Facile approach for C(sp3)-H bond thioetherification of isochroman

Article abstract of DOI:10.1055/s-0034-1380125

An unprecedented C-S formation protocol via the direct oxidative C(sp³)-H bond thioesterification of isochroman under metal-free conditions was developed. A series of isochroman derivatives could be afforded efficiently by the green, simple, and atom-economical method.

Full text of DOI:10.1055/s-0034-1380125

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 915–920
letter
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J. Feng et al.
Letter
Synlett
Facile Approach for C(sp3)–H Bond Thioetherification of Isochro-
man
Jie Feng
R1
R1
R2
Guoping Lu
Meifang Lv
Chun Cai*
120 °C, 6 h
S
H
• simple
+
O
O
• atom-economic
• green oxidant
• metal-, base-free
DTBP
S
H
R2
Chemical Engineering College, Nanjing University of Science &
Technology, 200 Xiaolingwei, Nanjing 210094, P. R. of China
c.cai@mail.njust.edu.cn
Received: 22.11.2014
Accepted after revision: 05.01.2015
Published online: 10.02.2015
achievements in this area mainly include C(sp3)–H bond
functionalization of cycloalkanes or benzylic C(sp3)–H
bonds,4 C(sp3)–H bond functionalization with the assis-
tance of a chelating group,5 and the functionalization of
C(sp3)–H bond adjacent to heteroatoms.6
Herein, we are primarily interested in investigating the
activation of C(sp3)–H bond of benzyl ethers such as iso-
chroman. Isochroman derivatives usually exhibit various
potential pharmaceutical activities7 and may serve as im-
portant building blocks in synthetic chemistry.8 As the ben-
zyl C–H bond adjacent to oxygen atom, direct C–H bond ad-
jacent to oxygen atom and benzyl C–H bond exist simulta-
neously in the isochroman ring, it is interesting and
challenging for researching selective C(sp3)–H bond func-
tionalization of isochroman.
DOI: 10.1055/s-0034-1380125; Art ID: st-2014-w0962-l
Abstract An unprecedented C–S formation protocol via the direct oxi-
dative C(sp3)–H bond thioesterification of isochroman under metal-free
conditions was developed. A series of isochroman derivatives could be
afforded efficiently by the green, simple, and atom-economical meth-
od.
Key words C–S coupling, thioetherification, peroxides, dehydrogena-
tion, isochroman
The direct C–H functionalization path is now being ex-
tensively investigated because of its atom economics and
the environmental sustainability.1 One such strategy, cross-
dehydrogenative coupling, the CDC protocol, is of immense
importance as it has been successfully employed to access a
diverse array of C–C and C–heteroatom bonds, by function-
alizing C–H bonds of all types (sp, sp2, sp3).2 Among all
types C–H bonds activation paths via CDC, the functional-
izations of inert C(sp3)–H bond have received special re-
search attention.3 In the past few years, the breakthrough
Screening of reference revealed that studies on the met-
al-catalyzed or noncatalytic C–C bond formations at the
C(1) position of isochroman via C(sp3)–H bond activation
have been widely reported (Scheme 1).9 However, fewer re-
ports deal with the CDC-mediated carbon–heteratom bond
formation, especially C–S bond formation.10
metal complex,
oxidants
HXR
+
O
O
or
organic oxidants
XR
previous work
X = C, N
DTBP
+
HSR
O
R
O
this work
S
Scheme 1 Thioetherification of isochromans
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 915–920

916
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Sulfur-containing compounds represent a class of im-
portant synthetic intermediates and excellent building
blocks for chemical biology.11 Traditional C–S bond-forma-
tion protocols, whether organocatalytic C–S bond forming12
or transition-metal-catalyzed C–S bond formation,13 usual-
ly need prefunctionalization of the substrate which means
more chemical wastes and less atom economy. Gratefully,
the emergence of the CDC method provides an alternative
method to synthesize thioether compounds. Recently, C–S
formation of disulfide and symmetric aliphatic ether has al-
ready been achieved with DTBP as oxidant.14 In particular,
the reactions under metal-free conditions are more appre-
ciable in the sulfur-containing pharmaceutical synthesis.
Encouraged by that, we report here the straightforward
and convenient CDC protocol for the syntheses of thioethers
through the direct oxidative cross-couplings of isochroman
with thiophenol (thiol) in the absence of metal catalysts.
The initial choice of reaction conditions was focused on
using isochroman and 4-chlorobenzenethiol as substrates
with DTBP as an oxidant. The desired product was observed
with the mentioned reagents stirred at 100 °C. Inspired by
this result, we examined other oxidants in a quest to im-
prove the yield. Among all other oxidant candidates, such as
TBHP (5–6 M in decane), K2S2O8, TBP, and BPO, DTBP was
found to be the most effective oxidant (Table 1, entries 1–
5). Further checking the oxidants equivalent revealed that
adding more oxidants was conductive to improve the yield
(Table 1, entry 6), but when three or more equivalents of
DTBP were added, the yield dropped in adverse (Table 1, en-
try 7). Next, we screened the reaction temperature. To our
delight, the product yield could further be improved when
the reaction was heated up to 120 °C. Under this tempera-
ture, the coupling reacted efficiently (within 6 h). Extension
of reaction time may lead to more nasty byproducts (Table
1, entry 9). It was encouraging that the C–S coupling
showed excellent selectivity throughout these conditions.
There is a slight decrease of the selectivity when conduct-
ing the reaction in a higher temperature (Table 1, entry 10).
Furthermore, it is worth to note that the air conditions do
not show significant inhibition to the reaction, but when
the reaction was performed under O2 atmosphere, the low-
er yield was obtained with more isochroman-1-one formed.
Table 1 Screening for Optimal Conditionsa
R
S
DTBP
(1.5 equiv)
Cl
S
R
O
R
+
+
+
O
O
120 °C
6 h
SH
O
S
3a
3a'
R = ClC6H4
3a''
Entry
Oxidants (equiv)
Time (h)
Temp (°C)
Yield of 3a/3a′/3a′′b
1
2
DTBPc (1.5)
DTBP (1)
6
6
120
100
100
100
100
100
100
110
120
130
120
120
81/0/1
33/0/0
0/0/0
3
K2S2O8 (1)
TBHPd (1)
BPOe (1)
6
4
6
25/0/0
3/0/0
5
6
6
DTBP (2)
6
66/0/0
59/1/1
72/0/1
56/2/3
68/3/4
78/1/1 (3)h
43/1/1 (23)h
7
DTBP (3)
6
8
DTBP (1.5)
DTBP (1.5)
DTBP (1.5)
DTBP (1.5)
DTBP (1.5)
6
9
24
6
10
11f
12g
6
6
a Reaction conditions: 4-chlorobenzenethiol (1.5 mmol), isochroman (1 mmol), DTBP (1.5 mmol), 120 °C, 6 h.
b The yield was determined by 1H NMR of crude products.
c DTBP = di-tert-butyl peroxide.
d TBHP = tert-butyl hydroperoxide.
e BPO = benzoyl peroxide.
f The reaction was conducted in the air.
g The reaction was conducted in oxygen atomosphere.
h The yield of 3,4-dihydronaphthalen-1(2H)-one.
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Having established the standard reaction conditions,
the oxidative thioetherification was then implemented on
cross-couplings between isochroman and substituted thio-
phenols.16 As can be seen in Table 2, the present methodol-
ogy was applicable to diverse thiophenols (Table 2, entries
1–6, 8, and 11). Comparatively, the electron-withdrawing
substrates showed higher yields than the electron-donating
ones, especially when 4-(tert-butyl)thiophenol was used,
more disulfide was obtained instead of the thioether (Table
2, entry 5). ortho-Substituted thiophenol gave an inferior
product yield to that of para- or meta-substituted thiophe-
nols (Table 2, entries 2, 6, and 8) due to the steric effect. In
case of 4-bromothiophenol, the C–Br bond cleavage prefer-
entially occurred with a mixture of aryl thioether obtained.
This protocol was also applied to heterocyclic thiophe-
nol {benzo[d]thiazole-2-thiol}. Interestingly, an open-ring
process occurred during the CDC protocol with the unex-
pected product 2-{2-[(benzo[d]thiazol-2-ylthio)meth-
yl]phenyl}acetaldehyde obtained in good yields instead of
the aimed C–S coupling products (Table 2, entry 17). Next,
we checked alkyl thiols. Along with the aimed products, a
collection of byproducts (the C–H activation adjacent to the
sulfur atom could also occur) was also formed which can
hardly be separated with the main products (Table 2, en-
tries 10 and 12). Finally, open-chain benzyl ethers were
investigated. Like isochroman, benzyl ethers, such as benzyl
methyl ether, afforded the corresponding coupling products
in good yields (Table 2, entries 13 and 14). But the coupling
between benzyl methyl ether and 4-fluorobenzenethiol is
an exception with ‘dithiother’ 3p′ obtained.
To demonstrate the general applicability of this method,
cyclic benzylic ethers bearing similar isochroman structure,
such as 1,3-dihydroisobenzofuran, isochroman-4-one were
then checked respectively. Moderate yield of the thioether
3r (Table 3, entry 1) could be obtained under the standard
conditions. Interestingly, small amount of the open-ring
product 3s (Table 3, entry 1) was also produced. Adding
more DTBP and extending the reaction time could lead to
more product 3s (Table 3, entry 2). Notably, this method
may have potential usage in total synthesis15 (provide alter-
native access to the unique ortho-bifunctionalized struc-
ture). Like isochroman, isochroman-4-one could also fur-
nish this C–S coupling, but the presence of the carbonyl
group put a negative effect on the product yield with the
thioether 3t (Table 3, entry 5) formed in the yield of 30%.
Moreover, we tried some other ethers which do not contain
a benzylic structure. Dioxane, tetrahydrofuran, and tetrahy-
dro-2H-pyran could couple with thiophenol smoothly, but
the linear ethers (diethyl ether) gave low yields. Also the
rigid 2,3-dihydrobenzo[1,4]dioxine showed less reactivity
even with extension of the reaction time.
Table 2 Scope of the Oxidative C–S Formationa
R1
R1
DTBP
R2SH
+
O
S
O
neat, 120 °C
R2
Entry Product
Yield (%)b
1
2
3
4
5
6
7
8
9
R = 4-Cl
R = 4-Me
R = 4-F
3a
3b
3c
77
75
80
68
O
R = 4-OMe 3d
R = 4-t-Bu
R = 2-Me
R = 2-Cl
R = 3-Me
R = 4-Br
3e
3f
3g
3h
3i
4c (80d)
16c (76d)
trace
78
S
R
0 (56e)
O
O
10
3j
30c
S
S
11
12
3k
3l
70
35c
O
O
S
S
Ph
13
3m
80
Cl
R
F
OMe
OMe
14
15
R = 4-Me
R = 4-Cl
3n
3o
81
84
S
S
16
3p
0
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Table 2 (continued)
Entry Product
Therefore the present coupling may follow the radical
mechanism. Also we conducted the reaction with 4-chloro-
benzenethiol and cyclohexane under the standard condi-
tions which indicated that unactivated C–H bond cleavage
Yield (%)b
F
F
S
Table 3 Oxidative C–S Formation of Cyclic Ethersa
3p′
52
S
SH
+
O
R
O
Cl
S
O
3q
0
S
Product and yield (%)b
S
Entry
Substrates
Conditions
N
H
17
O
O
S
R
3r 48%
3q′
75
S
DTBP (1.5 equiv),
120 °C, 6 h
1
O
R
S
N
S
a Reaction conditions: thiophenol or thiol (1.5 mmol), isochroman or benzyl-
ic ether (1 mmol), DTBP (1.5 mmol), 120 °C, 6 h.
b Isolated yield.
S
R
O
c The yield of was determined by GC–MS as the difficulty in separation.
d The yield of disulfide.
3s 3%
e Total yield of aryl thioether mixture.
R
S
DTBP (3 equiv), 120
°C, 16 h
S
R
2
To further investigate the details of the mechanism for
this convenient oxidative thioesterification of isochroman
with thiophenol or thiols, a series of controlled experi-
ments was carried out (Scheme 2).
O
3s 23%
O
O
DTBP
DTBP (1.5 equiv),
120 °C, 6 h
3
4
O
(a)
(b)
(c)
RSSR
88%
RSH
R = 4-ClC6H4
neat, 120 °C
O
S
R
30%c
DTBP
neat
RSH
+
O
O
S
S
36%
O
O
3m
SR
R
DTBP (3 equiv), 120
°C, 24 h
6 h, 120 °C
DTBP
trace
RSSR
+
O
O
O
neat
6 h,120 °C
O
O
O
R
S
DTBP (1.5 equiv),
120 °C, 6 h
42%
3a
5
6
R
O
3t 85%
DTBP
TEMPO (10 equiv)
(d)
RSH
+
O
R
O
S
S
neat, 120 °C
DTBP (1.5 equiv),
120 °C, 6 h
R
R
O
S
3a 0%
3u 77%
Scheme 2 Controlled experiments for the CDC C–S coupling
O
DTBP (1.5 equiv),
120 °C, 6 h
7
8
O
In the presence of DTBP, thiophenols could easily con-
vert into disulfide, but the disulfide could also couple with
isochroman in spite of the lower reactivity (Scheme 2, line
c). As similar CDC protocols commonly involve radical
mechanisms, excess TEMPO was then added as a radical in-
hibitor. As expected, no desired product was observed.
3v 70%
3w 5%c
DTBP (1.5 equiv),
120 °C, 6 h
Et2O
a R = ClC6H4.
b Isolated yield.
c by GC–MS.
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(t-BuO)2
t-BuO•
3a
RSSR
RSH
(t-BuO)2
t-BuO•
RSSR
RS•
path c
RS•
(t-BuO)2
t-BuO•
O+
O
O
O
t-BuOH
•
R
t-BuO•
t-BuOH
B
S
A
S
H
R
path a
RSSR
RS•
path b
3a
Scheme 3 Proposed mechanism for the for the CDC C–S coupling
could occur to form a cyclohexane radical which was cap-
tured by the disulfide or thiophenol. However, the reactivi-
ty showed the significant difference between benzylic
ethers and unbenzylic ethers, and almost all the substrates
tested showed excellent C(1) selectivity between the C–H
bonds at different positions of isochroman. It can be con-
cluded that the intermediate A (Scheme 3) owns higher re-
activity than other potential radical intermediate.
Based on the above experiments and reported litera-
tures, the plausible reaction mechanism is shown in
Scheme 3. DTBP decomposed into the tert-butoxyl radical
at first under heated conditions. Hydrogen abstraction of
the C–H bond adjacent to an oxygen atom produced inter-
mediate A. After that, intermediate A was further oxidized
to intermediate B. Thiol coupled with intermediate B,
thereafter gave the desired product. Alternatively, the radi-
cal intermediate A may directly react with disulfide to give
the product 3a and release thiyl radical. Of course, it is also
possible two radicals (intermediate A and thiyl radical)
quenched to form the desired product. Considering that
thiophenol showed higher yield than disulfide in compara-
ble time, path a was preferred.
2011, 111, 1293. (c) Campbell, A. N.; Stahl, S. S. Acc. Chem. Res.
2012, 45, 851. (d) Kozhushkov, S. I.; Ackermann, L. Chem. Sci.
2013, 4, 886.
(2) For selected reviews on C(sp)–H or C(sp2)–H bond functional-
ization via CDC protocols, see: (a) Yeung, C. S.; Dong, V. M.
Chem. Rev. 2011, 111, 1215. (b) Shi, W.; Liu, C.; Lei, A.-W. Chem.
Soc. Rev. 2011, 40, 2761. (c) Engle, K. M.; Mei, T. S.; Wasa, M.; Yu,
J.-Q. Acc. Chem. Res. 2012, 45, 788. (d) Wu, Y. N.; Wang, J.; Mao,
F.; Kwong, F. Y. Chem. Asian J. 2014, 9, 26.
(3) For selected reviews on C(sp3)–H bond functionalization involv-
ing CDC protocols, see: (a) McMurray, L.; Hara, F. O.; Gaunt, M.
Chem. Soc. Rev. 2011, 40, 1885. (b) Uyanik, M.; Ishihara, K.
ChemCatChem 2012, 4, 177. (c) Roizen, J. L.; Harvey, M. E.;
Du Bois, J. Acc. Chem. Res. 2012, 45, 911. (d) Girard, S. A.;
Knauber, T.; Li, C.-J. Angew. Chem. Int. Ed. 2014, 53, 74. (e) Guo,
X.-W.; Li, Z.-P.; Li, C.-J. Prog. Chem. 2010, 22, 1434.
(4) For selected references, see: (a) Guo, X. Y.; Li, C.-J. Org. Lett.
2011, 13, 4977. (b) Antonchick, A. P.; Burgmann, L. Angew.
Chem. Int. Ed. 2013, 52, 3267. (c) Hoshikawa, T.; Inoue, M. Chem.
Sci. 2013, 4, 3118. (d) Li, Z. J.; Zhang, Y.; Zhang, L. Z.; Liu, Z. Q.
Org. Lett. 2014, 16, 382. (e) Zhu, Y. F.; Wei, Y. Y. Chem. Sci. 2014,
5, 2379. (f) Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem.
Soc. 2012, 134, 2547. (g) Tran, B. L.; Li, B. J.; Driess, M.; Hartwig,
J. F. J. Am. Chem. Soc. 2014, 136, 2555. (h) Du, B.-G.; Jin, B.; Sun,
P.-P. Org. Lett. 2014, 16, 3032. (i) Li, Z.; Cao, L.; Li, C.-J. Angew.
Chem. Int. Ed. 2007, 46, 6505. (j) Wan, M.; Meng, Z.; Lou, H.; Liu,
L. Angew. Chem. Int. Ed. 2014, 53, 13845. (k) Chen, W.; Xie, Z.;
Zheng, H.; Lou, H.; Liu, L. Org. Lett. 2014, 16, 5988.
(5) For selected references, see: (a) Lou, S.-J.; Xu, D.-Q.; Shen, D.-F.;
Wang, Y.-F.; Liu, Y.-K.; Xu, Z.-Y. Chem. Commun. 2012, 48, 11993.
(b) Nakao, Y.; Morita, E.; Idei, H.; Hiyama, T. J. Am. Chem. Soc.
2011, 133, 3264. (c) Neufeldtand, S. R.; Sanford, M. S. Acc. Chem.
Res. 2012, 45, 936. (d) Majji, G.; Guin, S.; Gogoi, A.; Rout, S. K.;
Patel, B. K. Chem.Commun. 2013, 49, 3031. (e) Wu, Y.; Choy, P.
Y.; Mao, F.; Kwong, F. Y. Chem. Commun. 2013, 49, 689.
(f) Priebbenow, D. L.; Bolm, C. Org. Lett. 2014, 16, 1650.
In summary, an unprecedented C–S formation based on
the direct oxidative cross-couplings of isochroman deriva-
tives with thiophenol or thiols in the absence of a transition
metal has been developed. The major advantages of this
method include the use of DTBP as the green oxidant with-
out utilizing any other additives added, thus this simple and
atom-economic route can be conducted in an environment-
friendly way.
(6) For selected examples, see: (a) Conejero, S.; Paneque, M.;
Poveda, M. L.; Santos, L. L.; Carmona, E. Acc. Chem. Res. 2010, 43,
572. (b) Cheng, K.; Huang, L. H.; Zhang, Y. H. Org. Lett. 2009, 11,
2908. (c) Liu, X.; Sun, B.; Xie, Z.; Qin, X.; Liu, L.; Lou, H. X. J. Org.
Chem. 2013, 78, 3104. (d) Pan, S.; Liu, J.; Li, H.; Wang, Z.; Guo, X.;
Li, Z. Org. Lett. 2010, 12, 1932. (e) Xie, Z.; Cai, Y.; Hu, H.; Lin, C.;
References and Notes
(1) For selected reviews or books on transition-metal-catalyzed C–
H functionalization, see: (a) Yu, J.-Q.; Shi, Z.-J. C-H Activation;
Springer: Berlin, 2010. (b) Sun, C. L.; Li, B. J.; Shi, Z.-J. Chem. Rev.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 915–920

920
J. Feng et al.
Letter
Synlett
Jiang, J.; Chen, Z.; Wang, L.; Pan, Y. Org. Lett. 2013, 15, 4600.
(f) Liu, D.; Liu, C.; Li, H.; Lei, A.-W. Angew. Chem. Int. Ed. 2013,
52, 4453.
(c) Kondo, T.; Mitsudo, T. Chem. Rev. 2000, 100, 3205.
(d) Magens, S.; Plietker, B. Chem. Eur. J. 2011, 17, 8807.
(e) Limura, S.; Manabe, K.; Kobayashi, S. Chem. Commun. 2002,
94.
(7) (a) Martin, P.; Consroe, P. Science 1976, 194, 965. (b) de Groot,
M. J.; Alex, A. A.; Jones, B. C. J. Med. Chem. 2002, 45, 1983.
(c) Yamaori, S.; Kushihara, M.; Yamamoto, I.; Watanabe, K. Bio-
chem. Pharmacol. 2010, 79, 1691.
(8) For selected references, see: (a) Lehmann, F.; Pettersen, A.;
Currier, E. A.; Sherbukhin, V.; Olsson, R.; Hacksell, U.;
Luthman, K. J. Med. Chem. 2006, 49, 2232. (b) Maier, C. A.;
Wünsch, B. J. Med. Chem. 2002, 45, 438.
(9) For selected C–C bond formations at the C(1) position of iso-
chroman examples, see: (a) Li, Z.; Yu, R.; Li, H. Angew. Chem. Int.
Ed. 2008, 47, 7497. (b) Song, C.-X.; Cai, G.-X.; Farrell, T. R.; Jiang,
Z.-P.; Li, H.; Gan, L.-B.; Shi, Z.-J. Chem. Commun. 2009, 6002.
(c) Richter, H.; Rohlmann, R.; Mancheño, O. G. Chem. Eur. J.
2011, 17, 11622. (d) Pinter, A.; Klussmann, M. Adv. Synth. Catal.
2012, 354, 701. (e) Liu, X.; Sun, B.; Xie, Z.; Qin, X.; Liu, L.; Lou, H.
J. Org. Chem. 2013, 78, 3104. (f) Meng, Z.; Sun, S.; Yuan, H.; Lou,
H.; Liu, L. Angew. Chem. Int. Ed. 2014, 53, 543. (g) Park, S. J.;
Price, J. R.; Todd, M. H. J. Org. Chem. 2012, 77, 949.
(h) Muramatsu, W.; Nakano, K.; Li, C.-J. Org. Lett. 2013, 15, 3650.
(i) Qvortrup, K.; Rankic, D. A.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2014, 136, 626.
(12) Chauhan, P.; Mahajan, S.; Enders, D. Chem. Rev. 2014, 114, 8807.
(13) Beletskaya, I. P.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596.
(14) Guo, S.-R.; Yuan, Y.-Q.; Xiang, J.-N. Org. Lett. 2013, 15, 4654.
(15) Borovička, M.; Kvis, F.; Chromík, J.; Protiva, M. Collect. Czech.
Chem. Commun. 1967, 32, 1738.
(16) General Procedure for the Oxidative C–S Formation
A sealed tube was charged with isochroman (or benzylic ether;
1 mmol), DTBP (1.5 mmol), thiol (or thiophenol; 1.5 mmol). The
reaction mixture was stirred at 120 °C for 6 h. The reaction
mixture was then cooled to obtain a brown liquid. The organic
solutions could be purified directly by column chromatography
on silica gel to give the pure product (hexane–EtOAc, 20:1).
1-[(4-Chlorophenyl)thio]isochromane 3a
Colorless oil; yield: 212 mg (77%). 1H NMR (500 MHz, CDCl3):
δ = 7.56 (d, J = 8.3 Hz, 2 H), 7.40–7.30 (m, 3 H), 7.28–7.21 (m, 2
H), 7.20–7.11 (m, 1 H), 6.49 (s, 1 H), 4.55 (td, J = 11.5, 3.3 Hz, 1
H), 4.03 (dd, J = 11.3, 6.2 Hz, 1 H), 3.20–3.09 (m, 1 H), 2.72 (dd, J
= 16.5, 2.4 Hz, 1 H). 13C NMR (126 MHz, CDCl3): δ = 133.56,
132.90, 132.48, 132.27, 131.64, 128.06, 127.89, 126.93, 126.13,
125.16, 85.06, 76.39, 76.14, 75.89, 57.36, 26.75. Anal. Calcd for
(10) (a) Muramatsu, W.; Nakano, K. Org. Lett. 2014, 16, 2042.
(b) Chen, D.; Pan, F.; Gao, J.; Yang, J. Synlett 2013, 24, 2085.
(11) For selected references, see: (a) Marcincal-Lefebvre, A.;
Gesquiere, J. C.; Lemer, C. J. Med. Chem. 1981, 24, 889. (b) Ley, S.
V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003, 42, 5400.
C
15H13ClOS: C, 65.09; H, 4.73. Found: C, 64.88; H, 4.64. ESI-MS:
m/z = 276.
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