Silver-Catalyzed Asymmetric Dearomatization of Electron-Deficient Heteroarenes via Interrupted Barton–Zard Reaction

Article abstract of DOI:10.1002/anie.202107767

Herein we report a catalytic asymmetric dearomatization reaction of electron-deficient heteroarenes with α-substituted isocyanoacetates through an interrupted Barton–Zard reaction. A range of optically active pyrrolo[3,4-b]indole derivatives was obtained

Full text of DOI:10.1002/anie.202107767

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International Edition: doi.org/10.1002/anie.202107767
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Asymmetric Catalysis
Hot Paper
Silver-Catalyzed Asymmetric Dearomatization of Electron-Deficient
Heteroarenes via Interrupted Barton–Zard Reaction
Qian Wan, Jia-Hao Xie, Chao Zheng, Yao-Feng Yuan,* and Shu-Li You*
Abstract: Herein we report a catalytic asymmetric dearoma-
tization reaction of electron-deficient heteroarenes with a-
substituted isocyanoacetates through an interrupted Barton–
Zard reaction. A range of optically active pyrrolo[3,4-b]indole
derivatives was obtained in good yields (up to 97%) with high
stereoselectivities (up to > 20:1 dr and 97% ee), using
a catalytic system consisting of a cinchona-derived amino-
phosphine and silver oxide. This reaction features wide
substrate scope and mild conditions, and provides a new
strategy for developing asymmetric dearomatization reactions.
T
he Barton–Zard reaction[1] is an important method for the
preparation of 3,4-disubstituted pyrrole-2-carboxylates from
readily available isocyanoacetates and dipolarophiles includ-
ing electron-deficient alkenes,[2] alkynes,[3] and certain nitro-
arenes[4] (Scheme 1a). The nitro group acts as an activating
group in the initial nucleophilic addition and a leaving group
for the final formation of the pyrrole ring. This method has
been extensively applied in the synthesis of biologically active
pyrroles, porphyrins and dipyrromethene dyes.[5] Particularly,
the Barton–Zard reaction of 3-nitroindoles with isocyanoa-
cetates has been utilized in the synthesis of various isoindole
derivatives. Gribble and co-workers reported elegant exam-
ples in which both pyrrolo[2,3-b]indoles and pyrrolo[3,4-
b]indoles could be afforded. The regioselectivity of the
reactions could be fine-tuned by the N-protecting groups
(Scheme 1b).[6]
Catalytic asymmetric dearomatization (CADA) reactions
represent a class of attractive methods to access enantio-
enriched three-dimensional molecules from readily available
planar aromatic compounds.[7] Compared with the well-
studied reactions involving electron-rich heteroarenes, the
CADA reactions of electron-deficient heteroarenes remain
relatively limited.[8] In 2014, the Arai group pioneered
a dearomative formal [3+2] cyclization reaction of electron-
deficient indoles with imino esters catalyzed by a chiral Cu
complex (Scheme 1c).[9] Almost at the same time, the Trost
group reported a Pd-catalyzed asymmetric dearomative
Scheme 1. Catalytic asymmetric dearomatization reaction via inter-
rupted Barton–Zard reaction.
cyclization reaction of nitroarenes with trimethyleneme-
thane.[10] Since then, various cyclization modes have been
applied for the dearomatization of 3-nitroindoles and related
electron-deficient arenes.[11] Encouraged by these successes,
we envisioned that if an additional a-substituent is introduced
to the isocyanoacetates, the Barton–Zard reaction of 3-
nitroindoles might be interrupted after the dearomative
cycloaddition, since the final aromatization via the extrusion
of HNO2 is inhibited. This strategy provides a facile protocol
for the construction of chiral pyrrolo[3,4-b]indole skeleton,
which is found as core scaffold in many natural products and
pharmacologically active molecules.[12] Recently, we have
developed such a highly efficient interrupted Barton–Zard
reaction of 3-nitroindoles and related electron-deficient
hetereoarenes with a-substituted isocyanoacetates. The ste-
reoselectivity issue is tackled by a catalyst system consisting of
[*] Q. Wan, J.-H. Xie, C. Zheng, Prof. Dr. S.-L. You
State Key Laboratory of Organometallic Chemistry, Shanghai Insti-
tute of Organic Chemistry, Chinese Academy of Sciences
345 Lingling Lu, Shanghai 200032 (China)
E-mail: slyou@sioc.ac.cn
Q. Wan, Prof. Dr. Y.-F. Yuan
College of Chemistry, Fuzhou University
Fuzhou 350108 (China)
E-mail: yaofeng_yuan@fzu.edu.cn
a
cinchona-derived amino-phosphine and silver oxide.
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202107767.
Pyrrolo[3,4-b]indole derivatives bearing three contiguous
stereogenic centers are obtained in good to excellent yields
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and high stereoselectivity. Herein, we report the results from
this study.
reactivity and stereoselectivity (entry 9). Further lowering
the loadings of Ag2O and amino phosphine L1 to 1 mol% led
to significant decrease in both diastereoselectivity and
enantioselectivity with a longer reaction time (see the
Supporting Information for more details). Control experi-
ments proved that both Ag2O and amino-phosphine ligand
are critical for achieving high yield and stereoselectivity. As
determined by NMR analysis, the yield of 3aa decreased to
74% in the absence of amino-phosphine ligand, and no
reaction occurred without Ag2O (entries 10 and 11). After the
investigation on temperature and reactant concentration (see
the Supporting Information for more details), the optimized
conditions were established using Ag2O (2.5 mol%) and
amino phosphine L1 (2.5 mol%) in Et2O (0.025 M for 2a) at
room temperature. The desired product 3aa was delivered in
90% yield with 94% ee and 10:1 dr (entry 12).
With the optimized reaction conditions in hands (Table 1,
entry 12), we next studied the scope of a-substituted isocya-
noacetates 2 with 3-nitroindole 1a (Scheme 2). Firstly, the
variation of the ester moiety of a-methyl isocyanoacetates
(2a–2 f) was investigated and all tested esters (methyl, ethyl,
isopropyl, tert-butyl, benzyl, dibenzhydryl) could be tolerated
to afford 3aa–3af in moderate to good diastereoselectivities
(3:1–10:1 dr) and excellent enantioselectivities (92–96% ee).
Interestingly, the diastereoselectivity of this process increases
when a-methyl isocyanoacetates bearing sterically more
hindered ester group are used. We are pleased to find that
The initial studies were carried out using 3-nitroindole
(1a) and a-methyl isocyanoacetate (2a) as model substrates,
and the combination of silver oxide and chiral amino-
phosphine ligand L1 as the catalyst in DCM at room
temperature (Table 1). This catalytic system has been widely
applied in the asymmetric transformations of isocyanoace-
tates.[13] Gratifyingly, the target reaction proceeded well,
delivering the dearomative product 3aa in excellent yield
with moderate diastereoselectivity and promising enantiose-
lectivity (92% NMR yield, 3:1 dr, 88% ee; entry 1). The
absolute configuration of the major diastereoisomer 3aa was
determined by single-crystal X-ray diffraction analysis.
Further investigations of chiral amino-phosphine ligands
showed that L1 was the optimal one in terms of enantio- and
diastereoselectivity (entries 1–3). Subsequently, the examina-
tion of solvents (entries 4–8, see the Supporting Information
for more details) showed that the stereoselectivity of the
reaction could be improved by using Et2O (9:1 dr, 93% ee).
Remarkably, the loading of amino-phosphine L1 can be
lowered to 2.5 mol% without any notable influence on
Table 1: Optimization of reaction conditions.[a]
Entry Ag salt
L
Solvent
t
Yield[b]
dr[c]
ee[d]
1
2
3
4
5
6
7
8
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
–
L1 DCM
L2 DCM
L3 DCM
L1 DCE
1 h
1 h
1 h
1 h
92%
92%
97%
96%
95%
99%
99%
93%
95%
3:1
2:1
2:1
3:1
7:1
4:1
5:1
9:1
88%
80%
79%
85%
93%
89%
93%
93%
L1 toluene 1 h
L1 dixone
L1 THF
L1 Et2O
L1 Et2O
1 h
1 h
1 h
1 h
9[e]
10
11[e]
10:1 93%
2:1
–
–
Et2O
17 h 74%
17 h trace
1 h
–
–
L1 Et2O
L1 Et2O
12[e,f] Ag2O
97% (90%)[g] 10:1 94%
[a] Reaction conditions: 1a (0.12 mmol), 2a (0.1 mmol), Ag2O
(2.5 mol%) and L (10 mol%) in solvent (2.0 mL) at rt under argon
atmosphere. [b] NMR yield of 3aa using CH2Br2 as an internal standard.
[c] Determined by 1H NMR of the crude reaction mixture. [d] Determined
by HPLC analysis. [e] L1 (2.5 mol%) was used. [f] Et2O (4.0 mL) was
used. [g] Isolated yield of 3aa with both diastereoisomers under the
following conditions: 1a (0.24 mmol), 2a (0.2 mmol), Ag2O (2.5 mol%)
and L (2.5 mol%) in Et2O (8.0 mL).
Scheme 2. Substrate scope for a-substituted isocyanoacetates. Reac-
tion conditions: 1a (0.24 mmol), 2a (0.2 mmol), Ag2O (2.5 mol%)
and L1 (2.5 mol%) in Et2O (8.0 mL) at rt under argon atmosphere.
[a] Reaction at 508C.
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products 3ag–3am bearing different alkyl substituents (ethyl,
groups on N-1 of 3-nitroindoles, and it was found that various
n-butyl, isopropyl, allyl, benzyl, cyclopropanemethylene,
cyclohexanemethylene) on the a-position of tert-butyl iso-
cyanoacetates were obtained in excellent yields (90–99%),
with good diastereoselectivities (4:1–8:1 dr) and enantiose-
lectivities (88–93% ee). However, it is notable that a-phenyl
isocyanoacetate 2n was a less suitable substrate, affording the
corresponding product 3an with poor stereoselectivity (1:1 dr,
29% ee/31% ee). A diminished reactivity was observed for a-
methyl isocyanoacetamide 2o, delivering product 3ao in 58%
yield with moderate stereoselectivity (2:1 dr, 71% ee/61% ee)
at 508C in two days.
Subsequently, the scope of electron-deficient arenes was
explored (Scheme 3). It was found that 3-nitroindoles bearing
substituents with varied electronic properties (Me, OMe,
OBn, CO2Me, and halogen atom) at the different position of
the indole ring were converted to the corresponding products
3ba–3ma smoothly in good yields (64–90%) and good to
excellent diastereo- and enantio-selectivities (5:1–12:1 dr, 79–
97% ee). It is worth mentioning that stereoselectivity for the
reactions of the 3-nitroindoles bearing electron-donating
substituents is generally better than those with electron-
withdrawing substituents. Then we paid our attention to the
electron-withdrawing groups on N-1 could be accommodated
by the reaction (3na–3qa, 86–93% yield, 5:1- > 20:1 dr, 92–
97% ee). When sterically more demanding 2,4,6-(iPr)3-
substituted arylsulfonyl group was introduced, 3qa was
obtained in 87% yield, with much improved stereoselectivity
(> 20:1 dr, 97% ee). To further extend the scope, the reactions
of other electron-deficient heteroarenes were investigated.
When 7-aza-nitroindole was subjected to the standard con-
ditions, the desired product 3ra was obtained with good yield
(87%) and stereoselectivity (7:1 dr, 89% ee). The 3-nitro-
benzothiophene and 2-nitrobenzofuran also performed well
in this reaction to give products 3sa–3ta with reasonable
yields (71–72%), and diastereo- and enantio-selectivities
(3:1–4:1 dr, 89–95% ee). 5-Membered aromatic heterocycle,
such as pyrrole, was also well tolerated, affording the
compound 3ua in moderate yield (70%) with good diaste-
reoselectivity (6:1 dr) and excellent enantioselectivity (97%
ee).
The synthetic potential of the current protocol was
showcased by a gram-scale reaction and several transforma-
tions of product 3aa. As shown in Scheme 4, 3aa was
Scheme 4. Gram-scale reaction and transformations of 3aa.
obtained in 92% yield, 9:1 dr, and 95% ee, by treating 3-
nitroindole 1a (3.0 mmol) and a-methyl tert-butyl isocyanoa-
cetate 2a (2.5 mmol) in the presence of 2.5 mol% Ag2O and
2.5 mol% L1. The imine group of 3aa was efficiently reduced
by NaBH3CN/AcOH, delivering product 4 in 98% yield.
Moreover, the treatment of compound 4 by Mg/CH3OH
resulted in the reduction of the nitro group to hydroxylamine
accompanied by the removal of the Ts group. The reduction
of the nitro group and imine of 3aa proceeded smoothly by
NiCl2/NaBH4, providing 6 in 62% yield. Interestingly, the
intermolecular reductive dimerization of 3aa was observed in
the presence of Zn/AcOH, leading to product 7 in 66% yield.
The structure and relative stereochemistry of this compound
were unambiguously determined by X-ray crystallographic
analysis. Notably, during all these above transformations,
Scheme 3. Substrate scope for electron-deficient heteroarenes. Reac-
tion conditions: 1a (0.24 mmol), 2a (0.2 mmol), Ag2O (2.5 mol%)
and L1 (2.5 mol%) in Et2O (8.0 mL) at rt under argon atmosphere.
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products could be obtained as a single diastereoisomer and
Keywords: asymmetric catalysis · Barton–Zard ·
dearomatization · indole · isocyanoacetate
the enantiomeric purity was retained.
According to the above results and literature reports,[5i,13g]
a plausible mechanism and stereo-induction model are
proposed with the reaction of 3-nitroindole 1a and a-methyl
tert-butyl isocyanoacetate 2a as an example (Scheme 5). First
[1] a) D. H. R. Barton, S. Z. Zard, J. Chem. Soc. Chem. Commun.
1985, 1098; b) D. H. R. Barton, J. Kervagoret, S. Z. Zard,
Tetrahedron 1990, 46, 7587.
[2] For selected examples, see: a) J. G. Greger, S. J. P. Yoon-Miller,
N. R. Bechtold, S. A. Flewelling, J. P. MacDonald, C. R.
Downey, E. A. Cohen, E. T. Pelkey, J. Org. Chem. 2011, 76,
8203; b) R. E. Johnson, T. de Rond, V. N. G. Lindsay, J. D.
Keasling, R. Sarpong, Org. Lett. 2015, 17, 3474; c) X. Sheng, Q.
Xu, Z. Lin, Z. Hu, L. Pan, Q. Liu, Y. Li, Asian J. Org. Chem.
2020, 9, 2201; d) E. A. Silyanova, A. V. Samet, L. K. Salamandra,
V. N. Khrustalev, V. V. Semenov, Eur. J. Org. Chem. 2020, 2093.
[3] a) O. V. Larionov, A. de Meijere, Angew. Chem. Int. Ed. 2005,
44, 5664; Angew. Chem. 2005, 117, 5809; b) S. Kamijo, C.
Kanazawa, Y. Yamamoto, J. Am. Chem. Soc. 2005, 127, 9260;
c) S.-C. Zheng, Q. Wang, J. Zhu, Angew. Chem. Int. Ed. 2019, 58,
1494; Angew. Chem. 2019, 131, 1508.
[4] For selected examples, see: a) T. D. Lash, C. Wijesinghe, A. T.
Osuma, J. R. Patel, Tetrahedron Lett. 1997, 38, 2031; b) T. D.
Lash, M. L. Thompson, T. M. Werner, J. D. Spence, Synlett 2000,
213; c) T. Murashima, K. Nishi, K. Nakamoto, A. Kato, R.
Tamai, H. Uno, N. Ono, Heterocycles 2002, 58, 301.
Scheme 5. Proposed stereo-induction model.
[5] For a review on Barton–Zard reaction, see: a) N. Ono, Hetero-
cycles 2008, 75, 243; For selected examples, see: b) O. S.
Finikova, A. V. Cheprakov, I. P. Beletskaya, P. J. Carroll, S. A.
Vinogradov, J. Org. Chem. 2004, 69, 522; c) C. Guo, M.-X. Xue,
M.-K. Zhu, L.-Z. Gong, Angew. Chem. Int. Ed. 2008, 47, 3414;
Angew. Chem. 2008, 120, 3462; d) J. Tan, X. Xu, L. Zhang, Y. Li,
Q. Liu, Angew. Chem. Int. Ed. 2009, 48, 2868; Angew. Chem.
2009, 121, 2912; e) Y. Li, X. Xu, J. Tan, C. Xia, D. Zhang, Q. Liu,
J. Am. Chem. Soc. 2011, 133, 1775; f) X. Xu, L. Zhang, X. Liu, L.
Pan, Q. Liu, Angew. Chem. Int. Ed. 2013, 52, 9271; Angew. Chem.
2013, 125, 9441; g) H. Uno, M. Nakamura, K. Jodai, S. Mori, T.
Okujima, Heterocycles 2015, 90, 1158; h) L. M. Blair, J. Sperry,
Chem. Commun. 2016, 52, 800; i) X.-L. He, H.-R. Zhao, X. Song,
B. Jiang, W. Du, Y.-C. Chen, ACS Catal. 2019, 9, 4374; j) S.-C.
Zheng, Q. Wang, J. Zhu, Angew. Chem. Int. Ed. 2019, 58, 9215;
Angew. Chem. 2019, 131, 9313.
both 1a and 2a can be activated by the Ag2O-cinchona
complex via coordination and/or hydrogen bonding. This
highly pre-organized precursor allows the selective nucleo-
philic attack of the a-carbon of 2a (Re-face) to the C2-
position of 1a (Si-face) through TS-I, thus establishing the
absolute configuration of the first two stereogenic centers.
The subsequent cyclization is highly diastereoselective due to
the conformational restriction of the forming five-membered
ring. The nucleophile attack of the C3-position of 1a (Si-face)
to the terminal carbon of the isocyanide group of 2a occurs
via TS-II, leading to the final product 3aa.
In conclusion, we have successfully developed an Ag-
catalyzed asymmetric dearomatization reaction of electron-
deficient nitroheteroarenes with a-substituted isocyanoace-
tates through the interrupted Barton–Zard reaction. A
catalytic system consisting of a cinchona-derived amino-
phosphine and silver oxide displays high efficiency and
excellent stereo-control. This strategy provides a facile pro-
tocol for the asymmetric construction of optically active
pyrrolo[3,4-b]indole fragment featuring with wide substrate
scope, mild reaction conditions and operationally simple
procedure.
[6] a) E. T. Pelkey, L. Chang, G. W. Gribble, Chem. Commun. 1996,
1909; b) E. T. Pelkey, G. W. Gribble, Chem. Commun. 1997,
1873; c) E. T. Pelkey, G. W. Gribble, Synthesis 1999, 7, 1117.
[7] For reviews on catalytic asymmetric dearomatization reactions,
see: a) C.-X. Zhuo, W. Zhang, S.-L. You, Angew. Chem. Int. Ed.
2012, 51, 12662; Angew. Chem. 2012, 124, 12834; b) C.-X. Zhuo,
C. Zheng, S.-L. You, Acc. Chem. Res. 2014, 47, 2558; c) W.-T.
Wu, L. Zhang, S.-L. You, Chem. Soc. Rev. 2016, 45, 1570; d) C.
Zheng, S.-L. You, Chem 2016, 1, 830; e) J.-B. Chen, Y.-X. Jia,
Org. Biomol. Chem. 2017, 15, 3550; f) C. Zheng, S.-L. You, Nat.
Prod. Rep. 2019, 36, 1589; g) J. An, M. Bandini, Eur. J. Org.
Chem. 2020, 4087; h) F.-T. Sheng, J.-Y. Wang, W. Tan, Y.-C.
Zhang, F. Shi, Org. Chem. Front. 2020, 7, 3967; i) C. Zheng, S.-L.
You, ACS Cent. Sci. 2021, 7, 432; For selected recent examples,
see: j) J. A. Rossi-Ashton, A. K. Clarke, R. J. K. Taylor, W. P.
Unsworth, Org. Lett. 2020, 22, 1175; k) H. Egami, T. Rouno, T.
Niwa, K. Masuda, K. Yamashita, Y. Hamashima, Angew. Chem.
Int. Ed. 2020, 59, 14101; Angew. Chem. 2020, 132, 14205; l) X.
Liu, J. Zhang, L. Bai, L. Wang, D. Yang, R. Wang, Chem. Sci.
2020, 11, 671; m) Y. Ge, C. Qin, L. Bai, J. Hao, J. Liu, X. Luan,
Angew. Chem. Int. Ed. 2020, 59, 18985; Angew. Chem. 2020, 132,
19147; n) H. Liu, Y. Yan, J. Zhang, M. Liu, S. Cheng, Z. Wang, X.
Zhang, Chem. Commun. 2020, 56, 13591; o) D. J. Robinson, S. P.
Spurlin, J. D. Gorden, R. R. Karimov, ACS Catal. 2020, 10, 51;
p) Z. Pan, Y. Liu, F. Hu, Q. Liu, W. Shang, X. Ji, C. Xia, Org.
Lett. 2020, 22, 1589; q) M. W. Gribble, Jr., R. Y. Liu, S. L.
Acknowledgements
We thank MOST (2016YFA0202900) and NSFC (21772023,
21821002, and 21961132002) for financial support.
Conflict of Interest
The authors declare no conflict of interest.
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Buchwald, J. Am. Chem. Soc. 2020, 142, 11252; r) S. Zhao, S.
Y.-H. Wang, Q. Hu, Q.-H. Li, D.-Y. Shi, D. Gao, G. Ge, G.-Q.
Cheng, H. Liu, J. Zhang, M. Liu, W. Yuan, X. Zhang, Chem.
Commun. 2020, 56, 4200; s) H.-F. Tu, P. Yang, Z.-H. Lin, C.
Zheng, S.-L. You, Nat. Chem. 2020, 12, 838; t) R.-X. Liang, L.-J.
Song, J.-B. Lu, W.-Y. Xu, C. Ding, Y.-X. Jia, Angew. Chem. Int.
Ed. 2021, 60, 7412; Angew. Chem. 2021, 133, 7488; u) R. Jiang, L.
Ding, C. Zheng, S.-L. You, Science 2021, 371, 380; For a book,
see: v) Asymmetric Dearomatization Reactions (Ed.: S.-L. You),
Wiley-VCH, Weinheim, 2016.
Lin, P. Tian, Chem. Commun. 2020, 56, 10718; u) J.-P. Tan, X. Li,
Y. Chen, X. Rong, L. Zhu, C. Jiang, K. Xiao, T. Wang, Sci. China
Chem. 2020, 63, 1091; v) H. Wang, Q. Hu, M. Wang, C. Guo,
iScience 2020, 23, 100840; w) Z. Wang, D.-C. Wang, M.-S. Xie,
G.-R. Qu, H.-M. Guo, Org. Lett. 2020, 22, 164.
[12] a) M. Nakagawa, J. Heterocycl. Chem. 2000, 37, 567; b) D. Pagꢁ,
H. Yang, W. Brown, C. Walpole, M. Fleurent, M. Fyfe, F.
Gaudreault, S. St-Onge, Bioorg. Med. Chem. Lett. 2007, 17, 6183;
c) D. Solꢁ, M.-L. Bennasar, I. Jimꢁnez, Org. Biomol. Chem.
2011, 9, 4535; d) A. V. Ivachtchenko, E. B. Frolov, O. D. Mitkin,
S. E. Tkachenko, A. V. Khvat, Chem. Heterocycl. Compd. 2010,
46, 170; e) Z. Hu, H. Yuan, Y. Men, Q. Liu, J. Zhang, X. Xu,
Angew. Chem. Int. Ed. 2016, 55, 7077; Angew. Chem. 2016, 128,
7193.
[8] For reviews on CADA reactions with electron-deficient hetero-
arenes, see: a) A. Cerveri, M. Bandini, Chin. J. Chem. 2020, 38,
287; b) B. Rkein, A. Bigot, L. Birbaum, M. Manneveau, M.
De Paolis, J. Legros, I. Chataigner, Chem. Commun. 2021, 57, 27.
[9] A. Awata, T. Arai, Angew. Chem. Int. Ed. 2014, 53, 10462;
Angew. Chem. 2014, 126, 10630.
[10] B. M. Trost, V. Ehmke, B. M. OꢀKeefe, D. A. Bringley, J. Am.
Chem. Soc. 2014, 136, 8213.
[13] For selected reviews, see: a) S. Xu, J. Chen, J. Chen, W. Xiao,
Chin. J. Org. Chem. 2020, 40, 3493; b) I. V. Efimov, L. N.
Kulikova, D. I. Zhilyaev, L. G. Voskressensky, Eur. J. Org. Chem.
2020, 7284; c) J. Luo, G.-S. Chen, S.-J. Chen, Z.-D. Li, Y.-L. Liu,
Chem. Eur. J. 2021, 27, 6598; For selected recent examples, see:
d) F. Sladojevich, A. Trabocchi, A. Guarna, D. J. Dixon, J. Am.
Chem. Soc. 2011, 133, 1710; e) I. Ortꢂn, D. J. Dixon, Angew.
Chem. Int. Ed. 2014, 53, 3462; Angew. Chem. 2014, 126, 3530;
f) P.-L. Shao, J.-Y. Liao, Y. A. Ho, Y. Zhao, Angew. Chem. Int.
Ed. 2014, 53, 5435; Angew. Chem. 2014, 126, 5539; g) R.
de la Campa, I. Ortꢂn, D. J. Dixon, Angew. Chem. Int. Ed.
2015, 54, 4895; Angew. Chem. 2015, 127, 4977; h) J.-Y. Liao, P.-L.
Shao, Y. Zhao, J. Am. Chem. Soc. 2015, 137, 628; i) H. Cheng, R.
Zhang, S. Yang, M. Wang, X. Zeng, L. Xie, C. Xie, J. Wu, G.
Zhong, Adv. Synth. Catal. 2016, 358, 970; j) R. de la Campa,
A. D. Gammack Yamagata, I. Ortꢂn, A. Franchino, A. L.
Thompson, B. Odell, D. J. Dixon, Chem. Commun. 2016, 52,
10632; k) X.-J. Peng, Y. A. Ho, Z.-P. Wang, P.-L. Shao, Y. Zhao,
Y. He, Org. Chem. Front. 2017, 4, 81; l) R. de la Campa, R.
Manzano, P. Calleja, S. R. Ellis, D. J. Dixon, Org. Lett. 2018, 20,
6033; m) A. Franchino, J. Chapman, I. Funes-Ardoiz, R. S.
Paton, D. J. Dixon, Chem. Eur. J. 2018, 24, 17660.
[11] For selected examples, see: a) J.-Q. Zhao, Z.-J. Wu, M.-Q. Zhou,
X.-Y. Xu, X.-M. Zhang, W.-C. Yuan, Org. Lett. 2015, 17, 5020;
b) J.-Q. Zhao, M.-Q. Zhou, Z.-J. Wu, Z.-H. Wang, D.-F. Yue, X.-
Y. Xu, X.-M. Zhang, W.-C. Yuan, Org. Lett. 2015, 17, 2238;
c) A. L. Gerten, L. M. Stanley, Org. Chem. Front. 2016, 3, 339;
d) Q. Cheng, H.-J. Zhang, W.-J. Yue, S.-L. You, Chem 2017, 3,
428; e) D.-F. Yue, J.-Q. Zhao, X.-Z. Chen, Y. Zhou, X.-M. Zhang,
X.-Y. Xu, W.-C. Yuan, Org. Lett. 2017, 19, 4508; f) Q. Cheng, F.
Zhang, Y. Cai, Y.-L. Guo, S.-L. You, Angew. Chem. Int. Ed. 2018,
57, 2134; Angew. Chem. 2018, 130, 2156; g) M. Sun, Z.-Q. Zhu,
L. Gu, X. Wan, G.-J. Mei, F. Shi, J. Org. Chem. 2018, 83, 2341;
h) J.-J. Suo, W. Liu, J. Du, C.-H. Ding, X.-L. Hou, Chem. Asian J.
2018, 13, 959; i) J.-Q. Zhang, F. Tong, B.-B. Sun, W.-T. Fan, J.-B.
Chen, D. Hu, X.-W. Wang, J. Org. Chem. 2018, 83, 2882; j) J.-Q.
Zhao, X.-J. Zhou, Y. Zhou, X.-Y. Xu, X.-M. Zhang, W.-C. Yuan,
Org. Lett. 2018, 20, 909; k) J.-Q. Zhao, X.-J. Zhou, Y.-Z. Chen,
X.-Y. Xu, X.-M. Zhang, W.-C. Yuan, Adv. Synth. Catal. 2018,
360, 2482; l) X.-M. Chen, C.-W. Lei, D.-F. Yue, J.-Q. Zhao, Z.-H.
Wang, X.-M. Zhang, X.-Y. Xu, W.-C. Yuan, Org. Lett. 2019, 21,
5452; m) K. Li, T. P. GonÅalves, K.-W. Huang, Y. Lu, Angew.
Chem. Int. Ed. 2019, 58, 5427; Angew. Chem. 2019, 131, 5481;
n) L. Liang, H.-Y. Niu, D.-C. Wang, X.-H. Yang, G.-R. Qu, H.-M.
Guo, Chem. Commun. 2019, 55, 553; o) J.-J. Suo, J. Du, Y.-J.
Jiang, D. Chen, C.-H. Ding, X.-L. Hou, Chin. Chem. Lett. 2019,
30, 1512; p) H. Wang, J. Zhang, Y. Tu, J. Zhang, Angew. Chem.
Int. Ed. 2019, 58, 5422; Angew. Chem. 2019, 131, 5476; q) X.-H.
Yang, J.-P. Li, D.-C. Wang, M.-S. Xie, G.-R. Qu, H.-M. Guo,
Chem. Commun. 2019, 55, 9144; r) J.-Q. Zhao, L. Yang, X.-J.
Zhou, Y. You, Z.-H. Wang, M.-Q. Zhou, X.-M. Zhang, X.-Y. Xu,
W.-C. Yuan, Org. Lett. 2019, 21, 660; s) X.-J. Zhou, J.-Q. Zhao,
X.-M. Chen, J.-R. Zhuo, Y.-P. Zhang, Y.-Z. Chen, X.-M. Zhang,
X.-Y. Xu, W.-C. Yuan, J. Org. Chem. 2019, 84, 4381; t) M.-S. Mei,
[14] Deposition Numbers 2084012 (for 3aa), and 2084013 (for 7)
contain the supplementary crystallographic data for this paper.
These data are provided free of charge by the joint Cambridge
Crystallographic Data Centre and Fachinformationszentrum
Karlsruhe Access Structures service www.ccdc.cam.ac.uk/
structures.
Manuscript received: June 10, 2021
Accepted manuscript online: July 1, 2021
Version of record online: && &&, &&&&
Angew. Chem. Int. Ed. 2021, 60, 1 – 6
ꢀ 2021 Wiley-VCH GmbH
www.angewandte.org
5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Asymmetric Catalysis
Q. Wan, J.-H. Xie, C. Zheng, Y.-F. Yuan,*
S.-L. You*
&&&& — &&&&
Silver-Catalyzed Asymmetric
Dearomatization of Electron-Deficient
Heteroarenes via Interrupted Barton–
Zard Reaction
Catalytic asymmetric dearomatization
reaction of electron-deficient hetero-
arenes with a-substituted iso-
cyanoacetate ester through an inter-
rupted Barton–Zard reaction is reported.
A range of optically active pyrrolo[3,4-
b]indole derivatives was obtained in good
reactivity (up to 99% yield) with high
stereoselectivities (up to >20:1 dr, 97%
ee) in the presence of 2.5 mol% Ag2O and
amino-phosphine L1.
6
www.angewandte.org
ꢀ 2021 Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 1 – 6
These are not the final page numbers!