Palladium Catalyzed Carbonylative Coupling for Synthesis of Arylketones and Arylesters Using Chloroform as the Carbon Monoxide Source

Article abstract of DOI:10.1021/acs.joc.6b02711

We describe a modular, palladium catalyzed synthesis of aryl(hetero)aryl benzophenones and aryl benzoates from aryl(hetero)aryl halides using CHCl₃ as the carbonyl source in the presence of KOH. The reaction occurs in tandem through an initial carbonylation to generate an aroyl halide, which undergoes coupling with arylboronic acids, bornonates, and phenols. Direct carbonylative coupling of indoles at the third position has also been accomplished under slightly modified reaction conditions by in situ activation of the C-H bond. Notably, CHCl₃ is a convenient and safe alternation of CO gas, provides milder reaction conditions with high functional group tolerance, and gives the products in moderate to good yields.

Full text of DOI:10.1021/acs.joc.6b02711

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Article
Palladium catalyzed carbonylative coupling for synthesis of aryl-
ketones and arylesters using chloroform as the carbon monoxide source
Poonam Sharma, Sandeep Rohilla, and Nidhi Jain
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02711 • Publication Date (Web): 21 Dec 2016
Downloaded from http://pubs.acs.org on December 22, 2016
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Page 1 of 11
The Journal of Organic Chemistry
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Palladium catalyzed carbonylative coupling for synthesis of arylke-
tones and arylesters using chloroform as the carbon monoxide
source
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Poonam Sharma, Sandeep Rohilla, and Nidhi Jain*
Department of Chemistry, Indian Institute of Technology Delhi, New Delhi, India 110016
KEYWORDS: carbonylative coupling, chloroform, aryl boronic acids, phenols, indoles
ABSTRACT: We describe a modular, palladium catalyzed synthesis of aryl(hetero)aryl benzophenones and aryl benzoates from
aryl(hetero)aryl halides using CHCl3 as the carbonyl source in presence of KOH. The reaction occurs in tandem through an initial
carbonylation to generate an aroyl halide, which undergoes coupling with arylboronic acids, bornonates, and phenols. Direct carꢀ
bonylative coupling of indoles at the third position has also been accomplished under slightly modified reaction conditions by inꢀ
situ activation of the CꢀH bond. Notably, CHCl3 is a convenient and safe alternation of CO gas, provides milder reaction conditions
with high functional group tolerance, and gives the products in moderate to good yields.
monoxide gas,17 metal carbonyl precursors,2a or other CO surꢀ
INTRODUCTION
Transitionꢀmetal catalyzed insertion of a carbonyl group diꢀ
rogates.18 However, these reactions are challenged by competꢀ
ing side reactions, such as nonꢀcarbonylative Suzuki coupling,
and homocoupling.19 To the best of our knowledge, Pd cataꢀ
lyzed biaryl ketone synthesis via CO insertion using chloroꢀ
form as a source has not been investigated yet, though a recent
report demonstrates this transformation in PEGꢀ400 using
FeCl2 as catalyst, and pivalic acid and NaCl as additives.20
rectly into an organic molecule has evolved as one of the most
powerful methods for synthesizing diverse carbonyl comꢀ
pounds due to high atom economy, functional group tolerance,
regioselectivity, and easy availability of the starting materials.1
Carbonyl installation can be achieved by using carbon monoxꢀ
ide (CO), which represents an economical and attractive C1
building block. The challenge, however, is the handling of
CO; since it is a toxic gas available in pressurized cylinders
which limits its practical utility. To avoid its direct use, alterꢀ
native CO sources such as transition metal carbonyl complexꢀ
es,2 carbamoylsilane,3 Nꢀformylsaccharin,4 amoylstannanes,5
oxalyl chloride,6 and others have been developed. In a recent
report, Skrydstrup and coworkers have elaborated on two new
CO releasing molecules referred to as COgen and SilaCOgen
in a twoꢀchamber reactor for various carbonylation reacꢀ
tions.7 Although, each of these precursors has its own merits,
it is still important to find CO sources that are inexpensive,
less toxic, easily available, and do not require multistep synꢀ
thesis or complex reaction set up. In this context, generation of
CO by hydrolysis of CHCl3 in presence of strongly basic
aqueous hydroxide solution is a wellꢀknown practical apꢀ
proach.8 Since CHCl3 is inexpensive and easy to handle, its use
as a CO source is quite attractive in organic synthesis. In the
last few years, there have been some reports in which CO genꢀ
erated from CHCl3 has been used for Pdꢀcatalyzed carboxylaꢀ
tion,9 aminocarbonylations,10 Heckꢀtype domino cyclization,11
and carbonylative Sonogashira coupling.12
Scheme 1. Synthesis of arylketones and arylesters using
CHCl3
Inspired by the pioneering works of Hull, Gu, and Wang, and
continuing our efforts towards developing efficient synthetic
protocols using Pd,21 we explored the synthesis of benzopheꢀ
nones via carbonylative crossꢀcoupling of aryl iodides with
arylboronic acids using CO generated inꢀsitu from CHCl3
(Scheme 1). The method could also be successfully applied to
phenols as coupling partners yielding aryl esters in high yields.
The previous literature on Pdꢀcatalyzed ester synthesis with
aryl halide precursors has been reported using phenylformates
or formic acid,22 decarboxylative coupling using potassium
oxalate monoesters,23 and carbonylative coupling with pheꢀ
nols, wherein CO is delivered using a CO balloon24 or a metal
carbonyl source.25 Phenyl esters are known to serve as useful
acylating agents and can deliver libraries of carbonyl derivaꢀ
tives, including alkyl, allyl and thioesters under mild condiꢀ
tions.26
Arylketones are important structural building blocks present
in a wide variety of molecules such as pharmaceutical drugs,
natural products, and sunscreen agents.13 Their conventional
synthesis starting from acid halides can be executed via
FriedelꢀCrafts reaction,14 acylation of preꢀmetalated precurꢀ
sors,15 or Pdꢀmediated crossꢀcoupling with boronic acids.16
Direct carbonyl insertion into aryl halides via Pd catalyzed
carbonylative Suzuki pathway has been achieved with carbon
RESULTS AND DISCUSSION:
The work initiated with a carbonylative Suzuki coupling for
the synthesis of a benzophenone derivative. For this, 4ꢀiodoꢀ
nitrobenzene (1d, 1.0 equiv), phenylboronic acid (2a, 1.2
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equiv), KOH (6.0 equiv), CHCl3 (3.0 equiv), Pd(OAc)2 (2 BINAP, glucose, and DMAP (entries 9ꢀ12) showed that while
1
2
3
4
5
6
7
8
mol%), and PPh3 (20 mol%) were taken in toluene as the solꢀ
vent. The contents were heated at 80 °C for 12 h, and the deꢀ
sired product, 4ꢀnitrobenzophenone (3i) was isolated in 64%
yield (Table 1, entry 1). Motivated by this initial success, we
optimized the reaction with respect to solvent, base, catalyst,
ligand, time, and temperature.
pyridine exerted a similar effect as PPh3 (entries 1 and 9),
BINAP and glucose were ineffective in promoting the reaction
(entry 10 and 11). DMAP was found to be the best ligand givꢀ
ing 3i in 85% yield (entry 12). Lowering or raising the amount
of DMAP to 10 mol% or 40 mol% decreased the product yield
(entry 12). Other palladium precursors such as Pd(PPh3)2Cl2
and PdCl2 were also examined, but relatively lower yields
were obtained with them (entry 13, 14). Blank experiments
carried out without the addition of phenylboronic acid or palꢀ
ladium catalyst did not yield any product. Varying the temperꢀ
ature to 70, 90, or 100 °C gave the product in 64ꢀ81% yields
(entry 15) suggesting 80 °C to be the optimum reaction temꢀ
perature. Since base is vital for this reaction, other hydroxide
bases such as NaOH, LiOH, and Mg(OH)2 were tested but all
were found to be inferior to KOH and gave lower yield of 3i
(12ꢀ53%, entries 16ꢀ18), except CsOH.H2O which gave 3i in
86% yield (entry 19). In view of the higher cost and hygroꢀ
scopic nature of CsOH.H2O, we chose KOH. It is noteworthy
to mention that the reaction kinetics enabled carbonylation to
outcompete the nonꢀcarbonylative couplings reported previꢀ
ously as side reactions, when CO gas is used directly.19aꢀ19c
We noticed that the reaction atmosphere did not have any
affect, and similar yields were obtained both under air and
nitrogen.
Table 1. Optimization of the reaction conditionsa
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yield
(%)b
entry
solvent
Base
catalyst
ligand
1
2
3
4
5
6
7
8
toluene
CHCl3
DMSO
DCE
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
64
10
23
11
34
59
0
Employing the best optimized reaction conditions, a variety
of aryl and heteroaryl halides were treated with substituted
and unsubstituted arylboronic acids to establish the versatility
of this protocol. The results are summarized in Table 2. In
general, all the investigated arylboronic acids underwent
smooth carbonylative coupling with iodobenzene (1a) to proꢀ
vide the diarylketones in moderate to good yields (3a-3e, 68ꢀ
87%). Effect of substituents on aryl iodides was also examꢀ
ined. It was found that aryl iodides with substituents at the
paraꢀposition afforded slightly better yields (3i-3l) compared
to their metaꢀsubstituted analogues (3m-3p). A similar patꢀ
tern was seen while comparing the metaꢀsubstituted derivaꢀ
tives (3s-3u) with their corresponding orthoꢀsubstituted counꢀ
terparts (3v-3x) probably due to the prevalent steric effects.
Notably, with 2ꢀbromoboronic acid, chemoselectivity was
observed with carbonylation occurring exclusively on aryl
iodide to afford the corresponding bromosubstituted ketone
(3u, 3x) with an intact bromine handle for further functionaliꢀ
zation. Electronic effect of substituents present on aryl ioꢀ
dides and arylboronic acids did not influence the reaction
significantly. It was found that similar yields were obtained
whether electron donating (methyl, ethyl, methoxy) or elecꢀ
tron withdrawing (fluoro, nitro, cyano, trifluoromethyl, aceꢀ
tyl) groups were present on aryl iodides and arylboronic acꢀ
ids.
CH3CN
dioxane
H2O
DMF
29
Pyriꢀ
dine
9
toluene
KOH
Pd(OAc)2
63
10
11
toluene
toluene
KOH
KOH
Pd(OAc)2
Pd(OAc)2
BINAP
glucose
5
0
85, 43c,
12
toluene
KOH
Pd(OAc)2
DMAP
64d
Pd(PPh3)2C
l2
13
14
15
toluene
toluene
toluene
KOH
KOH
KOH
DMAP
DMAP
DMAP
Trace
PdCl2
47
79e, 81f,
64g
Pd(OAc)2
16
17
18
toluene
toluene
toluene
NaOH
LiOH
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
DMAP
DMAP
DMAP
53
29
15
Mg(OH)2
This offers a significant improvement over the conventional
carbonylative Suzuki couplings with unpressurized CO gas,
where electronꢀdeficient aryl halides show poor reactivity.22
Even heteroaryl substrates like 2ꢀbromopyridine and thioꢀ
pheneꢀ3ꢀboronic acid survived the reaction conditions, and
gave 3y, 3z, and 3aa in moderate yields. The reaction of 4,4’ꢀ
diiodoꢀ1,1’ꢀbiphenyl with (4ꢀethylphenyl) boronic acid yieldꢀ
ed the monocarbonylatedproduct, (4ꢀethylphenyl)(4'ꢀiodoꢀ
[1,1'ꢀbiphenyl]ꢀ4ꢀyl)methanone (3ab) exclusively in 64%
yield. This is in contrast to the previous report on carbonylaꢀ
tive Suzuki coupling of 4,4’ꢀdiiodoꢀ1,1’ꢀbiphenyl using CO
balloon or metal carbonyls and Pd(NHC) complex, where a
mixture of mono (3ab) and dicarbonylated products [biphenylꢀ
CsOH.H2
O
19
toluene
Pd(OAc)2
DMAP
86
aReaction conditions: 1d (0.5 mmol, 1.0 equiv.), 2a (0.6 mmol,
1.2 equiv.), base (6.0 equiv.), Pd(OAc)2 (2 mol%), ligand (20
mol%), CHCl3 (3.0 equiv.) and solvent (3 mL) were heated at 80
oC for 12 h, bHPLC yield, cDMAP (10 mol%), dDMAP (40
mol%) etemp. 70 oC, ftemp. 90 oC, gtemp. 100 oC.
Replacing toluene with other solvents such as CHCl3, DMSO,
DCE, CH3CN, dioxane, water and DMF (entries 2ꢀ8) lowered
the product yield suggesting a strong influence of the solvent
on this transformation. Screening of ligands such as pyridine,
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5d and 5e were obtained in 57% and 67% yields respectively.
4,4’ꢀdiyl bis(phenylmethanone)] was obtained in varied
yields.27 This method, therefore, offers a better selectivity for
synthesizing the monocarbonylated ketone derivatives. The
reaction was also applied for gramꢀscale synthesis starting
from 1g of iodobenzene and 883 mg of 4ꢀethylboronic acid to
yield 3b in 84% yield (870 mg).
In general, the reaction failed with electron withdrawing aryl
iodides. Reaction of 4ꢀnitroiodo benzene with 4b under optiꢀ
mized conditions did not yield the desired carbonylative couꢀ
pled product, and the corresponding Suzuki coupled biaryl
was obtained instead.
1
2
3
4
5
6
7
8
9
Table 2. Substrate scope of aryl halides and aryl boronic
acidsa
To further generalize the application of this protocol, we exꢀ
amined if the carbonyl generated from CHCl3 and KOH could
be inserted directly into the relatively inert CꢀH bonds. This
was explored with indoles as substrates, through an inꢀsitu
iodination followed by palladium catalyzed sequential carꢀ
bonylation and coupling in oneꢀpot. A similar carbonylative
coupling of indoles has been reported earlier using CO gas as
the carbonyl source.29 The reaction of Nꢀmethyl indole (1.0
mmol) with phenylboronic acid in the presence of Pd(OAc)2
(2.0 mol%), Iodine (1.2 equiv), chloroform (3.0 equiv), KOH
(6.0 equiv.) and DMAP (20 mol %) in toluene at 80 oC yieldꢀ
ed the desired product (7a) in 24% yield. To improve the reacꢀ
tion yield, amount of DMAP was increased up to 1.0 equiv,
which facilitated the reaction and gave 7a in 74% yield.
O
B(OH)2
X
Pd(OAc)2
,
DMAP
Y
CHCl3, KOH
Y
+
R2
R1
R2
R1
Toluene ,80 o
C
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2
3
O
1
3a-3z, 3ab
X = I, Y = CH (
X = Br, Y = N (3aa)
)
O
O
O
C2H5
Cl
F
3d(74%)
3a (75%)
3b
(87%)
3c
(75%)
O
O
O
O
H3COC
O
NC
CF3
NC
3h (77%)
3e (68%)
3f (72%)
3g
(79%)
O
O
Table 3. Scope with aryl boronatesa
MeO
O2N
O2N
3k (82%)
(83%)
3j
3i (83%)
O
O
O
O
MeO
C2H5
OMe
NO2
NO2
(71%)
O
3n(78%)
3o(73%)
3l
3m (82%)
O
O
F
C2H5
C2H5
MeO
OMe
NO2
3q
3r (74%)
(76%)
3p
(67%)
O
O
Br
O
OMe
O
Me
3t (71%)
OMe
aReaction conditions: 1 (1.0 mmol), 4 (1.2 mmol), Pd(OAc)2 (2
mol%), DMAP (20 mol%), CHCl3 (3.0 equiv), KOH (6.0 equiv)
in toluene at 80 oC for 12 h.
Me
3u (79%)
3v (76%)
3s (79%)
Br
Me
O
O
O
Me
O
MeO
After finding the best optimized conditions, we applied it to
different Nꢀalkylated indoles as substrates. The reaction served
well with unsubstituted as well as methoxy substituted Nꢀ
methyl indole derivative to give the carbonylated products
(7a-7g) in moderate to good yields (Table 4). However, with
5ꢀnitro substituted Nꢀmethylindole, the reaction failed and did
not yield any product.
S
S
3w (67%)
3x(76%)
3y (73%)
(72%)
3z
O
O
N
I
OMe
3aa (70%)
(64%)
3ab
C2H5
aReaction conditions: 1 (1.0 mmol), 2 (1.2 mmol), Pd(OAc)2 (2
mol%), DMAP (20 mol%), CHCl3 (3.0 equiv), KOH (6.0 equiv)
in toluene at 80 oC for 12 h.
Table 4. Substrate scope of N-alkyl indoles and aryl-
boronic acidsa
The substrate scope was further examined with boronic acid
esters as shown in Table 3. The reaction of 4ꢀ(4ꢀPhenylꢀ1ꢀ
piperazinylmethyl)benzeneboronic acid pinacol ester (4a) with
unsubstituted iodobenzene, as well as iodobenzene substituted
with 4ꢀmethyl or 2ꢀmethoxy groups proceeded well under the
optimized conditions to yield the piperazinyl substituted aroꢀ
matic ketones (5a-5c) in 46ꢀ62% yields. These compounds are
medicinally important as their analogues are being developed
as potent p38ꢀalpha MAPK inhibitors for treatment of Alzꢀ
heimer’s
disease.28
With
2ꢀ(Nꢀ
Phthalimidomethyl)benzeneboronic acid pinacol ester (4b),
the corresponding phthalimide substituted aromatic ketones
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aReaction conditions: 1a (0.5 mmol, 1.0 equiv), 8a (0.6 mmol, 1.2
1
2
3
4
equiv), Pd(OAc)2 (2 mol%), ligand (20 mol%), CHCl3 (3.0
equiv), KOH, solvent at 80 oC for 12 h under air atmosphere,
bisolated yield, cunder N2 atmosphere.
Table 6. Scope of carbonylative coupling with phenolsa
5
6
7
8
9
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46
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60
aReaction conditions: 6 (1.0 mmol), 2 (1.2 mmol), Pd(OAc)2 (2
mol%), DMAP (1.0 equiv), CHCl3 (3.0 equiv), KOH (6.0 equiv),
I2 (1.2 equiv) in toluene at 80 oC for 12 h.
aReaction conditions: 1 (1.0 mmol), 8 (1.2 mmol), Pd(OAc)2 (2
mol%), PPh3 (20 mol%), CHCl3 (3.0 equiv), KOH (10.0 equiv), in
4 mL H2O/CHCl3 (3:1) at 80 oC for 12 h under N2 atmosphere.
After successful execution of the carbonylative coupling stratꢀ
egy for benzophenone synthesis, we implemented it on oxygen
nucleophiles for synthesis of aryl esters. To establish this, we
tried the reaction of phenol (8a) with iodobenzene (1a) under
the optimized conditions, but failed to obtain any product (Taꢀ
ble 5, entry 1). Replacing DMAP with PPh3 as the ligand faꢀ
vored the reaction, and gave the desired product phenylbenzoꢀ
ate (9a) in 30% yield (Table 5, entry 2). To further improve
the yield, the reaction was attempted with an excess of KOH
(10 equiv) in a biphasic solvent system comprised of water
and CHCl3 in the ratio 3:1. Surprisingly, under these condiꢀ
tions, the reaction did not proceed at all. However, on carrying
it out under nitrogen atmosphere enabled a facile and smooth
coupling, and 9a was obtained in 80% yield (Table 5, entry 4).
To ascertain the relative reactivity of arylboronic acids and
phenols towards a competitive coupling with the intermediate
carbonylated aryl iodide, a mixed experiment was carried out
(Scheme 2). Equimolar amounts of 2a and 8a were added to
H2O/CHCl3 (3:1) containing 1a, Pd(OAc)2, PPh3, and KOH;
o
and the contents were heated at 80 C for 12 h under N2 atꢀ
mosphere (Scheme 2A). Chemoselectivity was not observed
under biphasic conditions, and a mixture of ketone 3a and
ester 9a was obtained in 46% and 24% yields respectively,
suggesting a faster kinetics for boronic acids compared to
phenols. However, replacing H2O with toluene selectively
gave the ketone 3a, and no traces of 9a were seen (Scheme
2B).
Scheme 2. Competitive palladium catalyzed carbonylative
coupling for synthesis of ketone versus estera
Subsequently, a library of aryl esters was synthesized using
PPh3 as the ligand in H2O:CHCl3 (3:1) under nitrogen atmosꢀ
phere (Table 6). Aryl iodides substituted with methyl, methꢀ
oxy, and nitro groups at varied positions underwent facile reꢀ
action with substituted phenols as well as βꢀnaphthol to yield
the aryl esters (9a-9i) in moderate to good yields (72ꢀ95%). As
was observed in the benzophenone series, the electronic influꢀ
ence of the substituents was not quite significant with esters as
well. The structure of 9g was also confirmed by single crystal
Xꢀray analysis (supporting information, Figure S1). Notably,
no product resulting from Oꢀarylation was observed.
Reaction conditions: 1a (1.0 mmol), 2a (0.6 mmol), 8a ( 0.6
mmol), Pd(OAc)2 (2 mol%), PPh3 (20 mol%), CHCl3 (3.0 equiv),
B
KOH (10.0 equiv) in 4 mL AH2O/CHCl3 (3:1),and toluene at 80
Table 5. Optimization of reaction conditions for aryl ester
synthesisa
oC for 12 h under N2 atmosphere.
The carbonylative coupling is believed to follow the mechaꢀ
nistic path shown in Scheme 3. It begins with the oxidative
addition of aryl(heteroaryl)iodide on Pd(0)L2 to yield complex
(I), which undergoes insertion of carbon monoxide generated
inꢀsitu from chloroform and KOH to form complex (II).
Thereafter, phenyl anion or phenoxide ion generated from
arylboronic acid(pinacol ester) or phenol, respectively, underꢀ
goes ligand displacement, resulting in the formation of comꢀ
plex (III).27,30
KOH
yield
(equiv)
entry
Solvent
Ligand
(%)b
1
2
3
4
Toluene
Toluene
6
6
DMAP
PPh3
ꢀ
30
ꢀ
Scheme 3. Proposed mechanism for palladium catalyzed
carbonylative coupling
H2O/CHCl3 (3:1)
H2O/CHCl3 (3:1)
10
10
PPh3
PPh3
80c
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spectra (HRMS) were recorded on a Mass spectrometer using
1
2
electrospray ionizationꢀtime of flight (ESIꢀTOF) reflectron
experiments.
3
4
5
6
7
8
9
10
11
12
13
14
15
16
General procedure for synthesis of benzophenones (3a-
3ab) and (5a-5e):
Iodobenzene (204 mg, 1 mmol), phenylboronic acid (hetꢀ
eroarylboronic acid pinacol ester) (146.32 mg, 1.2 mmol),
chloroform (250µL, 3 mmol), KOH (336.7 mg, 6 mmol),
DMAP (24.4 mg, 20 mol%), Pd(OAc)2 (4.5 mg, 2 mol%),
toluene (4 mL) were added to 8 mL ace pressure tube, sealed
o
tightly, and stirred vigorously at 80 C for 12h. After compleꢀ
tion of the reaction, the combined organic layer was extracted
with ethyl acetate, washed with water, dried over Na2SO4 and
concentrated under reduced pressure. The residue was purified
by column chromatography to afford benzophenone (3a) in
75% yield.
General Procedure for the synthesis of N- Protected
indole:
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In the final step, III undergoes reductive elimination to yield
the product and regenerate Pd(0) for the next catalytic cycle.
The faster insertion of CO into the Ar(HetAr)PdX intermediꢀ
ate (I) allows a tandem reaction, and prevents the formation of
Ar(HetAr)ꢀPdꢀAr’(OAr’) species responsible for generating
biaryls as side products. To confirm that the ester formation
goes via this route, and not through esterification of benzoic
acidwith phenol; the reaction was monitored at different time
intervals. Stopping the reaction at 2h, 5h and 12h did not indiꢀ
cate any traces of benzoic acid, confirming that the reaction
did not involve an intermediate benzoic acid which could subꢀ
sequently get esterified.
Indole (1 g, 8.54 mmol) and DMF (25 mL) were taken in a
round bottom flask, stirred and cooled in an ice bath, simultaꢀ
neously purging nitrogen gas (15 min) to create an inert atꢀ
mosphere. After that sodium hydride (0.82 g, 34.2 mmol) was
added and stirred stirred for 20 min under N2 atmosphere.
Then methyl iodide (1.82 g, 12.8 mmol) was added and the
flask was kept at room temperature for 15 min, then it was
heated at 120˚C for 12 h under nitrogen atmosphere. The proꢀ
tected indole was isolated using column chromatography on
silica and hexane as an eluent to give the product in 90 %
yield.
General Procedure for Carbonylation of Indoles with
Arylboronic Acids (7a-7g):
CONCLUSIONS
In summary we have developed a “COꢀfree”, Pd catalyzed
carbonylative coupling of aryl halides with arylboronic acids,
aryl boronates, and phenols using CHCl3. The protocol is an
extremely convenient and safe alternative to CO balloons or
pressured CO reactors essentially required for carbonylations.
The method allows the modular synthesis of an array of benꢀ
zophenones and arylesters with high functional group tolerꢀ
ance in good yields from available substrates, and is directly
amenable to structural diversification. The strategy can also be
applied for a direct carbonylative coupling of Nꢀalkylindoles
with arylboronic acids. The protocol is effective with a cheap
base like KOH in contrast to CsOH.H2O reported previously
for aminocarbonylations.10 Also, isotopically enriched organic
compounds can be prepared by direct incorporation of 13CO
and 14CO from the corresponding labelled CHCl3 available
commercially.
Nꢀmethyl indole (131 mg, 1 mmol), phenylboronic acid
(146.3 mg, 1.2 mmol), chloroform (250 µL, 3 mmol), KOH
(336.7 mg, 6 mmol), DMAP (122 mg, 1.0 equiv), Pd(OAc)2
(4.5 mg, 2 mol%), Iodine (151.2 mg,1.2 mmol) and toluene (4
mL) were added to 8 mL ace pressure tube sealed tightly, and
o
stirred vigorously at 80 C for 12h. After completion of the
reaction, the combined organic layer was extracted with ethyl
acetate, washed with water, dried over Na2SO4 and concentratꢀ
ed under reduced pressure. The residue was purified by colꢀ
umn chromatography to afford phenylbenzoate (7a) in 74 %
yield.
General procedure for synthesis of phenylbenzoate (9a-
9i):
Iodobenzene (204 mg, 1 mmol), phenol (112.8 mg, 1.2
mmol), 4 mL chloroform/water (1:3), KOH (56 mg, 10 mmol),
PPh3 (55.6 mg, 20 mol%), Pd(OAc)2 (4.5 mg, 2 mol %), were
added to 8 mL ace pressure tube and nitrogen was flushed for
10 min., then sealed tightly, and stirred vigorously at 80 oC for
12h. After completion of the reaction, the combined organic
layer was extracted with ethyl acetate, washed with water,
dried over Na2SO4 and concentrated under reduced pressure.
The residue was purified by column chromatography to afford
phenylbenzoate (9a) in 86 % yield.
Experimental Section
General Methods:
All reagents and solvents were of pure analytical grade.
Thin layer chromatography (TLC) was performed on 60 F254
silica gel, preꢀcoated on aluminium plates and revealed with
either a UV lamp (λmax = 254 nm) or iodine vapours. The
products were purified by column chromatography on silica
gel 230ꢀ400 mesh. 1H, 19F and 13C NMR spectra were recorded
on 300 MHz (1H 300 MHz, 19F 282 MHz, 13C 75 MHz) and
400 MHz spectrometer (1H 400 MHz) using CDCl3 as the
solvent with tetramethylsilane (TMS) as the internal standard
at room temperature. Chemical shifts are in δ (ppm) relative to
TMS. The coupling constants (J) in Hz. High resolution mass
Procedure for competitive palladium catalyzed car-
bonylative coupling for synthesis of ketone versus es-
ter:
Iodobenzene (204 mg, 1 mmol), phenyl boronic acid (73
mg, 0.6 mmol), phenol (56 mg, 0.6 mmol), Pd(OAc)2 (4.5 mg,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 11
2 mol%), PPh3 (55 mg, 20 mol%), CHCl3 (250 µL, 3.0 equiv),
and KOH (561 mg, 10.0 equiv) were added to 4 mL
H2O/CHCl3 (3:1) in 8 mL ace pressure tube and heated at 80
oC for 12 h under N2 atmosphere. After completion of the reacꢀ
tion, the combined organic layer was extracted with ethyl aceꢀ
tate, washed with water, dried over Na2SO4 and concentrated
under reduced pressure. The residue was purified by column
chromatography. 3a and 9a were obtained in 46% (83 mg) and
24% (48 mg) yields respectively. The same experiment was
repeated by replacing 4 mL H2O/CHCl3 (3:1) with 4 mL toluꢀ
ene as solvent.
Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H); 13
NMR (75 MHz, CDCl3): δ 193.0, 139.3, 138.5, 133.5 (q, J = 30
C
1
2
3
4
5
6
7
8
Hz), 131.4, 129.3, 129.2, 126.0 (q, J = 4.0 Hz), 124.7 (q, J = 3.4
19
Hz), 116.8, 115.3; F NMR (282 MHz, CDCl3) δ ꢀ63.2 (s, 1F);
MS (ESI) m/z 276 [M+H]+; HRMS Calculated for C15H9F3NO+
276.0631; Found: 276.0634 [M + H]+.
1ꢀ(4Benzoylphenyl)ethanone (3h).27 Brown liquid, Hexꢀ
1
ane/EtOAc = 96/4, yield 77% (172 mg); H NMR (300 MHz,
CDCl3): δ 7.98 (d, J = 6.9 Hz, 2H), 7.79 (d, J = 8.1 Hz,
2H),7.73 (d, J = 6.3 Hz, 2H), 7.62–7.52 (m, 1H), 7.44 (d, J =
6.6 Hz, 2H), 2.59 (s, 3H); 13C NMR (75 MHz, CDCl3): δ
197.5, 196.0, 141.4, 139.6, 136.9, 133.0, 130.1, 130.0, 128.5,
128.2, 26.8; MS (ESI) m/z 247 [M+Na]+; HRMS Calculated
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
Physical Properties and Characterization Data of the
Synthesized Compounds:
+
for C15H12NaO2 247.0730; Found: 247.0733 [M + Na]+.
Benzophenone (3a):31 White solid, Hexane/EtOAc = 98/2,
yield 75% (136 mg); 1H NMR (300 MHz, CDCl3): δ 7.81 (d, J
= 7.2 Hz, 4H), 7.57 (d, J = 6.6 Hz, 2H), 7.48 (d, J = 6.9 Hz,
4H); 13C NMR (75 MHz, CDCl3): δ 196.8, 137.6, 132.5,
130.1, 128.3; MS (ESI) m/z 183 [M+H]+; HRMS Calculated
for C13H11O+ 183.0804; Found: 183.0806 [M + H]+.
(4ꢀNitrophenyl)(phenyl)methanone (3i).27 Yellow solid,
1
Hexane/EtOAc = 96/4, yield 83% (189 mg); H NMR (400
MHz, CDCl3): δ 8.35 (d, J = 8.4 Hz, 2H), 7.94 (d, J = 8.8 Hz,
2H), 7.81 (d, J = 7.6 Hz, 2H), 7.66 (t, J = 7.2 Hz, 1H), 7.53 (t,
J = 7.6 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 194.9, 149.8,
142.9, 136.3, 133.5, 130.7, 130.1, 128.7, 123.6; MS (ESI) m/z
(4ꢀEthylphenyl)(phenyl)methanone (3b):32 White solid, Hexꢀ
+
1
228 [M+H]+; HRMS Calculated for C13H10NO3 228.0655;
ane/EtOAc = 98/2, yield 87% (182 mg); H NMR (300 MHz,
Found: 228.0663 [M + H]+.
CDCl3): 7.69–7.63 (m, 4H), 7.46 (t, J = 7.2 Hz, 1H), 7.35 (t, J
= 7.5 Hz, 2H), 7.19 (d, J = 8.1 Hz, 2H), 2.62 (q, J = 7.5 Hz,
2H), 1.71 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ
196.3, 149.4, 138.0, 135.2, 132.1, 130.4, 129.9, 128.2, 127.8,
29.0, 15.2; MS (ESI) m/z 211 [M+H]+; HRMS Calculated for
C15H15O+ 211.1117; Found: 211.1121 [M + H]+.
Naphthalenꢀ2ꢀyl(4ꢀnitrophenyl)methanone (3j).35 Yellow
1
solid, Hexane/EtOAc = 96/4, yield 83% (230 mg); H NMR
(300 MHz, CDCl3): δ 8.38 (d, J = 7.2 Hz, 2H), 8.25 (s, 1H),
8.01–7.94 (m, 6H), 7.68–7.60 (m, 2H); 13C NMR (75 MHz,
CDCl3): δ193.7, 148.8, 142.2, 134.6, 132.5, 131.4, 131.2,
129.7, 128.5, 128.0, 127.8, 126.9, 126.2, 124.2, 122.6; MS
(4ꢀChlorophenyl)(phenyl)methanone (3c).31 White solid,
+
1
(ESI) m/z 278 [M+H]+; HRMS Calculated for C17H12NO3
Hexane/EtOAc = 97/3, yield 75% (162 mg); H NMR (300
278.0812; Found: 278.0818 [M + H]+.
MHz, CDCl3) : 7.77–7.71 (m, 4H), 7.60–7.55 (m, 1H), 7.48–
7.41 (m, 4H); 13C NMR (75 MHz, CDCl3); δ 195.4, 138.9,
137.2, 135.9, 132.7, 131.5, 129.9, 128.6, 128.4; MS (ESI) m/z
217 [M+H]+; HRMS Calculated for C13H10ClO+ 217.0420;
Found: 217.0415 [M + H]+.
(4ꢀMethoxyphenyl)(naphthalenꢀ2ꢀyl)methanone
(3k).36
1
White solid, Hexane/EtOAc = 97/3, yield 82% (215 mg ); H
NMR (300 MHz, CDCl3): δ 8.44–8.42 (s, 1H), 8.3 (m, 6H),
7.60 (t, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H) , 3.93 (s,
3H); 13C NMR (75 MHz, CDCl3): δ 195.6, 163.2, 135.5,
135.1, 132.6, 132.3, 131.1, 130.5, 129.3, 128.2, 128.0, 127.8,
126.7, 125.9, 113.7, 55.5; MS (ESI) m/z 263 [M+H]+; HRMS
(4ꢀFluorophenyl)(phenyl)methanone (3d).31 Colourless oil,
1
Hexane/EtOAc = 97/3, yield 74% (148 mg); H NMR (400
MHz, CDCl3): δ 7.76–7.71 (m, 2H) 7.69–7.66 (m, 2H), 7.49 (t,
J = 7.6 Hz, 1H), 7.38 (t, J = 7.6 Hz, 2H), 7.08–7.03 (m, 2 H);
13C NMR (75 MHz, CDCl3): δ 195.2, 165.4 (d, J = 252.5 Hz),
+
Calculated for C18H15O2 263.1067; Found: 263.1062 [M +
H]+.
(4ꢀEthylphenyl)(4ꢀmethoxyphenyl)methanone (3l).37 White
137.5, 133.8 (d, J = 3 Hz), 132.7 (d, J = 9.2 Hz), 132.5, 132.4,
1
19
solid, Hexane/EtOAc = 97/3, yield 71% (171 mg); H NMR
129.9, 115.5 (d, J = 21.8 Hz); F NMR (282 MHz, CDCl3) δ ꢀ
106.0 (s, 1F); MS (ESI) m/z 201 [M+H]+; Calculated for
C13H10FO+ 201.0710; Found: 201.0713 [M + H]+.
(300 MHz, CDCl3) : δ 7.76–7.71 (m, 2H), 7.63–7.61 (m, 2H),
7.22–7.20 (m, 2H), 6.90ꢀ6.86 (m, 2H), 3.80 (s, 3H), 2.65 (q, J
= 7.5 Hz, 2H), 1.20 (t, J = 7.8 Hz, 3H); 13C NMR (75 MHz,
CDCl3): 195.3, 163.1, 148.8, 135.8, 132.4, 130.6, 130.1,
127.7, 113.5, 55.5, 28.9, 15.2; MS (ESI) m/z 241 [M+H]+;
Naphthalenꢀ2ꢀyl(phenyl)methanone (3e).31 White solid,
1
Hexane/EtOAc = 98/2, yield 68% (157 mg); H NMR (300
+
MHz, CDCl3): δ 8.36–8.30 (m, 1H), 8.02–7.89 (m, 6H), 7.65ꢀ
7.55 (m, 5H); 13C NMR (75 MHz, CDCl3): δ 197.1, 137.9,
135.3, 134.9, 132.4, 132.3, 131.9, 131.8, 130.1, 129.4, 128.4,
127.8, 126.8, 125.9, 125.8; MS (ESI) m/z 233 [M+H]+; HRMS
Calculated for C17H13O+ 233.0961; Found: 233.0964 [M +
H]+.
HRMS Calculated for C16H17O2 241.1223; Found: 241.1224
[M + H]+.
(3ꢀNitrophenyl)(phenyl)methanone (3m).38 Yellow solid,
1
Hexane/EtOAc = 96/4, yield 82% (186 mg); H NMR (400
MHz, CDCl3): δ 8.63 (s, 1H), 8.45 (d, J = 8.0 Hz, 1H), 8.15 (d,
J = 8.0 Hz, 1H), 7.81 (d, J = 7.6 Hz, 2H), 7.73–7.65 (m, 2H),
7.54 (t, J = 8.0 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 194.1,
148.1, 139.1, 136.3, 135.4, 133.3, 130.0, 129.6, 128.7, 126.7,
124.7; MS (ESI) m/z 228 [M+H]+; HRMS Calculated for
4ꢀBenzoylbenzonitrile (3f).33 White solid, Hexane/EtOAc =
1
97/3, yield 72% (149 mg); H NMR (400 MHz, CDCl3): δ
7.88 (d, J = 8.4 Hz, 2H), 7.81–7.78 (m, 4H), 7.65 (t, J = 7.6
Hz, 1H), 7.52 (t, J = 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3):
δ 195.0, 141.2, 136.3, 133.3, 132.2, 130.2, 130.1, 128.6, 118.0,
115.6; MS (ESI) m/z 208 [M+H]+; HRMS Calculated for
C14H10NO+ 208.0757; Found: 208.0760 [M + H]+.
+
C13H10NO3 228.0655; Found: 228.0658 [M + H]+.
Naphthalenꢀ2ꢀyl(3ꢀnitrophenyl)methanone (3n).Yellow solꢀ
o
id, Hexane/EtOAc = 96/4, mp: 110ꢀ125 C, yield 78% (216
mg); 1H NMR (300 MHz, CDCl3): δ 8.71 (s, 1H), 8.50 (d, J =
8.7 Hz, 1H), 8.35–8.20 (m, 2H), 8.01–7.95 (m, 4H), 7.78–7.61
(m, 3H); 13C NMR (75 MHz, CDCl3): δ 194.2, 148.4, 139.4,
4ꢀ(4ꢀ(Trifluoromethyl)benzoyl)benzonitrile (3g).34 White
1
solid, Hexane/EtOAc = 97/3, yield 79% (217 mg); H NMR
(400 MHz, CDCl3): δ 8.39 (d, J = 8.8 Hz, 2H), 7.98 (d, J = 8.8
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Page 7 of 11
The Journal of Organic Chemistry
135.6, 135.5, 133.6, 132.3, 132.1, 129.7, 129.6, 128.9, 128.9,
130.4, 128.9, 128.5, 128.0, 127.7, 127.3, 127.1, 21.7; MS
127.9, 127.2, 126.7, 125.3, 124.7; MS (ESI) m/z 278 [M+H]+;
(ESI) m/z 275 [M+H]+; HRMS Calculated for C14H12BrO+
1
2
3
4
5
6
7
8
+
HRMS Calculated for C17H12NO3 278.0810; Found: 278.0823
275.0066; Found: 275.0092 [M + H]+.
[M+H]+.
(2ꢀMethoxyphenyl)(phenyl)methanone (3v).30 White solid,
1
(4ꢀMethoxyphenyl)(naphthalenꢀ2ꢀyl)methanone
(3o).36
Hexane/EtOAc = 97/3, yield 76% (161 mg); H NMR (300
1
White solid, Hexane/EtOAc = 97/3, yield 82% (215 mg); H
NMR (400 MHz, CDCl3): δ 8.28 (s, 1H), 7.94–7.90 (m, 4H),
7.61–7.55 (m, 2H), 7.40 (d, J = 6.0 Hz, 3H), 7.18–7.15 (m,
1H), 3.87 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 195.6, 163.2,
135.5, 135.1, 132.6, 132.3, 131.1, 130.5, 129.3, 128.2, 128.0,
127.8, 126.7, 125.9, 113.7, 55.5; MS (ESI) m/z 285 [M+Na]+;
MHz, CDCl3): δ 7.84 (d, J = 7.2 Hz, 2H), 7.58–7.38 (m, 5H),
7.09–7.01 (m, 2H), 3.75 (s, 3H); 13C NMR: δ (75 MHz,
CDCl3): δ 196.5, 157.4, 137.9, 132.9, 131.9, 129.8, 129.6,
128.9, 128.2, 120.5, 111.5, 55.6; MS (ESI) m/z 235 [M+Na]+;
+
HRMS Calculated for C14H12NaO2
235.0730; Found:
9
235.0741 [M + Na]+.
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
+
Phenyl(oꢀtolyl)methanone (3w).31 White solid, Hexꢀ
ane/EtOAc = 98/2, yield 67% (135 mg); H NMR (300 MHz,
HRMS Calculated for C18H14NaO2 285.0886; Found:
285.0875 [M + Na]+.
1
(4ꢀEthylphenyl)(3ꢀmethoxyphenyl)methanone (3p).39 Yellow
oil, Hexane/EtOAc = 97/3, yield 67% (161 mg); 1H NMR (400
MHz, CDCl3): δ 7.76–7.74 (m, 2H), 7.37–7.29 (m, 5H), 7.13–
7.10 (m, 1H), 3.86 (s, 3H), 2.74 (q, J = 7.6 Hz, 2H), 1.29 (t, J
= 7.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 196.2, 159.6,
149.4, 139.3, 135.2, 130.4, 129.1, 127.8, 122.7, 118.6, 114.3,
55.5, 29.0, 15.2; MS (ESI) m/z 263 [M+Na]+; HRMS Calcuꢀ
lated for C16H16NaO2+ 263.1043; Found: 263.1048 [M + Na]+.
CDCl3): δ 7.83 (d, J = 7.2 Hz, 2H), 7.59 (d, J = 6.3 Hz, 1H),
7.50–7.40 (m, 3H), 7.33–7.27 (m, 3H), 2.36 (s, 3H); 13C NMR
(75 MHz, CDCl3): δ 198.7, 138.6, 137.8, 136.8, 133.2, 131.0,
130.3, 130.1, 128.5, 128.5, 125.2, 20.0; MS (ESI) m/z 197
[M+H]+; HRMS Calculated for C14H13O+ 197.0961; Found:
197.0960 [M + H]+.
(2ꢀBromophenyl)(oꢀtolyl)methanone (3x).43 Colourless oil,
1
Hexane/EtOAc = 98/2, yield 76% (208 mg); H NMR (400
(4ꢀEthylphenyl)(3ꢀnitrophenyl)methanone (3q). Yellow oil,
MHz, CDCl3): (400 MHz, CDCl3 ): 7.62 (d, J = 8.0 Hz, 1H),
7.44ꢀ7.42 (m, 1H), 7.40–7.39 (m, 2H), 7.34–7.30 (m, 3H),
7.19 (t, J = 7.6 Hz, 1H), 2.59 (s, 3H); 13C NMR (75 MHz,
CDCl3): δ198.0, 141.7, 139.9, 136.5, 133.5, 132.1, 131.9,
131.6, 131.4, 129.8, 127.2, 125.5, 120.2, 21.3; MS (ESI) m/z
296 [M+Na]+; HRMS Calculated for C14H11BrNaO+ 296.9886;
Found: 296.9873 [M + Na]+.
1
Hexane/EtOAc = 96/4, yield 76% (194 mg); H NMR (300
MHz, CDCl3): δ 8.62 (s, 1H), 8.44 (d, J = 8.1 Hz, 1H), 8.13 (d,
J = 7.8 Hz, 1H), 7.76– 7.67 (m, 3H), 7.35 (d, J = 8.1 Hz, 2H),
2.76 (q, J = 7.8 Hz, 2H), 1.30 (t, J = 7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3): δ 193.7, 150.6, 148.1, 139.5, 135.3, 133.8,
130.4, 129.6, 128.3, 126.5, 124.6, 29.0, 15.1; MS (ESI) m/z
+
256 [M+H]+; HRMS Calculated for C15H14NO3 256.0968;
Phenyl(thiophenꢀ3ꢀyl)methanone (3y).31 Yellow oil, Hexꢀ
Found: 256.0967 [M + H]+.
1
ane/EtOAc = 98/2, yield 73% (137 mg); H NMR (400 MHz,
(4ꢀFluorophenyl)(3ꢀmethoxyphenyl)methanone (3r).40 Yelꢀ
CDCl3): δ 8.03–7.93 (m, 1H), 7.86–7.84 (m, 1H), 7.75–7.64
(m, 1H), 7.62–7.57 (m, 1H), 7.55–7.44 (m, 3H), 7.40–7.38 (m,
1H); 13C NMR (75 MHz, CDCl3): δ 190.2, 141.3, 138.7,
133.9, 132.3, 129.4, 128.8, 128.6, 126.2; MS (ESI) m/z 189
[M+H]+; HRMS Calculated for C11H9OS+ 189.0369; Found:
189.0368 [M + H]+.
1
low oil, Hexane/EtOAc = 96/4, yield 74% (170 mg); H NMR
(300 MHz, CDCl3):δ 7.84–7.81 (m, 2H), 7.55–7.44 (m, 3H),
7.28–7.26 (m, 1H), 7.00–6.96 (m, 2H), 3.89 (s, 3H); 13C NMR
(75 MHz, CDCl3): δ 194.0, 163.5, 162.4 (d, J = 246.4), 140.4
(d, J = 6.3 Hz), 132.5, 129.9 (d, J = 7.7 Hz), 129.6, 125.4 (d, J
(3ꢀMethoxyphenyl)(thiophenꢀ3ꢀyl)methanone (3z).44 Yellow
= 2.9 Hz), 118.8 (d, J = 21.2 Hz), 116.5 (d, J = 22.2 Hz),
19
1
oil, Hexane/EtOAc = 97/3, yield 72% (157 mg); H NMR
113.7, 55.50; F NMR (282 MHz, CDCl3) δ ꢀ106.0 (s, 1F);
+
MS (ESI) m/z 231 [M+H]+; HRMS Calculated for C14H12FO2
(300 MHz, CDCl3) : δ 7.87 (s, 1H), 7.54 (d, J = 12.9 Hz, 1H),
7.31 (d, J = 7.8 Hz, 4H), 7.05 (d, J = 6 Hz, 1H), 3.78 (s, 3H);
13C NMR (75 MHz, CDCl3): δ 189.7, 159.7, 141.3, 139.9,
133.9, 129.3, 128.6, 126.2, 122.0, 118.7, 113.9, 55.5; MS
(ESI) m/z 241 [M+Na]+; HRMS Calculated for C12H10NaO2S+
241.0294; Found: 241.0298 [M + Na]+.
231.0816; Found: 231.0828 [M + H]+.
(3ꢀMethoxyphenyl)(phenyl)methanone (3s).41 White solid,
Hexane/EtOAc = 97/3, yield 79% (167 mg); H NMR (300
1
MHz, CDCl3): δ 7.81 (d, J = 7.2 Hz, 2H), 7.59 (t, J = 7.2 Hz,
2H), 7.51–7.46 (m, 2H), 7.41–7.33 (m, 2H), 7.14 (d, J = 6.9
Hz, 1H), 3.86 ( s, 3H); 13C NMR (75 MHz, CDCl3): δ 196.4,
159.8, 139.0, 137.8, 132.4, 130.1, 129.2, 128.3, 122.9, 118.9,
114.4, 55.5; MS (ESI) m/z 235 [M+Na]+; HRMS Calculated
(4ꢀMethoxyphenyl)(pyridinꢀ2ꢀyl)methanone (3aa).45 White
1
solid, Hexane/EtOAc = 96/4, yield 70% (149 mg); H NMR
(300 MHz, CDCl3): δ 8.61–8.60 (m, 1 H), 8.06–8.03 (m, 2H),
7.9 (d, J = 7.8 Hz, 1H), 7.81–7.78 (m, 1H), 7.39–7.35 (m, 1H),
6.90–6.87 (m, 2H), 3.79 (s, 3H); 13C NMR (75 MHz, CDCl3):
δ 192.2, 163.6, 155.8, 148.3, 137.0, 133.5, 129.0, 125.8, 124.5,
113.5, 55.5; MS (ESI) m/z 236 [M+Na]+; HRMS Calculated
+
for C14H12NaO2 235.0730; Found: 235.0737 [M + Na]+.
Phenyl(mꢀtolyl)methanone (3t).31 White solid, Hexꢀ
1
ane/EtOAc = 98/2, yield 71% (139 mg); H NMR (300 MHz,
CDCl3): 7.79 (d, J = 6.6 Hz, 2H), 7.62 (s, 1H), 7.56 (d, J = 2.4
Hz, 2H), 7.46 (d, J = 6.3 Hz, 2H), 7.35 (d, J = 6.6 Hz, 2H),
2.39 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 196.9, 138.2,
137.8, 137.7, 133.2, 132.4, 130.5, 130.1, 128.3, 128.1, 127.4,
21.4; MS (ESI) m/z 197 [M+H]+; HRMS Calculated for
C14H13O+ 197.0961; Found: 197.0959 [M + H]+.
+
for C13H11NNaO2 236.0682; Found: 236.0682 [M + Na]+.
(4ꢀEthylphenyl)(4'ꢀiodoꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀyl)methanone
o
(3ab). White solid, Hexane/EtOAc = 97/3, mp: 221ꢀ234 C,
yield 64%; 1H NMR (300 MHz, CDCl3): δ 7.88 (d, J = 8.4 Hz,
2H), 7.83–7.76 (m, 4H), 7.39 (d, J = 8.4 Hz, 2H), 7.33 (d, J =
8.4 Hz, 2H), 2.75 (q, J = 7.5 Hz, 2H), 1.30 (t, J = 7.5 Hz,
3H);13C NMR (75 MHz, CDCl3): 196.0, 149.6, 143.8, 139.6,
138.2, 137.1, 135.2, 130.7, 130.4, 129.1, 127.9, 126.7, 94.1,
29.0, 15.3; MS (ESI) m/z 413 [M+H]+; HRMS Calculated for
C21H18IO+ 413.0397; Found: 413.0409 [M + H]+.
(2ꢀBromophenyl)(mꢀtolyl)methanone (3u).42 Yellow semiꢀ
1
solid, Hexane/EtOAc = 98/2, yield 79% (216 mg); H NMR
(300 MHz, CDCl3): 7.59ꢀ7.55 (m, 2H), 7.49 (d, J = 7.2 Hz,
1H), 7.34–7.28 (m, 4H), 7.19 (s, 1H), 2.35 (s, 3H); 13C NMR
(75 MHz, CDCl3): δ 197.2, 138.1, 137.8, 134.6, 133.1 131.0,
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Phenyl(4ꢀ((4ꢀphenylpiperazinꢀ1yl)methyl)phenyl)methanone
Page 8 of 11
7.94–7.89 (m, 4H), 7.58–7.54 (m, 3H), 7.37–7.34 (m, 3H),
3.83 (s, 3H); 13C NMR (75 MHz, CDCl3) ; δ 190.8, 138.3,
137.8, 137.6, 134.7, 132.6, 129.2, 129.0, 128.2, 127.8, 127.5,
127.3, 126.6, 125.6, 123.7, 122.8, 122.7, 115.9, 109.6, 33.6;
MS (ESI) m/z 286 [M+H]+; HRMS Calculated for C20H16NO+
286.1226; Found: 286.1212 [M + H]+.
1
2
3
4
5
6
7
8
(5a). Brown liquid, Hexane/EtOAc = 95/5, yield 58%(206
1
mg); H NMR (400 MHz, CDCl3) : 7.80 (t, J = 7.6 Hz, 3H),
7.59 (t, J = 7.6 Hz, 1H), 7.50–7.47 (m, 4H), 7.28–7.24 (m,
3H), 6.93 (d, J = 8 Hz, 2H), 6.86 (t, J = 7.2 Hz,1H), 3.66 (s,
2H), 3.23 (t, J = 4.8 Hz, 4H), 2.66 (t, J = 4.8 Hz, 4H); 13C
NMR (75 MHz, CDCl3); δ 196.4, 151.3, 143.0, 137.8, 136.6,
132.3, 130.2, 130.0, 129.0, 128.7, 128.3, 119.8, 116.2, 62.6,
53.2, 49.1; MS (ESI) m/z 357 [M+H]+; HRMS Calculated for
C24H25N2O+ 357.1961; Found: 357.1976 [M + H]+.
(4ꢀethylphenyl)(1ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)methanone
(7c).
Yellow liquid, Hexane/EtOAc = 94/6, yield 71% (186 mg); 1H
NMR (400 MHz, CDCl3) : 8.43–8.41 (m, 1H), 7.76 (d, J = 8.0
Hz, 2H), 7.56 (s, 1H), 7.37–7.30 (m, 5H), 3.85 (s, 3H), 2.74
(q, J = 7.6 Hz, 2H), 1.30 (t, J = 7.6 Hz, 3H); 13C NMR (75
MHz, CDCl3); δ 197.7, 147.8, 138.4, 137.6, 137.5, 129.0,
127.8, 127.3, 123.6, 122.8, 122.6, 115.8, 109.5, 33.5, 28.9,
15.4; MS (ESI) m/z 264 [M+H]+; HRMS Calculated for
C18H18NO+ 264.1383; Found: 264.1379 [M + H]+.
9
(4ꢀ((4ꢀPhenylpiperazinꢀ1ꢀyl)methyl)phenyl)(pꢀ
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
tolyl)methanone (5b). Brown liquid, Hexane/EtOAc = 95/5,
yield 62% (229 mg); 1H NMR (400 MHz, CDCl3) : 7.80–7.71
(m, 4H), 7.48 (d, J = 8 Hz, 2H), 7.30–7.27 (m, 3H), 7.25–7.23
(m, 1H), 6.93 (d, J = 8 Hz, 2H), 6.88ꢀ6.84 (m, 1H), 3.66 (s,
2H), 3.23 (t, J = 4.8 Hz, 4H), 2.66 (t, J = 5.2 Hz, 4H), 2.45 (s,
3H); 13C NMR (75 MHz, CDCl3); δ 196.2, 151.3, 143.2,
137.0, 135.0, 134.9, 130.2, 130.1, 129.1, 129.0, 128.9, 119.8,
116.1, 62.6, 53.2, 49.1, 21.6; MS (ESI) m/z 371 [M+H]+;
HRMS Calculated for C25H27N2O+ 371.2118; Found: 371.2119
[M + H]+.
(1ꢀethylꢀ1Hꢀindolꢀ3ꢀyl)(phenyl)methanone (7d).29 Yellow
liquid, Hexane/EtOAc = 94/6, yield 66% (164 mg); H NMR
1
(400 MHz, CDCl3) : 8.43–8.41 (m, 1H), 7.83–7.81 (m, 2H),
7.59 (s, 1H), 7.55–7.53 (m, 1H), 7.51–7.47 (m, 2H), 7.42–7.40
(m, 1H), 7.37–7.33 (m, 2H), 4.23 (q, J = 7.2 Hz, 2H), 1.52 (t, J
= 7.6 Hz, 3H); 13C NMR (75 MHz, CDCl3); δ 190.9. 141.0,
136.7, 136.2, 131.0, 128.7, 128.3, 127.5, 123.6, 122.9, 122.7,
115.8, 109.8, 41.9, 15.3; MS (ESI) m/z 272 [M+Na]+; HRMS
Calculated for C17H15NNaO+ 272.1046; Found: 272.1046 [M +
Na]+.
(2ꢀMethoxyphenyl)(4ꢀ((4ꢀphenylpiperazinꢀ1ꢀ
yl)methyl)phenyl)methanone (5c). Brown liquid, Hexꢀ
1
ane/EtOAc = 94/6, yield 46% (177 mg); H NMR (400 MHz,
CDCl3) : 7.79 (d, J = 8.0 Hz, 2H), 7.49–7.42 (m, 3H), 7.36 ꢀ
7.34 (m, 1H), 7.28 (s, 1H), 7.24 (s, 1H), 7.06–7.00 (m, 2H),
6.92 (d, J = 7.6 Hz, 2H), 6.85 (t, J = 6.8 Hz, 1H), 3.74 (s, 3H),
3.63 (s, 2H), 3.21 (t, J = 4.8 Hz, 4H), 2.63 (t, J = 4.8 Hz, 4H);
13C NMR (75 MHz, CDCl3); δ 196.1, 157.3, 151.3, 143.6,
136.9, 131.7, 130.0, 129.5, 129.1, 128.8, 128.4, 120.5 119.7,
(1ꢀethylꢀ1Hꢀindolꢀ3ꢀyl)(naphthalenꢀ2ꢀyl)methanone
(7e).
1
Yellow oil, Hexane/EtOAc = 94/6, yield 80% (239 mg); H
NMR (400 MHz, CDCl3) : 8.44–8.42 (m, 1H), 8.3 (s, 1H),
7.96–7.91 (m, 4H), 7.65 (s, 1H), 7.60–7.55 (m, 2H), 7.43–7.41
(m, 1H), 7.37–7.35 (m, 2H), 4.23 (q, J = 7.2 Hz, 2H), 1.52 (t, J
= 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3); δ 197.9, 138.3,
136.7, 136.2, 134.7, 132.6, 129.2, 129.1, 128.2, 127.8, 127.5,
127.5, 126.6, 125.6, 123.6, 122.9, 122.7, 116.0,109.8, 41.8,
15.2; MS (ESI) m/z 322 [M+Na]+; HRMS Calculated for
C21H17NNaO+ 322.1202; Found: 322.1195 [M + Na]+.
116.1, 111.5, 62.7, 55.7, 53.2, 49.2; MS (ESI) m/z 387
+
[M+H]+; HRMS Calculated for C25H27N2O2
Found: 387.2071 [M + H]+.
387.2067;
2ꢀ(2ꢀBenzoylbenzyl)isoindolineꢀ1,3ꢀdione (5d).46 Brown solꢀ
id, Hexane/EtOAc = 96/4, yield 57% (195 mg); 1H NMR (400
MHz, CDCl3) : 7.85–7.83 (m, 2H), 7.81–7.78 (m, 2H), 7.71–
7.67 (m, 2H), 7.56–7.55 (m, 1H), 7.47–7.42 (m, 3H), 7.39 (t, J
= 6.8 Hz, 2H), 7.34–7.30 (m, 1H), 5.05 (s, 2H); 13C NMR (75
MHz, CDCl3); δ 197.8, 167.9, 138.0, 137.6, 136.1, 134.0,
133.1, 132.0, 130.9, 130.4, 129.4, 128.6, 128.4, 126.8, 123.3,
38.9; MS (ESI) m/z 364.0945 [M+Na]+; HRMS Calculated for
C22H15NNaO3+ 364.0944; Found: 364.0946 [M + Na]+.
(5ꢀmethoxyꢀ1ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)(phenyl)methanone
(7f).28 White solid, Hexane/EtOAc = 93/7, yield 78% (206
1
mg); H NMR (400 MHz, CDCl3) : 7.87 (d, J = 2.4Hz, 7.68ꢀ
7.66 (m, 2H), 7.41–7.39 (m, 1H), 7.11–7.08 (m, 1H), 6.87–
6.84 (m, 1H), 3.79 (s, 3H), 3.64 (s, 3H); 13C NMR (75 MHz,
CDCl3); δ 190.8, 156.6, 141.0, 138.0, 132.6, 131.0, 128.6,
128.3, 128.1, 115.2, 114.1, 110.5, 103.9, 55.8, 33.7; MS (ESI)
2ꢀ(2ꢀ(4ꢀMethylbenzoyl)benzyl)isoindolineꢀ1,3ꢀdione (5e).47
Brown semisolid, Hexane/EtOAc = 96/4, yield 67% (237 mg);
1H NMR (400 MHz, CDCl3) : 7.79–7.77 (m, 2H), 7.75–7.73
(m, 2H), 7.68–7.67 (m, 2H), 7.43–7.37 (m, 2H), 7.36–7.31 (m,
2H), 7.23 (d, J = 8 Hz, 2H), 5.02 (s, 2H), 2.40 (s, 3H); 13C
NMR (75 MHz, CDCl3); δ 197.3, 167.9, 138.4, 135.7, 135.0,
134.4, 133.9, 132.0, 131.2, 130.6, 129.1, 128.6, 126.8, 123.3,
39.0, 21.8; MS (ESI) m/z 378 [M+Na]+; HRMS Calculated for
C23H17NNaO3+ 378.1101; Found: 378.1108 [M + Na]+.
m/z 338 [M+H]+; HRMS Calculated for C17H16NO2
+
266.1175; Found: 266.1175 [M + H]+.
(5ꢀmethoxyꢀ1ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)(naphthalenꢀ2ꢀ
yl)methanone (7g). White solid, Hexane/EtOAc = 93/7, yield
76% (239 mg), mp: 97ꢀ115 C; 1H NMR (400 MHz, CDCl3) :
o
8.23 (s, 1H), 8.00 (d, J = 2.4 Hz, 1H), 7.95–7.89 (m, 4H),
7.56–7.52 (m, 3H), 7.25–7.24 (m, 1H), 7.01–6.98 (m, 1H),
3.92 (s, 3H), 3.80 (s, 3H); 13C NMR (75 MHz, CDCl3); δ
190.8, 156.7, 139.6, 138.3, 138.0, 134.7, 132.6, 129.0, 128.1,
127.8, 127.5, 126.6, 125.5, 115.5, 114.3, 110.5, 104.0, 55.9,
34.1, 33.7, 128.6, 128.3, 128.1, 115.2, 114.1, 110.5, 103.9,
(1ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)(phenyl)methanone (7a).29 White
1
solid, Hexane/EtOAc = 94/6, yield 74% (178 mg); H NMR
+
(400 MHz, CDCl3) : 8.36–8.34 (m, 1H), 7.73–7.71 (m, 2H),
7.45 ꢀ7.37 (m, 4H), 7.27–7.25 (m, 3H), 3.73 (s, 3H); 13C NMR
(75 MHz, CDCl3); δ 190.8, 141.0, 137.9, 137.6, 131.1, 128.7,
128.3, 127.2, 123.6, 122.7, 122.7, 115.6, 109.6, 33.5; MS
(ESI) m/z 258 [M+Na]+; HRMS Calculated for C16H13NNaO+
258.0889; Found: 258.0897 [M + Na]+.
55.8, 33.7; HRMS Calculated for C21H17NNaO2 338.1151;
Found: 338.1154 [M + Na]+.
Phenyl benzoate (9a).22 Yellowish liquid, Hexane/EtOAc =
98/2, yield 86% (170 mg) ; H NMR (300 MHz, CDCl3): δ
8.07 (d, J = 7.2 Hz, 2H), 7.46 (t, J = 7.5 Hz, 1H), 7.35 (d, J =
7.8 Hz, 2H), 7.31 (d, J = 4.2 Hz, 1H), 7.27 (s, 1H), 7.14–7.05
(m, 3H); 13C NMR (75 MHz, CDCl3): δ 165.2, 151.1, 133.7,
130.3, 129.7, 129.6, 128.7, 126.0, 121.8; MS (ESI) m/z
1
(1ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)(naphthalenꢀ2ꢀyl)methanone (7b).29
1
White solid, Hexane/EtOAc = 94/6, yield 77% ( 219 mg), H
NMR (400 MHz, CDCl3) : 8.45–8.42 (m, 1H), 8.29 (s, 1H),
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The Journal of Organic Chemistry
+
221[M+Na]+; HRMS Calculated for C13H10NaO2 221.0573;
(m, 1H), 7.53–7.50 (m, 1H), 7.40–7.25 (m, 3H); 13C NMR (75
Found: 221.0572 [M +Na]+.
MHz, CDCl3): δ 162.3, 148.5, 146.8, 135.9, 130.7, 130.6,
130.0, 128.3, 128.0, 127.6, 126.8, 125.3, 123.6; MS (ESI) m/z
1
2
3
4
5
6
7
8
mꢀTolyl benzoate (9b).48 White liquid, Hexane/EtOAc =
98/2, yield 64% (187 mg); H NMR (300 MHz, CDCl3): δ
8.27 (d, J = 6.9 Hz, 2H), 7.67 (d, J = 7.2 Hz, 1H), 7.57 (d, J =
7.5 Hz, 2H), 7.37 (t, J = 7.5 Hz, 1H), 7.16–7.10 (m, 3H); 13C
NMR(75 MHz, CDCl3): δ165.4, 151.0, 139.7, 133.6, 130.2,
129.7, 129.3, 128.6, 126.8, 122.4, 118.7; MS (ESI) [M+H]+
+
278[M+H]+; HRMS Calculated for C13H9ClNO4 278.0214;
1
Found: 278.0225 [M+H]+.
ASSOCIATED CONTENT
Copies of 1H NMR, 13C NMR, for all the synthesized compounds,
ORTEPs and associated Xꢀray crystallographic data for 9g (CIF)
have been included. This material is available free of charge via
the Internet at http://pubs.acs.org.
+
213 Calculated for C14H13O2 213.0910; Found: 213.0907
[M+H]+.
9
Naphthalenꢀ2ꢀyl benzoate (9c).48 Brown solid, Hexꢀ
ane/EtOAc = 98/2, yield 84% (208 mg); H NMR (300 MHz,
CDCl3): δ 8.26 (d, J = 7.5 Hz, 2H), 7.92–7.82 (m, 3H), 7.70–
7.64 (m, 1H), 7.54 (t, J = 7.8 Hz, 1H), 7.50–7.46 (m, 4H),
7.38–7.35 (m, 1H);13C NMR (75 MHz, CDCl3): δ 165.4,
148.6, 133.8, 133.7, 131.5, 130.2, 129.6, 129.5, 128.6, 127.8,
127.8, 126.6, 125.8, 121.3, 118.7; MS (ESI) m/z 271[M+Na]+;
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
1
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: njain@chemistry.iitd.ac.in
Notes
The authors declare no competing financial interest.
+
HRMS Calculated for C17H12NaO2 271.0730; Found:
271.0736 [M +Na]+.
ACKNOWLEDGMENT
Phenyl 2ꢀmethylbenzoate (9d).23 White liquid, Hexꢀ
ane/EtOAc = 98/2, yield 89% (189 mg); H NMR (400 MHz,
The authors thank Council of Scientific and Industrial Research
(CSIR), India (02(180)/14/EMRꢀII) for financially supporting this
work and DSTꢀFIST for funding the ESIꢀHRMS, and SCXRD
facility at IIT Delhi. PS and SR thank IIT Delhi and CSIR for
their graduate fellowships.
1
CDCl3): δ 8.19 (d, J = 7.6 Hz, 1H), 7.50–7.42 (m, 3H), 7.34–
7.27 (m, 2H), 7.25 (s, 1H), 7. 21 (d, J = 7.6 Hz, 2H), 2.68 (s,
3H); 13C NMR (75 MHz, CDCl3): δ 165.8, 151.0, 141.3,
132.7, 132.0, 131.2, 129.5, 128.6, 125. 9, 125.8, 121.8, 19.8;
MS (ESI) m/z 235[M+Na]+; HRMS Calculated for
C14H12NaO2+ 235.0730; Found: 235.0723 [M + Na]+.
Phenyl 4ꢀmethylbenzoate (9e).23 White liquid, Hexꢀ
ane/EtOAc = 98/2, yield 64%; 1H NMR (300 MHz, CDCl3): δ
8.13(d, J = 6.3 Hz, 2H), 7.45 (d, J = 5.7 Hz, 2H), 7.34 (d, J =
7.5 Hz, 2H), 7.29–7.23 (m, 3H), 2.48 (s, 3H); 13C NMR (75
MHz, CDCl3): δ 165.3, 151.1, 144.4, 130.2, 129.5, 129.3,
126.9, 125.8, 121.8, 21.8; MS (ESI) m/z 235 [M+Na]+; HRMS
Calculated for C14H12NaO2+ 235.0730; Found: 235.0727 [M +
Na]+.
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Chem.1974, 39, 3318. (c) Schoenberg, A.; Heck, R. F. J. Org.
Chem.1974, 39, 3327.
(2) (a) Jafarpour, F.; RashidiꢀRanjbar, P.; Kashani, A. O. Eur. J.
Org. Chem.2011, 2011, 2128. (b) Caldirola, P.; Chowdhury, R.; Joꢀ
hansson, A. M.; Hacksell, U. Organometallics 1995, 14, 3897. (c)
Brunet, J.ꢀJ.; El Zaizi, A. J. Organomet. Chem.1995, 486, 275. (d)
Enquist, P.ꢀA.; Nilsson, P.; Larhed, M. Org. Lett.2003, 5, 4875.
(3) (a) Cunico, R. F.; Maity, B. C. Org. Lett.2003, 5, 4947. (b) Cuꢀ
nico, R. F.; Maity, B. C. Org. Lett. 2002, 4, 4357. (c) Cunico, R. F.;
Pandey, R. K. J. Org. Chem. 2005, 70, 9048.
(4) Ueda, T.; Konishi, H.; Manabe, K. Angew. Chem. Int. Ed. 2013,
52, 8611.
(5) Lindsay, C. M.; Widdowson, D. A. J. Chem. Soc.Perkin 1
1988, No. 3, 569
(6) Markovič, M.; Lopatka, P.; Koóš, P.; Gracza, T. Org. Lett.
2015, 17, 5618.
(7) Friis, S. D.; Lindhardt, A. T.; Skrydstrup, T. Acc. Chem. Res.
2016, 49, 594.
Phenyl 3ꢀmethoxybenzoate (9f).49 White solid, Hexꢀ
ane/EtOAc = 97/3, yield 91% (207 mg); H NMR (300 MHz,
1
CDCl3): δ 7.86 (d, J = 7.5 Hz, 1H), 7.76 (s, 1H), 7.50–7.43
(m, 3H), 7.34–7.21 (m, 4H), 3.91 (s, 3H); 13C NMR (75 MHz,
CDCl3): δ 165.1, 159.8, 151.0, 130.9, 129.6, 129.5, 125.9,
122.6, 121.7, 120.2, 114.6, 55.5; MS (ESI) m/z 251[M+Na]+;
+
HRMS Calculated for C14H12NaO3
251.0679; Found:
251.0678 [M +Na]+.
Phenyl 3ꢀnitrobenzoate (9g).50 Yellow oil, Hexane/EtOAc =
96/4, yield 86% (209 mg); H NMR (300 MHz, CDCl3): δ
1
(8) Geuther, A. Justus LiebigsAnn. Chem. 1862, 123, 121.
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9.05 (d, J = 1.5 Hz, 1H), 8.55–8.50 (m, 2H), 7.77–7.72 (m,
1H), 7.50–7.44 (m, 2H), 7.35–7.23 (m, 3H); 13C NMR (75
MHz, CDCl3): δ 163.1, 150.5, 148.4, 135.8, 131.4, 129.9,
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Tidwell, J. H.; Romines, K. R.; Schaller, L. T.; Cowan, J. R.; Gonzaꢀ
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129.7, 128.0, 126.4, 125.1, 121.5; MS (ESI) m/z 266 [M+Na]+;
+
HRMS Calculated for C13H9NNaO4
266.0424; Found:
266.0427 [M +Na]+.
Phenyl 4ꢀnitrobenzoate (9h).51 Yellow solid, Hexane/EtOAc
= 96/4, yield 95% (231 mg); H NMR (300 MHz, CDCl3): δ
1
8.40–8.36 (m, 4 H), 7.49–7.44 (m, 2H), 7.33 (d, J = 7.2 Hz,
1H), 7.25–7.22 (m, 2H); 13C NMR (75 MHz, CDCl3): δ 163.4,
150.9, 150.5, 135.0, 131.3, 129.7, 126.5, 123.8, 121.5; MS
(ESI) m/z 266[M+Na]+; HRMS Calculated for C13H9NNaO4
+
266.0424; Found: 266.0423 [M +Na]+.
2ꢀChlorophenyl 3ꢀnitrobenzoate (9i).52 Yellow solid, Hexꢀ
ane/EtOAc = 96/4, yield 72% (200 mg); H NMR (300 MHz,
CDCl3): δ 8.53–8.50 (m, 1H), 7.78–7.73 (m, 2H), 7.78–7.73
1
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