Copper-catalyzed Pummerer type reaction of α-thio aryl/heteroarylacetates: Synthesis of aryl/heteroaryl α-keto esters

Article abstract of DOI:10.1016/j.tetlet.2017.03.069

A copper catalyzed Pummerer type reaction of α-thio aryl/heteroarylacetates is described for the first time. This transformation represents a new route to synthesize α-keto esters, which are important intermediates for pharmaceuticals and organic synthesis. The reaction proceeds via in situ generation of a thionium ion that undergoes hydrolysis to furnish α-keto esters in synthetically viable yields (up to 82%).

Full text of DOI:10.1016/j.tetlet.2017.03.069

Accepted Manuscript
Copper-Catalyzed Pummerer Type Reaction of α-Thio Aryl/Heteroarylacetates:
Synthesis of Aryl/Heteroaryl α-Keto Esters
Pipas Saha, Sumit Kumar Ray, Vinod K. Singh
PII:
S0040-4039(17)30390-8
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.03.069
TETL 48770
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
1 March 2017
20 March 2017
22 March 2017
Please cite this article as: Saha, P., Ray, S.K., Singh, V.K., Copper-Catalyzed Pummerer Type Reaction of α-Thio
Aryl/Heteroarylacetates: Synthesis of Aryl/Heteroaryl α-Keto Esters, Tetrahedron Letters (2017), doi: http://
dx.doi.org/10.1016/j.tetlet.2017.03.069
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Graphical Abstract
Copper-Catalyzed Pummerer Type Reaction of
α-Thio Aryl/Heteroarylacetates: Synthesis of
Aryl/Heteroaryl α-Keto Esters
Leave this area blank for abstract info.
Pipas Saha, Sumit Kumar Ray, and Vinod K. Singh

1
Tetrahedron Letters
journal homepage: www.els evier.com
Copper-Catalyzed Pummerer Type Reaction of α-Thio Aryl/Heteroarylacetates:
Synthesis of Aryl/Heteroaryl α-Keto Esters
Pipas Saha,a Sumit Kumar Ray,a and Vinod K. Singha,b,
∗
aDepartment of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal, MP-462 066, India
bDepartment of Chemistry, Indian Institute of Technology Kanpur, Kanpur, UP-208 016, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A copper catalyzed Pummerer type reaction of α-thio aryl/heteroarylacetates is described for the
first time. This transformation represents a new route to synthesize α-keto esters, which are
important intermediates for pharmaceuticals and organic synthesis. The reaction proceeds via in
situ generation of a thionium ion that undergoes hydrolysis to furnish α-keto esters in
synthetically viable yields (up to 82%).
Available online
Keywords:
Copper catalysts
Pummerer type reaction
Thionium ion
α-Keto esters
Disulfides
2009 Elsevier Ltd. All rights reserved.
Introduction
reports are known for the conversion of α-thio carbonyl
compounds into α-keto carbonyls.16 However, to the best of our
The Pummerer reaction is a process where an alkyl sulfoxide is
activated using acetic anhydride, trifluoroacetic anhydride
(TFAA), trifluoromethanesulfonic anhydride (Tf2O), or silyl
chloride, which then undergoes elimination to give a thionium
ion.1 A wide range of nucleophiles such as acetates, arenes,
alkenes, amides, and phenols then undergo nucleophilic addition to
the in situ generated thionium ion.1,2 The trapping of this ionic
intermediate by different nucleophiles has greatly expanded the
synthetic utility of the reaction.3 For example, the Pummerer
reaction has been used extensively for the synthesis of
thionucleosides,4 heterocycles,5 spirocyclic compounds6 and
natural products.7 In contrast, metal catalyzed Pummerer type
reactions of sulfides and sulfoxides are less explored.8 Moreover,
in some cases, stoichiometric amounts of metal catalysts have been
used for the reaction.8a,b
knowledge, there are no reports regarding the synthesis of α-keto
esters via C–S bond cleavage of α-thio aryl/heteroarylacetates.
Herein, we report a copper-catalyzed Pummerer type reaction of α-
thio aryl/heteroarylacetates for the synthesis of aryl/heteroaryl α-
keto esters in synthetically viable yields.
R'
O
R'
(Het)Ar
S
S
H
Copper catalyst
H2O
(Het)Ar
COOR
COOR
solvent, air
80 οC
(Het)Ar
COOR
Nu
R'
(Het)Ar
S
Nu
COOR
Scheme 1. Working hypothesis
Results and discussion
In continuation of our research interest for the synthesis of
organosulfur compounds,9 it was envisioned that upon treatment
with metal catalysts, α-thio aryl/heteroarylacetates would generate
a thionium ion in situ which could be trapped by a nucleophile
(Scheme 1). However, upon treatment with copper catalysts, α-thio
aryl/heteroarylacetates were converted into α-keto esters (Scheme
1) which are important intermediates for pharmaceuticals and
organic synthesis.10 Prominent literature reports reveal that α-keto
esters are usually prepared by the reaction of Grignard reagents
with oxalyl chloride,11 ethyl α-oxo-1H-imidazole-1-acetate12 or
diethyl oxalate.13 They are also prepared by the oxidation of
At the outset, we started our investigation with the reaction of
methyl 2-((4-bromophenyl)thio)-2-phenylacetate 1a (1 equiv) with
Cu(OAc)2 (10 mol%) in DMF at 80 °C under air. To our delight,
methyl 2-oxo-2-phenylacetate 2a was isolated in 46% yield along
with 28% of 1,2-bis(4-bromophenyl)disulfane 3a as a by-product
(Table 1, entry 1). Afterwards, a systematic optimization was
carried out using various solvents such as glacial AcOH, DMSO,
toluene and H2O, where glacial AcOH was found to be superior in
terms of yield (Entries 2-5). It was observed that 5 mol% catalyst
loading afforded the product 2a in 40% yield (Entry 7).
α-diazoesters14 and aryl ketones.15 In contrast, numerous literature
———
∗ Corresponding author. Tel.: +91-512-2597291; fax: +91-512-2597436; e-mail: vinodks@iitk.ac.in

2
Tetrahedron Letters
Surprisingly, there was no reaction at room temperature and in higher yields than α-thio arylacetate 1l with an electron
starting material 1a was fully recovered (Entry 8). Next, we turned withdrawing group (4-NO2) on the phenyl ring. This could be due
our attention towards the screening of various copper salts for this to stabilization of the in situ generated thionium ion by electron
transformation. Notably, Cu(OAc)2 was the most efficient catalyst, donating groups on the phenyl ring. Additionally, α-thio
affording product 2a in 73% yield (Entry 2). It is worth noting that arylacetates 1h-j with halogen functional groups (-F, -Cl, -Br),
CuOAc could also catalyze the reaction, but furnished 2a in lower afforded α-keto esters 2h-j in synthetically viable yields (up to
yield (Entry 9) and with unreacted starting material recovered. A 74%).
trace amount of 2a was obtained when methyl 2-((4-
bromophenyl)thio)-2-phenylacetate 1a (1 equiv.) was treated with
F
Br
S
S
S
Cu(OAc)2 (10 mol%) in dry toluene under an Ar atmosphere
(Entry 15). However, the presence of 4 Å molecular sieves
precluded the formation of 2a (Entry 16). Therefore, based on
extensive optimization studies, it was decided to carry out further
studies in the presence of Cu(OAc)2 (10 mol%) in glacial AcOH
solvent at 80 °C under air.
S
O
COOEt
COOMe
COOMe
O
1d
1c
1a
1b
Br
F
Br
S
S
S
S
COOEt
1f
COOEt
1h
COOEt
Ph
COOMe
COOMe
1g
MeO
1e
OMe
MeO
Table 1. Optimization of Reaction Conditions.a
Br
OMe
S
Br
S
S
O
S
COOMe
COOMe
S
S
COOMe
COOMe
S
10 mol% catalyst
solvent, air
COOMe
+
1l
O2N
Br
I
1k
1i
1j
Cl
Br
Br
COOMe
1a
3a
2a
80 ο
C
Br
S
S
COOMe
S
S
O
COOMe
Entry
Catalyst
Solvent
Time
Yield
Yield
2a (%)b
3a (%)b
COOEt
1p
O
(h)
50
50
50
55
48
50
50
48
55
55
48
55
55
48
48
48
O
1o
N
S
1n
1m
1
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
DMF
46
73
48
34
0
28
27
25
15
0
2
AcOH
DMSO
Toluene
H2O
S
O
3
S
O
1q
4
Figure 1. Different α-thio aryl/heteroarylacetates used for the
synthesis of aryl/heteroaryl α-keto esters.
5
6
Cu(OAc)2,H2O
Cu(OAc)2
Cu(OAc)2
CuOAc
AcOH
AcOH
AcOH
AcOH
AcOH
DMF
60
40
0
25
16
0
The α-thio arylacetate 1f (Fig. 1) with an alkyl group attached to
sulfur afforded α-keto ester 2f in 75% yield (Table 2). No
significant effect was observed when different aryl/alkyl
substituents attached to the sulfur in α-thio arylacetates were used.
7c
8d
9
42
28
0
20
17
0
Table 2. Synthesis of Aryl/Heteroaryl α-Keto Esters.a,b
10
11
12
13
14
15e
16f
CuCl2
CuCl2
O
R'
10 mol% Cu(OAc)2
S
H
Cu(OTf)2
Cu(OTf)2
Pd(OAc)2
Cu(OAc)2
Cu(OAc)2
AcOH
DMF
52
35
0
29
22
0
Ar
COOR
2a q
(Het)Ar
COOR
AcOH, air
80 οC
1a-q
-
O
O
O
O
AcOH
Toluene
Toluene
COOMe
COOMe
O
trace
trace
2b, 42 h, 66%
2a, 50 h, 73%
2c, 48 h, 80%
O
0
0
O
O
aReaction conditions: 1a (0.3 mmol), catalyst (0.03 mmol), solvent (3 mL), 80
COOEt
COOEt
COOMe
°C, under air.
MeO
OMe
2e, 48 h, 78%
2d, 48 h, 82%
bIsolated yield. Products (2a and 3a) were characterized by 1H, 13C NMR and
Mass spectroscopy.
2f, 34 h, 75%
O
O
O
COOEt
cReaction performed with Cu(OAc)2 (5 mol%).
dReaction performed at rt.
COOEt
COOMe
MeO
F
Cl
OMe
2i, 52 h, 57%
O
2h, 50 h, 53%
eReaction performed in dry toluene under an Ar atmosphere.
2g, 50 h, 64%
O
O
fReaction performed in dry toluene under an Ar atmosphere in the presence of
4 Å molecular sieves.
COOMe
COOMe
COOMe
I
O2N
Br
2l, 45 h, 50%
O
2k, 48 h, 44%
2j, 48 h, 74%
With the optimized reaction conditions in hand, the substrate
scope of the reaction was explored using various α-thio
aryl/heteroarylacetates (Fig. 1). It was noted that α-thio
aryl/heteroarylacetates 1 underwent the reaction, leading to
aryl/heteroaryl α-keto esters 2 in reasonable yields along with
disulfides as by-products (Table 2). Interestingly, the different aryl
substituents at the C-2 position of α-thio arylacetates 1 have a
promising effect on this reaction. It was observed that α-thio
arylacetates 1a-b (Fig. 1) with a phenyl ring at the C-2 position
afforded products 2a-b in 73% and 66% yields, respectively
O
O
COOMe
COOMe
COOEt
O
N
S
2n, 50 h, 48%
2o, 48 h, 42%
2m, 55 h, 48%
O
O
O
O
COOMe
S
O
O
2i
X-ray of
2q, 48 h, 44%
2p, 52 h, 50%
aReaction conditions: 1 (0.3 mmol), Cu(OAc)2 (0.03 mmol), AcOH (3 mL), 80
(Table 2). On the other hand, α-thio arylacetates 1c-g (Fig. 1) with °C, under air.
electron donating functional groups (4-Me, 4-OMe) furnished 2c-g

3
bIsolated yield. Compounds were characterized by 1H, 13C NMR and Mass
spectroscopy.
The ESI-MS study of the crude reaction mixture of 1a after 7 h
revealed the presence of thionium ion 7 in situ (Fig. 2) (see ESI for
more details).18 However, we were unable to isolate species 7 as a
single crystal.
However, lower yields were observed for compound 2k (44%) and
2m (48%), clearly suggesting that steric hindrance at the ortho
position to the phenyl ring has a crucial role in this transformation.
Rewardingly, α-thio heteroarylacetates 1n-q with a heteroaromatic
moiety at the C-2 position afforded the corresponding α-keto esters
2n-q in moderate yields (up to 50% yields). Recrystallization of 2i
from chloroform produced a single crystal whose structure was
confirmed by X-ray analysis (Fig. S1, ESI).17
In order to increase the versatility of this methodology, we then
directed our efforts to synthesize alkyl α-keto esters using the
optimized reaction conditions. Towards this, ethyl 2-((4-
Figure 2. Major species identified using ESI-MS analysis of the
reaction mixture of 1a.
chlorophenyl)thio)-3-phenylpropanoate
4
was treated with
Based on the results shown in Schemes 2 and 3, ESI-MS analysis
of the crude reaction mixture of 1a and previous reports on
copper(II)-catalyzed oxidative reactions,19 we postulate the
following catalytic cycle for the copper(II)-catalyzed Pummerer
type reaction of α-thio aryl/heteroarylacetates (Scheme 4).
Initially, the α-thio aryl/heteroarylacetate reacts with Cu(OAc)2 to
furnish α-sulfonium aryl/heteroarylacetate copper(II) species A,
from which the acetate anion abstracts a proton to generate
thionium ion B followed by the reduction of Cu(II) to Cu(I)
species. Subsequently, nucleophilic addition of H2O to thionium
ion B generates species C. Next, in situ generated CuOAc
promotes the removal of sulfur from species D to afford α-keto
ester along with species E. Species E then undergoes a
disproportionation reaction followed by an aerobic oxygen-
mediated reductive elimination to generate Cu(I) species along
with disulfide as a by-product.19h Eventually, the Cu(I) species in
the presence of aerobic oxygen and AcOH is converted to
Cu(OAc)2,19g thereby completing the catalytic cycle (Scheme 4).
Cu(OAc)2 (10 mol%) in glacial AcOH at 80 °C (Scheme 2, eq 1).
Unfortunately, the reaction did not proceed which clearly indicates
that only α-thio aryl/heteroarylacetates are favorable for this
copper catalyzed reaction to afford aryl/heteroaryl α-keto esters.
Next, to understand the role of the thiol moiety in this reaction,
methyl 2-(acetylthio)-2-phenylacetate
5
with an electron
withdrawing acetyl group directly attached to the sulfur was
subjected to the optimized reaction conditions (Scheme 2, eq 2).
However, no reaction was observed, which might be due to the
unavailability of the lone pair of electrons on sulfur to participate
in the reaction with Cu(OAc)2. To confirm that the copper
catalyzed Pummerer type reaction of α-thio aryl/heteroarylacetates
proceed through in situ formation of a thionium ion, methyl 2-(4-
bromophenyl)-2-(p-tolylthio)acetate 1j was treated with Cu(OAc)2
(0.1 equiv) in glacial AcOH with the addition of AcONa (1.2
equiv) as an external nucleophile at 80 °C (Scheme 2, eq 3). To
our
delight,
methyl
2-acetoxy-2-(4-bromophenyl)-2-(p-
tolylthio)acetate 6 was isolated in 25% yield along with methyl 2-
(4-bromophenyl)-2-oxoacetate 2j in 52% yield. The formation of
product 6 in this reaction confirms that the reaction proceeds
through the in situ generated thionium ion.
R'
S
(Het)Ar
COOR
1
H2O
1/2 O2, 2AcOH
COOEt
Cu(OAc)2
10 mol% Cu(OAc)2
OAc
S
3
(1)
R'
No reaction
R'
S
II
Cu
S
AcOH, air
80 ο
48 h
Cu(I)
R'
4
C
S
H
OAc
O2
RO2C
Cl
(Het)Ar
Cu(0) + (R'S)2Cu(II)
A
OAc
O
F
S
disproportionation
R'SCu(I)
10 mol% Cu(OAc)2
AcOH, air
CuOAc
+ AcOH
COOMe
(2)
No reaction
R'
S
80 ο
48 h
C
E
5
O
(Het)Ar
COOR
H2O
B
(Het)Ar
COOR
S
O
I
2
R'
Cu
R'
10 mol% Cu(OAc)2
S
COOMe
(3)
S
COOMe
+
S
OAc
AcOH, air
AcONa
COOMe
Br
Br
(Het)Ar
H
COOR
6 (25%)
(Het)Ar
H
COOR
2j (52%)
O
D
80 ο
48 h
C
O
1j
Br
C
H
AcOH CuOAc
Scheme 2. Control Experiments.
Scheme 4. Proposed Catalytic Cycle.
To gain insight into the reaction mechanism, an isotopic-labelling
experiment was performed using H218O. Methyl 2-((4-
bromophenyl)thio)-2-(4-methoxyphenyl)acetate 1e was treated
with Cu(OAc)2 (10 mol%) in glacial AcOH at 80 °C in the
presence of H218O (5.0 equiv). Upon reaction completion, the 18O
incorporated product was detected by HRMS analysis (see ESI for
more details).
Finally, in order to rationalize the practical applicability of this
copper catalyzed Pummerer type reaction of α-thio
aryl/heteroarylacetates, a gram scale reaction of methyl 2-((4-
bromophenyl)thio)-2-pheylacetate 1a was performed under the
optimized reaction conditions (Scheme 5). To our delight, product
2a was furnished in 70% yield.
Br
O
Br
10 mol% Cu(OAc)2
AcOH (30 mL)
S
18O
COOMe
(70%)
S
10 mol% Cu(OAc)2
COOMe
COOMe
2a
80 °C, air
50 h
COOMe
AcOH/H218O
80 οC, air
48 h
1a
MeO
(1 g, 2.97 mmol)
18O-2e (m/z = 197)
MeO
1e
Scheme 5. Gram-Scale Reaction.
Scheme 3. Isotope Labelling Experiment.

4
Tetrahedron Letters
(c) Xu G, Chen K, Zhou H. Synthesis. 2009;3565.
(a) Feldman KS, Vidulova DB, Karatjas AG. J Org Chem.
2005;70:6429;
(b) Ovens C, Martin NG, Procter, DJ. Org Lett.
2008;10:1441;
Conclusions
6.
In summary, we have developed a copper catalyzed Pummerer
type reaction of α-thio aryl/heteroarylacetates for the synthesis of
aryl/heteroaryl α-keto esters in moderate to good yields. This
process tolerates a broad range of functionalized substrates to
afford aryl/heteroaryl α-keto esters using catalytic Cu(OAc)2. A
gram scale reaction was also performed. The scope and synthetic
application of this reaction are currently under study in our
laboratory.
(c) Feldman KS, Nuriye AY. Tetrahedron Lett.
2009;50:1914.
7.
(a) Akai S, Kakiguchi K, Nakamura Y, Kuriwaki I, Dohi T,
Harada S, Kubo O, Morita N, Kita Y. Angew Chem.
2007;119:7602; Angew Chem Int Ed. 2007;46:7458;
(b) Feldman KS, Skoumbourdis AP, Fodor MD. J Org Chem.
2007;72:8076;
(c) Kuhakarn C, Seehasombat P, Jaipetch T, Pohmakotr M,
Reutrakul V. Tetrahedron. 2008;64:1663;
(d) Kobayashi S, Ishii A, Toyota M. Synlett. 2008;1086;
(e) Feldman KS, Fodor MD. J Am Chem Soc.
2008;130:14964;
(f) Feldman KS, Fodor MD. J Org Chem. 2009;74:3449; (g)
Feldman KS, Fodor MD, Skoumbourdis AP. Synthesis.
2009;3162.
(a) Ishibashi H, Matsuoka K, Ikeda M. Chem Pharm Bull.
1991;39:1854;
(b) Liao Y-J, Wu YL, Chuang CP. Tetrahedron.
2003;59:3511;
(c) Murakami K, Imoto J, Matsubara H, Yoshida S,
Yorimitsu H, Oshima K. Chem Eur J. 2013;19:5625.
(a) Rana NK, Singh VK. Org Lett. 2011;13:6520;
(b) Rana NK, Unhale R, Singh VK. Tetrahedron Lett.
2012;53:2121;
Acknowledgements
Financial support through the J.C. Bose fellowship (DST, India)
and SERB, DST (EMR/2014/001165), India for research grant are
gratefully acknowledged. P.S. and S.K.R. thanks IISER Bhopal for
research facilities. We thank Mr. Ajay Verma, IISER Bhopal, for
assistance with single crystal X-ray analysis.
8.
9.
References
1. (a) Pummerer R. Chem Ber. 1909;42:2282;
(b) Pummerer R. Chem Ber. 1910;43:1401.
2.
(a) Russell GA, Mikol GJ. Acid-Catalyzed Rearrangements
of Sulfoxides and Amine Oxides. The Pummerer and
Polonovski Reactions, ed. B. S. Thyagaragan, Wiley
Interscience, New York, 1968;
(c) Unhale RA, Rana NK, Singh VK. Tetrahedron Lett.
2013;54:1911.
(b) Oae S, Numata T, Yoshimura T. The Chemistry of the
Sulfonium Group, ed. C. J. M. Stirling and S. Patai, John
Wiley, New York, 1981;
10. (a) Li H, Wang B, Deng L. J Am Chem Soc. 2006;128:732;
(b) Kong J-R, Ngai, M-Y, Krische MJ. J Am Chem Soc.
2006;128:718;
(c) DeLucchi O, Miotti U, Modena G. The Pummerer
Reaction of Sulfinyl Compounds, ed. L. A. Paquette, John
Wiley, New York, 1991;
(d) Bur SK, Padwa A. Chem Rev. 2004;104:2401;
(e) Feldman KS. Tetrahedron 2006;62:5003;
(f) Smith LHS, Coote SC, Sneddon HF, Procter DJ. Angew
Chem Int Ed. 2010;49:5832.
(c) Steward KM, Gentry EC, Johnson JS. J Am Chem Soc.
2012;134:7329;
(d) Zhu T-S, Jin S-S, Xu M-H. Angew Chem Int Ed.
2012;51:780;
(e) Thai K, Langdon SM, Bilodeau F, Gravel M. Org Lett.
2013;15:2214;
(f) Hu Y, Xu K, Zhang S, Guo F, Zha Z, Wang Z. Org Lett.
2014;16:3564.
3. (a) Harmata M, Fletcher VR, ClaassenII RJ. J Am Chem Soc.
1991;113:9861;
11. Babudri F, Fiandanese V, Marchese G, Punzi A.
Tetrahedron. 1996;52:13513.
12. Nimitz JS, Mosher HS. J Org Chem. 1981;46:211.
13. (a) Creary X. J Org Chem. 1987;52:5026;
(b) Singh J, Kissick TP, Mueller RH. Org Prepr Proced Int.
1989;21:501.
(b) Abe H, Itani J, Masunari C, Kashino S, Harayama T. J
Chem Soc Chem Commun. 1995; 1197;
(c) Padwa A, Heidelbaugh TM, Kuethe JT. J Org Chem.
2000;65:2368;
(d) Montaño RG, Zhu J. Chem Commun. 2002;2448;
(e) Magnus P, Rainey T, Lynch V. Tetrahedron Lett.
2003;44:2459;
14. (a) Ma M, Li C, Peng L, Xie F, Zhang X, Wang J.
Tetrahedron Lett. 2005;46:3927;
(f) Akai S, Kawashita N, Satoh H, Wada Y, Kakiguchi K,
Kuriwaki I, Kita Y. Org Lett. 2004;6:3793;
(g) Akai S, Tsujino T, Fukuda N, Iio K, Takeda Y,
Kawaguchi K-i, Naka T, Higuchi K, Akiyama E, Fujioka H,
Kita Y. Chem Eur J. 2005;11:6286;
(h) Akai S, Kawashita N, Wada Y, Satoh H, Alinejad AH,
Kakiguchi K, Kuriwaki I, Kita Y. Tetrahedron Lett.
2006;47:1881;
(b) O’Connor NR, Bolgar P, Stoltz BM. Tetrahedron Lett.
2016;57:849.
15. Zhang Z, Su J, Zha Z, Wang Z. Chem Eur J. 2013;19:17711.
16. (a) McAllister LA, McCormick RA, James KM, Brand S,
Willetts N, Procter DJ. Chem Eur J. 2007;13:1032;
(b) Munive L, Bernes S, Sansinenea E, Ortiz A. Tetrahedron
Lett. 2010;51:6041;
(c) He Y, Guo C, Sun B, Quinn J, Li Y. Chem Commun.
(i) Padwa A, Nara S, Wang Q. Tetrahedron Lett.
2006;47:595;
(j) Yoshida S, Yorimitsu H, Oshima K. Org Lett.
2009;11:2185;
(k) Kobatake T, Fujino D, Yoshida S, Yorimitsu H, Oshima
K. J Am Chem Soc. 2010;132: 11838;
(l) Kobatake T, Yoshida S, Yorimitsu H, Oshima K. Angew
Chem Int Ed. 2010;49:2340;
2015;51:8093;
(d) Liao K, Zhou F, Yu J-S, Gao W-M, Zhou J. Chem
Commun. 2015;51:16255;
(e) Khanal HD, Kim SH, Lee YR. RSC Adv. 2016;6:58501.
17. The crystallographic data for compound 2i has been
deposited with the Cambridge Crystallographic Data Centre
and it has CCDC number 1476214.
18. (a) Wang L, Priebbenow DL, Dong W, Bolm C. Org Lett.
(m) Eberhart AJ, Cicoira C, Procter DJ. Org Lett.
2013;15:3994;
2014;16:2661;
(b) Sadhu P, Alla SK, Punniyamurthy T. J Org Chem.
2015;80:8245.
4. (a) O’Neil IA, Hamilton KM. Synlett. 1992;791;
(b) Yoshimura Y, Kitano K, Satoh H, Watanabe M, Miura S,
Sakata S, Sasaki T, Matsuda A. J Org Chem. 1996;61:822;
(c) Yoshimura Y, Yamazaki Y, Kawahata M, Yamaguchi K,
Takahata H. Tetrahedron Lett. 2007;48:4519;
(d) Denancé M, Legay R, Gaumont A-C, Gulea M.
Tetrahedron Lett. 2008;49:4329;
19. (a) Sherman ES, Chemler SR, Tan TB, Gerlits O. Org Lett.
2004;6:1573;
(b) King AE, Brunold TC, Stahl SS. J Am Chem Soc.
2009;131:5044;
(c) Guru MM, Ali MA, Punniyamurthy T. J Org Chem.
2011;76:5295;
(e) Haraguchi K, Matsui H, Takami S, Tanaka H. J Org
Chem. 2009;74:2616;
(f) Yoshimura Y, Yamazaki Y, Saito Y, Takahata H.
Tetrahedron 2009;65:9091.
(d) Turnpenny BW, Chemler SR. Chem Sci. 2014;5:1786;
(e) Liu J-Q, Hao B-Y, Zou H, Zhang W-H, Chen, X-Z.
ARKIVOC. 2014;5:72;
(f) Casavant BJ, Khoder ZM, Berhane IA, Chemler SR. Org
5. (a) Miyagawa T, Satoh T. Tetrahedron Lett. 2007;48:4849;
(b) Eggers ME, Jog PV, Bates DK. Tetrahedron.
2007;63:12185;
Lett. 2015;17:5958;
(g) McCann SD, Stahl SS. Acc Chem Res. 2015;48:1756;
(h) Zhu H, Yu J-T, Cheng J. Chem Commun. 2016;52:11908;

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(i) Yu J, Zhang-Negrerie D, Du Y. Org Lett. 2016;18:3322.
Supplementary Material
Experimental procedures and full spectroscopic data for all
compounds, isotope labelling experiment, single crystal X-ray data
of 2i, NMR spectra ( 1H and 13C) of the starting materials 1a-q, 4,
5 and products 2a-q, 6, ESI-MS spectra of 7 have been provided in
a separate electronic file as a supplementary data.

6
Tetrahedron Letters
Highlights
ꢀ Pummerer type reaction for the synthesis of
the α-keto ester is described.
ꢀ The reaction proceeds through the generation
of a thionium ion in situ.
ꢀ The source of oxygen in α-keto ester is
confirmed by isotopic-labeling experiment.

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