Palladium-Catalyzed Carbonylative Difunctionalization of C=N Bond of Azaarenes or Imines to Quinazolinones

Article abstract of DOI:10.1002/asia.202000359

Supporting information for this article is given via a link at the end of the document. By intercepting the acylpalladium species with C=N bond of azaarenes or imines other than free amines or alcohols, the difunctionalization of C=N bond was established via palladium-catalyzed carbonylation/nucleophilic addition sequence. This method is compatible with a diverse range of azaarenes and imines and allows for the efficient synthesis of a wide range of quinazolinones and derivatives. The synthetic utility has been demonstrated by one-step synthesis of evodiamine and its analogue with inexpensive starting materials.

Full text of DOI:10.1002/asia.202000359

CHEMISTRY
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Accepted Article
Title: Palladium-Catalyzed Carbonylative Difunctionalization of C=N
Bond of Azaarenes or Imines to Quinazolinones
Authors: Hanmin Huang, Xibing Zhou, and Yongzheng Ding
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COMMUNICATION
Palladium-Catalyzed Carbonylative Difunctionalization of C=N
Bond of Azaarenes or Imines to Quinazolinones
Xibing Zhou,[a] Yongzheng Ding,[a] and Hanmin Huang*[a,b]
Abstract: By intercepting the acylpalladium species with C=N bond
of azaarenes or imines other than free amines or alcohols, the
difunctionalization of C=N bond was established via palladium-
catalyzed carbonylation/nucleophilic addition sequence. This method
is compatible with a diverse range of azaarenes and imines, and
allows for the efficient synthesis of a wide range of quinazolinones
and derivatives. The synthetic utility has been demonstrated by one-
step synthesis of evodiamine and its analogue with inexpensive
starting materials.
and acids or their derivatives as starting materials.[7] Various
protocols by combination of Ullmann-type coupling reactions or
oxidative coupling with cyclocondensation reaction under harsh
conditions have been reported for this method. However, the
requirement of a pre-synthesized acid as well as a large amount
of dehydrating agents to construct the amide bond limits its
practicability and generality. Another alternative method is the
transition metal-catalyzed carbonylative coupling reaction with
halogenated azaarenes or halogenated imines as coupling
partners, which could avoid using acids and dehydrating agents
to build the amidic-bond.[8] In these reported reactions, one of
the most impressive methods is the intramolecular
pyridocarbonylations proceeded via dearomatizing carbonylation
of pyridine derivatives.[8e-8g] However, the required halogen or
amine prefunctionalization of the imines or azaarenes
significantly reduces its synthetic appeal and limits its
applications to only a few quinazolinones. Therefore, the
development of straightforward methods that enables the
construction of complex quinazolinones from simple starting
materials would have far-reaching implications for both the
synthetic and the medicinal chemistry communities. Although
the carbonylative transformation of electron deficient N-
toluenesulfonyl imines to corresponding 2,3-dihydro-4(1H)-
quinazolinones have been developed,[9] a general protocol for
the synthesis of quinazolinones from simple azaarenes and N-
alkyl substituted imines would be still desirable.
Quinazolinones are prevalent synthetics and important scaffolds
of natural products, which have been widely recognized as “core
structures” in drug discovery.[1] They are now known to possess
a wide spectrum of biological and pharmacological activities,
such
as
anti-inflammatory,
antioxidant,
antimicrobial,
antipsychotic, and antihypertensive activity, strong analgesic
activity, and many effects on the central nervous system
(CNS).[2] For example, rutaecarpine, euxylophoricine B, and
evodiamine are all effective ingredients of Chinese herbal
medicines.[3-4] Additionally, fenquizone[5] and raltitrexed[6]
containing this core structure have been on the market or are in
clinical trials for the treatment of edema, diuretic, and cancer
(Figure 1).
Figure 1. Representive drugs and natural products with quinazolinone core.
Despite their importance, the synthetic methods for making
quinazolinones are unsatisfactory. One of the most popular
methods is on the basis of condensation reaction with amines
Scheme 1. Palladium-catalyzed carbonylative difunctionalization of C=N
bonds.
[a]
X. Zhou, Y. Ding, and Prof. Dr. H. Huang
Hefei National Laboratory for Physical Sciences at the Microscale
and Department of Chemistry, Center for Excellence in Molecular
Synthesis
The development of catalytic systems for the functionalization
of multiple bonds as well as aryl derivatives remains one of the
main interests for the chemical and pharmaceutical industries,
providing economical and clean methods for various
functionalized molecular systems.[10] Among the reported efforts
in this area, many attractive procedures have been developed
for catalytic difunctionalization of alkene owing to its abundance,
diversity and predictable reactivity.[11-12] However, there are few
examples of these that bring about the catalytic
University of Science and Technology of China, Chinese Academy
of Sciences
Hefei, 230026, P. R. China
E-mail: hanmin@ustc.edu.cn
Prof. Dr. H. Huang
State Key Laboratory of Applied Organic Chemistry
Lanzhou University
Lanzhou, 730000, P. R. China
[b]
Supporting information for this article is given via a link at the end of
the document.
1
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10.1002/asia.202000359
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difunctionalization of polar C=N bond, although it would be
potentially utilized for the construction of complex nitrogenated
compounds. We reasoned that an operationally simple and
mechanistically distinct catalytic C=N bond difunctionalization
process involving available 2-iodoanilines, imines or azaarenes
as well as CO feedstocks would expand the capacity of C=N
bond difunctionalization-based strategy to the synthesis of
quinazolinones. In previous work,[13] we and others
demonstrated that the C=N bond contained in imines or
azaarenes could intercept the active acylpalladium species to
form N-acyliminium ions via reductive elimination.[14] Being
aware that N-acyliminium ions are capable of undergoing fast
nucleophilic addition with a suitable nucleophile to generate the
stable amide species, we envisioned that the difunctionalization
of C=N bond of imines or azaarenes 2 could be furnished with 2-
iodoaniline and CO via the palladium-catalyzed carbonylation
and nucleophilic addition sequence. However, the realization of
such a process is challenging, since the interception process is
reversible and a side reaction for the formation of the cyclic
amide 4 from the acylpalladium species A may take place to
compete with the desired C=N bond difunctionalization reaction
(Scheme 1). We believe that the competition would be controlled
by tuning the palladium catalyst and reaction condition to affect
the rate of the intramolecular nucleophilic addition process.
Herein, we report a new strategy for catalytic difunctionalization
of C=N bond of azaarenes and imines via palladium catalyzed
carbonylation and nucleophilic addition, which leads to the
development of an efficient reaction for the construction of
quinazolinones.
(Table 1, entries 2-4, and see Supporting Information), in which
the desired product 3aa was obtained in 84% yield with good
chemoselectivity. Other phosphine ligands including the
commonly used bidentate phosphines and monophosphines
were then examined with Pd(MeCN)2Cl2 as
a palladium
precursor (Table 1, entries 5−9). The screening experiments
demonstrated that the electron-rich and steric hindrance ligands
were found to be crucial for obtaining high chemoselectivity and
reactivity. Among these, t-Bu3P was the most effective ligand
which could deliver the desired quinazolinone 3aa in 77% yield,
together with the byproduct 4aa in 10% yield. It is worth pointing
out that the inverse chemoselectivity was obtained when DPPF
served as a ligand. Subsequently, the impact of the base over
the reactivity and chemoselectivity of this process was
investigated, and it was discovered that K3PO4 remained the
optimal choice (Table 1, entries 10-12). Additionally, screening
of some representative solvents revealed that toluene exhibited
the most significant effect to this carbonylative cyclization (Table
1, entries 13-16).
Scheme 2. Substrate scope for azaarenes or imines.[a]
Table 1. Optimization of Reaction Conditions.[a]
Initially, the palladium catalyzed difunctionalization of C=N
bond was investigated with 2-iodoaniline (1a) and pyridine (2a)
under 1 atm of CO. As expected, the desired product 3aa was
obtained in 49% yield by using Pd(t-Bu3P)2 and K3PO4 in toluene,
together with the side product 4aa in 32% yield (Table 1, entry 1).
To circumvent the formation of byproduct 4aa and maximize the
efficiency of the process, an extensive screening of various
reaction parameters was conducted. We assumed that the
formation of 3aa might be accelerated via aromatization in the
presence of oxidant. Screening of a variety of oxidants revealed
that the most efficient catalytic system was furnished with MnO2
With the optimal reaction conditions identified, investigation
into the substrate scope for the present carbonylative cyclization
of 2-iodoaniline with a variety of pyridines, imines and other C=N
bond containing molecules was pursued. As shown in Scheme 2,
the optimized reaction conditions proved to be effective for
2
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10.1002/asia.202000359
Chemistry - An Asian Journal
COMMUNICATION
treatment of 2-iodoaniline (1a) with a series of pyridines (2a-2e).
Both electron-donating and electron-withdrawing substituents on
the pyridine-ring were tolerated to give the corresponding
products in moderated to good yields. While the substituents
could be located on the meta, para-position, the pyridine with
substituent on the ortho-position led to lower activity. It is worth
noting that almost no other regioisomers were detected in the
reactions of para-substituted pyridines (2b-2d) due to the steric
effect. The analogues of pyridine, such as isoquinoline and
quinoline, were also suitable substrates (2f-2g) for the present
reaction. The regioselectivity of 2g might be related to the
electropositivity on isoquinoline ring.[7g] However, when the
aldimine 2h was subjected to the reaction conditions, the 3-
reaction was conducted in the absence of MnO2. Under this
reaction conditions, aldimines bearing fluoro (2i) and methoxyl
group (2j) gave the corresponding 2,3-dihydroquinazolin-4(1H)-
one in good yields. In addition, thienyl aldimine (2k) and
naphthyl aldimine (2l) could be smoothly converted to the
desired product in 81% yield and 72% yield, respectively.
Besides the imines derived from benzyl amines, the imine
originated from n-butylamine could also undergo the
carbonylative cyclization reaction to give the corresponding
cyclization product in 77% yield (3am). The imine 2n derived
from cyclopropanecarbaldehyde proved to be an efficient partner
for the present reaction and the desired product was
successfully prepared in 53% yield (3an). However, imines
derived from simple aliphatic aldehydes were not applicable for
the present reaction due to their aza-Mannich type self-
condensation[15] in the presence of K3PO4 at high temperature. It
is worth pointing out that when the coupling partner containing
both pyridine and imine moieties (2o), the difunctionalization of
C=N bond occured preferentially on imine-moiety and produced
the corresponding product 3ao in 61% yield. Moreover, 3,4-
dihydroisoquinoline (2p) was also compatible with this novel
reaction, giving the corresponding product 3ap in 97% yield.
However, no desired product was obtained when electro-
deficient imine, such as N-tosylbenzenemethanimine, was
utilized as a coupling partner.
benzyl-2-phenyl-2,3-dihydroquinazolin-4(1H)-one
3ah
was
obtained in 77% yield together with trace amount of 4aa and
almost no dehydrogenation product was observed. To our
delight, the yield of 3ah was improved to 90%, when the same
Scheme 3. Substrate scope of 2-iodoanilines.[a]
Next, we evaluated the substrate scope with respect to a
series of 2-iodoanilines. As shown in Scheme 3, in all cases, the
carbonylative cyclization reaction with pyridine proceeded
smoothly to afford their corresponding quinazolin-4(3H)-ones in
good yields. In general, both substituents on the para or meta
position to iodine of the aryl ring, such as alkyl-, alkoxy-, and
halogens can survive to efficiently couple with pyridine and CO,
while electron-withdrawing groups resulted in a slightly lower
yields (3ba-3ha). Notably, 2-iodo-N-methylaniline (1i) could
react with imine 2g to give the corresponding product in 53%
yield under 20 atm of CO. This method is also compatible with 2-
iodophenol to react with 4,9-dihydro-3H-pyrido[3,4-b]indole 2q to
give evodiamine analogue 3jq in 47% yield.
Scheme 4. One-step synthesis of rutaecarpine and evodiamine.
The synthetic value of the palladium catalyzed carbonylative
cyclization was further demonstrated through its application in
the one-step synthesis of evodiamine and its analogue (Scheme
4). Evodiamine is a quinazolinocarboline alkaloid isolated from
the fruit of Evodia rutaecarpa Bentham, which displays diverse
biological activities including anti-inflammatory, antiobesity, and
antitumor effects. Because of its broad-spectrum and multi-
targeting antitumor profile, evodiamine represents a good
3
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10.1002/asia.202000359
Chemistry - An Asian Journal
COMMUNICATION
starting point for the development of novel antitumor agents. In a
notable example, we obtained rutaecarpine directly from
inexpensive and commercially available 4,9-dihydro-3H-
pyrido[3,4-b]indole 2q and 2-iodoaniline 1a in 67% yield. In
addition, 2q could react with 2-iodo-N-methylaniline to afford the
corresponding analogue evodiamine (3iq).
also be employed in the one-step synthesis of evodiamine and
its analogues with inexpensive starting materials. Further
investigations on gaining a detailed mechanistic understanding
of this reaction and the application of this strategy in other
reactions are currently in progress.
On the basis of the above results and precedent reports,[12-13]
a tentative catalytic cycle for the formation of quinazolinones
was proposed in Figure 2. Initially, the reaction was initiated by
the formation of the arylpalladium complex I via the oxidative
addtion of 2-iodoaniline 1 to Pd(0). Next, migratory insertion of
CO into the C-Pd bond of complex I results in the formation of
acylpalladium intermediate II. The resultant acylpalladium
species II reacts with imime or pyridine via reductive elimination
in the presence of CO to generate N-acyliminium salt III and
regenerate the active Pd(0) species to complete the catalytic
cycle. Subsequent nucleophilic addition of the amino group of 2-
iodoaniline to N-acyliminium salt III leads to the formation of 2,3-
dihydroquinazolin-4(1H)-one.[7g] An alternative reaction pathway
is initiated by intermolecular nucleophilic addition of aniline to
C=N bond to generate intermediate IV, followed by palladium
catalyzed intramolecular aminocarbonylation to give 2,3-
dihydroquinazolin-4(1H)-one 3.[9] However, because of the
relatively poor electrophilicity of azaarenes and N-alkyl
substituted imines, the rate of intramolecular nucleophilic
addition of aniline to N-acyliminium salt III should be much faster
than that of intermolecular nucleophilic addition of aniline to
unactivated imine, which indicates path b might not be involved
in this reaction. It should be noted that the 2,3-
dihydroquinazolin-4(1H)-one generated from an azaarene could
be oxidized by MnO2 to give the corresponding dehydrogenation
product.
Acknowledgements
This project was supported by the National Natural Science
Foundation of China (21925111, 21790333, 21702197 and
21672199) and the Fundamental Research Funds for the
Central Universities (WK2060190086).
Keywords: palladium • carbonylation • quinazolinone •
cyclization • difunctionalization
[1]
[2]
a) J. Bartroli, E. Turmo, M. Algueró, E. Boncompte, M. L. Vericat, L.
Conte, J. Ramis, M. Merlos, J. García-Rafanell, J. Forn, J. Med.
Chem.,1998, 41, 1869-1882; b) S. B. Mhaske, N. P. Argade,
Tetrahedron 2006, 62, 9787-9826; c) A. Maity, S. Mondal, R. Paira, A.
Hazra, S. Naskar, K. B. Sahu, P. Saha, S. Banerjee, N. B. Mondal,
Tetrahedron Lett. 2011, 52, 3033-3037.
a) N. J. Liverton, D. J. Armstrong, D. A. Claremon, D. C. Remy, J. J.
Baldwin, R. J. Lynch, G. Zhang, R. J. Gould, Bioorg. Med. Chem. Lett.
1998, 8, 483-486; b) N. Malecki, P. Carato, B. Rigo, J.-F. Goossens, R.
Houssin, C. Bailly, J.-P. Hnichart, Bioorg. Med. Chem. 2004, 12, 641-
647; c) Z. Ma, Y. Hano, T. Nomura, Heterocycles 2005, 65, 2203-2219;
d) D. Arora, H. Kumar, D. Malhotra, M. Malhotra, Pharmacologyonline
2011, 3, 659-668; e) K. Nepali, S. Sharma, R. Ojha, K. L. Dhar, Med.
Chem. Res. 2013, 22, 1-15; f) A. Chawla, C. Batra, Int. Res. J. Pharm.
2013, 4, 49-58.
[3]
[4]
J. B. Koepfli, J. F. Mead, J. A. Brockman, J. Am. Chem. Soc. 1947, 69,
1837-1837.
a) J. Bergman, S. Bergman, J. Org. Chem. 1985, 50, 1246-1255; b) F.
Pin, S. Comesse, A. Daïch, Tetrahedron 2011, 67, 5564-5571; c) B. A.
Granger, K. Kaneda, S. F. Martin, Org. Lett. 2011, 13, 4542-4545; d) G.
Huang, D. Roos, P. Stadtmüller, M. Decker, Tetrahedron Lett. 2014, 55,
3607-3609.
[5]
[6]
C. Ferrando, J. M. Foy, F. W. Pratt, I. R. Purvis, J. Pharm. Pharmacol.
1981, 33, 219-222.
G. Cocconi, D. Cunningham, E. Van Cutsem, E. Francois, B.
Gustavsson, G. van HazelD Kerr, K. Possinger, S. M. Hietschold, J.
Clin. Oncol. 1998, 16, 2943-2952.
[7]
a) C. Huang, Y. Fu, H. Fu, Y. Jiang, Y. Zhao, Chem. Commun. 2008,
6333-6335; b) X. Liu, H. Fu, Y. Jiang, Y. Zhao, Angew. Chem. Int. Ed.
2009, 48, 348-351; c) M. Sharma, S. Pandey, K. Chauhan, D. Sharma,
B. Kumar, P. M. S. Chauhan, J. Org. Chem. 2012, 77, 929-937; d) L.
Colis, G. Ernst, S. Sanders, H. Liu, P. Sirajuddin, K. Peltonen, M.
DePasquale, J. C. Barrow, M. Laiho, J. Med. Chem. 2014, 57, 4950-
4961; e) D. Zhao, T. Wang, J.-X. Li, Chem. Commun. 2014, 50, 6471-
6474; f) J. Sun, Q. Tan, W. Yang, B. Liu, B. Xu, Adv. Synth. Catal. 2014,
356, 388-394; g) Y. Yang, C. Zhu, M. Zhang, S. Huang, J. Lin, X. Pan,
W. Su, Chem. Commun. 2016, 52, 12869-12872.
[8]
a) Z. Zheng, H. Alper, Org. Lett. 2008, 10, 829-832; b) B. Ma, Y. Wang,
J. Peng, Q. Zhu, J. Org. Chem. 2011, 76, 6362-6366; c) X.-F. Wu, L.
He, H. Neumann, M. Beller, Chem.-Eur. J. 2013, 19, 12635-12638; d) J.
Chen, K. Natte, A. Spannenberg, H. Neumann, P. Langer, M. Beller, X.-
F. Wu, Angew. Chem. Int. Ed. 2014, 53, 7579-7583; e) D. Liang, Y. He,
Q. Zhu, Org. Lett. 2014, 16, 2748-2751; f) T. Xu, H. Alper, Org. Lett.
2015, 17, 1569-1572; g) Z. Xie, S. Luo, Q. Zhu, Chem. Commun. 2016,
52, 12873-12876.
Figure 2. Proposed mechanism.
In summary, we have successfully developed a new and
efficient C=N bond difunctionalization protocol for the direct
synthesis of quinazolinones from simple starting materials via
palladium-catalyzed carbonylative cyclization reactions. Both
azaarenes and imines coud be ultilized as coupling partners to
give a wide range of quinazolinones in good to excellent yields.
The reaction could be performed under 1 atm of CO and can
[9]
K. Okuro, H. Alper, Tetrahedron Lett. 2012, 53, 2540-2542;
[10] a) T. E. Müller, M. Beller, Chem. Rev. 1998, 98, 675-704; b) B. M. Trost,
Acc. Chem. Res. 2002, 35, 695-705; c) M. Beller, J. Seayad, A. Tillack,
H. Jiao, Angew. Chem. Int. Ed. 2004, 43, 3368-3398; d) V. Kotov, C. C.
Scarborough, S. S. Stahl, Inorg. Chem. 2007, 46, 1910-1923; e) R. I.
4
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10.1002/asia.202000359
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McDonald, G. Liu, S. S. Stahl, Chem. Rev. 2011, 111, 2981-3019; f) R.
Chinchilla, C. Nájera, Chem. Rev. 2014, 114, 3, 1783-1826; g) L.
Huang, M. Arndt, K. Gooßen, H. Heydt, L. J. Gooßen, Chem. Rev. 2015,
115, 7, 2596-2697; h) X. Zeng, Chem. Rev. 2013, 113, 6864-6900.
[11] For leading reviews, see: a) J. P. Wolfe, Eur. J. Org. Chem. 2007, 571-
582; b) E. M. Beccalli, G. Broggini, M. Martinelli, S. Sottocornola, Chem. Rev.
2007, 107, 5318-5365; c) K. H. Jensen, M. S. Sigman, Org. Biomol. Chem.
2008, 6, 4083-4088; d) K. Muñiz, Angew. Chem. Int. Ed. 2009, 48, 9412-
9423; e) S. R. Chemler, Org. Biomol. Chem. 2009, 7, 3009-3019; f) P. A.
Sibbald, Palladium-catalyzed oxidative difunctionalization of alkenes: New
reactivity and new mechanisms, ProQuest, UMI Dissertation Publishing,
2011; g) C. Zhang, C. Tang, N. Jiao, Chem. Soc. Rev. 2012, 41, 3464-3484;
h) E. M. Beccalli, G. Broggini, S. Gazzola, A. Mazza, Org. Biomol.
Chem. 2014, 12, 6767-6789; i) G. Yin, X. Mu, G. Liu, Acc. Chem. Res.
2016, 49, 2413-2423; j) X.-W. Lan, N.-X. Wang, Y. Xing, Eur. J. Org.
Chem. 2017, 5821-5851; k) Z. J. Garlets, D. R. White, J. P. Wolfe,
Asian J. Org. Chem. 2017, 6, 636-653; l) J.-S. Zhang, L. Liu, T. Chen,
L.-B. Han, Chem. Asian J. 2018, 13, 2277-2291.
13843-13848; i) X. Qi, F. Yu, P. Chen, G. Liu, Angew. Chem. Int. Ed.
2017, 56, 12692-12696; j) M. Li, F. Yu, P. Chen, G. Liu, J. Org. Chem.
2017, 82, 11682-11690; k) J.-B. Peng. F.-P. Wu, D. Li, H.-Q. Geng, X.
Qi, J. Ying, X.-F. Wu. ACS Catal. 2019, 9, 2977-2983.
[13] For selected examples, see: a) S. Kacker, J. S. Kim, A. Sen, Angew.
Chem. Int. Ed. 1998, 37, 1251-1253; b) R. D. Dghaym, R. Dhawan, B.
A. Arndtsen, Angew. Chem. Int. Ed. 2001, 40, 3228-3230; c) J. L. Davis,
R. Dhawan, B. A. Arndtsen, Angew. Chem. Int. Ed. 2004, 43, 590-594;
d) R. Dhawan, B. A. Arndtsen, J. Am. Chem. Soc. 2004, 126, 468-469;
e) A. R. Siamaki, B. A. Arndtsen, J. Am. Chem. Soc. 2006, 128, 6050-
6051; f) D. A. Black, R. E. Beveridge, B. A. Arndtsen, J. Org. Chem.
2008, 73, 1906-1910; g) S. Bontemps, J. S. Quesnel, K. Worrall, B. A.
Arndtsen, Angew. Chem. Int. Ed. 2011, 50, 8948-8951; h) H. Yu, G.
Zhang, H. Huang, Angew. Chem. Int. Ed. 2015, 54, 10912-10916; i) G.
M. Torres, J. S. Quesnel, D. Bijou, B. A. Arndtsen, J. Am. Chem. Soc.
2016, 138, 7315-7324; j) H. Erguven, D. C. Leitch, E. N. Keyzer, B. A.
Arndtsen, Angew. Chem. Int. Ed. 2017, 22, 6078-6082; k) J. Tjutrins, B.
A. Arndtsen, Chem. Sci. 2017, 8, 1002-1007; k) X. Zhou, A. Chen, W.
Du, Y. Wang, Y. Peng, H. Huang, Org. Lett. 2019, 21, 9114-9118.
[14] a) G. Zhang, B. Gao, H. Huang, Angew. Chem. Int. Ed. 2015, 54, 7657-
7661; b) Y. Hu, Z. Shen, H. Huang, ACS Catal. 2016, 6, 6785-6789; c)
Y. Hu, H. Huang, Org. Lett. 2017, 19, 5070-5073; d) B. Gao, H. Huang,
Org. Lett. 2017, 19, 6260-6263; e) J. Zhu, B. Gao, H. Huang, Org.
Biomol. Chem. 2017, 15, 2910-2913; f) B. Gao, G. Zhang, X. Zhou, H.
Huang, Chem. Sci. 2018, 9, 380-386; g) X. Zhou, G. Zhang, B. Gao, H.
Huang, Org. Lett. 2018, 20, 2208-2212; h) S. Zou, B. Gao, Y. Huang, T.
Zhang, H. Huang, Org. Lett. 2019, 21, 6333-6336.
[12] For leading references on carbonylative difunctionalization of alkenes: a)
L. S. Hegedus, G. F. Allen, D. J. Olsen, J. Am. Chem. Soc. 1980, 102,
3583-3587; b) Y. Tamaru, T. Kobayashi, S.-I. Kawamura, H. Ochiai, Z.-I.
Yoshida, Tetrahedron Lett. 1985, 26, 4479-4482; c) Y. Tamaru, M. Hojo,
H. Higashimura, Z. Yoshida, J. Am. Chem. Soc. 1988, 110, 3994-4002;
d) H. Harayama, A. Abe, T. Sakado, M. Kimura, K. Fugami, S. Tanaka,
Y. Tamaru, J. Org. Chem. 1997, 62, 2113-2122; e) T. Shinohara, M. A.
Arai, K. Wakita, T. Arai, H. Sasai, Tetrahedron Lett. 2003, 44, 711-714;
f) T. Tsujihara, T. Shinohara, K. Takenaka, S. Takizawa, K. Onitsuka, M.
Hantanaka, H. Sasai, J. Org. Chem. 2009, 74, 9274-9279; g) J. Cheng,
X. Qi, M. Li, P. Chen, G. Liu, J. Am. Chem. Soc. 2015, 137, 2480-2483;
h) M. Li, F. Yu, X. Qi, P. Chen, G. Liu, Angew. Chem. Int. Ed. 2016, 55,
[15] W. S. Emerson, S. M. Hess, F. C. Uhle, J. Am. Chem. Soc. 1941, 63,
872-872.
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10.1002/asia.202000359
Chemistry - An Asian Journal
COMMUNICATION
Entry for the Table of Contents
The palladium-catalyzed carbonylative difunctionalization of C=N bond of azaarenes or imines is described for the first time, which
provides a reliable and rapid approach to quinazolinones. The synthetic utility of this reaction has further been demonstrated by its
application to one-step syntheses of rutaecarpin and evodiamine from inexpensive and commercially available materials.
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This article is protected by copyright. All rights reserved.