Palladium-Catalyzed Direct Oxidative Coupling of Iodoarenes with Primary Alcohols Leading to Ketones: Application to the Synthesis of Benzofuranones and Indenones

Article abstract of DOI:10.1002/ejoc.201900769

In the present study, a palladium-catalyzed direct oxidative acylation through cross-dehydrogenative coupling has been investigated, utilizing readily available primary alcohols as acylating sources. Overall, this oxidative coupling proceeds via three distinct transformations such as oxidation, radical formation, and cross-coupling in one catalytic process. This protocol does not involve the assistance of a directing group or activation of the carbonyl group by any other means. Furthermore, this reaction made use of no toxic CO gas as carbonylating agent; instead, feedstock primary alcohols have been utilized as acylation source. Notably, the synthesis of benzofuranones and indenones is enabled. This strategy was also applied to the synthesis of n-butylphthalide, fenofibrate, pitofenone, and neo-lignan.

Full text of DOI:10.1002/ejoc.201900769

A Journal of
Accepted Article
Title: Palladium-Catalyzed Direct Oxidative Coupling of Iodoarenes
with Primary Alcohols Leading to Ketones: Application to the
Synthesis of Benzofuranones and Indenones
Authors: Basuli Suchand, Chinnabattigalla Sreenivasulu, and Gedu
Satyanarayana
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900769
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900769
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
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Palladium-Catalyzed Direct Oxidative Coupling of Iodoarenes with
Primary Alcohols Leading to Ketones: Application to the Synthesis of
Benzofuranones and Indenones
Basuli Suchand, Chinnabattigalla Sreenivasulu and Gedu Satyanarayana*
Abstract: In the present study, a palladium- catalysis1 has stood forefront in the field of
catalyzed direct oxidative acylation through cross- synthetic organic chemistry. This has brought a
dehydrogenative coupling has been investigated, vast advance in the areas of catalysis as well. For
utilizing readily available primary alcohols as
acylating sources. Overall, this oxidative coupling
proceeds via three distinct transformations such as
oxidation, radical formation and cross-coupling in
one catalytic process. This protocol does not
involve the assistance of a directing group or
activation of the carbonyl group by any other
means. Further, this reaction made use of no toxic
CO gas as carbonylating agent; instead, feedstock
primary alcohols have been utilized as acylation
source. Notably, enabled the synthesis of
benzofuranones and indenones. Significantly, this
strategy was also applied to the synthesis of n-
butylphthalide, fenofibrate, pitofenone and neo-
lignan.
instance, acylation is an important CC bond
forming transformation, which has broad
application in organic synthesis.2 One of its major
uses is the preparation of aryl ketones, which are of
chemical feedstock.3 Also, ketone constitute the
structural framework of various natural and
pharmaceutical products.4 In this context, recently,
transition-metal catalyzed direct acylation has
turned out to be as an alternative viable strategy5
when compared with the traditional methods for
CC bond forming reactions, such as, Friedel-
Crafts acylation,6 Grignard/Barbier reaction with
aldehydes and followed by oxidation7 (Scheme-1a),
or Grignard reaction with nitriles8 and
organometallic 1,2-additions to Weinreb amides.9
In addition, transition-metal catalyzed acylation
utilizes a number of readily available chemical
precursors, namely aldehydes,10a α-diketones,10b α-
oxocarboxylic acids,10c benzylic ethers,10d methyl
arenes,10e styrenes10f and benzyl bromides.10g
Despite being functional, utilizing aldehydes bear
some sort of drawbacks. Apart from being
comparatively pricy and highly reactive, aldehydes
Introduction:
In the recent times, functionalization of
chemical compounds by virtue of transition metal-
[a]
Dr. Basuli Suchand, Mr. Chinnabattigalla Sreenivasulu,
Prof. Dr. Gedu Satyanarayana
Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi-
502285, Sangareddy, Telangana, INDIA
Phone: (040) 2301 6033; Fax: (040) 2301 6003 / 32,
E-mail: gvsatya@iith.ac.in
Homepage:
https://sites.google.com/site/gsresearchgrouphomepage/publications
Supporting information for this article is given via a link at the end of the
document.((Please delete this text if not appropriate))
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are prone to undergo aldol and Tishchenko-type primary alcohols are being more abundant acyl
side reactions.11 Moreover, by virtue, alcohols have surrogates that have been scarcely explored for the
also been identified as good acyl sources,12 due to formation of ketones. This prompted us to check
their low toxicity, economic, stable and the feasibility by using primary alcohols as
commercially available. However, they are seldom acylating agents, for the direct cross-coupling
(acylation) without the assistance of any directing
group. During the manuscript preparation a
seminal report has been published by Stephen G.
directly employed in the CC bond forming cross-
coupling reactions. Thus, this kind of reaction can
be proceeded through multiple oxidation state-
manipulating steps, in single catalytic process
through oxidation and acyl or benzoyl radical
formation and cross-coupling reactions (Scheme-
1c).
Newman
group
(Scheme
1b),
wherein
organotriflates and primary alcohols have been
employed for the cross dehydrogenative coupling
to synthesize ketones, in the presence of a nickel
catalyst.13
Aside from the direct acylation, the
strategic approach for the one-pot synthesis of
bioactive molecule displays good economy
concerning step count when compared to well-
established classical method(s). For instance,
indenone cores are omnipresent bicyclic motifs,
with proficient biological properties and can be
served as synthons as well,14 in the synthesis of
natural products. Till now, numerous synthetic
routes have been described for their synthesis. For
example, transition-metal catalyzed annulations of
alkynes were accomplished using carbon
monoxide (CO) as carbonylating agent.15 Also,
annulations of internal alkynes with 2-
Scheme 1: Classical approach and our strategy.
halobenzaldehydes
or
2-
Thus, investigative studies to develop such
(methoxycarbonyl)phenylboronic acids or 2-
bromophenylboronic acids or 2-iodobenzonitriles
have been developed,16 under transition-metal
strategies
could
aid
various
chemical
transformations and form multiple bonds in one-
pot operation. To the best of our knowledge,
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10.1002/ejoc.201900769
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catalysis.
Furthermore,
radical
mediated
To initiate our investigations to identify the
cyclizations have also been utilized for the optimal conditions, initially, we examined the
preparation of indenones.17 Despite good number reaction of ortho-iodomethylbenzoate 1a with
of attempts, some of the methods holds few benzyl alcohol 2a, under our established conditions
drawbacks. Particularly, regioselectivity is a major (i.e. reported conditions for acylations of
issue under transition-metal mediated cyclizations, iodoarenes with benzaldehydes20a). Notably, the
especially, when unsymmetrical alkynes were desired ketone 3aa was formed in 47% yield (Table
employed as annulation partners.18 Hence, it is 1, entry 1). From our earlier observations, it was
highly desirable to establish the synthesis of clear that t-butyl hydroperoxide (TBHP) was the
indenones with high regioselectivity.
best oxidant and silver oxide (Ag2O) was the
Extending our investigations in transition- optimum additive. Hence, it was thought to explore
metal catalysis,19 recently, a [Pd]-catalyzed the reaction with regards to the quantity of alcohol
environmentally benign acylations was reported, (acylating source) and also it was expected that the
for the synthesis of various ketones.20a alcohols would be converted into the
Subsequently, its precision was seen in the one-pot corresponding aldehydes in-situ by oxidizing agent
synthesis of indenones,20b 4-aryl-2-quinolinone,20c TBHP that in turn could acylate the iodoarene. As
phthalazine and phthalazinones.23d Herein, we expected, by increasing amount of benzyl alcohol
describe an oxidative strategy, in which alcohols 2a to 5.0 equiv, the yield of the ketone 3aa was
have been employed as acylating agents, under slightly improved (Table 1, entry 2). Fair amount
palladium-catalyzed direct acylations. Alcohols are of 3aa was obtained with 6.0 equiv of benzyl
less toxic, stable, and widely available and are alcohol 2a (Table 1, entry 3). However, further
inexpensive compared to α-oxocarboxylic acid and increase of 2a could not show notable improvement
aldehydes. Also, we applied this approach to the in the yield (Table 1, entry 4). Thus, it was
one-pot synthesis of indenones by employing concluded that 6.0 equiv of 2a be the optimal
intramolecular aldol condensation reaction on in- amount of alcohol 2a. From our previous reports, it
situ generated di-ketones. In addition, the strategy was also noted that sufficient amount of TBHP was
was applied to the synthesis of natural as well as necessary to facilitate the acylation and to furnish
pharmaceutical products.
the products in good yields. Since the present case
deals with alcohols, utilized 6.0 equiv of
TBHP/H2O (Table 1, entry 5). To our delight,
ketone 3aa was isolated in 64% yield. However,
Results and discussion:
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9
6.0
6.0
Ag2CO3 6.0
(1.2)
23
22
59
58
further increase of TBHP did not improve in the
product 3aa yield (Table 1, entry 6).
Table 1. Optimization studies for the acylation
product 3aa.a
10
AgOAc 6.0
(1.2)
aUnless otherwise mentioned, all the reactions were carried out by
using 105.0 mg (0.40 mmol) of aryl iodide 1a, 5 mol% of Pd(OAc)2,
at 120 °C temperature. bIsolated yields of chromatographically pure
products.
No further improvement was found upon
increasing the amount of both alcohol 2a and
TBHP/H2O (Table 1, entry 7). As identified by the
previous reports, silver salt (Ag2O) was an
effective additive for [Pd]-catalyzed direct
acylation reactions. Thus, the reaction with slightly
increased amount of Ag2O (1.5 equiv), could not
raise the yield (Table 1, entry 8). On the other hand,
the reaction in the presence of Ag2CO3 and AgOAc
were not much effective (Table 1, entries 9 & 10).
With the above conditions (Table 1, entry
Entry Alcohol Additive Oxidant Time Yield
(equiv) (equiv)
(equiv) (h)
(%)b
1
2
3
4
5
6
7
8
4.0
5.0
6.0
7.0
6.0
6.0
7.0
6.0
Ag2O
(1.2)
Ag2O
(1.2)
Ag2O
(1.2)
Ag2O
(1.2)
Ag2O
(1.2)
Ag2O
(1.2)
Ag2O
(1.2)
Ag2O
(1.5)
4.0
4.0
4.0
4.0
6.0
7.0
7.0
6.0
22
21
22
22
20
20
20
20
47
55
60
60
64
63
64
64
5), next, we evaluated the scope and generality of
this acylation between various iodoarenes 1a-v and
benzyl alcohols 2a-g. Gratifyingly, the process was
viable and delivered the corresponding diaryl
ketones 3aa-va, in moderate to fair yields (Table 2).
The method was successful with electron
withdrawing ester and ketone moieties connected
to iodoarenes. The acylation reaction was feasible
to a variety of benzyl alcohols bearing a wide range
of functional groups. For example, in addition to
the simple benzyl alcohol 2a, the reaction was
smooth with electron activating Me (2b) and OMe
(2g) groups on the aromatic ring of benzyl alcohols.
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Significantly, amenable to the electron deactivating
Besides this study, to describe the
substituents [e.g. F (2c), Cl (2d), Br (2e & 2f)]. permissibility of the process, we investigated the
Further, the reaction was also feasible with reaction with aliphatic alcohols 2k-m. As
iodoarenes bearing Me, OMe and methylenedioxy anticipated, the protocol was quite successful and
groups including simple iodobenzene (1q-u) and afforded variety of ketones 3am-vk possessing
afforded the ketones 3qa-ua (Table 2). different functionalities on their aromatic rings
Remarkably, acylation was successful with (Table 3).
iodoarene 1v having strong electron withdrawing
nitro functionality and gave the product 3va, albeit
in moderate yields (Table 2).
Table 2: Scope and generality of formation of ketones 3aa-va.a,b
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Reaction conditions: aall the reactions were carried out by using aryl iodide 1 (0.40 mmol), alcohol 2 (2.4 mmol), Pd(OAc)2 (5 mol%), Ag2O
(0.48 mmol) and TBHP (2.4 mmol). The resulting reaction mixture was stirred at 120 °C for 16-24 h. bIsolated yields of chromatographically
pure products.
Table 3: Scope and generality of formation of ketones 3am-vk.a,b
Reaction conditions: aall reactions were carried out by using aryl iodide 1 (0.40 mmol), alcohol 2 (2.4 mmol), Pd(OAc)2 (5 mol%), Ag2O
(0.48 mmol) and TBHP (2.4 mmol), the resulting reaction mixture was stirred at 120 °C for 16-24 h. bIsolated yields of chromatographically
pure products.
Furthermore, to illustrate the scope of the
present strategy, it was executed for the synthesis
of
biologically
significant
scaffolds,
benzofuranones (Table 4). Unlike our earlier report,
the desired lactones were obtained by reducing the
concentrated crude reaction mixture of ortho-
ketoesters (i.e. after work-up) with NaBH4. Thus,
benzofuranones 4ba-bm were isolated in moderate
overall yields (Table 4).
Table 4: Scope and generality of formation of
benzofuranones 4ba-bm.a,b
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Reaction conditions: ai) all reactions were carried out by using aryl
iodide 1 (0.40 mmol), alcohol 2 (2.4 mmol), Pd(OAc)2 (5 mol%),
Ag2O (0.48 mmol) and TBHP (2.4 mmol), the resulting reaction
mixture was stirred at 120 °C for 16-24 h; ii) then to the concentrated
crude reaction mixture of keto-ester, were added NaBH4 (0.80
mmol), CeCl37H2O (0.40 mmol), and MeOH (1 mL) and stirred at
Reaction conditions: ai) all reactions were carried out by using aryl
iodide 1 (0.40 mmol), alcohol 2 (2.4 mmol), Pd(OAc)2 (5 mol%),
Ag2O (0.48 mmol) and TBHP (2.4 mmol), the resulting reaction
mixture was stirred at 120 °C for 16-24 h; ii) then to the cooled
reaction mixture to rt, was added conc. H2SO4 (2.0 mmol) and stirred
at rt for 5-10 min. bIsolated yields of chromatographically pure
products.
b
0 °C to rt for 12-16 h. Isolated yields of chromatographically pure
products.
Furthermore, particularly, to demonstrate
the utility of the one-pot protocol, for the synthesis
of indenones, the reaction was carried out between
ortho-iodobenzophenones 1m-p with various
aliphatic alcohols 2k-m. Pleasingly, the strategy
exhibited good adaptability and delivered the
expected indenones 5mm-pm (Table 6).
Remarkably, the reaction was consistent with
heteroaromatic ortho-iodobenzophenone 1p. As a
matter of fact, in the involvement of electron-rich
aromatic systems (iodoarenes and benzyl alcohol)
the direct formation of indenones was seen in
minor quantities, before subjecting the aldol
condensation reaction of in-situ formed 1,2-
diketone intermediate with conc. H2SO4 (Table 6,
5ol). Presumably, the aldol condensation of 1,2-
To exemplify the synthetic significance of
this protocol, next, it was aimed for one-pot
synthesis of indenones. As established by our
previous report, this could be feasible via acid
mediated intramolecular aldol condensation of in-
situ generated diketone derivatives. Thus, after
confirming the formation of 1,2-diketobenzene,
using thin-layer-chromatography (TLC), to the
reaction mixture, was added to conc. H2SO4, at
room temperature. As predicted, the acylation
reaction and subsequent intramolecular aldol
condensation in one-pot was successful and gave
the desired indenones 5ja-lb (Table 5).
Table 5: Scope and generality of one-pot synthesis
of indenones 5ja-lb.a,b
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diketone bearing both electron rich aromatic rings, strategy was successfully applied to the synthesis
would have been triggered either by the silver ions of fenofibrate, pitofenone, n-butylpthalide and one-
(Ag+) of Ag2O or the carboxylic acid that might be pot synthesis of natural product neo-lignan
produced from the corresponding benzyl alcohol in (Scheme 2). Thus, the reaction between
the presence of oxidizing agent TBHP.
iododerivative 1w with p-chlorobenzyl alcohol 2d,
under the standard acylation conditions, furnished
fenofibrate 3wd with 52% yield (Scheme 2a).
Notably, the synthesis of n-butylphthalide 4bl was
accomplished
starting
from
ortho-
iodoethylbenzoate 1b with amyl alcohol 2l. It is
worth noting that 4bl was obtained by using a
Table 6: Scope and generality for the synthesis of single column chromatography technique upon
indenones 5mm-pm.a,b
reducing the concentrated crude reaction mixture
of keto-ester with NaBH4 and subsequent
intramolecular nucleophilic attack/condensation
step of alkoxide intermediate onto the ester
functionality (Scheme 2b). Delightfully, the
antispasmodic drug, pitofenone 6aj, was achieved
in just two steps (Scheme 2c). This certainly
illustrate the efficacy of the present strategy. Most
significant utility of the present protocol is its
application in the one-pot synthesis of the natural
product, neo-lignan 5kh. The compound was
afforded by subjecting ortho-iodoketone 1k with
benzyl alcohol 2h, under standard acylation
conditions and without the need of using conc.
H2SO4. This is because of the fact that either of
these aromatic rings are electron rich enough and
hence, a mild acidity present in the reaction either
in the form of silver ions or in the form of
carboxylic acid, would be good enough to drive the
Reaction conditions: ai) all reactions were carried out by using aryl
iodide 1 (0.40 mmol), alcohol 2 (2.4 mmol), Pd(OAc)2 (5 mol%),
Ag2O (0.48 mmol) and TBHP (2.4 mmol). The reaction mixture was
stirred at 120 °C for 16-24 h; ii) then to the cooled reaction mixture
to rt, was added conc. H2SO4 (2.0 mmol) and the resulting reaction
mixture was stirred at rt for 5-30 min. bIsolated yields of
chromatographically pure products.
Next, we turned our attention to highlight
the applications of this acylation protocol. The
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subsequent intramolecular aldol condensation step. applications, certifies the synthetic utility of the
The natural product neo-lignan 5kh was obtained present methodology.
in 50% yield in one-pot (Scheme 2d). These above
Scheme 2: Synthesis of fenofibrate, pitofenone, n-butylphthalide and neo-lignan.
Next, we sought to explore the mechanism of 7aa was also established by single crystal X-ray
the reaction. In our previous work,20a it was proved diffraction analysis (Figure 1). Even, para-
that the reaction proceeds via radical path from methoxybenzyl alcohol 2g was also underwent
aldehydes. Thus, it is predicted that the present case same reaction with 1a and furnished 7ag in
would follow a radical mechanism. Hence, to excellent yield (Scheme 3b). Based on the above
further prove it, the reaction was performed trapping experiments, it can be confirmed that
between ortho-iodoester 1a and benzyl alcohol 2a initially aldehyde is generated from the
in
the
presence
of
2,2,6,6- corresponding alcohol via oxidation reaction
tetramethylpiperidinyloxy (TEMPO), a free radical facilitated by TBHP. This aldehyde in turn will
scavenger, under standard conditions. Gratifyingly, undergo further oxidation and gets converted into
as predicted, the aldehyde radical trapped 2,2,6,6- aldehyde-radical by the same TBHP oxidant. The
tetramethylpiperidinyl ester 7aa was formed in insitu generated aldehyde radical can undergo
95% yield (Scheme 3a). The chemical structure of cross-coupling with aryl-palladium species which
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is formed from an independent pathway thruogh synthesis of indenones. Moreover, enabled the
the oxidative insertion of palldium catalyst across
synthesis of drug molecules such as fenofibrate,
the CI bond. Finally, reductive elimination leads
petofenone, n-butylphthalide and naturally
to the formation of target product ketone.
occurring neo-lignan.
Experimental:
IR spectra were recorded on
a
FTIR
spectrophotometer. 1H NMR spectra were recorded
on 400 MHz spectrometer at 295 K in CDCl3;
chemical shifts (δ ppm) and coupling constants
(Hz) are reported in standard fashion with reference
to either internal standard tetramethylsilane (TMS)
(δH =0.00 ppm) or CHCl3 (δH = 7.25 ppm). 13C
NMR spectra were recorded on 100 MHz
spectrometer at RT in CDCl3; chemical shifts (δ
ppm) are reported relative to CHCl3 [δC = 77.00
Scheme 3: Trapping of reactions with TEMPO.
13
ppm (central line of triplet)]. In the C NMR, the
nature of carbons (C, CH, CH2 and CH3) was
determined by recording the DEPT-135 spectra. In
Figure 1: Single crystal structure of 7aa
(CCDC: 1935118).
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
Conclusion:
In conclusion, we have described a [Pd]-
catalyzed direct coupling reaction of iodiarenes
with alcohols, for the synthesis of a wide range of
ketones. This protocol involves the use of simple
and readily available benchtop alcohols and in-situ
served as acyl radicals by the oxidizing agent
TBHP. This methodology has been utilized to
afford the variety of benzofuranones using a single
column chromatography technique and one-pot
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using a combination of hexane and ethyl acetate as column chromatography (petroleum ether/ethyl
eluents. Reactions were generally run under acetate) furnished the products 3aa-va (36.0-76.0
nitrogen atmosphere. Acme’s silica-gel (60–120 mg, 40-64%).
mesh) was used for column chromatography
(approximately 20 g per one gram of crude GP-2 [General Procedure for Preparation of
material). All catalysts, reagents and reactants were Benzofuranones 4]:
procured from commercial suppliers (Sigma To an oven dried Schlenk tube, were added ortho-
Aldrich, Merck, Hychem and Avra) and used as iodo ester 1b (110.0 mg, 0.40 mmol), alcohol 2
received. Solvents, used for work up and (177.0-293.0 mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5
chromatographic procedures were purchased from mol%), Ag2O (111.0 mg, 0.48 mmol) and TBHP
commercial suppliers (Madin Lifesciences, (308.0 mg, 2.4 mmol). The resulting reaction
Standard Reagents Spectrochem) and distilled mixture was stirred at 120 °C for 16-24 h. The
prior to use.
progress of the product 3 formation was monitored
by TLC till the reaction was completed. The
GP-1 [General Procedure for Preparation of reaction mixture was allowed to cool to room
ketones 3]: temperature, diluted with aqueous NaHCO3
To an oven dried Schlenk tube, were added aryl solution and then extracted with ethyl acetate (3 ×
iodide 1 (81.0-127.0 mg, 0.40 mmol), alcohol 2 15 mL). The organic layers were washed with
(259.0-448.0 mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5 saturated NaCl solution, dried (Na2SO4) and
mol%), Ag2O (111.0 mg, 0.48 mmol) and TBHP filtered. Evaporation of the solvent under reduced
(308.0 mg, 2.4 mmol). The resulting reaction pressure then kept in high vacuum for 10 minutes.
mixture was stirred at 120 °C for 16-24 h. TLC Then, to this magnetically stirred reaction mixture
monitored the progress of the reaction, for the solution of keto ester in MeOH (1 mL), were added
formation 3 until the reaction was completed. The sequentially CeCl3.7H2O (149.0 mg, 0.40 mmol)
reaction mixture was cooled to room temperature, and NaBH4 (30.0 mg, 0.80 mmol). The reaction
diluted with aqueous NaHCO3 solution and then mixture was stirred at 0 °C to room temperature for
extracted with ethyl acetate (3 × 15 mL). The 12 to 24 h. The progress of the product 4ba-bm
organic layers were washed with saturated NaCl formation was monitored by TLC. The reaction
solution, dried (Na2SO4) and filtered. Evaporation mixture was quenched with H2O and then extracted
of the solvent under reduced pressure and with ethyl acetate (3 × 10 mL). Purification of the
purification of the crude material by silica-gel crude
material
by
silica-gel
column
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chromatography (petroleum ether/ethyl acetate)
furnished the product 4ba-bm (32.0-43.0 mg, 44- Methyl-2-benzoyl-5-methylbenzoate (3fa): GP-1
51%).
was carried out with aryl iodide 1f (110.0 mg, 0.40
mmol), aromatic alcohol 2a (259.0 mg, 2.4 mmol),
GP-4 [General procedure for preparation of Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (111.0 mg, 0.48
indenones 5]: mmol) and TBHP (308.0 mg, 2.4 mmol). The
To an oven dried Schlenk tube, were added resulting reaction mixture was stirred at 120 °C for
ortho-iodoketone 1j-p (104.0-153.0 mg, 0.40 20 h. The progress of the product 3fa formation
mmol) and alcohols 2a-m (177.0-370.0 mg, 2.4 was monitored by TLC till the reaction was
mmol) in the presence of Pd(OAc)2 (5.0 mg, 5 completed. Purification of the crude material by
mol%), Ag2O (111.0 mg, 0.48 mmol) and TBHP silica-gel column chromatography (petroleum
(308.0 mg, 2.4 mmol) and allowed the reaction ether/ethyl acetate, 98:02 to 97:03) furnished the
mixture to stir at 120 °C for 18-28 h. Progress of product 3fa (63.0 mg, 62%) as a colourless viscous
the reaction was monitored by TLC till the ortho- liquid. [TLC control (petroleum ether/ethyl acetate
iodoketone 1i-p was completed. Then the reaction 95:05), Rf(1f)=0.80, Rf(3fa)=0.40, UV detection].
IR (MIR-ATR, 4000–600 cm-1): max=2934, 2853,
mixture was removed from oil bath and allow to
1728, 1673, 1444, 1273, 1091, 929, 836, 714 cm-1.
reach room temperature and then added conc.
1H NMR (CDCl3, 400 MHz): δ=7.82 (s, 1H Ar-H),
H2SO4 (0.1 mL, 2.0 mmol) and allowed the
reaction mixture stirred at room temperature.
Progress of the products 5 formation was
monitored by TLC till the reaction was completed.
The reaction mixture was quenched by the addition
of aqueous NaHCO3 solution and then extracted
with ethyl acetate (3 × 15 mL). The organic layers
were washed with saturated NaCl solution, dried
(Na2SO4) and filtered. Evaporation of the solvent
under reduced pressure and purification of the
7.73 (dd, 2H, J=8.3 and J=1.4 Hz, Ar-H), 7.54-7.50
(m, 1H Ar-H), 7.43-7.38 (m, 3H Ar-H), 7.31 (d,
1H, J=7.8 Hz, Ar-H), 3.55 (s, 3H, OCH3), 2.45 (s,
3H, CH3) ppm. 13C NMR (CDCl3, 100 MHz):
δ=197.1 (s, C=O), 166.7 (s, O–C=O), 140.0 (s, Ar-
C), 138.6 (s, Ar-C), 137.4 (s, Ar-C), 132.9 (d, Ar-
CH), 132.8 (d, Ar-CH), 130.4 (d, Ar-CH), 129.4 (s,
Ar-C), 129.1 (d, 2C, Ar-CH), 128.4 (d, 2C, Ar-
CH), 128.0 (d, Ar-CH), 52.0 (q, OCH3), 21.1 (q,
CH3) ppm. HR-MS (ESI+) m/z calculated for
[C16H15O3]+=[MH]+: 255.1016; found 255.1006.
crude material
by silica gel
column
chromatography (petroleum ether/ethyl acetate)
furnished the products 5ja-pm (48.0-71.0 mg, 45-
57%) as viscous liquid/solid.
Methyl 2-benzoyl-5-bromobenzoate (3ga): GP-1
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
FULL PAPER
was carried out with aryl iodide 1g (136.0 mg, 0.40
1-[2-(4-Fluorobenzoyl)phenyl]propan-1-one
mmol), aromatic alcohol 2a (259.0 mg, 2.4 mmol), (3jc): GP-1 was carried out with aryl iodide 1j
Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (111.0 mg, 0.48 (104.0 mg, 0.40 mmol), aromatic alcohol 2c (302.0
mmol) and TBHP (308.0 mg, 2.4 mmol). The mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O
resulting reaction mixture was stirred at 120 °C for (111.0 mg, 0.48 mmol) and TBHP (308.0 mg, 2.4
22 h. The progress of the product 3ga formation mmol). The resulting reaction mixture was stirred
was monitored by TLC till the reaction was at 120 °C for 23 h. The progress of the product 3jc
completed. Purification of the crude material by formation was monitored by TLC till the reaction
silica-gel column chromatography (petroleum was completed. Purification of the crude material
ether/ethyl acetate, 98:02 to 97:03) furnished the by silica-gel column chromatography (petroleum
product 3ga (74.0 mg, 58%) as a colourless viscous ether/ethyl acetate, 90:10 to 85:15) furnished the
liquid. [TLC control (petroleum ether/ethyl acetate product 3jc (51.2 mg, 50%) as a colourless viscous
95:05), Rf(1g)=0.70, Rf(3ga)=0.30, UV detection]. liquid. [TLC control (petroleum ether/ethyl acetate
IR (MIR-ATR, 4000–600 cm-1): max=2927, 2855,
90:10), Rf(1j)=0.90, Rf(3jc)=0.30, UV detection].
IR (MIR-ATR, 4000–600 cm-1): max=3059, 2927,
1722, 1674, 1596, 1501, 1435, 1278, 1142, 1086,
1
935, 848, 762 cm-1. H NMR (CDCl3, 400 MHz): 2857, 1675, 1583, 1479, 1362, 1263, 1163, 1089,
δ=8.17 (d, 1H, J=1.9 Hz, Ar-H), 7.76 (dd, 1H, J = 1020, 930, 732 cm-1. 1H NMR (CDCl3, 400 MHz):
8.1, 2.0 Hz, Ar-H), 7.74-7.70 (m, 2H, Ar-H), 7.58- δ=7.87 (dd, 1H, J=6.8 and 1.9 Hz, Ar-H), 7.78–
7.53 (m, 1H Ar-H), 7.45-7.41 (m, 2H Ar-H), 7.28 7.73 (m, 2H, Ar-H), 7.64–7.53 (m, 2H, Ar-H),
(d, 1H, J=8.3 Hz, Ar-H), 3.61 (s, 3H, OCH3) ppm. 7.38–7.35 (m, 1H, Ar-H), 7.10–7.04 (m, 2H, Ar-
13C NMR (CDCl3, 100 MHz): δ=195.9 (s, C=O), H), 2.92 (q, 2H, J=7.3 Hz, CH2), 1.09 (t, 3H, J=7.3
165.1 (s, O–C=O), 140.3 (s, Ar-C), 136.8 (s, Ar-C), Hz, CH3) ppm. 13C NMR (CDCl3, 100 MHz):
135.3 (d, Ar-CH), 133.3 (d, Ar-CH), 133.0 (d, Ar- δ=201.4 (s, C=O), 196.3 (s, C=O), 165.5 (d, 1J=254
CH), 131.0 (s, Ar-C), 129.4 (d, Ar-CH), 129.2 (d, Hz, Ar-CF), 140.6 (s, Ar-C), 137.4 (s, Ar-C), 133.6
2C, Ar-CH), 128.6 (d, 2C, Ar-CH), 123.8 (s, Ar- (d, 4J=2.9 Hz, Ar-C-CF), 131.9 (d, 2C, CH), 131.8
C), 52.5 (q, OCH3) ppm. HR-MS (ESI+) m/z (d, Ar-CH), 129.7 (d, CH), 128.6 (d, Ar-CH), 128.1
calculated
318.9964;
for
[C15H12Br79O3]+=[M+H]+: (d, Ar-CH), 115.6 (d, Ar-CH), 115.4 (d, Ar-CH),
found
318.9949; 32.8 (t, CH2), 7.9 (q, CH3) ppm. HR-MS (ESI+) m/z
[C15H12Br81O3]+=[M+H]+:
320.9944;
found
calculated for [C16H14FO2]+=[MH]+: 257.0972;
320.9928.
found 257.0968.
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
FULL PAPER
(104.0 mg, 0.40 mmol), aromatic alcohol 2e (449.0
1-[2-(4-Chlorobenzoyl)phenyl]propan-1-one
(3jd): GP-1 was carried out with aryl iodide 1j mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O
(104.0 mg, 0.40 mmol), aromatic alcohol 2d (342.0 (111.0 mg, 0.48 mmol) and TBHP (308.0 mg, 2.4
mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O mmol). The resulting reaction mixture was stirred
(111.0 mg, 0.48 mmol) and TBHP (308.0 mg, 2.4 at 120 °C for 24 h. The progress of the product 3je
mmol). The resulting reaction mixture was stirred formation was monitored by TLC till the reaction
at 120 °C for 23 h. The progress of the product 3jd was completed. Purification of the crude material
formation was monitored by TLC till the reaction by silica-gel column chromatography (petroleum
was completed. Purification of the crude material ether/ethyl acetate, 90:10 to 85:15) furnished the
by silica-gel column chromatography (petroleum product 3je (62.0 mg, 49%) as a colourless viscous
ether/ethyl acetate, 90:10 to 85:15) furnished the liquid. [TLC control (petroleum ether/ethyl acetate
product 3jd (57.8 mg, 53%) as a colourless viscous 90:10), Rf(1j)=0.80, Rf(3je)=0.30, UV detection].
IR (MIR-ATR, 4000–600 cm-1): max=3059, 2926,
liquid. [TLC control (petroleum ether/ethyl acetate
90:10), Rf(1j)=0.80, Rf(3jd)=0.30, UV detection].
2856, 1676, 1584, 1480, 1409, 1263, 1090, 929,
IR (MIR-ATR, 4000–600 cm-1): max=3060, 2927,
730 cm-1. 1H NMR (CDCl3, 400 MHz): δ=7.88 (dd,
1
2857, 1675, 1583, 1263, 1089, 929, 730 cm-1. H 1H, J=6.8 and 1.9 Hz, Ar-H), 7.63–7.52 (m, 6H,
NMR (CDCl3, 400 MHz): δ=7.88 (dd, 1H, J=6.8 Ar-H), 7.37–7.34 (m, 1H, Ar-H), 2.92 (q, 2H, J=7.3
13
and 1.9 Hz, Ar-H), 7.68–7.65 (m, 2H, Ar-H), 7.63– Hz, CH2), 1.08 (t, 3H, J=7.3 Hz, CH3) ppm. C
7.55 (m, 2H, Ar-H), 7.39–7.35 (m, 3H, Ar-H), 2.92 NMR (CDCl3, 100 MHz): δ=201.2 (s, C=O), 196.8
(q, 2H, J=7.3 Hz, CH2), 1.08 (t, 3H, J=7.3 Hz, CH3) (s, C=O), 140.3 (s, Ar-C), 137.3 (s, Ar-C), 135.9 (s,
ppm. 13C NMR (CDCl3, 100 MHz): δ=201.3 (s, Ar-C), 132.0 (d, Ar-CH), 131.7 (d, 2C, CH), 130.7
C=O), 196.6 (s, C=O), 140.4 (s, Ar-C), 139.3 (s, (d, 2C, CH), 129.8 (d, Ar-CH), 128.7 (d, Ar-CH),
Ar-C), 137.4 (s, Ar-C), 135.6 (s, Ar-C), 132.0 (d, 128.0 (d, Ar-CH), 128.0 (s, Ar-C), 32.7 (t, CH2),
Ar-CH), 130.6 (d, 2C, CH), 129.8 (d, Ar-CH), 7.9 (q, CH3) ppm. HR-MS (ESI+) m/z calculated
for [C16H14Br79O2]+=[MH]+: 317.0172; found
128.7 (d, 2C, CH), 128.7 (d, Ar-CH), 128.1 (d, Ar-
317.0158; [C16H14Br81O2]+=[M+H]+: 319.0151;
CH), 32.7 (t, CH2), 7.9 (q, CH3) ppm. HR-MS
(ESI+) m/z calculated for [C16H14ClO2]+=[MH]+:
found 319.0138.
273.0677; found 273.0665.
1-[2-(4-Methoxybenzoyl)phenyl]propan-1-one
(3jg): GP-1 was carried out with aryl iodide 1j
1-[2-(4-Bromobenzoyl)phenyl]propan-1-one
(3je): GP-1 was carried out with aryl iodide 1j (104.0 mg, 0.40 mmol), aromatic alcohol 2g (331.0
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
FULL PAPER
mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O mmol) and TBHP (308.0 mg, 2.4 mmol). The
(111.0 mg, 0.48 mmol) and TBHP (308.0 mg, 2.4 resulting reaction mixture was stirred at 120 °C for
mmol). The resulting reaction mixture was stirred 24 h. The progress of the product 3am formation
at 120 °C for 23 h. The progress of the product 3jg was monitored by TLC till the reaction was
formation was monitored by TLC till the reaction completed. Purification of the crude material by
was completed. Purification of the crude material silica-gel column chromatography (petroleum
by silica-gel column chromatography (petroleum ether/ethyl acetate, 98:02 to 97:03) furnished the
ether/ethyl acetate, 90:10 to 85:15) furnished the product 3am (56.2 mg, 60%) as a colourless
product 3jg (54.7 mg, 51%) as a colourless viscous viscous liquid. [TLC control (petroleum ether/ethyl
liquid. [TLC control (petroleum ether/ethyl acetate acetate 95:05), Rf(1a)=0.90, Rf(3am)=0.40, UV
90:10), Rf(1j)=0.80, Rf(3jg)=0.20, UV detection]. detection]. IR (MIR-ATR, 4000–600 cm-1):
IR (MIR-ATR, 4000–600 cm-1): max=2924, 2855,
max=2916, 1723, 1662, 1491, 1440, 1271, 1038,
1667, 1581, 1351, 1271, 1195, 1014, 873, 716 cm- 942, 751 cm-1. 1H NMR (CDCl3, 400 MHz): δ=7.85
1
1. H NMR (CDCl3, 400 MHz): δ=7.82 (dd, 1H, (dd, 1H, J=7.3 and 1.4 Hz, Ar-H), 7.53 (td, 1H,
J=7.3 and 1.9 Hz, Ar-H), 7.74–7.70 (m, 2H, Ar-H), J=7.3 and 1.4 Hz, Ar-H), 7.45 (td, 1H, J=7.3 and
7.59–7.52 (m, 2H, Ar-H), 7.38–7.36 (m, 1H, Ar- 1.4 Hz, Ar-H), 7.32 (dd, 1H, J=7.3 and 1.4 Hz, Ar-
H), 6.90–6.87 (m, 2H, Ar-H), 3.83 (s, 3H, OCH3), H), 3.85 (s, 3H, OCH3), 2.76 (t, 2H, J=7.8 Hz,
2.89 (q, 2H, J=7.3 Hz, CH2), 1.08 (t, 3H, J=7.3 Hz, CH2), 1.74–1.67 (m, 2H, CH2), 1.37–1.30 (m, 4H,
CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ=201.8 CH2), 0.89–0.86 (m, 3H, CH3) ppm. 13C NMR
(s, C=O), 196.5 (s, C=O), 163.4 (s, Ar-C), 140.8 (s, (CDCl3, 100 MHz): δ=205.8 (s, C=O), 167.2 (s, O–
Ar-C), 137.8 (s, Ar-C), 131.8 (d, 2C, Ar-CH), C=O), 143.2 (s, Ar-C), 132.0 (d, Ar-CH), 129.8 (d,
131.5 (d, Ar-CH), 130.1 (s, Ar-C), 129.5 (d, Ar- Ar-CH), 129.6 (d, Ar-CH), 128.4 (s, Ar-C), 126.2
CH), 128.4 (d, Ar-CH), 128.2 (d, Ar-CH), 113.6 (d, (d, Ar-CH), 52.4 (q, CH3), 42.7 (t, CH2), 31.3 (t,
Ar-CH), 55.4 (q, CH3), 33.2 (t, CH2), 8.0 (q, CH3) CH2), 23.7 (t, CH2), 22.4 (t, CH2), 13.9 (q, CH3)
ppm. HR-MS (ESI+) m/z calculated for ppm. HR-MS (ESI+) m/z calculated for
[C17H17O3]+=[MH]+: 269.1172; found 269.1165.
[C14H19O3]+=[MH]+: 235.1329; found 235.1332.
Methyl 2-hexanoylbenzoate (3am): GP-1 was Ethyl-2-hexanoylbenzoate (3bm): GP-1 was
carried out with aryl iodide 1a (105.0 mg, 0.40 carried out with aryl iodide 1b (110.0 mg, 0.40
mmol), aromatic alcohol 2m (245.0 mg, 2.4 mmol), mmol), aromatic alcohol 2m (245.0 mg, 2.4 mmol),
Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (111.0 mg, 0.48 Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (111.0 mg, 0.48
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
FULL PAPER
mmol) and TBHP (308.0 mg, 2.4 mmol). The Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (111.0 mg, 0.48
resulting reaction mixture was stirred at 120 °C for mmol) and TBHP (308.0 mg, 2.4 mmol). The
xx h. The progress of the product 3bm formation resulting reaction mixture was stirred at 120 °C for
was monitored by TLC till the reaction was 24 h. The progress of the product 3ck formation
completed. Purification of the crude material by was monitored by TLC till the reaction was
silica-gel column chromatography (petroleum completed. Purification of the crude material by
ether/ethyl acetate, 98:02 to 97:03) furnished the silica-gel column chromatography (petroleum
product 3bm (61.5 mg, 62%) as a colourless ether/ethyl acetate, 98:02 to 97:03) furnished the
viscous liquid. [TLC control (petroleum ether/ethyl product 3ck (53.4 mg, 57%) as a colourless viscous
acetate 95:05), Rf(1b)=0.90, Rf(3bm)=0.30, UV liquid. [TLC control (petroleum ether/ethyl acetate
detection]. IR (MIR-ATR, 4000–600 cm-1): 95:05), Rf(1c)=0.90, Rf(3ck)=0.40, UV detection].

max=2927, 1663, 1593, 1456, 1252, 1180, 1025, IR (MIR-ATR, 4000–600 cm-1): max=3064, 2982,
1
929, 755, 604 cm-1. H NMR (CDCl3, 400 MHz): 1712, 1676, 1585, 1472, 1388, 1272, 1089, 926,
δ=7.86 (dd, 1H, J=7.5 and 1.2 Hz, Ar-H), 7.52 (td, 843,737 cm-1. 1H NMR (CDCl3, 400 MHz): δ=7.86
1H, J = 7.5 and 1.4 Hz, Ar-H), 7.45 (td, J = 7.6 and (dd, 1H, J=7.8 and 0.9 Hz, Ar-H), 7.52 (td, J = 7.5
1.4 Hz, Ar-H), 7.32 (dd, J = 7.5 and 1.0 Hz, Ar-H), and 1.4 Hz, 1H), 7.45 (td, J = 7.6 and 1.4 Hz, 1H),
4.33 (q, 2H, J=7.0 Hz, OCH2CH3), 2.77 (t, 2H, 7.31 (m, 1H, Ar-H), 5.20 (sep, 1H, J=6.3
J=7.0 Hz, CH2), 1.77–1.65 (m, 2H, CH2), 1.35– CH(CH3)2), 2.78 (m, 2H), 1.78–1.69 (m, 2H, CH2),
1.30 (m, 7H, CH2), 0.87 (t, 3H, J=7.0 Hz, 1.32 (d, 6H, J=6.3 CH(CH3)2), 0.98 (t, 3H, J=7.3
OCH2CH3) ppm. 13C NMR (CDCl3, 100 MHz): Hz, CH3) ppm. 13C NMR (CDCl3, 100 MHz):
δ=205.8 (s, C=O), 166.7 (s, O–C=O), 143.2 (s, Ar- δ=205.7 (s, C=O), 166.2 (s, O–C=O), 143.1 (s, Ar-
C), 131.9 (d, Ar-CH), 129.8 (d, Ar-CH), 129.5 (d, C), 131.7 (d, Ar-CH), 129.8 (d, Ar-CH), 129.5 (d,
Ar-CH), 128.8 (s, Ar-C), 126.2 (d, Ar-CH), 61.5 (t, Ar-CH), 129.3 (s, Ar-C), 126.2 (d, Ar-CH), 69.2 (d,
CH2), 42.8 (t, CH2), 31.3 (t, CH2), 22.7 (t, CH2), CH(CH3)2), 44.8 (t, CH2), 21.6 (q, 2C, CH(CH3)2),
22.4 (t, CH2), 14.0 (q, CH3), 13.8 (q, CH3) ppm. 17.4 (t, CH2), 13.7 (q, CH3) ppm. HR-MS (ESI+)
[C14H19O3]+=[MH]+:
HR-MS
(ESI+)
m/z
calculated
for
m/z
calculated
for
[C15H21O3]+=[MH]+: 249.1485; found 249.1487.
235.1329; found 235.1330.
Isopropyl 2-butyrylbenzoate (3ck): GP-1 was Isopropyl 2-hexanoylbenzoate (3cm): GP-1 was
carried out with aryl iodide 1c (116.0 mg, 0.40 carried out with aryl iodide 1c (116.0 mg, 0.40
mmol), aromatic alcohol 2k (177.0 mg, 2.4 mmol), mmol), aromatic alcohol 2m (245.0 mg, 2.4 mmol),
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10.1002/ejoc.201900769
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FULL PAPER
Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (111.0 mg, 0.48 Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (111.0 mg, 0.48
mmol) and TBHP (308.0 mg, 2.4 mmol). The mmol) and TBHP (308.0 mg, 2.4 mmol). The
resulting reaction mixture was stirred at 120 °C for resulting reaction mixture was stirred at 120 °C for
23 h. The progress of the product 3cm formation 24 h. The progress of the product 3dm formation
was monitored by TLC till the reaction was was monitored by TLC till the reaction was
completed. Purification of the crude material by completed. Purification of the crude material by
silica-gel column chromatography (petroleum silica-gel column chromatography (petroleum
ether/ethyl acetate, 98:02 to 97:03) furnished the ether/ethyl acetate, 98:02 to 97:03) furnished the
product 3cm (55.6 mg, 53%) as a colourless product 3dm (59.6 mg, 54%) as a colourless
viscous liquid. [TLC control (petroleum ether/ethyl viscous liquid. [TLC control (petroleum ether/ethyl
acetate 95:05), Rf(1c)=0.90, Rf(3cm)=0.40, UV acetate 95:05), Rf(1d)=0.90, Rf(3dm)=0.40, UV
detection]. IR (MIR-ATR, 4000–600 cm-1): detection]. IR (MIR-ATR, 4000–600 cm-1):

max=2982, 1674, 1585, 1472, 1392, 1273, 1089,
max=2979, 2929, 1712, 1672, 1587, 1465, 1392,
1
1014, 927, 844, 736 cm-1. H NMR (CDCl3, 400 1269, 1089, 927, 843, 744 cm-1. 1H NMR (CDCl3,
MHz): δ=7.85 (d, 1H, J=7.8 Hz, Ar-H), 7.51 (td, 400 MHz): δ=7.88 (dd, 1H, J=7.8 and 0.9 Hz, Ar-
1H, J = 7.5 and 1.2 Hz, Ar-H), 7.44 (td, 1H, J = 7.6 H), 7.54 (td, 1H, J = 7.5 and 1.3 Hz, Ar-H), 7.47
and 1.3 Hz, Ar-H), 7.31 (dd, 1H, J = 7.5, 0.9 Hz, (td, 1H, J = 7.6 and 1.4 Hz, Ar-H), 7.33 (dd, 1H,
Ar-H), 5.20 (sep, 1H, J=6.3 CH(CH3)2), 2.78 (m, J=7.5 and 1.2 Hz, Ar-H), 4.28 (t, 2H, J=6.6 Hz,
2H), 1.74–1.67 (m, 2H, CH2), 1.34–1.31 (m, 10H), OCH2CH2CH2CH3), 2.88–2.73 (m, 2H), 1.73–1.66
13
0.90–0.86 (m, 3H, CH3) ppm. C NMR (CDCl3, (m, 4H, CH2), 1.47–1.38 (m, 2H), 1.36–1.31 (m,
100 MHz): δ=205.8 (s, C=O), 166.2 (s, O–C=O), 4H), 0.95 (t, 3H, J=7.3 Hz, CH3), 0.90–0.87 (m,
143.2 (s, Ar-C), 131.7 (d, Ar-CH), 129.8 (d, Ar- 3H, CH3) ppm. 13C NMR (CDCl3, 100 MHz):
CH), 129.5 (d, Ar-CH), 129.2 (s, Ar-C), 126.1 (d, δ=206.0 (s, C=O), 166.8 (s, O–C=O), 143.4 (s, Ar-
Ar-CH), 69.2 (d, CH), 42.9 (t, CH2), 31.3 (t, CH2), C), 131.9 (d, Ar-CH), 129.9 (d, Ar-CH), 129.6 (d,
23.7 (t, CH2), 22.4 (t, CH2), 21.6 (q, 2C, CH3), 13.9 Ar-CH), 128.8 (s, Ar-C), 126.2 (d, Ar-CH), 65.5 (t,
(q, CH3) ppm. HR-MS (ESI+) m/z calculated for CH2), 42.9 (t, CH2), 31.4 (t, CH2), 30.5 (t, CH2),
[C16H23O3]+=[MH]+: 263.1642; found 263.1647.
23.7 (t, CH2), 22.5 (t, CH2), 19.2 (t, CH2), 13.9 (q,
CH3), 13.7 (q, CH3) ppm. HR-MS (ESI+) m/z
calculated for [C17H25O3]+=[MH]+: 277.1798;
Butyl 2-hexanoylbenzoate (3dm): GP-1 was
carried out with aryl iodide 1d (121.0 mg, 0.40 found 277.1800.
mmol), aromatic alcohol 2m (245.0 mg, 2.4 mmol),
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
FULL PAPER
Pentyl 2-butyrylbenzoate (3ek): GP-1 was
carried out with aryl iodide 1e (127.0 mg, 0.40 Pentyl 2-hexanoylbenzoate (3em): GP-1 was
mmol), aromatic alcohol 2k (177.0 mg, 2.4 mmol), carried out with aryl iodide 1e (127.0 mg, 0.40
Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (111.0 mg, 0.48 mmol), aromatic alcohol 2m (211 mg, 2.4 mmol),
mmol) and TBHP (308.0 mg, 2.4 mmol). The Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (111.0 mg, 0.48
resulting reaction mixture was stirred at 120 °C for mmol) and TBHP (308.0 mg, 2.4 mmol). The
23 h. The progress of the product 3ek formation resulting reaction mixture was stirred at 120 °C for
was monitored by TLC till the reaction was 23 h. The progress of the product 3em formation
completed. Purification of the crude material by was monitored by TLC till the reaction was
silica-gel column chromatography (petroleum completed. Purification of the crude material by
ether/ethyl acetate, 98:02 to 97:03) furnished the silica-gel column chromatography (petroleum
product 3ek (57.7 mg, 55%) as a colourless viscous ether/ethyl acetate, 98:02 to 97:03) furnished the
liquid. [TLC control (petroleum ether/ethyl acetate product 3em (67.3 mg, 58%) as a colourless
95:05), Rf(1e)=0.90, Rf(3ek)=0.30, UV detection]. viscous liquid. [TLC control (petroleum ether/ethyl
IR (MIR-ATR, 4000–600 cm-1): max=2949, 2866,
acetate 95:05), Rf(1e)=0.90, Rf(3em)=0.30, UV
detection]. IR (MIR-ATR, 4000–600 cm-1):
1718, 1669, 1584, 1457, 1265, 1128, 1080, 929,
726 cm-1. 1H NMR (CDCl3, 400 MHz): δ=7.87 (dd,

max=2953, 1718, 1670, 1584, 1458, 1267, 1132,
1H, J=7.3 and 0.9 Hz, Ar-H), 7.53 (td, 1H, J = 7.5 1082, 929, 726 cm-1. 1H NMR (CDCl3, 400 MHz):
and 1.4 Hz, Ar-H), 7.46 (td, 1H, J = 7.6 and 1.4 Hz, δ=7.87 (dd, 1H, J=7.8 and 0.9 Hz, Ar-H), 7.53 (td,
Ar-H), 7.33 (dd, 1H, J=7.8 and 0.9 Hz, Ar-H), 4.26 1H, J = 7.5 and 1.4 Hz, Ar-H), 7.46 (td, 1H, J = 7.6
(t, 2H, J=6.8 Hz, OCH2), 2.79–2.75 (m, 2H), 1.76– and 1.4 Hz, Ar-H), 7.32 (dd, 1H, J=7.5 and 1.2 Hz,
1.67 (m, 4H, CH2), 1.38–1.32 (m, 4H), 0.98 (t, 3H, Ar-H), 4.26 (t, 2H, J=6.8 Hz, OCH2), 2.84–2.73
J=7.3 Hz, CH3), 0.92–0.88 (m, 3H, CH3) ppm. 13C (m, 2H), 1.75–1.68 (m, 4H, CH2), 1.37–1.31 (m,
NMR (CDCl3, 100 MHz): δ=205.8 (s, C=O), 166.8 8H), 0.92–0.87 (m, 6H, CH3) ppm. 13C NMR
(s, O–C=O), 143.3 (s, Ar-C), 131.9 (d, Ar-CH), (CDCl3, 100 MHz): δ=205.9 (s, C=O), 166.8 (s, O–
129.8 (d, Ar-CH), 129.5 (d, Ar-CH), 128.8 (s, Ar- C=O), 143.3 (s, Ar-C), 131.9 (d, Ar-CH), 129.8 (d,
C), 126.2 (d, Ar-CH), 65.8 (t, CH2), 44.8 (t, CH2), Ar-CH), 129.5 (d, Ar-CH), 128.8 (s, Ar-C), 126.2
28.2 (t, CH2), 28.0 (t, CH2), 22.3 (t, CH2), 17.5 (t, (d, Ar-CH), 65.8 (t, CH2), 42.9 (t, CH2), 31.4 (t,
CH2), 13.9 (q, CH3), 13.7 (q, CH3) ppm. HR-MS CH2), 28.2 (t, CH2), 28.0 (t, CH2), 23.7 (t, CH2),
(ESI+) m/z calculated for [C16H23O3]+=[MH]+:
22.5 (t, CH2), 22.3 (t, CH2), 13.9 (q, CH3) ppm.
HR-MS
(ESI+)
m/z
calculated
for
263.1642; found 263.1643.
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
FULL PAPER
[C18H27O3]+=[MH]+: 291.1955; found 291.1955.
1-(2-(4-Methoxybenzoyl)phenyl)butan-1-one
(3nk): GP-1 was carried out with aryl iodide 1n
(135.0 mg, 0.40 mmol), aromatic alcohal 2k (177.0
mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O
(111.0 mg, 0.48 mmol) and TBHP (308.0 mg, 2.4
mmol). The resulting reaction mixture was stirred
at 120 °C for 24 h. The progress of the product 3nk
formation was monitored by TLC till the reaction
was completed. Purification of the crude material
by silica-gel column chromatography (petroleum
ether/ethyl acetate, 95:05 to 94:06) furnished the
product 3nk (64.3 mg, 57%) as a colourless viscous
liquid. [TLC control (petroleum ether/ethyl acetate
90:10), Rf(1n)=0.90, Rf(3nk)=0.30, UV detection].
IR (MIR-ATR, 4000–600 cm-1): max=2926, 1662,
Methyl 2-hexanoyl-5-methylbenzoate (3fm):
GP-1 was carried out with aryl iodide 1f (110.0 mg,
0.40 mmol), aromatic alcohol 2m (245.0 mg, 2.4
mmol), Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (111.0
mg, 0.48 mmol) and TBHP (308.0 mg, 2.4 mmol).
The resulting reaction mixture was stirred at 120 °C
for 23 h. The progress of the product 3fm formation
was monitored by TLC till the reaction was
completed. Purification of the crude material by
silica-gel column chromatography (petroleum
ether/ethyl acetate, 98:02 to 97:03) furnished the
product 3fm (61.5 mg, 62%) as a colourless
viscous liquid. [TLC control (petroleum ether/ethyl
acetate 95:05), Rf(1f)=0.80, Rf(3fm)=0.30, UV
detection]. IR (MIR-ATR, 4000–600 cm-1): 1593, 1507, 1455, 1252, 1151, 1025, 930, 844, 757,
605 cm-1. 1H NMR (CDCl3, 400 MHz): δ=7.82 (dd,

max=2953, 2864, 1718, 1669, 1585, 1452, 1261,
1126, 1080, 927, 727 cm-1. H NMR (CDCl3, 400
MHz): δ=7.61 (s, 1H, Ar-H), 7.33-7.28 (m, 2H, Ar-
H), 3.85 (s, 3H, OCH3), 2.76 (t, 2H, J=7.8 Hz,
CH2), 2.38 (s, 3H, CH3), 1.73–1.65 (m, 2H, CH2),
1.34–1.30 (m, 4H, CH2), 0.89–0.86 (m, 3H, CH3)
ppm. 13C NMR (CDCl3, 100 MHz): δ=205.1 (s,
C=O), 167.8 (s, O–C=O), 140.4 (s, Ar-C), 139.6 (s,
Ar-C), 132.2 (d, Ar-CH), 130.1 (d, Ar-CH), 129.3
(s, Ar-C), 126.7 (d, Ar-CH), 52.4 (q, CH3), 42.2 (t,
CH2), 31.3 (t, CH2), 23.8 (t, CH2), 22.4 (t, CH2),
21.1 (q, CH3), 13.9 (q, CH3) ppm. HR-MS (ESI+)
m/z calculated for [C15H20O3]+=[M]+: 248.1412;
found 248.1438.
1
1H, J=7.3 and 0.9 Hz, Ar-H), 7.73–7.70 (m, 2H,
Ar-H), 7.59–7.52 (m, 2H, Ar-H), 7.38–7.36 (m,
1H, Ar-H), 6.90–6.87 (m, 2H, Ar-H), 3.84 (s, 3H,
OCH3), 2.83 (t, 2H, J=7.0 Hz, CH2), 1.67–1.58 (m,
2H, CH2), 0.88 (t, 3H, J=7.3 Hz, CH3) ppm. 13C
NMR (CDCl3, 100 MHz): δ=201.4 (s, C=O), 196.4
(s, C=O), 163.4 (s, Ar-C), 140.9 (s, Ar-C), 138.2 (s,
Ar-C), 131.8 (d, 2C, 2 × Ar-CH), 131.5 (d, Ar-CH),
130.3 (s, Ar-C), 129.4 (d, Ar-CH), 128.5 (d, Ar-
CH), 128.3 (d, Ar-CH), 113.7 (d, 2C, 2 × Ar-CH),
55.4 (q, CH3), 41.8 (t, CH2), 17.5 (t, CH2), 13.7 (q,
CH3) ppm. HR-MS (ESI+) m/z calculated for
[C18H19O3]+=[MH]+: 283.1329; found 283.1326.
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10.1002/ejoc.201900769
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FULL PAPER
[C19H21O3]+=[MH]+: 297.1485; found 297.1485.
1-(2-(4-Methoxybenzoyl)phenyl)pentan-1-one
(3nl): GP-1 was carried out with aryl iodide 1n
(135.0 mg, 0.40 mmol), aromatic alcohal 2l (211.0
mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O
(111.0 mg, 0.48 mmol) and TBHP (308.0 mg, 2.4
mmol). The resulting reaction mixture was stirred
at 120 °C for 23 h. The progress of the product 3nl
formation was monitored by TLC till the reaction
was completed. Purification of the crude material
by silica-gel column chromatography (petroleum
ether/ethyl acetate, 95:05 to 94:06) furnished the
product 3nl (72.3 mg, 61%) as a colourless viscous
liquid. [TLC control (petroleum ether/ethyl acetate
90:10), Rf(1n)=0.90, Rf(3nl)=0.30, UV detection].
IR (MIR-ATR, 4000–600 cm-1): max=2926, 1662,
3-(4-Hydroxy-3-methoxyphenyl)-2-methyl-1H-
inden-1-one (5ji): GP-3 was carried out with
ortho-iodoketone 1j (104.0 mg, 0.40 mmol) and
alcohol 2i (370.0 mg, 2.4 mmol), Pd(OAc)2 (5.0
mg, 5 mol%), Ag2O (111.0 mg, 0.48 mmol) and
TBHP (308.0 mg, 2.4 mmol) and allowed the
reaction mixture to stir at 120 °C for 20 h then Then
reaction mixture was removed from oil bath and
allow to reach room temperature and then added
conc. H2SO4 (0.1 mL, 2.0 mmol) and allowed the
reaction mixture stirred at room temperature for 10
minute for the product 5ji formation. Purification
of the crude material by silica gel column
chromatography (petroleum ether/ethyl acetate,
1593, 1507, 1455, 1252, 1149, 1025, 930, 843, 756, 97:03 to 95:05) furnished the product 5ji (48.0 mg,
604 cm-1. 1H NMR (CDCl3, 400 MHz): δ=7.82 (dd, 45%) as a yellow viscous liquid. [TLC control
1H, J=7.3 and 0.9 Hz, Ar-H), 7.72–7.69 (m, 2H, (petroleum ether/ethyl acetate 96:04), Rf(1j)=0.50,
Ar-H), 7.56–7.51 (m, 2H, Ar-H), 7.38–7.36 (m, Rf(5ji)=0.80, UV detection]. IR (MIR-ATR, 4000–
600 cm-1): max=3233, 2961, 1696, 1651, 1584,
1H, Ar-H), 6.89–6.87 (m, 2H, Ar-H), 3.83 (s, 3H,
1
1516, 1443, 1365, 1295, 1199, 992, 752 cm-1. H
OCH3), 2.84 (t, 2H, J=7.3 Hz, CH2), 1.61–1.53 (m,
2H, CH2), 1.31–1.23 (m, 2H, CH2), 0.85 (t, 3H,
J=7.3 Hz, CH3) ppm. 13C NMR (CDCl3, 100 MHz):
δ=201.5 (s, C=O), 196.4 (s, C=O), 163.4 (s, Ar-C),
140.9 (s, Ar-C), 138.2 (s, Ar-C), 131.7 (d, 2C, 2 ×
Ar-CH), 131.5 (d, Ar-CH), 130.2 (s, Ar-C), 129.4
(d, Ar-CH), 128.4 (d, Ar-CH), 128.2 (d, Ar-CH),
113.6 (d, 2C, 2 × Ar-CH), 55.4 (q, CH3), 39.6 (t,
CH2), 26.1 (t, CH2), 22.2 (t, CH2), 13.8 (q, CH3)
ppm. HR-MS (ESI+) m/z calculated for
NMR (CDCl3, 400 MHz): δ=7.45 (d, 1H, J=7.3 Hz,
Ar-H), 7.29 (td, 1H, J=7.2 and J=1.2 Hz, Ar-H),
7.20-7.16 (m, 1H, Ar-H), 7.10 (d, 1H, J=7.3 Hz,
Ar-H), 7.06-7.03 (m, 2H, Ar-H), 6.98 (s, 1H, Ar-
H), 5.90 (s, 1H, Ar-OH), 3.93 (s, 3H, -OCH3), 1.93
13
(s, 3H, CH3) ppm. C NMR (CDCl3, 100 MHz):
δ=198.3 (s, C=O), 154.8 (s, C=C), 146.6 (s, Ar-C),
146.6 (s, Ar-C), 145.7 (s, Ar-C), 133.0 (d, Ar-CH),
131.4 (s, Ar-C), 130.1 (s, Ar-C), 128.0 (d, Ar-CH),
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
FULL PAPER
124.8 (s, C=C), 122.3 (d, Ar-CH), 121.9 (d, Ar- 164.1 (d, J=249 Hz, Ar-CF), 152.4 (s, C=C), 152.1
CH), 120.3 (d, Ar-CH), 114.7 (d, Ar-CH), 110.5 (d, (s, Ar-C), 148.4 (s, Ar-C), 140.0 (s, Ar-C), 129.9
Ar-CH), 56.1 (q, OCH3), 8.7 (q, CH3) ppm. HR- (s, Ar-C), 129.9 (d, Ar-CH), 129.8 (d, Ar-CH),
MS
(ESI+)
m/z
calculated
for 123.2 (s, C=C), 116.1 (d, Ar-CH), 115.8 (d, Ar-
CH), 114.5 (s, Ar-C), 107.6 (d, Ar-CH), 105.2 (d,
Ar-CH), 56.3 (q, Ar-OCH3), 56.3 (q, Ar-OCH3),
8.6 (q, CH3) ppm. HR-MS (ESI+) m/z calculated
for [C18H16FO3]+=[MH]+: 299.1078; found
[C17H15O3]+=[MH]+: 267.1016; found 267.1021.
3-(4-Fluorophenyl)-5,6-dimethoxy-2-methyl-
1H-inden-1-one (5kc): GP-3 was carried out with
ortho-iodoketone 1k (128.0 mg, 0.40 mmol) and 299.1078.
alcohol 2c (302.0 mg, 2.4 mmol), Pd(OAc)2 (5.0
mg, 5 mol%), Ag2O (111.0 mg, 0.48 mmol) and
4,5,6-Trimethoxy-2-methyl-3-phenyl-1H-inden-
TBHP (308.0 mg, 2.4 mmol) and allowed the 1-one (5la): GP-3 was carried out with ortho-
reaction mixture to stir at 120 °C for 24 h then Then iodoketone 1l (140.0 mg, 0.40 mmol) and alcohol
reaction mixture was removed from oil bath and 2a (259.0 mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5
allow to reach room temperature and then added mol%), Ag2O (111.0 mg, 0.48 mmol) and TBHP
conc. H2SO4 (0.1 mL, 2.0 mmol) and allowed the (308.0 mg, 2.4 mmol) and allowed the reaction
reaction mixture stirred at room temperature for 10 mixture to stir at 120 °C for 24 h then Then reaction
minute for the product 5kc formation. Purification mixture was removed from oil bath and allow to
of the crude material by silica gel column reach room temperature and then added conc.
chromatography (petroleum ether/ethyl acetate, H2SO4 (0.1 mL, 2.0 mmol) and allowed the
90:10 to 85:15) furnished the product 5kc (62.0 reaction mixture stirred at room temperature for 5
mg, 52%) as a yellow viscous liquid. [TLC control minute for the product 5la formation. Purification
(petroleum ether/ethyl acetate 85:15), Rf(1k)=0.50, of the crude material by silica gel column
Rf(5kc)=0.70, UV detection]. IR (MIR-ATR, chromatography (petroleum ether/ethyl acetate,
4000–600 cm-1): max=2925, 1705, 1601, 1464,
90:10 to 75:25) furnished the product 5la (64.5 mg,
1
1385, 1269, 1096, 1034, 934, 807, 743 cm-1. H
52%) as a yellow viscous liquid. [TLC control
(petroleum ether/ethyl acetate 75:25), Rf(1l)=0.30,
Rf(5la)=0.80, UV detection]. IR (MIR-ATR, 4000–
NMR (CDCl3, 400 MHz): δ=7.46 (dd, 2H, J=8.8
and J=5.3 Hz, Ar-H), 7.25-7.20 (m, 2H, Ar-H),
7.13 (s, 1H, Ar-H), 6.58 (s, 1H, Ar-H), 3.90 (s, 3H,
600 cm-1): max=2924, 1705, 1602, 1463, 1384,
1
OCH3), 3.87 (s, 3H, OCH3), 1.87 (s, 3H, CH3) ppm. 1266, 1185, 1091, 1032, 936, 807, 739 cm-1. H
13C NMR (CDCl3, 100 MHz): δ=197.5 (s, C=O), NMR (CDCl3, 400 MHz): δ=7.45-7.36 (m, 5H, Ar-
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
FULL PAPER
1
H), 6.98 (s, 1H, Ar-H), 3.87 (s, 3H, OCH3), 3.84 (s, 930, 844, 732 cm-1. H NMR (CDCl3, 400 MHz):
3H, OCH3), 3.28 (s, 3H, OCH3), 1.75 (s, 3H, CH3) δ=7.46-7.41 (m, 3H, Ar-H), 7.28 (t, 1H, J=7.3 Hz,
ppm. 13C NMR (CDCl3, 100 MHz): δ=197.2 (s, Ar-H), 7.18 (t, 1H, J=7.3Hz, Ar-H), 7.04 (d, 3H,
C=O), 155.4 (s, Ar-C), 153.5 (s, C=C), 148.4 (s, J=8.3 Hz, Ar-H), 3.88 (s, 3H, OCH3), 2.35 (q, 2H,
Ar-C), 147.3 (s, Ar-C), 134.2 (s, Ar-C), 130.7 (s, J=7.6 Hz, -CH2CH3), 1.12 (t, 3H, J=7.6 Hz, -
Ar-C), 129.3 (s, Ar-C), 128.4 (d, Ar-CH), 128.0 (d, CH2CH3) ppm. 13C NMR (CDCl3, 100 MHz):
2C, 2 × Ar-CH), 127.7 (d, 2C, 2 × Ar-CH), 127.1 δ=198.2 (s, C=O), 160.3 (s, Ar-C), 154.4 (s, C=C),
(s, C=C), 104.7 (d, Ar-CH), 61.1 (q, Ar-OCH3), 145.8 (s, Ar-C), 135.8 (s, Ar-C), 132.9 (d, Ar-CH),
61.0 (q, Ar-OCH3), 56.4 (q, Ar-OCH3), 8.3 (q, 131.3 (s, Ar-C), 129.3 (d, 2C, 2 × Ar-CH), 128.1
CH3) ppm. HR-MS (ESI+) m/z calculated for (d, Ar-CH), 125.0 (s, C=C), 122.2 (d, Ar-CH),
[C19H19O4]+=[MH]+: 311.1278; found 311.1275.
120.5 (d, Ar-CH), 114.2 (d, 2C, 2 × Ar-CH), 55.3
(q, Ar-OCH3), 16.7 (t, -CH2CH3), 13.9 (q, -
CH2CH3) ppm. HR-MS (ESI+) m/z calculated for
2-Ethyl-3-(4-methoxyphenyl)-1H-inden-1-one
[C18H17O2]+=[MH]+: 265.1223; found 265.1219.
(5nk): GP-3 was carried out with ortho-iodoketone
1n (135.0 mg, 0.40 mmol) and alcohol 2k (177.0
2-Ethyl-3-(thiophen-2-yl)-1H-inden-1-one
mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O (5pk): GP-3 was carried out with ortho-iodoketone
(111.0 mg, 0.48 mmol) and TBHP (308.0 mg, 2.4 1p (125.0 mg, 0.40 mmol) and alcohol 2k (177.0
mmol) and allowed the reaction mixture to stir at mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5 mol%), Ag2O
120 °C for 20 h then Then reaction mixture was (111.0 mg, 0.48 mmol) and TBHP (308.0 mg, 2.4
removed from oil bath and allow to reach room mmol) and allowed the reaction mixture to stir at
temperature and then added conc. H2SO4 (0.1 mL, 120 °C for 20 h then Then reaction mixture was
2.0 mmol) and allowed the reaction mixture stirred removed from oil bath and allow to reach room
at room temperature for 20 minute for the product temperature and then added conc. H2SO4 (0.1 mL,
5nk formation. Purification of the crude material 2.0 mmol) and allowed the reaction mixture stirred
by silica gel column chromatography (petroleum at room temperature for 15 minute for the product
ether/ethyl acetate, 97:03 to 95:05) furnished the 5pk formation. Purification of the crude material
product 5nk (53.9 mg, 51%) as a yellow viscous by silica gel column chromatography (petroleum
liquid. [TLC control (petroleum ether/ethyl acetate ether/ethyl acetate, 97:03 to 95:05) furnished the
95:05), Rf(1n)=0.30, Rf(5nk)=0.50, UV detection]. product 5pk (48.0 mg, 50%) as a yellow viscous
IR (MIR-ATR, 4000–600 cm-1): max=2947, 2864,
liquid. [TLC control (petroleum ether/ethyl acetate
96:04), Rf(1p)=0.50, Rf(5pk)=0.80, UV detection].
1717, 1675, 1586, 1468, 1395, 1271, 1134, 1086,
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
FULL PAPER
IR (MIR-ATR, 4000–600 cm-1): max=2924, 2857,
1720, 1593, 1453, 1284, 1133, 1087, 928, 755 cm-
mg, 53%) as a yellow viscous liquid. [TLC control
(petroleum ether/ethyl acetate 96:04), Rf(1p)=0.50,
Rf(5pm)=0.80, UV detection]. IR (MIR-ATR,
4000–600 cm-1): max=2924, 2857, 1716, 1448,
1
1. H NMR (CDCl3, 400 MHz): δ=7.57 (dd, 1H,
J=5.1 and J=1.2 Hz, Ar-H), 7.50-7.49 (m, 2H, Ar-
H), 7.44 (d, 1H, J=7.3 Hz, Ar-H), 7.36 (td, 1H, 1281, 1128, 1085, 939, 749 cm-1. 1H NMR (CDCl3,
J=6.3 and J=1.4 Hz, Ar-H), 7.26-7.21 (m, 2H, Ar- 400 MHz): δ=7.58 (dd, 1H, J=4.8 and J=0.9 Hz,
H), 2.56 (q, 2H, J=7.5 Hz, Ar-H), 1.17 (t, 3H, J=7.5 Ar-H), 7.50-7.48 (m, 2H, Ar-H), 7.44 (d, 1H, J=7.3
Hz, Ar-H) ppm. 13C NMR (CDCl3, 100 MHz): Hz, Ar-H), 7.37 (td, 1H, J=7.8 and J=1.4 Hz, Ar-
δ=197.3 (s, C=O), 146.8 (s, Ar-C), 144.9 (s, C=C), H), 7.26-7.22 (m, 2H, Ar-H), 2.54 (t, 2H, J=7.3 Hz,
136.3 (s, Ar-C), 134.2 (s, C=C), 133.1 (d, Ar-CH), - CH2CH2 CH2CH3), 1.55-1.50 (m, 2H, -
131.2 (s, C=C), 128.6 (d, Ar-CH), 128.3 (d, Ar- CH2CH2CH2CH3), 1.45-1.38 (m, 2H,
-
CH), 128.1 (d, Ar-CH), 127.8 (d, Ar-CH), 122.4 (d, CH2CH2CH2CH3), 0.93 (t, 3H, J=7.3 Hz, -
Ar-CH), 120.8 (d, Ar-CH), 17.0 (t, -CH2CH3), 13.7 CH2CH2CH3) ppm. 13C NMR (CDCl3, 100 MHz):
(q, -CH2CH3) ppm. HR-MS (ESI+) m/z calculated δ=197.5 (s, C=O), 147.0 (s, C=C), 144.9 (s, Ar-C),
for [C15H13OS]+=[MH]+: 241.0682; found
135.2 (s, Ar-C), 134.3 (s, Ar-C), 133.0 (d, Ar-CH),
131.2 (s, C=C), 128.6 (d, Ar-CH), 128.3 (d, Ar-
CH), 128.1 (d, Ar-CH), 127.8 (d, Ar-CH), 122.4 (d,
Ar-CH), 120.8 (d, Ar-CH), 31.3 (t, -CH2CH2
CH2CH3), 23.5 (t, -CH2CH2CH2CH3), 23.0 (t, -
CH2CH2CH2CH3), 13.9 (q, -CH2CH2CH2CH3)
ppm. HR-MS (ESI+) m/z calculated for
[C17H17OS]+=[MH]+: 269.0995; found 269.1001.
241.0680.
2-Butyl-3-(thiophen-2-yl)-1H-inden-1-
one (5pm): GP-3 was carried out with ortho-
iodoketone 1p (125.0 mg, 0.40 mmol) and alcohol
2m (245.0 mg, 2.4 mmol), Pd(OAc)2 (5.0 mg, 5
mol%), Ag2O (111.0 mg, 0.48 mmol) and TBHP
(308.0 mg, 2.4 mmol) and allowed the reaction
mixture to stir at 120 °C for 21 h then Then reaction
mixture was removed from oil bath and allow to
reach room temperature and then added Conc.
H2SO4 (0.1 mL, 2.0 mmol) and allowed the
reaction mixture stirred at room temperature for 15
minute for the product 5pm formation. Purification
of the crude material by silica gel column
chromatography (petroleum ether/ethyl acetate,
97:03 to 95:05) furnished the product 5pm (56.8
2,2,6,6-Tetramethylpiperidin-1-yl
benzoate
(7aa): To an oven dried Schlenk tube, were added
1a (104 mg, 0.4 mmol), alcohol 2a (259 mg, 2.4
mmol), TEMPO (374 mg, 2.4 mmol), Pd(OAc)2
(5.0 mg, 5 mol %), Ag2O (111 mg, 0.48 mmol), and
TBHP (151 mg, 2.4 mmol). The resulting reaction
mixture was stirred at 120 °C for 20 h. Progress of
the reaction was monitored by TLC until the
reaction was completed. The reaction mixture was
quenched by the addition of aqueous NaHCO3
solution and then extracted with ethyl acetate (3 ×
15 mL). The organic layers were washed with
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10.1002/ejoc.201900769
European Journal of Organic Chemistry
FULL PAPER
saturated NaCl solution, dried (Na2SO4) and 6H), 1.09 (s, 6H) ppm. 13C NMR (CDCl3, 100
filtered. Evaporation of the solvent under reduced
pressure and purification of the crude material by
silica-gel column chromatography (petroleum
MHz): δ=165.9 (s, O-C=O), 163.0 (s, Ar-C), 131.3
(d, 2C, 2 × Ar-CH), 121.6 (s, Ar-C), 113.4 (d, 2C,
2 × Ar-CH), 60.0 (s, C(CH3)4), 55.2 (q, Ar-OMe),
38.7 (t, 2 × CH2), 31.6 (q, 2 × CH3), 20.6 (q, 2 ×
CH3), 16.7 (t, -CH2) ppm. HR-MS (ESI+) m/z
calculated for [C17H26NO3]+=[MH]+: 292.1907;
found 292.1909.
ether/ethyl acetate, 55:45−50:50) furnished the
product 7aa (596 mg, 95%) as white solid. [TLC
control (petroleum ether/ethyl acetate 50:50), Rf
(2a) = 0.99, Rf (7aa) = 0.50, UV detection].
2,2,6,6-Tetramethylpiperidin-1-yl
4-
methoxybenzoate: To an oven dried Schlenk tube,
were added 1a (104 mg, 0.4 mmol), alcohol 2g
(331 mg, 2.4 mmol), TEMPO (374 mg, 2.4 mmol),
Pd(OAc)2 (5.0 mg, 5 mol %), Ag2O (111 mg, 0.48
mmol), and TBHP (151 mg, 2.4 mmol). The
resulting reaction mixture was stirred at 120 °C for
26 h. Progress of the reaction was monitored by
TLC until the reaction was completed. The reaction
mixture was quenched by the addition of aqueous
NaHCO3 solution and then extracted with ethyl
acetate (3 × 15 mL). The organic layers were
washed with saturated NaCl solution, dried
ACKNOWLEDGMENTS:
We are grateful to the Department of Science
and Technology-Science and Engineering
Research
Board
(DST-SERB)
[No.EMR/2017/005312], New Delhi, for financial
support. S.B. thanks MHRD and C.B.S thanks to
UGC for the research fellowship.
Keywords: Primary alcohols, Ketones, oxidative coupling,
n-butylphthalide, neo-lignan.
Reference:
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Entry for the Table of Contents (Please choose one layout)
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Palladium-catalyzed
oxidative acylation through
cross-dehydrogenative
direct
Key Topic*
Acylation,
Indenone,
Benzofuranone
coupling
has
been
the
demonstrated,
for
synthesis of a wide varity of
ketones. Readily available
primary alcohols have been
utilized as acylating sources.
Author(s),
Corresponding
Author(s)*
Overall,
this
oxidative
Basuli
Suchand,
coupling proceeds via three
distinct transformations such
Chinnabattigalla
Sreenivasulu And
Gedu
as
oxidation,
radical
Satyanarayana*
formation and cross-coupling
in one catalytic process. This
protocol does not involve the
Page No. – Page
No.
assistance of
a
directing
Title
Palladium-
Catalyzed
Oxidative Coupling
of Iodoarenes with
Primary Alcohols
group or activation of the
carbonyl group by any other
means. Further, this reaction
made use of no toxic CO gas
Direct
as
carbonylating
agent;
instead, feedstock primary
alcohols have been utilized
as acylation source. Notably,
enabled the synthesis of
Leading
Ketones:
Application to the
Synthesis
Benzofuranones
and Indenones
to
of
benzofuranones
and
indenones. Significantly, this
divergent coupling strategy
has been applied to the
synthesis of n-butylphthalide,
fenofibrate, pitofenone and
neo-lignan.
*one or two words that highlight the emphasis of the paper or the field of the study
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