Palladium-catalyzed oxidative C-O cross-coupling of ketene dithioacetals and carboxylic acids

Article abstract of DOI:10.1039/c3ra47282e

Direct oxidative C-O cross-coupling reaction between active alkenes and carboxylic acids is presented. By utilizing Pd(OAc)₂ as a catalyst and PhI(OAc)₂ as an oxidant, ketene dithioacetals were smoothly acyloxylated in carboxylic acid-water solution, affording a variety of vinyl esters in a highly selective way with high efficiency and good functional group tolerance. A plausible mechanism is proposed that features a vinyl iodonium species as key intermediate.

Full text of DOI:10.1039/c3ra47282e

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
Palladium-catalyzed oxidative C–O cross-coupling
of ketene dithioacetals and carboxylic acids†
Cite this: RSC Adv., 2014, 4, 6564
a
a
a
a
Deqiang Liang,ab Mang Wang, Ying Dong, Yaru Guo and Qun Liu
*
*
Received 4th December 2013
Accepted 24th December 2013
DOI: 10.1039/c3ra47282e
www.rsc.org/advances
Direct oxidative C–O cross-coupling reaction between active alkenes
a-Oxo ketene dithioacetals are kinds of polarized alkenes
and carboxylic acids is presented. By utilizing Pd(OAc)2 as a catalyst which have been used as versatile synthons for the synthesis of
and PhI(OAc)2 as an oxidant, ketene dithioacetals were smoothly various carbo- and heterocyclic compounds.8 The a-C–H func-
acyloxylated in carboxylic acid–water solution, affording a variety of tionalization of them has become attractive transformation as it
vinyl esters in a highly selective way with high efficiency and good furnishes more densely functionalized molecules with synthetic
functional group tolerance. A plausible mechanism is proposed that potential.9 Our continuing interest in the a-functionalization of
features a vinyl iodonium species as key intermediate.
ketene dithioacetals prompted us to investigate their reactivity in
new C–O cross-coupling reactions. Herein, we report a novel
Pd(OAc)2-catalyzed olenic C–H acyloxylation of ketene dithioa-
cetals by using carboxylic acids as coupling partner and
PhI(OAc)2 as oxidant, furnishing the target vinyl esters.
Alkene functionalization is an important and long-standing
goal in organic chemistry.1 In this eld, oxygenation of olens
represents a key step for the synthesis of numerous structurally
interesting compounds.1,2 However, direct olenic C–H
oxygenation has received less attention likely due to the large
driving force for addition reaction or allylation reaction of the
double bonds upon coupling reaction.1–7
Limited methodologies have been developed for the acetoxy-
lation of some active olens (e.g., enol silyl ethers,3 enamines,4
ketene N/S,S-acetals5). Pb(OAc)4 proved to be an efficient acetoxy-
lating reagent for this purpose though the employment of a large
amount of highly toxic lead salt is not encouraged.4d,e,5 Addition-
ally, the acetoxylation was found to accompany with a-iodination
and N-arylation of enol silyl ethers3 when treating enol silyl ethers
with PhI(OAc)2. The acetoxylation of acyclic enamines was also
observed when performing the homocoupling of them by the
action of PhI(OAc)2 in the presence of BF3$Et2O.4 However, those
reactions involving PhI(OAc)2 as acetoxylating reagent are usually
available to only one or few specic substrates.3,4b–d,5b–e,6,7 As a
consequence, it is highly desirable to develop an environmentally
benign approach toward the goal of direct olenic C–H acyloxy-
lation with high efficiency and a wide substrate scope.4a
At the outset of the present investigation, a-oxo ketene
dithioacetal 1a was employed as model substrate to screen the
reaction conditions. The results were summarized in Table 1.
First of all, several oxidants were evaluated to perform the
coupling reaction under the catalysis of 10 mol% of Pd(OAc)2 in
ꢀ
acetic acid at 50 C. It proved that the use of AgOAc, Cu(OAc)2,
Oxone, para-benzoquinone (BQ) and PhI(O2CCF3)2 was unsuc-
cessful (Table 1, entries 1–5). To our delight, upon treatment of
1a with 1.2 equivalents of PhI(OAc)2 as the oxidant for 1 h, a
satisfactory yield (81%) of 2a was achieved (Table 1, entry 6).
Next, other solvents instead of acetic acid were tested under
otherwise the same conditions. Reactions carried out in CH2Cl2,
CH3CN and DMF were found to result in very low yields (Table 1,
entries 7–9), even the addition of 10 equivalents of HOAc did not
bring forth any improvement (Table 1, entry 10). Interestingly,
water proved to benet the acetoxylation (Table 1, entries
11–14). When the ratio of HOAc to H2O was 20 : 1 or 10 : 1 (v/v),
2a was separated in nearly quantitative yields (Table 1, entries
12 and 13).‡ Temperature also signicantly affected this trans-
formation. When the reaction was run at ambient temperature
ꢀ
or 80 C, a decrease in the yield of 2a was observed (Table 1,
entries 15 and 16). Then, other Pd catalysts, such as PdCl2 and
[Pd(PPh3)4], were tested in comparison with Pd(OAc)2 and found
to be less efficient (Table 1, entries 17 and 18). It is worthy of
notice that a reduced catalyst loading of 5 mol% of Pd(OAc)2 was
sufficient to give a satisfactory yield (84%) within 2 h (Table 1,
entry 19). However, in the absence of any Pd catalyst under
aDepartment of Chemistry, Northeast Normal University, Changchun 130024, China.
E-mail: wangm452@nenu.edu.cn; liuqun@nenu.edu.cn; Fax: +86-431-85099759;
Tel: +86-431-85099759
bDepartment of Chemistry, Kunming University, Kunming 650214, China
† Electronic supplementary information (ESI) available: Experimental details,
characterization data, copies of the 1H and 13C NMR spectra of all nal
products and ESI/MS spectra of E. See DOI: 10.1039/c3ra47282e
6564 | RSC Adv., 2014, 4, 6564–6567
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
Table 1 Optimization of the reaction conditionsa
Entry
Catalyst
Oxidant
Solvent
T/ꢀC
t/h
Yieldb (%)
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
AgOAcc
Cu(OAc)2
Oxone
BQc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
CH2Cl2
CH3CN
50
50
50
50
50
50
50
50
50
50
50
50
50
50
rt
12
12
12
12
12
1
12
12
12
12
1
1
1
1
12
1
Trace
Trace
Trace
17
12
81
11
8
15
12
81
95
98
91
64
87
23
60
c
PhI(O2CCF3)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
9
DMF
DMF
10d
11
12
13
14
15
16
17
18
19
20
21
HOAc/H2O(50 : 1)
HOAc/H2O(20 : 1)
HOAc/H2O(10 : 1)
HOAc/H2O(5 : 1)
HOAc/H2O(10 : 1)
HOAc/H2O(10 : 1)
HOAc/H2O(10 : 1)
HOAc/H2O(10 : 1)
HOAc/H2O(10 : 1)
HOAc/H2O(10 : 1)
HOAc/H2O(10 : 1)
80
50
50
50
50
50
1
1
2
1
[Pd(PPh3)4]
e
Pd(OAc)2
84
—
0f
g
Pd(OAc)2
1
92
a
Reaction conditions: 1a (1.0 mmol), Pd catalyst (0.1 mmol), oxidant (1.2 mmol), solvent (10 mL). b Isolated yields. c 2.4 equiv. of oxidant was used.
d
10 equiv. of HOAc was added. e 5 mol% of Pd(OAc)2 was used. f Only an unidentied great polar product was detected. g 10 mol% of Pd(OAc)2 was
added aer 1a had reacted with PhI(OAc)2 for 0.5 h, then the mixture was stirred for another 1 h.
otherwise optimized conditions, no target product was gener- reaction efficiency, 20 mol% of Pd(OAc)2 should be used. It
ated (Table 1, entry 20).
proved that all of the substrates having phenyl (Table 3, entry 1),
Aer achieving the optimized reaction conditions, the scope of electron-rich (Table 3, entries 2 and 3), electron-decient (Table 3,
ketene dithioacetals 1 was explored by varying the electron-with-
drawing groups (EWGs) and SR groups (Table 2). We are pleased
to nd that the reactions of a series of ketene cyclic dithioacetals
Table 2 Acetoxylation of ketene dithioacetals 1a
with various a-EWGs, including alkanoyl (Table 2, entries 1 and 2),
electron-rich/-decient aroyl (Table 2, entries 3–6) and alkoxy-
carbonyl groups (Table 2, entry 7), proceeded smoothly to afford
the expected acetoxylated products 2a–g in moderate to nearly
quantitative yields within 1–6 h. In addition, the conditions were
mild enough to be compatible with an aryl C–Br bond, which
could be further transformed into different functionalities (Table
2, entry 5). The electron-rich furan ring (Table 2, entry 6) was also
Entry
1
EWG
R
t/h
2
Yieldb (%)
tolerant to the reaction, without any side oxidation processes
detected. In the case of using acyclic ketene dithioacetal 1h as
substrate, low yield of 2h was obtained (Table 2, entry 8). We also
attempted to optimize the reaction with substrate 1h by increasing
the amounts of Pd(OAc)2 and PhI(OAc)2 or changing the ratio of
mixed solvent, but the reaction yield could not be improved.
With the purpose of further probing the reactivity and regio-
selectivity of this new procedure, a range of reactions was carried
out with various a-alkenoyl ketene dithioacetals 1i–p, and the
results are summarized in Table 3. In order to improve the
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
MeCO
t-BuCO
PhCO
4-MePhCO
4-BrPhCO
2-furylCO
CO2Et
–CH2CH2–
–CH2CH2–
–CH2CH2–
–CH2CH2–
–CH2CH2–
–CH2CH2–
–CH2CH2–
Et
1
6
3
3
3
3
3
3
2a
2b
2c
2d
2e
2f
98
70
80
61
76
66
67
23
1g
1h
2g
2h
MeCO
a
Reaction conditions: 1 (1.0 mmol), Pd(OAc)2 (0.1 mmol) and PhI(OAc)2 (1.2
mmol) were stirred in HOAc/H2O (10 : 1, 10 mL) at 50 ꢀC. b Isolated yields.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 6564–6567 | 6565

View Article Online
RSC Advances
Communication
Table 4 Cross-coupling reactions of ketene dithioacetal 1a with
entries 4 and 5) aromatic and hetero aromatic groups (Table 3,
entry 6) at the b0-position of the a-alkenoyl moiety can efficiently
furnish the corresponding a-C–O coupling products 2i–n in
moderate to good yields. Triene 1o gave the desired polyene
product 2o in good yield as well (Table 3, entry 7). a-Alkenoyl
dithioacetal 1p with aliphatic substitutent at the b0-position was
also suitable substrate and provided 2p in 87% yield (Table 3,
entry 8). It is noteworthy that in all cases, no a0-acetoxylated
products were detected. Thus, we provided here a highly regio-
selective C–O cross-coupling reaction.
In order to investigate the reaction mechanism, we next
carried out the above reaction by using other carboxylic acids as
solvents. As expected, propanoic acid–water (10 : 1) worked well
as an alternative solvent under otherwise optimized conditions
described in Table 1, entry 13, providing the acyloxylation product
carboxylic acidsa
Entry
R00
3
Yield of 3b (%)
Yield of 4b (%)
1
Et
CHCl2
CF3
3a
3b
—
50
13
—
0
40
24
2
3c
a
Reaction conditions: 1a (1.0 mmol), Pd(OAc)2 (0.1 mmol) and
3a in moderate yield (Table 4, entry 1). When dichloroacetic acid– PhI(OAc)2 (1.2 mmol) were stirred in R00COOH/H2O (10 : 1, 10 mL) at
b
c
50 ꢀC for 3 h. Isolated yields. Anhydrous TFA was used as solvent,
water (10 : 1) was employed, the acyloxylation product 3b was
only obtained in 13% yield along with the formation of the
hydrolyzed product 4 in 40% yield (Table 4, entry 2). Whereas, the
reaction of 1a with triuoroacetic acid (TFA) afforded 4 as the sole
˚
with the addition of 4 A MS (400 mg).
In present investigation, as shown in Table 1, entry 20,
product in the yield of 24% (Table 4, entry 3). These ndings ketene dithioacetal 1a disappeared rapidly within 20 minutes in
suggest that the acyloxy groups incorporated in products 2 and 3 the absence of any Pd catalyst under otherwise optimized
did not ultimately originate from hypervalent iodine reagents but conditions, however, no target product was generated even with
rather from the solvents.
a somewhat prolonged reaction time (1 h), leading to the
In general, it is considered that Pd-catalyzed direct acetoxylation formation of a great polar product which was not stable enough
using PhI(OAc)2 as a terminal oxidant in acetic acid, conditions to be isolated and characterized, but identied as a vinyl iodo-
developed by Crabtree,10 involves palladation of a C–H bond with nium salt14,15 by ESI/MS experiment.16 By contrast, acetylated
Pd(II) species as the rst step.11 However, Suna recently revealed product 2a could be obtained in excellent yield by a subsequent
that the acetoxylation of electron-rich heterocycles (i.e., indoles, addition of 10 mol% of Pd(OAc)2 aer the disappearance of
pyrroles) under Crabtree condition occurs via the initial formation starting material 1a (Table 1, entry 21).
of heteroaryl(phenyl)iodonium acetates rather than via the initial
On the basis of the above observations and seminal works,12,13
carbopalladation by C–H activation. The key iodonium interme- a plausible mechanism for this transformation is outlined in
diates, which could be isolated, are then smoothly transformed Scheme 1. To start with, ketene dithioacetals 1 react with
into acetoxylated products in the presence of a Pd catalyst.12,13
PhI(O2CR00)2, generated in situ by ligand metathesis of PhI(OAc)2
with carboxylic acids, to form the intermediate vinyl iodonium
salts A, which are subsequently coordinated to Pd-catalyst via the
Table 3 Acetoxylation of a-alkenoyl dithioacetals 1i–pa
Entry
1
R0
2
Yieldb (%)
1
2
3
4
5
6
7
8
1i
1j
Ph
2i
2j
55
75
68
79
66
53
70
87
4-MePh
3,4-O2CH2Ph
4-CF3Ph
2-ClPh
2-Thienyl
PhCH]CH
t-Bu
1k
1l
1m
1n
1o
1p
2k
2l
2m
2n
2o
2p
a
Reaction conditions: 1i–p (1.0 mmol), Pd(OAc)2 (0.2 mmol) and
Scheme 1 Proposed mechanism for acyloxylation of ketene dithioa-
cetals 1.
PhI(OAc)2 (1.2 mmol) were stirred in HOAc/H2O (10 : 1, 10 mL) at 50
b
ꢀC for 3 h. Isolated yields.
6566 | RSC Adv., 2014, 4, 6564–6567
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
sulfur atom, furnishing intermediates B. Then, Pd-catalyst coor-
dinates both the sulfur atom and the double bond, affording the
h3-coordination complexes C, which ensure the high regiose-
lectivity of the ketene dithioacetal moiety transfer to the Pd center.
Subsequent oxidative addition would generate transient Pd(IV)17 or
dinuclear Pd(III) complexes18 D. Finally, reductive elimination of D
delivers acyloxylated products 2 or 3, as well as regenerates Pd(II)
salts to nish the catalytic cycle.
1183; (e) C. R. Dorn, F. J. Koszyk and G. R. Lenz, J. Org.
Chem., 1984, 49, 2642–2644.
5 (a) L. Bhat, A. Thomas, H. Ila and H. Junjappa, Tetrahedron,
1991, 47, 305–312; (b) A. Thomas, J. N. Vishwakarma,
S. Apparao, H. Ila and H. Junjappa, Tetrahedron, 1988, 44,
1667–1672; (c) K. Hiroi, S. Sato and K. Matsuo, Chem.
Pharm. Bull., 1980, 28, 558–566; (d) B. M. Trost, K. Hiroi
and L. N. Jungheim, J. Org. Chem., 1980, 45, 1839–1847; (e)
K. Hiroi and S. Sato, Chem. Lett., 1979, 923–926.
6 (a) W. H. Henderson, C. T. Check, N. Proust and
J. P. Stambuli, Org. Lett., 2010, 12, 824–827; (b) A. M. Balija,
K. J. Stowers, M. J. Schultz and M. S. Sigman, Org. Lett.,
2006, 8, 1121–1124; (c) S. Fukuzawa, K. Takahashi, H. Kato
and H. Yamazaki, J. Org. Chem., 1997, 62, 7711–7716.
7 S. E. Mann, A. E. Aliev, G. J. Tizzard and T. D. Sheppard,
Organometallics, 2011, 30, 1772–1775.
8 For a recent review on ketene dithioacetal chemistry, see:
L. Pan, X. Bi and Q. Liu, Chem. Soc. Rev., 2013, 42, 1251–
1286.
Conclusions
In conclusion, a novel palladium-catalyzed oxidative acyloxy-
lation reaction of ketene dithioacetals with carboxylic acids has
been successfully developed to synthesize functionalized vinyl
esters in a highly regioselective way with high efficiency and
tolerance of diverse functional groups. This protocol could
complement the powerful direct cross-coupling strategy and
make it more universal. Detailed mechanistic investigations are
currently underway in our group.
9 Recent examples for a-functionalization of ketene
dithioacetals, see: (a) Y. Liu, J. Liu, M. Wang, J. Liu and
Q. Liu, Adv. Synth. Catal., 2012, 354, 2678–2682; (b)
H. Yuan, M. Wang, Y. Liu, L. Wang, J. Liu and Q. Liu,
Chem. – Eur. J., 2010, 16, 13450–13457; (c) D. Liang,
M. Wang, B. Bekturhun, B. Xiong and Q. Liu, Adv. Synth.
Catal., 2010, 352, 1593–1599; (d) Y. Liu, M. Wang, H. Yuan
and Q. Liu, Adv. Synth. Catal., 2010, 352, 884–892.
10 T. Yoneyama and R. H. Crabtree, J. Mol. Catal. A: Chem.,
1996, 108, 35–40.
11 It has been shown that C–H activation by a Pd catalyst is the
rate-determining step: (a) M. H. Emmert, A. K. Cook, Y. J. Xie
and M. S. Sanford, Angew. Chem., Int. Ed., 2011, 50, 9409–
9412; (b) L. V. Desai, K. J. Stowers and M. S. Sanford, J. Am.
Chem. Soc., 2008, 130, 13285–13293.
12 E. Suna, Chem. Heterocycl. Compd., 2012, 48, 44–48.
13 (a) D. Lubriks, I. Sokolovs and E. Suna, J. Am. Chem. Soc.,
2012, 134, 15436–15442; (b) E. Suna, I. Sokolovs and
D. Lubriks, Org. Lett., 2011, 13, 4324–4327.
14 M. S. Yusubov, A. V. Maskaev and V. V. Zhdankin, ARKIVOC,
2011, i, 370–409.
15 K. Miyamoto, T. Okubo, M. Hirobe, M. Kunishima and
M. Ochiai, Tetrahedron, 2010, 66, 5819–5826.
16 A vinyl iodonium salt E was recognized under the conditions
described in Table 1, entry 20 by ESI/MS experiment. For
details of ESI/MS spectra, see the ESI.†
Acknowledgements
Financial support of this research by the NCET-11-0613, NNSFC
(21172031/21272034/21372040) is gratefully acknowledged.
Notes and references
‡ General procedure for cross-coupling reactions of 1 with carboxylic acids (1a as
example): a 25 mL ask, equipped with a magnetic-stirring bar, was charged with
ketene dithioacetal 1a (160 mg, 1.0 mmol), PhI(OAc)2 (387 mg, 1.2 mmol), and
Pd(OAc)2 (23 mg, 0.1 mmol), followed by addition of 9.1 mL acetic acid and 0.91
mL water. The reaction mixture was stirred at 50 ꢀC for 1 h. Then it was cooled to
room temperature and poured into 50 mL ice-water under stirring. Aer
neutralized by saturated aqueous K2CO3 solution, the resulting mixture was
extracted with CH2Cl2 three times. The extract was dried over anhydrous MgSO4.
Aer removal of solvents, the residue was puried by column chromatography on
silica gel (petroleum ether : diethyl ether ¼ 7 : 1, V/V) to afford the product 2a as a
white solid (213 mg, 98% yield).
1 Recent reviews on alkenyl C–H functionalization, see: (a)
M. S. Sigman and E. W. Werner, Acc. Chem. Res., 2012, 45,
874–884; (b) R. I. McDonald, G. Liu and S. S. Stahl, Chem.
Rev., 2011, 111, 2981–3019; (c) E. M. Beccalli, G. Broggini,
M. Martinelli and S. Sottocornola, Chem. Rev., 2007, 107,
5318–5365.
2 For selected examples, see: (a) S. R. Chidipudi,
M. D. Wieczysty, I. Khan and H. W. Lam, Org. Lett., 2013,
15, 570–573; (b) M. Yamamoto, S. Nakaoka, Y. Ura and
Y. Kataoka, Chem. Commun., 2012, 48, 1165–1167; (c)
W. Liu, Y. Li, K. Liu and Z. Li, J. Am. Chem. Soc., 2011, 133,
10756–10759; (d) T. P. Pathak, K. M. Gligorich, B. E. Welm
and M. S. Sigman, J. Am. Chem. Soc., 2010, 132, 7870–7871.
3 I. I. Brunovlenskaya, K. M. Kusainova and A. N. Kashin, Zh.
Org. Khim., 1988, 24, 358–363.
17 L. Xu, B. Li, Z. Yang and Z. Shi, Chem. Soc. Rev., 2010, 39,
712–733.
18 (a) D. Powers and T. Ritter, Top. Organomet. Chem., 2011, 35,
129–156; (b) D. C. Powers and T. Ritter, Nat. Chem., 2009, 1,
302–309.
4 (a) X. Liu, R. Cheng, F. Zhao, D. Zhang-Negrerie, Y. Du and
K. Zhao, Org. Lett., 2012, 14, 5480–5483; (b) Y. Chen, T. Ju,
J. Wang, W. Yu, Y. Du and K. Zhao, Synlett, 2010, 231–234;
(c) J. Wang, S. Liu and W. Yu, Synlett, 2009, 2529–2533; (d)
G. R. Lenz and C. Costanza, J. Org. Chem., 1988, 53, 1176–
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 6564–6567 | 6567