Tandem Phospha-Michael Addition/N-Acylation/ Intramolecular Wittig Reaction of aza-o-Quinone Methides: Approaches to 2,3-Disubstituted Indoles

Article abstract of DOI:10.1002/adsc.202000343

A tandem phospha-Michael addition/N-acylation/intramolecular Wittig reaction of in situ formed aza-o-QMs is disclosed. This approach features high functional group tolerance and provides a convenient and practical access to biologically significant indole derivatives (37 examples, up to 91% yield) under mild reaction conditions. (Figure presented.).

Full text of DOI:10.1002/adsc.202000343

Title: Tandem Phospha-Michael Addition/N-Acylation/ Intramolecular
Wittig Reaction of aza-o-Quinone Methides: Approaches to 2,3-
Disubstituted Indoles
Authors: Ting-Bi Hua, Fei Chao, Long Wang, Chen-Yang Yan, Cong
Xiao, Qing-Qing Yang, and Wen-Jing Xiao
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000343
Link to VoR: https://doi.org/10.1002/adsc.202000343

10.1002/adsc.202000343
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Tandem Phospha-Michael Addition/N-Acylation/
Intramolecular Wittig Reaction of aza-o-Quinone Methides:
Approaches to 2,3-Disubstituted Indoles
Ting-Bi Hua,a,bFeiChao,a Long Wang,a Chen-Yang Yan,a Cong Xiao,c Qing-Qing
Yang,a,b,* Wen-Jing Xiaod,*
a
College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy
Conversion Materials, China Three Gorges University, 8 Daxue Road, Yichang, Hubei 443002, People’s Republic of
China.
E-mail: qingqing_yang@ctgu.edu.cn
Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, 8 Daxue Road,
b
Yichang, Hubei 443002, People’s Republic of China
Wuhan Glycolipid Co. Ltd., NO.666, East Lake High-tech Development Zone, Wuhan, Hubei430075, People’s
c
Republic of China
d
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal
University, 152 Luoyu Road, Wuhan, Hubei 430079, People’s Republic of China.
Email: wxiao@mail.ccnu.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
scaffolds in many natural isolates and therapeutic
agents.[10] In this context, our group[7a],[7b] and
Scheidt’s group[7d],[7e] developed formal [4+1]
cycloaddition reactions of aza-o-QMs with sulfur
ylides or enolate equivalents viaN-heterocyclic
carbene catalysis to access 2-acyl indole and 2-aryl
indole scaffolds, respectively (Scheme 1b). Despite
these advances, the further development of novel and
efficient procedures towards the construction of
indole skeletons with good functional group
compatibility, through aza-o-QMs intermediates,
remains highly desirable.
Abstract.A
tandem
phospha-Michael
addition/N-
acylation/intramolecular Wittig reaction of in situ formed
aza-o-QMs is disclosed. This approach features high
functional group tolerance and provides a convenient and
practical access to biologically significant indole
derivatives (37 examples, up to 91% yield) under mild
reaction conditions.
Keywords:aza-o-Quinone
Methides•ndoles•Intramolecular Wittig Reaction• Tandem
Reaction•Phospha-Michael Addition
Phosphines, often served as nucleophiles, can react
with a series of electron-deficient species. The
resultant phosphonium zwitterions can subsequently
participate in Wittig reactions by the interception of
carbonyl electrophiles to form several heterocyclic
compounds[11],[12] such as benzofurans and indoles.
Based on these developments and our ongoing
research interests in the development of heterocycle-
oriented methodologies,[7a],[7b],[13] we envisioned that a
phosphorus ylide can be first generated from the
addition of phosphines to aza-o-QMs, and the
following intramolecular Wittig reactions with the
corresponding amide groups take place to produce
highly funcitionalized indole compounds (Scheme
1d). To the best of our knowledge, there has hitherto
been no known literatures related to the Michael
additions of aza-o-QMs with phosphine nucleophiles
and their further applications. Herein we report an
efficient tandem phospha-Michael addition/N-
acylation/intramolecular Wittig reaction of aza-o-
Aza-ortho-quinone methides (aza-o-QMs) are a
versatilereactive intermediates which have found
broad applications in synthetic chemistry.[1] To date,
several strategies have been developed for the in situ
generation of aza-o-QMs, including pyrolysis,[2]
photolysis,[3] as well as Brønsted acid[4] or base[5-8]
mediated 1,4-elimination. Pioneering works from the
Corey and Steinhagen’s group disclosed a formal
[4+2]
cycloaddition
reaction
of
N-(o-
chloromethyl)aryl amides with electron-rich olefins
involving a Brønsted base promoted elimination step
(Scheme 1a).[6a] After that, aza-o-QMs have been
widely used for the construction of a variety of
biologically important N-containing heterocycles
through cycloaddition reactions, e.g., [4+1], [4+2],
[4+3] cycloaddition reactions (Schemes 1a-c).[6-8] In
this scenario, the [4+1] cycloaddition reactions of
aza-o-QMs turn out to be an efficient and reliable
method to indole derivatives,[9] which are privileged
1
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10.1002/adsc.202000343
Advanced Synthesis & Catalysis
QMs, which allows the rapid access to 2,3-
disubsituted indole derivatives (Scheme 1d).
5
6
Et3N
DABCO
TMG
CH3CN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PBu3
12
12
12
12
12
12
12
12
25
trace
0
7
8
t-BuOK
NaOH
12
41
64
75
9
9
10
11
12
13
Cs2CO3
CsOH∙H2O CH2Cl2
CsOH∙H2O CH2Cl2
CsOH∙H2O CH2Cl2 PPh2Et 12
35
81
89
14[c] CsOH∙H2O CH2Cl2
PPh3
PPh3
24
72
15 CsOH∙H2O CH2Cl2
Scheme 1. Cycloaddtion Reactions Involving aza-o-QMs
from N-(o-chloromethyl)aryl amides.
[a] Reaction condition: 1a (0.3 mmol), 2a (0.36 mmol),
PR3 (0.33 mmol), and base (2.5 equiv.), solvent (3.0
mL).
[b] Isolated yield.
We began our investigation by examining the
[c] 83% yield for 48 h.
reaction
of
N-(2-(chloromethyl)phenyl)-4-
Ts = 4-toluene-1-sulfonyl; DABCO: 1,4-diazabicyclo
[2.2.2]octane; TMG: tetramethylguanidine.
methylbenzenesulfonamide (1a) with PPh3 and
PhCOCl (2a) in the presence of Et3N in CH2Cl2 at 25
oC. The desired indole product 3aa was obtained in
55% isolated yield after 12 hours (Table 1, entry 1).
Encouraged by these results, we then started to
optimize the reaction conditions to improve the
chemical yield (Table 1).[14] A brief survey of
solvents revealed that CH2Cl2 was still the best choice
in terms of yields (Table 1, entries 1-5). Next, we
evaluated a series of bases, which were found to have
a dramatic impact on the reaction efficiency (Table 1,
entries 1 and 6-11). Notably, CsOH∙H2O was
identified as the optimal base for the formation of 3aa
(75% yield, Table 1, entry 11). Unfortunately, no
positive result was observed with other phosphines
(Table 1, entries 12-13). The protection group on the
nitrogen of anilines plays an important role. When Bz
group was employed as the protection group, the
reaction is very slow at room temperature and only
trace product was detected. In the case of Ns as the
protection group, the isolated desired product
contains the anhydride derived from benzoyl chloride.
Finally, by prolonging reaction time to 72 hours, the
yield of 3aa was further improved to 89% (Table 1,
entry 14)
With the optimal reaction conditions established,
we then examined the substrate scope of this tandem
reaction by employing a variety of N-(ortho-
chloromethyl)aryl amides. As highlighted in Table 2,
aside from 1a, various N-(ortho-chloromethyl)aryl
amides with electronically varied substituents, such
as OMe, Me, OH, Br, Cl, at the para position relative
to the sulfonamidenitrogen atom could readily
participate in the tandem process, providing the
corresponding cycloadducts in good yields (Table 2,
3ba-3fa: 70%-89% yields). The tolerance of
substituents at different positions on the benzene ring
was also investigated (Table 2, 3ga-3ha: 25%-83%
yields). The low yield observed for 3ha was probably
due to the steric hindrance. The reaction of
disubstituted
N-(ortho-chloromethyl)aryl
amide
substrate 1i also afforded the expected products 3ia in
73% yield. Additionally, as shown in the reactions of
1j and 1k, variation of the protecting group can also
be tolerated, and products 3ja and 3ka were obtained
in 52%-90% yields. Notably, substrates bearing
substituents at benzylic position were also suitable for
this transformation and were converted to 2,3-
disubstituted indole products 3la-3nb (Table 2, 30%-
85% yields). These results suggested that electronic
variations of substituents at benzylic position affected
the efficiency of the process owing to the stability of
generated phosphorus ylides during the process.
Table1. Reaction Optimization [a]
Entry
Base
Solvent PR3
T(h)
Yield
[%][b]
55
The substrate scope with respect to acyl chloride 2
was also investigated. As summarized in Table 3, the
reaction demonstrated wide scope and high functional
group tolerance. An array of aromatic acyl chlorides
(2b-2h) with various electron-donating (e.g., OMe,
Me) or electron-withdrawing (e.g., NO2, Br, Cl)
substituents at the para-, ortho-, or meta-position of
the phenyl ring were suitable substrates for the
1
2
3
4
Et3N
Et3N
Et3N
Et3N
CH2Cl2
Et2O
PPh3
12
12
12
12
PPh3
PPh3
PPh3
46
33
52
toluene
THF
2
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10.1002/adsc.202000343
Advanced Synthesis & Catalysis
reaction And the corresponding products 3ab-3ah
were obtained in generally high yields (81-91%). The
reaction of 2,4-disubstituted benzoyl chloride 2i also
provided the desired product 3ai in 86% yield.
Moreover, heteroaromatic acyl chlorides, such as 2j
and 2k, could be tolerated under the reaction
conditions, and cinnamoyl chloride (2l) and ester-
substituted acyl chloride 2m were also applicable in
the reaction to give the products in 17-73% yields.
Table 2. Scope of N-(ortho-chloromethyl)aryl amides[a],[b]
[a]Reaction conditions: 1 (0.5 mmol), 2a or 2b (0.6
mmol),PPh3 (0.33 mmol), and CsOH∙H2O (2.5 equiv.),
anhydrous CH2Cl2 (5.0 mL) were used.
[b] Isolated yield.
Bs = benzenesulfonyl; Ms = methanesulfonyl.
[a]Reaction conditions: 1a(0.5 mmol), 2 (0.6 mmol), PPh3
(0.55 mmol), and CsOH∙H2O (2.5 equiv.) in anhydrous
CH2Cl2 (5 mL) were used, 72 h.
Gratifyingly, the influence of aliphatic acyl chlorides
with varying steric parameters on the reaction
outcome was also examined. Methyl, ethyl, n-
propyl,benzyl, i-propyl, cyclopropyl and cyclohexyl
substituents are all well tolerated, leading to indole
products 3an-3at in good yields (75-88%).
Additionally, trifluoroacetic acid anhydride (2u)
smoothly underwent the developed reaction, and
indole 3au bearing a CF3 substituent was delivered in
50% yield. Remarkably, reaction using chiral acyl
chloride 2v also furnished the desired product 3av in
86% yield. To further demonstrate the synthetic
utility of this method in a medicinal chemistry setting,
we also tested the model reaction of pharmaceutical-
derived acyl chlorides (Table 3B). To our delight,
both probenecid- and dehydrocholic acid-derived acyl
chlorides participated in the tandem reactions
smoothly to give the coressponidng products (3aw
and 3ax) in 77% and 50% yields, respectively. These
results showed the potential application of the current
reaction in late-stage structural elaboration of drugs.
[b] Isolated yield.
[c]The acyl chloride was freshly prepared and used directly,
see the supporting information for details..
[d]4-Dimethylaminopyridine (0.05 mmol) was used.
[e]Trifluoroacetic acid anhydride (2u) (0.6 mmol) was used.
Furthermore, the reaction performed on a gram
scale also worked well to furnish product 3af in 80%
yield (Scheme2a). As a proof of concept, we
demonstrated an efficient tandem reaction of 1a and
2a and the deprotection of Ts group in a one-pot
reaction, providing N-H indole 4aa in 85% yield
(Scheme 2b).
Table 3. Scope of acyl chlorides[a],[b]
3
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10.1002/adsc.202000343
Advanced Synthesis & Catalysis
mmol, 1.0 equiv.), dichloromethane (5.0 mL), PPh3 (0.55 mmol,
1.1 equiv.), CsOH·H2O (1.25 mmol, 2.5 equiv.) and acyl
chloride2a (0.6 mmol, 1.2 equiv.). The reaction mixture was
stirred for 72 h at 25oC, the reaction was monitored via TLC
(petroleum ether/ethyl acetate =8:1). Thereafter, the reaction
mixture was purified by flash chromatography on silica gel
(petroleum ether/ ethyl acetate = 10:1-40:1) to give the desired
product 3aaas a white solid in 89% yield.
Acknowledgements
Scheme 2.Follow-up Chemistry.
We are grateful to the National Natural Science Foundation
of China (No. 21702121), Open fund from Hubei Key
Laboratory of Natural Products Research and Development
of China Three Gorges University (No. NPRD-2018010),
and the 111 project of Hubei Province 2018-19-1 for
Based on the above experimental results and
previous reports,[1b],[6-8],[12g] a tentative mechanism for
this model reaction of 1a, 2a as an example is
exemplified in Scheme 3. Initially, the reaction of
PPh3 with 1a generates the phosphonium salt IIvia
the in situ generated aza-o-QMs I. Then, the
phosphonium salt II undergoes an acylation with
benzoyl chloride 2a under basic conditions to provide
intermediate III, which could be further deprotonated
by another equivalent of base to afford phosphorus
ylide IV. This step is followed by intramolecular
Wittig reaction with generation of triphenylphosphine
oxide, completing the reaction process. On the basis
of the proposed mechanism, we also wished to
explore the possibility of employing catalytic
phosphine in our protocol. Unfortunately,
nosatisfactory results were obtained probably because
of the stability of phosphonium intermediates.[14]
financial support
.
References
[1] a) K.Wojciechowski, Eur. J. Org. Chem.,2001, 2001,
3587-3605; b)Rokita, S. E. Quinone Methides; Wiley:
Hoboken, NJ, 2009; c) A. A.Jaworski, J. Org.
Chem.,2016, 81, 10145-10153; d) A. Spivey, C.
Nielsen, H. Abas, Synthesis, 2018, 50, 4008-4018; e) B.
Yang and S. Gao, Chem. Soc. Rev., 2018, 47, 7926-
7953.
[2] a) Y.-L.Mao,V. Boekelheide, J. Org. Chem.,1980,45,
1547-1548; b) R.Consonni, P. D. Croce, R.Ferraccioli,
C.La Rosa, J. Chem. Soc., Perkin Trans.11996,1, 1809-
1814; c) N.Martín, A.Martínez-Grau, L. Sánchez, C.
Seoane, M.Torres, J. Org. Chem.,1998, 63, 8074-8076;
d) M.Ohno, H.Sato, S. Eguchi, Synlett,1999,1999, 207-
209; e) P. Zakrzewski,M.Gowan, L. A.Trimble, C. K.
Lau,Synthesis,1999, 1999, 1893-1902; f) K.
Wojciechowski,S.Kosinski, Eur. J. Org. Chem.,2002,
2002, 947-954.
[3] a)
E. M. Burgess,L.McCullagh, J. Am. Chem.
Soc.,1966, 88, 1580-1581; b) O. A.Mukhina, N. N.
Bhuvan Kumar, T. M. Arisco, R. A.Valiulin, G.
A.Metzel, A. G.Kutateladze,Angew. Chem. Int.
Ed.,2011,50, 9423-9428; c) D. M.Kuznetsov, O. A.
Mukhina, A. G.Kutateladze, Angew. Chem,Int.
Ed.,2016, 55, 6988-6991; d) Y.-Y.Liu, X.-Y. Yu, J.-R.
Chen, M.-M.Qiao, X.Qi, D.-Q. Shi, W.-J. Xiao, Angew.
Chem. Int. Ed.,2017, 56, 9527-9531; e) D.
M.Kuznetsov, A. G. Kutateladze, J. Am. Chem.
Soc.,2017, 139, 16584-16590; f) D. Liang, L. Rao, C.
Xiao, J.-R.Chen, Org. Lett.,2019,21, 8783-8778.
Scheme 3.Plausible Reaction Mechanism
In summary, we have developed a tandem
phospha-Michael addition/N-acylation/intramolecular
Wittig reaction of aza-o-QMs from N-(ortho-
chloromethyl)aryl amides under mild conditions. This
protocol features broad substrate scope, mild and
simple reaction procedures, providing a practical
access to valuable indole derivatives in moderate and
good yields. Further studies of additional applications
of aza-o-QMs toward the synthesis of heterocyclic
compounds are currently underway in our laboratory.
[4] a) B. Mugrage, C. Diefenbacher, J. Somers, D. T.
Parker, T. Parker, Tetrahedron Lett.,2000, 41, 2047-
2050; b) G. Li, H. Liu, G. Lv, Y. Wang, Q. Fu, Z. Tang,
Org. Lett.,2015, 17, 4125-4127; c) G.-J. Mei, Z.-Q. Zhu,
J.-J. Zhao, C.-Y. Bian, J. Chen, R.-W. Chen, F. Shi,
Chem. Commun.,2017, 53, 2768-2771.
[5] Y. Ito, S. Miyata, M.Nakatsuka, T.Saegusa, J. Am.
Chem. Soc.,1981, 103, 5250-5251.
Experimental Section
[6] For examples on [4+2] cycloaddition with aza-o-QMs,
generated from N-(o-chloromethyl)aryl amides,see: a)
H.Steinhagen, E. J. Corey, Angew. Chem. Int.
General procedure:A dry 10 mL Schlenk flask equipped with a
magnetic stirring bar, was sequentially charged with N-(2-
(chloromethyl)phenyl)-4-methylbenzenesulfonamide1a
(0.5
4
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10.1002/adsc.202000343
Advanced Synthesis & Catalysis
Ed.,1999,38,
1928-1931;
b)
F.
Avemaris,S.
9608-9644; d) A. J.Kochanowska-Karamyan, M.
T.Hamann, Chem. Rev.,2010, 110, 4489-4497; e) S.
Lal,T. J.Snape, Curr. Med. Chem.,2012, 19, 4828-4837;
f) N. K. Kaushik, N. Kaushik, P. Attri, N.Kumar, C. H.
Kim, A. K. Verma, E. H.Choi, Molecules,2013,
18,6620-6662; g) J. Y. Mao, Z. T. Wang, X. Y. Xu, G.
Q. Liu, R. S. Jiang, H. X. Guan, Z. P. Zheng, P. J.
Walsh,Angew. Chem. Int. Ed.,2019, 58, 11033-11038;h)
Y.-C. Zhang, F. Jiang, F. Shi, Acc. Chem. Res. 2020, 53,
425-446.
Vanderheiden,S. Bräse, Tetrahedron,2003, 59, 6785-
6796; c) A. Lee, A. Younai, C. K. Price, J. Izquierdo, R.
K.Mishra, K. A. Scheidt, J. Am. Chem. Soc.,2014, 136,
10589-10592; d) S.-P. Jiang, W.-Q. Lu, Z. Liu, G.-
W.Wang,J. Org. Chem.,2018,83, 1959-1968; e) Q. Jin,
M. Gao, D. Zhang, C. Jiang,N.Yao, J. Zhang, Org.
Biomol. Chem.,2018, 16, 7336-7339; f) Y. Zheng, L.
Tu, N. Li, R. Huang, T. Feng, H. Sun, Z.Li, J.Liu,Adv.
Synth. Catal.,2019, 361, 44-48; g) L. Lei, Y.-Y. Yao,
L.-J. Jiang, X. Lu, C. Liang, D.-L. Mo, J. Org.
Chem.2020, 85, 3059-3070.
[11] For reviews, see: a) R. Zhou, Z.He,Eur. J. Org.
Chem.,2016, 11, 1937-1954; b) P. Karanam, G. M.
Reddy, S. R. Koppolu, W.Lin, Tetrahedron Letters,
2018, 59, 59-76;c) L.-W.Ye, J. Zhou, Y. Tang, Chem.
Soc. Rev.,2008,37, 1140-1152; d) S. Xu, Z. He, RSC
Adv.,2013, 3, 16885-16940; e) U. Das, Y.-L.Tsaia, W.
Lin, Org. Biomol. Chem.,2014, 12, 4044-4050; f) D. H.
A.Rocha, D. C. G. A. Pinto, A. M. S. Silva, Eur. J. Org.
Chem.,2018, 2018, 2443-2457.
[7] For examples on [4+1] cycloaddition with aza-o-QMs,
generated from N-(o-chloromethyl)aryl amides, see: a)
Q.-Q. Yang, C. Xiao, L.-Q. Lu, J. An, F. Tan, B.-J. Li,
W.-J. Xiao, Angew. Chem. Int. Ed.,2012, 51, 9137-
9140; b) Q.-Q. Yang, Q. Wang, J. An, J.-R. Chen, L.-Q.
Lu, W.-J. Xiao, Chem. Eur. J.,2013, 19, 8401-8404; c)
H. Huang, Y. Yang, X. Zhang, W. Zeng, Y. Liang,
Tetrahedron Lett.,2013, 54, 6049-6052; d) M. T.
Hovey, C. T. Check, A. F. Sipher, K. A. Scheidt,
Angew. Chem. Int. Ed.,2014, 53, 9603-9607; e) H. A.
Sharma, M. T. Hoveya and K. A. Scheidt, Chem.
Commun.,2016,52, 9283-9286; f) J. A. W. Jong, X.
Bao, Q. Wang, J. Zhu, Helv. Chim. Acta,2019, 102,
e1900002; g) H.-Z. Gui, X.-Y. Wu, Y. Wei, M. Shi,
Adv. Synth. Catal.2019, 361, 5466-5471.
[12] For selected examples, see: a) Y. Wang, Y.-C. Luo,
X.-Q. Hu, P.-F.Xu, Org. Lett., 2011, 13, 5346-5349; b)
J.-B. Zhu, P.Wang, S. Liao, Y. Tang, Org. Lett.,2013,
15, 3054-3057; c) L. Wang, Y.-B. Xie, N.-Y. Huang,
J.-Y. Yan, W.-M. Hu, M.-G. Liu, M.-W.Ding, ACS
Catal.,2016, 6, 4010-4016; d) L. Wang, M. Sun, M.-W.
Ding, Eur. J. Org. Chem.,2017, 2568-2578;e) S.-M.
Yang, C.-Y. Wang, C.-K. Lin, P. Karanam, G. M.
Reddy, Y.-L.Tsai, W.Lin, Angew. Chem. Int.
Ed.,2018,57, 1668-1672; f) N. Liu, F. Chao, M.-G.Liu,
N.-Y. Huang, K. Zou, L. Wang, J. Org. Chem.,2019,
84, 2366-2371; g) P. V. Khaitnar, T.-H. Lung, Y.-J. Lin,
C.-Y. Wu, S. R. Koppolu, A. Edukondalu, P. Karanam,
W. Lin, Org. Lett.,2019, 21,4219-4223; h) Y.-C. Liou,
P. Karanam, Y.-J. Jang, W. Lin, Org. Lett.,2019, 21,
8008-8012; i) Y.-C. Liou, Y.-H. Su, K.-C.Ku,
A.Edukondalu, C.-K. Lin, Y.-S.Ke, P.Karanam, C.-J.
Lee, W. Lin,Org. Lett.,2019, 21, 8339-8343.
[8] For examples on [4+3] cycloaddition with aza-o-QMs,
generated from N-(o-chloromethyl)aryl amides, see: a)
G. Zhan, M.-L. Shi, Q. He, W. Du, Y.-C. Chen, Org.
Lett.,2015, 17, 4750-4753; b) L. Chen, G. Yang, J.
Wang, Q. Jia, J. Wei, Z. Du, RSC Adv.,2015, 5, 76696-
76699; c) J.-Y. Liu, H. Lu, C.-G. Li, Y.-M. Liang, P.-F.
Xu, Synlett,2016, 27, A-E; d) Y. Zhi, K. Zhao, T. Shu,
E. Dieter, Synthesis,2016, 48, 238-244; e) Z. Guo, H.
Jia, H. Liu, Q. Wang, J. Huang, H. Guo, Org.
Lett.,2018, 20, 2939-2943; f) Q. Jin, J. Zhang, C. Jiang,
D. Zhang, M. Gao, S. Hu, J. Org. Chem.,2018, 83,
8410-8416; g) W. Long, S. Chen, X. Zhang, L. Fang, Z.
Wang, Tetrahedron,2018, 74, 6155-6165; h) X. Zhang,
Y. Pan,P. Liang, L. Pang, X. Ma, W. Jiao, H. Shao,
Adv. Synth. Catal.,2018, 360, 3015-3019; i) Y.-S.
Zheng, L. Tu, L.-M. Gao, R. Huang, T. Feng, H. Sun,
W.-X. Wang, Z.-H. Li, J.-K. Liu, Org. Biomol.
Chem.,2018, 16, 2639-2642; j) Z. Meng, W. R. Yang, J.
Zheng, Tetrahedron Lett.,2019, 60, 1758-1762.
[13] a) Q.-Q. Yang, W.-J. Xiao, Eur. J. Org. Chem.,2017,
2017, 233-236; b) X.-K. He, B.-G. Cai, Q.-Q. Yang, L.
Wang, J. Xuan, Chem. Asian. J.,2019, 14, 3269-3273;
c) T.-B. Hua, Q.-Q. Yang, Y.-Q. Zou,
Molecules,2019,24, 3191-3213;d) T.-B. Hua, C. Xiao,
Q.-Q.Yang, J.-R. Chen, Chin. Chem. Lett.,2020, 31,
311-323; e) Q.-Q. Yang, N. Liu, J.-Y. Yan, Z.-L. Ren,
L. Wang, Asian. J. Org. Chem.,2020, 9, 116-120; f) X.
Cheng, S.-J. Zhou, G.-Y.Xu, L. Wang, Q.-Q. Yang, J.
Xuan, Adv. Synth. Catal.,2020, 362, 1-6.
[9] J.-R. Chen, X.-Q. Hu, L.-Q. Lu, W.-J. Xiao, Chem.
Rev.,2015, 115, 5301-5365.
[14]For more details, please see the supporting information.
[10]a) J. A.Joule,Thieme, Stuttgart, 2001; b) T. Kawasaki,
K.Higuchi, Nat. Prod.Rep.,2005, 22, 761-793; c) M.
Bandini, A.Eichholzer, Angew. Chem. Int.Ed.,2009, 48,
5
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10.1002/adsc.202000343
Advanced Synthesis & Catalysis
COMMUNICATION
Tandem Phospha-Michael Addition/N-Acylation/
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Methides: Approaches to 2,3-Disubstituted Indoles
Adv. Synth. Catal.Year, Volume, Page – Page
Ting-Bi Hua, Fei Chao, Long Wang, Chen-Yang
Yan, Cong Xiao, Qing-Qing Yang,* Wen-Jing
Xiao*
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