Lactamization of sp2C?H Bonds with CO2: Transition-Metal-Free and Redox-Neutral

Article abstract of DOI:10.1002/anie.201602095

The first direct use of carbon dioxide in the lactamization of alkenyl and heteroaryl C?H bonds to synthesize important 2-quinolinones and polyheterocycles in moderate to excellent yields is reported. Carbon dioxide, a nontoxic, inexpensive, and readily available greenhouse gas, acts as an ideal carbonyl source. Importantly, this transition-metal-free and redox-neutral process is eco-friendly and desirable for the pharmaceutical industry. Moreover, these reactions feature a broad substrate scope, good functional group tolerance, facile scalability, and easy product derivatization.

Full text of DOI:10.1002/anie.201602095

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201602095
German Edition: DOI: 10.1002/ange.201602095
Sustainable Chemistry
2
À
Lactamization of sp C H Bonds with CO2: Transition-Metal-Free and
Redox-Neutral
Zhen Zhang, Li-Li Liao, Si-Shun Yan, Lei Wang, Yun-Qi He, Jian-Heng Ye, Jing Li, Yong-
Gang Zhi, and Da-Gang Yu*
Dedicated to Professor Peter Kꢀndig and Professor Gerhard Erker on the occasion of their 70th birthdays
Abstract: The first direct use of carbon dioxide in the
2-Quinolinones and polyheterocycles containing a free
(NH)-lactam are common motifs in drugs, bioactive natural
products, photoelectric materials, and important intermedi-
ates in organic synthesis (Figure 1).[6] Multiple methods to
generate such structures have been disclosed.[7] One of the
À
lactamization of alkenyl and heteroaryl C H bonds to
synthesize important 2-quinolinones and polyheterocycles in
moderate to excellent yields is reported. Carbon dioxide,
a nontoxic, inexpensive, and readily available greenhouse gas,
acts as an ideal carbonyl source. Importantly, this transition-
metal-free and redox-neutral process is eco-friendly and
desirable for the pharmaceutical industry. Moreover, these
reactions feature a broad substrate scope, good functional
group tolerance, facile scalability, and easy product derivati-
zation.
C
arbon dioxide (CO2) is an important and ideal one-carbon
(C1) source and it shows great potential in organic synthesis
owing to its nontoxicity, abundance, availability, and recycla-
bility.[1] Transformations of CO2 to useful chemicals have been
attracting increasing attention for a long time. Although it is
challenging to activate and utilize CO2 owing to its thermo-
dynamic stability and kinetical inertness, a variety of efficient
CO2 transformations have been discovered in the past
decades.[2] In addition to transformations in the presence of
reductants,[3] various kinds of non-reductive processes have
been realized to generate organic carboxylates,[4a–c] (poly)-
carbonates,[4d,e] carbamates/oxazolidinones,[4f] ureas,[4g] and
lactones.[4h] Notably, the leading groups of Nolan and
Cazin,[5a–c] Hou,[5d–f] and Iwasawa,[4h,5g,h] as well as others,[5i–l]
Figure 1. Selected biologically active 2-quinolinones and polyhetero-
cycles containing a lactam moiety.
most efficient methods is the transition-metal-catalyzed
oxidative carbonylation of ortho-alkenyl or -aryl anilines
with CO by direct sp2 C H bond transformation
À
(Scheme 1).[8] For example, the Alper group developed the
efficient Pd-catalyzed synthesis of 2-quinolinones using sub-
stoichiometric copper acetate and air as the terminal oxidant
(Scheme 1A).[8a] Meanwhile, the groups of Zhu,[8b] Chuang,[8c]
have reported elegant progress toward the direct carboxyla-
2
À
tion and lactonization of sp C H bonds, which are highly
attractive owing to the high step- and atom-economy. How-
2
À
ever, the challenging lactamization of sp C H bonds with
CO2 remains unresolved.
[*] Z. Zhang, L.-L. Liao, S.-S. Yan, L. Wang, Y.-Q. He, J.-H. Ye, Dr. J. Li,
Prof. Dr. D.-G. Yu
Key Laboratory of Green Chemistry & Technology
Ministry of Education
College of Chemistry, Sichuan University
29 Wangjiang Road, Chengdu 610064 (P. R. China)
E-mail: dgyu@scu.edu.cn
Z. Zhang, Prof. Dr. Y.-G. Zhi
Chengdu Institute of Organic Chemistry
Chinese Academy of Sciences
Chengdu, Sichuan, 610041 (P. R. China)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under
À
http://dx.doi.org/10.1002/anie.201602095.
Scheme 1. Lactamization of alkenyl and aryl C H bonds.
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Table 1: Test of different substituents on nitrogen of anilines.[a]
and Zhang[8d] independently reported the oxidative carbon-
ylation of ortho-aryl anilines with CO using stoichiometric
copper or silver salts as the oxidants (Scheme 1B). Although
these methods are step-efficient, atom-economic, and display
a good substrate scope, the use of highly toxic CO and high-
valence transition metals as the oxidants causes safety issues,
high cost, and risk for heavy metal residues, all of which
hamper industrial applications, especially in the pharmaceut-
ical sector. Therefore, developing a method that avoids toxic
CO or heavy metal salts is highly desirable.[9] In principle,
CO2, with its higher oxidation state than CO, might act
[a] Reaction conditions: 1 (0.2 mmol), NaOtBu (4.5 equiv.), 1 atm of
CO2, 2 mL of diglyme, 24 h, 1408C. The yields are isolated yields. [b] 2a
was obtained as the product. n.d.=not detected.
similarly to the combination of CO and oxidants. Herein, we
2
À
report the first lactamization of sp C H bonds with CO2 to
generate diverse 2-quinolinones and polyheterocycles under
transition-metal-free and redox-neutral conditions (Sche-
me 1C). Our process is scalable and green, with broad
substrate scope and good functional group tolerance. More-
over, the products readily can be transformed into diverse
derivatives and important drugs.
Table 2: Lactamization of 2-alkenylanilines with CO2.[a]
It is well known that anilines can react with CO2 under
À
basic conditions by nucleophilic attack/C N bond formation
to generate carbamates/carbamic acids.[4g,10] We envisioned
that the electron-rich alkene at the ortho position of an aniline
might undergo an intramolecular nucleophilic attack on the
in situ generated carbamates/carbamic acids to provide the
corresponding lactams. Based on this hypothesis, we first
tested the direct lactamization of 2-(prop-1-en-2-yl)aniline 1a
to generate 2-quinolinone 2a in the presence of 1 atm of CO2
(Supporting Information, Table S1). We explored a variety of
bases using 1,4-dioxane as the solvent. Although many kinds
of bases elicited no reactivity (Table S1, entries 1–3), several
alkali metal tert-butoxides promoted the reaction to generate
2a in moderate to good yields (Table S1, entries 4–6). Many
other solvents, including tetrahydrofuran (THF), N,N-dime-
thylformamide (DMF), and diglyme, were tested to generate
2a with KOtBu as the base (Table S1, entries 7–11). Mean-
while, NaOtBu also promoted the reaction to give 2a in 82%
yield when diglyme was applied as the solvent (Table S1,
entry 12). Excess of base and high temperature are important
for high efficiency. For example, no conversion was observed
when no or 1 equivalent of NaOtBu was used, demonstrating
the critical role of the base (Table S1, entries 12–15). The
yield improved to 95% when 4.5 equivalent of NaOtBu was
used at 1408C (Table S1, entry 17). Under these conditions,
good conversion was observed in just 2.5 hours (Table S1,
entry 18). Importantly, the inductively coupled plasma atomic
emission spectrometer (ICP-AES) detection of transition
metal sources demonstrated that this reaction is free of
transition metals (see the Supporting Information for details).
With the best reaction conditions in hand, we investigated
the effect of substituents on the aniline nitrogen (Table 1).
Neither alkyl (1b) nor aryl (1c) substituted anilines afforded
the desired products. When amide 1d and carbamate 1e were
applied as substrates, 2a was obtained in 22% and 95% yield,
respectively. This might arise from in situ generation of free
aniline 1a or the intermediates under the reaction conditions
(see the Supporting Information).
[a] Reaction conditions: the same as Table 1. [b] 1 (0.3 mmol), NaOtBu
(3.0 equiv).
(Table 2). First, varying the substitution on the alkene moiety
was tested. We found that both terminal alkenes (1a) and
internal alkenes (1 f and 1g) could be applied in the reaction
to give the products in good yields. Moreover, the substrate
with a methyl group on the alkene (1a) showed better
reactivity than those with a hydrogen (1h) or an ethyl group
(1i). Secondly, we tested various kinds of substituents on the
arene. It was found that the steric hindrance did not hamper
the reaction, forming 2j in 81% yield. The anilines with
electron-donating groups (EDGs; 1k and 1p) showed similar
reactivity to those with electron-withdrawing groups (EWGs;
1l and 1q). Many kinds of functional groups, including OMe
(2k and 2p), CF3 (2l and 2q), Cl (2m and 2r), and Br (2s),
were well tolerated, providing great opportunities for drug
synthesis[6c,11] and further functionalization.[12]
Considering the high importance of 4-aryl-2-quinolinones,
we further tested the reactivities of ortho a-styrenyl-substi-
tuted anilines (Table 3), which can be easily synthesized from
simple anilines with alkynes.[14] We found that most of the 2-
Based on these results, we further investigated the
reactivities of free anilines with ortho-alkenyl substitution
2
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Table 3: Lactamization of 2-alkenylanilines with CO2.[a]
enes, including imidazo[1,2-a]pyridine (1ae and 1af), pyra-
zole (1ag), and pyrole (1ah), could undergo the base-
mediated lactamization to give the desired products in
moderate to excellent yields. Notably, 2ah is the core
structure of PARP-1 inhibitors (Figure 1).[6e]
After developing the methodology, we further demon-
strated its utility by applying it toward the synthesis of some
valuable intermediates and biologically active compounds.
First, we found that the reaction with aniline 1a is amenable
to scale-up to gram quantities with comparable yield and
efficiency (Scheme 2A). Second, the important 4-aryl-2-
[a] Reaction conditions: the same as Table 1. [b] 1 (0.3 mmol), NaOtBu
(3.0 equiv).
(1-arylvinyl)anilines could undergo the reaction to generate
the corresponding 4-aryl-2-quinolinones in moderate to
excellent yields. Similarly, many kinds of functional groups
did not affect the reaction. The aniline motifs with para
substituents (2u) showed higher yields than those with ortho
functionality (2w). Naphthylamine 1x also successfully
underwent this transformation. The electron-rich aryl
groups on the alkenes (2y) showed higher reactivity than
the electron-poor ones (2z, 2aa, and 2ad), which might be
a result of the different alkene nucleophilicities. Moreover,
À
the substrates with two carbon halide bonds, either with the
same (2ac) or different (2ad) halogen, also afforded the
desired products in good yields.
Based on the success of ortho-alkenyl anilines in this
Scheme 2. Large scale reaction and synthetic applications.
KSF=Montmorillonite KSF.
2
À
reaction and the similar reactivity in many kinds of sp C H
transformations, we further investigated the reactions of
ortho-aryl anilines 1 (Table 4) with CO2 to generate poly-
heterocycles containing a free (NH)-lactam and their deriv-
atives, which are also common motifs in bioactive compounds.
To our delight, anilines with many kinds of ortho-heteroar-
quinolinones 2ai (HBV inhibitor)[6d] and 2aj (a key inter-
mediate to Tipifarnib)[6c] were both rapidly accessed in good
yields by application of the appropriate 2-(1-arylvinyl)ani-
lines 1ai[13b] and 1aj,[14a] readily obtained from the heteroge-
neously catalyzed reactions between a para-haloaniline 3 and
a simple arylalkyne 4, to our reaction conditions (Sche-
me 2B). Moreover, 4-phenyl-2-quinolinones 2t was selected
as a model substrate for scaffold diversification (Scheme 2C).
For example, selective methylation of nitrogen[14] was realized
to give 5 in good yield, which provides opportunities for the
Table 4: Lactamization of 2-heteroarylanilines with CO2.[a]
À
selective bromination of the alkenyl C H bond and further
transformations.[12a,15] Meanwhile, 2t could be transformed
easily to 2-alkoxyquinolines (such as a known LTB4 antag-
onist),[6b] 2-chloroquinolines 6, as well as 2-aminoquinolines
(such as a known MCH-1R receptor modulator).[6a] This
versatility demonstrates that the products rapidly obtained
[a] Reaction conditions: the same as Table 1.
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Am. Chem. Soc. 2015, 137, 6476; e) C. C. Chong, R. Kinjo,
Angew. Chem. Int. Ed. 2015, 54, 12116; Angew. Chem. 2015, 127,
12284.
from our method are highly useful and attractive in synthetic
and medicinal chemistry.
Furthermore, a series of experiments were performed to
investigate the mechanism. Based on the results, we propose
that both 1e and urea 7 may be the intermediate to the highly
reactive isocyanate 8,[16a] which undergoes irreversible cycli-
zation to generate the product 2a (see the Supporting
Information for details).[16b]
[4] a) A. Correa, R. Martꢀn, Angew. Chem. Int. Ed. 2009, 48, 6201;
Angew. Chem. 2009, 121, 6317; b) Y. Zhang, S. N. Riduan,
Angew. Chem. Int. Ed. 2011, 50, 6210; Angew. Chem. 2011, 123,
6334; c) D. Yu, S. P. Teong, Y. Zhang, Coord. Chem. Rev. 2015,
293 – 294, 279; d) C. Martꢀn, G. Fiorani, A. W. Kleij, ACS Catal.
2015, 5, 1353; e) D. J. Darensbourg, Chem. Rev. 2007, 107, 2388;
f) S. Pulla, C. M. Felton, P. Ramidi, Y. Gartia, N. Ali, U. B.
Nasini, A. Ghosh, J. CO2 Util. 2013, 2, 49; g) Z.-Z. Yang, L.-N.
He, J. Gao, A.-H. Liu, B. Yu, Energy Environ. Sci. 2012, 5, 6602;
h) K. Sasano, J. Takaya, N. Iwasawa, J. Am. Chem. Soc. 2013,
135, 10954.
[5] a) I. I. F. Boogaerts, S. P. Nolan, J. Am. Chem. Soc. 2010, 132,
8858; b) I. I. F. Boogaerts, G. C. Fortman, M. R. L. Furst, C. S. J.
Cazin, S. P. Nolan, Angew. Chem. Int. Ed. 2010, 49, 8674; Angew.
Chem. 2010, 122, 8856; c) I. I. F. Boogaerts, S. P. Nolan, Chem.
Commun. 2011, 47, 3021; d) L. Zhang, J. Cheng, T. Ohishi, Z.
Hou, Angew. Chem. Int. Ed. 2010, 49, 8670; Angew. Chem. 2010,
122, 8852; e) H. Inomata, K. Ogata, S. Fukuzawa, Z. Hou, Org.
Lett. 2012, 14, 3986; f) A. Ueno, M. Takimoto, W. N. O. Wylie, M.
Nishiura, T. Ikariya, Z. Hou, Chem. Asian J. 2015, 10, 1010; g) H.
Mizuno, J. Takaya, N. Iwasawa, J. Am. Chem. Soc. 2011, 133,
1251; h) T. Suga, H. Mizuno, J. Takaya, N. Iwasawa, Chem.
Commun. 2014, 50, 14360; i) O. Vechorkin, N. Hirt, X. Hu, Org.
Lett. 2010, 12, 3567; j) G. A. Olah, B. Tçrçk, J. P. Joschek, I.
Bucsi, P. M. Esteves, G. Rasul, G. K. S. Prakash, J. Am. Chem.
Soc. 2002, 124, 11379; k) K. Nemoto, H. Yoshida, N. Egusa, N.
Morohashi, T. Hattori, J. Org. Chem. 2010, 75, 7855; l) M. Gu, Z.
Cheng, Ind. Eng. Chem. Res. 2014, 53, 9992.
[6] a) K. Hino, K. Furukawa, Y. Nagai, H. Uno, Chem. Pharm. Bull.
1980, 28, 2618; b) R. Labaudiniꢂre, W. Hendel, B. Terlain, F.
Cavy, O. Marquis, N. Dereu, J. Med. Chem. 1992, 35, 4306;
c) P. R. Angibaud, M. G. Venet, W. Filliers, R. Broeckx, Y. A.
Ligny, P. Muller, V. S. Poncelet, D. W. End, Eur. J. Org. Chem.
2004, 479; d) P. Cheng, Q. Zhang, Y. B. Ma, Z. Y. Jiang, X. M.
Zhang, F. X. Zhang, J. J. Chen, Bioorg. Med. Chem. Lett. 2008,
18, 3787; e) J. Miyashiro, K. W. Woods, C. H. Park, X. Liu, Y. Shi,
E. F. Johnson, J. J. Bouska, A. M. Olson, Y. Luo, E. H. Fry, V. L.
Giranda, T. D. Penning, Bioorg. Med. Chem. Lett. 2009, 19, 4050.
[7] Selected examples, see: a) T. Iwai, T. Fujihara, J. Terao, Y. Tsuji,
J. Am. Chem. Soc. 2010, 132, 9602; b) J. Chen, K. Natte, A.
Spannenberg, H. Neumann, M. Beller, X.-F. Wu, Chem. Eur. J.
2014, 20, 14189; c) Y. Deng, W. Gong, J. He, J. Yu, Angew. Chem.
Int. Ed. 2014, 53, 6692; Angew. Chem. 2014, 126, 6810; d) X. Li,
X. Li, N. Jiao, J. Am. Chem. Soc. 2015, 137, 9246.
In conclusion, we have developed a lactamization of sp2
À
C H bonds to synthesize important 2-quinolinones and
polyheterocycles containing a free (NH)-lactam motif in
moderate to excellent yields with CO2 as the ideal carbonyl
source. Importantly, this transition-metal-free and redox-
neutral process is efficient and eco-friendly, making it an
attractive method for the pharmaceutical industry. Finally,
these reactions feature a broad substrate scope, good func-
tional group tolerance, facile scalability, and easy derivatiza-
tion of the products to drugs and bioactive compounds.
Acknowledgements
We thank the “1000-Youth Talents Plan”, a Start-up Grant
from Sichuan University, and the National Natural Science
Foundation of China (21502124) for financial support. We
thank Prof. Jason J. Chruma (Sichuan University) for helpful
manuscript revisions. We also thank the comprehensive
training platform of the Specialized Laboratory in the College
of Chemistry at Sichuan University for compound testing.
À
Keywords: 2-quinolinones · carbon dioxide · C H activation ·
lactamization · transition-metal-free reactions
[1] a) Carbon Dioxide as Chemical Feedstock (Ed.: M. Aresta),
Wiley-VCH, Weinheim, 2010; b) Green Carbon Dioxide:
Advances in CO2 Utilization (Eds.: G. Centi, S. Perathoner),
Wiley-VCH, Weinheim, 2014.
[2] a) P. Braunstein, D. Matt, D. Nobel, Chem. Rev. 1988, 88, 747;
b) T. Sakakura, J.-C. Choi, H. Yasuda, Chem. Rev. 2007, 107,
2365; c) D. Dong, P. Yang, W. Hu, Prog. Chem. 2009, 21, 1217;
d) S. N. Riduan, Y. Zhang, Dalton Trans. 2010, 39, 3347; e) K.
Huang, C.-L. Sun, Z.-J. Shi, Chem. Soc. Rev. 2011, 40, 2435; f) R.
Martꢀn, A. W. Kleij, ChemSusChem 2011, 4, 1259; g) M. Cokoja,
C. Bruckmeier, B. Rieger, W. A. Herrmann, F. E. Kꢁhn, Angew.
Chem. Int. Ed. 2011, 50, 8510; Angew. Chem. 2011, 123, 8662;
h) J. L. Wang, C. X. Miao, X. Y. Dou, J. Gao, L. N. He, Curr. Org.
Chem. 2011, 15, 621; i) Y. Tsuji, T. Fujihara, Chem. Commun.
2012, 48, 9956; j) L. Zhang, Z. Hou, Pure Appl. Chem. 2012, 84,
1705; k) L. Zhang, Z. Hou, Chem. Sci. 2013, 4, 3395; l) M.
Aresta, A. Dibenedetto, A. Angelini, Chem. Rev. 2014, 114,
1709; m) C. Maeda, Y. Miyazaki, T. Ema, Catal. Sci. Technol.
2014, 4, 1482; n) C. S. Yeung, V. M. Dong, Top. Catal. 2014, 57,
1342; o) Q. Liu, L. Wu, R. Jackstell, M. Beller, Nat. Commun.
2015, 6, 5933.
[8] a) J. Ferguson, F. Zeng, N. Alwis, H. Alper, Org. Lett. 2013, 15,
1998; b) D. Liang, Z. Hu, J. Peng, J. Huang, Q. Zhu, Chem.
Commun. 2013, 49, 173; c) V. Rajeshkumar, T. Lee, S. Chuang,
Org. Lett. 2013, 15, 1468; d) Z. Liang, J. Zhang, Z. Liu, K. Wang,
Y. Zhang, Tetrahedron 2013, 69, 6519.
[9] C.-L. Sun, Z.-J. Shi, Chem. Rev. 2014, 114, 9219.
[10] a) D. B. Dell’Amico, F. Calderazzo, L. Labella, F. Marchetti, G.
Pampalon, Chem. Rev. 2003, 103, 3857; b) W. McGhee, D. Riley,
K. Christ, Y. Pan, B. Parnas, J. Org. Chem. 1995, 60, 2820; c) M.
Yoshida, N. Hara, S. Okuyama, Chem. Commun. 2000, 151;
d) R. N. Salvatore, S. I. Shin, A. S. Nagle, K. W. Jung, J. Org.
Chem. 2001, 66, 1035; e) S. L. Peterson, S. M. Stucka, C. J.
Dinsmore, Org. Lett. 2010, 12, 1340.
[11] C. Alonso, E. M. de Marigorta, G. Rubiales, F. Palacios, Chem.
Rev. 2015, 115, 1847.
[12] a) Metal-Catalyzed Cross-Coupling Reactions and More (Eds.:
A. de Meijere, S. Brꢃse, M. Oestreich), Wiley-VCH, Weinheim,
2014; b) J. Cornella, C. Zarate, R. Martꢀn, Chem. Soc. Rev. 2014,
43, 8081.
[3] For reviews, see: a) Y.-N. Li, R. Ma, L.-N. He, Z.-F. Diao, Catal.
Sci. Technol. 2014, 4, 1498; b) A. Taheri, L. A. Berben, Chem.
Commun. 2016, 52, 1768. For selected examples, see: c) Y. Li, T.
Yan, K. Junge, M. Beller, Angew. Chem. Int. Ed. 2014, 53, 10476;
Angew. Chem. 2014, 126, 10644; d) X. Wang, Y. Liu, R. Martin, J.
4
www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Communications
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[13] a) A. Arienti, F. Bigi, R. Maggi, E. Marzi, P. Moggi, M. Rastelli,
G. Sartori, F. Tarantola, Tetrahedron 1997, 53, 3795; b) N.
Mameda, S. Peraka, S. Kodumuri, D. Chevella, M. R. Marri, N.
Nama, RSC Adv. 2015, 5, 78374.
[16] a) V. L. K. Valli, H. Alper, J. Org. Chem. 1995, 60, 257; b) L. Luo,
M. D. Bartberger, W. R. Dolbier, Jr., J. Am. Chem. Soc. 1997,
119, 12366.
[14] K. K. Park, J. J. Lee, Tetrahedron 2004, 60, 2993.
[15] T. N. Glasnov, W. Stadlbauer, C. O. Kappe, J. Org. Chem. 2005,
70, 3864.
Received: February 29, 2016
Revised: March 25, 2016
Published online: && &&, &&&&
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Communications
Sustainable Chemistry
Z. Zhang, L.-L. Liao, S.-S. Yan, L. Wang,
Y.-Q. He, J.-H. Ye, J. Li, Y.-G. Zhi,
D.-G. Yu*
&&&& — &&&&
=
CO2 CO+O: Carbon dioxide was used
directly as the carbonyl source for the
lactamization of alkenyl and heteroaryl
À
terocycles. These transition-metal-free
and redox-neutral reactions featured
a broad substrate scope, good functional
group tolerance, scalability, and facile
product derivatization.
2
À
Lactamization of sp C H Bonds with
CO2: Transition-Metal-Free and Redox-
Neutral
C H bonds, allowing for the synthesis of
important 2-quinolinones and polyhe-
6
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