Asymmetric Dearomatization of Indole by Palladium/PC-Phos-Catalyzed Dynamic Kinetic Transformation

Article abstract of DOI:10.1002/anie.202010164

A palladium-catalyzed intermolecular dynamic kinetic asymmetric dearomatization of 3-arylindoles with internal alkynes was developed with the use of achiral Xantphos and chiral sulfinamide phosphine ligand (PC-Phos) as the co-ligands. This method could deliver various spiro[indene-1,3′-indole] compounds in good yields (up to 95 % yield) with up to 98 % ee. The salient features of the transformation include the use of readily available substrates, ease of scale-up and the versatile functionalization of the products. The mechanistic experiments gave some insights on active intermediates.

Full text of DOI:10.1002/anie.202010164

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Accepted Article
Title: Asymmetric Dearomatization of Indole via Palladium/PC-Phos-
Catalyzed Dynamic Kinetic Transformation
Authors: Junliang Zhang, Haoke Chu, Jie Cheng, Junfeng Yang, and
Yin-Long Guo
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Asymmetric Dearomatization of Indole via Palladium/PC-Phos-
Catalyzed Dynamic Kinetic Transformation
Haoke Chu, Jie Cheng, Junfeng Yang, Yin-Long Guo,* Junliang Zhang*
Abstract: A palladium-catalyzed intermolecular dynaymic kinetic
asymmetric dearomatization of 3-arylindoles with internal alkynes
was developed with the use of achiral Xantphos and chiral
sulfinamide phosphine ligand (PC-Phos) as the co-ligands. This
method could deliver various spiro[indene-1,3'-indole] compounds in
good yields (up to 95% yield) with up to 98% ee. The salient features
of the transformation include the use of readily available substrates,
ease of scale-up and the versatile functionalization of the products.
The mechanistic experiments gave some insights on active
intermediates.
sulfinamide phosphine ligand (PC-Phos) as the co-ligands,
which provides a facile access to a series of chiral spiro[indene-
1,3'-indole] bearing an all-carbon quaternary stereocenter in
good yields and high ees (Scheme 1, d).
Figure 1. Biologically active alkaloids containing spirocyclopentaneindoline
derivatives.
Chiral spirocyclopentaneindoline derivatives units are
prevalent and valuable scaffolds which show a wide spectrum of
biological activity (Figure 1).[1] The potential clinical significance
has led to the development of method for the efficient and
enantioselective synthesis of this core structure.[2] Common
methods for the asymmetric preparation include organometallic
approach[3] and organocatalytic approach.[4] In recently years,
one particularly attractive strategy to construct enantiomerically
enriched molecules is dynamic kinetic resolution (DKR),[5] which
allows for full conversion the racemic mixture to desired chiral
products (Scheme 1, a). One particular example was reported
by Luan and co-workers,[6] they developed an elegant Pd/chiral-
NHC-catalyzed intermolecular dearomatization of 1-naphthol via
a
dynamic kinetic asymmetric transformation, delivering
spironaphthalenones with high enantioselectivities (Scheme 1,
b). It is rare to realize this axial-to-central stereoconvergent
transformation. In this context, DKR of the atropisomeic
arylindole combined with dearomatization of indole to construct
a stereogenic quaternary spirocyclic center would be one
straightforward method for the synthesis of chiral
spirocyclopentaneindolenine. However, existing ligand failed in
this asymmetric protocol (Scheme 1, c).[7]
Over past few years, a series of novel chiral sulfinamide
phosphine (Sadphos), ligands such as Ming-Phos,[8] Xiang-
Phos[9], PC-Phos[10] and Xu-Phos[11] have been designed and
developed in our group, and they have shown excellent
performance in asymmetric transition-metal catalysis.[12] Inspired
by the successful applications and with regard to the
significance of spiroindolenine, we speculated whether these
chiral ligands could address the Pd-catalyzed intermolecular
dearomatization of indoles with alkynes. Herein, we present the
Scheme 1. Transition-metal-catalyzed dynamic kinetic asymmetric
dearomatization.
first
example
of
palladium-catalyzed
enantioselective
We began our study with 3-(2-bromophenyl)-1H-indole 1a and
diphenylacetylene 2a as the model substrates and [Pd(allyl)Cl]2
as a precatalyst. A series of commercially available privileged
chiral ligands were investigated (Figure 2). The bidentate N,P-
ligands PHOX L1−L2, could not deliver the product but the (R)-
(S)-PPFA L3 could deliver 2aa in 67% yield and with 8% ee.
Subsequently, bisphosphone ligands such as (R)-DTBM-
BIPHEP L4, (R)-BINAP L5, (R)-Segphos L6, (R)-SKP L7 and
(R)-SDP L8 could slightly improve the ee of 2aa. Additionally,
chiral phosphoramidite ligands L9-L10 failed to further improve
the enantioselectivity. Afterwards, the representative chiral
sulfinamide phosphine ligands developed by our goup were
investigated (Table 1). The diastereomers of Ming-Phos (M1
and M2) were not efficient either (Table 1, entries 1-2), while
intermolecular asymmetric dearomatization of indole derivatives
with internal alkynes by the use of achiral Xantphos and chiral
[*]
[*]
H. Chu, J. Yang, Prof. Dr. J. Zhang
Department of Chemistry, Fudan University, 2005 Songhu Road,
Shanghai, 200438, China
E-mail: junliangzhang@fudan.edu.cn
J. Cheng, Prof. Dr. Y.-L. Guo
Stake Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai, China
E-mail: ylguo@sioc.ac.cn
Supporting information for this article is given via a link at the end
of the document. ((Please delete this text if not appropriate))
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provide higher enantioselectivity than toluene (Table 1, entries
19-22). Finally, the optimal conditions were achieved with the
o
temperature reduced to 70 C and the time prolonged to 72 h,
providing 3aa in 92% yield with 92% ee (Table 1, entry 23).
With the optimal conditions in hand, we next examined the
scope of substituent 3-(2-bromophenyl)-1H-indole
1
with
diphenylacetylene 2a, and the results are summarized in
Scheme 2. High enantioselectivities (90-95% ee) were obtained
for the new quaternary stereogenic centers generated from
indole substrates 1 containing electron-donating groups and
electron-withdrawing groups at the various positions of indole
ring and 2-bromophenyl ring. For example,
a series of
substituted indoles with methyl at 4-, 5-, 6- and 7- positions have
been respectively investigated, and the corresponding spiro-
products 3ba-3ea were obtained in 80-87% yields with 90-94%
ees. It was noteworthy that 4-methyl (1b) and 7-methyl (1e)
substrates gave the full conversions within 48 hours. The
substrate containing a methoxyl at the 6-position (1f) of indole
ring notably reacted smoothly to generate the desired product
3fa in 69% yield with 93% ee. Optimally, 5-chloro (1g) and 6-
fluoro (1h) indoles have been confirmed as the effective
halogen-substituted starting materials with 2a to deliver the
desired 3ga-3ha in 61% yield with 91% ee and 70% yield with
90% ee respectively. Moreover, different substituents on o-
bromophenyl of the substrates could be tolerated in the reaction
conditions, delivering 3ia-3ma in 51-95% yield with 90-94% ee.
Figure 2. Screened chiral ligands in this work.
Table 1. Screening reaction conditions.
Yield
[%]b
NR
Entry
[M]
L
Solvent
ee [%]c
1
2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
Pd(OAc)2
(S, RS)-M1
(R, RS)-M1
(S, RS)-P1
(R, RS)-P1
(S, RS)-P2
(R, RS)-P2
(S, RS)-P3
(S, RS)-P4
(S, RS)-P5
(S, RS)-P6
(S, RS)-P7
(S, RS)-P8
(S, RS)-P9
(S, RS)-P6
(S, RS)-P6
(S, RS)-P6
(S, RS)-P6
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
-
NR
45
51
65
47
68
75
78
82
68
35
22
71
75
83
90
95
-
3
0
4
33
72
3
5
6
7
74
72
67
80
69
26
35
66
70
77
81
89
83
81
44
75
92
81
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23d
24d
Pd2(dba)3
Pd(MeCN)2Cl2
Pd(PPh3)2Cl2
Pd(Xantphos)Cl2 (S, RS)-P6
Pd(Xantphos)Cl2 (S, RS)-P6 mesitylene 85
Pd(Xantphos)Cl2 (S, RS)-P6
Pd(Xantphos)Cl2 (S, RS)-P6
Pd(Xantphos)Cl2 (S, RS)-P6
Pd(Xantphos)Cl2 (S, RS)-P6
xylene
dioxane
PhCF3
85
68
71
toluene
toluene
92e
91e
PdCl2
(S, RS)-P6
[a] Reaction condition: 1a (0.1 mmol), 2a (0.15 mmol), [Pd] (10 mol%),
ligand (15 mol%), K2CO3 (1.0 equiv) in 1.0 mL solvent at 80 ºC under N2
for 24-48 h. [b] NMR yield with CH2Br2 as an internal standard. [c]
Determined by chiral HPLC. [d] At 70 ºC for 72 h. [e] Isolated yield.
PC-Phos gratifyingly showed promising results (Table 1, entries
3-13), among which (S, RS)-P6 bearing a biphenyl group as the
R substituent gave the highest ee (Table 1, entry 10, 80% ee).
After the screening of different palladium catalysts (Table 1,
entries 14-18), we were pleased to observe an increase of the
ee to 89% by using Pd(Xantphos)Cl2 as the precatalyst (Table 1,
entry 18). The solvent study revealed that no other solvent could
Scheme 2. Effect of the Substitution of the Indole Substrates.
The scope of internal alkynes with indole 1a was
subsequently examined (Scheme 3). Firstly, a diverse array of
symmetrical alkynes containing two substituent phenyl rings
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were tolerated on the para- (2b−h) and meta- (2i), delivering
products 3ab−ai in 51−76% yield with up to 93% ee. Moreover,
di(thiophen-2-yl)acetylene 2j, bearing two heteroaryl groups,
could undergo the intermolecular annulation efficiently, leading
to 3aj in 80% yield with 90% ee. To our delight, dialkylacetylene
such as 4-octyne (2k) and 5-decyne (2l) showed more
adaptable in this process, and they gave the corresponding
products 3ak and 3al in better yields (90-92%) with higher ees
(94-96%). Therefore, more functionalized dialkylacetylene (2m-
2t) have been employed in our reaction. Diverse functionalized
spirocompounds bearing phenyl (3am), chloro (3an-3ao),
alkoxyl (3ap-3aq), vinyl (3ar), ester (3as) and phthalimino (3at)
are well furnished in 61-85% yield with 90-98% ee. Specifically,
the reactions of 1a with nonsymmetrical internal alkynes 2u−2y
proceeded smoothly to give products 3au−3ay in 85−87% yields
with 92−96% ee, and the silyl functionality remained untouched
(3ay). It is noteworthy that the products with the alkyl groups
installed closer to the spirocyclic carbon centers have higher ee
values than their corresponding regioisomers.
Scheme 4. Gram-scale synthesis and transformations of the products.
Scheme 3. Exploration of the effect of internal alkynes.
Figure 3. Controlled experiment.
A gram-scale synthesis of 3al was successfully carried out in
90% yield with 94% ee with the use of Pd(Xantphos)Cl2 (5 mol%)
and (S, RS)-P6 (7.5 mol%) (Scheme 4). The redcution of the
imine moiety of chiral spiroindolenine 3al (94% ee) was
achieved by the treatment with sodium cyanoborohydride,
delivering the chiral spiroindoline 4 in 75% yield with 94% ee.
The indoline-based polycyclic compound 5 could be formed via
the annulation of 3ay (95% ee) in the presence of TBAF in the
solution of THF at room temperature (89% yield, 95% ee). The
absolute configuration of the product 3 was established by the
X-ray crystallography of 6 obtained from 3nf by reduction and
sulfonylation (Scheme 4).
Three control experiments were then carried out to gain
some insights of the reaction (Figure 3). The reaction rate in the
absence of (S, RS)-P6 was lower than that under the standard
conditions. When PdCl2 was used instead of Pd(Xantphos)Cl2,
the reaction rate was faster than those under the above-
mentioned two conditions but with inferior ees. These results
indicated that a new in-situ generated palladium complex from
Pd(Xantphos)Cl2
and
(S,
RS)-P6
delivered
higher
enantioselectivity. It is also intereting to find there is an obvious
induction period for those two reactions under the standard
consitions with and without P6, indicating that it takes time to
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generate the real active catalyst. Next, Pd[(S, RS)-P6]Cl2 was
made according to our previous work[11b] and 10 mol% of Pd[(S,
RS)-P6]Cl2 was subjected to a series of reactions in the
presence of 0-20 mol% of Xantphos (Figure 4). The results
showed that Pd[(S, RS)-P6]Cl2 itself has high catalytic activity but
only delivers 51% ee. Interestingly, with the increasing of the
amount of Xantphos to 5 mol%, the ee of 3aa increased. The
yields and ees have no big difference when 5-10 mol% of
Xantphos was added. The ees decrease with the amount of
Xantphos more than 12.5 mol%. These experimental results
showed that a ligand-hybridized Pd complex from Pd[(S, RS)-
P6]Cl2 and Xantphos may be formed and is responsible to
deliver higher ee than Pd[(S, RS)-P6]Cl2.
Based on above results, we consequently proposed the
plausible catalytic cycle (Scheme 5). Firstly, unlike PdCl2 and
Pd(MeCN)2Cl2, the precatalyst Pd(Xantphos)Cl2 could not be
complete exchange by (S, RS)-P6, and they formed the ligand-
hybridized Pd(0) species Pd[(S, RS)-P6](Xantphos), which was
detected by the 31P NMR spectroscopy (see Supporting
Information, Figure S2). Then, the oxidative addition of Pd(0)
complex with 1a would give ArPd[(S, RS)-P6](Xantphos)Br (Ar =
2-(1H-indol-3-yl)phenyl) (A). Subsequent migratory insertion and
β-H elimination would furnish chiral spiro product 3aa with high
enantioselectivity. The Pd(0) could be regenerated after
reductive elimination of intermediate D which was promoted by
the base.[13] We also tried to detect the key reaction
intermediates by solvent-assisted electrospray ionization mass
spectrometry (SAESI-MS, see Supporting Information), which is
a direct and reliable method for the characterization of reactive
intermediates in-situ[14] and we indeed detected some reactive
species (see Supporting Information, Figure S4 and S5).
Figure 4. Predicted chiral catalyst and its catalytic activity.
For the non-linear effect study, Pd(Xantphos)Cl2 or Pd2(dba)3
was used as the precatalyst, and the linear relationship between
the ees of the (S, RS)-P6 and those of product 3aa suggested
that only one molecule of chiral ligand (S, RS)-P6 bonded to the
active palladium catalyst, and the reaction possessed a first-
order dependence on the catalyst (Figure 5).
Scheme 5. Proposed catalytic cycle.
In summary, we have developed the highly enantioselective
palladium-catalyzed intermolecular dynaymic kinetic asymmetric
dearomatization of indole derivatives with internal alkynes to
give chiral spiroindolenine compounds bearing an all-carbon
quaternary stereocenter with excellent enantioselectivities (up to
96% ee). Considered its operational simplicity, high efficiency,
high enantioselectivity, broad substrate scope and various
transformations, the present method can be expected to be used
in synthesis of alkaloids and pharmaceuticals containing chiral
spiroindolenine and spiroindoline skeletons. The mechanistic
investigations proved a ligand-hybridized Pd(0) complex may be
responsible for the high enantioselectivity. In addition, further
applications of chiral sulfonamide phosphine ligand we designed
and synthesized in other intermolecular transition-metal-
catalyzed asymmetric dearomatization are underway.
Acknowledgements
Figure 5. Non-linear effect study.
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H. Zhu, Y.-J. Chen, X.-D. Yang, X.-W. Sun, G.-Q. Lin, Angew. Chem.
Int. Ed. 2015, 54, 13253; Angew. Chem. 2015, 127, 13451; q) L. Wang,
S. Li, M. Blümel, R. Puttreddy, A. Peuronen, K. Rissanen, D. Enders,
Angew. Chem. Int. Ed. 2017, 56, 8516; Angew. Chem. 2017, 129, 8636.
a) F. F. Huerta, A. B. E. Minidis, J. E. Backvall, Chem. Soc. Rev. 2001,
30, 321; b) B. M. Trost, D. R. Fandrick, Aldrichimica Acta 2007, 40, 59;
c) J. Steinreiber, K. Faber, H. Griengl, Chem. Eur. J. 2008, 14, 8060; d)
M. Rachwalski, N. Vermue, F. P. J. T. Rutjes, Chem. Soc. Rev. 2013,
42, 9268; e) V. Bhat, E. R. Welin, X. Guo, B. M. Stoltz, Chem. Rev.
2017, 117, 4528.
We gratefully acknowledge the funding support of NSFC
(21672067, 21921003), and the Program of Eastern Scholar at
Shanghai Institutions of Higher Learning.
[5]
Keywords: Catalytic Asymmetric Dearomatization • Palladium •
Alkyne • Chiral Spiroindolenine• Dynamic Kinetic Transformation
How to cite: Angew. Chem. Int. Ed. xxxx, xx, xxxx-xxxx
Angew. Chem. xxxx, xx, xxxx-xxxx
[6]
[7]
[8]
L. Yang, H. Zheng, L. Luo, J. Nan, J. Liu, Y. Wang, X. Luan, J. Am.
Chem. Soc. 2015, 137, 4876.
[1]
a) S. Chowdhury, M. Chafeev, S. Liu, J. Sun, V. Raina, R. Chui, W.
Young, R. Kwan, J. Fu, J. A. Cadieux, Bioorg. Med. Chem. Lett. 2011,
21, 3676; b) L. Peng, W. Qin, H. Yan (Chongqing University, Peop. Rep.
China) CN109206430A, 2019; c) L. Peng, D. Xu, X. Yang, J. Tang, X.
Feng, S.-L. Zhang, H. Yan, Angew. Chem. Int. Ed. 2019, 58, 216;
Angew. Chem. 2019, 131, 222; d) J. Zhu, J. Cai, G. Li, Z. You, Y. Wu,
R. Han, Y. Ge, L. Wang, J. Wang (Sichuan Kelun-Biotech
Biopharmaceutical Co., Ltd., Peop. Rep. China) CN109928979A, 2019;
e) M. Chafeev, S. Chowdhury, R. Fraser, J. Fu, R. Kamboj, D. Hou, S.
Liu, M. Seid Bagherzadeh, S. Sviridov, S. Sun, J. Sun, N. Chakka, T.
Hsieh, V. Raina (Xenon Pharmaceuticals Inc., Can.) WO2008060789A2,
2008; f) M. Chafeev, S. Chowdhury, R. Fraser, J. Fu, R. Kamboj, D.
Hou, S. Liu, M. S. Bagherzadeh, S. Sviridov, S. Sun, J. Sun, N. Chakka,
T. Hsieh, V. Raina (Xenon Pharmaceuticals Inc., Can.)
WO2006110917A2, 2006.
L. Bai, J. Liu, W. Hu, K. Li, Y. Wang, X. Luan, Angew. Chem. Int. Ed.
2018, 57, 5151; Angew. Chem. 2018, 130, 5245.
a) Z.-M. Zhang, P. Chen, W. Li, Y. Niu, X. Zhao, J. Zhang, Angew.
Chem. Int. Ed. 2014, 53, 4350; Angew. Chem. 2014, 126, 4439; b) M.
Chen, Z.-M. Zhang, Z. Yu, H. Qiu, B. Ma, H.-H. Wu, J. Zhang, ACS
Catal. 2015, 5, 7488; c) Z.-M. Zhang, B. Xu, S. Xu, H.-H. Wu, J. Zhang,
Angew. Chem. Int. Ed. 2016, 55, 6324; Angew. Chem. 2016, 128, 6432;
d) B. Xu, Z.-M. Zhang, S. Xu, B. Liu, Y. Xiao, J. Zhang, ACS Catal.
2017, 7, 210; e) B. Liu, Z.-M. Zhang, B. Xu, S. Xu, H.-H. Wu J. Zhang,
Adv. Synth. Catal. 2018, 360, 2144; f) Y. Wang, Z.-M. Zhang, F. Liu, Y.
He, J. Zhang, Org. Lett. 2018, 20, 6403; g) X. Di, Y. Wang, L. Wu, Z.-M.
Zhang, Q. Dai, W. Li, J. Zhang, Org. Lett. 2019, 21, 3018.
[9]
a) H. Hu, Y. Wang, D. Qian, Z.-M. Zhang, L. Liu, J. Zhang, Org. Chem.
Front. 2016, 3, 759; b) P.-C. Zhang, Y. Wang, Z.-M. Zhang, J. Zhang,
Org. Lett. 2018, 20, 7049.
[2]
[3]
For reviews, see: a) R. Rios, Chem. Soc. Rev. 2012, 41, 1060; b) A.
Ding, M. Meazza, H. Guo, J. W. Yang, R. Rios, Chem. Soc. Rev. 2018,
47, 5946; c) P. W. Xu, J. S. Yu, C. Chen, Z. Y. Cao, F. Zhou, J. Zhou,
ACS Catal 2019, 9, 1820; d) C. Zheng, S.-L. You, Chem 2016, 1, 830.
For selectied examples, see: a) B. M. Trost, N. Cramer, S. M.
Silverman, J. Am. Chem. Soc. 2007, 129, 12396; b) C. P. Grugel, B.
Breit, Org. Lett. 2019, 21, 5798; c) C.-X. Zhuo, W. Zhang, S.-L. You,
Angew. Chem. Int. Ed. 2012, 51, 12662; Angew. Chem. 2012, 124,
12834; d) N. R. Ball-Jones, J. J. Badillo, N. T. Tran, A. K. Franz, Angew.
Chem. Int. Ed. 2014, 53, 9462; Angew. Chem. 2014, 126, 9462; e) S.
Afewerki, G. Ma, I. Ibrahem, L. Liu, J. Sun, A. Córdova, ACS Catal
2015, 5, 1266; f) Z.-S. Liu, W.-K. Li, T.-R. Kang, L. He, Q.-Z. Liu, Org.
Lett. 2015, 17, 150; g) X. Zhao, X. Liu, H. Mei, J. Guo, L. Lin, X. Feng,
Angew. Chem. Int. Ed. 2015, 54, 4032; Angew. Chem. 2015, 127, 4104;
h) X. Zhao, X. Liu, Q. Xiong, H. Mei, B. Ma, L. Lin, X. Feng, Chem.
Commun. 2015, 51, 16076; i) Y. Wang, C. Zheng, S.-L. You, Angew.
Chem. Int. Ed. 2017, 56, 15093; Angew. Chem. 2017, 129, 15289; j)
Q.-F. Wu, C. Zheng, S.-L. You, Angew. Chem. Int. Ed. 2012, 51, 1680;
Angew. Chem. 2012, 124, 1712; k) K.-J. Wu, L.-X. Dai, S.-L. You, Org.
Lett. 2012, 14, 3772; l) Q.-F. Wu, C. Zheng, C.-X. Zhuo, S.-L. You,
Chem. Sci. 2016, 7, 4453; m) Q.-F. Wu, H. He, W.-B. Liu, S.-L. You, J.
Am. Chem. Soc. 2010, 132, 11418
[10] a) Y. Wang, P. Zhang, X. Di, Q. Dai, Z.-M. Zhang, J. Zhang, Angew.
Chem. Int. Ed. 2017, 56, 15905; Angew. Chem. 2017, 129, 16121; b) L.
Wang, M. Chen, P. Zhang, W. Li, J. Zhang, J. Am. Chem. Soc. 2018,
140, 3467; c) P.-C. Zhang, J. Han, J. Zhang, Angew. Chem. Int. Ed.
2019, 58, 11444; Angew. Chem. 2019, 131, 11566.
[11] a) Z.-M. Zhang, B. Xu, L. Wu, Y. Wu, Y. Qian, L. Zhou, Y. Liu, J. Zhang,
Angew. Chem. Int. Ed. 2019, 58, 14653; Angew. Chem. 2019, 131,
14795; b) Z.-M. Zhang, B. Xu, L. Wu, L. Zhou, D. Ji, Y. Liu, Z. Li, J.
Zhang, J. Am. Chem. Soc. 2019, 141, 8110.
[12] For a general review: Y. Liu, W. Li, J. Zhang, Natl. Sci. Rev. 2017, 4,
326.
[13] a) C. Amatore, A. Jutand, A. Thuilliez, Organometallics 2001, 20, 3241;
b) L. M. Klingensmith, E. R. Strieter, T. E. Barder, S. L. Buchwald,
Organometallics 2006, 25, 82; c) H. Li, G. A. Grasa, T. J. Colacot, Org.
Lett. 2010, 12, 3332, d) C. S. Wei, G. H. M. Davies, O. Soltani, J.
Albrecht, Q. Gao, C. Pathirana, Y. Hsiao, S. Tummala, M. D. Eastgate,
Angew. Chem. Int. Ed. 2013, 52, 5822; e) C. Amatore, L. El Kaïm, L.
Grimaud, A. Jutand, A. Meignié, G. Romanov, Eur. J. Org. Chem. 2014,
4709.
[14] J.-T. Zhang, H.-Y. Wang, W. Zhu, T.-T. Cai, Y.-L. Guo, Anal. Chem.
2014, 86, 8937.
[15] CCDC 2018773 (6) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre.
[4]
For selectied examples, see: a) K. Jiang, B. Tiwari, Y. R. Chi, Org. Lett.
2012, 14, 2382; b) A. Noole, K. Ilmarinen, I. Järving, M. Lopp, T.
Kanger, J. Org. Chem. 2013, 78, 8117; c) G. Zhan, M.-L. Shi, Q. He,
W.-J. Lin, Q. Ouyang, W. Du, Y.-C. Chen, Angew. Chem. Int. Ed. 2016,
55, 2147; Angew. Chem. 2016, 128, 2187; d) Y.-M. Li, X. Li, F.-Z. Peng,
Z.-Q. Li, S.-T. Wu, Z.-W. Sun, H.-B. Zhang, Z.-H. Shao, Org. Lett. 2011,
13, 6200; e) J.-Q. Zhang, N.-K. Li, S.-J. Yin, B.-B. Sun, W.-T. Fan, X.-W.
Wang, Adv. Synth. Catal. 2017, 359, 1541; f) B. Tan, N. R. Candeias, C.
F. Barbas, Nat. Chem. 2011, 3, 473; g) B. Tan, N. R. Candeias, C. F.
Barbas, J. Am. Chem. Soc. 2011, 133, 4672; h) B. Xiang, K. M. Belyk,
R. A. Reamer, N. Yasuda, Angew. Chem. Int. Ed. 2014, 53, 8375;
Angew. Chem. 2014, 126, 8515; i) J. Zhang, D. Cao, H. Wang, C.
Zheng, G. Zhao, Y. Shang, J. Org. Chem. 2016, 81, 10558; j) W. Tan, X.
Li, Y.-X. Gong, M.-D. Ge, F. Shi, Chem. Commun. 2014, 50, 15901; k)
F. Zhong, X. Han, Y. Wang, Y. Lu, Angew. Chem. Int. Ed. 2011, 50,
7837; Angew. Chem. 2011, 123, 7983; l) Y. Zheng, J. Cleaveland, D.
Richardson, Y. Yuan, Org. Lett. 2015, 17, 4240; m) A. Voituriez, N.
Pinto, M. Neel, P. Retailleau, A. Marinetti, Chem. Eur. J. 2010, 16,
12541; n) W. Sun, G. Zhu, C. Wu, L. Hong, R. Wang, Chem. Eur. J.
2012, 18, 13959; o) S. Bera, C. G. Daniliuc, A. Studer, Angew. Chem.
Int. Ed. 2017, 56, 7402; Angew. Chem. 2017, 129, 7508; p) Q.-S. Sun,
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10.1002/anie.202010164
Angewandte Chemie International Edition
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H. Chu, J. Cheng, J. Yang, Y.-L. Guo,* J.
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Asymmetric Dearomatization of Indole
via
Palladium/PC-Phos-Catalyzed
Dynamic Kinetic Transformation
A
palladium-catalyzed intermolecular asymmetric dearomatization of 3-
arylindoles with internal alkynes was developed with the use of achiral Xantphos
and chiral sulfinamide phosphine ligand (PC-Phos) as the co-ligands. This method
could deliver various spiro[indene-1,3'-indole] compounds in good yields (up to
95% yield) with up to 98% ee.
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