Organocatalytic Asymmetric Cascade Aerobic Oxidation and Semipinacol Rearrangement Reaction: A Visible Light-Induced Approach to Access Chiral 2,2-Disubstituted Indolin-3-ones

Article abstract of DOI:10.1002/asia.201800446

An enantioselective cascade aerobic oxidation and semipinacol rearrangement reaction of 2-aryl-3-alkyl-substituted indoles via visible-light-driven cooperative organophotoredox and H-bonding catalysis is reported. The current method provides an expedient and sustainable approach to furnish a variety of valuable chiral 2-aryl-2-alkyl-substituted indolin-3-ones in 64–90 % yield with 58–94 % ee. Preliminary control experiments present important insights into the stereochemistry.

Full text of DOI:10.1002/asia.201800446

DOI: 10.1002/asia.201800446
Communication
Organocatalysis
Organocatalytic Asymmetric Cascade Aerobic Oxidation and
Semipinacol Rearrangement Reaction: A Visible Light-Induced
Approach to Access Chiral 2,2-Disubstituted Indolin-3-ones
+
[a]
+ [a]
[a, b]
[a]
[c]
[a]
Liwei Bu , Jiangtao Li , Yanli Yin,
Baokun Qiao, Guobi Chai, Xiaowei Zhao,* and
[a]
Zhiyong Jiang*
lished, leading to diverse significant chiral indolin-3-ones with
Abstract: An enantioselective cascade aerobic oxidation
and semipinacol rearrangement reaction of 2-aryl-3-alkyl-
substituted indoles via visible-light-driven cooperative or-
ganophotoredox and H-bonding catalysis is reported. The
current method provides an expedient and sustainable
approach to furnish a variety of valuable chiral 2-aryl-2-
alkyl-substituted indolin-3-ones in 64–90% yield with 58–
a wealth of quaternary carbon centers at 2-position. Neverthe-
less, the novel and expedient method to access new chiral var-
iants still remains highly desirable.
Inspired by the tremendous success in organic synthesis as
providing an attractive and powerful open-shell electron-trans-
[5]
fer approach, visible light-driven photocatalysis has recently
been adopted to realize the synthesis of the valuable 2-aryl-2-
alkyl-substituted indolin-3-ones from the readily available feed-
94% ee. Preliminary control experiments present impor-
[6]
tant insights into the stereochemistry.
stocks. In 2014, Brasholz and co-workers described an anthra-
quinone-enabled tandem organocatalysis and photocatalysis,
allowing the transformation of indoles with benzyl amines to
such indolin-3-ones through an alkylation-photooxidation-1,2-
[6a]
2
,2-Disubstituted indolin-3-ones are privileged structural scaf-
shift sequence (Scheme 1A). Almost at the same time, Xiao
and Lu and co-workers reported cascade photooxidation and
semipinacol rearrangement (i.e. 1,2-shift) directly from 2-aryl-3-
alkyl-substituted indoles by using Ru(byp) Cl as the photore-
[
1]
folds widely existing in a number of pseudoindoxyl alkaloids.
Moreover, they are frequently harnessed as common synthetic
intermediates for the total synthesis of many indole alkaloids
3
2
[
2]
[6b]
and other molecules with important bioactivities. As such,
the development of catalytic enantioselective methods to
access chiral 2,2-disubstituted indolin-3-ones has attracted a
special attention of chemists in the past few years. To date,
two asymmetric addition strategies involving with 2-monosub-
dox catalyst (Scheme 1B).
Meanwhile, they attempted an
enantioselective manifold, and presented a representative
chiral product with 60% ee by using an extra BINOL-derived
chiral phosphoric acid (CPA) catalyst. While the enantioselectiv-
ity was moderate, the promising result reveals the viability of
such a synergetic asymmetric catalytic platform.
[3]
stituted indoline-3-ones and their derivatives as nucleophiles
[
4]
and using 3H-indol-3-ones as electrophiles have been estab-
In recent years, we were keen on the development of visible
[7,8]
light-driven enantioselective reactions via cooperative
orga-
+
+
nocatalysis with our developed dicyanopyrazine-derived chro-
[
a] L. Bu, J. Li, Y. Yin, Dr. B. Qiao, X. Zhao, Prof. Dr. Z. Jiang
Key Laboratory of Natural Medicine and Immuno-Engineering of Henan
Province
[9]
mophore (DPZ) as the photoredox catalyst and a chiral orga-
[9c–f]
nocatalyst.
Probably due to the decreased interference of
Henan University
Jinming Campus, Kaifeng, Henan, 475004 (P. R. China)
E-mail: rosamary0530@sina.com
DPZ to chiral catalysts in the stereocontrol process for its high
catalytic efficacy-enabled low catalyst loading, the cooperative
catalysis with DPZ usually provided higher enantioselectivity
than utilizing other commonly used photocatalysts. Given the
comparability of DPZ and Ru(bpy) Cl in the electrochemical
chmjzy@henu.edu.cn
[
b] Y. Yin
College of Bioengineering
Henan University of Technology
Zhengzhou, Henan, 450001 (P. R. China)
3
2
properties, accordingly, we were intrigued to challenge such a
pendent but important task by using DPZ as the photocatalyst.
The method will offer a sustainable transition-metal free cata-
[
c] Dr. G. Chai
Key Laboratory of Tobacco Flavor Basic Research of CNTC
Zhengzhou Tobacco Research Institute of CNTC
Zhengzhou, Henan, 450001 (P. R. China)
[5e]
lytic manifold to synthesize chiral 2-aryl-2-alkyl-substituted
indolin-3-ones. Notoriously, how to conquer a racemic back-
ground process occurring directly via the intrinsic redox cata-
lytic cycle, which will decrease the enantioselectivity, consti-
tutes an elusive challenge. In this communication, we would
like to report our preliminary results (Scheme 1C).
+
[
] These authors contributed equally to this work.
Supporting information and the ORCID identification number(s) for the au-
thor(s) of this article can be found under:
https://doi.org/10.1002/asia.201800446.
This manuscript is part of a special issue on homogeneous catalysis. A link
to the Table of Contents of the special issue will appear here when the
complete issue is published.
We began our investigation by using 2-phenyl-3-benyl
indole (1a) as the model substrate. The initial study revealed
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Scheme 1. Visible light-driven photocatalysis to access 2,2-disubstituted indolin-3-ones and the development of enantioselective manifolds. BINOL=1-(2-hy-
droxynaphthalen-1-yl)naphthalen-2-ol; SPINOL=1,1’-spirobiindane-7,7’-diol; LED=light-emitting diode.
that the reaction of 1a in the presence of 0.5 mol% of DPZ in
CH Cl solvent at 258C under ambient atmosphere and irradiat-
We then conducted control experiments to determine the sig-
nificance of DPZ, chiral catalyst, visible light and oxygen (en-
tries 8–12). Both DPZ and CPA C1 are significant to improve
the reactivity (entries 8–9). When in the absence of both C1
and DPZ, the reaction became sluggish and afforded rac-2a
in 30% yield (entry 10). Finally, no reaction occurred when
2
2
ed by a 3 W blue LED could be finished within 12 hours, lead-
ing to the desired product rac-2a in 35% yield (See entry 1,
Table S1 in the Supporting Information [SI]). The low yield was
stemmed from the poor chemoselectivity, but the obtained
rac-2a indicated the capability of DPZ to
[10]
allow 1a to undergo an aerobic oxidation
and semipinacol rearrangement sequence.
Afterwards, we were engaged in examining
[
a]
Table 1. Optimization of reaction conditions.
an array of reaction parameters and explor-
ing a range of CPAs as an extrinsic chiral H-
bonding catalyst to provide a possible ste-
reocontrol (See Table S1 in SI). We were
pleased to find that 2a was obtained in
87% yield with 92% ee when the reaction
was carried out in tBuPh at 88C for 40 hours
in the presence of 10 mol% of SPINOL-
based spirocyclic CPA C1 and 25 mg 4 ꢁ
molecular sieves (MS) as an additive
[
b]
[c]
Entry
Variation from the standard conditions
Yield [%]
Ee [%]
(
entry 1, Table 1). The use of other SPINOL-
1
2
3
4
5
6
7
8
9
None
87
65
77
80
60
72
68
57
60
30
N.R.
N.R.
92
79
53
–63
–28
84
85
N.A.
88
derived spirocyclic CPAs C2-3 with 9-phen-
anthryl and 2-MeO-5-MeC H instead of 4-
C2 instead of C1
C3 instead of C1
C4 instead of C1
C5 instead of C1
Rose Bengal instead of DPZ
[Ru(bpy)
No C1
No DPZ
6
3
pyrenyl at the 6,6’-position and BINOL-CPAs
C4-5 afforded 2a with lower ee (entries 2–
5
), which showed the important effect of
3
]Cl
2
instead of DPZ
the substituent and the backbone of cata-
lyst on the enantioselectivity. It is notewor-
thy that the absolute configuration was in-
versed when BINOL-CPA was employed (en-
tries 4–5). Other photoredox catalysts, such
as Rose Bengal and [Ru(bpy) ]Cl , were also
1
0
No C1 and DPZ
No light
No air
N.A.
N.A.
N.A.
11
12
[a] The reaction was conducted on a 0.05-mmol scale. [b] Yields were determined from the isolat-
ed compound following chromatographic purification. [c] Enantiomeric excesses were determined
by HPLC analysis on a chiral stationary phase. MS=molecular sieves. N.R.=no reaction. N.A.=not
available.
3
2
examined (entries 6–7), but the yield and
enantioselectivity were decreased slightly.
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without light and oxygen (entries 11–12) indicate that this is
an aerobic and visible light-driven transformation.
were complete within 40 hours, affording a series of 2-aryl-2-
alkyl-substituted indolin-3-ones 2a-x in 64–90% yield with 58–
94% ee. The introduction of the substituent group on the aro-
matic ring of indoles (2b–d), 3-benzyls (2e–p) and 2-aryls (2t-
With the optimized reaction conditions in hand, we began
to evaluate the substrate scope (Scheme 2). All the reactions
Scheme 2. Substrate scope. The reaction was conducted on a 0.10-mmol scale. Yields were determined from the isolated compound following chromato-
graphic purification. Enantiomeric excesses were determined by HPLC analysis on a chiral stationary phase. [a] When the reaction was performed in a
1.0 mmol scale, 2a was obtained in 89% yield with 88% ee after 96 hours.
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x) was found to generally decrease the enantioselectivity and
With respect to the reaction mechanism, the Xiao group has
contributed an elegant and systematic work to reveal a plausi-
ble single-electron transfer process triggered from the reduc-
tive quenching of visible light-excited photoredox catalyst with
[
11]
gave the products with moderate to good ee values. The re-
sults also indicated that the meta-substituent on the 3-benzyl
group presented a comparative higher enantioselectivity than
the para-substituent (i.e. 2e vs. 2 f, 2g vs. 2h, 2k vs. 2l and
[6b]
indoles. Our investigations using Stern–Volmer experiments
also demonstrated the viability of DPZ as a photoredox cata-
2
2
o vs. 2p), and the ortho-substituent gave the lowest ee (i.e.
i vs. 2g and 2h) probably due to the steric hindrance. While
[13]
lyst to oxidize such indoles via single-electron transfer. Nev-
ertheless, we were intrigued to further investigate the mecha-
nism on the stereochemistry. Of note, with the transformation
of 1a to 2a as an example, at the beginning of generating the
product 3a, 3-benzyl-2-phenyl-3H-indolin-3-ol 3a as an inter-
mediate could be detected by the TLC analysis. Accordingly,
we carried out the reaction of 1a under the standard reaction
conditions and examined the results after 17 hours
(Scheme 3A). It was found that the conversion was 65% and
the ratio of 2a:3a was determined as 3:2, in which the ee
values of 2a and 3a were 81% and 59% respectively. The
enantioenriched 3a indicated that the chiral CPA has furnished
it is difficult to conclude a discipline of the electronic effect of
the substituent groups to the enantioselectivity, the bulkier iPr
(
2m) and tBu (2n) were capable of giving higher ee than
methyl (2k). Certainly, the replacement of 3-benzyl group
could improve the enantioselectivity occasionally; when thio-
phen-2-ylmethyl was introduced at 3-position, the correspond-
ing product 2r was obtained in 94% ee. Cyclohexylmethyl as a
representative 3-alkyl group was also examined, affording
product 2s with 67% ee. To evaluate the utility of this method,
the transformation of 1a was carried out in a 1.0 mmol scale
(
footnote a). It was observed that the reaction became slightly
sluggish but still was complete after 96 hours, furnishing 2a in
9% yield with 88% ee. The stereochemistry of the products
[6b]
a stereocontrol to the OÀO cleavage process after aerobic
oxidation.
8
2
a–q and 2s-x was assigned based on the structure of 2r, as
To probe the effect of chiral CPA in the process of semipina-
[
12]
[14]
solved by single-crystal X-ray diffraction.
col rearrangement, rac-3a was directly treated under the es-
1
Scheme 3. Experimental studies to elucidate the mechanism. The conversion and the ratio of 2a:3a were determined by crude H NMR analysis. Enantiomeric
excesses were determined by HPLC analysis on a chiral stationary phase.
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Communication
tablished reaction conditions (Scheme 3B). After 13 hours, 80%
of rac-3a was transformed to 2a with 8% ee and the rest 20%
of 3a was determined with À22% ee. When the reaction was
complete after 24 hours, the ee value of 2a was 0%. The same
reaction conducted without the irradiation of visible light gave
the similar results. Therefore, it is reasonable that the semipina-
col rearrangement does not require the visible light and the
transformation of 2a to 3a with chiral CPA catalyst should be
a kinetic resolution process as the observation of a chiral inver-
sion of 3a. Furthermore, given the finally obtained 0% ee of
(50 mg), tert-butylbenzene (1.0 mL) were added successively. The
reaction mixture was stirred under irradiation by 3W blue LED (l=
4
50–455 nm) at 88C (the temperature was maintained in an incu-
bator) from a 4.0 cm distance. The reaction was monitored by TLC.
Upon complete consumption of 1, the solvent was removed in
vacuo and the residue was purified by column chromatography on
silica gel with hexane/ethyl acetate (100/1–50/1 ratio) to give the
desired products 2.
Acknowledgements
2
a, chiral CPA should not be responsible to the increased
Grants from the NSFC (21672052), Provincial Innovation Scien-
tists and Technicians Troop Construction Projects and Henan
provincial science and technology department natural science
project (162300410002, 162102210193) are gratefully acknowl-
edged.
enantioselectivity of 2a from the lower ee of 3a (see
Scheme 3A). We next attempted the transformation of 3a with
50% ee under the standard reaction conditions but using an
achiral phosphoric acid 4 and without the visible-light irradia-
tion (Scheme 3C). It was found that 2a with 70% ee and 3a
with an unchanged optical purity were detected in a 3.5:1
ratio after 12 hours. The results described in Scheme 3D ex-
cluded the possibility of chiral product 2 as a chiral promoter
to enhance the enantioselectivity but led to a clear clue that
phosphoric acid is indispensable to tremendously increase the
reactivity for this process. In this context, it is plausible that
CPA is responsible to the enantioselectivity of the first aerobic
oxidation and the resulted chiral 3-hydroxy intermediate acts
as a chiral promoter to the semipinacol rearrangement. Given
the finally excellent ee of 2a obtained (Scheme 3A), higher
enantioselectivity to the semipinacol rearrangement would
probably be engaged by chiral 3a when its concentration was
decreased at the end of the transformation. On the basis of
this proposed mechanism, the elusive enantioselectivity for di-
verse 2-aryl-3-alkyl indoles would be derived from the generat-
ed different chiral 3-hydroxy intermediates affording distinct
enantiofacial induction.
Conflict of interest
The authors declare no conflict of interest.
Keywords: cooperative photoredox and asymmetric catalysis ·
indolin-3-ones · organocatalysis · oxidation · semipinacol
rearrangement
[
1] a) M. Kawada, H. Sugihara, I. Mikami, K. Kawai, S. Kuzuna, S. Noguchi, Y.
Sanno, Chem. Pharm. Bull. 1981, 29, 1912; b) R. M. Williams, T. Glinka, E.
Kwast, H. Coffman, J. K. Stille, J. Am. Chem. Soc. 1990, 112, 808; c) A.
Asai, S. Nagamura, E. Kobajashi, K. Gomi, H. Saito, Bioorg. Med. Chem.
Lett. 1996, 6, 1215; d) J.-F. Liu, Z.-Y. Jiang, R.-R. Wang, Y.-T. Zeng, J.-J.
Chen, X.-M. Zhang, Y.-B. Ma, Org. Lett. 2007, 9, 4127; e) C.-J. Tan, Y.-T. Di,
Y.-H. Wang, Y. Zhang, Y.-K. Si, Q. Zhang, S. Gao, X.-J. Hu, X. Fang, S.-F. Li,
X.-J. Hao, Org. Lett. 2010, 12, 2370; f) C. V. S. Kumar, V. G. Puranik, C. V.
Ramana, Chem. Eur. J. 2012, 18, 9601; g) T. Abe, A. Kukita, K. Akiyama, T.
Naito, D. Uemura, Chem. Lett. 2012, 41, 728; h) W. Gu, Y. Zhang, X.-J.
Hao, F.-M. Yang, Q.-Y. Sun, S. L. Morris-Natschke, K.-H. Lee, Y.-H. Wang,
C.-L. Long, J. Nat. Prod. 2014, 77, 2590.
In summary, we have developed an enantioselective cascade
aerobic oxidation and semipinacol rearrangement reaction of
2-aryl-3-alkyl-substituted indoles via visible-light-driven syner-
[
2] a) W. H. Pearson, Y. Mi, I. Y. Lee, P. Stoy, J. Am. Chem. Soc. 2001, 123,
6724; b) Y. Liu, W. W. McWhorter, Jr., C. E. Hadden, Org. Lett. 2003, 5,
getic photoredox and asymmetric organocatalysis. The current
methodology presents an efficient and transition-metal free
approach to access a range of pharmaceutically and biological-
ly significant enantioenriched 2-aryl-2-alkyl-substituted indolin-
333; c) Y. Liu, W. W. McWhorter, J. Am. Chem. Soc. 2003, 125, 4240; d) K.
Higuchi, Y. Sato, M. Tsuchimochi, K. Sugiura, M. Hatori, T. Kawasaki, Org.
Lett. 2009, 11, 197; e) X. Qi, H. Bao, U. Tambar, J. Am. Chem. Soc. 2011,
1
33, 10050; f) S. Han, M. Movassaghi, J. Am. Chem. Soc. 2011, 133,
3
-ones in 64–90% yield with 58–94% ee. The mechanism study
10768; g) T. Buyck, Q. Wang, J. Zhu, Org. Lett. 2012, 14, 1338; h) B. Nar-
endraprasad Reddy, C. V. Ramana, Chem. Commun. 2013, 49, 9767; i) B.
Zhao, X.-Y. Hao, J.-X. Zhang, S. Liu, X.-J. Hao, Org. Lett. 2013, 15, 528;
j) S. Han, K. C. Morrison, P. J. Hergenrother, M. Movassaghi, J. Org. Chem.
via control experiments demonstrates that the used chiral
phosphoric acid catalyst presents stereocontrol for aerobic oxi-
dation and the generated chiral 3-hydroxy intermediate plays a
key role to affect the enantioselectivity of semipinacol rear-
rangement. The high enantioselectivity obtained herein in-
spired us to further pursue novel and challenging transforma-
tions by means of visible-light-driven cooperative catalysis in-
volving DPZ and chiral H-bonding catalysts.
2
014, 79, 473; k) N. David, R. Pasceri, R. R. A. Kitson, A. Pradal, C. J.
Moody, Chem. Eur. J. 2016, 22, 10867; l) C. Wang, Z. Wang, X. Xie, X. Yao,
G. Li, L. Zu, Org. Lett. 2017, 19, 1828.
3] For selected examples, see: a) Y.-L. Zhao, Y. Wang, J. Cao, Y.-M. Liang, P.-
F. Xu, Org. Lett. 2014, 16, 2438; b) T.-G. Chen, P. Fang, X.-L. Hou, L.-X.
Dai, Synthesis 2015, 47, 134; c) J.-S. Li, Y.-J. Liu, G.-W. Zhang, J.-A. Ma,
Org. Lett. 2017, 19, 6364.
[
[
4] For selected examples, see: a) Q. Yin, S.-L. You, Chem. Sci. 2011, 2, 1344;
b) L. Li, M. Han, M. Xiao, Z. Xie, Synlett 2011, 2011, 1727; c) M. Rueping,
S. Raja, A. NfflÇez, Adv. Synth. Catal. 2011, 353, 563; d) M. Rueping, R. Ra-
sappan, S. Raja, Helv. Chim. Acta 2012, 95, 2296; e) A. Parra, R. Alfaro, L.
Marzo, A. Moreno-Carrasco, J. L. G. Ruano, J. Alemµn, Chem. Commun.
Experimental Section
General experimental procedures: 35.4 mL (0.0005 mmol,
2
012, 48, 9759; f) J.-X. Liu, Q.-Q. Zhou, J.-G. Deng, Y.-C. Chen, Org.
0
.005 equiv) of DPZ solution (1.0 mg of DPZ in 200 mL of toluene)
Biomol. Chem. 2013, 11, 8175; g) R.-R. Liu, S.-C. Ye, C.-J. Lu, G.-L. Zhuang,
J.-R. Gao, Y.-X. Jia, Angew. Chem. Int. Ed. 2015, 54, 11205; Angew. Chem.
was syringed into a 10 mL reaction bottle which equipped with a
stir bar, and then solvent was removed in vacuo. Subsequently, 2-
phenyl-3-alkyl indoles 1 (0.1 mmol), C1 (0.01 mmol), 4 ꢁ MS
2
2
015, 127, 11357; h) S. Nakamura, N. Matsuda, M. Ohara, Chem. Eur. J.
016, 22, 9478.
Chem. Asian J. 2018, 00, 0 – 0
www.chemasianj.org
5
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&
&
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Communication
[
5] For selected reviews, see: a) C. K. Prier, D. A. Rankic, D. W. C. MacMillan,
Chem. Rev. 2013, 113, 5322; b) D. M. Schultz, T. P. Yoon, Science 2014,
1073; l) J. Ma, A. R. Rosales, X. Huang, K. Harms, R. Riedel, O. Wiest, E.
Meggers, J. Am. Chem. Soc. 2017, 139, 17245; m) E. D. Nacsa, D. W. C.
MacMillan, J. Am. Chem. Soc. 2018, 140, 3322.
343, 985; c) J. W. Beatty, C. R. J. Stephenson, Acc. Chem. Res. 2015, 48,
1474; d) M. H. Shaw, J. Twilton, D. W. C. MacMillan, J. Org. Chem. 2016,
81, 6898; e) N. A. Romero, D. A. Nicewicz, Chem. Rev. 2016, 116, 10075;
[9] a) X. Liu, X. Ye, F. Bure sˇ , H. Liu, Z. Jiang, Angew. Chem. Int. Ed. 2015, 54,
11443; Angew. Chem. 2015, 127, 11605; b) C. Zhang, S. Li, F. Bure sˇ , R.
Lee, X. Ye, Z. Jiang, ACS Catal. 2016, 6, 6853; c) G. Wei, C. Zhang, F.
Bure sˇ , X. Ye, C.-H. Tan, Z. Jiang, ACS Catal. 2016, 6, 3708; d) Y. Liu, J. Li,
X. Ye, X. Zhao, Z. Jiang, Chem. Commun. 2016, 52, 13955; e) L. Lin, X.
Bai, X. Ye, X. Zhao, C.-H. Tan, Z. Jiang, Angew. Chem. Int. Ed. 2017, 56,
13842; Angew. Chem. 2017, 129, 14030; f) T. Shao, Y. Yin, R. Lee, X. Zhao,
G. Chai, Z. Jiang, Adv. Synth. Catal. 2018, 360, 1754; g) Y. Yin, Y. Dai, H.
Jia, J. Li, L. Bu, B. Qiao, X. Zhao, Z. Jiang, J. Am. Chem. Soc. 2018, 140,
6083.
f) J. Twilton, C. C. Le, P. Zhang, M. H. Shaw, R. W. Evans, D. W. C. MacMil-
lan, Nat. Rev. Chem. 2017, 1, 0052.
[
[
6] a) S. Lerch, L.-N. Unkel, M. Brasholz, Angew. Chem. Int. Ed. 2014, 53,
6558; Angew. Chem. 2014, 126, 6676; b) W. Ding, Q.-Q. Zhou, J. Xuan, T.-
R. Li, L.-Q. Lu, W.-J. Xiao, Tetrahedron Lett. 2014, 55, 4648.
7] For selected reviews, see: a) C. Wang, Z. Lu, Org. Chem. Front. 2015, 2,
179; b) R. Brimioulle, D. Lenhart, M. M. Maturi, T. Bach, Angew. Chem. Int.
Ed. 2015, 54, 3872; Angew. Chem. 2015, 127, 3944; c) E. Meggers, Chem.
Commun. 2015, 51, 3290; d) S. Poplata, A. Trçster, Y.-Q. Zou, T. Bach,
Chem. Rev. 2016, 116, 9748.
1
[10] The chemical conversion was 33% determined by crude H NMR.
[11] For the products obtained with moderate ee values, other chiral CPAs
were further examined to improve the enantioselectivity, but no better
result was obtained.
[8] For selected recent examples, see: a) O. Gutierrez, J. C. Tellis, D. N.
Primer, G. A. Molander, M. C. Kozlowski, J. Am. Chem. Soc. 2015, 137,
4
896; b) L. Ruiz Espelt, I. S. McPherson, E. M. Wiensch, T. P. Yoon, J. Am.
[12] CCDC 1830642 (3r) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre.
Chem. Soc. 2015, 137, 2452; c) D. Uraguchi, N. Kinoshita, T. Kizu, T. Ooi,
J. Am. Chem. Soc. 2015, 137, 13768; d) T. Kizu, D. Uraguchi, T. Ooi, J. Org.
Chem. 2016, 81, 6953; e) Z. Zuo, H. Cong, W. Li, J. Choi, G. C. Fu, D. W. C.
MacMillan, J. Am. Chem. Soc. 2016, 138, 1832; f) A. G. Amador, E. M.
Sherbrook, T. P. Yoon, J. Am. Chem. Soc. 2016, 138, 4722; g) C. Wang, K.
Harms, E. Meggers, Angew. Chem. Int. Ed. 2016, 55, 13495; Angew.
Chem. 2016, 128, 13693; h) X. Huang, R. D. Webster, K. Harms, E. Meg-
gers, J. Am. Chem. Soc. 2016, 138, 12636; i) J. J. Murphy, D. Bastida, S.
Paria, M. Fagnoni, P. Melchiorre, Nature 2016, 532, 218; j) Q. Yang, L.
Zhang, C. Ye, S. Luo, L.-Z. Wu, C.-H. Tung, Angew. Chem. Int. Ed. 2017,
[13] See the Supporting Information for the details.
[14] a) L. A. Paquette, J. E. Hofferberth in Organic Reactions, Vol. 62, Wiley,
2004, pp. 477–567; b) E. Schendera, S. Lerch, T. von Drathen, L.-N.
Unkel, M. Brasholz, Eur. J. Org. Chem. 2017, 3134.
Manuscript received: March 26, 2018
Revised manuscript received: May 28, 2018
56, 3694; Angew. Chem. 2017, 129, 3748; k) A. G. Capacci, J. T. Malinow-
ski, N. J. McAlpine, J. Kuhne, D. W. C. MacMillan, Nat. Chem. 2017, 9,
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ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
COMMUNICATION
Organocatalysis
Liwei Bu, Jiangtao Li, Yanli Yin,
Baokun Qiao, Guobi Chai, Xiaowei Zhao,*
Zhiyong Jiang*
&& – &&
Organocatalytic Asymmetric Cascade
Aerobic Oxidation and Semipinacol
Rearrangement Reaction: A Visible
Light-Induced Approach to Access
Chiral 2,2-Disubstituted Indolin-3-ones
An enantioselective cascade aerobic
oxidation and semipinacol rearrange-
ment reaction of 2-aryl-3-alkyl-substitut-
ed indoles via visible-light-driven coop-
erative photoredox and H-bonding cat-
alysis has been developed. Such an or-
ganocatalytic system provides an effi-
cient approach to access an array of val-
uable enantioenriched 2-aryl-2-alkyl-
substituted indolin-3-ones in 64–90%
yield with 58–94% ee.
Chem. Asian J. 2018, 00, 0 – 0
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7
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers! ÞÞ