Pd-PEPPSI: A General Pd-NHC Precatalyst for Suzuki-Miyaura Cross-Coupling of Esters by C-O Cleavage

Article abstract of DOI:10.1021/acs.organomet.7b00565

The Suzuki-Miyaura cross-coupling of aryl esters by selective C-O bond cleavage represents a powerful methodology in organic synthesis. Here, we report that versatile, easily prepared, well-defined Pd-PEPPSI type precatalysts serve as highly reactive catalysts for the direct Suzuki-Miyaura cross-coupling of esters. Sterically and electronically diverse aryl esters couple with arylboronic acids in good to excellent yields using a single, operationally simple protocol. Kinetic studies demonstrate that the cross-coupling of aryl esters proceeds with rates similar to the cross-coupling of amides. This study strongly supports the use of well-defined Pd(II)-NHC precatalysts bearing pyridine throw-away ligands for the selective C(acyl) cleavage of bench-stable carboxylic acid derivatives. Considering the modular scaffold of Pd-NHC precatalysts, we envision that the method will be of general interest for the development of new catalysts for C-O cleavage reactions.

Full text of DOI:10.1021/acs.organomet.7b00565

Article
pubs.acs.org/Organometallics
Pd-PEPPSI: A General Pd-NHC Precatalyst for Suzuki−Miyaura Cross-
Coupling of Esters by C−O Cleavage
Shicheng Shi,† Peng Lei,† and Michal Szostak*
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States
S
* Supporting Information
ABSTRACT: The Suzuki−Miyaura cross-coupling of aryl
esters by selective C−O bond cleavage represents a powerful
methodology in organic synthesis. Here, we report that
versatile, easily prepared, well-defined Pd-PEPPSI type
precatalysts serve as highly reactive catalysts for the direct
Suzuki−Miyaura cross-coupling of esters. Sterically and
electronically diverse aryl esters couple with arylboronic
acids in good to excellent yields using a single, operationally
simple protocol. Kinetic studies demonstrate that the cross-coupling of aryl esters proceeds with rates similar to the cross-
coupling of amides. This study strongly supports the use of well-defined Pd(II)-NHC precatalysts bearing pyridine “throw-away”
ligands for the selective C(acyl) cleavage of bench-stable carboxylic acid derivatives. Considering the modular scaffold of Pd-
NHC precatalysts, we envision that the method will be of general interest for the development of new catalysts for C−O cleavage
reactions.
xidative addition of a metal to acyl electrophile represents
a fundamental step in catalysis.1 Historically, the use of
cross-coupling of aryl esters proceeds with rates similar to those
for the cross-coupling of amides. Considering the modular
scaffold of Pd(II)-NHC precatalysts bearing a pyridine “throw-
away” ligand,17 we envision that the method will be of general
interest for the development of new catalysts for acyl C−O
cleavage reactions.18
The use of Pd-PEPPSI catalysts in the acyl C−O coupling
manifold involves two immediate advantages. (i) PEPPSI type
complexes are prepared in a single operationally straightforward
step, which is typically not the case with other Pd-NHC type
complexes. This may facilitate a general use of Pd-NHC
catalysts in ester C−O cross-couplings. (ii) A variety of PEPPSI
type complexes can be easily accessed by appending alkyl or
halide groups on the NHC scaffold, which may result in the
development of even more active catalysts for the acyl C−O
cross-coupling. We also report for the first time that, in terms of
steric demand, IPr may be the preferred NHC scaffold for
achieving high efficiency in the acyl cross-coupling, consistent
with the steric properties of acyl-Pd complexes.2a
Our motivation for studying Pd-PEPPSI type precatalysts for
the Suzuki−Miyaura cross-coupling of esters stems from their
unique catalytic properties are as follows. (1) Pd-PEPPSI
complexes are among the most active catalysts for palladium-
catalyzed cross-coupling reactions.14 (2) PEPPSI types of Pd-
NHC complexes represent a modular class of Pd-NHC
catalysts, which is crucial for the rational design of catalysts
through changes in the ancillary and throw-away ligand.18 (3)
PEPPSI type complexes are easy and inexpensive to
O
aryl esters in cross-coupling manifolds has been difficult due to
the low reactivity of the C−O bond toward metal insertion as a
result of nO → π*CO conjugation.2,3 A recent advance has
been the development of an array of decarbonylative cross-
couplings of common aryl esters fueled by the design of new
electron-rich, chelating phosphine ligands for Ni and Pd to
trigger oxidative addition.4,5 Intriguingly, the ability to promote
previously inaccessible catalytic pathways engaging ubiquitous
C−O bonds offers a unique potential to develop valuable bond-
forming reactions in chemical synthesis.
Recently, our laboratory introduced a new amide bond
activation manifold that allows the activation and subsequent
cross-coupling of the C−N acyl amide bond via ground-state
destabilization.6−8 Expanding upon this theme, we recently
demonstrated that this amide activation platform could be
extended to the cross-coupling of aryl esters.9 This catalytic
manifold hinges on the decreased rotational barrier in aryl
esters (ER = 9.3 kcal/mol) and ground-state-destabilized amides
(ER < 10 kcal/mol)10 to enable selective metal insertion into
the acyl bond using synthetically attractive bench-stable
carboxylic acid derivatives.11,12 The prevalence of aryl esters
in organic synthesis provides new avenues for modular cross-
coupling processes of common electrophiles.
To realize the full potential of the acyl cross-coupling
manifold, it is critical that it be possible to employ new general
catalyst systems that operate under operationally simple
conditions.
In this article, we report that versatile, easily prepared, well-
defined Pd-PEPPSI type precatalysts13−15 serve as highly
reactive catalysts for the direct Suzuki−Miyaura cross-
coupling16 of esters. Moreover, we demonstrate that the
Received: July 25, 2017
© XXXX American Chemical Society
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DOI: 10.1021/acs.organomet.7b00565
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prepare,14,15 which may spearhead the widespread use of acyl
cross-couplings in organic synthesis.
Various PEPPSI type catalysts were screened under different
conditions for the model reaction between phenyl benzoate
(1a) and 4-tolylboronic acid (2b) (Table 1). The optimized
C−O acyl cross-coupling, and (2) changes in the “throw-away”
ligand attached to the palladium center may lead to the
development of more active catalysts for cross-coupling.18
Finally, the use of close to stoichiometric amounts of base and
boronic acid leads to efficient coupling, providing an entry
point for further development (entries 15−18).
a
The scope of this cross-coupling was next investigated (Table
2). As shown, the reaction accommodates a broad range of
Table 1. Optimization of the Reaction Conditions
Table 2. Pd-PEPPSI-Catalyzed Suzuki−Miyaura Cross-
a b
,
Coupling of Esters
b
entry
catalyst
base
solvent
T (°C)
yield (%)
1
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4c
4d
4e
4a
4a
4a
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
KOH
THF
toluene
dioxane
DME
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
80
80
80
80
80
80
80
80
60
40
110
80
80
80
80
80
80
80
84
80
83
48
69
32
13
<5
76
39
88
75
53
42
45
72
75
71
2
3
4
5
6
7
Cs2CO3
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
8
9
10
11
12
13
14
15
c
16
d
17
e
18
a
Conditions unless stated otherwise: 1 (1.0 equiv), R-B(OH)2 (3.0
equiv), [Pd] (3 mol %), K2CO3 (4.5 equiv), THF (0.80 mL), T, 16 h.
b
c
d
GC/1H NMR yields. K2CO3 (1.0 equiv). R-B(OH)2 (1.2 equiv).
e
K2CO3 (1.0 equiv), R-B(OH)2 (1.2 equiv).
a
Conditions unless stated otherwise: ester, Ar-B(OH)2 (3.0 equiv),
[4a] (3 mol %), K2CO3 (4.5 equiv), THF (0.80 mL), 80 °C, 16 h.
b
c
Isolated yields. [4a] (6 mol %).
catalyst system uses Pd-PEPPSI-IPr (3 mol %), 4-Tol-B(OH)2
(3.0 equiv), K2CO3 (4.5 equiv), THF, and 80 °C, affording the
desired product in 84% yield. Selected optimization results are
summarized in Table 1. THF, toluene, and dioxane proved to
be the most effective solvents (entries 1−4). The reaction
showed strong dependence on the base used, with K2CO3 and
K3PO4 providing the best results (entries 5−8). The reaction
showed good efficiency at temperatures as low as 40 °C
(entries 9 and 10). Increasing the temperature to 110 °C did
not significantly affect the reaction (entry 11). The reaction was
inefficient at room temperature. As anticipated, the reaction
showed a profound dependence on the PEPPSI type scaffold
(entries 11−14). The pyridine “throw-away” ligand 4b cleanly
produced the coupling product (entry 11). A 1-methylimida-
zole ligand (4c) at the palladium also resulted in efficient cross-
coupling (entry 12), with no observable side products.
Intriguingly, the use of the more bulky PEPPSI-IPent (4d)14b
and less sterically demanding PEPPSI-IMes (4e) gave inferior
results (entries 13 and 14). Overall, these findings suggest that
(1) PEPPSI-IPr may serve as a privileged NHC scaffold for the
ester and boronic acid cross-coupling partners. Electronically
diverse ester electrophiles are well-tolerated in this coupling
(3a−d), including deactivated electron-rich arenes (3d).
Sensitive electrophilic functional groups such as alkyl esters
(3e) are readily accommodated. Sterically demanding esters
(3f) and even sensitive substrates such as polyfluorinated (3g),
heterocyclic (3h), and aliphatic esters (3i) were smoothly
converted into the desired products. The scope of the boronic
acid component is also broad. In general, high to excellent
yields of the cross-coupling products were obtained for
electron-neutral (3b′), electron-rich (3c′), electron-deficient
(3j,e′), and sterically demanding (3f′,l) arylboronic acids.
Moreover, polyaromatic (3n) and heterocyclic boronic acids
(3o) are suitable substrates for this transformation. Of note, the
product biaryl ketones are prevalent motifs in biologically active
compounds, organic materials, and agrochemicals.12 Boronic
acid is typically used in excess. Transmetalation is generally
considered as the rate-determining step in Suzuki−Miyaura
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couplings using Pd-NHC.13a A turnover number (TON) of 230
was determined for the coupling of ester 1a (Pd-PEPPSI-IPr,
0.10 mol %, 110 °C). Side products, such as decarbonylation
and unselective cleavage of the O−Ph bond, have not been
observed.
strong σ donation of the NHC ligand facilitates oxidative
addition, leading to a modular approach to the historically
challenging C−O cross-coupling. Studies to address the design
of catalysts in the catalytic C−O cross-coupling will be
forthcoming.
To further demonstrate the high activity of Pd-PEPPSI-IPr in
cross-coupling, for comparison, we have conducted representa-
tive reactions catalyzed by Pd(IPr)(cinnamyl)(Cl) (eight
representative examples; see the Supporting Information).
The obtained results clearly demonstrate that under the
developed reaction conditions Pd-PEPPSI-IPr shows reactivity
comparable to or higher than that of Pd(IPr)(cinnamyl)-
(Cl).11a,20
EXPERIMENTAL SECTION
■
General Considerations. All starting materials reported in the
paper have been previously described in the literature and prepared by
the method reported previously. Esters were prepared by standard
methods.4b,9,11 All experiments were performed using standard
Schlenk techniques under nitrogen or argon unless stated otherwise.
All products have been previously reported. General methods have
been reported.7a All products have been previously reported. The
Kinetic studies were employed to investigate the effect of
1
ester electronic destabilization9 on the coupling (Figure 1).
purity has been established by H NMR analysis (CDCl3, 500 MHz).
1
All compounds are estimated to be >95% pure as determined by H
NMR.
General Procedure for the Suzuki−Miyaura Cross-Coupling
of Esters. An oven-dried vial equipped with a stir bar was charged
with an ester substrate (neat, 1.0 equiv), potassium carbonate
(typically, 4.5 equiv), boronic acid (typically, 3.0 equiv), and
PEPPSI-IPr ([1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-
chloropyridyl)palladium(II) dichloride, typically 3 mol %), placed
under a positive pressure of argon, and subjected to three evacuation/
back-filling cycles under high vacuum. THF (typically, 0.25 M) was
added with vigorous stirring at room temperature; the reaction mixture
was placed in a preheated oil bath and stirred for the indicated time.
Note: all reactions have been carried out in microwave vials with
heavy-walled, Type I, Class A borosilicate. These vials are designed to
withstand pressures up to 300 psi (20 bar) and are equivalent to
Fisher−Porter tubes. After the indicated time, the reaction mixture was
cooled to room temperature, diluted with CH2Cl2 (10 mL), filtered,
and concentrated. The sample was analyzed by 1H NMR (CDCl3, 500
MHz) and GC-MS to obtain conversion, selectivity, and yield using an
internal standard and comparison with authentic samples. Purification
by chromatography on silica gel (EtOAc/hexanes) afforded the title
product.
Figure 1. Kinetic profile of 1a. Kinetic profiles of 1j (PhCONBocPh)
and 1k (PhCONTsPh) are shown for comparison. Conditions: 1, 4-
Tol-B(OH)2 (2.0 equiv), 4a (3 mol %), K2CO3 (3.0 equiv), THF, 60
°C.
Representative Cross-Coupling Procedure. An oven-dried vial
equipped with a stir bar was charged with phenyl benzoate (neat, 1.0
mmol, 198.0 mg, 1.0 equiv), potassium carbonate (4.5 mmol, 621.9
mg, 4.5 equiv), p-tolylboronic acid (3.0 mmol, 407.9 mg, 3.0 equiv),
and PEPPSI-IPr (3 mol %, 20.4 mg), placed under a positive pressure
of argon, and subjected to three evacuation/back-filling cycles under
high vacuum. THF (0.25 M) was added with vigorous stirring at room
temperature; the reaction mixture was placed in a preheated oil bath at
80 °C and stirred for 16 h at 80 °C. After the indicated time, the
reaction mixture was cooled to room temperature, diluted with
CH2Cl2 (20 mL), filtered, and concentrated. Purification by
chromatography on silica gel (EtOAc/hexanes) afforded the title
product. Yield: 80% (157.2 mg) as a white solid. Characterization data
are included in the section below.
Generally speaking, these acyl activation reactions are
subclassified as either C−N or C−O, depending on the bond
that undergoes the cross-coupling.2a Our study demonstrates
that the cross-coupling of aryl esters proceeds with rates similar
to those for the cross-coupling of amides (1j, PhCONBoc/Ph;
1k, PhCONTs/Ph).19 The generality of this acyl activation
platform should enable the productive engagement in modular
cross-coupling reactions without restriction to a particular
acylmetal precursor.
Preliminary studies into the activation of PEPPSI-IPr and
(IPr)Pd(cinnamyl)Cl20 show more facile activation of PEPPSI-
IPr under the developed conditions (PEPPSI, 30 min/70%
yield, 60 min/77% yield; (IPr)Pd(cinnamyl)Cl, 30 min/41%
yield, 60 min/48% yield), which opens the door to the
development of even more active catalysts. In agreement with
these findings, kinetic studies revealed higher catalytic activity
of Pd-PEPPSI-IPr in comparison to (IPr)Pd(cinnamyl)Cl (see
the Supporting Information). Further studies on catalytic
properties of well-defined Pd-NHC catalysts in the acyl cross-
coupling manifold are ongoing.
Synthesis of Pd-NHC Complexes. Pd-PEPPSI complexes 4a,d
are commercially available. Complexes 4b,c,e were prepared by
procedures reported in the literature.14d,21
Benzophenone (Table 2, 3a). According to the general procedure,
the reaction of phenyl benzoate (0.20 mmol, 1.0 equiv), phenylboronic
acid (3.0 equiv), K2CO3 (4.5 equiv), and PEPPSI-IPr (3 mol %) in
THF (0.25 M) for 15 h at 80 °C afforded after filtration and
chromatography the title compound in 85% yield (30.9 mg) as a white
solid. 1H NMR (500 MHz, CDCl3): δ 7.81 (d, J = 7.7 Hz, 4 H), 7.59
(t, J = 7.5 Hz, 2 H), 7.49 (t, J = 7.6 Hz, 4 H). 13C NMR (125 MHz,
CDCl3): δ 196.84, 137.77, 132.52, 130.18, 128.40. Spectroscopic data
matched literature values.7a
Phenyl(p-tolyl)methanone (Table 2, 3b). According to the general
procedure, the reaction of phenyl 4-methylbenzoate (0.20 mmol, 1.0
equiv), phenylboronic acid (3.0 equiv), K2CO3 (4.5 equiv), and
PEPPSI-IPr (3 mol %) in THF (0.25 M) for 15 h at 80 °C afforded
after filtration and chromatography the title compound in 80% yield
(31.4 mg) as a white solid. 1H NMR (500 MHz, CDCl3): δ 7.79 (d, J
In summary, we report that versatile Pd-PEPPSI type
precatalysts serve as highly reactive catalysts for the direct
Suzuki−Miyaura cross-coupling of esters. This reaction features
modular, easily prepared Pd-NHC precatalysts, which can be
used under operationally convenient conditions. We have
further shown that the cross-coupling of esters proceeds at rates
similar to those for the cross-coupling of amides. Evidently, the
C
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= 8.2 Hz, 2 H), 7.74 (d, J = 8.2 Hz, 2 H), 7.59 (t, J = 7.3 Hz, 1 H),
7.48 (t, J = 7.5 Hz, 2 H), 7.29 (d, J = 7.9 Hz, 2 H), 2.45 (s, 3 H). 13C
NMR (125 MHz, CDCl3): δ 196.64, 143.36, 138.08, 135.00, 132.28,
130.43, 130.06, 129.10, 128.33, 21.79. Spectroscopic data matched
literature values.7a
Phenyl(4-(trifluoromethyl)phenyl)methanone (Table 2, 3c). Ac-
cording to the general procedure, the reaction of phenyl 4-
methoxybenzoate (0.20 mmol, 1.0 equiv), phenylboronic acid (3.0
equiv), K2CO3 (4.5 equiv), and PEPPSI-IPr (3 mol %) in THF (0.25
M) for 15 h at 80 °C afforded after filtration and chromatography the
title compound in 68% yield (28.8 mg) as a white solid. 1H NMR (500
MHz, CDCl3): δ 7.83 (d, J = 8.0 Hz, 2 H), 7.77 (d, J = 7.6 Hz, 2 H),
7.57 (t, J = 7.3 Hz, 1 H), 7.48 (t, J = 7.4 Hz, 2 H), 6.98 (d, J = 8.0 Hz,
2 H), 3.90 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ 195.69, 163.34,
138.41, 132.68, 132.01, 130.28, 129.85, 128.31, 113.67, 55.62.
Spectroscopic data matched literature values.7a
Phenyl(4-(trifluoromethyl)phenyl)methanone (Table 2, 3d).
According to the general procedure, the reaction of phenyl 4-
(trifluoromethyl)benzoate (0.20 mmol, 1.0 equiv), phenylboronic acid
(3.0 equiv), K2CO3 (4.5 equiv), and PEPPSI-IPr (3 mol %) in THF
(0.25 M) for 15 h at 80 °C afforded after filtration and
chromatography the title compound in 97% yield (48.5 mg) as a
white solid. 1H NMR (500 MHz, CDCl3): δ 7.91 (d, J = 8.0 Hz, 2 H),
7.82 (dd, J = 7.1 Hz, 2 H), 7.77 (d, J = 8.1 Hz, 2 H), 7.67−7.62 (m, 1
H), 7.51 (t, J = 7.7 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ 195.67,
140.86, 136.86, 133.86 (q, JF = 32.5 Hz), 133.23, 130.27, 130.24,
128.67, 125.48 (q, J = 3.8 Hz), 123.81 (q, JF = 271.3 Hz). 19F NMR
(471 MHz, CDCl3): δ −63.02. Spectroscopic data matched literature
values.7a
Methyl 4-Benzoylbenzoate (Table 2, 3a). According to the general
procedure, the reaction of methyl phenyl terephthalate (0.20 mmol,
1.0 equiv), phenylboronic acid (3.0 equiv), K2CO3 (4.5 equiv), and
PEPPSI-IPr (3 mol %) in THF (0.25 M) for 15 h at 80 °C afforded
after filtration and chromatography the title compound in 72% yield
(34.6 mg) as a white solid. 1H NMR (500 MHz, CDCl3): δ 8.16 (d, J
= 8.0 Hz, 2 H), 7.85 (d, J = 8.0 Hz, 2 H), 7.81 (d, J = 8.0 Hz, 2 H),
7.63 (t, J = 7.5 Hz, 1 H), 7.51 (t, J = 7.5 Hz, 2 H), 3.98 (s, 3 H). 13C
NMR (125 MHz, CDCl3): δ 196.17, 166.45, 141.45, 137.08, 133.35,
133.08, 130.24, 129.91, 129.63, 128.60, 52.61. Spectroscopic data
matched literature values.7a
71% yield (24.4 mg) as a dolorless oil. 1H NMR (500 MHz, CDCl3): δ
7.98 (d, J = 7.0 Hz, 2 H), 7.73 (s, 1 H), 7.61 (t, J = 7.5 Hz, 1 H), 7.51
(t, J = 7.5 Hz, 2 H), 7.25 (d, J = 3.5 Hz, 1 H), 6.61 (dd, J = 3.5, 1.5 Hz,
1 H). 13C NMR (125 MHz, CDCl3): δ 182.71, 152.44, 147.23, 137.41,
132.71, 129.43, 128.56, 120.69, 112.34. Spectroscopic data matched
literature values.11a
1-Phenyldecan-1-one (Table 2, 3i). According to the general
procedure, the reaction of phenyl decanoate (0.20 mmol, 1.0 equiv),
phenylboronic acid (3.0 equiv), K2CO3 (4.5 equiv), and PEPPSI-IPr
(6 mol %) in THF (0.25 M) for 15 h at 80 °C afforded after filtration
and chromatography the title compound in 68% yield (31.6 mg) as a
white solid. 1H NMR (500 MHz, CDCl3): δ 7.96 (d, J = 7.5 Hz, 2 H),
7.55 (t, J = 7.5 Hz, 1 H), 7.46 (t, J = 7.5 Hz, 2 H), 2.96 (t, J = 7.0 Hz, 2
H), 1.73 (p, J = 7.0, 6.5 Hz, 2 H), 1.40−1.25 (m, 12 H), 0.88 (t, J = 6.0
Hz, 3 H). 13C NMR (125 MHz, CDCl3): δ 200.76, 137.25, 132.98,
128.67, 128.19, 38.79, 32.02, 29.63, 29.62, 29.53, 29.43, 24.54, 22.81,
14.25. Spectroscopic data matched literature values.7a
Phenyl(p-tolyl)methanone (Table 2, 3b′). According to the general
procedure, the reaction of phenyl benzoate (1.0 mmol, 1.0 equiv), p-
tolylboronic acid (3.0 equiv), K2CO3 (4.5 equiv), and PEPPSI-IPr (3
mol %) in THF (0.25 M) for 15 h at 80 °C afforded after filtration and
chromatography the title compound in 80% yield (157.2 mg) as a
white solid. 1H NMR (500 MHz, CDCl3): δ 7.79 (d, J = 8.2 Hz, 2 H),
7.74 (d, J = 8.2 Hz, 2 H), 7.59 (t, J = 7.3 Hz, 1 H), 7.48 (t, J = 7.5 Hz,
2 H), 7.29 (d, J = 7.9 Hz, 2 H), 2.45 (s, 3 H). 13C NMR (125 MHz,
CDCl3): δ 196.64, 143.36, 138.08, 135.00, 132.28, 130.43, 130.06,
129.10, 128.33, 21.79. Spectroscopic data matched literature values.7a
(4-Methoxyphenyl)(phenyl)methanone (Table 2, 3c′). According
to the general procedure, the reaction of phenyl benzoate (0.20 mmol,
1.0 equiv), (4-methoxyphenyl)boronic acid (3.0 equiv), K2CO3 (4.5
equiv), and PEPPSI-IPr (3 mol %) in THF (0.25 M) for 15 h at 80 °C
afforded after filtration and chromatography the title compound in
98% yield (41.6 mg) as a white solid. 1H NMR (500 MHz, CDCl3): δ
7.83 (d, J = 8.0 Hz, 2 H), 7.77 (d, J = 7.6 Hz, 2 H), 7.57 (t, J = 7.3 Hz,
1 H), 7.48 (t, J = 7.4 Hz, 2 H), 6.98 (d, J = 8.0 Hz, 2 H), 3.90 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ 195.69, 163.34, 138.41, 132.68,
132.01, 130.28, 129.85, 128.31, 113.67, 55.62. Spectroscopic data
matched literature values.7a
(4-Fluorophenyl)(phenyl)methanone (Table 2, 3j). According to
the general procedure, the reaction of phenyl benzoate (0.20 mmol,
1.0 equiv), (4-fluorophenyl)boronic acid (3.0 equiv), K2CO3 (4.5
equiv), and PEPPSI-IPr (3 mol %) in THF (0.25 M) for 15 h at 80 °C
afforded after filtration and chromatography the title compound in
75% yield (30.0 mg) as a white solid. 1H NMR (500 MHz, CDCl3): δ
7.85 (dd, J = 8.5, 5.5 Hz, 2 H), 7.77 (d, J = 8.0 Hz, 2 H), 7.59 (t, J =
7.5 Hz, 1 H), 7.49 (t, J = 7.5 Hz, 2 H), 7.16 (t, J = 8.5 Hz, 2 H). 13C
NMR (125 MHz, CDCl3): δ 195.37, 165.54 (d, JF = 252.5 Hz),
137.68, 133.97 (d, JF = 3.8 Hz), 132.80 (d, JF = 8.8 Hz), 132.59,
130.00, 128.49, 115.59 (d, JF = 21.2 Hz). 19F NMR (471 MHz,
CDCl3): δ −106.06. Spectroscopic data matched literature values.7a
Methyl 4-Benzoylbenzoate (Table 2, 3e′). According to the general
procedure, the reaction of phenyl benzoate (0.20 mmol, 1.0 equiv), (4-
(methoxycarbonyl)phenyl)boronic acid (3.0 equiv), K2CO3 (4.5
equiv), H2O (5.0 equiv), and PEPPSI-IPr (3 mol %) in THF (0.25
M) for 15 h at 80 °C afforded after filtration and chromatography the
title compound in 54% yield (25.9 mg) as a white solid. 1H NMR (500
MHz, CDCl3): δ 8.16 (d, J = 8.0 Hz, 2 H), 7.85 (d, J = 8.0 Hz, 2 H),
7.81 (d, J = 8.0 Hz, 2 H), 7.63 (t, J = 7.5 Hz, 1 H), 7.51 (t, J = 7.5 Hz,
2 H), 3.98 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ 196.17, 166.45,
141.45, 137.08, 133.35, 133.08, 130.24, 129.91, 129.63, 128.60, 52.61.
Spectroscopic data matched literature values.7a
Phenyl(o-tolyl)methanone (Table 2, 3f). According to the general
procedure, the reaction of phenyl 2-methylbenzoate (0.20 mmol, 1.0
equiv), phenylboronic acid (3.0 equiv), K2CO3 (4.5 equiv), and
PEPPSI-IPr (3 mol %) in THF (0.25 M) for 15 h at 80 °C afforded
after filtration and chromatography the title compound in 83% yield
1
(32.5 mg) as a colorless oil. H NMR (500 MHz, CDCl3): δ 7.87−
7.81 (m, 2 H), 7.64−7.59 (m, 1 H), 7.49 (t, J = 7.7 Hz, 2 H), 7.43 (td,
J = 7.5, 1.5 Hz, 1 H), 7.37−7.31 (m, 2 H), 7.31−7.28 (m, 1 H), 2.37
(s, 3 H). 13C NMR (125 MHz, CDCl3): δ 198.77, 138.75, 137.87,
136.87, 133.25, 131.12, 130.36, 130.25, 128.64, 128.58, 125.32, 20.12.
Spectroscopic data matched literature values.7a
(3,4-Difluorophenyl)(phenyl)methanone (Table 2, 3g). According
to the general procedure, the reaction of phenyl 3,4-difluorobenzoate
(0.20 mmol, 1.0 equiv), phenylboronic acid (3.0 equiv), K2CO3 (4.5
equiv), and PEPPSI-IPr (3 mol %) in THF (0.25 M) for 15 h at 80 °C
afforded after filtration and chromatography the title compound in
84% yield (36.6 mg) as a white solid. 1H NMR (500 MHz, CDCl3): δ
7.77 (d, J = 7.5 Hz, 2 H), 7.69 (t, J = 9.0 Hz, 1 H), 7.61 (t, J = 13.2 Hz,
2 H), 7.51 (t, J = 8.0 Hz, 2 H), 7.27 (q, J = 8.0 Hz, 1 H). 13C NMR
(125 MHz, CDCl3): δ 194.21, 154.41 (dd, JF = 254.8, 12.3 Hz), 150.32
(dd, JF = 255.0, 12.4 Hz), 137.00, 134.57 (t, JF = 3.7 Hz), 132.93,
129.97, 128.62, 127.25 (q, JF = 3.8 Hz), 119.45 (dd, JF = 17.5, 1.3 Hz),
117.40 (d, JF = 17.5 Hz). 19F NMR (471 MHz, CDCl3): δ −130.60 (d,
J = 21.2 Hz), −136.18 (d, J = 21.2 Hz). Spectroscopic data matched
literature values.9
(3-Methoxyphenyl)(phenyl)methanone (Table 2, 3k). According
to the general procedure, the reaction of phenyl benzoate (0.20 mmol,
1.0 equiv), (3-methoxyphenyl)boronic acid (3.0 equiv), K2CO3 (4.5
equiv), and PEPPSI-IPr (3 mol %) in THF (0.25 M) for 15 h at 80 °C
afforded after filtration and chromatography the title compound in
85% yield (36.0 mg) as a white solid. 1H NMR (500 MHz, CDCl3): δ
7.82 (d, J = 7.7 Hz, 2 H), 7.60 (t, J = 7.4 Hz, 1 H), 7.49 (t, J = 7.4 Hz,
2 H), 7.41−7.34 (m, 3 H), 7.14 (d, J = 8.6 Hz, 1 H), 3.87 (s, 3 H). 13C
NMR (125 MHz, CDCl3): δ 196.66, 159.70, 139.03, 132.55, 130.17,
Furan-2-yl(phenyl)methanone (Table 2, 3h). According to the
general procedure, the reaction of phenyl furan-2-carboxylate (0.20
mmol, 1.0 equiv), phenylboronic acid (3.0 equiv), K2CO3 (4.5 equiv),
and PEPPSI-IPr (6 mol %) in THF (0.25 M) for 15 h at 80 °C
afforded after filtration and chromatography the title compound in
D
DOI: 10.1021/acs.organomet.7b00565
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
129.34, 128.39, 123.01, 119.00, 114.44, 55.61. Spectroscopic data
matched literature values.22
obtain conversion, selectivity, and yield using an internal standard and
comparison with authentic samples.
Phenyl(o-tolyl)methanone (Table 2, 3f′). According to the general
procedure, the reaction of phenyl benzoate (0.20 mmol, 1.0 equiv), o-
tolylboronic acid (3.0 equiv), K2CO3 (4.5 equiv), and PEPPSI-IPr (3
mol %) in THF (0.25 M) for 15 h at 80 °C afforded after filtration and
chromatography the title compound in 88% yield (34.5 mg) as a
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.7b00565.
■
S
1
colorless oil. H NMR (500 MHz, CDCl3): δ 7.87−7.81 (m, 2 H),
7.64−7.59 (m, 1 H), 7.49 (t, J = 7.7 Hz, 2 H), 7.43 (td, J = 7.5, 1.5 Hz,
1 H), 7.37−7.31 (m, 2 H), 7.31−7.28 (m, 1 H), 2.37 (s, 3 H). 13C
NMR (125 MHz, CDCl3): δ 198.77, 138.75, 137.87, 136.87, 133.25,
131.12, 130.36, 130.25, 128.64, 128.58, 125.32, 20.12. Spectroscopic
data matched literature values.7a
NMR data, comparison of reactivity of Pd-PEPPSI-IPr
and (IPr)Pd(cin)Cl, and kinetic profile of (IPr)Pd(cin)
Cl (PDF)
(2-Methoxyphenyl)(phenyl)methanone (Table 2, 3l). According to
the general procedure, the reaction of phenyl benzoate (0.20 mmol,
1.0 equiv), (2-methoxyphenyl)boronic acid (3.0 equiv), K2CO3 (4.5
equiv), and PEPPSI-IPr (3 mol %) in THF (0.25 M) for 15 h at 80 °C
afforded after filtration and chromatography the title compound in
92% yield (39.0 mg) as a white solid. 1H NMR (500 MHz, CDCl3): δ
7.82 (d, J = 7.8 Hz, 2 H), 7.56 (t, J = 7.1 Hz, 1 H), 7.49 (d, J = 7.7 Hz,
1 H), 7.44 (t, J = 7.5 Hz, 2 H), 7.37 (d, J = 7.4 Hz, 1 H), 7.05 (t, J =
7.4 Hz, 1 H), 7.00 (d, J = 8.3 Hz, 1 H), 3.73 (s, 3 H). 13C NMR (125
MHz, CDCl3): δ 196.58, 157.46, 137.93, 133.03, 131.99, 129.94,
129.70, 128.97, 128.33, 120.60, 111.57, 55.72. Spectroscopic data
matched literature values.11a
(3,4-Dimethoxyphenyl)(phenyl)methanone (Table 2, 3m). Ac-
cording to the general procedure, the reaction of phenyl benzoate
(0.20 mmol, 1.0 equiv), (3,4-dimethoxyphenyl) boronic acid (3.0
equiv), K2CO3 (4.5 equiv), and PEPPSI-IPr (3 mol %) in THF (0.25
M) for 15 h at 80 °C afforded after filtration and chromatography the
title compound in 77% yield (37.3 mg) as a white solid. 1H NMR (500
MHz, CDCl3): δ 7.76 (d, J = 8.1 Hz, 2 H), 7.57 (t, J = 7.0 Hz, 1 H),
7.51−7.44 (m, 3 H), 7.38 (d, J = 8.3 Hz, 1 H), 6.89 (d, J = 8.3 Hz, 1
H), 3.96 (s, 3 H), 3.95 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ
195.71, 153.13, 149.14, 138.42, 132.01, 130.35, 129.85, 128.30, 125.64,
112.24, 109.85, 56.24, 56.19. Spectroscopic data matched literature
values.11a
(6-Methoxynaphthalen-2-yl)(phenyl)methanone (Table 2, 3n).
According to the general procedure, the reaction of phenyl benzoate
(0.20 mmol, 1.0 equiv), (6-methoxynaphthalen-2-yl)boronic acid (3.0
equiv), K2CO3 (4.5 equiv), and PEPPSI-IPr (3 mol %) in THF (0.25
M) for 15 h at 80 °C afforded after filtration and chromatography the
title compound in 75% yield (39.3 mg) as a white solid. 1H NMR (500
MHz, CDCl3): δ 8.21 (d, J = 1.7 Hz, 1 H), 7.94 (dd, J = 8.6, 1.7 Hz, 1
H), 7.88−7.79 (m, 4 H), 7.65−7.58 (m, 1 H), 7.51 (dd, J = 8.4, 7.0
Hz, 2 H), 7.24−7.17 (m, 2 H), 3.96 (s, 3 H). 13C NMR (125 MHz,
CDCl3): δ 196.70, 159.81, 138.33, 137.13, 132.81, 132.24, 132.11,
131.15, 130.10, 128.41, 127.72, 127.13, 126.68, 119.85, 105.88, 55.57.
Spectroscopic data matched literature values.22
Furan-3-yl(phenyl)methanone (Table 2, 3o). According to the
general procedure, the reaction of phenyl benzoate (0.20 mmol, 1.0
equiv), furan-3-yl boronic acid (3.0 equiv), K2CO3 (4.5 equiv), and
PEPPSI-IPr (3 mol %) in THF (0.25 M) for 15 h at 80 °C afforded
after filtration and chromatography the title compound in 81% yield
(27.9 mg) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 7.92 (s, 1
H), 7.86 (d, J = 8.3 Hz, 2 H), 7.59 (t, J = 7.4 Hz, 1 H), 7.53−7.46 (m,
3 H), 6.91 (d, J = 1.8 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ
189.56, 148.69, 144.09, 138.96, 132.61, 128.96, 128.68, 126.65, 110.35.
Spectroscopic data matched literature values.7a
AUTHOR INFORMATION
Corresponding Author
*E-mail for M.S.: michal.szostak@rutgers.edu.
ORCID
Shicheng Shi: 0000-0001-8124-9235
Michal Szostak: 0000-0002-9650-9690
■
Present Address
‡P.L.: Department of Applied Chemistry, College of Science,
China Agricultural University, Beijing 100193, People’s
Republic of China.
Author Contributions
†S.S. and P.L. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Rutgers University and the NSF (CAREER CHE-1650766) are
gratefully acknowledged for support. The Bruker 500 MHz
spectrometer used in this study was supported by the NSF-MRI
grant (CHE-1229030). P.L. thanks the China Scholarship
Council (No. 201606350069) for a fellowship.
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Determination of Relative Reaction Rates. An oven-dried vial
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1
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