Palladium-catalyzed cascade reactions of alkene-tethered carbamoyl chlorides with: N-tosyl hydrazones: Synthesis of alkene-functionalized oxindoles

Article abstract of DOI:10.1039/c9ob01672d

A palladium-catalyzed cascade reaction of alkene-tethered carbamoyl chlorides with N-tosyl hydrazones is described. It provided a new way to synthesize various alkene-functionalized oxindoles bearing an all-carbon quaternary center. The olefin moieties co

Full text of DOI:10.1039/c9ob01672d

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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
View Article Online
DOI: 10.1039/C9OB01672D
COMMUNICATION
Palladium-Catalyzed Cascade Reactions of Alkene-tethered
Carbamoyl Chlorides with N‑Tosyl Hydrazones: Synthesis of
Alkene-functionalized Oxindoles
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
a
a
a
DOI: 10.1039/x0xx00000x
Wan Sun, Chen Chen,* Yuan Qi, Jinghui Zhao, Yinwei Bao and Bolin Zhu*
Carbamoyl chlorides10 are useful precursors for preparing
oxindoles moieties via transition-metal-catalyzed domino
A
palladium-catalyzed cascade reaction of alkene-tethered
carbamoyl chlorides with N-tosyl hydrazones is described. It
provided a new way to synthesize various alkene-functionalized
oxindoles bearing an all-carbon quaternary center. The olefin
moieties could serve as versatile handles for further elaboration.
This transformation was highly efficient and showed good
functional group tolerance.
1
1-15
reactions,
which could be readily prepared from
corresponding secondary amines by treatment with
1
2
triethylamine and triphosgene. For examples, Takemoto and
co-workers reported a new strategy for rapid access to various
3
oxindoles from carbamoyl chlorides via C(sp )-H activation and
13
14
carbosilylation. Lautens and Tong reported transition-
metal-catalyzed intramolecular borylacylation and
iodoacylation for the synthesis of boryl- and iodo-substituted
Oxindoles represent a class of fused heterocyclic motifs
found universally in numerous pharmaceuticals, agrochemicals
and natural products. Especially for 3,3-disubstituted
oxindoles, which exhibit all kinds of biological activities. Well
known members include dioxibrassanin, convolutamydines,
and horsifiline (Figure 1). Therefore, it is important to develop
efficient methodologies for the synthesis of 3,3-disubstituted
oxindoles. Traditional synthesis of 3,3-disubstituted oxindoles
typically involve alkylation of 3-unsubstituted oxindoles and
are limited only to aliphatic substitution. When the
disubstituents are not identical, this approach was proven to
be very challenging. In recent years, a variety of new synthetic
strategies were developed for the construction of 3,3-
disubstituted oxindoles, which include: a) Olefin
1
5
oxindoles, respectively. Furthermore, Lautens
and co-
1
workers reported palladium-catalyzed intramolecular cross-
coupling of alkyne-tethered carbamoyl chlorides for the
synthesis of methylene oxindoles (Scheme 1a).
2
3
4
5
Since
Noyori16
and
co-workers
reported
the
6
cyclopropanation of alkenes with diazo compounds in 1966,
diazo chemistry draws much attention from organic chemists.
In the past decade, diazo compounds have been extensively
explored as carbene precursors in transition-metal-catalyzed
1
7
18
transformations. In 2001, Vranken and co-workers reported
the first palladium-catalyzed cross-coupling reaction of
(trimethylsilyl)diazomethane and benzyl halides. However, the
7
stability and safety issues related to diazo compounds limit
their wide applications. In 2007, a major breakthrough was
difunctionalization of acrylamide via a free radical pathway; b)
Heck-type reaction via N-(2-halophenyl)acrylamide; c)
Difunctionalization of acrylamide via
catalyzed Friedel-Crafts type pathway.
8
1
9
reported by Barluenga, who first utilized N-tosyl hydrazones
as the precursor of diazo compounds in palladium-catalyzed
cross-coupling reactions. Since then, a variety of useful
transformations in palladium carbene involved cross-
a
transition-metal-
9
Cl
20
21
22
couplings have been developed by Wang, Valdés, Van
S
Br
HO
N
R
23
24
HO
SMe
Vranken and others.
N
H
O
OMe
O
O
N
Br
N
Although palladium-catalyzed cross-coupling reactions using
N-tosyl hydrazones as carbene precursors have been
extensively investgated in the past few years, studies on the
N
H
O
N
H
H
Cl
convolutamydines
horsifiline
H
dioxibrassanin
A. R = CH2COCH3
B. R = CH2CH2Cl
anti-cancer reagent
Hoffmann-La Roche)
(
reactions between alkylpalladium and carbenes have been
Figure 1. Representative Examples of 3,3-Disubstituted Oxindoles
rarely reported,8b, 24a which might be a new protocol for the
construction of functionalized alkenes. With the combination
of the pioneering works and our continuous effort on
2
5
transition-metal-catalyzed synthetic transformations. We
envisioned that alkyl palladium(II) species from the
palladium(0) catalyst and alkene-tethered carbamoyl chlorides
would also be capable of carbene formation and alkyl
a. Address here. Tianjin Key Laboratory of Structure and Performance for Functional
Molecules, MOE Key Laboratory of Inorganic-Organic Hybrid Functional Material
Chemistry, College of Chemistry, Tianjin Normal University, Tianjin 300387, P. R.
China. E-mail: hxxycc@tjnu.edu.cn, hxxyzbl@tjnu.edu.cn
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See DOI:
migratory insertion. Herein, we report
a palladium(0)-
catalyzed intramolecular Heck type reaction of alkene-
1
0.1039/x0xx00000x
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Page 2 of 6
COMMUNICATION
Journal Name
tethered carbamoyl chlorides with N-tosyl hydrazones to give
-vinyloxindoles (Scheme 1b).
7
8
9
1
1
P(4-F-C H )
DMSO
12 h
45%
View Article Online
6
6
6
6
6
4
4
4
4
4
3
3
3
3
3
3
3
3
DOI: 10.1039/C9OB01672D
P(4-F-C
P(4-F-C
P(4-F-C
P(4-F-C
H
H
H
H
)
)
)
)
Toluene
1, 4-Dioxane
MeCN
12 h
80%
82%
85%
93%
94%
95%
12 h
0e
1
12 h
a) Synthesis of substituted oxindoles from carbamoyl chlorides:
MeCN
6 h
Bpin
*
R'
O
12
13f
P(4-F-C H )
MeCN
30 min
30 min
6
4
N
I
PG
TMS
P(4-F-C H )
MeCN
6
4
a
R'
O
R'
O
All reactions were performed with 1a (0.2 mmol), 2a (0.4 mmol) Pd(OAc)
ligand (20 mol%) in solvent (2.0 mL) at 90 C under a nitrogen atmosphere. Isolated
yield. c Ligand (30 mol%). d Ligand (15 mol%). e The reaction temperature was 70 C.
2
(10 mol%),
b
N
N
o
PG
[Pd]
TMSTMS
PG
[
Pd]
KI
[Cu]
B2(pin)2
R''
o
f
R =
R''
Without N
2
.
R =
R =
R''
Cl
R
N
O
[Pd]
R'
[Pd]
R = Me
R'
O
With an optimized set of conditions in hand, we then
surveyed the substrate scope of alkene-tethered carbamoyl
chlorides 1 in order to survey the generality of this reaction. As
shown in Table 2, 1b-1f bearing electron-donating substituents
on aromatic ring reacted effectively, to provide the
corresponding products (3ba-3fa) in moderate to good yields
(55%-88%). Moreover, electron-withdrawing substituents of
the phenyl groups were also tolerated, which included fluoro,
chloro and nitro groups, and the corresponding products 3ga-
3ia were isolated in 75%-99% yields. Notably, halide
substituents were found to be compatible with this reaction,
providing an opportunity to further functionalization.
Furthermore, 3ja was also readily obtained under our
optimized reaction conditions albeit in a lower yield. In the
R'
O
Cl
N
R =
R''
N
PG
PG
PG
b) This work: Synthesis of 3-vinyloxindoles via palladium-catalyzed cascade reactions:
R2
R2
R4
NHTs
[
Pd]
N
R1
Cl
O
+
R1
O
R4
N
H
N
R3
R3
Scheme 1. Synthesis of 3,3-Disubstituted Oxindoles from Carbamoyl Chlorides
We initiated our studies with the screening of reaction
conditions by reacting alkene-tethered carbamoyl chloride 1a
with N-tosyl hydrazone 2a in the presence of Pd(OAc)
(0.3 equiv), LiO Bu (3.0 equiv) in MeCN (2.0 mL) at
atmosphere. Gratifyingly, the desired cyclization
product 3aa was obtained in 78% yield (Table1, entry 1).
Subsequently, a series of ligands including monophosphines methyl group at the R
position, afforded 3na in quantitative
2
(0.1
2
presence of substituent on aromatic ring at the R position,
t
equiv), PPh
3
such as fluoro and chloro, the desired products 3ka-3ma were
obtained in high yields (93%, 96% and 74%, respectively). To
our delight, the reaction of substrate 1n, which contained a
o
9
0 C under N
2
2
and diphosphines were evaluated, and to our delight, the yield yield. The scope of the reaction by varying the substituent on
of 3aa was significantly increased to 91% with the use of P(4-F- the nitrogen atom was also investigated, both p-
methoxybenzyl(PMB) (1o) and cyclopentyl group (1p) were
tolerated, providing the corresponding products 3oa and 3pa
in 57% and 99% yields, respectively.
C
6
H
4
)
3
as the ligand (Table 1, entries 2-4). Decreasing the
amount of P(4-F-C ligand to 20 mol% delivered similar
result (Table1, entry 5). Other solvents, including DMF, DMSO,
toluene and 1, 4-dioxane failed to show better results (Table 1,
6 4 3
H )
Table 2. Variation of Alkene-tethered Carbamoyl Chlorides 1a,b
o
entries 6-9). When the reaction was conducted at 70 C, a
lower yield was obtained because of the low conversion of 1a
(Table1, entry 10). To our delight, the reaction was finished
within 30 minutes in air and the desired product 3aa was
isolated in 95% yield (Table1, entries 11-13). Thus, the optimal
condition for this transformation was determined to be as
follows: simply mixing 1a (0.2 mmol), 2a (0.4 mmol), Pd(OAc)
2
t
(0.02 mmol), P(4-F-C
6
o
H
)
4 3
(0.04 mmol) and LiO Bu (0.6 mmol) in
MeCN (2.0 mL) at 90 C in air for 30 minutes.
Table 1. Optimization of the Reaction Conditionsa
Pd(OAc)2 (10 mol%)
Ph
ligand (20 mol%)
Ph
Ph
NHTs
Ph
t
N
LiO Bu (3.0 equiv)
solvent, 90 o
Cl
O
+
O
C
N
N
H
Bn
Bn
2a
3aa
1
a
entry
ligand
PPh
P(4-Me-C
solvent
time
3aab
1c
2c
3c
4d
5
MeCN
MeCN
MeCN
MeCN
MeCN
DMF
12 h
12 h
12 h
12 h
12 h
12 h
78%
75%
91%
70%
89%
62%
3
6
4 3
H )
P(4-F-C
DPPB
6
H
4
)
3
P(4-F-C
P(4-F-C
6
6
H
4
4
)
)
3
3
6
H
2
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 3 of 6
O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
COMMUNICATION
Pd(OAc)2 (10 mol%)
P(4-F-C H ) (20 mol%)
Pd(OAc)2 (10 mol%)
Ph
View Article Online
Ph
DOI: 10.1039/C9OB01672D
R4
R2
R2
6 4 3
P(4-F-C6H4)3 (20 mol%)
Ph
NHTs
R4
t
NHTs
Ph
t
N
LiO Bu (3.0 equiv)
N
LiO Bu (3.0 equiv)
+
O
R1
Cl
O
+
R1
Cl
O
MeCN, 90 oC, 30 min
O
MeCN, 90 oC, 30 min
N
R3
N
H
N
N
R3
H
Bn
Bn
1a
2
3
1
2a
3
F
Cl
Br
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
tBu
MeO
Ph
Ph
Ph
Ph
O
O
O
O
N
N
N
N
Bn
Bn
Bn
Bn
O
O
O
N
O
N
N
N
3
aa (95%)
3ba (81%)
3ca (80%)
3da (55%)
Bn
ab (82%)
Bn
3ac (78%)
Bn
Bn
3ae (62%)
3
3ad (66%)
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
MeO
F
Cl
O
O
O
O
NO2
CF3
N
N
N
N
Bn
Bn
Bn
Bn
Ph
Ph
Ph
Ph
3
ea (72%)
3fa (88%)
3ga (99%)
F
3ha (89%)
Cl
O
O
N
O
N
O
N
N
Bn
3af (33%)c
Bn
Bn
Bn
Ph
N
Ph
Ph
Ph
3ai (93%)
Ph
Ph
3ag (55%)
3ah (67%)
O2N
O
O
MeO
O
O
N
OMe
OMe
N
N
Bn
ia (75%)
Bn
Bn
Bn
3la (96%)
3
3ja (33%)
Ph
Ph
Ph
Ph
S
3
ka (93%)
Br
O
N
O
O
O
N
Ph
N
N
Bn
Bn
3ak (52%)
Bn
3al (57%)
Bn
Ph
Ph
Ph
Ph
F
O
Cl
3aj (57%)
3am (68%)
N
O
O
O
N
N
N
Bn
ma (74%)
Bn
3na (99%)
PMB
a
All reactions were performed with 1a (0.2 mmol), 2a (0.4 mmol), Pd(OAc)
2
(10 mol%),
3
3oa (57%)
3pa (99%)
o
b
c
P(4-F-C
6
H
4
)
3
(20 mol%) in MeCN (2.0 mL) at 90 C for 30 min. Isolated yield. 2 h
a
All reactions were performed with 1a (0.2 mmol), 2a (0.4 mmol) Pd(OAc)
2
(10 mol%),
(20 mol%) in MeCN (2.0 mL) at 90 C for 30 min. b Isolated yield.
o
P(4-F-C
6
H
4
)
3
On the basis of the well-known transition-metal-catalyzed
1
1-15
transformations of carbamoyl chloride.
A plausible
The scope of N-tosyl hydrazones 2 was also investigated. As
shown in Table 3, variety of electronically distinct
mechanism for this palladium-catalyzed intramolecular Heck-
type cascade reaction is proposed. As shown in Scheme 2, the
reaction is initiated by oxidative addition of Pd(0) to carbamoyl
chlorides to afford Pd(II) intermediate A. Then, intramolecular
insertion of the alkene into the C-Pd(II) bond via 5-exo
cyclization to form alkylpalladium species B. Diazo compound E
is generated in situ from N-tosylhydrazone 2a with treatment
of base. Decomposition of diazo compound E by Pd(II) species
B leads to palladium carbene intermediate C, followed by alkyl
migratory insertion to give intermediate D. Finally, a syn β-
hydride elimination process may occur to afford the 3-
vinyloxindoles 3aa and regenerates the Pd(0) catalyst.
a
substituents on N-tosyl hydrazones were tested. Substrates
bearing methyl at the para-position of phenyl ring proceeded
smoothly, afforded 3ab in 82% yield. The N-tosyl hydrazones
bearing a halide substitution (2c-2e) tolerated well, the desired
products 3ac-3ae were obtained in moderate yields, which
could be easily transformed into more complex molecules via
cross-couplings reactions. Strong electron-withdrawing groups
were also tolerated, such as nitro and trifluoromethyl groups
could provide the products in relatively low yield (3af and 3ag).
Furthermore, m-, o- and multisubstituted N-tosyl hydrazones
reacted smoothly to give the corresponding products in
5
2%−93% yields (3ah−3ak). Reaction with N-tosyl 1-
naphthaldehyde hydrazones 2l provided 3al in 57% yield.
Notably, heteroaryl contained substrate 2m was also tolerated,
which reacted with 1a to afford 3am in 68% yield.
Ph
Ph
O
N
Bn
aa
Ph
3
Pd(0)
Table 3. Variation of N-Tosyl Hydrazones 2a,b
Cl
O
N
Ph
Ph
Pd(II)
Bn
1a
O
N
D
Bn
Ph
Ph
Pd(II)
O
Ph
N
H
N
Pd(II)
Bn
O
A
Bn
Ph
C
Pd(II)
NHTs
Ph
N2
E
O
N
tBuOLi
N
H
Ph
Bn
H
2a
B
Ligands on palladium complexes have been omitted for clarity
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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COMMUNICATION
Journal Name
(a) Y. Kamano, H.-P. Zhang, Y. Ichihara, VHiew. AKrtiiczleuO,nlKine.
Scheme 2. Plausible Reaction Mechanism
4
Komiyama, G. R. Pettit, Tetrahedron Lett., 1995, 36, 2783; (b)
DOI: 10.1039/C9OB01672D
S. Miah, C. J. Moody, I. C. Richards, A. M. Z. Slawin, J.
Chem. Soc., Perkin. Trans., 1997, 1, 2405.
A. Jossang, P. Jossang, H. A. Hadi, T. Sevenet, B. Bodo, J.
Org. Chem., 1991, 56, 6527.
To further showcase the practical utility of this protocol, two
synthetic transformations were conducted. As shown in
Scheme 3, a hydrogenation reaction of 3aa proceeded
5
6
2
6
smoothly to give 4 in 79% yield. Moreover, 3aa could be
successfully deprotected by AIBN/NBS reagent to give N-
(a) F. Zhou, Y.-L. Liu, J. Zhou, Adv. Synth. Catal., 2010, 352,
1
381; (b) J. F. M. Silva, S. J. Garden, A. C. Pinto, J. Braz.
2
7
Chem. Soc., 2001, 12, 273; (c) C. Marti, E. M. Carreira, Eur.
J. Org. Chem., 2003, 12, 2209; (d) S. Peddibhotla, Curr.
Bioact. Compd., 2009, 5, 20; (e) A. Millemaggi, R. J. K.
Taylor, Eur. J. Org. Chem., 2010, 24, 4527; (f) J. E. M. N.
Klein, R. J. K. Taylor, Eur. J. Org. Chem., 2011, 34, 6821; (g)
A. Kumar, S. S. Chimni, RSC Adv., 2012, 2, 9748; (h) R.
Dalpozzo, G. Bartoli, G. Bencivenni, Chem. Soc. Rev., 2012,
unprotected 3-vinyloxindoles 5 in 82% yield.
Ph
Ph
Ph
Ph
Ph
Ph
Pd/C
AIBN, NBS
PhCl, 130 o
HCOONH4
O
O
O
MeOH, 80 o
C
C
N
N
N
H
5
2% yield
Bn
3aa
Bn
4
8
79% yield
41, 7247; (i) K. Shen, X. Liu, L. Lin, X. Feng, Chem. Sci.,
2012, 3, 327; (j) L. Hong, R. Wang, Adv. Synth. Catal., 2013,
355, 1023; (k) Z.-Y. Cao, Y.-H. Wang, X.-P. Zeng, J. Zhou,
Scheme 3. Synthetic Transformations
Tetrahedron Lett., 2014, 55, 2571.
7
For reviews, see: (a) J.-R. Chen, X.-Y. Yu, W.-J. Xiao,
Synthesis, 2015, 5, 604; (b) R.-J. Song, Y. Liu, Y.-X. Xie, J.-
H. Li, Synthesis, 2015, 47, 1195; (c) C.-C. Li, S.-D. Yang,
Org. Biomol. Chem., 2016, 14, 4365. For selected examples:
Conclusions
In conclusion, we have developed a palladium-catalyzed
Heck-type intramolecular cyclization of alkene-tethered
carbamoyl chlorides with N‑tosyl hydrazones. This reaction
demonstrates excellent reactivity, good functional group
tolerance and high efficiency. It provided a new way to
synthesize a range of functionalized 3-vinyloxindoles bearing
an all-carbon quaternary center. Investigation of the further
applications of this methodology is currently underway in our
laboratory.
(d) Z. Xu, C. Yan, Z.-Q. Liu, Org. Lett., 2014, 16, 5670; (e) B.
Schweitzer-Chaput, M. A. Horwitz, E. P. Beato, P.
Melchiorre, Nat. Chem., 2019, 11, 129; (f) J. Wu, J.-Y. Zhang,
P. Gao, S.-L. Xu, L.-N. Guo, J. Org. Chem., 2018, 83, 1046;
(g) Y. Zhao, N. Sharma, U. K. Sharma, Z. Li, G. Song, E. V.
V. Eycken, Chem. - Eur. J., 2016, 22, 5878; (h) Z. Li, Y.
Zhang, L. Zhang, Z.-Q. Liu, Org. Lett., 2014, 16, 382; (i) S.-
L. Zhou, L.-N. Guo, S. Wang, X.-H. Duan, Chem. Commun.,
2
014, 50, 3589; (j) H. Wang, L.-N. Guo, X.-H. Duan, Chem.
We gratefully acknowledge the National Natural Science
Foundation of China (21901184, 21572160); the
Science&Technology Development Fund of Tianjin Education
Commission for Higher Education (2018KJ159); Doctoral
Program Foundation of Tianjin Normal University (043135202-
XB1703); the Foundation of Development Program of Future
Expert in Tianjin Normal University (WLQR201811;
WLQR201914) and the Program for Innovative Research Team
in University of Tianjin (TD13-5074) for generous financial
support.
Commun., 2013, 49, 10370; (k) Y.-Y. Jiang, G.-Y. Dou, K.
Xu, C.-C. Zeng, Org. Chem. Front., 2018, 5, 2573.
8
For selected examples: (a) Y. Ping, Y. Li, J. Zhu, W. Kong,
Angew. Chem., Int. Ed., 2019, 58, 1562; (b) X. Liu, X. Ma, Y.
Huang, Z. Gu, Org. Lett., 2013, 15, 4814; (c) K. Wang, Z.
Ding, Z. Zhou, W. Kong, J. Am. Chem. Soc., 2018, 140,
12364; (d) Y. Li, K. Wang, Y. Ping, Y. Wang, W. Kong, Org.
Lett., 2018, 20, 921; (e) W. Kong, Q. Wang, J. Zhu, Angew.
Chem., Int. Ed., 2017, 56, 3987; (f) J. F. Rodriguez, A. D.
Marchese, M. Lautens, Org. Lett., 2018, 20, 4367; (g) A. Yen,
M. Lautens, Org. Lett., 2018, 20, 4323; (h) I. Franzoni, H.
Yoon, J.-A. Garcia-Lopez., A. I. Poblador-Bahamonde, M.
Lautens, Chem. Sci., 2018, 9, 1496.
9
For selected examples: (a) S. Jaegli, J. Dufour, H.-L. Wei, T.
Piou, X.-H. Duan, J.-P. Vors, L. Neuville, J. Zhu, Org. Lett.,
Conflicts of interest
There are no conflicts to declare.
2
010, 12, 4498; (b) T. Wu, X. Mu, G. Liu, Angew. Chem., Int.
Ed., 2011, 50, 12578; (c) X. Mu, T. Wu, H.-Y. Wang, Y.-L.
Guo, G. Liu, J. Am. Chem. Soc., 2012, 134, 878; (d) L. Shi, Y.
Wang, H. Yang, H. Fu, Org. Biomol. Chem., 2014, 12, 4070;
(
2
2
e) B. Zhou, W. Hou, Y. Yang, H. Feng, Y. Li, Org. Lett.,
014, 16, 1322; (f) C.-C. Li, S.-D. Yang, Org. Lett., 2015, 17,
142.
Notes and references
1
R. T. Brown, The Chemistry of Heterocyclic Compounds;
Saxton, J. E., Ed.; Part 4. Indoles: The Monoterpenoid Indole
Alkaloids; John Wiley and Sons, New York, 1983, 25, 85.
(a) B. M. Trost, M. K. Brennan, Synthesis, 2009, 18, 3003; (b)
A. D. Huters, E. D. Styduhar, N. K. Garg, Angew. Chem., Int.
Ed., 2012, 51, 3758; (c) R. Liu, E. H. Heiss, D. Schachner, B.
Jiang, W. Liu, J. M. Breuss, V. M. Dirsch, A. G. Atanasov, J.
Nat. Prod., 2017, 80, 2146; (d) Y.-T. Ma, Y. Yang, P. Cai,
D.-Y. Sun, P. A. Sanchez-Murcia, X.-Y. Zhang, W.-Q. Jia, L.
Lei, M. Guo, F. Gago, H. Wang, W.-S. Fang, J. Nat. Prod.,
1
0 (a) W. Dong, G. Xu, W. Tang, Tetrahedron, 2019, 75, 3239;
b) J. A. Grzyb, R. A. Batey, Tetrahedron Lett., 2008, 49,
279; (c) T. Iwai, T. Fujihara, J. Terao, Y. Tsuji, J. Am. Chem.
(
5
2
Soc., 2010, 132, 9602.
1
1 (a) A. Dufert, D. B. Werz, Chem. Eur. J. 2016, 22, 16718; (b)
L. F. Tietze, G. Brasche, K. M. Gericke, Domino Reactions in
Organic Synthesis 1st edition, Wiley-VCH, Weihnheim, 2006;
(c) L. F. Tietze, Chem. Rev. 1996, 96, 115; (d) Domino
Reactions, Concepts for Efficient Organic Synthesis (Ed.: L.
F. Tietze), Wiley-VCH, Weinheim, 2014.
2 (a) C. Tsukano, M. Okuno , Y. Takemoto, Angew. Chem., Int.
Ed., 2012, 51, 2763; (b) S. M. Hande, M. Nakajima, H.
Kamisaki, C. Tsukano, Y. Takemoto, Org. Lett., 2011, 13,
2018, 81, 524; (e) S.-J. Dai, K. Xiao, L. Zhang, Q.-T. Han, J.
1
Asian Nat. Prod. Res., 2016, 18, 456.
3
K. Monde, K. Sasaki, A. Shirata, M. Takasugi,
Phytochemistry, 1991, 30, 2915.
4
| J. Name., 2012, 00, 1-3
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Please do not adjust margins

Page 5 of 6
O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
828; (c) H. Kamisaki, Y. Yasui, Y. Takemoto, Tetrahedron
COMMUNICATION
1079; (j) J. Barluenga, N. Quiñones, M.-P. CabaVl,ieFw.AArticzlenOarn,linCe.
1
Lett., 2009, 50, 2589.
Valdés, Angew. Chem., Int. Ed., 2011, 50, 2350; (k) R.
DOI: 10.1039/C9OB01672D
1
1
1
3 A. Whyte, K. I. Burton, J. Zhang, M. Lautens, Angew. Chem.,
Int. Ed., 2018, 57, 13927.
4 C. Chen, J. Hu, J. Su, X. Tong, Tetrahedron Lett., 2014, 55, 23 For selected examples: (a) S. K. Devine, D. L. V. Vranken,
Barroso, M.-P. Cabal, R. B.-Laiño, C. Valdés, Chem. – Eur.
J., 2015, 21, 16463.
3229.
Org. Lett., 2008, 10, 1909; (b) R. Kudirka, D. L. V. Vranken,
J. Org. Chem., 2008, 73, 3585; (c) R. Kudirka, S. K. J.
Devine, C. S. Adams, D. L. V. Vranken, Angew. Chem., Int.
Ed., 2009, 48, 3677; (d) V. Arredondo, S. C. Hiew, E. S.
Gutman, I. D. U. A. Premachandra, D. L. V. Vranken, Angew.
Chem., Int. Ed., 2017, 56, 4156; (e) A. Khanna, C. Maung, K.
R. Johnson, T. T. Luong, D. L. Van Vranken, Org. Lett., 2012,
14, 3233; (f) M. Kitamura, R. Yuasa, D. L. V. Vranken,
Tetrahedron Lett., 2015, 56, 3027; (g) I. D. U. A.
Premachandra, T. A. Nguyen, C. Shen, E. S. Gutman, D. L. V.
Vranken, Org. Lett., 2015, 17, 5464; (h) E. S. Gutman, V.
Arredondo, D. L. V. Vranken, Org. Lett., 2014, 16, 5498.
5 (a) C. M. Le, X. Hou, T. Sperger, F. Schoenebeck, M.
Lautens, Angew. Chem., Int. Ed., 2015, 54, 15897; (b) C. M.
Le, T. Sperger, R. Fu, X. Hou, Y. H. Lim, F. Schoenebeck,
M. Lautens, J. Am. Chem. Soc., 2016, 138, 14441; (c) T.
Sperger, C. M. Le, M. Lautens, F. Schoenebeck, Chem. Sci.,
2017, 8, 2914.
16 H. Nozaki, S. Moriuti, H. Takaya, R. Noyori, Tetrahedron
Lett., 1966, 7, 5239.
17 (a) Y. Xia, D. Qiu, J. Wang, Chem. Rev., 2017, 117, 13810;
(b) M. P. Doyle, M. A. McKervey, T. Ye, Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds,
Wiley, New York, 1998; (c) P. A. Evans, Modern Rhodium- 24 For selected examples: (a) J. Li, X. Chi, L. Meng, L. Jiao, W.
Catalyzed Organic Reactions, Wiley-VCH, Weinheim, 2005;
d) F. Z. Dörwald, Metal Carbenes in Organic Synthesis,
Wiley-VCH, Weinheim, 1999; (e) T. Ye, M. A. McKervey,
Chem. Rev., 1994, 94, 1091.
8 K. L. Greenman, D. S. Carter, D. L. V. Vranken,
Tetrahedron, 2001, 57, 5219.
9 J. Barluenga, P. Moriel, C. Valdes, F. Aznar, Angew. Chem.,
Int. Ed., 2007, 46, 5587.
0 For some reviews, see: (a) N. M. G. Franssen, A. J. C.
Walters, J. N. H. Reek, B. Bruin, Catal. Sci. Technol., 2011,
Shang, P. Wang, D. Zhang, Y. Dong, Q. Liu, H. Liu, Org.
Biomol. Chem., 2018, 16, 7356; (b) E. Brachet, A. Hamze, J.-
F. Peyrat, J.-D. Brion, M. Alami, Org. Lett., 2010, 12, 4042;
(c) Z.-S. Chen, X.-H. Duan, L.-Y. Wu, S. Ali, K.-G. Ji, P.-X.
Zhou, X.-Y. Liu, Y.-M. Liang, Chem. – Eur. J., 2011, 17,
6918; (d) F. Zhou, K. Ding, Q. Cai, Chem. – Eur. J., 2011, 17,
12268; (e) I. Meana, A. C. Albeniz, P. Espinet,
Organometallics, 2012, 31, 5494; (f) I. Meana, A. Toledo, A.
C. Albeniz, P. Espinet, Chem. – Eur. J., 2012, 18, 7658; (g)
M. Roche, A. Hamze, J.-D. Brion, M. Alami, Org. Lett., 2013,
15, 148; (h) H. Chen, L. Huang, W. Fu, X. Liu, H. Jiang,
Chem. – Eur. J., 2012, 18, 10497; (i) M. Roche, A. Hamze, O.
Provot, J.-D. Brion, M. Alami, J. Org. Chem., 2013, 78, 445;
(j) Q. Yang, H. Chai, T. Liu, Z. Yu, Tetrahedron Lett., 2013,
54, 6485; (k) M.-C. Belhomme, D. Wang, K. J. Szabó, Org.
Lett., 2016, 18, 2503; (l) J. Feng, B. Li, Y. He, Z. Gu, Angew.
Chem., Int. Ed., 2016, 55, 2186; (m) Y. Xie, P. Zhang, L.
Zhou, J. Org. Chem., 2016, 81, 2128.
(
1
1
2
1
(
, 153; (b) Z. Zhang, J. Wang, Tetrahedron, 2008, 64, 6577;
c) Y. Zhang, J. Wang, Top. Curr. Chem., 2012, 327, 239; (d)
J. Barluenga, C. Valdes, Angew. Chem., Int. Ed., 2011, 50,
7
1
486; (e) Z. Zhang, Y. Zhang, J. Wang, ACS Catal., 2011, 1,
621; (f) Z. Shao, H. Zhang, Chem. Soc. Rev., 2012, 41, 560;
(g) Y. Zhang, J. Wang, Eur. J. Org. Chem., 2011, 6, 1015; (h)
Q. Xiao, Y. Zhang, J. Wang, Acc. Chem. Res., 2013, 46, 236.
1 For selected examples: (a) X. Wang, Y. Xu, Y. Deng, Y.
2
Zhou, J. Feng, G. Ji, Y. Zhang, J. Wang, Chem. – Eur. J., 25 (a) F. Han, W. Yang, A. Zhao, R. Zheng, C. Ji, X. Liu, G. Liu,
2
014, 20, 961; (b) S. Chen, J. Wang, Chem. Commun., 2008,
C. Chen, Asian J. Org. Chem., 2018, 7, 1124; (b) Z. Wang, T.
Li, J. Zhao, X. Shi, D. Jiao, H. Zheng, C. Chen, B. Zhu, Org.
Lett., 2018, 20, 6640; (c) Y. Bao, Z. Wang, C. Chen, B. Zhu,
Y. Wang, J. Zhao, J. Gong, M. Han, C. Liu, Tetrahedron,
2019, 75, 1450; (d) Y. Wang, J. Ding, J. Zhao, W. Sun, C.
Lian, C. Chen, B. Zhu, Org. Chem. Front., 2019, 6, 2240; (e)
J. Zhao, Y, Bao, Y. Wang, C. Chen, B. Zhu, Asian J. Org.
Chem., 2019, 8, 1317; (f) C. Chen, J. Ding, Y. Wang, X. Shi,
D. Jiao, B. Zhu, Tetrahedron Lett., 2019, DOI:
10.1016/j.tetlet.2019.151000; (g) T. Li, C. Liu, S. Wu, C.
Chen, B. Zhu, Org. Biomol. Chem., 2019, DOI:
10.1039/C9OB01531K; (h) T. Li, Z. Wang, C. Chen, B. Zhu,
Adv. Synth. Catal., 2019, 361, 2855.
35, 4198; (c) Z. Liu, J. Huo, T. Fu, H. Tan, F. Ye, M. L.
Hossain, J. Wang, Chem. Commun., 2018, 54, 11419; (d) Q.
Xiao, J. Ma, Y. Yang, Y. Zhang, J. Wang, Org. Lett., 2009,
11, 4732; (e) Y. Liu, Z. Zhang, S. Zhang, Y. Zhang, J. Wang,
Z. Zhang, Chem. – Asian J., 2018, 13, 3554; (f) L. Zhou, F.
Ye, Y. Zhang, J. Wang, J. Am. Chem. Soc., 2010, 132, 13590;
(g) X. Zhao, G. Wu, C. Yan, K. Lu, H. Li, Y. Zhang, J. Wang,
Org. Lett., 2010, 12, 5580; (h) L. Zhou, F. Ye, Y. Zhang, J.
Wang, Org. Lett., 2012, 14, 922; (i) Y. Zhou, F. Ye, X. Wang,
S. Xu, Y. Zhang, J. Wang, J. Org. Chem., 2015, 80, 6109; (j)
K. Wang, S. Chen, H. Zhang, S. Xu, F. Ye, Y. Zhang, J.
Wang, Org. Biomol. Chem., 2016, 14, 3809; (k) L. Zhou, F.
Ye, J. Ma, Y. Zhang, J. Wang, Angew. Chem., Int. Ed., 2011, 26 Y.-L. Liu, Z.-Z. Zhang, S.-Y. Yan, Y.-H. Liu, B.-F. Shi,
0, 3510; (l) Q. Xiao, B. Wang, L. Tian, Y. Yang, J. Ma, Y. Chem. Commun., 2015, 51, 7899.
Zhang, S. Chen, J. Wang, Angew. Chem., Int. Ed., 2013, 52, 27 J. Zhu, W. Zhang, L. Zhang, J. Liu, J. Zheng, J. Hu, J. Org.
305. Chem., 2010, 75, 5505.
5
9
2
2 For selected examples: (a) M. Paraja, R. Barroso, M. P. Cabal,
C. Valdés, Adv. Synth. Catal., 2017, 359, 1058; (b) J.
Barluenga, M. Escribano, P. Moriel, F. Aznar, C. Valdés,
Chem. – Eur. J., 2009, 15, 13291; (c) J. Barluenga, M.
Tomas-Gamasa, P. Moriel, F. Aznar, C. Valdés, Chem. – Eur.
J., 2008, 14, 4792; (d) J. Barluenga, M. Tomas-Gamasa, F.
Aznar, C. Valdés, Chem. – Eur. J., 2010, 16, 12801; (e) J.
Barluenga, M. Tomas-Gamasa, F. Aznar, C. Valdés, Adv.
Synth. Catal., 2010, 352, 3235; (f) J. Barluenga, M. Escribano,
F. Aznar, C. Valdés, Angew. Chem., Int. Ed., 2010, 49, 6856;
(g) J. Barluenga, L. Florentino, F. Aznar, C. Valdés, Org.
Lett., 2011, 13, 510; (h) L. Florentino, F. Aznar, C. Valdés,
Org. Lett., 2012, 14, 2323; (i) A. Jimenez-Aquino, J. A. Vega,
A. A. Trabanco, C. Valdés, Adv. Synth. Catal., 2014, 356,
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Pd(OAc)2 (10 mol%)
DOI: 10.1039/C9OB01672D
R2
R2
R4
P(4-F-C6H4)3 (20 mol%)
NHTs
R4
t
N
LiO Bu (3.0 equiv)
R1
+
R1
O
Cl
O
MeCN, 90 oC, 30 min
N
R3
H
N
R3
palladium-catalyzed cascade reaction
highly efficient reaction speed
good functional group compatibility
28 examples, up to 99% yield
all-carbon quaternary center construction
diversiform alkene-functionalized oxindoles
An efficient approach for the construction of alkene-functionalized oxindoles was developed via
palladium-catalyzed cascade reactions of alkene-tethered carbamoyl chlorides with N‑tosyl
hydrazones.