Copper(II) Acetate-Catalyzed Hydroxysulfenylation-Initiated Lactonization of Unsaturated Carboxylic Acids with Oxygen as Oxidant and Oxygenation Reagent

Article abstract of DOI:10.1002/adsc.201700036

A copper(II) acetate-catalyzed aerobic thiolation of C=C double bonds, oxygenation, and intramolecular cyclization reactions of unsaturated carboxylic acids with thiols has been explored. The reaction proceeds through a new hydroxysulfenylation-initiated lactonization pathway with carboxyl as electrophilic group, which provides an efficient access to assembly highly valuable thio-substituted lactone derivatives with good yields under mild conditions. Several control experiments, as well as an isotope labelling experiment disclose that oxygen acts as both oxidant and reactant being transferred into the final product. The mechanistic studies support the discovery of a new strategy through difunctionalization of alkenes based on unsaturated carboxylic acids to construct the diversely substituted lactones. (Figure presented.).

Full text of DOI:10.1002/adsc.201700036

FULL PAPERS
DOI: 10.1002/adsc.201700036
Copper(II) Acetate-Catalyzed Hydroxysulfenylation-Initiated
Lactonization of Unsaturated Carboxylic Acids with Oxygen as
Oxidant and Oxygenation Reagent
a
a
a,b
a,b,
a,b
Bingnan Du, Yang Wang, Haibo Mei, Jianlin Han, * and Yi Pan
a
School of Chemistry and Chemical Engineering, State Key Laboratory of Coordination Chemistry, Nanjing University,
Nanjing 210093, Peopleꢀs Republic of China
E-mail: hanjl@nju.edu.cn
b
MaAnShan High-Tech Research Institute of Nanjing University, MaAnShan 238200, Peopleꢀs Republic of China
Received: January 12, 2017; Revised: February 23, 2017; Published online: && &&, 0000
Supporting information for this article can be found under http://dx.doi.org/10.1002/adsc.201700036.
Abstract: A copper(II) acetate-catalyzed aerobic thi- ling experiment disclose that oxygen acts as both oxi-
olation of C=C double bonds, oxygenation, and in- dant and reactant being transferred into the final
tramolecular cyclization reactions of unsaturated car- product. The mechanistic studies support the discov-
boxylic acids with thiols has been explored. The re- ery of a new strategy through difunctionalization of
action proceeds through a new hydroxysulfenylation- alkenes based on unsaturated carboxylic acids to
initiated lactonization pathway with carboxyl as elec- construct the diversely substituted lactones.
trophilic group, which provides an efficient access to
assembly highly valuable thio-substituted lactone de- Keywords: aerobic oxidation; copper catalysis; hy-
rivatives with good yields under mild conditions. Sev- droxysulfenylation; lactonization; unsaturated car-
eral control experiments, as well as an isotope label- boxylic acids
Introduction
as Nifuratel (Figure 1, C), showing a broad antibacte-
[4]
rial spectrum of action. Consequently, the synthesis
g-Lactones represent the most prolific class of O-het- of thio-substituted g-lactones has received some at-
eroaromatic compounds in organic chemistry. Particu- tention in the past, but still remains largely underde-
[
5]
larly, functionalized lactones are prevalent structural veloped.
[
1]
motifs, being found in many bioactive compounds
Unsaturated carboxylic acids represent attractive
[
2]
and natural products. More specifically, thio-substi- intermediates, which could serve to construct substi-
tuted g-lactones have been demonstrated to show an- tuted lactone derivatives by functionalization of the
tiviral activity against poliovirus, RNA virus and C=C double bond and an intramolecular cyclization
herpes simplex virus type 1 (HSV-1) (Figure 1, A and reaction. In recent years, several strategies based on
[
3]
B). Also, this structure unit exists in the drugs, such unsaturated carboxylic acids have been explored to
construct modified lactones (Scheme 1a). One way is
that the nucleophilic carboxyl group attacks the
cation or onium cation intermediates, generated from
the addition of halogen, trifluoromethyl or trifluoro-
[
6]
methylthio to the C=C double bond. The other way
is that the carboxyl group attacks the intermediates
[
7]
from radical SET (single electron transfer) or reduc-
tive elimination from the redox-active metal com-
[
8]
plex. These previously reported reactions usually
were triggered by the functionalization of the C=C
double bond, and used carboxyl groups as nucleophil-
ic reagents. However, the difunctionalization of a C=
Figure 1. Examples of biologically active thio-substituted g- C double bond-initiated lactonization of unsaturated
lactones.
carboxylic acids still remained unexplored.
Adv. Synth. Catal. 0000, 000, 0 – 0
1
ꢁ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Table 1. Optimization of the reaction conditions for the Cu-
[a]
catalyzed hydroxysulfenylation.
[b]
Entry
Atmosphere
Time [h]
Solvent
Yield [%]
1
2
3
4
5
6
7
8
9
air
air
air
air
air
air
argon
O2
O2
O2
O2
O2
12
12
12
12
12
12
12
12
6
18
12
12
12
CH CN
21
<5
<5
<5
7
3
DMF
DMSO
toluene
dixone
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
32
0
55
34
53
10
11
12
13
Scheme 1. Synthesis of lactones.
[c]
28[
d]
81[
e]
O2
43
To explore the new strategy to construct modified
lactones through the difunctionalization of alkenes,
we envisioned a new process for the preparation of
substituted lactones incorporating the features dis-
[
a]
Reaction conditions: 1a (0.2 mmol) and 2a (2.0 equiv.),
with Cu(OAc) (10 mol%) as catalyst in solvent (2.0 mL)
at 508C in a flask.
Isolated yield based on 1a.
2a (1.0 equiv.).
2
[
[
[
b]
[6–8]
cussed above,
hydroxysulfenylation of olefins and our own work
recently established elegant work on
c]
[9]
d]
[
10,11]
2a (3.0 equiv.).
about Cu-catalyzed aerobic oxidation
and thiola-
We suggested that dioxygen reacts
with the active thiolated radical intermediate
Scheme 1b), to form a more nucleophilic hydroxy of 32% (entry 6). As expected, no reaction was ob-
[e]
2
a (3.0 equiv.) without Cu(OAc)2.
[12]
tion reactions.
(
[9]
species. Then an intramolecular nucleophilic reac- served when the reaction was conducted under an
tion affords the desired thio-substituted lactone. argon atmosphere (entry 7), because the thiol radical
Herein, we would like to report a novel Cu-catalyzed cannot be formed. Oxygen was proved to be superior
aerobic oxidative hydroxysulfenylation-initiated lacto- over air as oxidant for this reaction. Thus, reacting of
nization reaction of unsaturated carboxylic acids with 1a with 2a in DCE in the presence of O for 12 h
2
thiols through a sequence of thiolation of the C=C gave the desired product 3aa with dramatically in-
double bond, oxygenation and lactonization. To the creased isolated yield (55%, entry 8). Although dis-
best of our knowledge, use of a carboxyl group as continuing the reaction after 6 h gave a lower chemi-
electrophile in the lactonization of unsaturated car- cal yield (34%, entry 9), prolonging the reaction to
boxylic acids group has never been reported. Further- 18 h did not offer any significant improvement
more, this reaction provides a new difunctionalization (entry 10). It was found that the stoichiometry influ-
of alkenes-initiated lactonization strategy to construct ences the efficiency of this reaction. Using 1 equiv. of
substituted lactones.
2a resulted in poor yield mainly because of thiol con-
version into the sulfonic acid under an oxygen atmos-
phere (entry 11). The yield could be increased to 81%
by using 3.0 equiv. of 2a (entry 12). Finally, the reac-
tion was markedly suppressed without the use of Cu
Results and Discussion
We first examined the reaction of unsaturated carbox- catalyst, suggesting that the metal catalyst is essential
ylic acids 1a with p-toluenethiol 2a catalyzed by for this reaction (entry 13).
Cu(OAc) under air (Table 1). With acetonitrile as
Subsequently, we investigated the scope of thiols in
2
solvent, the reaction proceeded but yielded the thio- the Cu-catalyzed hydroxysulfenylation-initiated cycli-
substituted lactone 3aa only in 21% yield after 12 h zation reaction (Scheme 2). As presented in
(
entry 1). Other common solvents, including DMF, Scheme 2, all the examined thiols could work well in
DMSO, toluene, dioxane and DCE, have been exam- the reaction, affording the corresponding thio-substi-
ined for this radical reaction (entries 2–6), and the re- tuted g-lactones in up to 86% chemical yields (3aa–
sults suggest that DCE is the best choice with a yield 3al). It was found that the electronegativity of the
Adv. Synth. Catal. 0000, 000, 0 – 0
2
ꢁ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Figure 2. X-ray single crystal analysis of 3aa.
[
13]
confirmed by X-ray single crystal analysis
of 3aa
(
Figure 2).
Encouraged by these straightforward reactions with
4-phenyl-4-pentenoic acid 1a and various thiols, we
further investigated the substrate scope by using sev-
eral unsaturated carboxylic acids (Scheme 3). To our
delight unsaturated carboxylic acids containing substi-
tuted aromatic rings were also well tolerated in this
reaction, affording the corresponding products in 58–
77% yields (3ba–3ea). Then, 5-phenyl-5-pentenoic
acid (1f), bearing a longer alkyl chain, was tried in
the reaction to construct a larger cycle. We found that
such an unsaturated carboxylic acid was compatible
with the current catalytic system to give a six-mem-
bered lactone in good yield (81%, 3da). A steric hin-
drance effect in the unsaturated carboxylic acids also
was found. The reaction of unsaturated carboxylic
acids containing a non-terminal vinyl group could
take place, however a dramatically decreased yield
was obtained (33% yield, 3ga). Additionally, the ali-
phatic vinyl carboxylic acid (1i) was investigated, and
was not amenable to our procedure. Finally, a simple
alkene without a carboxylic group, a-methylstyrene
Scheme 2. Cu-catalyzed hydroxysulfenylation reaction with
various thiols. Reaction conditions: 1a (0.2 mmol),
2
(
0.6 mmol), Cu(OAc) (10 mol%), DCE (2 mL) in a flask was examined in the reaction. It could react with 2a
under an O balloon at 508C for 12 h. Isolated yields based smoothly resulting in the hydroxyethyl thioether with
2
2
on 1a.
84% yield under the standard conditions (see the
Supporting Information).
To gain insights into the reaction mechanism, two
substituent groups influences the yield of this reac- preliminary mechanistic studies were carried out
tion. In general, thiols with electron-donating groups (Scheme 4). First, a radical inhibition experiment was
show higher reactivity, and give good to ideal yields examined with the addition of TEMPO (Scheme 4a).
(
77–86%, 3aa–3ac, 3ai, and 3al). In contrast, thiol 2g The formation of 3aa was suppressed and only
with a strong electron-withdrawing CF group on the TEMPO adduct 2a-TEMPO was detected, elucidating
3
aromatic ring gave the g-lactone (3ag) in only 23% that a radical pathway is involved in this process.
yield. It is clear that steric hindrance affects the reac- Then, another potential thiophenyl radical source, di-
tion efficiency. For example, when the ortho-methyl- phenyl sulfide was tested under standard conditions.
benzenethiol is subjected to the reaction, a lower No desired product was detected in the reaction mix-
yield was found (69%, 3aj) comparing to para-methyl- ture, which indicates that the thiol hydrogen has been
benzenethiol (81% yield, 3aa). In addition, the naph- transferred into the intermediate in the subsequent
thyl thiol was also a suitable substrate, and afforded procedure (Scheme 4b).
product 3ak in acceptable yield 63%. The chemical
Then, we tried to obtain the reaction intermediate.
structure of these thio-substituted g-lactones has been In the initial stage of the reaction, we fortunately iso-
Adv. Synth. Catal. 0000, 000, 0 – 0
3
ꢁ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Scheme 4. Radical-trapping experiments.
Scheme 3. Cu-catalyzed hydroxysulfenylation reaction with
various unsaturated carboxylic acids. Reaction conditions:
1
(0.2 mmol), 2a (0.6 mmol), Cu(OAc)2 (10 mol%), DCE
(
2 mL) in a flask under an O balloon at 508C for 12 h. Iso-
2
lated yields based on 1.
lated
4-hydroxy-4-phenyl-5-(phenylthio)pentanoic
acid 4 with 23% yield after 2 h, while 4 disappeared
at the end of reaction (Scheme 5a). The intermediate
4
has been confirmed by careful analysis using
1
H NMR spectroscopy and HR-MS (see the Support-
ing Informatiion). To further confirm whether 4 is the
key intermediate, we used it as a substrate to check
whether it could be converted into the final product.
To our delight, 4 could be converted to the expected
product 3aa slowly at room temperature without any
additive after 48 h (Scheme 5b), which discloses that Scheme 5. Intermediate verification experiments.
such a hydroxy group attached 4 is the key intermedi-
ate of this reaction. To support our rationalization,
two control experiments were carried out. As the thiols could be easily oxidized into sulfonic acids in
result, an additional organic acid, p-toluenesulfonic the presence of oxgyen. Thus, the current system may
acid, could accelerate the transformation, giving the be a self-catalyzed esterification process, which is ac-
product 3aa with 87% yield after 2 h. On the other counts for the use of 3.0 equiv. of thiols in the reac-
hand, an additional organic base, 1,5,7-triazabicy- tion.
clo[4.4.0]dec-5-ene (TBD), suppressed the procedure
If the reaction proceeds via an oxygenation step ac-
and only 42% yield was found (Scheme 5c). The cording to our assumption, the final lactone product
Adv. Synth. Catal. 0000, 000, 0 – 0
4
ꢁ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
should have incorporated an oxygen atom from the
hydroxy group. To examine if the oxygen atom origi-
1
8
nates from the hydroxy group, an O labelling ex-
2
18
periment was carried out. As a result, the O-labelled
product 3aa’ was obtained in 83% yield and in 65%
isotopic purity (Scheme 6). This result indicates that
O also was involved in this reaction and was trans-
2
ferred into the final product.
Scheme 6. Isotope labelling experiment.
As the final objective of this study, we decided to Scheme 8. Proposed mechanism.
carry out a gram-scale synthesis due to the simple
access to valuable products. We conducted the reac-
tion with 6.0 mmol of starting thiol 1a under the stan- situ generated sulfonic acid (detected by HR-MS, see
dard reaction conditions. As shown in Scheme 7, the the Supporting Information) as catalyst.
corresponding product 3aa can be easily obtained
without a decrease in yield (66%) after prolonging
the reaction time to 48 h.
Conclusions
In conclusion, we have developed a novel and effi-
cient copper-mediated strategy for the synthesis of
thio-substituted lactones through difunctionalization
of alkenes. This reaction proceeds through an unpre-
cedented pathway involving hydroxysulfenylation of
the C=C double bond with carboxyl as electrophilic
group and dioxygen as reactant and oxidant. Further-
more, the mechanistic studies support the discovery
of new strategies to construct substituted lactones
based on unsaturated carboxylic acids through difunc-
tionalization of alkenes. Further studies toward the
development of this new process are currently under-
Scheme 7. Gram-scale examination of the current system.
On the basis of our findings and previous stud- way.
[6–8]
ies,
a
possible mechanism is illustrated in
Scheme 8. Initially, the Cu catalyst is oxidized by O2
to form a CuOO radical A, then HAT (hydrogen
atom abstraction) from ArSH by this radical happens
Experimental Section
[
9]
to give the thiophenyl radical B, which adds to the
General
C=C double bond of the unsaturated carboxylic acid
[
14]
Except where otherwise stated, all reagents were commer-
cially available and used without purification. The unsaturat-
ed carboxylic acids were prepared according to the previous
1
a to form intermediate C. Then, B is trapped by
dioxygen to give peroxy radical D, and intermediate
[
15]
D is reduced by the redox-active copper species to
[8d]
report.
Solvents were dried by a solvent purification
generate the key intermediate 4-hydroxy-4-phenyl-5-
system before use. Melting points (mp) were measured on
a Mel-Temp apparatus and are uncorrected. For flash silica
gel chromatography, silica gel (200–300 mesh) was per-
(
phenylthio)pentanoic acid E. The Cu catalyst could
be regenerated via reduction by thiol 2. Subsequent
intramolecular nucleophilic esterification occurs, af-
1
13
formed by standard technique. The H NMR and C NMR
fording the final product 3 by release of H O. This spectra were recorded on a Bruker model DRX 400 spec-
2
lactonization step could also be accelerated by the in trometer in deuterated chloroform (CDCl ) [using (CH ) Si
3
3 4
Adv. Synth. Catal. 0000, 000, 0 – 0
5
ꢁ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
1
3
(
for 1H, d=0.00; for C, d=77.00) as internal standard].
[3] a) N. Gouault, M. David, J. F. Cupif, A. Sauleau, M.
Amoros, Pharm. Pharmacol. Commun. 1999, 5, 159–
163; b) O. Yonemitsu, J. Uenishi, N. Kobayashi, T.
Sasaki, Y. Yamada, Heterocycles 1997, 44, 277–287.
[4] Q. Liang, N. Li, S. R. Song, A. H. Zhang, N. Li, Y.
Duan, J. Obstet. Gynaecol. Res. 2016, 42, 1354–1360.
[5] a) S. E. Denmark, D. J. P. Kornfilt, T. Vogler, J. Am.
Chem. Soc. 2011, 133, 15308–15311; b) M. C. CarreÇo,
M. J. Sanz-Cuesta, J. Org. Chem. 2005, 70, 10036–
All coupling constants (J) are reported in Hertz (Hz). Infra-
red (IR) spectra were performed on Agilent Cary 630 FT-
IR instrument with the attenuated total reflection (ATR)
technique. High resolution mass spectra (HR-MS) were
measured on a Bruker micr OTOF-Q III mass spectrometer
with the ESI technique.
Typical Procedure for the Cu-Catalyzed Hydroxysul-
fenylation Reaction
1
0045; c) Z. K. M. Abd El Samii, M. I. Al Ashmawy,
J. M. Mellor, J. Chem. Soc. Perkin Trans. 1 1988, 2517–
522; d) M. Yoshida, T. Suzuki, N. Kamigata, J. Org.
Unsaturated carboxylic acids
0.6 mmol) and Cu(OAc) (10 mol%) were added to a 25-
mL Schlenk tube under an O balloon, followed by addition
of DCE (2 mL). The mixture was stirred at 508C for 12 h,
then filtered and the residue was washed with ethyl acetate.
The organic phase was dried by anhydrous Na SO and con-
centrated under vacuum. Finally, the residue was purified by
flash chromatography to give the desired product 3.
-Phenyl-5-((p-tolylthio)methyl)dihydrofuran-2(3H)-one
3aa): Pale yellow solid; mp 64–658C; H NMR (400 MHz,
CDCl ): d=7.42–7.27 (m, 5H), 7.25 (d, J=8.4 Hz, 2H), 7.07
d, J=7.9 Hz, 2H), 3.42 (q, J=14.2 Hz, 2H), 2.84–2.64 (m,
H), 2.59–2.40 (m, 2H), 2.30 (s, 3H); C NMR (101 MHz,
CDCl ): d=176.0, 142.5, 137.0, 132.3, 130.9, 129.8, 128.6,
28.1, 124.8, 88.4, 47.9, 32.6, 29.1, 21.0; IR (neat): nmax
920, 2851, 1761, 1493, 1172, 1016, 805, 699 cm ; HR-MS:
1
(0.2 mmol), thiols
2
2
(
2
Chem. 1992, 57, 383–386; e) D. Crich, B. Surve, M. San-
nigrahi, Heterocycles 2004, 62, 827–830.
2
[
6] a) Y. Yasu, Y. Arai, R. Tomita, T. Koike, M. Akita,
Org. Lett. 2014, 16, 780–783; b) K. D. Ashtekar, M.
Vetticatt, R. Yousefi, J. Jackson, B. Borhan, J. Am.
Chem. Soc. 2016, 138, 8114–8119; c) C. S. Meng, Z. H.
Liu, Y. X. Liu, Q. M. Wang, Org. Biomol. Chem. 2015,
2
4
5
1
1
3, 6766–6772; d) C. F. Xu, Q. L. Shen, Org. Lett. 2015,
7, 4561–4563; e) M. L. Campbell, S. A. Rackley, L. N.
1
(
3
Giambalvo, D. C. Whitehead, Tetrahedron 2015, 71,
(
2
3
1
895–3902; f) W. Niu, Y. Y. Yeung, Org. Lett. 2015, 17,
660–1663; g) T. Chen, T. J. Y. Foo, Y. Y. Yeung, ACS
1
3
3
Catal. 2015, 5, 4751–4755; h) K. Moriyama, C. Nishino-
hara, T. Sugiue, H. Togo, RSC Adv. 2015, 5, 85872–
1
2
=
À1
8
5878; i) Y. B. Kang, X. M. Chen, C. Z. Yao, X. S. Ning,
+
m/z=299.1100, calcd. for C H O S [M+H] : 299.1100.
1
8
18
2
Chem. Commun. 2016, 52, 6193–6196; j) G. C. Geary,
G. Hope, A. M. Stuart, Angew. Chem. 2015, 127,
Intermediate Verification Experiment
1
5124–15127; Angew. Chem. Int. Ed. 2015, 54, 14911–
1
4914; k) D. H. Paull, C. Fang, J. R. Donald, A. D. Pan-
1
a (0.2 mmol), 2a (0.6 mmol) and Cu(OAc)2 (10 mol%)
sick, S. F. Martin, J. Am. Chem. Soc. 2012, 134, 11128–
1131; l) X. Jiang, C. K. Tan, L. Zhou, Y. Y. Yeung,
were added to a 25-mL Schlenk tube under an O balloon,
2
1
followed by addition of DCE (2 mL). The mixture was
stirred at 508C for 2 h, then filtered and the residual was
washed with ethyl acetate. The organic phase was dried over
Na SO and concentrated under vacuum. The crude product
was purified by flash chromatography to give the desired
product 4.
Angew. Chem. 2012, 124, 7891–7895; Angew. Chem.
Int. Ed. 2012, 51, 7771–7775; m) H. Nakatsuji, Y. Sawa-
mura, A. Sakakura, K. Ishihara, Angew. Chem. 2014,
1
6
Org. Lett. 2012, 14, 5884–5887; o) G. E. Veitch, E. N.
Jacobsen, Angew. Chem. 2010, 122, 7490–1493; Angew.
Chem. Int. Ed. 2010, 49, 7332–7335.
2
4
26, 7094–7097; Angew. Chem. Int. Ed. 2014, 53, 6974–
977; n) J. E. Tungen, J. M. J. Nolsøe, T. V. Hansen,
[
7] a) A. Bunescu, Q. Wang, J. P. Zhu, Chem. Eur. J. 2014,
Acknowledgements
2
0, 14633–14636; b) Y. Z. Gao, X. Q. Li, J. Xu, Y. L.
Wu, W. Z. Chen, G. Tang, Y. F. Zhao, Chem. Commun.
015, 51, 1605–1607; c) Y. Z. Gao, J. Xu, P. B. Zhang,
H. Fang, G. Tang, Y. F. Zhao, RSC Adv. 2015, 5, 36167–
6170; d) W. Guo, H. G. Cheng, L. Y. Chen, J. Xuan,
We gratefully acknowledge the financial support from the Na-
tional Natural Science Foundation of China (No. 21102071
and 21472082). The Jiangsu 333 program (for Y. Pan) and
Changzhou Jin-Feng-Huang program (for J. Han) are also
acknowledged.
2
3
Z. J. Feng, J. R. Chen, L. Q. Lu, W. J. Xiao, Adv. Synth.
Catal. 2014, 356, 2787–2793; e) Y. Gao, X. Li, W. Chen,
G. Tang, Y. Zhao, J. Org. Chem. 2015, 80, 11398–11406.
8] a) R. Zhu, S. L. Buchwald, Angew. Chem. 2013, 125,
12887–12890; Angew. Chem. Int. Ed. 2013, 52, 12655–
[
References
1
2658; b) R. Zhu, S. L. Buchwald, J. Am. Chem. Soc.
[
1] a) J. D. Lambert, J. E. Rice, J. Hong, Z. Hou, C. S.
Yang, Bioorg. Med. Chem. Lett. 2005, 15, 873–876;
b) T. Janecki, E. Błaszczyk, K. Studzian, A. Janecka, U.
Krajewska, M. Rꢂ z˙ alski, J. Med. Chem. 2005, 48, 3516–
2012, 134, 12462–12465; c) R. Zhu, S. L. Buchwald, J.
Am. Chem. Soc. 2015, 137, 8069–8077; d) B. N. Hemric,
K. Shen, Q. Wang, J. Am. Chem. Soc. 2016, 138, 5813–
5816.
3
521.
[9] a) H. Xi, B. Deng, Z. Zong, S. Lu, Z. Li, Org. Lett.
2015, 17, 1180–1183; b) S. F. Zhou, X. Pan, Z. H. Zhou,
A. Shoberu, J. P. Zou, J. Org. Chem. 2015, 80, 3682–
3687; c) J. J. Zhao, M. Tang, H. H. Zhang, M. M. Xu, F.
Shi, Chem. Commun. 2016, 52, 5953–5956.
[
2] a) B. N. Ravi, R. W. Armstrong, D. J. Faulkner, J. Org.
Chem. 1979, 44, 3109–3113; b) M. W. Sumarah, E. Pu-
niani, D. Sorensen, B. A. Blackwell, J. D. Miller, Phyto-
chemistry 2010, 71, 760–765.
Adv. Synth. Catal. 0000, 000, 0 – 0
6
ꢁ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
[
10] a) B. N. Du, P. Qian, Y. Wang, H. B. Mei, J. L. Han, Y.
Pan, Org. Lett. 2016, 18, 4144–4147; b) B. N. Du, Z. Li,
P. Qian, J. L. Han, Y. Pan, Chem. Asian J. 2016, 11,
Dong, X. F. Xu, J. C. Mao, Org. Lett. 2015, 17, 5444–
5447; c) Q. Q. Lu, Z. L. Liu, Y. Luo, G. H. Zhang, Z. Y.
Huang, H. M. Wang, C. Liu, J. T. Miller, A. W. Lei,
Org. Lett. 2015, 17, 3402–3405; d) Q. Q. Lu, H. M.
Wang, P. Peng, C. Liu, Z. Y. Huang, Y. Luo, A. W. Lei,
Org. Chem. Front. 2015, 2, 908–912; e) Y. J. Su, X. Sun,
G. L. Wu, N. Jiao, Angew. Chem. 2013, 125, 9990–9994;
Angew. Chem. Int. Ed. 2013, 52, 9808–9812; f) H. W.
Huang, J. H. Cai, X. C. Ji, F. H. Xiao, Y. Chen, G. J.
Deng, Angew. Chem. 2016, 128, 315–319; Angew.
Chem. Int. Ed. 2016, 55, 307–311.
4
78–481.
[
11] For reviews, see: a) A. E. Wendlandt, A. M. Suess, S.
Stahl, Angew. Chem. 2011, 123, 11256–11283; Angew.
Chem. Int. Ed. 2011, 50, 11062–11087; b) Z. Shi, C.
Zhang, C. Tang, N. Jiao, Chem. Soc. Rev. 2012, 41,
3
381–3430; c) T. Punniyamurthy, S. Velusamy, J. Iqbal,
Chem. Rev. 2005, 105, 2329–2364; d) S. McCann, S.
Stahl, Acc. Chem. Res. 2015, 48, 1756–1766.
[
12] a) J. C. Zhao, H. Fang, J. L. Han, Y. Pan, G. G. Li, Adv.
Synth. Catal. 2014, 356, 2719–2724; b) S. Y. Ni, L. J.
Zhang, W. Z. Zhang, H. B. Mei, J. L. Han, Y. Pan, J.
Org. Chem. 2016, 81, 9470–9475.
[
15] a) H. Xi, B. C. Deng, Z. Z. Zong, S. L. Lu, Z. P. Li,
Org. Lett. 2015, 17, 1180–1183; b) H. G. Wang, Y.
Wang, D. D. Liang, L. Y. Liu, J. C. Zhang, Q. Zhu,
Angew. Chem. 2011, 123, 5796–5799; Angew. Chem.
Int. Ed. 2011, 50, 5678–5681; c) C. Zhang, P. Feng, N.
Jiao, J. Am. Chem. Soc. 2013, 135, 15257–15262;
d) A. S. K. Tsang, A. Kapat, F. Schoenebeck, J. Am.
Chem. Soc. 2016, 138, 518–526; e) C. Zhang, C. H.
Tang, N. Jiao, Chem. Soc. Rev. 2012, 41, 3464–3484;
f) S. E. Allen, R. R. Walvoord, R. P. Salinas, M. C. Ko-
zlowski, Chem. Rev. 2013, 113, 6234–6458.
[
13] CCDC 1513113 (3aa) contains the supplementary crys-
tallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
14] a) T. Keshari, V. K. Yadav, V. P. Srivastava, L. D. S.
Yadav, Green Chem. 2014, 16, 3986–3992; b) Y. Zheng,
Y. He, G. W. Rong, X. L. Zhang, Y. C. Weng, K. Y.
[
Adv. Synth. Catal. 0000, 000, 0 – 0
7
ꢁ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
8
Copper(II) Acetate-Catalyzed Hydroxysulfenylation-
Initiated Lactonization of Unsaturated Carboxylic Acids
with Oxygen as Oxidant and Oxygenation Reagent
Adv. Synth. Catal. 2017, 359, 1 – 8
Bingnan Du, Yang Wang, Haibo Mei, Jianlin Han,* Yi Pan
Adv. Synth. Catal. 0000, 000, 0 – 0
8
ꢁ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!