complex
lacks
catalytic
activity
and
its
conversion
to
Fe[TPP][phenolate B] (I), which enters the catalytic cycle, is
probably the selectivity-determining step of the process. The
oxidation of complex I affords a high valance Fe(IV)=O
porphyryl radical intermediate (II, ‘Compound I’)23a,35 that
selectively oxidizes phenol A to the phenoxyl A• radical (EoxA
< EoxB). This transient radical species reacts with a persistent
phenoxyl radical B• ligand (complex III) via an intermolecu-
lar radical-radical coupling mechanism4b,4c,9c to afford an
unsymmetrical biphenol A−B ligand (complex V). The cata-
lytic cycle is terminated by a second ligand-exchange process
that releases the biphenol product (see SI-II file, section 8,
Figure S5) while regenerating resting state complex I.
according to the persistent radical effect (PRE) principle.
30b,34
CONCLUSION
ACS Paragon Plus Environment

Page 9 of 12
Journal of the American Chemical Society
In summary, a novel catalytic system based on a biomimetic
probing the racemization rates of (R)-BINOL in the presence
1
2
3
4
5
6
7
8
iron porphyrin catalyst in HFIP was developed for mediating
the cross-coupling between pairs of phenols with a non-
complementary relationship (ꢀN < 0). The efficient and scal-
able conditions offer a method to prepare unsymmetrical
biphenols — assembled from an inactivated phenolic unit —
that would otherwise not be accessible in an efficient man-
ner. It is postulated that the mechanism involves an intermo-
lecular radical-radical coupling between a transient phenoxyl
radical A• with a ligated persistent phenoxyl radical B•. With
of Fe[TPP]Cl and competitive axial ligands.
Finally, in addition to its well-known roles in oxidative cou-
pling of phenols,4b,10d,11a,30b the importance of HFIP in the
Fe[TPP]Cl/t-BuOOH/HFIP catalytic system lies in the facts
that: 1) it efficiently distinguishes between phenols of the red
group (A) that have low oxidation potentials and phenols of
the blue group (B) that bind to the iron porphyrin complex;
2) it serves as a competitive axial ligand that prevents the
formation of the undesired ꢁ-(Fe[TPP])2O complex and in so
9
1
the aid of H-NMR spectroscopy of paramagnetic iron[TPP]
doing it preserves the catalytic activity of the iron porphyrin;
and 3) it releases the biphenol A−B product from the iron
complex, thereby reducing consecutive oxidation processes.
This work thus demonstrates that selective formation of
biaryl bonds is possible by mechanistically controlled oxida-
tive cross-coupling reactions of phenols.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
complexes, the phenols were successfully classified according
to their ability to serve as anionic phenolic B ligands in the
presence of a competitive HFIP ligand. The existence of a
‘push effect’ between the phenolic ligands was proved by
Scheme 2. Postulated mechanism for the oxidative cross-coupling of phenols by Fe[TPP]Cl in HFIP.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 12
1
2
3
4
5
6
7
8
Lett. 2001, 3, 1137-1140. (l) Hon, S.-W.; Li, C.-H.; Kuo, J.-H.;
ASSOCIATED CONTENT
Supporting Information
Barhate, N. B.; Liu, Y.-H.; Wang, Y.; Chen, C.-T. Org. Lett. 2001, 3,
869-872. (m) Smrcina, M.; Polakova, J.; Vyskocil, S.; Kocovsky, P.
J. Org. Chem. 1993, 58, 4534-4538. (n) Smrcina, M.; Lorenc, M.;
Hanus, V.; Sedmera, P.; Kocovsky, P. J. Org. Chem. 1992, 57,
1917-1920.
Full experimental procedures, characterization data, and
NMR spectra is available free of charge via the Internet at
http://pubs.acs.org.
(10) (a) Lips, S.; Wiebe, A.; Elsler, B.; Schollmeyer, D.; Dyballa, K.
M.; Franke, R.; Waldvogel, S. R. Angew. Chem. Int. Ed. 2016, 55,
10872-10876. (b) Wiebe, A.; Schollmeyer, D.; Dyballa, K. M.;
Franke, R.; Waldvogel, S. R. Angew. Chem. Int. Ed. 2016, 55,
11801-11805. (c) Morimoto, K.; Sakamoto, K.; Ohshika, T.; Dohi,
T.; Kita, Y. Angew. Chem. Int. Ed. 2016, 128, 3716-3720. (d) Elsler,
B.; Wiebe, A.; Schollmeyer, D.; Dyballa, K. M.; Franke, R.;
Waldvogel, S. R. Chem. Eur. J. 2015, 21, 12321-12325. (e) More,
N. Y.; Jeganmohan, M. Org. Lett. 2015, 17, 3042-3045. (f) Lee, Y.
E.; Cao, T.; Torruellas, C.; Kozlowski, M. C. J. Am. Chem. Soc.
2014, 136, 6782-6785. (g) Elsler, B.; Schollmeyer, D.; Dyballa, K.
M.; Franke, R.; Waldvogel, S. R. Angew. Chem. Int. Ed. 2014, 53,
5210-5213. (h) Smrcina, M.; Vyskocil, S.; Maca, B.; Polasek, M.;
Claxton, T. A.; Abbott, A. P.; Kocovsky, P. J. Org. Chem. 1994, 59,
2156-2163. (i) Hovorka, M.; Zavada, J. Tetrahedron 1992, 48,
9517-9530. (j) Hovorka, M.; Ščigel, R.; Gunterová, J.; Tichý, M.;
Závada, J. Tetrahedron 1992, 48, 9503-9516. (k) Hovorka, M.;
Gunterova, J.; Zavada, J. Tetrahedron Lett. 1990, 31, 413-416.
(11) (a) Gaster, E.; Vainer, Y.; Regev, A.; Narute, S.; Sudheendran,
K.; Werbeloff, A.; Shalit, H.; Pappo, D. Angew. Chem. Int. Ed.
2015, 54, 4198-4202. (b) Morimoto, K.; Sakamoto, K.; Ohnishi, Y.;
Miyamoto, T.; Ito, M.; Dohi, T.; Kita, Y. Chem. -Eur. J. 2013, 19,
8726-8731. (c) Kirste, A.; Schnakenburg, G.; Stecker, F.; Fischer,
A.; Waldvogel, S. R. Angew. Chem. Int. Ed. 2010, 49, 971-975.
(12) (a) Vershinin, V.; Dyadyuk, A.; Pappo, D. Tetrahedron 2017,
73, 3660-3668. (b) Dyadyuk, A.; Sudheendran, K.; Vainer, Y.;
Vershinin, V.; Shames, A. I.; Pappo, D. Org. Lett. 2016, 18, 4324-
4327.
AUTHOR INFORMATION
Corresponding Author
pappod@bgu.ac.il
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Author Contributions
†H.S. and A.L. contributed equally.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This research was supported by the Israel Science Founda-
tion (grant No. 164/16).
REFERENCES
(1) (a) Wencel-Delord, J.; Panossian, A.; Leroux, F. R.; Colobert, F.
Chem. Soc. Rev. 2015, 44, 3418-3430. (b) Kočovský, P.; Vyskočil,
Š.; Smrčina, M. Chem. Rev. 2003, 103, 3213-3246.
(2) (a) Campeau, L.-C.; Fagnou, K. Chem. Commun. 2006, 1253-
1264. (b) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire,
M. Chem. Rev. 2002, 102, 1359-1470. (c) Beletskaya, I. P.;
Cheprakov, A. V. Chem. Rev. 2000, 100, 3009-3066. (d) Miyaura,
N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483.
(3) (a) Trost, B. M. Acc. Chem. Res. 2002, 35, 695-705. (b) Trost,
B. M. Angew. Chem., Int. Ed. 1995, 34, 259-281. (c) Trost, B. M.
Science 1991, 254, 1471-1477.
(4) (a) Narute, S.; Parnes, R.; Toste, F. D.; Pappo, D. J. Am. Chem.
Soc. 2016, 138, 16553-16560. (b) Libman, A.; Shalit, H.; Vainer, Y.;
Narute, S.; Kozuch, S.; Pappo, D. J. Am. Chem. Soc. 2015, 137,
11453-11460. (c) Egami, H.; Matsumoto, K.; Oguma, T.; Kunisu,
T.; Katsuki, T. J. Am. Chem. Soc. 2010, 132, 13633-13635. (d)
Ashenhurst, J. A. Chem. Soc. Rev. 2010, 39, 540-548.
(13) (a) Domingo, L. R.; Perez, P. Org. Biomol. Chem. 2011, 9,
7168-7175. (b) Pratihar, S.; Roy, S. J. Org. Chem. 2010, 75, 4957-
4963. (c) Domingo, L. R.; Chamorro, E.; Pérez, P. J. Org. Chem.
2008, 73, 4615-4624.
(14) Matsumoto, K.; Egami, H.; Oguma, T.; Katsuki, T. Chem.
Commun. 2012, 48, 5823-5825.
(5) Kozlowski, M. C. Acc. Chem. Res. 2017, 50, 638-643.
(6) (a) Wang, H. Chirality 2010, 22, 827-837. (b) Brunel, J. M.
Chem. Rev. 2005, 105, 857-898.
(7) Hay, A. S. J. Polym. Sci. A Polym. Chem. 1998, 36, 505-517.
(8) Kobayashi, S.; Higashimura, H. Prog. polym. sci. 2003, 28,
1015-1048.
(15) (a) Boaz, N. C.; Bell, S. R.; Groves, J. T. J. Am. Chem. Soc.
2015, 137, 2875-2885. (b) Wang, X.; Ullrich, R.; Hofrichter, M.;
Groves, J. T. Proc. Natl. Acad. Sci. 2015, 112, 3686-3691. (c)
Poulos, T. L. Chem. Rev. 2014, 114, 3919-3962. (d) Yosca, T. H.;
Rittle, J.; Krest, C. M.; Onderko, E. L.; Silakov, A.; Calixto, J. C.;
Behan, R. K.; Green, M. T. Science 2013, 342, 825-829. (e) Bell, S.
R.; Groves, J. T. J. Am. Chem. Soc. 2009, 131, 9640-9641. (f)
Collman, J. P.; Boulatov, R.; Sunderland, C. J.; Fu, L. Chem. Rev.
2004, 104, 561-588. (g) Sono, M.; Roach, M. P.; Coulter, E. D.;
Dawson, J. H. Chem. Rev. 1996, 96, 2841-2888. (h) Dawson, J. H.
Science 1988, 240, 433-439. (i) Smith, K. M. Porphyrins and
metalloporphyrins; Elsevier Amsterdam, 1975; Vol. 9.
(16) (a) Lu, H.; Kobayashi, N. Chem. Rev. 2016, 116, 6184-6261.
(b) Gopalaiah, K. Chem. Rev. 2013, 113, 3248-3296. (c) Jiang, Q.;
Sheng, W.; Tian, M.; Tang, J.; Guo, C. Eur. J. Org. Chem. 2013,
2013, 1861-1866. (d) Que, L.; Tolman, W. B. Nature 2008, 455,
333-340. (e) Groves, J. T. J. Inorg. Biochem. 2006, 100, 434-447.
(f) Green, M. T.; Dawson, J. H.; Gray, H. B. Science 2004, 304,
1653-1656.
(9) (a) Sako, M.; Takizawa, S.; Yoshida, Y.; Sasai, H. Tetrahedron:
Asymmetry 2015, 26, 613-616. (b) Jiang, Q.; Sheng, W.; Tian, M.;
Tang, J.; Guo, C. Eur. J. Org. Chem. 2013, 2013, 1861-1866. (c)
Egami, H.; Katsuki, T. J. Am. Chem. Soc. 2009, 131, 6082-6083. (d)
Hewgley, J. B.; Stahl, S. S.; Kozlowski, M. C. J. Am. Chem. Soc.
2008, 130, 12232-12233. (e) Takizawa, S.; Katayama, T.; Sasai, H.
Chem. Commun. 2008, 4113-4122. (f) Takizawa, S.; Katayama, T.;
Somei, H.; Asano, Y.; Yoshida, T.; Kameyama, C.; Rajesh, D.;
Onitsuka, K.; Suzuki, T.; Mikami, M.; Yamataka, H.; Jayaprakash,
D.; Sasai, H. Tetrahedron 2008, 64, 3361-3371. (g) Guo, Q.-X.;
Wu, Z.-J.; Luo, Z.-B.; Liu, Q.-Z.; Ye, J.-L.; Luo, S.-W.; Cun, L.-F.;
Gong, L.-Z. J. Am. Chem. Soc. 2007, 129, 13927-13938. (h)
Temma, T.; Hatano, B.; Habaue, S. Tetrahedron 2006, 62, 8559-
8563. (i) Li, X.; Hewgley, J. B.; Mulrooney, C. A.; Yang, J.;
Kozlowski, M. C. J. Org. Chem. 2003, 68, 5500-5511. (j) Luo, Z.;
Liu, Q.; Gong, L.; Cui, X.; Mi, A.; Jiang, Y. Angew. Chem. Int. Ed.
2002, 41, 4532-4535. (k) Li, X.; Yang, J.; Kozlowski, M. C. Org.
(17) (a) Liu, W.; Groves, J. T. Acc. Chem. Res. 2015, 48, 1727-
1735. (b) Huang, X.; Bergsten, T. M.; Groves, J. T. J. Am. Chem.
Soc. 2015, 137, 5300-5303.
ACS Paragon Plus Environment

Page 11 of 12
Journal of the American Chemical Society
(18) (a) Campomanes, P.; Rothlisberger, U.; Alfonso-Prieto, M.;
(32) (a) Cheng, R. J.; Latos-Grazynski, L.; Balch, A. L. Inorg. Chem.
1
2
3
4
5
6
7
8
Rovira, C. J. Am. Chem. Soc. 2015, 137, 11170-11178. (b)
Hohenberger, J.; Ray, K.; Meyer, K. Nat. Commun. 2012, 3, 720-
733. (c) Krest, C. M.; Silakov, A.; Rittle, J.; Yosca, T. H.; Onderko,
E. L.; Calixto, J. C.; Green, M. T. Nat. Chem. 2015, 7, 696-702.
(19) (a) Chen, Z.; Yin, G. Chem. Soc. Rev. 2015, 44, 1083-1100. (b)
Wirstam, M.; Blomberg, M. R. A.; Siegbahn, P. E. M. J. Am. Chem.
Soc. 1999, 121, 10178-10185.
(20) (a) Vidossich, P.; Alfonso-Prieto, M.; Rovira, C. J. Inorg.
Biochem. 2012, 117, 292-297. (b) Ogliaro, F.; Harris, N.; Cohen,
S.; Filatov, M.; de Visser, S. P.; Shaik, S. J. Am. Chem. Soc. 2000,
122, 8977-8989.
1982, 21, 2412-2418. (b) Murray, K. S. Coord. Chem. Rev. 1974,
12, 1-35. (c) Hoffman, A.; Collins, D.; Day, V.; Fleischer, E.;
Srivastava, T.; Hoard, J. J. Am. Chem. Soc. 1972, 94, 3620-3626.
(33) (a) Lucarini, M.; Pedulli, G. F.; Guerra, M. Chem. - Eur. J.
2004, 10, 933-939. (b) Lucarini, M.; Mugnaini, V.; Pedulli, G. F.;
Guerra, M. J. Am. Chem. Soc. 2003, 125, 8318-8329.
(34) (a) Fischer, H. Chem. Rev. 2001, 101, 3581-3610. (b) Studer,
A. Chem. Eur. J. 2001, 7, 1159-1164. (c) Eberson, L.; Hartshorn,
M. P.; Persson, O.; Radner, F. Chem. Commun. 1996, 2105-2112.
(d) Focsaneanu, K.-S.; Scaiano, J. C. Helv. Chim. Acta 2006, 89,
2473-2482.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(21) Groves, J. T. J. Porphyrins Phthalocyanines 2000, 4, 350-352.
(22) (a) Cho, K.-B.; Hirao, H.; Shaik, S.; Nam, W. Chem. Soc. Rev.
2016, 45, 1197-1210. (b) Schöneboom, J. C.; Cohen, S.; Lin, H.;
Shaik, S.; Thiel, W. J. Am. Chem. Soc. 2004, 126, 4017-4034. (c)
Meunier, B.; de Visser, S. P.; Shaik, S. Chem. Rev. 2004, 104,
3947-3980. (d) Groves, J. T. J. Chem. Edu. 1985, 62, 928. (e)
Groves, J. T.; Nemo, T. E. J. Am. Chem. Soc. 1983, 105, 6243-
6248.
(23) (a) Groves, J. T. Nat. Chem. 2014, 6, 89-91. (b) Kang, Y.;
Chen, H.; Jeong, Y. J.; Lai, W.; Bae, E. H.; Shaik, S.; Nam, W. Chem.
Eur. J. 2009, 15, 10039-10046. (c) Ogliaro, F.; de Visser, S. P.;
Shaik, S. J. Inorg. Biochem. 2002, 91, 554-567. (d) Yamaguchi, K.;
Watanabe, Y.; Morishima, I. J. Am. Chem. Soc. 1993, 115, 4058-
4065.
(24) (a) Šmejkalová, D.; Piccolo, A. Environ. Sci. Technol. 2006, 40,
1644-1649. (b) Chauhan, S. M. S.; Kalra, B.; Mohapatra, P. P. J.
Mol. Catal. A: Chem. 1999, 137, 85-92. (c) Brovo, A.; Fontana, F.;
Minisci, F. Chem. Lett. 1996, 25, 401-402.
(25) Huang, Q.; Huang, Q.; Pinto, R. A.; Griebenow, K.;
Schweitzer-Stenner, R.; Weber, W. J. J. Am. Chem. Soc. 2005,
127, 1431-1437.
(26) (a) Egami, H.; Matsumoto, K.; Oguma, T.; Kunisu, T.; Katsuki,
T. J. Am. Chem. Soc. 2010, 132, 13633-13635. (b) Temma, T.;
Habaue, S. Tetrahedron Lett. 2005, 46, 5655-5657.
(27) (a) Bhowmik, S.; Dey, S.; Sahoo, D.; Rath, S. P. Chem. – Eur. J.
2013, 19, 13732-13744. (b) Takahashi, A.; Kurahashi, T.; Fujii, H.
Inorg. Chem. 2009, 48, 2614-2625.
(28) (a) Evgeny, D.; Taisa, D.; InTech: 2011, p 405-440. (b) Klein,
E.; Lukeš, V. Chem. Phys. 2006, 330, 515-525. (c) Klein, E.; Lukeš,
V. J. Mol. Struct. 2006, 767, 43-50. (d) Chandra, A.; Uchimaru, T.
Int. J. Mol. Sci. 2002, 3, 407-422. (e) de Heer, M. I.; Korth, H.-G.;
Mulder, P. J. Org. Chem. 1999, 64, 6969-6975. (f) Borges dos
Santos, R. M.; Martinho Simões, J. A. J. Phys. Chem. Ref. Data
1998, 27, 707-739.
(29) (a) Berlicka, A.; Latos-Grażyński, L.; Lis, T. Inorg. Chem. 2005,
44, 4522-4533. (b) Jimenez, H. R.; Moratal, J. M.; Loock, B. New J.
Chem. 2002, 26, 323-329. (c) Arasasingham, R. D.; Balch, A. L.;
Cornman, C. R.; De Ropp, J. S.; Eguchi, K.; La Mar, G. N. Inorg.
Chem. 1990, 29, 1847-1850. (d) Balch, A. L.; Renner, M. W. Inorg.
Chem. 1986, 25, 303-307.
(35) Wang, X.; Peter, S.; Kinne, M.; Hofrichter, M.; Groves, J. T. J.
Am. Chem. Soc. 2012, 134, 12897-12900.
(30) (a) Hollóczki, O.; Berkessel, A.; Mars, J.; Mezger, M.; Wiebe,
A.; Waldvogel, S. R.; Kirchner, B. ACS Cat. 2017, 1846-1852. (b)
Dohi, T.; Yamaoka, N.; Kita, Y. Tetrahedron 2010, 66, 5775-5785.
(c) Regev, A.; Shalit, H.; Pappo, D. Synthesis 2015, 47, 1716-1725.
(31) (a) Gaster, E.; Kozuch, S.; Pappo, D. Angew. Chem. Int. Ed.
2017, 56, 5912-5915. (b) Khaksar, S. J. Fluorine Chem. 2015, 172,
51-61. (c) Shuklov, I. A.; Dubrovina, N. V.; Börner, A. Synthesis
2007, 2007, 2925-2943. (d) Berkessel, A.; Adrio, J. A. J. Am. Chem.
Soc. 2006, 128, 13412-13420. (e) Bégué, J.-P.; Bonnet-Delpon, D.;
Crousse, B. Synlett 2004, 2004, 18-29. (f) Willis, C. Coord. Chem.
Rev. 1988, 88, 133-202.
11
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 12 of 12
1
2
TOC
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
12
ACS Paragon Plus Environment