PPh3·HBr-DMSO mediated expedient synthesis of γ-substituted β,γ-unsaturated α-ketomethylthioesters and α-bromo enals: Application to the synthesis of 2-methylsulfanyl-3(2 H)-furanones

Article abstract of DOI:10.1002/chem.201303755

An efficient chemoselective general procedure for the synthesis of γ-substituted β,γ-unsaturated α-ketomethylthioesters from α,β-unsaturated ketones has been achieved through an unprecedented PPh₃·HBr-DMSO mediated oxidative bromination and Kornblum oxidation sequence. The newly developed reagent system serves admirably for the synthesis of α-bromoenals from enals. Furthermore, AuCl ₃-catalyzed efficient access to 3(2H)-furanones from the above intermediates under extremely mild conditions are described. Copyright

Full text of DOI:10.1002/chem.201303755

DOI: 10.1002/chem.201303755
Communication
&
Oxidation
PPh3·HBr-DMSO Mediated Expedient Synthesis of g-Substituted
b,g-Unsaturated a-Ketomethylthioesters and a-Bromo Enals:
Application to the Synthesis of 2-Methylsulfanyl-3(2H)-furanones
Kanchan Mal, Abhinandan Sharma, Prakas R. Maulik, and Indrajit Das*[a]
unexplored reagent combination of PPh3·HBr-DMSO and pro-
Abstract: An efficient chemoselective general procedure
for the synthesis of g-substituted b,g-unsaturated a-keto-
methylthioesters from a,b-unsaturated ketones has been
achieved through an unprecedented PPh3·HBr-DMSO
mediated oxidative bromination and Kornblum oxidation
sequence. The newly developed reagent system serves ad-
mirably for the synthesis of a-bromoenals from enals. Fur-
thermore, AuCl3-catalyzed efficient access to 3(2H)-fura-
nones from the above intermediates under extremely mild
conditions are described.
ceeding through conversion of ketomethyl groups into a-keto-
methylthioesters. We also demonstrate that the newly devel-
oped reagent system is equally useful for the synthesis of a-
bromoenals from enals. Furthermore, we demonstrate AuCl3-
catalyzed cyclization of 2-oxo-3-butynoic methylthioester into
2-methylsulfanyl-3(2H)-furanones.
In connection with our other projects dealing with a,b- un-
saturated ketones and utilizing PPh3·HBr as a reagent, we no-
ticed the formation of some intriguing products when DMSO
was used as the solvent instead of CH2Cl2.[8] Subsequently, we
examined the reaction of 1a with PPh3·HBr (2.0 equiv) in
DMSO.
Following the usual work-up and purification, we obtained
b,g-unsaturated a-ketothioester 2a in 47% yield (entry 1,
Table 1). Importantly, we did not observe any bromination at
the aromatic ring or at alkenyl olefinic bond. Intrigued by our
findings, we initiated a systematic study of this transformation
and the scope of the reagent system towards other transfor-
Oxygen-transfer reactions using DMSO, either through the acti-
vation of sulfoxides, such as Swern oxidation and its variants,[1]
or through a non-activation pathway, such as the Kornblum
oxidation, are of fundamental importance in chemical transfor-
mations.[2] On the other hand, addition of HX or X2 (X=Br, I) to
DMSO induce deoxygenation to generate dimethyl sulfide.[3]
Taken together, a variety of unique oxidative transformations
through oxidative halogenations followed by DMSO-based oxi-
dation have been developed by using the X2/HX-DMSO
system.[4] Such reactions often lead to the formation of aryl-
glyoxals, or their acids, in good yields through oxidative hy-
drolysis, and, occasionally, a-ketothioesters as minor products.
Although a-ketothioesters find widespread applications as
a synthetic intermediates, there is a lack of general methods to
synthesize them; the few methods available involve the use of
the pyrophoric reagent, tBuLi.[5] The related g-substituted b,g-
unsaturated a-ketothioesters are also potentially important
building blocks; however, their utility is very much under-
explored owing to the paucity of methods available to access
them.[6]
Table 1. Reaction optimization for a-ketomethylthioesters.[a]
Entry
Reagent
Equiv
t [h]
Yield[b][%]
1
2
3
4
5
6
7
8
PPh3·HBr
2.0
2.0
2.0
2.0
2.0
2.0
0.5
1.0
3.0
2.0
2.0
2.0
2.0
2.0
3
15
12
2
47
n.d.[c]
n.d.[c]
n.d.[c]
n.d.[c]
19
6
28
53
43[d]
33[e]
n.d.[f]
n.d.[g]
42[h]
33% HBr-AcOH
pyridine·HBr
pyrrolidone hydrotribromide
pyridinium tribromide
dry HBr
PPh3·HBr
PPh3·HBr
PPh3·HBr
PPh3·HBr
PPh3·HBr
PPh3·HBr
PPh3·HBr
PPh3·HBr
2
12
17
8
1
4
9
Herein, we report the synthesis of g-substituted b,g-unsatu-
rated a-ketomethylthioesters under oxidative bromination[7]
and Kornblum oxidation conditions, mediated by the hitherto
10
11
12
13
14
4
15
15
4
[a] K. Mal, A. Sharma, Dr. P. R. Maulik, Dr. I. Das
Chemistry Division
[a] 1a (0.05 g, 0.24 mmol, 1.0 equiv), reagent in dry DMSO (2 mL) under
Ar atmosphere, 508C, employing time as mentioned. PPh3·HBr (2.0 equiv)
was used as optimized reaction conditions from an economical point of
view. n.d.=not detected. [b] Yields of isolated product. [c] Complex reac-
tion mixtures. [d] Reaction was carried out in open atmosphere. [e] DMSO
was used without drying. [f] 10.0 equiv of H2O was used. [g] 0.050 g of
4 ꢀ molecular sieves was used. [h] 1 g (4.85 mmol) of 1a batch size and
DMSO (30 mL) were used. Ar=3,4-(OMe)2-C6H3
CSIR-Indian Institute of Chemical Biology
4, Raja S. C. Mullick Road, Jadavpur
Kolkata 700032 (India)
Fax: (+91)33-2473-5197
E-mail: id@csiriicb.in
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201303755.
Chem. Eur. J. 2014, 20, 662 – 667
662
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
mations. As shown in Table 1, treating 1a with 33% HBr-AcOH,
py·HBr, pyrrolidone hydrotribromide, or pyridinium hydrotri-
bromide in DMSO (entries 2–5, Table 1) did not result in 2a,
but the use of dry HBr in DMSO furnished 2a in 19% yield
(entry 6, Table 1). We observed that a catalytic amount of
PPh3·HBr was not enough to drive the reaction to completion
(entries 7 and 8, Table 1). The use of PPh3·HBr in stoichiometric
ratios accelerated the transformation, and a higher yield was
obtained with an excess of reagents (entry 9, Table 1). Interest-
ingly, the reaction may be carried out in open atmosphere
(43%; entry 10, Table 1) or with DMSO that hadn’t been dried
(33%; entry 11, Table 1), but with a lower yield and the necessi-
ty to conduct the reaction for a longer reaction time.
Table 2. Synthesis of g-substituted b,g-unsaturated a-ketomethylthioes-
ters.[a]
Entry
R
Product
t [h] Yield[b][%]
1
2
3
4
5
6
7
8
3,4-(OMe)2-C6H3
3-OMe,4-OBn-C6H3
2,3-(OMe)2-C6H3
4-OMe-C6H4
4-OH-C6H4
2a
2b
2c
2d
2e
2 f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
2r
3
3
3
47
45
47
5.5 46
5
3
4
5
41
54
52
65
4-Me-C6H4
C6H5
In order to explore the influence of water in the reaction
system, as it was generated in situ in the reaction medium
through an oxidation–reduction cycle, we conducted the reac-
tion with 10.0 equiv of H2O or 4 ꢀ molecular sieves in dry
DMSO; no product, 2a, was formed even by conducting the
reaction at 808C for several hours, only starting material being
recovered (entries 12 and 13, Table 1). To demonstrate the
PPh3·HBr-DMSO mediated procedure on a large scale, we con-
ducted the reaction with one gram of compound 1a
(4.85 mmol). We isolated 2a in 42% yield (entry 14, Table 1)
without compromising to the reaction efficiency. The use of
other solvents (DMF, THF and CH3CN) failed to deliver the re-
quired products.
4-NO2-C6H4
3-NO2-C6H4
2-NO2-C6H4
2,4-(NO2)2-C6H3
4-CN-C6H4
3-CN-C6H4
4-Cl-C6H4
3-Cl-C6H4
2-Br-C6H4
2,4-(Cl)2-C6H3
2,6-(Cl)2-C6H3
2-Cl-6-F-C6H3
4-OAc-C6H4
4-OBz-C6H4
2-Naphthyl
2-Thienyl
9
2.5 64
2.5 62
2.5 73
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
2
70
1.5 71
4
2
3
6
56
58
65
59[c]
3.5 64
2s
2t
5
18
3
2
3
6
16
3
51
56[c]
65
2u
2v
2w
2x
2y
70
56
22[d]
16[c]
49
PhCH2CH2
Cyclohexyl
Subsequently, we investigated the substrate scope and gen-
erality for this transformation. As shown in Table 2, several b-
substituted a,b-unsaturated ketomethyl derivatives underwent
methylthioesterification to give g-substituted b,g-unsaturated
a-ketomethylthioesters with an excellent level of chemoselec-
tivity. In general, the reaction is tolerant to variation in sub-
stituents in the aryl ring. It was found that the substrates con-
taining an electron-donating (2a–f, 41–54%) and
PhCꢀCCOMe (1z)!PhCꢀCCOCOSMe (2z)
[a] Reactions were performed with 1a–y,
z
(0.05 g, 1.0 equiv) and
PPh3·HBr (2.0 equiv) in dry DMSO at 508C under Ar atmosphere. [b] Yields
of isolated product. [c] Reactions were performed at r.t. [d] Reaction was
performed at 458C.
electron-neutral substituents (2g, 52%) on the aro-
matic ring or heteroaromatic substituent (2w, 56%)
gave ketothioesters in moderate yields. Substrates
containing strong electron-withdrawing (2h–m, 62–
73%) and electron-deficient (2n–u, 51–65%) sub-
stituents on the aromatic ring or with a polynuclear
aromatic hydrocarbon (2v, 70%) delivered the corre-
sponding ketothioesters in moderate to good yields.
An a,b-alkynyl derivative was also found to be com-
patible under the reaction conditions (2z; entry 26,
Table 2). However, replacement of the b-aryl group
with an alkyl group dramatically lowered the yield
Figure 1. ORTEP diagram showing the molecular structure of 2g at the 30% probability
level.
(2x–y, 16–22%), perhaps owing to the lack of aro-
matic conjugation, competitive allylic bromination, or
both. The structure of 2g was unambiguously estab-
lished by single-crystal X-ray diffraction analysis (Figure 1).[9]
Complete retention of the trans-alkene stereochemistry with
respect to the double bond was observed in all products (2a–
y, Table 2), as established by the large coupling constant for
the olefinic protons (3J~15–16 Hz) in the 1H NMR spectrum.
The modest yields achieved in the reaction sequences (Table 2)
were thought to be due to the formation of aldehyde (hydrat-
ed form) from the corresponding a-bromo intermediate
through Kornblum oxidation (see Scheme 1). However, when
the reaction was quenched midway, no such derivatives were
isolated.
A plausible reaction mechanism is outlined in Scheme 1.
Based on earlier reports,[4,10a] we presumed that PPh3·HBr in
presence of DMSO would generate Br2, Ph3PO, (CH3)2S, and
H2O through an oxidation–reduction cycle.[10b] The initial oxida-
tive bromination of 1 could then lead to the corresponding a-
Chem. Eur. J. 2014, 20, 662 – 667
www.chemeurj.org
663
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
ceed through the corresponding a-bromoketone intermedi-
ates.
To gain further mechanistic insights on this transformation,
an NMR experiment was carried out with 1a (0.01 g,
0.048 mmol), [D6]DMSO (0.4 mL), and PPh3·HBr (0.097 mmol) at
508C for 3 h (Scheme 3). Exclusive formation of 2aa with incor-
poration of -CD3 confirmed that the methyl group originated
from DMSO and not from any other source (for details, see the
Supporting Information).
Scheme 3. Synthesis of a-keto deutrated-methylthioester with [D6]DMSO.
Scheme 1. Possible reaction mechanism pathway leading to 2.
To determine whether substrates with a conjugated double
bond are necessary, we performed experiments with acetophe-
none/p-nitroacetophenone and PPh3·HBr-DMSO. However, we
did not observe any expected a-ketothioester from acetophe-
none even upon heating the reaction mixture for several
hours; the use of p-nitroacetophenone did lead to product,
but only in 13% yield. The poor yield obtained in the reaction
may be due to the lack of a conjugated double bond in the
substrate (see the Supporting Information).
bromo derivative I, followed by immediate formation of II
through nucleophilic substitution with dimethyl sulfide and
concomitant release of trimethylsulfonium bromide salts
(Scheme 1). Further bromination of intermediate II would lead
to III, and subsequent DMSO-mediated Kornblum oxidation to
the b-g-unsaturated-a-ketomethylthioesters 2 via IV. However,
DMSO-mediated direct oxidation of I to V was not observed.[4]
Since, HBr was regenerated at the end of the reaction in the
proposed reaction pathway (Scheme 1), we expected PPh3·HBr
could be used in catalytic amount. However, we observed that
a catalytic amount of PPh3·HBr was not sufficient to drive the
reaction to completion (entries 7–8, Table 1). Whereas, the use
of PPh3·HBr in stoichiometric ratios only accelerated the trans-
formations, and we isolated 2a in good yield. Further, we ob-
served that use of dry HBr in DMSO only furnished 2a in 19%
yield (entry 6, Table 1). As a result, although HBr was regenerat-
ed at the end of the reaction (Scheme 1), upon addition of cat-
alytic PPh3·HBr, the product was obtained in only a poor yield
owing to the inefficiency of regenerated HBr reacting with
DMSO. We are also not sure about the role, if any, played by
Ph3PO in this proposed mechanistic cycle and further investi-
gations are ongoing to settle this.
To confirm Br2 as the active reagent formed in situ through
an oxidation–reduction cycle, we conducted control experi-
ments with 1-tetralone/6-methoxytetralone/7-methoxytetra-
lone and PPh3·HBr-DMSO separately under the standard reac-
tion conditions. We isolated only a’-monobrominated products
in high yields, thus confirming that Br2 is generated in situ (see
the Supporting Information).[11b]
Inspired by the above results and to further exploit the po-
tential of the PPh3·HBr-DMSO reagent system, we became in-
terested in investigating the scope and feasibility of these re-
agent systems with b-substituted enal derivatives. As indicated
in Table 3, electron-donating (entries 1–4, Table 3), electron-
neutral (entry 5, Table 3), and strong electron-withdrawing
(entry 6, Table 3) substituents on the aromatic ring, as well as
a heteroaromatic substituent (entry 7, Table 3) were well-toler-
ated, and produced the corresponding Z-a-bromoenal deriva-
tives with moderate to excellent yields (61–94%).[2b,12] Howev-
er, the presense of an alkyl group on the b-position did not
result in any a-bromoenal derivative, ostensibly owing to lack
of aromatic conjugation. The mechanism of the transformation
may involve an initial oxidative dibromination of the olefinic
double bond, followed by the displacement of the bromine
atom at the b-position by DMSO to form alkoxysulfonium in-
termediate, and finally elimination of the a hydrogen atom,
thus leading to dehydrobromination.[2b,13a] Or, the intermediate
bromonium derivative eliminates a proton from the a-carbon
atom to directly give the product.[13b] Synthesis of such aromat-
ic a-bromoenal derivatives generally involves two steps with
highly corrosive and toxic Br2, followed by base treatment. We
To determine if the corresponding a-bromoketone is an in-
termediate, 3a and 3b were prepared following the literature
procedure,[11a] and subjected to PPh3·HBr-DMSO reaction condi-
tions (Scheme 2). Corresponding a-ketothioesters 2g and 2n
were obtained in 61% and 63% yield, respectively, thus sug-
gesting that the transformation of a-ketothioesters 2a–z pro-
Scheme 2. Control experiments with a-bromo styryl ketones.
Chem. Eur. J. 2014, 20, 662 – 667
www.chemeurj.org
664
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
lyzed cyclization have been developed for their synthesis.[15]
On the other hand, cationic gold(III) species have been report-
ed as a powerful catalysts for the activation of alkynes toward
addition of a variety of nucleophiles.[16] We envisioned that the
highly activated 2-oxo-3-butynoic methylthioester might also
undergo a gold(III)-catalyzed cyclization and offer an easy
access to 3(2H)-furanones.
Table 3. PPh3·HBr-DMSO catalyzed synthesis of Z-a-bromoenal deriva-
tives.[a]
Entry
Ar
Product
t [h]
Yield[b][%]
Subsequently, when we treated 2z (0.15 mmol) with AuCl3
(2 mol%) and MeOH in CH2Cl2 at room temperature, the corre-
sponding 2-methylsulfanyl-3(2H)-furanone was isolated in 72%
yield (entry1, Table 4). The structure of 6a was unambiguously
established by single-crystal X-ray diffraction analysis
(Figure 2).[9]
1
2
3
4
5
6
7
4-OMe-C6H4
3,4-(OMe)2-C6H3
3-OMe,4-OBn-C6H3
4-Me-C6H4
C6H5
5a
5b
5c
5d
5e
5 f
6
11
20
12
12
21
6
94
85
74
82
81
68
61[c]
4-NO2-C6H4
2-furyl
5g
The mechanism of the reaction can be explained on the
basis of the formation of an activated alkyne–gold complex in-
termediate, followed by either a domino nucleophilic attack/
anti-endo-dig cyclization or the formation of cyclic oxonium
[a] Reactions were performed with 4a–g (1.0 equiv) and PPh3·HBr
(2.0 equiv) in dry DMSO (2 mL) under Ar atmosphere. [b] Yields of isolated
product. [c] Reaction was carried out at 70–758C.
envision that our one-step
PPh3·HBr-DMSO method will be
a viable alternative to the exist-
ing method. Another interesting
feature is the base-free reaction
conditions, thus suggesting new
opportunities for the synthesis
of base-sensitive and highly sub-
stituted compounds. More im-
portantly, the yields reported in
Table 3 are comparable with the
precedent results reported by
other research groups.[12,13a]
Figure 2. ORTEP diagram showing the molecular structure of 6a at the 30% probability level.
To demonstrate the potential
utility of the current g-substitut-
ed
b,g-unsaturated
a-keto-
methylthioester intermediate, we have shown the synthesis of
3(2H)-furanones under extremely mild conditions (Table 4).
3(2H)-Furanones are a key structural unit in medicines and bio-
logically active natural products. Their diverse arrays of phar-
macological significance includes antibiotic, anticancer, anti-
ulcer, and antiallergical activities.[14] Owing to their potential
applications, several methods including transition-metal-cata-
ion with subsequent nucleophilic attack, as described in the lit-
erature.[14b,16a] Similarly, when we used other alcohols, for ex-
ample, ethanol (entry 2, Table 4), isopropanol (entry 3, Table 4;
Figure 3),[9] benzyl alcohol (entry 4, Table 4), allyl alcohol
(entry 5, Table 4), and cinnamyl alcohol (entry 6, Table 4), the
respective 3(2H)-furanones (6b–f) were isolated in high yields.
Table 4. AuCl3-catalyzed synthesis of 2-methylsulfanyl-3(2H)-furanones.[a]
Entry
R
Product
t [h]
Yield[b][%]
1
2
3
4
5
6
Me
Et
6a
6b
6c
6d
6e
6 f
4
3
4
2
2
3
72
82
77
78
88
80
CH(CH3)2
CH2Ph
CH2-CH=CH2(E)
CH2-CH=CHPh(E)
[a] Reactions were performed with 2z (0.15 mmol), ROH (0.30 mmol),
AuCl3 (2 mol%) in CH2Cl2 (4 mL) at r.t. [b] Yields of isolated product.
Figure 3. ORTEP diagram showing the molecular structure of 6c at the 50%
probability level.
Chem. Eur. J. 2014, 20, 662 – 667
www.chemeurj.org
665
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
[3] T. Aida, T. Akasaka, N. Furukawa, S. Oae, Bull. Chem. Soc. Jpn. 1976, 49,
1117–1121.
In conclusion, we have successfully developed an efficient
chemoselective general route to g-substituted b,g-unsaturated
a-ketomethylthioesters from a,b-unsaturated ketones through
an unprecedented PPh3·HBr-DMSO mediated oxidative bromin-
ation followed by Kornblum oxidation in moderate to good
yields. We further demonstrate that the newly developed re-
agent system is equally useful for the synthesis of a-bromo-
enals from enals. Furthermore, AuCl3-catalyzed highly efficient
access to 3(2H)-furanones from 2-oxo-3-butynoic methyl-
thioester with different alcohols under mild reaction conditions
are described. We believe that it opens up a splendid opportu-
nity for exploiting g-substituted b,g-unsaturated a-ketothioest-
ers as versatile synthons in both metal- and organocatalyzed
asymmetric synthesis towards biologically active heterocycles.
[4] a) H. Saikachi, J. Matsuo, Chem. Pharm. Bull. 1969, 17, 1260–1263; b) N.
Furukawa, T. Akasaka, T. Aida, S. Oae, J. Chem. Soc. Perkin Trans. 1 1977,
372–374; c) M. B. Floyd, M. T. Du, P. F. Fabio, L. A. Jacob, B. D. Johnson,
J. Org. Chem. 1985, 50, 5022–5027; d) W.-M. Shu, Y. Yang, D.-X. Zhang,
L.-M. Wu, Y.-P. Zhu, G.-D. Yin, A.-X. Wu, Org. Lett. 2013, 15, 456–459.
[5] a) S. Kukolja, S. E. Draheim, J. L. Pfeil, R. D. G. Cooper, B. J. Graves, R. E.
Holmes, D. A. Neel, G. W. Huffman, J. A. Webber, J. Med. Chem. 1985, 28,
1886–1896; b) I. Degani, S. Dughera, R. Fochi, A. Gatti, Synthesis 1996,
467–469.
[6] a) I. Saikawa, S. Takano, JP. Pat. 44011128B, 1969; b) C.-T. Chen, S. Betti-
geri, S.-S. Weng, V. D. Pawar, Y.-H. Lin, C.-Y. Liu, W.-Z. Lee, J. Org. Chem.
2007, 72, 8175–8185.
[7] Reviews: a) K. V. V. Krishna Mohan, N. Nama, Synthesis 2012, 15–26;
ˇ
b) A. Podgorsek, M. Zupan, J. Iskra, Angew. Chem. 2009, 121, 8576–
8603; Angew. Chem. Int. Ed. 2009, 48, 8424–8450.
[8] The details will be reported in due course.
[9] 2g: C11H10O2S, M=206.25, monoclinic, P21/n, a=9.281(2), b=5.417(1),
c=21.152(4) ꢀ,
b=102.47(1)8,
V=1038.3(4) ꢀ3,
Z=4,
1cald =
1.319 gcmꢁ3, m=0.281 mmꢁ1, F(000)=432, l(MoKa)=0.71073 ꢀ, yellow
block, crystal size: 0.26ꢂ0.1ꢂ0.04 mm, 14222 reflections measured
(Rint =0.0511), 1551 unique reflections, wR(F2)=0.1367 for all data and
conventional R=0.0349 for 1320 F values with I>2s(I), (D/s)max =0.001,
Experimental Section
Representative procedure
(e/ꢀ3)=0.197,
PPh3·HBr (0.20 g, 0.58 mmol, 2.0 equiv) was placed in a 25 mL two-
neck round bottom flask under Ar with condenser. Dry DMSO
(2.0 mL) was added dropwise at room temperature. 1m (0.05 g,
0.29 mmol, 1.0 equiv) was introduced into the reaction mixture,
and the resulting mixture was stirred at 508C for 1.5 h. After com-
pletion of the reaction (TLC), saturated ammonium chloride solu-
tion was added, and the product was extracted with EtOAc. The
combined organic layers were dried over Na2SO4 and filtered, and
the filtrate was concentrated under reduced pressure to get a resi-
due. The crude residue was purified over silica gel (230–400 mesh)
flash column chromatography to obtain 2m (0.048 g, 71%);
eluent, EtOAc/hexane (20%); yellow amorphous solid; m.p. 1508C;
1H NMR (600 MHz, CDCl3): d=7.87–7.92 (m, 3H), 7.73 (d, J=7.2 Hz,
1H), 7.57 (t, J=7.8 Hz, 1H), 7.47 (d, J=16.2 Hz, 1H), 2.42 ppm (s,
3H); 13C NMR (150 MHz, CDCl3): d=192.7, 182.4, 145.6, 135.4,
134.3, 132.6, 132.3, 130.0, 119.9, 117.9, 113.7, 11.5 ppm; IR (KBr): n˜ =
2230, 1677, 1671, 1605 cmꢁ1; HRMS (EI): m/z calcd for C12H9NO2S:
231.0354 [M]+; found: 231.0359.
S=1.116 for all data and 129 parameters, D1max min
,
ꢁ0.165; 6a: C12H12O3S, M=236.28, monoclinic, P21/n, a=7.332(2), b=
9.937(2), c=16.090(3 ꢀ, b=100.96(3)8, V=1150.9(4) ꢀ3, Z=4, 1cald
=
1.364 gcmꢁ3, m=0.269 mmꢁ1, F(000)=496, l(MoKa)=0.71073 ꢀ, color-
less block, crystal size: 0.23ꢂ0.23ꢂ0.13 mm, 2841 reflections measured
(Rint =0.087), 1871 unique reflections, wR(F2)=0.1620 for all data and
conventional R=0.0437 for 682 F values with I>2s(I), S=0.635 for all
data and 147 parameters, D1max min
C14H16O3S, M=264.33, monoclinic, P21/c, a=11.979(5), b=10.808(5), c=
11.992(5 ꢀ, b=115.946(8)8, V=1396.1(11) ꢀ3, Z=4, 1cald =1.258 gcmꢁ3
,
(e/ꢀ3)=0.208, ꢁ0.220; 6c:
,
m=0.229 mmꢁ1, F(000)=560, l(MoKa)=0.71073 ꢀ, colorless block, crys-
tal size: 0.23ꢂ0.21ꢂ0.2 mm, 11382 reflections measured (Rint =0.0374),
2919 unique reflections, wR(F2)=0.2177 for all data and conventional
R=0.0736 for 2544 F values with I>2s(I), (D/s)max =0.000, S=1.281 for
all data and 166 parameters, D1max,min (e/ꢀ3)=0.552, ꢁ0.814.
CCDC 960814 (2g), 960815 (6a), and 967757 (6c) contains the supple-
mentary crystallographic data for this paper. These data can be ob-
tained free of charge from the Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif; for more details see the Sup-
porting Information.
[10] a) Z. Wan, C. D. Jones, D. Mitchell, J. Y. Pu, T. Y. Zhang, J. Org. Chem.
2006, 71, 826–828; b) For detection of Ph3PO in the reaction mixture,
see the Supporting Information.
[11] a) K. S. Babu, X.-C. Li, M. R. Jacob, Q. Zhang, S. I. Khan, D. Ferreira, A. M.
Clark, J. Med. Chem. 2006, 49, 7877–7886; b) M. Voets, A. Antes, C.
Scherer, U. Mꢃller-Vieira, K. Biemel, S. Marchais-Oberwinkler, R. W. Hart-
mann, J. Med. Chem. 2006, 49, 2222–2231.
[12] Exclusive formation of Z-a-bromoenals was confirmed by NMR experi-
ments and comparison with literature NMR values; see: a) A. V. Shastin,
A. L. Reznichenko, O. N. Lenkova, E. S. Balenkova, V. G. Nenaidenko,
Russ. Chem. Bull. 2005, 54, 1733–1736; b) I. G. Collado, R. H. Galan,
G. M. Massanet, M. S. Alonso, Tetrahedron 1994, 50, 6433–6440; c) F.
Wille, F. Knorr, Chem. Ber. 1952, 85, 841–851.
[13] a) W. Li, J. Li, Z.-K. Wan, J. Wu, W. Massefski, Org. Lett. 2007, 9, 4607–
4610; b) One of the reviewers suggested another plausible mechanism
for the formation of a-bromoenal. After initial oxidative dibromination
of the olefinic double bond, instead of DMSO, Me2S might act as an S
nucleophile to substitute Br in the more active benzylic position; finally,
elimination of the a hydrogen atom and Me2S would lead to a-bro-
moenal.
Acknowledgements
I.D. thanks CSIR-IICB (Start-up grant), CSIR-New Delhi (Network
Project ORIGIN-CSC0108) for financial support, and Drs. Rama-
lingam Natarajan, Basudeb Achari, and Anup Bhattacharjya for
valuable discussions. K. M. thanks CSIR, India for a fellowship
and P.R.M. for an emeritus scientistship. A.S. thanks NIPER-Kol-
kata for a fellowship. We thank the reviewers for their valuable
comments and suggestions, which helped to significantly im-
prove the quality of the manuscript.
Keywords: chemoselectivity · cyclization · gold · oxidative
bromination · triphenylphosphine hydrobromide
[1] a) A. J. Mancuso, D. Swern, Synthesis 1981, 165–185; b) V. Y. Kukushkin,
Coord. Chem. Rev. 1995, 139, 375–407; c) A. M. Khenkin, R. Neumann, J.
Am. Chem. Soc. 2002, 124, 4198–4199.
[2] a) N. Kornblum, J. W. Powers, G. J. Anderson, W. J. Jones, H. O. Larson,
O. Levand, W. M. Weaver, J. Am. Chem. Soc. 1957, 79, 6562–6562; b) W.
Li, J. Li, M. Lin, S. Wacharasindhu, K. Tabei, T. S. Mansour, J. Org. Chem.
2007, 72, 6016–6021.
[14] a) A. G. Mal’kina, O. G. Volostnykh, K. B. Petrushenko, O. A. Shemyakina,
V. V. Nosyreva, I. A. Ushakov, B. A. Trofimov, Tetrahedron 2013, 69, 3714–
3720; b) Y. Liu, M. Liu, S. Guo, H. Tu, Y, Zhou, H. Gao, Org. Lett. 2006, 8,
3445–3448; c) P. G. Steel, Chem. Commun. 1999, 2257–2258.
[15] a) T. Kusakabe, T. Takahashi, R. Shen, A. Ikeda, Y. D. Dhage, Y. Kanno, Y.
Inouye, H. Sasai, T. Mochida, K. Kato, Angew. Chem. 2013, 125, 7999–
8003; Angew. Chem. Int. Ed. 2013, 52, 7845–7849; b) J. John, H. Hopf,
Chem. Eur. J. 2014, 20, 662 – 667
www.chemeurj.org
666
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
Eur. J. Org. Chem. 2013, 841–845; c) Y. Wei, S. Lin, H. Xue, F. Liang, B.
Zhao, Org. Lett. 2012, 14, 712–715; d) Y. Wei, S. Lin, J. Zhang, Z. Niu, Q.
Fu, F. Liang, Chem. Commun. 2011, 47, 12394–12396.
2462; c) A. Arcadi, Chem. Rev. 2008, 108, 3266–3325; d) A. S. K. Hashmi,
M. Rudolph, Chem. Soc. Rev. 2008, 37, 1766–1775.
[16] a) W. Wang, G. B. Hammond, B. Xu, J. Am. Chem. Soc. 2012, 134, 5697–
5705; b) M. Rudolph, A. S. K. Hashmi, Chem. Soc. Rev. 2012, 41, 2448–
Received: September 25, 2013
Revised: October 28, 2013
Published online on December 11, 2013
Chem. Eur. J. 2014, 20, 662 – 667
www.chemeurj.org
667
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim