A synthesis of biaryl ketones via the C–S bond cleavage of thiol ester by a Cu/Ag salt

Article abstract of DOI:10.1016/j.tetlet.2017.05.091

We report the synthesis of biaryl ketones via an unprecedented copper/silver catalyzed acylative cross-coupling of thiol esters with either an arylboronic acid or a potassium aryltrifluoroborate. This new method proceeds without a requisite Pd-catalyst and Cu(I)TC mediator, and is efficient, versatile, operationally simple, and accommodating functionally diverse thiol esters, arylboronic acids, and potassium aryltrifluoroborates.

Full text of DOI:10.1016/j.tetlet.2017.05.091

Accepted Manuscript
A synthesis of Biaryl Ketones via the C-S bond cleavage of Thiol ester by a Cu/
Ag salt
Prasanjit Ghosh, Bhaskar Ganguly, Eliyahu Perl, Sajal Das
PII:
S0040-4039(17)30697-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.05.091
TETL 48984
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
23 April 2017
29 May 2017
31 May 2017
Please cite this article as: Ghosh, P., Ganguly, B., Perl, E., Das, S., A synthesis of Biaryl Ketones via the C-S bond
cleavage of Thiol ester by a Cu/Ag salt, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.
2017.05.091
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Tetrahedron Letters
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A synthesis of Biaryl Ketones via the C-S bond cleavage of Thiol ester by a Cu/Ag
salt
Prasanjit Ghosha, Bhaskar Gangulya, Eliyahu Perlb, and Sajal Dasa∗
aDepartment of Chemistry, University of North Bengal, Darjeeling 734013, India.
b Department of Chemistry and Biochemistry, Queens College of the City University of New York,65-30 Kissena Blvd, Flushing, NY 11367, USA
ARTICLE INFO
ABSTRACT
Article history:
Received
We report the synthesis of biaryl ketones via an unprecedented copper/silver catalyzed acylative
cross-coupling of thiol esters with either an arylboronic acid or a potassium aryltrifluoroborate.
This new method proceeds without a requisite Pd-catalyst and Cu(I)TC mediator, and is
efficient, versatile, operationally simple, and accommodating functionally diverse thiol esters,
arylboronic acids, and potassium aryltrifluoroborates.
Received in revised form
Accepted
Available online
Keywords:
Biaryl ketones
2009 Elsevier Ltd. All rights reserved.
Thiolester
Potassium aryltrifluoroborates
Cooperative catalysis
1. Introduction
Previous Work
(Liebeskind-Srogl Reaction)
Biaryl ketones are found in numerous photosensitizers,
advanced organic materials, natural products, and
O
O
A)
R
1.2 equiv CuTC
1.0 equiv Cs2CO3
0.05 equiv Pd(PPh3)4
R1 R2
R1
S
pharmaceutically apposite agents.1 For instance Evista,2 Tricor3
and Sector4, which contain biaryl ketone cores, are commonly
prescribed medications, due to their extraordinary biological and
therapeutic properties (e.g., in selective estrogen receptor
modulation, cholesterol regulation, and anti-inflammation,
respectively). Predictably, the development of methodologies
towards the synthesis of functionally diverse biaryl ketones that
are economical, practical, synthetically effective, and
nonhazardous is of both great importance and interest to
medicinal chemists. Traditionally, transition metal catalyzed
cross-coupling methods, such as acylative Suzuki couplings,
Friedel-Crafts acylations, and nucleophilic additions of an
organometallic to a carbonyl moiety, are commonly used for the
synthesis of aryl ketones. However, the cross coupling of
arylboronic acids with carboxylic acid derivatives is far superior
to these previous methods, not only with respect to the reaction’s
conditions and reagent compatibility, but also with regard to its
regioselectivity and efficiency.5 Bumagin and colleagues
introduced Pd-catalyzed cross-coupling reactions of acid
chlorides in 1997 for the synthesis of aryl ketones.6 Later, this
method was extended to acylative Suzuki couplings with
anhydrides,7 esters,8 and carboxylic acids, in the presence of
activating agents.7c-9
O
R2
R2
R2B(OH)2
1.2 equiv
O
SR
SR
THF 45 OC, 16 h
21-90%
+
O
O
5 mol % Cu(I)-3-methyl salicylate
50 OC, DMF, 24 h
O
O
R2B(OH)2
2.5 equiv
R1
S
R1 R2
+
B)
O
NHt-Bu
S-pendant linkage = S-acyl-NHt-Bu thiosalicylamides
Present Work
Pd free & no requirement of ligating functional group ortho position to S-pendant linkage
O
O
O
Cu catalyst
Ag2CO3
R1
O
O
ArB(OH)2
or
+
S
R2
(Het)ArBF3K
1.5 equiv
Solvent, Temp
8-24hr
R
R
47 examples
up to 85% yield
O
Naphthyl phenstatin
Biologically active
molecule
Figure 1: (A & B) General strategies for the synthesis of biaryl ketones
using CuTC and a Pd catalyst, as previously reported. A Nucleophilic
addition of ArB(OH)2/(Het)ArBF3K in the absence of S-pendant, CuTC, and
a Pd catalyst is proposed herein.
More recently, a Pd-catalyzed thiol ester–boronic acid
coupling towards the synthesis of biaryl ketones was developed
by Liebeskind and Srogl.10 Catalytic amount of Pd(0) salt and
stoichiometric amount of Cu(I)TC [Copper(I)-thiophene-2-
carboxylate], an expensive salt are essential requirements of this
———
∗ Corresponding author.
Tel.: +91-353-269-9001; fax: +91-353-277-6381; e-mail: sajal.das@hotmail.com

2
thioorganic–boronic acid coupling reaction.10 No reaction was
observed on replacing Cu(I)TC with Cu(I) salts like, Cu(I)halide
or CuCN.10a As per the mechanism described by the authors,
Cu(I)-carboxylate plays a vital role in this reaction. It not only
polarizes the Pd-S bond by coordination through Cu(I) to sulfur
centre, but also simultaneously activates the boronic acid through
another coordination from carboxylate to boron centre.
Table 1. Screening of the reaction conditions
O
O
S
+
B(OH)2
1a
2a
1.5 equiv
entry
catalyst
( mol %)
CuI (10)
additive
( mol %)
TEMPO
TEMPO
solvent
temp
(°C)
100
time
( h)
24
yield
(%)[a]
38
1
2
DMF
DMF
In 2007, the same group produced an aerobic, Cu-catalyzed,
and Pd-free coupling of thiol esters with boronic acids. Still, this
transformation is relatively limited to thiol esters, as it essentially
requires a ligating functional group positioned ortho to the S-
Pendant linkage (e.g., S-aryl-NHt-Bu thiosalicylamides).10c
Obviously, it is a great challenge to develop an alternative
method for the synthesis of biaryl ketones from thiol esters,
without using an expensive catalyst, a mediator, or any special
functional group in the thiol esters moiety.10c
Cu(OAc)2.H2O
(10)
100
24
35
3
4
5
CuI (20)
CuI (20)
Cu(OAc)2.H2O
(20)
-
-
-
CH2Cl2
DMF
rt
24
24
24
NR
48
120
120
DMF
45
6
7
CuI (20)
Ag2CO3
(5)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
120
rt
8
64
40
62
42
59
44
52
CuI (20)
CuI (20)
Ag2CO3
(5)
48
15
24
15
24
24
To the best of our knowledge, there is no example of a silver
salt mediated process for carbon–sulfur bond scission. Herein, we
disclose an unprecedented, simple copper salt catalyzed cross-
coupling of thiol esters with either potassium aryltrifluoroborates
or arylboronic acids, in the presence of silver carbonate as an
additive. It is worth noting that both boronic acids and
organotrifluoroborates are equally effective in the acylative
Suzuki coupling of thiol esters.
8
Pd(OAc)2
(5)
120
120
120
60
9
Pd(OAc)2 (5)
CuI (10)
Ag2CO3
(5)
10
11
12
Ag2CO3
(20)
CuI (20)
Ag2CO3
(5)
2. Results and discussion
CuI (20)
Ag2CO3
(5)
90
Our initial attempts to couple a phenylboronic acid with a
thiol ester, which was readily prepared from a dehydration
reaction between a thiol and a carboxylic acid (see supporting
information for details), e.g., S-phenyl benzothioate (1a), was
met with difficulty. Even in the presence of oxidants, the reaction
did not proceed at all. This was improved, albeit to a modest
yield, when DMF was used as solvent. Under this condition, both
CuI and Cu(OAc)2•H2O imparted nearly equal catalytic activity,
resulting in benzophenone (2a) in 38% and 35% yield,
respectively. The yield of the biaryl ketone (2a) was further
enhanced to 50%, by increasing the amount of catalyst to 20 mol
percent, under the same reaction conditions.
13
14
15
CuI (20)
CuI (20)
-
Ag2O (5)
AgOAc (5)
Ag2CO3
(5)
DMF
DMF
DMF
120
120
120
24
24
24
47
40
NR
[a]Isolated yields. All reactions were carried out using 0.25
mmol S-phenyl benzothioate and 0.375 mmol arylboronic acid,
stirred in 2 mL DMF. NR = No reaction
The scope of a Cu(I)/Ag catalyzed acylative cross coupling of
thiol ester with arylboronic was also briefly explored. Both steric
hindrance and electronic effects were negligible with respect to
the arylboronic acids. Likewise, the coupling of phenylboronic
acids bearing either electron-donating or electron-withdrawing
substituents with thiol ester (1a) was highly facile and resulted in
moderate to excellent yields of the corresponding biaryl ketones
(Table 2).12
We next turned our attention for enhancing the yield of the
biaryl ketone, by improving the activity of the target thiol ester’s
acyl-sulfur bond, as this technique has been widely used to
achieve site-specific transformations in organic synthesis.11
Surprisingly, in the presence of catalytic amounts of silver
carbonate (5 mol %), the reaction between S-phenyl benzothioate
and phenylboronic acid in DMF at 120 °C was completed within
8 h, and a 64% yield of the product 2a was obtained upon
isolation (Table 1, entry-6). By comparison, the same reaction, at
room temperature resulted in only a 40% yield of compound 2a,
after 48 h (Table 1, entry 7). Using Pd(OAc)2 as an additive, in
the presence of CuI the thiolester was succesfully coupled with
phenylboronic acid, resulting in a 62% yield of the desired
product after 15 h (Table 1, entry 8). In the presence of Pd(OAc)2
and Ag2CO3, the reaction kinetics were markedly reduced and
also resulted in a decreased yield of 2a (Table 1, entry 9). It is
noteworthy that the presence of other oxidants or ligands appear
to be redundant in this reaction. Additionally, among the
different varieties of silver salts utilized, silver carbonate proved
to be a privileged supporting catalyst for the reaction (Table 1,
entries 6-14). In absence of the Cu(I) catalyst the reaction did not
proceed even after 24 h (Table 1, entry 15). Eventually, the
combination of CuI (20 mol %) and Ag2CO3 (5 mol %), in DMF
at 120 °C, was found to be optimal for the coupling of thiol esters
and arylboronic acids, leading to benzophenone in high yield
(64%) after only 8 h.
We also varied the –SPh moiety of thiol ester functionality to
observe the lability of the leaving group. Both S-4-fluoro and S-
4-chlorophenyl
benzothioate efficiently coupled with
phenylboronic acid, to furnish benzophenone at yields of 76%
and 85%, respectively (Table 2, entry 2a). On account of the
stabilization of the departing group (-SPh group), the reaction
kinetics improved markedly. 1-Naphthyl and 2-naphthylboronic
acid coupled with thiol ester (1a), producing 65% and 60% (2h,
2j) yields, respectively. Cyclopropylboronic acid, the only
aliphaticboronic acid that we explored, produced no product. A
promising yield (75%) was obtained in the cross coupling
reaction of thiol ester (1a) with 3, 5-difluorophenylboronic acid
(2k). 5-Methyl-2-thienylboronic acid was also found to
participate in coupling, yielding a satisfactory amount of the
desired product (63%; 2l). Substrate containing sensitive
functional groups like –CHO and –COOMe also participated in
smooth coupling reaction under optimized condition to afford the
desired cross coupled products in 69% and 58% yields ( 2m, 2n)
respectively.

3
[a] Isolated yields. All reactions were carried out using 0.25
Table 2.The scope of arylboronic acid in the silver catalyzed
synthesis of biaryl ketones
mmol S-phenyl benzothioate and 0.375 mmol arylboronic acid,
stirred in 2 mL DMF at 120 °C. [b] 0.75mmol arylboronic acid
was used. [c] Starting material was MeCOSPh.
O
B(OH)2
20 mol % CuI
5 mol % Ag2CO3
O
R1
+
R
1.5 equiv
O
R
S
120 ΟC DMF
8-24 h
Our protocol was also employed to investigate the scope of
acylative cross couplings between S-phenyl benzothioate and
potassium aryltrifluoroborates. Potassium phenyltrifluoroborate
was effectively coupled with functional diverse aryl-thiol esters,
resulting in an efficient yield of each final product (Table 4).
O
O
O
F
O
2a, 64%[a], 8 h
2b, 72%[a], 15 h
2c, 71%[a], 15 h
2d, 70%[a], 24 h
R1 =4-F, 76%a, 10 h
R1 =4-Cl, 85%a, 7 h
O
O
O
Table 4.The scope of Potassium aryltriflouroborate in the
synthesis of Biaryl ketones
O
NO2
CN
Br
F
2h, 65%[a], 24 h
O
2f, 68%[a], 24 h
2g, 57%[a], 24 h
2e, 48%[a], 24 h
O
20 mol% CuI
5 mol% Ag2CO3
O
O
Ar(Het)
O
O
S
(Het) ArBF3K
R
R
1200C, DMF, 24hr
S
Cl
O
O
F
O
O
2k, 75%[a], 24 h
2l, 63%[a], 24 h
2i, 52%[a], 24 h
2j, 60%[a], 24 h
O
O
F
O
3k, 78%a
3a, 63%a
3e, 57%a
2a, 60%a
O
OMe
H
O
O
O
O
O
2n, R1 = 4-F, 58%[a], 24 h
2m, R1 = 4-F, 69%[a], 24 h
O2N
S
Br
[a]
Cl
Isolated yields. All reactions were carried out using 0.25
mmol S-phenyl benzothioate and 0.375 mmol arylboronic acid,
stirred in 2 mL DMF at 120 °C; entries 2b-2l (R1 = H).
3h, 73%a
2l, 51%a
3m, 70%a
4a, 57%a
aIsolated yields. All reactions were carried out using 0.25
mmol S-phenylbenzothioate and 0.375 mmol potassium
(Het)aryltrifluoroborate in 2 mL DMF for 24 h stirring at 120oC.
With a facile and practical protocol at hand, we next explored
the lability of various thiol esters and arylboronic acids as
coupling partners, under the optimized conditions (Table 3). A
functionally diverse group of both thiol esters and arylboronic
acids were tested, and all responded well under the optimized
conditions. Notably, aryl-thiol esters bearing either electron-
donating or electron-withdrawing substituents (-CH3, -OMe, -Cl,
-F,-NO2,-COMe) participated readily, producing their
corresponding biaryl ketone at yields ranging between 55 and
81% (3a,3e,3h,3k,3m,3u). Reaction with S-phenyl thioacetate
under the optimized condition was also resulted in the good yield
of the corresponding ketone (3v).
A proposed mechanism for this acylative cross-coupling of
thiol ester with arylboronic acids is shown in scheme 1. During
optimization of the reaction, we observed that in presence of CuI,
the cross coupling reaction was slow and consistently resulted in
low yield of the final product. Upon introduction of
additive/promoter the rate as well as the yield of the biaryl ketone
(2a) was increased. A variety of Cu(II) or Ag salts were
employed as promoter but the best results were obtained in the
case of Ag2CO3. Silver has a strong affinity for sulfur13 and hence
can coordinate with it strongly thereby weakening acyl-Sulfur
bond of thiol ester. Eventually, it formed the ArCOSAg complex
which readily getting into the catalytic cycle with the formation
of complex A with the elimination of disulfide product RSSR and
Ag(I). We have isolated the disulfide as a byproduct and
Table 3.The Scope of substituted thiolester and substituted
arylboronic acid in the silver catalyzed synthesis of Biaryl
ketones
B(OH)2
O
20 mol % CuI
5 mol % Ag2CO3
accordingly it has been characterized using H and 13C NMR
1
O
R2
spectroscopy. Like the Cham-Lam coupling reaction,14 the CuII
complex (A) is participated in transmetallation reaction to afford
CuIII complex (B). Then the complex B might undergo reductive
elimination to furnish the desired biaryl ketone with subsequent
regeneration of the catalyst.
R1
R2
+
120 ΟC, DMF
S
R1
O
O
O
O
NO2
O
3a, 65%[a], 24 h
3c, 67%[a], 24 h
3d, 62%[a], 24 h
3b, 80%[a], 24 h
O
O
O
O
20 mol% CuI
5 mol% Ag2CO3
NO2
O
O
R
O
O
O
Cl
Ar'B(OH)2
Ar
S
Ar
Ar'
3e, 55%[a], 24 h
3f, 77%[a], 15 h
71%[a], 24 h
O
3g, 60%[a], 20 h
3h,
Ag(I)
O
O
O
CuI
NO2
O
F
F
F
Cl
Cl
R
Ar
S
3j, 74%[a], 18 h
3k, 81%[a], 17 h
3i, 66%[a], 24 h
3l, 67%[a], 24 h
I
Cu S
Ag
O
O
O
O
O
O
S
O
O2N
O
O2N
Br
I
Cu
Ar'
O
3n, 68%[a], 24 h
3o, 71%[a], 24 h
3p, 51%[a], 24 h
3m, 73%[a], 22 h
Ar
B
O
S
O
O
O
O
+
RSSR
Ag(I)
I
Cu
S
Ar
S
3s, 56%[a], 24 h
F
A
3q, 45%[b], 24 h
3r, 65%[a], 24 h
3t, 61%[a], 24 h
F
Ar'B(OH)2
S = solvent (DMF)
O
O
Scheme 1 Plausible mechanism
After the establishment of a general protocol for the synthesis
of biaryl ketones via the cross-coupling of thiol ester–boronic
O
3u, 76%[a], 13 h
3v, 63%[c], 24 h

4
4.
5.
Kantor, T. G. Pharmacotherapy. 1986, 6, 93-103.
Blangetti, M.; Rosso, H.; Prandi, C.; Deagostino, A.; Venturello,
P. Molecules. 2013, 18, 1188-1213.
acids, we sought to establish a proof-of-concept by exploring the
utility of this protocol in the modular synthesis of
pharmaceutically important Phenstatin scaffolds. We selected the
spindle poison, Phenstatin, as it has been found to inhibit tubulin
polymerization and tumor cell growth activities.15
6.
7.
Bykov, V. V.; Korolev, D. N.; Bumagin, N. A. Russ. Chem. Bull.
1997, 46, 1631-1632.
(a) Frost, C. G.; Wadsworth, K. J. Chem. Commun. 2001, 2316-
2317. (b) Kakino, R.; Yasumi, S.; Shimizu, I.; Yamamoto, A. Bull.
Chem. Soc. Jpn. 2002, 75, 137-148. (c) Kakino, R.; Yasumi, S.;
Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn. 2002, 75, 1333-
1345. (d) Gooßen, L. J.; Ghosh, K. Angew. Chem. 2001, 113,
3566. (Angew. Chem., Int. Ed)., 2001, 40, 3458-3460; (e) Xin, B.;
Zhang, Y.; Cheng, K. J. Org. Chem. 2006, 71, 5725-5731. (f)
Shen, X. B.; Gao, T. T.; Lu, J. M.; Shao, L. X. Appl. Organomet.
Chem. 2011, 25, 497-501. (g) Yu, A.; Shen, L.; Cui, X.; Peng, D.;
Wu, Y. Tetrahedron. 2012, 68, 2283-2288.
(a) Kakino, R.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn.
2001, 74, 371-376. (b) Tatamidani, H.; Yokota, K.; Kakiuchi, F.;
Chatani, N. J. Org. Chem. 2004, 69, 5615-5621. (c) Tatamidani,
H.; Kakiuchi, F.; Chatani, N. Org. Lett. 2004, 6, 3597-3599.
(a) Gooßen, L. J.; Ghosh, K. Chem. Commun. 2001, 2084-2085.
(b) Gooßen, L. J.; Ghosh, K. Eur. J. Org. Chem. 2002, 3254-3267.
(c) Kwon, Y. B.; Choi, B. R.; Lee, S. H.; Seo, J.; Yoon, C. M.
Bull. Korean Chem. Soc. 2010, 31, 2672-2674.
O
O
20 mol % CuI
5 mol % Ag2CO3
O
O
B(OH)2
O
O
S
+
120 oC, DMF
24 h
O
O
69%
5a
Naphthyl Phenstatin
Scheme 2 Application: A modular synthesis of Naphthyl
Phenstatin.
8.
9.
Subsequently, we attempted to upscale the synthesis of
benzophenone to the gram scale, affording a 58% yield of
benzophenone. Both of these investigations demonstrate that our
protocol has pharmaceutically applicability at the level of both
process and medicinal chemistry.
10. (a) Liebeskind, L. S.; Srogl, J. J. Am. Chem. Soc. 2000, 122,
11260-11261. (b) Savarin, C.; Srogl, J.; Liebeskind, L. S. Org.
Lett. 2000, 2, 3229-3231. (c) Villalobos, J. M.; Srogl, J.;
Liebeskind, L. S. J. Am. Chem. Soc. 2007, 129, 15734-15735. (d)
Zhang, Z.; Lindale, M.G.; Liebeskind, L. S. J. Am. Chem. Soc.
2011, 133, 6403-6410; (e) Pan, F.; Shi, Z.-J. ACS. Catal., 2014, 4,
280-288.
O
B(OH)2
O
20 mol % CuI
5 mol % Ag2CO3
S
+
120 oC DMF; 8 h
58%
5 mmol
7.5 mmol
Scheme 3 Gram scale synthesis
11. (a) Wang, L.; He, W.; Yu, Z. Chem. Soc. Rev. 2013, 42, 599. (b)
Oviedo, A.; Arevalo, A.; Alamo, M. F.; Garcia, J. J.
Organometallics. 2012, 31, 4039-4045.
3. Conclusions
In summary, here we report the first simple copper/silver salt-
catalyzed cross couplings of thiol esters with arylboronic acids
and potassium aryltrifluoroborates. Notably, this silver-catalyzed
synthesis of biaryl ketones proceeds efficiently, and is the first
documented approach utilizing this method. Moreover, this
versatile method is unprecedented as it accommodates a wide
variety of functionally diverse aryl-thiol esters (and varying
12. General procedure for the synthesis of Biaryl ketones from
thiolester: Thiolester (0.25 mmol), arylboronic acids (0.375
mmol), CuI (20 mol %, 10 mg), Ag2CO3 (5 mol %, 4 mg) and
DMF (3 ml) were taken in a 25ml round bottomed flask. The
reaction mixture was heated at 120 °C for 8-24 h. The reaction
monitored using TLC. Upon completion, the reaction mixture was
diluted with water and extracted with DCM (3 x 10 ml). The
combined organic layer was dried over anhydrous sodium sulphate
and concentrated under reduced pressure. The resulting ketone
was purified was purified using silica gel column chromatography
(EtOAc and petroleum ether 60-80 ºC).
–SPh
moieties),
arylboronic
acids,
and
potassium
aryltrifluoroborate analogues, enabling the facile synthesis of
biaryl ketones in high yield. Sensitive functional groups like-
CHO, -COMe, -COOMe are well tolerated under this condition.
Importantly, our operationally simple method was successfully
applied at the gram-scale and in the synthesis of a naphthyl
Phenstatin analogue, a potent spindle poison. Studies to expand
this copper/silver-catalyzed synthesis to other reactions, and to
elucidate its actual mechanistic pathway, are ongoing in our
laboratory and will be reported in due course.
13. Bell, R. A.; Kramer, J. R. Environ. Toxicol. Chem. 1999, 18, 9-22.
14. King, A. E.; Brunold, T. C.; Stahl, S. S. J. Am. Chem. Soc. 2009,
131, 5044-5045.
15. (a) A´lvarez, C.; A´lvarez, R.; Corchete, P.; Melero, C. P.; Pela´ez,
R.; Medarde, M. Bioorg. Med. Chem. Lett. 2007, 17, 3417-3420.
(b) A´lvarez, C.; A´lvarez, R.; Corchete, P.; Melero, C. P.;
Pela´ez, R.; Medarde, M. Bioorg. Med. Chem. Lett. 2008, 16,
8999-9008.
Acknowledgements
P. Ghosh is thankful to UGC for his fellowship.
References and notes
1. (a) Maeyama, K.; Yamashita, K.; Saito, H.; Aikawa, S.; Yoshida,
Y. Polym. J. 2012, 44, 315-320. (b) Chan, C. Y. K.; Zhao, Z. J.;
Lam, J. W. Y.; Liu, J. Z.; Chen, S. M.; Lu, P.; Mahtab. F.; Chen,
X. J.; Sung, H. H. Y.; Kwok, H. S.; Ma, Y. G.; Williams, I. D.;
Wong, K. S.; Tang, B. Z. Adv. Funct. Mater. 2012, 22, 378-389.
(c) Wen, A.; Wang, Z.; Hang, T.; Jia, Y.; Zhang, T.; Wu, Y.; Gao,
X.; Yang, Z. J. Chromatogr. B: Anal. Technol. Biomed. Life Sci.
2007, 856, 348-352. (d) Zhao, W. L.; Carreira, E. M.; Org. Lett.
2006, 8, 99-102. (e) Ong, A. L.; Kamaruddin, A. H.; Bhatia, S.
Process Biochem. 2005, 40, 3526-3535. (f) Bosca, F.; Miranda,
M. A.; J. Photochem. Photobiol. B, 1998, 43, 1-26. (g) De Kimpe,
N., Keppens, M.; Froncg, G. Chem. Commun. 1996, 635-636.
2.
Jeong, E. J.; Liu, Y.; Lin, H.; Hu, M. Drug Metab. Dispos. 2005,
33, 785-794.
3. Lindhardt, A. T.; Simmonsen, R.; Taaning, R. H.; Gøgsig, T. M.;
Nilsson, G. N.; Stenhagen, G.; Elmore, C. S.; Skrydstrup, T. J.
Labelled Compd. Radiopharm. 2012, 55, 411-418.

5
Highlights:
ꢀ
Synthesis of biaryl ketones from thiolester in
presence of Cu/Ag salt.
ꢀ This protocol is free from expensive
Palladium catalyst and Cu(I)Tc mediator.
ꢀ
ꢀ
ꢀ
It is a modification of Liebeskind and Srogl
reaction and has broad substrate scope
Sensitive functional groups are well
tolerated.
Protocol could be used for gram scale synthesis
of biaryl ketones.

6
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Graphical Abstract
A synthesis of Biaryl Ketones via the C-S
bond cleavage of Thiol esters by a Cu/Ag salt
Leave this area blank for abstract info.
Prasanjit Ghosha, Bhaskar Gangulya, Eliyahu Perlb and Sajal Dasa*
a Department of Chemistry, University of North Bengal, Darjeeling 734013, India.
b Department of Chemistry and Biochemistry, Queens College of the City University of New York,65-30 Kissena
Blvd, Flushing, NY 11367, USA