Regiospecific Acylation of Cycloplatinated Complexes: Scope, Limitations, and Mechanistic Implications

Article abstract of DOI:10.1021/acs.organomet.6b00174

A series of platinum complexes based on the tridentate cyclometalating ligand derivatives 6-arylamino-2,2′-bipyridine, 6-phenoxy-2,2′-bipyridine, 6-phenylthio-2,2′-bipyridine, 6-benzyl-2,2′-bipyridine, and 6-benzoyl-2,2′-bipyridine were synthesized, and their acylation reactions were studied. Acylation of platinum complexes based on 6-(4-R-phenylamino)-2,2′-bipyridine derivatives (R = CH₃O, CH₃, Cl, COOEt) tolerates both electron-donating and electron-withdrawing substituents on the aryl ring that are para to the amino group. However, platinum complexes based on 6-(3-R′-phenylamino)-2,2′-bipyridine (R′ = CH₃, Cl, Br) did not undergo the acylation reaction under the same conditions. Interestingly, the acylation of the platinum complexes based on 6-(3-fluorophenylamino)-2,2′-bipyridine proceeded smoothly, and the results indicate that the acylation is regiospecific and occurs at the metalated carbon. Complexes based on 6-phenoxy-2,2′-bipyridine, 6-phenylthio-2,2′-bipyridine, and 6-benzyl-2,2′-bipyridine are also regioselectively acylated. A cyclometalated platinum complex based on 6-benzoyl-2,2′-bipyridine, where the benzene is more electron deficient than those in other cyclometalated platinum complexes, failed to undergo the acylation reaction. The acylation can be carried out in acetic acid, 1,2-dichloroethane, benzonitrile, and acetonitrile. Other acyl halides such as benzoyl chloride and crotonyl chloride are also effective acylating reagents. On the basis of the fact that the reaction is discouraged by the electron deficiency of the phenyl ring and contrasting results of the acylation of platinum complexes based on 6-(3-R′-phenylamino)-2,2′-bipyridine (R′ = CH₃, F, Cl, Br), an unprecedented electrophilic addition-platinum migration-rearomatization cascade mechanism is proposed for the regiospecific acylation reaction.

Full text of DOI:10.1021/acs.organomet.6b00174

Article
pubs.acs.org/Organometallics
Regiospecific Acylation of Cycloplatinated Complexes: Scope,
Limitations, and Mechanistic Implications
Jeffrey Carroll, Hannah G. Woolard, Robert Mroz, Charles A. Nason, and Shouquan Huo*
Department of Chemistry, East Carolina University, Greenville, North Carolina 27858, United States
S
* Supporting Information
ABSTRACT: A series of platinum complexes based on the tridentate
cyclometalating ligand derivatives 6-arylamino-2,2′-bipyridine, 6-phe-
noxy-2,2′-bipyridine, 6-phenylthio-2,2′-bipyridine, 6-benzyl-2,2′-bipyri-
dine, and 6-benzoyl-2,2′-bipyridine were synthesized, and their acylation
reactions were studied. Acylation of platinum complexes based on 6-(4-
R-phenylamino)-2,2′-bipyridine derivatives (R = CH3O, CH3, Cl,
COOEt) tolerates both electron-donating and electron-withdrawing
substituents on the aryl ring that are para to the amino group. However,
platinum complexes based on 6-(3-R′-phenylamino)-2,2′-bipyridine (R′
= CH3, Cl, Br) did not undergo the acylation reaction under the same
conditions. Interestingly, the acylation of the platinum complexes based on 6-(3-fluorophenylamino)-2,2′-bipyridine proceeded
smoothly, and the results indicate that the acylation is regiospecific and occurs at the metalated carbon. Complexes based on 6-
phenoxy-2,2′-bipyridine, 6-phenylthio-2,2′-bipyridine, and 6-benzyl-2,2′-bipyridine are also regioselectively acylated. A
cyclometalated platinum complex based on 6-benzoyl-2,2′-bipyridine, where the benzene is more electron deficient than
those in other cyclometalated platinum complexes, failed to undergo the acylation reaction. The acylation can be carried out in
acetic acid, 1,2-dichloroethane, benzonitrile, and acetonitrile. Other acyl halides such as benzoyl chloride and crotonyl chloride
are also effective acylating reagents. On the basis of the fact that the reaction is discouraged by the electron deficiency of the
phenyl ring and contrasting results of the acylation of platinum complexes based on 6-(3-R′-phenylamino)-2,2′-bipyridine (R′ =
CH3, F, Cl, Br), an unprecedented electrophilic addition−platinum migration−rearomatization cascade mechanism is proposed
for the regiospecific acylation reaction.
substituted with a strongly electron donating alkoxy group(s).
Further experiments showed that the reaction of L1 with
K2PtCl4 in acetic acid and acetic anhydride can directly produce
1b in moderate yield.7 This reaction also represents a rare case
of the cyclometalation of a ligand accompanied by function-
alization of the cyclometalated complex.10 In order to further
understand the regioselective acylation of cyclometalated
platinum complexes, the scope and limitations of this reaction
have been investigated, particularly regarding the role of the
hydrogen bonding, substituent effects, and mechanistic aspects.
INTRODUCTION
■
Cyclometalated complexes constitute an important family of
organometallic compounds and have been rigorously studied
over the last five decades in terms of their formation, reactivity,
and various applications.1−3 Cyclometalated complexes based
on group 10 metals, especially palladium and platinum, are
among the earliest reported and most extensively studied
species. In comparison to cyclometalated palladium complexes,
which show a wide range of reactivity of the carbon−palladium
bonds such as carbonylation, insertion of alkenes and alkynes,
and insertion of isocyanates,4 the platinum counterparts are
relatively less reactive.5 Therefore, cycloplatinated complexes
are frequently studied as functional materials in a variety of
applications in chemical, biological, and organic optoelectronic
fields.6 Recently, we discovered that regioselective acylation of
complex 1a, prepared from the cycloplatination of ligand L1,
produced 1b in high yield (Scheme 1).7 There is strong
intramolecular hydrogen bonding in the acylated product with
an H−O bond length of 1.8 Å revealed by the X-ray crystal
structure of the alkynyl-substituted derivative 1c. The acylation
of cyclometalated complexes has been scarcely reported.4 Only
in two papers were acylations of palladacycles derived from
substituted benzylamine derivatives reported, but the products
did not preserve a carbon−palladium bond.8,9 The reaction
only worked when the phenyl ring was unsubstituted or
RESULTS AND DISCUSSION
■
Role of Hydrogen Bonding. Since there is strong
hydrogen bonding in the acylated product 1b, it is necessary
to examine whether the hydrogen bonding plays a role in
directing the regioselective acylation. The ligands L2−L5 were
designed and prepared as shown in Scheme 2, and the
corresponding complexes 2a−5a were synthesized, where the
atom or group that links the bipyridyl and the phenyl rings does
not offer an acidic proton for hydrogen bonding with the
incoming carbonyl group. For ligands with oxygen (L2) and
sulfur (L3) linker atoms, the synthesis was accomplished by
Received: March 1, 2016
© XXXX American Chemical Society
A
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Scheme 1. Preparation and Regioselective Acylation of Complex 1a
Scheme 2. Synthesis of Ligands L2−L5 and Complexes 2a−5a
Buchwald−Hartwig cross-coupling of 6-bromo-2,2′-bipyridine
with phenol and thiophenol, respectively.11 The synthesis of
ligands with methylene (L4) and carbonyl (L5) linker groups
was accomplished by different synthetic strategies. Ligand L4
was synthesized by the Negishi coupling of 6-bromo-2,2′-
bipyridine with a benzyl zinc reagent12 in 74% yield. Ligand L5
was synthesized by a multistep synthesis. Lithium−bromine
exchange of 2,6-dibromopyridine with n-BuLi13 followed by
treatment of the lithiated intermediate with benzaldehyde
produced, after aqueous workup, the corresponding secondary
alcohol in 72% yield. Oxidation of the secondary alcohol with
pyridinium chlorochromate (PCC)14 gave the corresponding
ketone, which was cross-coupled with 2-pyridylzinc chloride15
to form ligand L5 in 50% yield. The cycloplatination of these
ligands with K2PtCl4 proceeds smoothly in acetic acid to give
the desired complexes 2a−5a in good to high yields (Scheme
2).
Acylation of Complexes 2a−5a. Acylation of complexes
2a−5a would allow assessment of the role of hydrogen bonding
in the regioselectivity. For example, if the acylation of 1a were
directed to the position ortho to the amino linker group by
hydrogen bonding, in the absence of hydrogen bonding,
acylation of 2a should occur, at least to some degree, at the
position para to the oxygen linker atom. In addition to the
absence of hydrogen bonding in their potential regioselective
acylation products, complexes 2a−5a also differ in electronic
richness of the phenyl groups because of the different electronic
effects of the linker atoms or groups. The electron richness of
the phenyl ring may have an effect on the acylation of the
complexes. An electron-rich phenyl ring is more susceptible to
electrophilic attack by the acylium ion, a possible step involved
in the mechanism of the reaction.
The acylation of cycloplatinated complex 1a was previously
carried out by refluxing it in a 1/1 mixture of acetic acid and
acetic anhydride.7 A long reaction time is required for complete
conversion. Cyclometalated platinum complexes generally tend
to decompose if they are heated for a prolonged period of time.
When 2a was refluxed in a 1/1 mixture of acetic acid and acetic
anhydride for 3 days, the desired compound 2b was only
isolated in 34% yield along with unreacted starting materials
(entry 1, Table 1). Considering the higher reactivity of acetyl
chloride, we decided to use an excess amount of acetyl chloride
(40 equiv) instead of acetic anhydride as the acylating reagent.
Even though acetyl chloride may react with acetic acid to form
acetic anhydride, hydrogen chloride generated in the reaction
should promote the formation of active acylium ion. Indeed,
the acylation of 2a was complete within 1 h to afford 2b in 84%
isolated yield. Since the use of acetic acid as the solvent limits
the use of acylating reagents other than acetyl halides, a series
of other solvents were screened in the reaction of 2a with acetyl
chloride. The reaction in acetonitrile with 40 equiv of acetyl
chloride was slow and black precipitates formed, likely platinum
metal, due to the decomposition of platinum complexes. The
yield of 2b was low (entry 3). The reaction in benzonitrile with
20 equiv of acetyl chloride proceeded cleanly at 150 °C and was
complete in 3 h to give 2b in 75% isolated yield. Using 1,2-
dichloroethane as the solvent afforded a 75% yield of complex
2b. When chlorobenzene and 1,2-dichlorobenzene were used,
the reaction proceeded initially but did not go to completion
even with an excess amount of the acetyl chloride. The
acylation reaction in THF and DMF did not proceed. Acetic
B
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Article
to the platinum. On the other hand, in the spectrum of 2b, the
doublet of doublets at 8.6 ppm, having the platinum satellites
overlapping with adjacent signals, can be assigned to the H
ortho to the platinum in 2b. Complexes 6a and 2b showed
different affinities on TLC: 6a moved slightly faster than 2b.
TLC analysis of the crude products from the acylation of 2a
showed that there was no formation of 6a.
Table 1. Acylation of 2a−5a under Various Conditions
The fact that acylation of complexes 2a−4a occurs at the
position ortho to the linker atom/group suggests that the
hydrogen bonding is not a necessary factor in the regiocontrol
of the acylation.
entry
X (a)
conditions
time (h)
b, yield (%)
1
2
3
4
5
6
7
8
9
O (2a)
O (2a)
O (2a)
O (2a)
O (2a)
S (3a)
AcOH/Ac2O
AcOH/AcCl
MeCN/AcCl
PhCN/AcCl
72
1
2b, 34
2b, 84
2b, 35
2b, 75
2b, 75
Substituent Effect on the Acylation Reaction. In-
troduction of a substituent to the phenyl ring in L1 would allow
us to examine the substituent effect on the acylation reaction.
Since the acylation occurs at the position ortho to the amino
linker, the electronic effect on the acylation can be elucidated
without interference of steric effects by introducing electron-
donating and electron-withdrawing groups at the position para
to the amino linker. Although the acylation of 1a occurs
regioselectively at the position ortho to the amino linker group,
which of the two ortho carbons of the phenyl ring is acylated is
unclear: namely the metalated carbon or the unmetalated
carbon (Scheme 4, R = H). By introduction of a substituent to
6
3
a
DCE /AcCl
1
b
AcOH/AcCl
AcOH/Ac2O
AcOH/AcCl
AcOH/AcCl
3
3b, 40
c
S (3a)
48
6
3b, 54
CH2 (4a)
CO (5a)
4b, 62
d
12
5b, NR
a
b
c
1,2-Dichloroethane. 12% of 3a was recovered. 24% of 3a was
recovered. No reaction.
d
acid, 1,2-dichloroethane, and benzonitrile turned out to be the
most effective solvents.
The reactions of complexes 3a and 4a with acetyl chloride in
acetic acid gave 3b and 4b in 40% and 62% yields, respectively.
In the reaction of 3a, the starting material did not decompose
and 12% of this was collected after column chromatography.
When 1/1 acetic acid/acetic anhydride was used as the solvent,
the reaction of 3a also proceeded, but not to completion. Some
of the starting material remained unreacted even after 2 days of
refluxing. A 54% yield of 3b was isolated and 24% of the
starting material 3a was recovered after column chromatog-
raphy. There was no reaction observed for complex 5a, and
93% of the starting material was recovered. This is probably due
to the electron-withdrawing effect of the carbonyl group, which
deactivates the metalated phenyl ring toward the acylation
reaction.
Scheme 4. Possible Outcomes of Acylation of Complexes
with a Substituent at the Position Meta to the Amino Linker
Group
the position meta to the amino linker, the acylated complex can
then be characterized by NMR experiments or other tools if
necessary, which allows for determination of the site of
acylation: site A or site B (Scheme 4). To this end, ligands L7−
L16 were synthesized by Buchwald−Hartwig cross-coupling of
6-bromo-2,2′-bipyridine with an aniline or phenol derivative
with a substituent on the phenyl ring. Their cycloplatination
and subsequent acylation of the formed cycloplatinated
complexes were studied. The results are summarized in Table 2.
Cycloplatination of L7−L16 proceeds smoothly to produce
7a−16a in high yields. The complexes formed cleanly as
precipitates with little to no reduction of the Pt(II) to platinum
metal, which can be easily isolated by filtration and washing
sequentially with methanol, water, and methanol. The crude
products were used directly for the subsequent acylation study.
Cyclometalation occurred at the position ortho to the linker
group. In the case of meta-substituted ligands L11−L14, the
metalation occurs at the position para to the methyl or halogen
substituent, presumably because of the steric effect of the
substituent.
1
The acylated products 2b−4b were characterized by H
1
NMR and elemental analysis. The H NMR spectra of 2b−4b
are consistent with the proposed structure resulting from an
acylation at the position ortho rather than para to the linker
atoms O, S, and C. In order to evaluate the degree of
regioselectivity, complex 6a was synthesized. Ligand L6 was
synthesized by reacting 6-bromo-2,2′-bipyridine with 4-
hydroxyacetophenone in the presence of cesium carbonate.16
Ligand L6 was then reacted with K2PtCl4 at reflux in acetic acid
to yield complex 6a (Scheme 3). This complex has an acetyl
Scheme 3. Synthesis of L6 and 6a
The reaction of complexes 7a−10a with acetyl chloride (20
equiv) in acetic acid proceeded cleanly to form the acylated
complexes 7b−10b in high yields (entries 1−4, Table 2).
Although the acylation reaction was not significantly affected by
the difference in electron richness of the phenyl ring due to the
electron-withdrawing or electron-donating effect of the
substituents, the reaction of 10a required a longer reaction
group para to the oxygen linker, making it a structural isomer of
2b. The H NMR spectra of complexes 6a and 2b show
different splitting patterns due to different positions of the
acetyl group. Whereas the spectrum of 2b consists of only
doublets and triplets, 6a shows a downfield singlet at 9.12 ppm
with platinum satellites, which can be assigned to the H ortho
1
C
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Table 2. Synthesis of Ligands L6−L16 and Complexes 6a−16a and Acylation of 6a−16a
entry
X
R
L, yield (%)
a, yield (%)
acylation conditions
time (h)
b, yield (%)
1
NH
NH
NH
NH
NH
NH
NH
NH
O
4-OMe
4-Me
L7, 51
7a, 76
AcOH/AcCl
AcOH/AcCl
AcOH/AcCl
AcOH/Ac2O
AcOH/AcCl
AcOH/AcCl
AcOH/AcCl
AcOH/AcCl
AcOH/AcCl
AcOH/AcCl
AcOH/AcCl
1
1
7b, 69
8b, 91
9b, 94
10b, 75
2
L8, 73
8a, 91
3
4-Cl
L9, 66
9a, 82
1
4
4-COOEt
3-Me
L10, 15
L11, 63
L12, 62
L13, 21
L14, 25
L15, 81
L16, 99
10a, 89
11a, 89
12a, 89
13a, 97
14a, 99
15a, 74
16a, 67
6a, 51
21
12
1
a
5
11b, NR
6
3-F
12b, 83
13b, NR
14b, NR
15b, 61
16b, 90
6b, NR
7
3-Cl
12
12
24
1
8
3-Br
10
11
12
4-OMe
4-Me
O
b
O
4-COMe
L6, 43
12
a
b
No reaction. L6 was synthesized according to a literature procedure.16
time. The regioselectivity can be easily established by the
characteristic downfield N−H signal in the 1H NMR spectra of
the acylated products, which appear in the region of 13−14
ppm due to the hydrogen bonding, while the N−H signals of
the unacylated compounds 7a−10a appear in the region of
10.5−11 ppm.
Scheme 5. Synthesis of 12c,d
Complexes 11a, 13a, and 14a were initially prepared to
examine the site of acylation; however, no reaction was
observed when these complexes reacted with 20 equiv of acetyl
chloride at reflux in acetic acid. The starting materials
essentially remained unreacted, although some decomposition
and formation of a black precipitate was observed in the
reaction of 13a after prolonged heating. These results were
initially thought to be quite disappointing, because the acylation
of these complexes would provide information on the specific
site of the regioselective reaction and should shed light on the
reaction mechanism. It is obvious that the lack of reactivity is
not due to the electronic effect of the substituents. Presumably,
the steric effect may be the factor that restricts the
regioselective acylation of complexes 11a, 13a, and 14a.
Therefore, we turned our attention to complex 12a, bearing a
fluoro substituent, because fluorine is a smaller group and the
C−F bond is shorter. To our delight, acylation of 12a with
acetyl chloride in acetic acid was completed in 1 h, and the
acylated product was isolated in 83% yield.
downfield shift of the N−H signal from 10.80 ppm in 12a
ppm to 14.01 ppm (not displayed in Figure 1) in 12c because
of the hydrogen bonding. To further establish the location of
1
the fluorine substituent, the H NMR spectrum of complex 1c
is shown in Figure 1 (top) as a comparison. The structure of 1c
has been determined by X-ray crystallography.7 The most
striking difference between the two spectra is the doublet
centered at 9.35 ppm with typical Pt satellite peaks (3JPtH = 41.3
Hz) in the spectrum of complex 1c, which is assigned to the
hydrogen proximal to the metalated carbon. The significant
downfield shift of the signal in comparison with the rest of
hydrogens on the phenyl ring is due to the deshielding effect of
the alkynyl group. The absence of such a signal with platinum
satellite peaks in a similar region of the spectrum of 12c
suggests that the fluorine group is bonded to the carbon
adjacent to the metalated carbon. In addition, the 19F NMR of
12c shows a doublet of doublets (3JFH = 8.5 Hz, 4JFH = 5.8 Hz)
at −63.04 ppm (DMSO-d6, TFA as reference at −76.55 ppm),
displaying platinum satellites with an F−Pt coupling constant of
337.7 Hz. Thus, the acylation of 12a is regiospecific and occurs
at the metalated carbon. For further comparison, phenyl-
As mentioned above, the characterization of the acylated
cycloplatinated complex 12b is the key to understanding the
regioselective acylation, but the poor solubility of complex 12b
makes it difficult to grow a crystal for X-ray structural
determination. Therefore, the chloride ligand was replaced by
a phenylacetylide to yield 12c (Scheme 5) to increase the
solubility. Although attempts to grow crystals of 12c for X-ray
structural determination have been unsuccessful, 1H NMR
spectra with reasonable quality have been obtained and used to
characterize the structure of 12c (Figure 1, middle). All signals
1
have been assigned on the basis of its H-1H COSY spectrum,
as shown in Figure 1. The protons of the phenylacetylide were
not labeled because their resonances can be easily identified in
the spectrum. The ortho acylation is confirmed by the
D
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1
Figure 1. H NMR spectra of 1c (top, NH at 13.8 ppm), 12c (middle, NH at 14.01 ppm), and 12d (bottom).
1
acetylide complex 12d was prepared from 12a, and the H
NMR spectrum of 12d is also displayed in Figure 1 (bottom).
The triplet at 8.88 ppm with platinum satellite peaks can be
assigned to the hydrogen proximal to the metalated carbon.
The triplet splitting is due to the three-bond coupling with the
adjacent hydrogen and the four-bond coupling with the
fluorine, which display very similar coupling constants.17 This
spectroscopic feature also clearly indicates that the cyclo-
platination of L12 occurs regioselectively at the carbon para to
the fluorine to produce 12a. The varied results of the acylation
reactions of complexes 11a−14a suggest that the acylation of
cycloplatinated complexes may be hindered by larger
substituents on the phenyl ring at the position meta to the
linker group.
Scheme 6. Acylation of Cyclometalated Platinum Complexes
with Benzoyl Chloride and Crotonyl Chloride
The acylation of 15a and 16a produced 15b and 16b in 61%
and 79% yields, respectively. However, the reaction of 6a did
not proceed, indicating that the electron-withdrawing acetyl
group in 6a inhibited the acylation reaction.
Use of Alternate Electrophiles. The successful use of
organic solvents such as 1,2-dichloroethane and benzonitrile
allows for electrophiles other than acetyl chloride to be used in
the reaction. Benzoyl chloride and crotonyl chloride success-
fully participated in the regioselective acylation reaction of
complex 8a to give the acylated products 8c,d in good yields
(Scheme 6). Both 1,2-dichloroethane and benzonitrile could be
used as solvents and gave comparable yields. No reaction was
observed when 2a was refluxed in 1,2-dichloroethane or
benzonitrile with 10 equiv of benzoyl chloride for 5 h. All of
the starting material was recovered. These results indicate that
the complex based on 6-phenoxy-2,2′-bipyridine is less reactive
than those based on 6-arylamino-2,2′-bipyridine and benzoyl
chloride is less reactive than acetyl chloride.
Tandem Cyclometalation−Acylation Process. As an
alternative to the two-step synthetic route of ligand complex-
ation followed by acylation, the cycloplatinated acylated
complexes can also be synthesized in a cascade cyclo-
platination−acylation reaction (Scheme 7). At reflux in acetic
acid for 18 h, ligand L2 also reacted with 1 equiv of K2PtCl4
E
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intermediate 1d. Platinum may bond to the benzene ring
through a π-allyl system (1e). The benzene ring would adopt a
perpendicular orientation to the coordination plane of the
complex. Following allylic 1,3-rearrangement to form inter-
mediate 1f, the newly metalated carbon is deprotonated and the
aromaticity of the benzene ring is restored, affording the planar
complex 1b.
Scheme 7. Cascade Cycloplatination−Acylation of L2
The electrophilic attack−platinum migration−rearomatiza-
tion mechanism is also consistent with the experimental
observations in this work. Most importantly, the unsuccessful
acylation of complexes 11a, 13a, and 14a with bulky groups
meta to the linker group can be explained in the context of this
mechanism. First of all, the electronic effect of the substituents
on 11a, 13a, and 14a should not be a factor because similar
complexes 7a−10a bearing either electron-donating or
electron-withdrawing groups were successfully acylated. Most
likely, the steric effect plays a role. The rearomatization requires
the rotation of the phenyl ring to restore the coplanar geometry
of the complex, but the rotation would suffer from unfavorable
steric effects between the platinum and the substituent, and
probably more so between the chloride ligand and the
substituent as the rotation is approaching the coplanar
geometry. Significant steric interactions caused by the methyl,
chloro, and bromo groups in 11a, 13a, and 14a prohibit the
rearomatization (Scheme 10). Therefore, the intermediate
would fall back to the starting material and the reaction favors
the more stable reactants. The cleavage of a chelating C−Pt
bond may be less favorable than deacylation. In the case of 12a,
the fluoro group is much smaller so that its steric interaction
with the chloride ligand is not significant enough to block the
rotation of phenyl ring for rearomatization. The aryl C−F bond
(1.363 Å) is slightly longer than the C−H bond (1.083 Å), but
much shorter than the aryl C−Cl (1.739 Å) and C−Br bonds
(1.899 Å).18
and 20 equiv of acetyl chloride to give 2b in 59% yield. After 1
h of the reaction, TLC analysis of the reaction mixture
indicated that L2 and 2a,b were all present in the reaction
mixture. After 18 h, there was only a small amount of the
unacylated complex 2a present, and the ligand L2 was
consumed. It should be pointed out that, in the absence of
the platinum salt, there was no acylation at the phenyl ring of
L2 under otherwise identical conditions. When the NH-bridged
ligand L1 was used, only N-acylation was detected in the
absence of the platinum salt.
Mechanisms of Acylation−Cyclometalation Reaction.
In our previous paper,7 two possible mechanisms were
proposed for the acylation of 1a. One involves a classical
Friedel−Crafts acylation at the unmetalated carbon, and the
other involves oxidative addition−reductive elimination fol-
lowed by recyclometalation. As the site of acylation has been
identified as the metalated carbon in the acylation of 12a, the
Friedel−Crafts reaction at the unmetalated carbon can be ruled
out. The oxidative addition−reductive elimination8 and
insertion−elimination9 mechanisms have been suggested for
the regioselective acylation of palladacycles; however, these
mechanisms fail to explain the fact that complexes 11a, 13a,
and 14a are not reactive toward acylation. If either of the
mechanisms were operating, for example, in the acylation of
11a, N,N-coordinated platinum complexes 11c should be
formed initially (Scheme 8), even though the steric hindrance
of the bromo group in 11a may prohibit the recyclometalation
of 11c to give 11b. Instead, the starting material 11a remained
unreacted. Electronic effects should not play a role here because
the methyl group is electron-donating.
CONCLUSIONS
■
The acylation of cyclometalated platinum complexes based on
6-substituted 2,2′-bipyridine derivatives has been investigated.
The acylation reaction is regiospecific and occurs at the
metalated carbon. The results indicate that the reaction likely
proceeds via an unprecedented electrophilic addition−platinum
migration−rearomatization cascade mechanism. The acylation
reaction of cyclometalated platinum complexes based on 6-
arylamino-2,2′-bipyridines tolerates both electron-donating and
electron-withdrawing substituents on the phenyl ring but is
affected by the steric hindrance of a substituent that is meta to
A plausible mechanism involves electrophilic attack by the
acylium ion at the metalated carbon, followed by allylic 1,3-
rearrangement (platinum migration), and finally rearomatiza-
tion with the removal of a proton, as illustrated in Scheme 9. In
this proposed mechanism, complex 1a undergoes electrophilic
attack by the acylium ion at the metalated carbon to form
Scheme 8. Possible Oxidative Addition−Reductive Elimination and Insertion−Elimination Pathways for the Acylation Reaction
of 11b
F
DOI: 10.1021/acs.organomet.6b00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Scheme 9. Proposed Mechanism: Electrophilic Attack−Platinum Migration−Rearomatization
1
Complex 3a. Yellow solid, 93%. H NMR (400 MHz, DMSO): δ
Scheme 10. Steric Effects in the Acylation of 11a, 13a, and
14a
9.57 (d, 3JHH = 5.6, 1H), 8.68 (d, JHH = 8.2 Hz, 1H), 8.52 (d, JHH
=
3
3
7.9 Hz, 1H), 8.40 (td, 3JHH = 7.9 Hz, 4JHH = 1.6 Hz, 1H), 8.29 (t, 3JHH
= 7.8 Hz, 1H), 8.13 (dd, 3JHH = 8.0 Hz, 4JHH = 1.2 Hz, 1H), 8.02 (dd,
3JHH = 7.8 Hz, JHH = 1.6 Hz, 1H), 7.94 (t, JHH = 6.5 Hz, 1H), 7.41
4
3
(dd, 3JHH = 7.5 Hz, 4JHH = 1.5 Hz, 1H), 7.00 (td, 3JHH = 7.4 Hz, 4JHH
=
1.7 Hz, 1H), 6.94 (td, 3JHH = 7.3 Hz, 4JHH = 1.6 Hz, 1H). MS: calcd for
C16H11N2PtS (M−Cl)+ 458.0; found 457.9.
1
Complex 4a. Brownish yellow solid, 87%. H NMR (400 MHz,
DMSO): δ 9.40 (d, 3JHH = 5.2, 1H), 8.62 (d, 3JHH = 8.1 Hz, 1H), 8.47
(d, 3JHH = 7.9 Hz, 1H), 8.37 (t, 3JHH = 8.2 Hz, 1H), 8.28 (t, 3JHH = 7.8
3
Hz, 1H), 8.02−7.64 (m, 3H), 7.06 (d, JHH = 6.8 Hz, 1H), 6.94−6.77
(m, 2H), 4.37 (s, 2H). MS: calcd for C17H13N2Pt (M−Cl)+ 440.1;
the amino group, which prohibits the rearomatization to form
the new carbon−platinum bond. The acylation did not proceed
when the metalated phenyl ring was sufficiently electron
deficient, which is consistent with the mechanism involving an
electrophilic addition of an acylium ion. Intramolecular
hydrogen bonding is not a required factor in the regiocontrol
of the acylation reaction. The acylation can be carried out in
several different solvents, such as acetic acid, 1,2-dichloro-
ethane, benzonitrile, and acetonitrile, and other acylating
reagents such as benzoyl chloride and crotonyl chloride have
also been used successfully.
found 440.0.
1
Complex 5a. Brown solid, 63%. H NMR (400 MHz, DMSO): δ
9.56 (d, 3JHH = 5.4 Hz, 1H), 8.82 (d, 3JHH = 8.0 Hz; Pt satellites, JPtH
3
3
3
= 88.2 Hz, 1H), 8.72 (d, JHH = 8.1 Hz, 1H), 8.58 (t, JHH3 = 7.9 Hz,
3
3
1H), 8.43 (t, JHH = 7.8 Hz, 2H), 8.31 (d, JHH = 8.0 Hz, JPtH = 46.0
Hz, 1H), 7.99 (t, JHH = 6.5 Hz, 1H), 7.84 (dd, JHH = 7.8 Hz, 4JHH
=
3
3
1.6 Hz, 1H), 7.26 (t, 3JHH = 7.3 Hz, 1H), 7.18 (t, 3JHH = 7.4 Hz, 1H).
MS: calcd for C17H11N2OPt (M − Cl)+ 454.1; found 454.0.
Complex 6a. Yellow solid, 27 mg, 51%. 1H NMR (400 MHz,
3
3
DMSO): δ 9.62 (d, JHH3 = 5.6 Hz, 1H), 9.12 (s, Pt satellites, JPtH
=
53.6 Hz, 1H), 8.74 (d, JHH = 8.2 Hz, 1H), 8.59−8.46 (m, 2H), 8.41
3
4
3
(td, JHH = 7.8 Hz, JHH = 1.6 Hz, 1H), 7.96 (t, JHH = 6.8 Hz, 1H),
3
7.78−7.65 (m, 2H), 7.26 (d, JHH = 8.4 Hz, 1H), 2.55 (s, 3H). MS:
calcd for C18H13N2O2Pt (M − Cl)+ 484.1; found 484.0.
EXPERIMENTAL SECTION
■
1
Complex 7a. Red solid, 76%. H NMR (400 MHz, DMSO): δ
All reactions involving moisture- and/or oxygen-sensitive organo-
metallic complexes were carried out under nitrogen or argon
atmosphere and anhydrous conditions. Tetrahydrofuran (THF) and
diethyl ether were distilled from sodium and benzophenone under
nitrogen before use. All other anhydrous solvents were purchased from
Aldrich Chemical Co. and were used as received. All other reagents
were purchased from chemical companies and were used as received.
NMR spectra were measured on a Bruker 400 or a Varian 500
spectrometer. Spectra were taken in CDCl3 or DMSO-d6 using
tetramethylsilane as the standard for 1H NMR chemical shifts and the
solvent peak (CDCl3, 77.0 ppm; DMSO, 39.5 ppm) as the standard for
13C NMR chemical shifts. 19F NMR spectra were measured on a
Bruker 400 using DMSO-d6 as the solvent and TFA (trifluoroacetic
acid) as the internal standard (−76.55 ppm). Coupling constants (J)
are reported in Hz. Mass spectra were measured on a Waters ESI-Q-
TOF mass spectrometer. Elemental analyses were performed at
Atlantic Microlab, Inc. Norcross, GA. Synthesis details and character-
ization data of ligands L1−L16 are provided in the Supporting
Information.
3
3
10.80 (s, 1H), 9.73 (d, JHH = 5.2 Hz, 1H), 8.63 (d, JHH = 8.4 Hz,
1H), 8.31 (t, 3JHH = 7.7 Hz, 1H), 8.25 (s, Pt satellites, 3JPtH = 36.2 Hz,
1H), 8.07 (t, 3JHH = 8.1 Hz, 1H), 7.99 (d, 3JHH = 7.1 Hz, 1H), 7.85 (t,
3JHH = 6.8 Hz, 1H), 7.51 (d, JHH = 8.3 Hz, 1H), 7.13 (d, JHH = 8.5
3
3
3
4
Hz, 1H), 6.68 (dd, JHH = 8.7 Hz, JHH = 2.9 Hz, 1H), 3.70 (s, 3H).
MS: calcd for C17H14N3OPt (M − Cl)+ 471.1; found 471.0.
Complex 8a. Bright orange solid, 91%. 1H NMR (400 MHz,
DMSO): δ 10.62 (s, 1H), 9.75 (d, 3JHH = 5.4 Hz, 1H), 8.63 (d, 3JHH
8.2 Hz, 1H), 8.41 (s, Pt satellites, 3JPtH = 33.2 Hz, 1H), 8.31 (t, 3JHH
=
=
7.7 Hz, 1H), 8.11 (t, 3JHH = 8.4 Hz, 1H), 8.02 (d, 3JHH = 7.0 Hz, 1H),
7.85 (t, 3JHH = 6.7 Hz, 1H), 7.45 (d, 3JHH = 8.5 Hz, 1H), 7.00 (d, 3JHH
3
4
= 8.0 Hz, 1H), 6.87 (dd, JHH = 8.0 Hz, JHH = 1.9 Hz, 1H), 2.21 (s,
3H). MS: calcd for C17H14N3Pt (M − Cl)+ 455.1; found 455.0.
Complex 9a. Bright orange solid, 82%. 1H NMR (400 MHz,
DMSO): δ 10.81 (s, 1H), 9.71 (d, 3JHH = 5.3 Hz, 1H), 8.66 (d, 3JHH
8.2 Hz, 1H), 8.59 (s, Pt satellites, 3JPtH = 44.0 Hz, 1H), 8.33 (t, 3JHH
=
=
7.9 Hz, 1H), 8.16 (t, 3JHH = 8.3 Hz, 1H), 8.08 (d, 3JHH = 7.3 Hz, 1H),
3
3
7.87 (t, JHH = 6.5 Hz, 1H), 7.47 (d, JHH = 8.5 Hz, 1H), 7.18−7.04
(m, 2H). MS: calcd for C16H11ClN3Pt (M − Cl)+ 475.0; found 474.9.
Complex 10a. Orange solid, 89%. 1H NMR (400 MHz, DMSO): δ
10.95 (s, 1H), 9.73 (d, 3JHH = 5.3 Hz, 1H), 9.28 (s, 1H), 8.65 (d, 3JHH
= 8.2 Hz, 1H), 8.33 (t, 3JHH = 7.6 Hz, 1H), 8.20 (t, 3JHH = 8.1 Hz, 1H),
8.11 (d, 3JHH = 7.4 Hz, 1H), 7.88 (t, 3JHH = 6.7 Hz, 1H), 7.70 (dd, 3JHH
Cycloplatination of L1−16. Synthesis of Complex 1a.7 In a 50
mL, dry, three-necked round-bottom flask with condenser and drying
tube were placed ligand L1 (40 mg, 0.25 mmol), K2PtCl4 (66 mg, 0.25
mmol), and acetic acid (6 mL). The mixture was heated at reflux for
24 h. After the mixture was cooled to room temperature, the
precipitates were collected by filtration, washed with acetic acid, water,
methanol, and ethyl acetate: yellow solid, 67 mg, 89%. Complexes 2a−
16a were synthesized using the same procedure.
3
3
= 8.4 Hz, JHH = 2.0 Hz, 1H), 7.52 (d, JHH = 8.5 Hz, 1H), 7.15 (d,
3JHH = 8.3 Hz, 1H), 4.28 (q, 3JHH = 7.1 Hz, 2H), 1.33 (t, 3JHH = 7.1 Hz,
3H). MS: calcd for C19H16N3O2Pt (M − Cl)+ 513.1; found 513.0.
1
1
Complex 11a. Red solid, 89%. H NMR (400 MHz, DMSO): δ
Complex 2a. Yellow solid, 52%. H NMR (400 MHz, DMSO): δ
3
3
3
3
10.62 (s, 1H), 9.74 (d, JHH = 5.8 Hz, 1H), 8.65 (d, JHH = 8.3 Hz,
1H), 8.45 (d, 3JHH = 8.1 Hz, 1H), 8.32 (t, 3JHH = 8.0 Hz, 1H), 8.14 (t,
3JHH = 8.4 Hz, 1H), 8.05 (d, 3JHH = 7.4 Hz, 1H), 7.86 (t, 3JHH = 6.6 Hz,
1H), 7.49 (d, 3JHH = 8.6 Hz, 1H), 6.94 (s, 1H), 6.62 (d, 3JHH = 8.2 Hz,
9.61 (d, JHH = 5.5, 1H), 8.72 (d, JHH = 8.3 Hz, 1H), 8.57−8.32 (m,
3
4H), 7.93 (t, JHH = 6.6 Hz, 1H), 7.67 (m, 1H), 7.22−7.07 (m, 2H),
3
6.97 (t, JHH = 7.4 Hz, 1H). MS: calcd for C16H11N2OPt (M − Cl)+
442.1; found 441.9.
G
DOI: 10.1021/acs.organomet.6b00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
1H), 2.27 (s, 3H). MS: calcd for C17H14N3Pt (M − Cl)+ 455.1; found
455.0.
= 7.6 Hz, 1H), 4.47 (s, 2H), 2.60 (s, 3H). Anal. Calcd for
C19H15ClN2OPt: C, 44.07; H, 2.92; N, 5.41. Found: C, 43.88; H,
2.97; N, 5.46.
Complex 12a. Orange solid, 89%. 1H NMR (400 MHz, DMSO): δ
3
3
10.80 (s, 1H), 9.73 (d, JHH = 5.6 Hz, 1H), 8.66 (d, JHH = 8.3 Hz,
1H), 8.58 (t, 3JHH = 8.4 Hz, 1H), 8.34 (t, 3JHH = 7.9 Hz, 1H), 8.19 (t,
3JHH = 8.3 Hz, 1H), 8.11 (d, 3JHH = 7.2 Hz, 1H), 7.88 (t, 3JHH = 6.5 Hz,
1H), 7.46 (d, 3JHH = 8.5 Hz, 1H), 6.93 (dd, 3JFH = 11.4 Hz, 4JHH = 2.8
Hz, 1H), 6.63 (td, 3JHH = 3JFH = 8.8 Hz, 4JHH = 2.8 Hz, 1H). MS: calcd
for C16H11FN3Pt (M − Cl)+ 459.1; found 459.0.
Complex 7b. Dark red solid, 69%. 1H NMR (400 MHz, DMSO): δ
3
3
13.49 (s, 1H), 9.72 (d, JHH = 5.6 Hz, 1H), 8.67 (d, JHH = 8.4 Hz,
4
3
4
1H), 8.65 (d, JHH = 3.1 Hz, 1H), 8.35 (td, JHH = 7.9 Hz, JHH = 1.7
Hz, 1H), 8.19 (t, 3JHH = 8.3 Hz, 1H), 8.12 (d, 3JHH = 7.6 Hz, 1H), 7.89
(t, 3JHH = 6.6 Hz, 1H), 7.45 (d, 3JHH = 8.4 Hz, 1H), 7.42 (d, 4JHH = 3.0
Hz, 1H), 3.80 (s, 3H), 2.77 (s, 3H). Anal. Calcd for
C19H16ClN3O2Pt.0.5CH2Cl2: C, 39.61; H, 2.90; N, 7.11. Found: C,
39.33; H, 2.81; N, 7.12.
Complex 13a. Orange solid, 82%. 1H NMR (400 MHz, DMSO): δ
3
3
10.79 (s, 1H), 9.70 (d, JHH = 5.7 Hz, 1H), 8.65 (d, JHH = 8.2 Hz,
1H), 8.57 (d, 3JHH = 8.6 Hz, 1H), 8.33 (t, 3JHH = 7.8 Hz, 1H), 8.18 (t,
3JHH = 8.3 Hz, 1H), 8.09 (d, 3JHH = 7.5 Hz, 1H), 7.87 (t, 3JHH = 6.6 Hz,
1
Complex 8b. Red solid, 91%. H NMR (400 MHz, DMSO): δ
3
4
13.63 (s, 1H), 9.74 (d, JHH = 5.7 Hz, 1H), 8.77 (d, JHH = 1.6 Hz,
3
3
4
3
3
1H), 8.68 (d, JHH = 8.2 Hz, 1H), 8.35 (td, JHH = 7.6 Hz, JHH = 1.6
Hz, 1H), 8.22 (t, 3JHH = 8.3 Hz, 1H), 8.15 (d, 3JHH = 7.5 Hz, 1H), 7.90
(t, 3JHH = 6.7 Hz, 1H), 7.75 (d, 4JHH = 1.2 Hz 1H), 7.46 (d, 3JHH = 8.5
Hz, 1H), 2.76 (s, 3H), 2.30 (s, 3H). Anal. Calcd for C19H16ClN3OPt:
C, 42.82; H, 3.03; N, 7.89. Found: C, 42.65; H, 2.97; N, 7.82.
Complex 8c. In a 25 mL three-necked round-bottom flask with
condenser and drying tube were placed 8a (40 mg, 0.081 mmol),
benzoyl chloride (47 μL, 0.41 mmol), and 1,2-dichloroethane (5 mL).
The mixture was stirred and heated at reflux for 24 h. After the mixture
was cooled to room temperature, the solvent was evaporated and the
product was collected by suction filtration and washed with hexane,
1H), 7.45 (d, JHH = 8.6 Hz, 1H), 7.16 (d, JHH = 2.3 Hz, 1H), 6.79
3
4
(dd, JHH = 8.7 Hz, JHH = 2.4 Hz, 1H). MS: calcd for C16H11ClN3Pt
(M − Cl)+ 475.0; found 474.9.
Complex 14a. Orange solid, 99%. 1H NMR (400 MHz, DMSO): δ
3
3
10.78 (s, 1H), 9.71 (d, JHH = 5.5 Hz, 1H), 8.66 (d, JHH = 8.3 Hz,
1H), 8.52 (d, 3JHH = 8.6 Hz, 1H), 8.33 (t, 3JHH = 7.5 Hz, 1H), 8.19 (t,
3JHH = 8.1 Hz, 1H), 8.10 (d, 3JHH = 7.2 Hz, 1H), 7.87 (t, 3JHH = 6.6 Hz,
3
3
1H), 7.45 (d, JHH = 8.5 Hz, 1H), 7.30 (d, JHH = 2.1 Hz, 1H), 6.91
3
3
(dd, JHH = 8.5 Hz, JHH = 2.1 Hz, 1H). MS: calcd for C16H11BrN3Pt
(M − Cl)+ 519.0; found 518.9.
Complex 15a. Orange solid, 74%. 1H NMR (400 MHz, DMSO): δ
1
3
3
water, and methanol: 8c, yellow solid, 35.2 mg, 72%. H NMR (400
9.60 (d, JHH = 5.5 Hz, 1H), 8.70 (d, JHH = 8.1 Hz, 1H), 8.57−8.31
MHz, DMSO): δ 12.58 (s, 1H), 9.76 (d, 3JHH = 5.6 Hz, 1H), 8.81 (d,
4JHH = 2.0 Hz, 1H), 8.71 (d, 3JHH = 8.3 Hz, 1H), 8.37 (t, 3JHH = 7.7 Hz,
1H), 8.24 (t, 3JHH = 8.2 Hz, 1H), 8.19 (d, 3JHH = 8.0 Hz, 1H), 7.91 (t,
(m, 3H), 8.00 (d, 4JHH = 3.1 Hz, 1H), 7.92 (t, 3JHH = 6.9 Hz, 1H), 7.62
3
3
3
(t, JHH = 4.8 Hz, 1H), 7.12 (d, JHH = 8.8 Hz, 1H), 6.70 (dd, JHH
=
8.9 Hz, 4JHH = 3.1 Hz, 1H), 3.72 (s, 3H). MS: calcd for C17H13N2O2Pt
(M − Cl)+ 472.1; found 472.0.
4
3JHH = 6.6 Hz, 1H), 7.73−7.50 (m, 6H), 7.14 (d, JHH = 2.0 Hz, 1H),
Complex 16a. Yellow-orange solid, 67%. 1H NMR (400 MHz,
2.20 (s, 3H). Anal. Calcd for C24H18ClN3OPt: C, 48.45; H, 3.05; N,
7.06. Found: C, 48.38; H, 2.96; N, 7.18.
3
3
DMSO): δ 9.60 (d, JHH = 5.1 Hz, 1H), 8.89 (d, JHH = 8.1 Hz, 1H),
8.51−8.33 (m, 3H), 8.21 (s, Pt satellites, 3JPtH = 54.6 Hz, 1H), 7.91 (t,
3JHH = 6.9 Hz, 1H), 7.61 (dd, 3JHH = 6.9 Hz, 4JHH = 2.8 Hz, 1H), 7.04
(d, 3JHH = 8.2 Hz, 1H), 6.92 (d, 3JHH = 8.0 Hz, 1H), 2.24 (s, 3H). MS:
calcd for C17H13N2OPt (M − Cl)+ 456.1; found 456.0.
Complex 8d. In a 50 mL three-necked round-bottom flask fitted
with a condenser and drying tube were placed 8a (50 mg, 0.1 mmol),
crotonyl chloride (100 μL, 1.0 mmol), and benzonitrile (5 mL). The
reaction mixture was stirred and heated at 150 °C for 1 h. After
cooling, the product was precipitated from the reaction mixture with 5
mL of hexane and collected by filtration. The product was purified by
column chromatography on silica gel with dichloromethane and then
dichloromethane and ethyl acetate (v/v 40/1): bright orange solid, 40
mg, 72%. 1H NMR (400 MHz, DMSO): δ 13.77 (s, 1H), 9.74 (d, 3JHH
Acylation Reactions. Preparation of 2b: General Procedure. In a
25 mL three-necked round-bottom flask with condenser and drying
tube were placed 2a (50 mg, 0.1 mmol), acetic acid (5 mL), and acetyl
chloride (1 mL). The mixture was stirred and heated at reflux for 1 h.
The mixture was stirred and heated at reflux for 1 h. After the solvent
was evaporated, the crude product was dissolved in dichloromethane
and purified by column chromatography on silica gel first with
dichloromethane and then with dichloromethane and ethyl acetate (v/
v 1/1): 2b, yellow solid, 45.4 mg, 84%. 1H NMR (400 MHz, DMSO):
4
3
= 5.7 Hz, 1H), 8.77 (d, JHH = 1.6 Hz, 1H), 8.67 (d, JHH = 8.2 Hz,
3
4
3
1H), 8.34 (td, JHH = 7.9 Hz, JHH = 1.7 Hz, 1H), 8.22 (t, JHH = 7.9
Hz, 1H), 8.15 (dd, 3JHH = 7.6 Hz, 4JHH = 1.1 Hz, 1H), 7.89 (td, 3JHH
=
4
4
6.8 Hz, JHH = 1.2 Hz, 1H), 7.82 (d, JHH = 1.9 Hz, 1H), 7.50−7.43
(m, 2H), 7.09 (m, 1H), 2.30 (s, 3H), 2.03 (d, JHH = 7.0 Hz, 3H).
3
3
3
δ 9.61 (d, JHH = 5.1 Hz, 1H), 8.75 (d, JHH = 8.1 Hz, 1H), 8.59 (dd,
3JHH = 7.9 Hz, JHH = 1.7 Hz, 1H), 8.50 (d, JHH = 5.1 Hz, 2H), 8.41
(td, JHH = 8.0 Hz, JHH = 1.5 Hz, 1H), 7.96 (t, JHH = 6.7 Hz, 1H),
7.74 (t, JHH = 4.8 Hz, 1H), 7.33 (dd, JHH = 7.3 Hz, JHH = 1.7 Hz,
1H), 7.05 (t, JHH = 7.6 Hz, 1H), 2.73 (s, 3H). Anal. Calcd for
4
3
Anal. Calcd for C21H18ClN3OPt: C, 45.13; H, 3.25; N, 7.52. Found: C,
44.99; H, 3.07; N, 7.55.
3
4
3
3
3
4
In a 50 mL three-necked round-bottom flask fitted with a condenser
and drying tube were placed 8a (50 mg, 0.1 mmol), crotonoyl chloride
(100 μL, 1.0 mmol), and 1,2-dichloroethane (5 mL). The reaction
mixture was stirred and heated to reflux for 5 h. After cooling, the
product was precipitated from the reaction mixture with 5 mL of
hexane and collected by filtration. The product was purified by column
chromatography on silica gel with dichloromethane and then
dichloromethane and ethyl acetate (v/v 40/1): bright orange solid,
45 mg, 79%.
3
C18H13ClN2O2Pt: C, 41.59; H, 2.52; N, 5.39. Found: C, 41.59; H,
2.45; N, 5.45. Following the general procedure, acylation of 2a with
acetic acid/acetic anhydride, AcCl (20 equiv) in acetic acid,
acetonitrile, benzonitrile, and 1,2-dichloroethane gave 2b in 34%,
77%, 35%, 75%, and 75% yields, respectively.
The following compounds were prepared following the general
procedure by using acetyl chloride and with acetic acid as the solvent
unless specified otherwise.
1
Complex 9b. Red solid, 94%. H NMR (400 MHz, DMSO): δ
13.50 (s, 1H), 9.68 (d, 3JHH = 5.5 Hz, 1H), 8.88 (s, Pt satellites, 3JPtH
=
1
Complex 3b. Orange solid, 40%. H NMR (400 MHz, DMSO): δ
3
3
9.49 (d, 3JHH = 5.6 Hz, 1H), 8.67 (d, 3JHH = 8.2 Hz, 1H), 8.50 (d, 3JHH
48.0 Hz, 1H), 8.69 (d, JHH = 8.3 Hz, 1H), 8.37 (td, JHH = 7.9 Hz,
4JHH = 1.6 Hz, 1H), 8.26 (t, 3JHH = 8.2 Hz, 1H), 8.19 (d, 3JHH = 7.5 Hz,
1H), 7.94 (d, 4JHH = 2.4 Hz, 1H), 7.90 (t, 3JHH = 6.8 Hz, 1H), 7.49 (d,
3JHH = 8.2 Hz, 1H), 2.78 (s, 3H). Anal. Calcd for C18H13Cl2N3OPt: C,
39.07; H, 2.37; N, 7.59. Found: C, 39.23; H, 2.22; N, 7.62.
3
4
= 8.1 Hz, 1H), 8.40 (td, JHH = 7.9 Hz, JHH = 1.6 Hz, 1H), 8.24 (t,
3JHH = 8.0 Hz, 1H), 8.17−8.00 (m, 2H), 7.94 (t, JHH = 6.6 Hz, 1H),
3
3
4
3
7.60 (dd, JHH = 7.4 Hz, JHH = 1.5 Hz, 1H), 7.00 (t, JHH = 7.7 Hz,
1H), 2.63 (s, 3H). Anal. Calcd for C18H13ClN2OPtS: C, 40.34; H,
2.45; N, 5.23. Found: C, 39.94; H, 2.56; N, 5.25.
Complex 10b. In a 25 mL three-necked round-bottom flask with
condenser and drying tube were placed 10a (40 mg, 0.072 mmol),
acetic acid (3 mL), and acetic anhydride (3 mL). The mixture was
stirred and heated at reflux for 21 h. After cooling to room
temperature, water (3 mL) was added and the precipitate was filtered
and washed with hexane, methanol, water, and ethyl acetate: 10b,
1
Complex 4b. Brownish yellow solid, 68%. H NMR (400 MHz,
DMSO): δ 9.37 (d, JHH = 5.5 Hz, 1H), 8.62 (d, JHH = 8.0 Hz, 1H),
8.46 (d, JHH = 8.1 Hz, 1H), 8.38 (td, JHH = 7.9 Hz, JHH = 1.6 Hz,
1H), 8.27 (t, 3JHH = 7.8 Hz, 1H), 8.03−7.86 (m, 2H), 7.79 (d, 3JHH
7.8 Hz, 1H), 7.29 (dd, 3JHH = 7.6 Hz, 4JHH = 1.3 Hz, 1H), 6.93 (t, 3JHH
3
3
3
3
4
=
H
DOI: 10.1021/acs.organomet.6b00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
orange solid, 35.4 mg, 75%. 1H NMR (400 MHz, DMSO): δ 13.76 (s,
1H), 9.72 (d, 3JHH = 5.7 Hz, 1H), 9.52 (d, 4JHH = 2.0 Hz; Pt satellites,
spectra of complexes 2a−16a, 2b−4b, 7b−10b, 8c,d,
12b, 15b, and 16b (PDF)
3
3JPtH = 36.2 Hz, 1H), 8.71 (d, JHH = 8.1 Hz, 1H), 8.47 (d, 4JHH = 2.0
3
3
Hz, 1H), 8.37 (t, JHH = 8.0 Hz, 1H), 8.31 (t, JHH = 8.2 Hz, 1H),
AUTHOR INFORMATION
Corresponding Author
*E-mail for S.H.: huos@ecu.edu.
3
3
■
8.28−8.22 (m, 1H), 7.92 (t, JHH = 6.6 Hz, 1H), 7.56 (d, JHH = 8.4
Hz, 1H), 4.35 (q, 3JHH = 7.2 Hz, 2 H), 2.81 (s, 3H), 1.36 (t, 3JHH = 7.1
Hz, 3H). Anal. Calcd for C21H18ClN3O3Pt: C, 42.68; H, 3.07; N, 7.11.
Found: C, 42.79; H, 3.16; N, 6.81.
Notes
Complex 12b. Orange solid, 94%. 1H NMR (400 MHz, DMSO): δ
The authors declare no competing financial interest.
3
3
13.64 (s, 1H), 9.67 (d, JHH = 5.6 Hz, 1H), 8.66 (d, JHH = 8.1 Hz,
3
1H), 8.38 (t, JHH = 7.7 Hz, 1H), 8.27−8.16 (m, 2H), 8.04−7.91 (m,
ACKNOWLEDGMENTS
3
3
3
■
2H), 7.49 (d, JHH = 8.2 Hz, 1H), 6.69 (t, JFH = JHH = 8.8 Hz, 1H),
2.73 (s, 3H). Anal. Calcd for C18H13ClFN3OPt: C, 40.27; H, 2.44; N,
7.83. Found: C, 40.28; H, 2.32; N, 7.78.
Acknowledgment is made to the donors of the American
Chemical Society Petroleum Research Fund (51147UR3),
Burroughs-Wellcome fellowship (J.C. and R.M.), and ECU
Undergraduate Research and Creative Activity Award
(H.G.W.).
Complex 15b. Orange solid, 16% recovered. The second band gave
15b, orange solid, 61%. 1H NMR (400 MHz, DMSO): δ 9.58 (d, 3JHH
3
3
= 5.4 Hz, 1H), 8.72 (d, JHH = 8.1 Hz, 1H), 8.46 (d, JHH = 4.8 Hz,
2H), 8.40 (t, 3JHH = 7.7 Hz, 1H), 8.16 (d, JHH = 3.2 Hz; Pt satellites,
4
3JPtH = 52 Hz, 1H), 7.94 (t, 3JHH = 6.5 Hz, 1H), 7.69 (t, 3JHH = 4.8 Hz,
REFERENCES
4
■
1545.
1H), 6.85 (d, JHH = 3.2 Hz, 1H), 3.75 (s, 3H), 2.73 (s, 3H). Anal.
(1) Kleiman, J. P.; Dubeck, M. J. Am. Chem. Soc. 1963, 85, 1544−
Calcd for C19H15ClN2O3Pt: C, 41.50; H, 2.75; N, 5.09. Found: C,
41.73; H, 2.60; N, 5.25.
(2) Cope, A. C.; Siekman, R. W. J. Am. Chem. Soc. 1965, 87, 3272−
3273.
Complex 16b. Yellow solid, 90%. 1H NMR (400 MHz, DMSO): δ
3
3
9.59 (d, JHH = 5.7 Hz, 1H), 8.72 (d, JHH = 8.2 Hz, 1H), 8.52−8.28
(m, 4H), 7.93 (t, 3JHH = 6.6 Hz, 1H), 7.69 (t, 3JHH = 4.8 Hz, 1H), 7.11
(d, JHH = 2.1 Hz, 1H), 2.70 (s, 3H), 2.25 (s, 3H). Anal. Calcd for
(3) For selected reviews, see: (a) Bruce, M. I. Angew. Chem., Int. Ed.
Engl. 1977, 16, 73−86. (b) Omae, I. Chem. Rev. 1979, 79, 287−321.
(c) Newkome, G. R.; Puckett, W. E.; Gupta, V. K.; Kiefer, G. E. Chem.
Rev. 1986, 86, 451−489. (d) Dunina, V. V.; Zalevskaya, O. A.;
Potapov, V. M. Russ. Chem. Rev. 1988, 57, 434−473. (e) Ryabov, A. D.
Chem. Rev. 1990, 90, 403−424. (f) van der Boom, M. E.; Milstein, D.
Chem. Rev. 2003, 103, 1759−1792. (g) Lowry, M. S.; Bernhard, S.
Chem. - Eur. J. 2006, 12, 7970−7977. (h) Albrecht, M. Chem. Rev.
2010, 110, 576−623. (i) Omae, I. J. Organomet. Chem. 2011, 696,
1128−1145. (j) van Koten, G. Top. Organomet. Chem. 2013, 40, 1−20.
(k) Omae, I. Coord. Chem. Rev. 2014, 280, 84−95. (l) Lobana, T. S.
RSC Adv. 2015, 5, 37231−31274.
(4) For selected reviews, see: (a) Dehand, J.; Pfeffer, M. Coord. Chem.
Rev. 1976, 18, 327−352. (b) Ryabov, A. D. Synthesis 1985, 1985, 233−
252. (c) Albrecht, M.; van Koten, G. Angew. Chem., Int. Ed. 2001, 40,
3750−3781. (d) Omae, I. J. Organomet. Chem. 2007, 692, 2608−2854.
(e) Palladacycles: Synthesis, Characterization and Applications; Dupont,
J., Pfeffer, M., Eds.; Wiley-VCH: Weinheim, Germany, 2008.
(5) Tan, K.-W.; Yang, X.-Y.; Li, Y.; Huang, Y.; Pullarkat, S. A.; Leung,
P.-H. Organometallics 2012, 31, 8407−8413.
(6) For selected reviews, see: (a) Lai, S.-W.; Che, C.-M. Top. Curr.
Chem. 2004, 241, 27−63. (b) Williams, G. J. A.; Develay, S.;
Rochester, D. L.; Murphy, L. Coord. Chem. Rev. 2008, 252, 2596−
2611. (c) Thorp-Greenwood, F. L. Organometallics 2012, 31, 5686−
5692. (d) Huo, S.; Carroll, J.; Vezzu, D. A. K. Asian J. Org. Chem. 2015,
4, 1210−1245.
(7) Carroll, J.; Gagnier, J. P.; Garner, A. W.; Moots, J. G.; Pike, R. D.;
Li, Y.; Huo, S. Organometallics 2013, 32, 4828−4836.
(8) Holton, R. A.; Natalie, K. J., Jr. Tetrahedron Lett. 1981, 22, 267−
270.
4
C19H15ClN2O2Pt·0.25 CH2Cl2: C, 41.65; H, 2.81; N, 5.05. Found: C,
41.46; H, 2.73; N, 5.17.
Preparation of Phenylacetylide Complexes. Preparation of
Complex 12c. In a 50 mL three-necked round-bottom flask under
argon were placed complex 12b (100 mg, 0.19 mmol), phenyl-
acetylene (61 μL, 0.66 mmol), copper iodide (2.8 mg, 0.015 mmol),
triethylamine (1.7 mL, 12.1 mmol), and anhydrous dichloromethane
(15 mL). The reaction mixture was stirred at room temperature for 1 h
and then quenched with water (15 mL) and extracted with
dichloromethane. The organic phase was washed with brine and
dried over MgSO4. After filtration, the solvent was removed and the
crude product was purified by column chromatography on silica gel
with dichloromethane and ethyl acetate (v/v 3/1): red solid, 80 mg,
71%. 1H NMR (400 MHz, DMSO): δ 14.01 (s, 1H), 10.10 (d, 3JHH
=
=
3
3
5.5 Hz, 1H), 8.71 (d, JHH = 8.2 Hz, 1H), 8.39 (td, JHH = 7.9, 4JHH
3
3
1.5 Hz, 1H), 8.31−8.20 (m, 2H), 8.07 (dd, JFH = 8.7 Hz, JHH = 5.7
Hz, 1H), 7.95 (t, 3JHH = 6.6 Hz, 1H), 7.56 (d, 3JHH = 8.3, 1H), 7.40−
7.26 (m, 4H), 7.16 (t, JHH = 7.3 Hz, 1H), 6.78 (t, JFH = JHH = 8.7
Hz, 1H), 2.77 (s, 3H). 19F NMR (376.46 Hz, DMSO): δ − 63.04 (dd,
3
3
3
4
3
3JFH = 8.5, JFH = 5.8 Hz; Pt satellites, JPtF = 337.7 Hz). Anal. Calcd
for C26H18FN3OPt·0.25CH2Cl2: C, 50.55; H, 2.99; N, 6.74. Found: C,
50.45; H, 3.26; N, 6.57.
Preparation of 12d. This compound was prepared from 12a using
the same procedure described above for 12c: red solid, 76%. 1H NMR
(400 MHz, DMSO): δ 10.74 (s, 1H), 9.89 (dd, 3JHH = 5.7 Hz, 4JHH
=
0.9 Hz, 1H), 8.88 (t, 3JHH = 8.4 Hz; Pt satellites, 3JPtH = 72.3 Hz, 1H),
3
3
4
8.60 (d, JHH = 8.2 Hz, 1H), 8.35 (td, JHH = 7.9 Hz, JHH = 1.6 Hz,
3
3
1H), 8.16 (m, 2H), 7.87 (t, JHH = 6.6 Hz, 1H), 7.54 (dd, JHH = 8.8
Hz, 4JHH = 0.8 Hz, 1H), 7.43 (dd, JHH = 6.8 Hz, 3JHH = 1.2 Hz, 2H),
3
(9) Clark, P. W.; Dyke, H. J.; Dyke, S. F.; Perry, G. J. Organomet.
Chem. 1983, 253, 399−413.
3
3
4
7.31 (t, JHH = 7.8 Hz, 2H), 7.20 (tt, JHH = 7.4 Hz, JHH = 1.3 Hz,
3
4
3
1H), 6.99 (dd, JFH = 11.6 Hz, JHH = 2.7 Hz, 1H), 6.63 (td, JFH
=
(10) Zucca, A.; Cinellu, M. A.; Pinna, M. V.; Stoccoro, S.; Minghetti,
G.; Manassero, M.; Sansoni, M. Organometallics 2000, 19, 4295−4304.
(11) Hartwig, J. Palladium-catalyzed amination of aryl halides and
related reactions. In Handbook of Organopalladium Chemistry for
Organic Synthesis; Negishi, E., Ed.; Wiley: New York, 2002; Vol. 1, pp
1051−1096.
4
3JHH = 8.6 Hz, JHH = 2.8 Hz, 1H). Anal. Calcd for C24H16FN3Pt·
0.25CH2Cl2: C, 50.07; H, 2.86; N, 7.22. Found: C, 50.07; H, 2.84; N,
7.51.
ASSOCIATED CONTENT
■
(12) (a) Negishi, E.; King, A. O.; Okukado, N. J. Org. Chem. 1977,
42, 1821−1823. (b) Minato, A.; Tamao, K.; Hayashi, T.; Suzuki, K.;
Kumada, M. Tetrahedron Lett. 1980, 21, 845−848.
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.6b00174.
(13) Cai, D.; Hughes, D. L.; Verhoeven, T. R. Tetrahedron Lett. 1996,
37, 2537−2540.
(14) (a) Corey, E. J.; Suggs, J. W. Tetrahedron Lett. 1975, 16, 2647−
2650. (b) Piancatelli, G.; Scettri, A.; D’Auria, M. Synthesis 1982, 1982,
245−258.
1
Synthesis and characterization data of L1−L16, H and
1
13C NMR spectra of the ligands L2−L16, and H NMR
I
DOI: 10.1021/acs.organomet.6b00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
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DOI: 10.1021/acs.organomet.6b00174
Organometallics XXXX, XXX, XXX−XXX