Palladium-Catalyzed Environmentally Benign Acylation

Article abstract of DOI:10.1021/acs.joc.6b01064

Recent trends in research have gained an orientation toward developing efficient strategies using innocuous reagents. The earlier reported transition-metal-catalyzed carbonylations involved either toxic carbon monoxide (CO) gas as carbonylating agent or functional-group-assisted ortho sp² C-H activation (i.e., ortho acylation) or carbonylation by activation of the carbonyl group (i.e., via the formation of enamines). Contradicting these methods, here we describe an environmentally benign process, [Pd]-catalyzed direct carbonylation starting from simple and commercially available iodo arenes and aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct coupling of iodoarenes with aldehydes without activation of the carbonyl and also without directing group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide and pitofenone.

Full text of DOI:10.1021/acs.joc.6b01064

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Article
A Palladium Catalyzed Environmentally Benign Acylation
Basuli Suchand, and Gedu Satyanarayana
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01064 • Publication Date (Web): 05 Jul 2016
Downloaded from http://pubs.acs.org on July 5, 2016
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A Palladium Catalyzed Environmentally Benign Acylation
Basuli Suchand, and Gedu Satyanarayana*
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Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi – 502 285, Sangareddy,
Telangana, INDIA
Phone: (040) 2301 6033; Fax: (040) 2301 6003 / 32, E-mail: gvsatya@iith.ac.in
ABSTRACT:
Recent trends in research have gained an orientation towards developing efficient strategies using
innocuous reagents. The earlier reported transition-metal catalyzed carbonylations involved either toxic
2
carbon monoxide (CO) gas as carbonylating agent or functional group assisted ortho sp C-H activation
(
i.e. ortho acylation) or carbonylation by the activation of carbonyl group (i.e. via the formation of
enamines). Contradicting to these methods, here we describe an environmentally benign process, [Pd]-
catalyzed direct carbonylation starting from simple and commercially available iodo arenes and
aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct
coupling of iodo-arenes with aldehydes without the activation of carbonyl and also without directing
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group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide
and pitofenone.
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Introduction:
Aryl ketones are ubiquitous structural units that can be found in natural products, pharmaceuticals,
1
agrochemicals, fragrances, dyes, and electronic materials. Also; ketones have been recognized as crucial
synthones in the realm of organic chemistry, as their electrophilic nature permits broad range of bond-
2
forming transformations. Classical methods for their synthesis include: a) Friedel–Crafts acylation; b)
3
3f
Grignard/Barbier reaction with aldehydes and followed by oxidation or Grignard reaction with nitriles
and c) organometallic 1,2-additions to Weinreb amides. Among these, the Friedel-Crafts acylation has
drawbacks, as usually leads to isomeric mixtures and fails with electron-deficient arenes; latter one
provides clean products, but involves a two-step process; while Weinreb amides afford pure products,
however, the reaction works under strong nucleophilic conditions, therefore, might not be suitable to
aromatic systems with sensitive functionalities (e.g., esters etc.). On the other hand, recently, transition-
4
metal catalysis proved to be effective to furnish ketones such as: a) Nickel catalyzed coupling between
4a
5
iodoarenes and benzaldehydes; b) Stille coupling of acyl chlorides with organostannanes; c) metal-
mediated carbonylation between halo arenes and transmetalation reagents using toxic carbon
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monoxide (CO) gas as the carbonylating agent [(e.g., organostannanes, boronic acids etc.), Figure 1]; d)
metal-catalyzed direct acylations through activation of the carbonyl group of aldehydes via the
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formation of enamine (Figure 1); e) directing group assisting metal-catalyzed ortho acylations (Figure
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1
) and f) alkene hydroacylations.
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To the best of our knowledge, there are no reports on direct acylations of aldehydes without the
directing group assistance or without activating the carbonyl group of the aldehydes with secondary
amines, such as, pyrrolidine (in-situ enamine formation), under [Pd]-catalysis. With this background, we
intended the design and development of sustainable catalytic methods. Particularly, the development of
methods based on acylations becomes indispensable when the reaction can be executed: i) under
environmentally benign conditions; ii) without the use of toxic carbon monoxide (CO) gas; iii) using
direct carbonylation without the activation of carbonyl group of aldehydes; iv) without the assistance of
functional groups (so that enables the accomplishment of structurally diverse carbonyl compounds); v)
using simple, non-toxic, inexpensive and bench-top chemicals.
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In continuation of our research interests on transition-metal mediated efficient transformations,
herein we disclose a novel and environmentally benign new one-pot method based on [Pd]-catalyzed
direct carbonylation reaction of iodo arenes with aldehydes (alkyl/aryl), leading to alkyl-aryl and aryl-aryl
ketones. This straightforward catalytic protocol does not require any directing group assistance or in-situ
enamine formation. Interestingly, this reaction made use of water present in the oxidizing agent
(
aqueous TBHP) as the sole reaction medium. Notably, this process was successful by using simple and
commercially available bench-top iodo arenes and aldehydes as coupling partners. Unlike other earlier
reports on [Pd]-catalysis, which were applied to limited number of examples or either limited to
synthesis of benzophenone derivatives or restricted to the accomplishment of acetophenone
derivatives. This protocol was successfully applied for the synthesis of both benzophenones as well as
acetophenone derivatives. Thus, showed broad substrate scope and accomplished 67 examples. In
addition, significantly, the present strategy was extended to the synthesis of biologically important
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benzofuranones and also to the synthesis of the anti-platelet drug n-butylphthalide (NBP) and further
applied to the synthesis of pitofenone, an antispasmodic which is used in Spasmalgon as combined drug.
methods using toxic "CO" gas as the carbonylating agent:
O
O
X
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Ar ArH, [Pd]/CO
Ar[M], [Pd]/CO
Ar
ref. 7e
M = B(OH)2 , AlR26g,
6f
SiR36h, SnBu36i
methods involving activation of carbonyl group:
XR1
XR1
O
R
Ar Br
+
R2
[Pd]
R2
H O
2
R2
H
base
Ar
Ar
7i
X = O or N
ref.
t
tBu
Bu
HN
N
HN
O
[Pd]
ref. 7j
N
H O
2
Ar Br
+
Ar
H
R
Ar
R
H
methods with assistance of DG (directing group):
DG
DG
O
[Pd]
+
oxidising agent
O
H
Ar
ref. 8
Ar
this work: straightforward coupling
O
O
[
Pd]
Ar
I
+
additive
H
R
Ar
R
oxidising agent
R = alkyl or aryl
i) environmentally benign; ii) eliminates the use of toxic "CO" gas;
iii) activation of carbonyl group is not required;
iv) DG assistance is not needed; and v) simple benchtop chemicals used
Figure 1: Reported approaches vs present method for the carbonyl compounds.
Results and Discussion:
Initially, we explored the reaction between 2-iodomethylbenzoate 1a and benzaldehyde 2a, in the
presence of Pd(OAc) (3 mol %)/Ag O (0.5 equiv) and aqueous TBHP in DCE at 80 °C for 18 h. As
2
2
anticipated, the di-aryl ketone 3aa was obtained, however, in poor yield (Table 1, entry 1). Increase of
benzaldehyde 2a and Pd(OAc) /Ag O improved the product 3aa yield (Table 1, entries 2 to 4). Rather
2
2
than using more amount of [Pd]-catalyst, further increase of aldehyde 2a and aqueous TBHP, proved to
be effective (Table 1, entries 5 to 7). To our delight, the reaction at elevated temperature (120 °C)
without solvent DCE, furnished the product 3aa, in good yield (Table 1, entry 8). Similarly, other solvents
also proved to be inefficient (Table 1, entries 9 to 10). This may be due to further increase of dilution
with solvents (Table 1, entries 1 to 5, 9 to 10 & 21). With PdCl (5 mol %), the product 3aa was obtained
2
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in moderate yield (Table 1. entry 11). While with AgOAc and Ag CO , the phenome 3aa was formed in
2
3
good and fair yields, respectively (Table 1, entries 12 to 13). Also, with TBHP in decane, the reaction
furnished 3aa in good yield (Table 1, entry 14). On the other hand, other oxidants were found to be
inferior (Table 1, entries 15 to 17). Even TBAI (30 mol %) as additive does not show improvement (Table
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, entry 18). The role of [Pd]-catalyst found vital, as no product 3aa was formed without the catalyst
(Table 1, entry 19). Also, the reaction without silver salt or the oxidant gave very poor yield of the
product 3aa (Table 1, entries 20 to 21). On the other hand, the reaction with other bases, such as, K CO3
2
and Cs CO , gave 3aa in low yields, respectively (Table 1, entries, entries 22 to 23). The reaction in the
2
3
presence of Pd(0)-catalyst with and without Ag O, furnished the product in fair and poor yields,
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respectively (Table 1, entries 24 to 25). Thus, the optimization studies revealed that the [Pd]-catalyst,
silver salt and the oxidant TBHP are very much crucial to drive the reaction.
a
Table 1. Optimization studies for the carbonylation product 3aa.
Entry
Additives
equiv)
Oxidants
(equiv)
Temp Time
Yield
b
(%)
(h)
(
(°C)
c,d,e
1
Ag O (0.5)
TBHP in H O (3.0)
80
18
18
18
18
34
47
52
50
2
2
d,f
2
Ag O (0.5)
TBHP in H O (3.0)
80
80
80
2
2
d,f,g
3
Ag O (1.2)
TBHP in H O (3.0)
2
2
d,f,h
4
Ag O (1.2)
TBHP in H O (3.0)
2
2
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d
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Ag O (1.2)
TBHP in H O (5.0)
80
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TBHP in H O (5.0)
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120
80
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i
Ag O (1.2)
TBHP in H O (5.0)
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Ag O (1.2)
TBHP in H O (5.0)
2
2
j
Ag O (1.2)
TBHP in H O (5.0)
2
2
k
l
0
1
2
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5
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8
Ag O (1.2)
TBHP in H O (5.0)
120
120
120
120
120
120
120
80
2
2
Ag O (1.2)
TBHP in H O (5.0)
2
2
AgOAc (1.2)
Ag CO (1.2)
TBHP in H O (5.0)
2
TBHP in H O (5.0)
2
3
2
Ag O (1.2)
TBHP in Decane (5.0)
DTBP (5.0)
2
Ag O (1.2)
2
Ag O (1.2)
H O (3.0)
2 2
2
d
Ag O (1.2)
m-CPBA (5.0)
2
Ag O (1.2) +
TBHP in H O (5.0)
2
120
2
TBAI (30 mol
%
)
m
1
2
9
0
Ag O (1.2)
TBHP in H O (5.0)
120
120
12
12
−
2
2
TBHP in H O (5.0)
15
−
2
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d
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Ag O (1.2)
−
80
17
15
15
14
15
24
50
30
69
34
2
K CO (3.0)
TBHP in H O (5.0)
2
120
120
120
120
2
3
Cs CO (3.0)
TBHP in H O (5.0)
2
2
3
10
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n
n
Ag O (1.2)
TBHP in H O (5.0)
2
2
2
_
TBHP in H O (5.0)
2
a
Unless otherwise mentioned, all the reactions were carried out by using 104.8 mg (0.40 mmol) of aryl iodide 1a, 5 mol% of
b
Pd(OAc) , 169.8 mg (1.6 mmol) of aldehyde 2a, and TBHP in H O (5.0 equiv). Isolated yields of chromatographically pure
2
2
c
d
e
f
products. 1.5 equiv of aldehyde 2a was used. 1.5 mL of DCE was used as solvent. 3 mol % of Pd(OAc) was used. 2.0 equiv of
2
g
h
i
aldehyde 2a used. 10 mol % of Pd(OAc) was used. 20 mol % of Pd(OAc) was used. 6.0 equiv of aldehyde 2a was used.
2
2
j
k
l
Reaction was carried out in 1.5 mL of MeCN. Reaction was carried out in 1.5 mL of DMSO. 5 mol % of PdCl was used.
2
m
n
Reaction was performed without palladium catalyst. 5 mol % of Pd(PPh ) was used.
3
4
Therefore, the best optimized conditions were identified as 1a (1.0 equiv), 2a (4.0 equiv), Pd(OAc) (5
2
mol %)/Ag O (1.2 equiv), aqueous TBHP (5.0 equiv) at 120 °C for 12 h to give 3aa (Table 1, entry 8). With
2
these optimized conditions in hand, to check the scope and generality of the method, we explored the
reaction between electron deficient iodo arenes 1a-g and benzaldehydes 2a-q. Gratifyingly, the reaction
was found amenable with various benzaldehydes 2a-q, it showed broad substrate scope and afforded
the corresponding aryl-aryl ketones 3aa-ga, in moderate to very good yields (Table 2). Interestingly, the
reaction was successful with benzaldehydes 2 having F, Cl, Br substituents. Notably, the reaction was
also amenable with 2-furaldehyde 2m (Table 2, 3am). However, the reaction was unsuccessful with
benzaldehyde having strong electron withdrawing nitro group (Table 2, 3aq); even after many trials with
varying amounts of the aldehydes and at different temperatures (i.e. neither the starting materials nor
the products were isolated). In fact, these observations were in good agreement with that of reactions
under such oxidative conditions. This may be probably due to the radical stabilizing effect of the
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electron withdrawing substituent. Also; the reaction was unsuccessful with heterocyclic (pyridine and
thiophene) aldehydes. It was also observed that the reaction with bromo arene did not afford the
ketone, which implies that the more reactive iodo arenes are essential for the success of the reaction.
On the other hand, the reaction with the amide 1g was unsuccessful to give 3ga and furnished only the
reductive de-iodinated by-product in 41% yield (Table 2).
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1
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a
Table 2: Scope and generality of formation of aryl-aryl ketone 3aa-ga.
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a
b
c
Isolated yields of chromatographically pure products 3aa-ga. Neither starting material nor product has isolated. De-iodinated
by-product isolated with 41% yield.
To further check the scope and applicability of the strategy, the reaction was carried out between
electron deficient iodo arenes 1a-f and aliphatic aldehydes 4a-e, under standard conditions. To our
delight, the reaction was amenable with the aliphatic aldehydes 4a-e as well, showed very good
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substrate scope and furnished the corresponding alkyl-aryl ketones 5aa-fa, in moderate to good yields,
and thus reveals the importance of the present protocol (Table 3).
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a
Table 3: Scope and generality of formation of alkyl-aryl ketone 5aa-fa.
a
Isolated yields of chromatographically pure products 5aa-fa.
In addition, to the spectroscopic data, the structure of aryl-aryl ketones 3 was further confirmed by the
single crystal x-ray diffraction analysis of 3ah (Figure 2), for details (CIF file) see; supporting information.
Figure 2: X-ray crystal structure of compound 3ah. Ellipsoids are drawn at 50% probability level.
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Furthermore, to show the applicability and significance of the present protocol, the reaction was also
performed between simple to electron rich iodo arenes 6a-j and aldehydes 2a-q or 4a-e, under
established conditions. Gratifyingly, the reaction was quite successful and gave the corresponding di-aryl
ketones 7aa-ja, in moderate to good yields (Table 4). Notably, the reaction was compatible with strong
electron withdrawing meta-nitroiodobenzene 6h (Table 4, 7ha & 8hc). Also, found suitable with hetero-
aryl iodides (Table 4, 7ia & 7ja). Significantly, the reaction was also amenable with the aliphatic
aldehydes (4c & 4e) and afforded the products 8ea-hc in fair yields (Table 4).
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60
a
Table 4: Scope and generality of formation of aryl-aryl and aryl-alkyl ketone 7aa-ja and 8ae-hc.
O
Pd(OAc)2 (5 mol%)
I
R6
R5
6
Ag2O (1.2 equiv)
R5
+
R CHO
7
0% TBHP in H2O (5 equiv)
120 C, 12 h
6
a-j
2a-q & 4a-e
7aa-ja & 8ae-hc
O
O
O
O
OMe
7aa (52 %)
7aj (60%)
7am (62%)
O
O
O
Me
MeO
MeO
Me
7ba (54%)
7da (64%)
7db (64%)
O
O
O
MeO
MeO
2
O N
O
O
7
fa (67%)
7ga (65%)
7ha (51 %)
O
O
O
N
S
7ia (42 %)
7ja (45%)
8
ae (49%)
O
O
O
MeO
Me
Me
Me
MeO
8ea (45%)
8be (55%)
8ee (60%)
O
O2N
8hc (49%)
a
Isolated yields of chromatographically pure products 7aa-ja & 8ae-hc.
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To further demonstrate the synthetic utility of the present strategy, it was extended to the
synthesis of benzofuranones, the biologically important scaffolds. To our delight, as anticipated,
selective reduction of the keto group of 3ba, 5bd, 3be with NaBH and in-situ intramolecular
4
0
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nucleophilic attack of the secondary hydroxyl group upon to ester moiety, afforded the
benzofuranones 9ba-be (Table 5). Significantly, this strategy was also successfully applied to the
1
synthesis of n-butylphthalide (NBP) 9bd. The NBP is currently serving as an antiplatelet drug in
2
the market for ischemia-cerebral apoplexy.
a
Table 5: Synthesis of benzofuranones 9ba-be.
a
Isolated yields of chromatographically pure products 9ba-be.
Most importantly, the strategy was further applied to the synthesis of the antispasmodic
pitofenone, a combined drug in Spasmalgon. This drug helps in releasing pain and spasms of
smooth muscles. Notably, the present protocol proved to be efficient as it enables the synthesis
1
3
of pitofenone 10ap in just two steps (Scheme 1).
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Scheme 1: Synthesis of pitofenone 10ap.
To further investigate the mechanism of the reaction, we assumed that the reaction may proceed via
the formation of an acyl radical from the aldehydes (2 & 4) by TBHP. To prove the formation of radical,
the reaction was performed in the presence of (2,2,6,6-tetramethylpiperidin-1-yl)oxy (TEMPO), a free
radical scavenger, under standard conditions. Gratifyingly, as predicted, the aldehyde radical trapped
14
ester 11a was formed in 95% yield with TEMPO (Scheme 2). On the other hand; the iodo ester 1a was
transformed into to the simple methyl benzoate in 15% yield via reductive de-iodination (Scheme 2).
Scheme 2: Synthesis of tempoester 11a.
Though, the exact reaction mechanism is not clearly known, a plausible mechanism is depicted in
Scheme 3. In this context, we presumed that the reaction might proceeds via Pd(0)/Pd(II)
15,16,17
intermediates
and Ag O could act as a base [as reaction is working in presence of K CO /Cs CO
2 2 3 2 3
15c
(
Table 1, entries 22 & 23)]. Pd(OAc) could be reduced to Pd(0) by the solvent. Thus, oxidative addition
2
of Pd(0) onto the Ar-I bond leads to the formation of Pd(II)-intermediate A. In an independent path, the
acyl radical B formed from aldehyde by the reaction of TBHP. Now, combination of A and B would
furnishes the Pd(II)-intermediate C which undergo reductive elimination and affords the ketones
3/5/7/8 along with the Pd(0)-catalyst and thus completes the catalytic cycle. However, the halophilic
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+
nature of Ag ions, it might be reasonable to form AgI while combining B with A. On the other hand,
18
acceleration of the reaction in the presence of Ag O might also be due to salt effect on [Pd]-catalysis.
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0
1
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9
0
Scheme 3: Plausible reaction mechanism for the synthesis of ketones 3/5/7/8 from aldehydes 2 and 4.
In summary, we have disclosed a simple [Pd]-catalyzed direct acylation of iodo arenes with alkyl/aryl
aldehydes, for the synthesis of wide variety of aryl-aryl and alkyl-aryl ketones with good substrate scope.
Unlike some of the transition metal catalyzed reactions that made use of toxic carbon monoxide (CO) gas
as carbonylating agent or activation of the carbonyl group or directing group assistance, the present
protocol was successful under environmentally benign conditions, without the need to activate the
carbonyl group and also without directing group assistance. Significantly, the strategy was extended to
the synthesis of anti-platelet drug n-butylphthalide (NBP) and the antispasmodic drug pitofenone.
Currently, the studies for the extension of this protocol to identify other substrates as aldehyde are
under progress.
Experimental: General considerations:
1
IR spectra were recorded on a FTIR spectrophotometer. H NMR spectra were recorded on 400 MHz
spectrometer at 295 K in CDCl ; chemical shifts (δ ppm) and coupling constants (Hz) are reported in
3
standard fashion with reference to either internal standard tetramethylsilane (TMS) (δ =0.00 ppm) or
H
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CHCl (δ = 7.25 ppm). C NMR spectra were recorded on 100 MHz spectrometer at RT in CDCl3;
3
H
13
chemical shifts (δ ppm) are reported relative to CHCl [δ = 77.00 ppm (central line of triplet)]. In the C
3
C
NMR, the nature of carbons (C, CH, CH and CH ) was determined by recording the DEPT-135 spectra. In
2
3
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1
the H-NMR, the following abbreviations were used throughout: s = singlet, d = doublet, t = triplet, q =
quartet, qui =quintet, sept = septet, dd = doublet of doublet, m = multiplet and br. s = broad singlet.
High-resolution mass spectra (HR-MS) were recorded on Q-TOF electron spray ionization (ESI) mode and
atmospheric pressure chemical ionization (APCI) modes. Melting points were determined on an
electrothermal melting point apparatus and are uncorrected. All small scale reactions were carried out
using Schlenk tube. Reactions were monitored by TLC on silica gel using a combination of hexane and
ethyl acetate as eluents. Reactions were generally run under argon or a nitrogen atmosphere. Solvents
were distilled prior to use; petroleum ether with a boiling range of 60 to 80 °C was used. Acme’s silica-
gel (60–120 mesh) was used for column chromatography (approximately 20 g per one gram of crude
material).
The compounds 1a-f, 6a-j, 2a-q and 4a-e which have been used are commercially available.
GP-1 [General Procedure for Preparation of Benzophenones and Acetophenones (3, 5, 7 & 8)]:
To an oven dried Schlenk tube, were added aryl iodide 1/6 (81.3-127.3 mg, 0.40 mmol), aldehyde 2/4
(169.8-366.5 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and TBHP (257.1
2
2
mg, 2.0 mmol). The resulting reaction mixture was stirred at 120 °C for 12 h. The progress of the product
/5/7/8 formation was monitored by TLC till the reaction was completed. The reaction mixture was
3
allowed to cool to room temperature, diluted with aqueous NaHCO solution and then extracted with
3
ethyl acetate (3 × 15 mL). The organic layers were washed with saturated NaCl solution, dried (Na SO )
2
4
and filtered. Evaporation of the solvent under reduced pressure and purification of the crude material
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by silica-gel column chromatography (petroleum ether/ethyl acetate) furnished the products 3/ 5/7/8
(
32.0-117.8 mg, 42-89%) as viscous liquid/solid.
0
1
2
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4
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7
8
9
0
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0
GP-2 [General Procedure for Preparation of Benzofuranones (9)]:
To a cold (0°C), magnetically stirred solution of keto ester 3ba/5bd/5be (117.1-130.2 mg, 0.50 mmol) in
MeOH (1 mL), were added sequentially CeCl .7H O (186.3 mg, 0.50 mmol) and NaBH (38 mg, 1.0 mmol).
3
2
4
The reaction mixture was stirred at 0 °C to room temperature for 12 to 24 h. The progress of the
product 9ba/9bd/9be formation was monitored by TLC. The reaction mixture was quenched with H O
2
and then extracted with ethyl acetate (3 × 10 mL). Purification of the crude material by silica-gel column
chromatography (petroleum ether/ethyl acetate) furnished the product 9ba/9bd/9be (112.5-146.0 mg,
7
8-95%) as a liquid/solid.
19a
Ethyl-2-benzoylbenzoate (3aa): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40 mmol),
aldehyde 2a (169.8 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and TBHP
2
2
(
257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
(petroleum ether/ethyl acetate, 95:05 to 93:07) furnished the product 3aa (71.1 mg, 74%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1a)=0.80, R (3aa)=0.30,
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2930, 17190, 1686, 1599, 1450, 1287, 1089, 934, 718
-
1 1
cm . H NMR (CDCl , 400 MHz): δ=8.03 (d, 1H, J=7.3), 7.73 (dd, 2H, J=8.5 and J=1.2 Hz), 7.65-7.61 (m,
3
13
1
1
H), 7.58-7.51 (m, 2H), 7.44-7.39 (m, 1H), 3.59 (s, 3H), ppm. C NMR (CDCl , 100 MHz): δ= 51.1 (CH ),
3 3
27.8 (CH), 128.5 (2×CH), 129.2 (2×CH), 129.6 (CH), 130.0 (CH), 131.4 (C ), 132.4 (CH), 133.0 (CH), 137.2
q
+
+
+
(C ), 141.6 (C ), 166.4 (C ), 197.0(C ) ppm. HR-MS (ESI ) m/z calculated for [C H O ] =[M+H] : 241.0859;
q
q
q
q
15 13
3
found 241.0868.
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Methyl-2-(4-methylbenzoyl) benzoate (3ab): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2b (192.2 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3ab (68.1 mg, 67%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1a)=0.90, R (3ab)=0.30,
10
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(
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2980, 1722, 1678, 1591, 1451, 1278, 1084, 953, 715
-
1 1
cm . H NMR (CDCl , 400 MHz): δ=8.02 (dd, 1H, J=7.8 and J=0.9 Hz), 7.65-7.60 (m, 3H), 7.54 (td, 1H,
3
J=7.7 and J=1.2 Hz), 7.38 (dd, 1H, J=7.5 and J=1.2 Hz), 7.21 (d, 2H, J=7.8 Hz), 3.60 (s, 3H), 2.39 (s, 3H)
1
3
ppm. C NMR (CDCl , 100 MHz): δ= 21.7 (CH ), 52.1 (CH ), 127.5 (CH), 129.2 (2 × CH), 129.4 (2 × CH),
3
3
3
1
29.5 (CH), 130.1 (CH), 130.2 (C ), 132.3 (CH), 134.7 (C ), 141.9 (C ), 143.9 (C ), 166.5 (C ), 196.7 (C )
q q q q q q
+
+
+
ppm. HR-MS (ESI ) m/z calculated for [C H O ] =[M+H] : 255.1016; found 255.1016.
16
15
3
1
9b
Methyl-2-(4-ethylbenzoyl) benzoate (3ad): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2d (214.7 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
(petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3ad (73.0 mg, 68%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1a)=0.90, R (3ad)=0.30,
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2992, 1724, 1685, 1588, 1451, 1279, 1088, 9334, 712
-
1 1
cm . H NMR (CDCl , 400 MHz): δ=8.03 (d, 1H, J=7.8 Hz), 7.66 (d, 2H, J=7.3 Hz), 7.61 (td, 1H, J=7.5 and
3
J=1.4 Hz), 7.54 (td, 1H, J=7.5 and J=1.4 Hz), 7.38 (dd, 1H, J=7.3 and J=0.9 Hz), 7.24 (d, 2H, J=7.8 Hz), 3.61
1
3
(
s, 3H), 2.68 (q, 2H, J=7.6 Hz), 1.23 (t, 3H, J=7.6 Hz ) ppm. C NMR (CDCl , 100 MHz): δ=15.1 (CH ), 28.9
3 3
(t, ArCH CH ), 52.2 (CH ), 127.7 (CH), 128.0 (2×CH), 129.1 (C ), 129.4 (CH), 129.5 (2×CH), 130.0 (CH),
2
3
3
q
+
1
32.3 (CH), 134.8 (C ), 141.9 (C ), 150.1 (C ), 166.4 (C ), 196.8 (C ), ppm. HR-MS (ESI ) m/z calculated for
q q q q q
+
+
[
C H O ] =[M+H] : 269.1172; found 269.1178.
17
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9c
Methyl-2-(4-bromobenzoyl) benzoate (3ae): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2e (296.0 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
0
1
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7
8
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0
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7
8
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4
5
6
7
8
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0
1
2
3
4
5
6
7
8
9
0
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 96:04) furnished the product 3ae (83.0 mg, 65%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1a)=0.90, R (3ae)=0.40,
(
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2946, 1725, 1685, 1598, 1490, 1287, 1023, 999, 722
-
1 1
cm . H NMR (CDCl , 400 MHz): δ=8.04 (d, 1H, J=7.8), 7.64 (ddd, 1H, J=7.8, J=5.8 and 1.4 Hz), 7.61-7.58
3
13
(m, 2H), 7.58-7.55 (m, 3H), 7.37 (dd, 1H, J=7.5 and 1.2 Hz), 3.64 (s, 3H), ppm. C NMR (CDCl , 100 MHz):
3
δ=52.3 (CH ), 127.6(CH), 128.3 (C ), 129.0 (C ), 129.8 (CH), 130.2 (CH), 130.6 (CH), 131.8 (2×CH), 132.6
3
q
q
+
(
CH), 136.0 (C ), 141.3 (C ), 166.2 (C ), 196.0 (C ) ppm. HR-MS (ESI ) m/z calculated for
q q q q
+
+
[
C H BrO ] =[M+H] : 318.9964; found 318.9951.
15 12
3
Methyl-2-(2-bromobenzoyl) benzoate (3af): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2f (296.0 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 96:04) furnished the product 3af (76.6 mg, 60%) as a colourless
viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1a)=0.90, R (3af)=0.40, UV
(
f
f
-
1
-1
detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2960, 1722, 1679, 1591, 1458, 1287, 1093, 943, 722 cm .
1
H NMR (CDCl , 400 MHz): δ=7.85 (dd, 1H, J=5.8 and J=2.9, Ar-H), 7.69-7.66 (m, 1H), 7.57 (dd, 2H,J=5.8
3
13
and 3.4 Hz), 7.47 (dd, 1H, J=5.8 and 2.9 Hz), 7.37-7.34 (m, 1H), 7.29-7.32 (m, 2H), 3.67 (s, 3H), ppm. C
NMR (CDCl , 100 MHz): δ=52.5 (CH ), 121.3 (C ), 127.0 (CH), 129.4 (CH), 129.8(CH), 131.0 (CH), 131.1
3
3
q
+
(
C ), 131.6 (CH), 132.5 (CH), 134.5 (CH), 138.2 (C ), 139.9 (C ), 167.4 (C ), 195.3 (C ) ppm. HR-MS (ESI )
q q q q q
+
+
m/z calculated for [C H BrO ] =[M+H] : 318.9964; found 318.9957.
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9d
Methyl-2-(4-chlorobenzoyl) benzoate (3ag): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2g (224.9 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
10
11
12
13
14
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45
46
47
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TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3ag (71.4 mg, 65%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1a)=0.80, R (3ag)=0.30,
(
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2960, 1721, 1695, 1588, 1450, 1277, 1088, 943, 723
-
1 1
cm . H NMR (CDCl , 400 MHz): δ=8.04 (d, 1H, J=7.3 Hz), 7.69-7.62 (m, 3H), 7.57 (ddd, 1H,J=7.3, 6.5 and
3
1
3
1.4 Hz), 7.41-7.36 (m, 3H), 3.64 (s, 3H), ppm. C NMR (CDCl , 100 MHz): δ= 52.3 (CH ), 127.6 (CH), 128.9
3
3
(
2×CH), 129.0 (C ), 129.8 (CH), 130.2 (CH), 132.5 (2×CH), 135.6 (C ), 139.5 (C ), 141.3 (C ), 166.2 (C ),
q q q q q
+
+
+
1
95.8 (C ) ppm. HR-MS (ESI ) m/z calculated for [C H ClO ] =[M+H] : 275.0469; found 275.0476.
q
15 12
3
19e
Methyl-2-(4-fluorobenzoyl) benzoate (3ah): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2h (198.6 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
(petroleum ether/ethyl acetate, 97:03 to 96:04) furnished the product 3ah (64.0 mg, 62%) as a white
solid (m.p. 80-83 °C). [TLC control (petroleum ether/ethyl acetate 95:05), R (1a)=0.90, R (3ah)=0.40, UV
f
f
-
1
-1
detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2960, 1730, 1695, 1592, 1451, 1271, 1081, 932, 710 cm .
1
H NMR (CDCl , 400 MHz): δ=8.04 (d, 1H, J=7.8 Hz), 7.76 (dd, 2H, J=8.8 and J=5.3 Hz), 7.63 (ddd, 1H,
3
J=7.3, J=5.3and J=1.4 Hz), 7.58-7.54 (m, 1H), 7.37 (dd, 1H, J=7.5 and J=1.2 Hz), 7.08 (t, 2H, J=8.8 Hz), 3.64
1
3
(
s, 3H), ppm. C NMR (CDCl , 100 MHz): δ= 52.3 (CH ), 115.7 (2×CH), 127.6 (CH), 129.1 (C ), 129.7 (CH),
3 3 q
1
130.2 (CH), 131.9 ( 2 × CH), 132.5 (CH), 133.7 (C ), 141.5 (C ), 166.3 (C ), 166.9( d, JC-F = 255.3 Hz ),
q
q
q
+
+
+
1
95.5 (C ) ppm. HR-MS (ESI ) m/z calculated for [C H FO ] =[M+H] : 259.0765; found 259.0774.
q
15 12
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Methyl-2-(3-methoxybenzoyl) benzoate (3ai): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2i (217.8 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 93:07 to 88:12) furnished the product 3ai (73.5 mg, 68%) as a colourless
viscous liquid. [TLC control (petroleum ether/ethyl acetate 90:10), R (1a)=0.90, R (3ai)=0.30, UV
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
f
f
-
1
-1
detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2966, 1721, 1670, 1599, 1450, 1278, 1083, 933, 716 cm .
1
H NMR (CDCl , 400 MHz): δ=8.03 (dd, 1H, J=7.5 and J=1.2 Hz), 7.62 (td, 1H, J=7.4 and J=1.2 Hz), 7.55 (td,
3
1
H, J=7.7 and J=1.2 Hz), 7.41-7.39 (m, 2H), 7.29 (t, 1H, J=7.8 Hz), 7.18-7.16 (m, 1H), 7.08 (ddd, 1H, J=8.0,
1
3
J=2.6 and J=0.9 Hz), 3.83 (s, 3H), 3.62 (s, 3H), ppm. C NMR (CDCl , 100 MHz): δ= 52.2 (CH ), 55.4 (CH ),
3
3
3
1
12.8 (CH), 119.8 (CH), 122.5 (CH), 127.8 (CH), 129.2 (C ), 129.5 (2×CH), 129.6 (CH), 132.4 (CH), 138.5
q
+
(
C ), 141.7 (C ), 159.8 (C ), 166.4 (C ), 196.8 (C ) ppm. HR-MS (ESI ) m/z calculated for
q
q
q
q
q
+
+
[
C H O ] =[M+H] : 271.0965; found 271.0968.
16 15
4
Methyl-2-(4-methoxybenzoyl) benzoate (3aj): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2j (217.8 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 93:07 to 88:12) furnished the product 3aj (77.8 mg, 72%) as a colourless
viscous liquid. [TLC control (petroleum ether/ethyl acetate 90:10), R (1a)=0.90, R (3aj)=0.30, UV
(
f
f
-
1
-1
detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2950, 1721, 1675, 1578, 1451, 1282, 1084, 934, 719 cm .
1
H NMR (CDCl , 400 MHz): δ=8.02 (dd, 1H, J=7.8 and J=0.9 Hz), 7.71 (d, 2H, J=8.8 Hz), 7.61 (td, 1H, J=7.5
3
and J=1.4 Hz), 7.53 (td, 1H, J=7.5 and J=1.4 Hz), 7.37 (dd, 1H, J=7.3and J=0.9 Hz), 6.89(d, 1H, J=8.8 Hz),
1
3
3.84 (s, 3H), 3.62 (s, 3H), ppm. C NMR (CDCl , 100 MHz): δ= 52.2 (CH ), 55.4 (CH ), 113.7 (2×CH),
3
3
3
1
1
27.7(CH), 129.1 (C ), 129.3 (CH), 130.1 (CH), 130.2 (C ), 131.6 (2×CH), 132.3 (CH), 142.0 (C ), 163.5 (C ),
q q q q
+
+
+
66.5 (C ), 195.8 (C ) ppm. HR-MS (ESI ) m/z calculated for [C H O ] =[M+H] : 271.0965; found
q
q
16 15
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71.0967.
20b
Methyl-2-(3,4-dimethoxybenzoyl)benzoate (3ak): GP-1 was carried out with aryl iodide 1a (104.8 mg,
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
0
.40 mmol), aldehyde 2k (265.9 mg,1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol)
2
2
and TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
(petroleum ether/ethyl acetate, 88:12 to 85:15) furnished the product 3ak (91.3 mg, 76%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 85:15), R (1a)=0.95, R (3ak)=0.30,
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2966, 1723, 1645, 1598, 1430, 1272, 1083, 936, 719
-
1 1
cm . H NMR (CDCl , 400 MHz): δ=8.02 (dd, 1H, J=7.5 and J=1.2 Hz), 7.63-7.52 (m, 3H), 7.38 (dd, 1H,
3
J=7.5 and J=1.2 Hz), 7.06 (dd, 1H, J=8.3 and J=1.9 Hz), 6.77 (d, 1H, J=8.8 Hz), 3.93 (s, 3H), 3.90 (s, 3H),
13
3
1
1
.64 (s, 3H), ppm. C NMR (CDCl , 100 MHz): δ=52.2 (CH ), 55.9 (CH ), 56.0 (CH ), 109.8 (CH), 110.2 (CH),
3 3 3 3
25.1 (CH), 127.7 (CH), 129.1 (C ), 129.4 (CH), 130.0 (CH), 130.4 (C ), 132.2 (CH), 141.8 (C ), 149.1 (C ),
q
q
q
q
+
+
+
53.3 (C ), 166.4 (C ), 195.8 (C ) ppm. HR-MS (ESI ) m/z calculated for [C H O ] =[M+H] : 301.1071;
q
q
q
17 17
5
found 301.1071.
Methyl-2-(benzo[d][1,3]dioxole-5-carbonyl)benzoate (3al): GP-1 was carried out with aryl iodide 1a
(
104.8 mg, 0.40 mmol), aldehyde 2l (240.2 mg,1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg,
2 2
0
.48 mmol) and TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column
chromatography (petroleum ether/ethyl acetate, 95:05 to 92:08) furnished the product 3al (84.1 mg,
4%) as a colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 90:10), R (1a)=0.95,
7
f
-
1
R (3al)=0.30, UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2970, 1721, 1672, 1592, 1451, 1277,
f
-
1 1
1082, 933, 723 cm . H NMR (CDCl , 400 MHz): δ=8.02 (d, 1H, J=7.3 Hz), 7.60 (td, 1H, J=7.5 and J=1.2
3
Hz), 7.53 (td, 1H, J=7.5 and J=1.4 Hz), 7.37-7.34 (m, 2H), 7.18-7.15 (m, 1H), 6.76 (d, 1H, J=8.3 Hz), 6.02 (s,
13
2
H), 3.67 (s, 3H), ppm. C NMR (CDCl , 100 MHz): δ=52.2 (CH ), 101.9 (CH ), 107.8 (CH), 108.5 (CH),
3 3 2
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26.4 (CH), 127.6 (CH), 128.9 (C ), 129.4 (CH), 130.1 (CH), 132.1 (C ), 132.3 (CH), 141.9 (C ), 148.2 (C ),
q
q
q
q
+
+
+
51.9(C ), 166.3 (C ), 195.3 (C ) ppm. HR-MS (ESI ) m/z calculated for [C H O ] =[M+H] : 285.0757;
q
q
q
16 13
5
found 285.0766.
0
1
2
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8
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0
1
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4
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7
8
9
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8
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0
1
2
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7
8
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0
19e
Methyl-2-(furan-2-carbonyl)benzoate (3am): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2m (153.7 mg,1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 92:08 to 88:12) furnished the product 3am (69.5 mg, 75%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 90:10), R (1a)=0.90,
R (3am)=0.30, UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2929, 1721, 1689, 1598, 1450, 1277,
(
f
-
1
f
-1
1
1
7
084, 938, 719 cm . H NMR (CDCl , 400 MHz): δ=8.00 (dd, 1H, J=7.5 and J=1.2 Hz), 7.64-7.57 (m, 3H),
3
.49 (dd, 1H, J=7.3 and J=1.4 Hz), 6.98 (d, 1H, J=3.4 Hz), 6.51 (dd, 1H, J=3.4 and J=1.4 Hz), 3.69 (s, 3H),
13
ppm. C NMR (CDCl , 100 MHz): δ=52.4 (CH ), 112.3 (CH), 119.0 (CH), 128.1 (CH), 129.7 (C ), 130.0 (CH),
3
3
q
+
1
30.2 (CH), 132.2 (CH), 140.0 (C ), 147.1 (CH), 152.7 (C ), 166.6 (C ), 184.2 (C ) ppm. HR-MS (ESI ) m/z
q
q
q
q
+
+
calculated for [C H O ] =[M+H] : 231.0652; found 231.0653.
13 11
4
Methyl-2-(4-hydroxybenzoyl) benzoate (3an): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2n (195.4 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 93:07 to 90:10) furnished the product 3an (46.0 mg, 45%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 90:10), R (1a)=0.90, R (3an)=0.30,
(
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax= 3421, 2951, 1722, 1670, 1592, 1451, 1272, 1088, 933,
-
1 1
7
3
12 cm . H NMR (CDCl , 400 MHz): δ=8.00 (dd, 1H, J=7.5 and J=1.2 Hz), 7.82 (br.s, 1H), 7.63-7.59 (m,
3
H), 7.53 (td, 1H, J=7.7and J=1.2 Hz), 7.36 (dd, 1H, J=7.5 and J=1.2 Hz) 6.78-6.76 (m, 2H), 3.63 (s, 3H),
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ppm. C NMR (CDCl , 100 MHz): δ=52.4 (CH ), 115.5 (2×CH), 127.7(CH), 128.9 (C ), 129.3 (C ), 129.5
3
3
q
q
(
CH), 130.1 (CH), 132.1 (2×CH), 132.5 (CH), 141.7 (C ), 161.4 (C ), 166.9 (C ), 196.9 (C ) ppm. HR-MS
q q q q
+
+
+
(ESI ) m/z calculated for [C H O ] =[M+H] : 271.0965; found 271.0969.
16
15
4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
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29
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31
32
33
34
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38
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46
47
48
49
50
51
52
53
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55
56
57
58
59
60
Methyl-2-(4-propoxybenzoyl) benzoate (3ao): GP-1 was carried out with aryl iodide 1a (104.8 mg, 0.40
mmol), aldehyde 2o (262.7 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3ao (75.2 mg, 63%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1a)=0.90, R (3ao)=0.40,
(
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2932, 1730, 1690, 1593, 1451, 1278, 1088, 934, 717
-1
1
cm . H NMR (CDCl , 400 MHzδ=8.02 (dd, 1H, J=7.8 and J=0.9 Hz), 7.71-7.62 (m, 2H), 7.60 (td, 1H, J=7.4
3
and J=1.2 Hz), 7.53 (td, 1H, J=7.4 and J=1.2 Hz), 7.36 (dd, 1H, J=7.8 and J=0.9 Hz) 6.89-6.87 (m, 2H), 3.95
1
3
(
t, 2H, J=6.6 Hz) 3.63 (s, 3H), 1.85-1.76 (m, 2H), 1.02 (t, 3H, J=7.5 Hz) ppm. C NMR (CDCl , 100 MHz):
3
δ= 10.4 (CH ), 22.4 (CH ), 52.4 (CH ), 69.7 (CH ), 114.1 (2×CH), 127.6(CH), 129.0 (C ), 129.3 (CH), 129.9
3
2
3
2
q
+
(
C ), 130.0 (CH), 131.6 ( 2×CH), 132.2 (CH), 142.0 (C ), 163.1 (C ), 166.4 (C ), 195.8 (C ) ppm. HR-MS (ESI )
q q q q q
+
+
m/z calculated for [C H NaO ] =[M+Na] : 321.1097; found 321.1097.
18
18
4
Methyl-2-(4-(2-bromoethoxy)benzoyl)benzoate (3ap): GP-1 was carried out with aryl iodide 1a (104.8
mg, 0.40 mmol), aldehyde 2p (916.6 mg, 4.0 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48
2
2
mmol) and TBHP (514.2 mg, 4.0 mmol). Purification of the crude material by silica-gel column
chromatography (petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3ap (72.0 mg,
49%) as a colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1a)=0.90,
f
-
1
R (3ap)=0.50, UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2966, 1722, 1685, 1598, 1450, 1277,
f
-
1 1
1
083, 933, 715 cm . H NMR (CDCl , 400 MHz δ=8.03 (dd, 1H, J=7.5 and J=1.2 Hz), 7.74-7.71 (m, 2H),
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
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4
4
4
4
4
4
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.62 (td, 1H, J=7.3 and J=1.4 Hz), 7.54 (td, 1H, J=7.3 and J=1.4 Hz), 7.37 (dd, 1H, J=7.5 and J=1.2 Hz), 6.93-
1
3
.89 (m, 2H), 4.36 (t, 2H, J=6.3 Hz) 3.64 (s, 3H), 3.64 (t, 2H, J=6.3 Hz), ppm. C NMR (CDCl , 100 MHz):
3
δ=28.5 (CH ), 52.2 (CH ), 67.8 (CH ), 114.3 (2×CH), 127.6(CH), 129.1 (C ), 129.4 (CH), 130.1 (CH), 130.9
2
3
2
q
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
(
C ), 131.7 ( 2×CH), 132.3 (CH), 141.9 (C ), 161.9 (C ), 166.4 (C ), 195.7 (C ) ppm. HR-MS (ESI ) m/z
q q q q q
+
+
calculated for [C H BrO ] =[M+H] : 365.0208; found 365.0206.
17
16
4
19f
Methyl-4-benzoylbenzoate (3fa): GP-1 was carried out with aryl iodide 1f (104.8 mg, 0.40 mmol),
aldehyde 2a (169.8 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and TBHP
2
2
(257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3fa (59.6 mg, 62%) as a colourless
viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1f)=0.90, R (3fa)=0.30, UV
(
f
f
-
1
-1
detection]. IR (MIR-ATR, 4000–600 cm ): νmax=3000, 1780, 1685, 1620, 1490, 1310, 1110, 988, 763 cm .
1
H NMR (CDCl , 400 MHz): δ=8.14 (d, 2H, J=8.8 Hz), 7.80 (dd, 4H, J=8.8 and J=7.5 Hz), 7.61 (t, 1H, J=7.5
3
13
Hz), 7.49 (t, 2H, J=7.5 Hz), 3.95 (s, 3H), ppm. C NMR (CDCl , 100 MHz): δ=52.4 (CH ), 128.4 (2×CH),
3
3
1
29.5 (2×CH), 129.7 (2×CH), 130.1 (2×CH), 132.9 (CH), 133.2 (C ), 136.9 (C ), 141.3 (C ), 166.3 (C ), 196.0
q q q q
+
+
+
(C ) ppm. HR-MS (ESI ) m/z calculated for [C H O ] =[M+H] : 241.0859; found 241.0869.
q
15 13
3
Ethyl-2-benzoylbenzoate (3ba): GP-1 was carried out with aryl iodide 1b (110.4 mg, 0.40 mmol),
aldehyde 2a (169.8 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and TBHP
2
2
(
(
257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 96:04) furnished the product 3ba (76.3 mg, 75%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1b)=0.90, R (3ba)=0.30,
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2919, 2850, 1715, 1670, 1596, 1446, 1366, 1276,
-
1 1
1
130, 1040, 931, 714 cm . H NMR (CDCl , 400 MHz): δ=8.05 (d, 1H, J=7.3), 7.74 (d, 2H, J=6.5 Hz), 7.64-
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7
.52 (m, 3H), 7.40 (dd, 3H, J=7.3 and J=6.5 Hz), 4.05 (q, 2H, J=7.3 Hz), 1.04 (t, 2H, J=7.3 Hz) ppm. C NMR
(
CDCl , 100 MHz): δ=13.7 (CH ), 61.4 (CH ), 127.6 (CH), 128.4 (2×CH), 129.3 (2×CH), 129.5 (CH), 130.1
3
3
2
+
(CH), 132.3 (CH), 133.0 (CH), 137.1 (C ), 141.5 (C ), 165.9 (C ), 196.9 (C ) ppm. HR-MS (ESI ) m/z
q
q
q
q
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
+
+
calculated for [C H O ] =[M+H] : 255.1016; found 255.1017.
16
15
3
Ethyl-2-(4-methylbenzoyl) benzoate (3bb): GP-1 was carried out with aryl iodide 1b (110.4 mg, 0.40
mmol), aldehyde 2b (192.2 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
(petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3bb (75.3 mg, 70%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1b)=0.90, R (3bb)=0.30,
f
f
-1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2921, 2853, 1719, 1670, 1605, 1446, 1366, 1277,
-
1 1
1
130, 1050, 981, 714 cm . H NMR (CDCl , 400 MHz): δ=8.04 (d, 1H, J=7.3 Hz), 7.6 (d, 2H, J=8.3 Hz), 7.59
3
(
dd, 1H, J=7.3 and J=1.4 Hz), 7.54 (ddd, 1H, J=8.3, J=7.3 and J=1.4 Hz), 7.36 (d, 1H, J=7.8 Hz), 7.20 (d, 2H,
13
J=7.8 Hz), 4.06 (q, 2H, J=7.1 Hz), 2.38 (s, 3H), 1.05 (t, 2H, J=7.1 Hz) ppm. C NMR (CDCl , 100 MHz):
3
δ=13.6 (CH ), 21.6 (CH ), 61.4 (CH ), 129.1 (3×CH), 129.3 (CH), 129.5 (2×CH), 130.1 (C ), 132.2 (CH), 134.7
3
3
2
q
+
(C ), 141.8 (C ), 143.9 (C ), 166.0 (C ), 196.6 (C ) ppm. HR-MS (ESI ) m/z calculated for
q
q
q
q
q
+
+
[
C H O ] =[M+H] : 269.1172; found 269.1172.
17
17
3
Ethyl-2-(2-methylbenzoyl) benzoate (3bc): GP-1 was carried out with aryl iodide 1b (110.4 mg, 0.40
mmol), aldehyde 2c (192.2 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
(petroleum ether/ethyl acetate, 95:05 to 94:06) furnished the product 3bc (69.7 mg, 65%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1b)=0.90, R (3bc)=0.30,
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2956, 1720, 1675, 1598, 1450, 1277, 1083, 933, 713
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
-1
1
cm . H NMR (CDCl , 400 MHz): δ=7.93 (d, 1H, J=8.8 Hz), 7.60-7.51 (m, 2H), 7.42-7.34 (m, 2H), 7.28 (d,
3
1
H, J=7.8 Hz), 7.23 (d, 1H, J=7.8 Hz), 7.11 (t, 1H, J=7.8 Hz), 4.08 (q, 2H, J=7.3 Hz), 2.65 (s, 3H), 1.09 (t, 2H,
13
J=7.3 Hz) ppm. C NMR (CDCl , 100 MHz): δ=13.7 (CH ), 21.6 (CH ), 61.4 (CH ), 125.3 (CH), 128.3 (CH),
3
3
3
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
1
29.8 (CH), 130.3 (C ), 131.6 (CH), 131.8 (CH), 131.9 (CH), 136.5 (C ), 140.0 (C ), 142.5 (C ), 166.5 (C ),
q q q q q
+
+
+
98.6 (C ) ppm. HR-MS (ESI ) m/z calculated for [C H O ] =[M+H] : 269.1172; found 269.1179.
q
17 17
3
Ethyl-2-(4-ethylbenzoyl) benzoate (3bd): GP-1 was carried out with aryl iodide 1b (110.4 mg, 0.40
mmol), aldehyde 2d (214.7 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 96:04) furnished the product 3bd (76.8 mg, 68%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1b)=0.90, R (3bd)=0.30,
(
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2921, 2853, 1719, 1671, 1607, 1453, 1363, 1277,
-
1 1
1
130, 1050, 981, 814, 810,713 cm . H NMR (CDCl , 400 MHz): δ=8.07 (dd, 1H, J=7.5 and J=1.2 Hz), 7.69
3
(
d, 2H, J=8.3 Hz), 7.66-7.62 (m, 1H), 7.59-7.55 (m, 1H), 7.39 (dd, 1H, J=7.3 and J=0.9 Hz), 7.27 (d, 2H,
J=1.4 Hz), 4.09 (q, 2H, J=7.3 Hz), 2.71 (q, 2H, J=7.8 Hz), 1.25 (t, 2H, J=7.8 Hz), 1.07 (t, 2H, J=7.8 Hz) ppm.
13
C NMR (CDCl , 100 MHz): δ=13.6 (CH ), 15.1 (CH ), 28.9 (CH ), 61.4 (CH ), 127.6 (CH), 128.0 (2×CH),
3
3
3
2
2
1
1
29.4 (CH), 129.4 (C ), 129.6 (2×CH), 130.1 (CH), 132.2 (CH), 135.0 (C ), 141.9 (C ), 150.1 (C ), 166.0 (C ),
q q q q q
+
+
+
96.7 (C ) ppm. HR-MS (ESI ) m/z calculated for [C H O ] =[M+H] : 283.1329; found 283.1332.
q
18 19
3
Ethyl-2-(2-bromobenzoyl) benzoate (3bf): GP-1 was carried out with aryl iodide 1b (110.4 mg, 0.40
mmol), aldehyde 2f (296.0 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3bf (87.9 mg, 66%) as a colourless
viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1b)=0.90, R (3bf)=0.40, UV
(
f
f
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detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2959, 2921, 2851, 1720, 1671, 1603, 1462, 1279, 1129,
-
1 1
1
084, 1015, 933, 847, 751, 714 cm . H NMR (CDCl , 400 MHz): δ=7.87-6.85 (m, 1H), 7.68-7.65 (m, 1H),
3
7.58-7.53 (m, 2H), 7.44-7.40 (m, 2H), 7.33-7.30 (m, 2H), 4.16 (q, 2H, J=7.0 Hz, OCH CH 1.18 (t, 2H, J=7.0
2
3
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
13
Hz, CH ) ppm. C NMR (CDCl , 100 MHz): δ=13.9 (CH ), 61.6 (CH ), 121.4(C ), 127.0 (CH), 129.2 (CH),
3
3
3
2
q
1
29.7 (CH), 130.9 (CH), 131.4 (CH), 131.5 (C ), 131.8 (CH), 132.5 (CH), 134.5 (CH), 138.2 (C ), 140.0 (C ),
q q q
+
+
+
167.0 (C ), 195.4 (C ) ppm. HR-MS (ESI ) m/z calculated for [C H BrO ] =[M+H] : 333.0121; found
q
q
16 14
3
3
33.0125.
Ethyl-2-(4-chlorobenzoyl) benzoate (3bg): GP-1 was carried out with aryl iodide 1b (110.4 mg, 0.40
mmol), aldehyde 2g (224.9 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 96:04) furnished the product 3bg (79.7 mg, 69%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1b)=0.90, R (3bg)=0.35,
(
f
f
-1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2959, 2921, 2851, 1720, 1671, 1603, 1463, 1279,
-
1
1
1
139, 1084, 1015, 935, 899, 857, 751, 710 cm .. H NMR (CDCl , 400 MHz): δ=8.06 (dd, 1H, J=7.5 and
3
J=1.2 Hz), 7.70-7.67 (m, 2H), 7.65-7.54 (m, 2H), 7.41-7.35 (m, 3H), 4.10 (q, 2H, J=7.3 Hz), 1.09 (t, 2H,
13
J=7.3 Hz) ppm. C NMR (CDCl , 100 MHz): δ=13.7(CH ), 61.6 (CH ), 127.5 (CH), 128.8 (2×CH), 129.3 (C ),
3
3
2
q
1
29.7 (CH), 130.2 (CH), 130.7 (2×CH), 132.4 (CH), 135.6 (C ), 139.5 (C ), 141.2 (C ), 165.7 (C ), 195.8 (C )
q q q q q
+
+
+
ppm. HR-MS (ESI ) m/z calculated for [C H ClO ] =[M+H] : 289.0626; found 289.0633.
16
14
3
Ethyl-2-(benzo[d][1,3]dioxole-5-carbonyl)benzoate (3bl): GP-1 was carried out with aryl iodide 1b
(110.4 mg, 0.40 mmol), aldehyde 2l (240.2 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg,
2
2
0
.48 mmol) and TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column
chromatography (petroleum ether/ethyl acetate, 95:05 to 92:08) furnished the product 3bl (93.0 mg,
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
7
8%) as a colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 90:10), R (1b)=0.90,
f
-
1
R (3bl)=0.30, UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2925, 2857,1718, 1668, 1598, 1456,
f
-
1 1
1364, 1277, 1230, 1050, 983, 713 cm H NMR (CDCl , 400 MHz): δ=8.03 (d, 1H, J=7.3 Hz), 7.62-7.50 (m,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
H), 7.36-7.32 (m, 2H), 7.16 (dd, 1H, J=8.0 and J=1.7 Hz), 6.75 (d, 1H, J=7.8 Hz), 6.01 (s, 2H), 4.12 (q, 2H,
13
J=6.8 Hz), 1.11 (t, 2H, J=6.8 Hz) ppm. C NMR (CDCl , 100 MHz): δ=13.7 (CH ), 61.4 (CH ), 101.8 (CH ),
3
3
2
2
107.8 (CH), 108.5 (CH), 126.5 (CH), 127.5 (CH), 129.1 (C ), 129.3 (CH), 130.1 (CH), 132.1 (C ), 132.2 (CH),
q
q
+
1
41.8 (C ), 148.1 (C ), 151.8 (C ), 165.8 (C ), 195.3 (C ) ppm. HR-MS (ESI ) m/z calculated for
q q q q q
+
+
[C H O ] =[M+H] : 299.0914; found 299.0919.
17
15
5
Isopropyl-2-benzoylbenzoate (3ca): GP-1 was carried out with aryl iodide 1c (116.0 mg, 0.40 mmol),
aldehyde 2a (169.8 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and TBHP
2
2
(
(
257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3ca (75.1 mg, 70%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1c)=0.90, R (3ca)=0.40,
f
f
-
1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2980, 2924, 2853, 1716, 1673, 1594, 1451, 1347,
-1
1
1
2
279 1081, 932, 709, 639 cm . H NMR (CDCl , 400 MHz): δ=8.06 (dd, 1H, J=7.8 and J=0.9 Hz), 7.75 (dd,
3
H, J=8.3 and J=1.4 Hz), 7.63-7.51 (m, 3H), 7.43-7.35 (m, 3H), 4.97 (sep, 1H, J=6.3 Hz), 1.00 (d, 6H, J=6.3
1
3
Hz), ppm. C NMR (CDCl , 100 MHz): δ=21.1 (2×CH ), 69.4 (CH), 128.4 (2×CH), 129.4 (CH), 129.5 (2×CH),
3
3
1
29.5 (C ), 130.1 (CH), 132.2 (CH), 133.1 (CH), 137.2 (C ), 141.5 (C ), 165.3 (C ), 196.9 (C ) ppm. HR-MS
q q q q q
+
+
+
(
ESI ) m/z calculated for [C H O ] =[M+H] : 269.1172; found 269.1165.
17
17
3
Isopropyl-2-(4-methylbenzoyl) benzoate (3cb): GP-1 was carried out with aryl iodide 1c (116.0 mg, 0.40
mmol), aldehyde 2b (192.2 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
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TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
(
petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3cb (83.5 mg, 74%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1c)=0.90, R (3cb)=0.40,
f
f
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
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2981, 2851, 1715, 1669, 1604, 1351, 1311, 1278,
-
1 1
1
106, 1079, 932, 714 cm . H NMR (CDCl , 400 MHz): δ=8.04 (dd, 1H, J=7.8 and J=0.9 Hz), 7.65 (d, 2H,
3
J=8.3 Hz), 7.58 (td, 1H, J=7.3 and J=1.4 Hz), 7.57-7.51 (m, 1H) 7.33 (dd, 1H, J=7.5 and J=1.2 Hz), 7.20 (d,
13
2
H, J=8.3 Hz), 4.97 (sep, 1H, J=6.3 Hz), 2.38 (s, 3H), 1.01 (d, 6H, J=6.3 Hz), ppm. C NMR (CDCl , 100
3
MHz): δ=21.2 (2×CH ), 21.6 (CH ), 69.3 (CH), 127.5 (CH), 129.1 (2×CH), 129.2 (CH), 129.6 (C ), 129.6
3
3
q
+
(2×CH), 130.1 (CH), 132.1 (CH), 134.8 (C ), 141.7 (C ), 143.9 (C ), 165.3 (C ), 196.5 (C ) ppm. HR-MS (ESI )
q
q
q
q
q
+
+
m/z calculated for [C H O ] =[M+H] : 283.1329; found:283.1330.
18
19
3
Isopropyl-2-(4-ethylbenzoyl) benzoate (3cd): GP-1 was carried out with aryl iodide 1c (116.0 mg, 0.40
mmol), aldehyde 2d (214.7 mg, 1.6 mmol), Pd(OAc) (5.0 mg, 5 mol %), Ag O (111.3 mg, 0.48 mmol) and
2
2
TBHP (257.1 mg, 2.0 mmol). Purification of the crude material by silica-gel column chromatography
petroleum ether/ethyl acetate, 97:03 to 95:05) furnished the product 3cd (85.3 mg, 72%) as a
colourless viscous liquid. [TLC control (petroleum ether/ethyl acetate 95:05), R (1c)=0.90, R (3cd)=0.40,
(
f
f
-1
UV detection]. IR (MIR-ATR, 4000–600 cm ): νmax=2971, 2931, 2874, 1715, 1671, 1605, 1415, 1351,
-
1 1
1
278, 1106, 1079, 933, 714,579 cm H NMR (CDCl , 400 MHz): δ=8.04 (dd, 1H, J=7.8 and J=0.9 Hz), 7.67
3
(d, 2H, J=8.3 Hz), 7.59 (td, 1H, J=7.3 and J=1.4 Hz), 7.55-7.51 (m, 1H) 7.34 (dd, 1H, J=7.3 and J=1.4 Hz),
.22 (d, 2H, J=8.3 Hz), 4.97 (sep, 1H, J=6.3 Hz), 2.67 (q, 2H, J=7.3 Hz), 7.67 (t, 3H, J=7.3 Hz), 1.01 (d, 6H,
7
13
J=6.3 Hz), ppm. C NMR (CDCl , 100 MHz): δ=15.2 (CH ), 21.1 (2×CH ), 28.9 (CH ), 69.3(CH), 127.5 (CH),
3
3
3
2
127.9 (2×CH), 129.2 (CH), 129.6 (C ), 129.7 (2×CH), 130.1 (CH), 132.1 (CH), 135.0 (C ), 141.7 (C ), 150.1
q
q
q
+
+
+
(
C ), 165.4 (C ), 196.6 (C ) ppm. HR-MS (ESI ) m/z calculated for [C H O ] =[M+H] : 297.1485; found
q
q
q
19 21
3
2
97.1496.
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