Divergent Construction of Diverse Scaffolds through Catalyst-Controlled C?H Activation Cascades of Quinazolinones and Cyclopropenones

Article abstract of DOI:10.1002/chem.202101839

A transition-metal-catalyzed C?H activation cascade strategy to rapidly construct diverse quinazolinone derivatives in a one-pot manner is reported. The catalysts play an important role in the different transformations. Additionally, the procedure is scal

Full text of DOI:10.1002/chem.202101839

Communication
doi.org/10.1002/chem.202101839
Chemistry—A European Journal
Divergent Construction of Diverse Scaffolds through
Catalyst-Controlled CÀ H Activation Cascades of
Quinazolinones and Cyclopropenones
Yuesen Shi,[a] Tianle Huang,[a] Ting Wang,[a] Jian Chen,[a] Xuexin Liu,[a] Zhouping Wu,[a]
Xiaofang Huang,[a] Yao Zheng,[a] Zhongzhen Yang,*[a] and Yong Wu*[a]
Cyclopropenone, the smallest strained aromatic ring, has
Abstract: A transition-metal-catalyzed CÀ H activation cas-
been employed as privileged chemical building blocks to
cade strategy to rapidly construct diverse quinazolinone
construct complicated molecules in the CÀ H activation field.[14]
derivatives in a one-pot manner is reported. The catalysts
Representative synthetic works included the construction of
play an important role in the different transformations.
cyclopentene spiroisoindolinones developed by Wu,[14b] and the
Additionally, the procedure is scalable, proceeds with high
synthesis of chalcones reported by Li.[14c] Our group has also
efficiency and good chemo-/regio-selectivity, and tolerates
been interested in this kind of moiety for a long time.[14d–f] For
a range of functional groups.
example, we have already reported a divergent synthesis of
chalcones, quinolones and indoles through CÀ H activation.[14d]
Given in the significant bioactivity of quinazolinones, we
envisaged the possibility of transition-metal-catalyzed CÀ H
Quinazolinone moiety is an ubiquitous in biological materials
and natural products,[1] which have shown broad bioactivity,
such as anticancer,[2] antibacterial,[3] anti-diabetes,[4] hypnotic,[5]
sedative,[6] and analgesics activity[7] (Figure 1A). Therefore,
chemical workers have devoted themselves to synthesizing
such kind of structures and derivatives.[8] Over the past decades,
metal-catalyzed CÀ H activation has emerged as a powerful
strategy for the step-economical construction of a wide variety
of value-added arenes.[9] In particular, high-valent RhIII[10] and
RuII[11] complexes have stood out as highly efficient catalysts for
the construction of CÀ C bonds by CÀ H activation. With the
rapid development of transition-metal-catalyzed CÀ H activation,
quinazolinone, the natural nitrogen-containing scaffold, has
been used as a directing group (DG) to assist metal-catalyzed
ortho-CÀ H activation progress.[12] For example, Cui demon-
strated a PdII-catalyzed reaction of quinazolinones with alkynes,
leading to fused poly-heterocycles.[12b] Then, constructing
dihydroisoquinoline-fused quinazolinone scaffolds through a
RuII-catalyzed CÀ H allylation/hydroamination cascade was re-
ported by Jana.[12c] Besides, through the RhIII-catalyzed cascade,
Szostak successfully developed a strategy for the synthesis of
isoquinolino[1,2-b]quinazolines from 2-arylquinazolinones and
sulfoxonium ylides (Figure 1B).[13]
activation using cyclopropenones as building blocks to con-
stitute a new route to quinazolinone derivatives. We com-
menced our study by choosing 2-phenylquinazolin-4-(3H)-one
1a and diphenylcyclopropenone 2a as the model substrates
under the catalysis of metal catalysts. Transition metals, like Rh,
Ir, Ru, Co, were used respectively (Table 1, entries 1–4). To our
delight, a spiro-fused heterocycle-containing product 3a was
obtained when employing [Ru(p-cymene)Cl2]2 as the catalyst.
Polycyclic structures fused at a central carbon are of great
interest due to their appealing conformational features and
Table 1. Optimization of conditions.[a]
Catalyst
Additives
Solvent
Yield [%][b]
3a
4a
1
2
3
4
5
6
7
8
[IrCp*Cl2]2
–
–
–
–
–
–
–
–
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
–
41
–
–
6
–
–
–
–
–
–
–
5
–
–
–
–
–
–
12
75
81
[Ru(p-cymene)Cl2]2
CoCp*(CO)I2
Pd(OAc)2
[RhCp*Cl2]2
Ru(bpy)3Cl2 6H2O
Grubb’s catalyst
RuCl3
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p–cymene)Cl2]2
[RhCp*Cl2]2
*
[a] Y. Shi, T. Huang, T. Wang, J. Chen, X. Liu, Z. Wu, X. Huang, Y. Zheng,
Z. Yang, Prof. Y. Wu
Department Key Laboratory of Drug-Targeting and Drug Delivery Systems
of the Education Ministry and Sichuan Province
Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan
Research Center for Drug Precision Industrial Technology
West China School of Pharmacy
9
10
11
PivOK
AdCOOH
AdCOOH
–
–
–
–
64
84
–
–
–
12[c]
13[c,d,e]
14[e,d,f,g]
TFE
TFE
TFE
[RhCp*(OAc)2]
[RhCp*(OAc)2]
Sichuan University
Chengdu 610041 (P. R. China)
[a] Reaction conditions: 1a (0.20 mmol), 2a (0.21 mmol), Catalyst
E-mail: zhongzhenyang1991@163.com
(5 mol%), AgSbF6 (30 mol%), Additive (2.0 equiv.), Solvent (2.0 mL), at
wyong@scu.edu.cn
°
°
130 C for 24 h; [b] Isolated yields; [c] 3.0 equiv. of 2a, 100 C; [d] 48 h; [e]
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/chem.202101839
°
10 mol% Catalyst, without AgSbF6; [f] 4.0 equiv. of 2a; [g] 110 C.
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Figure 1. Quinazolinones and their CÀ H activation research.
their structural implications in biological system and organic
materials.[15] These rapid [4+1] and [1+4] cycloadditions are
attractive and step-economical process for the construction of a
spiral heterocycle. Therefore, a series of optimal experiments
were carried out to improve the yield of 3a. We speculated that
Ru-catalyst might play a crucial role in the transformation.
The tests of other Ru catalysts were followed, and the
results revealed that [Ru(p-cymene)Cl2]2 remained the best one
(Table 1, entries 5–7). [Ru(p-cymene)Cl2]2 and Ag salts were
proved to be indispensable in the following investigation (see
the Supporting Information for details). Subsequently, various
acid additives were examined to improve the yield.[16] Among
various additives we tested, AdCOOH could give a better yield
of 63%. When the temperature of the reaction was increased to
[RhCp*(OAc)2], which needs no anion exchange with the Ag
salts at the beginning of the CÀ H activation, as the catalyst.[17]
As expected, the yield of 4a could be improved under the
catalysis of [RhCp*(OAc)2]. Thus, we successfully developed a
reaction that could selectively construct the sequential unsym-
metrical twofold CÀ H activation product under the optimum
conditions: 1a (0.1 mmol), 2a (0.4 mmol), [RhCp*(OAc)2]
°
(10 mol%), TFE (2.0 mL) at 110 C for 48 h.
After the efficient methods were developed for the syn-
thesis of 3a and 4a, the substrate scope of the Ru- and Rh-
catalyzed reactions between quinazolinones and cycloprope-
nones were examined (Figure 2). Generally, the synthesis of
products 3 was found to be efficient for a wide range of
substrates. 2-Phenylquinazolin-4-(3H)-one containing substitu-
ents on the para-site of the benzene ring such as methyl,
isopropyl, tert-butyl, and trifluoromethyl could be efficiently
converted into spiro-fused heterocycles 3a–3j in high yields.
Both electron-donating and -withdrawing groups were compat-
ible with these conditions. Significantly, this protocol was
readily scaled up to produce grams of spiro-fused quinazoli-
nones, highlighting its industrial application foreground (3i).
When the meta-site of the benzene ring was occupied by the
methoxy group, trifluoromethoxy group and chlorine group,
the compounds could be given on the side with less steric
hindrance (3l–3n). However, when the methoxy group turned
to the ortho-site of the benzene ring, the corresponding
°
130 C and DCE was employed as the solvent, the reaction
could proceed in high efficiency, furnishing 3a in the best yield
(84%). Thus, the reaction conditions in entry 11 were selected
as the optimal conditions.
It is worth noting that when [RhCp*Cl2]2 was employed as
the catalyst, a new product was detected (Table 1, entry 5). By
analyzing the structure data, we found it was an unsymmetrical
difunctionalized product containing an indenol moiety and a
chalcone side. Then, we started to screen the reaction
conditions. When using TFE as the solvent, the yield could be
improved. To reduce interference caused by self-coupling
product from 2a catalyzed by Ag salts, we tried to use active
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Figure 2. The substrate scope of the reactions.
product 3o could not be detected. Compared with the previous
compounds we got, it may be caused by the steric hindrance
(3f and 3l). Bis-substituted quinazolinone and 2-naphthylquina-
zolin-4-(3H)-one were tolerated as well, providing the corre-
sponding products 3p–3s in good yields. Electron-donating
group substituted groups were proved to be sluggish to take
part in the transformation compared with the electron-with-
drawing substituted ones (3t–3v). We also tried to examine the
scope of cyclopropenones, and the results suggested that
substituted cyclopropenone could bear the conditions to form
corresponding products 3w–3y. The scope for the synthesis of
compound 4 was next assessed with different substituted
quinazolinones (Figure 2). Products 4a–4f could also be
generated in a high efficiency when 2-phenylquinazolin-4-(3H)-
one was substituted by other groups.
compound containing a spiro-fused ring. When the separated
product 4a reacted under the optimal conditions for construct-
ing 3a, we could obtain the desired product 5a (Figure 2).
°
Elevating the temperature to 150 C, 5a could be obtained in
78% yield. The transformation could also be achieved in a
slightly lower yield through a two-step one-pot manner.
We hoped that the chalcone chain in 5a could couple with
the meta-site CÀ H bond of the benzene ring and occur a direct
functionalization to form an indanone derivative product 6a. It
would be a valuable attempt for synthesis of indanone
derivatives, which are important moiety of some widely used
biological products.[18] Moreover, the challenging research on
intramolecular CÀ C coupling reactions through the activation of
two CÀ H bonds directed by a functional group are not fully
explored.[19] After the screening of reaction conditions (see the
Supporting Information for details), we found that 5a could be
transformed into 6a in a moderate yield under the catalysis of
Considering the indenol moiety of 4a, we anticipated that
the structure could undergo dehydration way to form a
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Pd(OAc)2 (Figure 2). Notably, the efficient one-pot synthesis of
tetra-substituted product 6a starting from 1a and 2a could be
smoothly implemented, albeit involving sequential activation of
five CÀ H bonds.
atom of 1a to the metal center, followed by reversible
displacement of aromatic CÀ H bond to form five-membered
metal-cycle A. Intermolecular oxidative addition by cycloprope-
none then generates an intermediate C. Subsequent reductive
elimination and intramolecular CÀ H activation then lead to the
formation of an intermediate D. When using [Ru(p-cymene)Cl2]2
as the catalyst and AdCOOH as the additive, the intermediate E
is produced from D by an intramolecular nucleophilic attack.
Oxidative addition gives ruthenium/π-allylic intermediate F,
which undergoes reductive elimination to offer the product 3a.
Meanwhile, the RuII catalyst is regenerated for a next catalysis
cycle. Under the catalysis of [RhCp*(OAc)2], the intermediate D
goes through the same intramolecular nucleophilic attack
pathway to form an intermediate product with an indenol
moiety, followed by Rh-catalyzed ortho-CÀ H activation to
selectively form an intermediate G. The other cyclopropenone
suffers the oxidative addition/reductive elimination way to form
a stable chelation intermediate H, which retards the further
synthesis of the second indenol moiety. Finally, the disubsti-
tuted product 4a is obtained by the release of the active Rh
catalyst and protonation.
To reveal how the product 3a and 4a were synthesized,
some preliminary mechanism studies were conducted (Fig-
ure 3). H/D exchange between 1a and CD3OD was firstly
performed, and the starting material was recovered with 59%
deuteration at the ortho positions, indicating the reversibility of
CÀ H activation in the absence of cyclopropenones (Figure 3a).
Another ortho-H/D exchange was observed in the NMR
spectrum when treating [D5]-1a with 2a under the standard
conditions, again confirming that the initial ortho-ruthenation
was reversible (Figure 3b). Moreover, the competition reaction
determined the reaction slightly favored the electron-donating
quinazolinones (Figure 3c). Finally, the competitive and parallel
kinetic isotope effects were measured. The kH/kD and PH/PD
values were 3.3 and 6.1, respectively, thus suggesting that the
ortho-CÀ H cleavage of 1a was probably involved in the rate-
limiting step (Figure 3d).
Based on mechanism experiments and the reported CÀ H
activation works,[12c,14g,20] a plausible mechanism was illustrated
in Figure 4. Initial anion exchange affords the active [MLX2]
species, which likely involves the coordination of the nitrogen
In summary, we have developed a divergent CÀ H activation
cascade reaction strategy to rapidly construct structurally differ-
ent scaffolds from 2-arylquinazolin-4-(3H)-one and cycloprope-
Figure 3. Mechanistic studies.
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Figure 4. Proposed mechanism.
Keywords: cascade · cyclopropenone · divergent synthesis ·
one-pot synthesis · quinazolinone
none. Different catalytic conditions are crucial for the outcome
of the reaction. These methodologies are characterized by high
chemo- and regioselectivity, good functional group tolerance,
and amenability to gram-scale synthesis. We hope that these
reactions can provide a reference for future derivation of new
chemical scaffolds by CÀ H activation.
[1] J. P. Michael, Nat. Prod. Rep. 2000, 17, 603–620.
[2] J. B. Jiang, D. P. Hesson, B. A. Dusak, D. L. Dexter, G. J. Kang, E. Hamel, J.
Med. Chem. 1990, 33, 1721–1728.
[3] R. Bouley, D. Ding, Z. Peng, M. Bastian, E. Lastochkin, W. Song, M. A.
Suckow, V. A. Schroeder, W. R. Wolter, S. Mobashery, M. Chang, J. Med.
Chem. 2016, 59, 5011–5021.
[4] J. Rudolph, W. P. Esler, S. O’Connor, P. D. G. Coish, P. L. Wickens, M.
Brands, D. E. Bierer, B. T. Bloomquist, G. Bondar, L. Chen, C.-Y. Chuang,
T. H. Claus, Z. Fathi, W. Fu, U. R. Khire, J. A. Kristie, X.-G. Liu, D. B. Lowe,
A. C. McClure, M. Michels, A. A. Ortiz, P. D. Ramsden, R. W. Schoenleber,
T. E. Shelekhin, A. Vakalopoulos, W. Tang, L. Wang, L. Yi, S. J. Gardell,
J. N. Livingston, L. J. Sweet, W. H. Bullock, J. Med. Chem. 2007, 50, 5202–
5216.
Acknowledgements
We are grateful for financial support from the National NSF of
China (grant no. 81373259) and the Sichuan Science and
Technology Program (grant no. 2020YJ0221).
[5] V. Alagarsamy, K. Chitra, G. Saravanan, V. R. Solomon, M. T. Sulthana, B.
Narendhar, Eur. J. Med. Chem. 2018, 151, 628–685.
[6] V. Jatav, P. Mishra, S. Kashaw, J. P. Stables, Eur. J. Med. Chem. 2008, 43,
Conflict of Interest
1945–1954.
[7] A. Yesilada, S. Koyunoglu, N. Saygilia, E. Kupeli, E. Yesilada, E. Bedir, I.
Khanc, Arch. Pharm. 2004, 337, 96–104.
[8] a) S. U. Dighe, S. Batra, Tetrahedron 2013, 69, 9875–9885; b) Y.-B. Wang,
S.-C. Zheng, Y.-M. Hu, B. Tan, Nat. Commun. 2017, 8, 15489–15497; c) W.
The authors declare no conflict of interest.
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www.chemeurj.org
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Yang, R. Qiao, J. Chen, X. Huang, M. Liu, W. Gao, J. Ding, H. Wu, J. Org.
Chem. 2015, 80, 482–489; d) J.-Q. Liu, Y.-G. Ma, M.-M. Zhang, X.-S. Wang,
J. Org. Chem. 2017, 82, 4918–4923.
Chem. Front. 2020, 7, 2944–2949; g) K. Komatsu, T. Kitagawa, Chem. Rev.
2003, 103, 1371–1428.
[15] a) P. A. Crooks, H. E. Rosenberg, J. Med. Chem. 1978, 21, 585–587; b) R. J.
Parry, R. Mafoti, J. M. Ostrander, J. Am. Chem. Soc. 1987, 109, 1885–1886;
c) P. M. Petrone, B. Simms, F. Nigsch, E. Lounkine, P. Kutchukian, A.
Cornett, Z. Deng, J. W. Davies, J. L. Jenkins, M. Glick, ACS Chem. Biol.
2012, 7, 1399–1409; d) H. Chen, H. Shang, Y. Liu, R. Guo, W. Lin, Adv.
Funct. Mater. 2016, 26, 8128–8136; e) P. Saraswat, G. Jeyabalan, M. Z.
Hassan, M. U. Rahman, N. K. Nyola, Synth. Commun. 2016, 46, 1643–
1664; f) S. Sharma, Y. Oh, N. K. Mishra, U. De, H. Jo, R. Sachan, H. S. Kim,
Y. H. Jung, I. S. Kim, J. Org. Chem. 2017, 82, 3359–3367; g) V. K. Valeriya,
N. M. Andrey, Mini-Rev. Org. Chem. 2019, 16, 173–192; h) M. Kubo, K.
Noguchi, K. Nakano, ChemPlusChem 2021, 86, 171–175.
[16] a) L. Ackermann, R. Vicente, A. Althammer, Org. Lett. 2008, 10, 2299–
2302; b) L. Ackermann, R. Vicente, H. K. Potukuchi, V. Pirovano, Org. Lett.
2010, 12, 5032–5035; c) P. B. Arockiam, C. Fischmeister, C. Bruneau, P. H.
Dixneuf, Angew. Chem. Int. Ed. 2010, 49, 6629–6632; Angew. Chem.
2010, 122, 6779–6782.
[17] a) C. Wang, Y. Huang, Org. Lett. 2013, 15, 5294–5297; b) K. R. Bettadapur,
V. Lanke, K. R. Prabhu, Chem. Commun. 2017, 53, 6251–6254.
[18] a) D. G. Nagle, Y.-D. Zhou, P. U. Park, V. J. Paul, I. Rajbhandari, C. J. G.
Duncan, D. S. Pasco, J. Nat. Prod. 2000, 63, 1431–1433; b) M. L. Tang, C.
Zhong, Z. Y. Liu, P. Peng, X. H. Liu, X. Sun, Eur. J. Med. Chem. 2016, 113,
63–74; c) S. A. Patil, R. Patil, S. A. Patil, Eur. J. Med. Chem. 2017, 138, 182–
198.
[19] a) T. Yao, K. Du, ACS Sustainable Chem. Eng. 2019, 7, 6068–6077; b) P.
Zhou, W. T. Yang, A. U. Rahman, G. Li, B. Jiang, J. Org. Chem. 2020, 85,
360–366; c) B. Liégault, D. Lee, M. P. Huestis, D. R. Stuart, K. Fagnou, J.
Org. Chem. 2008, 73, 5022–5028; d) Y. Hu, B. Zhou, H. Chen, C. Wang,
Angew. Chem. Int. Ed. 2018, 57, 12071–12075; Angew. Chem. 2018, 130,
12247–12251.
[9] a) P. Gandeepan, T. Müller, D. Zell, G. Cera, S. Warratz, L. Ackermann,
Chem. Rev. 2019, 119, 2192–2452; b) C. Sambiagio, D. Schonbauer, R.
Blieck, T. Dao-Huy, G. Pototschnig, P. Schaaf, T. Wiesinger, M. F. Zia, J.
Wencel-Delord, T. Besset, B. U. W. Maes, M. Schnurch, Chem. Soc. Rev.
2018, 47, 6603–6743; c) T. Gensch, M. N. Hopkinson, F. Glorius, J.
Wencel-Delord, Chem. Soc. Rev. 2016, 45, 2900–2936; d) L. Yang, H.
Huang, Chem. Rev. 2015, 115, 3468–3517; e) B.-J. Li, Z.-J. Shi, Chem. Soc.
Rev. 2012, 41, 5588–5598; f) C. S. Yeung, V. M. Dong, Chem. Rev. 2011,
111, 1215–1292; g) J. Wencel-Delord, T. Dröge, F. Liu, F. Glorius, Chem.
Soc. Rev. 2011, 40, 4740–4761; h) W. R. Gutekunst, P. S. Baran, Chem.
Soc. Rev. 2011, 40, 1976–1991; i) S. H. Cho, J. Y. Kim, J. Kwak, S. Chang,
Chem. Soc. Rev. 2011, 40, 5068–5083; j) D. Kalyani, N. R. Deprez, L. V.
Desai, M. S. Sanford, J. Am. Chem. Soc. 2005, 127, 7330–7331.
[10] a) T. Piou, T. Rovis, Acc. Chem. Res. 2018, 51, 170–180; b) G. Song, X. Li,
Acc. Chem. Res. 2015, 48, 1007–1020; c) G. Song, F. Wang, X. Li, Chem.
Soc. Rev. 2012, 41, 3651–3678; d) D. A. Colby, A. S. Tsai, R. G. Bergman,
J. A. Ellman, Acc. Chem. Res. 2012, 45, 814–825; e) T. Satoh, M. Miura,
Chem. Eur. J. 2010, 16, 11212–11222; f) D. A. Colby, R. G. Bergman, J. A.
Ellman, Chem. Rev. 2010, 110, 624–655.
[11] a) G. Duarah, P. Kaishap, T. Begum, S. Gogoi, Adv. Synth. Catal. 2019,
361, 654–672; b) Y.-F. Liang, L. Yang, T. Rogge, L. Ackermann, Chem. Eur.
J. 2018, 24, 16548–16552; c) A. Molnar, A. Papp, Curr. Org. Chem. 2016,
20, 381–458; d) S. De Sarkar, W. Liu, S. I. Kozhushkov, L. Ackermann, Adv.
Synth. Catal. 2014, 356, 1461–1479; e) L. Ackermann, Acc. Chem. Res.
2014, 47, 281–295; f) P. B. Arockiam, C. Bruneau, P. H. Dixneuf, Chem.
Rev. 2012, 112, 5879–5918.
[12] a) P. Ghosh, B. Ganguly, S. Das, Org. Biomol. Chem. 2020, 18, 4497–4518;
b) Y. Feng, N. Tian, Y. Li, C. Jia, X. Li, L. Wang, X. Cui, Org. Lett. 2017, 19,
1658–1661; c) G. Bairy, S. Das, H. M. Begam, R. Jana, Org. Lett. 2018, 20,
7107–7112; d) S. Devkota, H. J. Lee, S. H. Kim, Y. R. Lee, Adv. Synth. Catal.
2019, 361, 5587–5595; e) N. Umadevi, G. Kumar, N. C. G. Reddy, B. V. S.
Reddy, Curr. Org. Chem. 2021, 25, 601–634; f) A. B. Viveki, S. B. Mhaske, J.
Org. Chem. 2018, 83, 8906–8913.
[20] a) L. Kong, X. Zhou, Y. Xu, X. Li, Org. Lett. 2017, 19, 3644–3647; b) J.
Zhou, J. Li, Y. Li, C. Wu, G. He, Q. Yang, Y. Zhou, H. Liu, Org. Lett. 2018,
20, 7645–7649; c) Y. Luo, C. Shan, S. Liu, T. Zhang, L. Zhu, K. Zhong, R.
Bai, Y. Lan, ACS Catal. 2019, 9, 10876–10886; d) H.-W. Wang, Y. Lu, B.
Zhang, J. He, H.-J. Xu, Y.-S. Kang, W.-Y. Sun, J.-Q. Yu, Angew. Chem. Int.
Ed. 2017, 56, 7449–7453; Angew. Chem. 2017, 129, 7557–7561; e) S.
Mizuno, H. Tsuji, Y. Uozumi, M. Kawatsura, Chem. Lett. 2020, 49, 645–
647; f) Y. Maruyama, T. Sezaki, M. Tekawa, T. Sakamoto, I. Shimizu, A.
Yamamoto, J. Organomet. Chem. 1994, 473, 257–264.
[13] J. Zhang, X. Wang, D. Chen, Y. Kang, Y. Ma, M. Szostak, J. Org. Chem.
2020, 85, 3192–3201.
[14] a) M. Nakamura, H. Isobe, E. Nakamura, Chem. Rev. 2003, 103, 1295–
1326; b) T. Yuan, C. Pi, C. You, X. Cui, S. Du, T. Wan, Y. Wu, Chem.
Commun. 2018, 55, 163–166; c) S. Yu, X. Li, Org. Lett. 2014, 16, 1220–
1223; d) Y. Shi, H. Xing, T. Huang, X. Liu, J. Chen, X. Guo, G. B. Li, Y. Wu,
Chem. Commun. 2020, 56, 1585–1588; e) H. Xing, J. Chen, Y. Shi, T.
Huang, L. Hai, Y. Wu, Org. Chem. Front. 2020, 7, 672–677; f) J. Chen, B.
Tang, X. Liu, G. Lv, Y. Shi, T. Huang, H. Xing, X. Guo, L. Hai, Y. Wu, Org.
Manuscript received: May 25, 2021
Version of record online: ■■■, ■■■■
Chem. Eur. J. 2021, 27, 1–7
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COMMUNICATION
Y. Shi, T. Huang, T. Wang, J. Chen, X.
Liu, Z. Wu, X. Huang, Y. Zheng, Z.
Yang*, Prof. Y. Wu*
1 – 7
Divergent Construction of Diverse
Scaffolds through Catalyst-Con-
trolled CÀ H Activation Cascades of
Quinazolinones and Cycloprope-
nones
Controlled cascades: We have suc-
cessfully developed attractive CÀ H ac-
tivation cascade reactions between
quinazolinones and cyclopropenones.
Different structures can be selectively
synthesized under the precise control
of the catalysts in a one-pot manner.
The high efficiency, excellent chemo-/
regioselectivity, wide substrate scope,
and amenability to gram-scale
synthesis for both quinazolinones and
cyclopropenones demonstrated the
promising applicability of reactions.