Visible-light induced copper(i)-catalyzed oxidative cyclization of: O -aminobenzamides with methanol and ethanol via HAT

Article abstract of DOI:10.1039/d0ob02234a

The use of the in situ generated ligand-copper superoxo complex absorbing light energy to activate the alpha C(sp3)-H of MeOH and EtOH via the hydrogen atom transfer (HAT) process for the synthesis of quinazolinones by oxidative cyclization of alcohols with o-aminobenzamide has been investigated. The synthetic utility of this protocol offers an efficient synthesis of a quinazolinone intermediate for erlotinb (anti-cancer agent) and 30 examples were reported.

Full text of DOI:10.1039/d0ob02234a

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: A. Ramasamy, B.
R. Mandapati and K. Prasanth, Org. Biomol. Chem., 2020, DOI: 10.1039/D0OB02234A.
Volume 15
Number 47
21 December 2017
Pages 9945-10124
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
Accepted Manuscripts are published online shortly after acceptance,
rsc.li/obc
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
ISSN 1477-0520
PAPER
I . J. Dmochowski et al.
Oligonucleotide modifi cations enhance probe stability for
shall the Royal Society of Chemistry be held responsible for any errors
single cell transcriptome in vivo analysis (TIVA)
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
rsc.li/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 6
View Article Online
DOI: 10.1039/D0OB02234A
COMMUNICATION
Visible-Light Induced Copper(I)-Catalyzed Oxidative Cyclization of
o-Aminobenzamides with Methanol and Ethanol via HAT
Mandapati Bhargava Reddy,a Kesavan Prasanth,a Ramasamy Anandhan*,a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The in-situ generated Ligand-Copper superoxo complex absorbing under microwave at higher temperature and Cu(II) catalyst22
light energy that activate the alpha C(sp3)–H of MeOH and EtOH with TBHP as oxidants at higher temperature. In 2020, S.
via hydrogen atom transfer (HAT) process for the synthesis of Kerdphon et al23 investigated methanol as a C1 Source for the
quinazolinones from oxidative cyclization of alcohol with o- oxidative condensation by Cu(II) catalyst with molecular
aminobenzamide has been investigated. The synthetic utility of oxygen as oxidants at higher temperature. However, these
this protocol offers an efficient synthesis of quinazolinone methods require costly metal complexes, stoichiometric
intermediate for Erlotinb (Anti-cancer agent) and 30 examples amount of oxidants and harsh reaction conditions. To
were reported.
Quinazolinones are one of the important scaffolds and ambient conditions are on high demand.
overcome that, the activation of C(sp3)-H of MeOH under
frequently occur in various natural products and biologically
The use of visible light-promoted photoredox catalysis has
active molecules including anti-inflammatory, anitimicrobial, been attracted significantly towards the development of alpha
antitubercular, antiviral activities, and anticancer etc.1-4 Due to C(sp3)-H of alcohols via the HAT process.24-26 Macmillan et al.27
their broad range of bioactive molecules, various synthetic and Hwang et al.28 have reported the activation of C(sp3)-H
strategies have been employed.5-9 Among the various synthetic methanol to α-oxy radical by visible light induced photoredox
efforts, the direct oxidative condensation of alcohols with o- catalyst. Recently, our group established a visible-light-driven
aminobenzamides to quinazolinones by the molecular oxygen Cu(I)-catalysed aerobic oxidative C(sp)-S coupling reaction and
has received significant attention because O2 is inexpensive the resulting alkynyl sulfides were converted to 2-
and green oxidant, and produces water as the only by- phenylbenzothiazole via “thia-Wolff rearrangement”.29 To
product.10-12 So far, Many transition metals including continue our research interest in visible light mediated Cu-
vanadium13, Iron14, Copper complexes15 and organic dye as catalyst, we wish to report herein the visible-light induced
photosensitizer16 has been employed for oxidative Ligand-copper superoxo catalyzed oxidative cyclization of
condensation of alcohols to quinazolinones, although the MeOH with o-aminobenzamides via HAT process for the
scope of aliphatic alcohol was respectively limited. Therefore, synthesis of quinazolinones.
the development of green, atom-economic functionalization of
aliphatic alcohol for oxidative condensation is highly desirable.
With growing environmental awareness in aliphatic
alcohols, MeOH is a renewable feedstock from value-added
chemicals, cost-effective reagent and environmental
friendliness, and is frequently used in pharmaceuticals, and
materials.17,18 So far, the synthetic utilization of MeOH have
used as
a C1 source in methylation, methoxylation, Scheme 1. Visible light induced synthesis of quinazolinones
formylation, methoxycarbonylation, and oxidative methyl using ethanol and methanol via HAT
ester formation reactions.19,20 Recent years, the oxidative
condensation of MeOH has attracted significant interest in
The initial studies were carried out using the reaction of
organic synthesis. The use of methanol as a C1 Source for the anthranilamide 1a (0.36 mmol) and MeOH (0.18 M) in the
oxidative condensation have been reported by Ir-complexes21 presence of CuCl (5 mol %), K2CO3 (0.36 mmol) with molecular
oxygen under blue LED afforded quinazolinone 2a in 65%
isolated yield for enabling the optimization of the reaction
condition. Among the other bases, Cs2CO3 offered upto 70%
yield (Table 1, entry 2). However, the reaction was failed to
provide 2a with NaH and Et3N. The different mole amount of
Cs2CO3 improved the formation of 2a upto 80% (Table 1, entry
a. Department of Organic Chemistry University of Madras, Chennai -025, Tamilnadu,
India. Email: ananthanramasamy@gmail.com.
b. †Electronic Supplementary Information (ESI) available: [Experimental procedures,
spectral data for all new compounds. See DOI: 10.1039/x0xx00000x
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 6
COMMUNICATION
Journal Name
5). When CuCl was replaced by other CuX (X=Br, I) catalysts, Table 2: Substrate scope of o-aminobenzamides with
View Article Online
DOI: 10.1039/D0OB02234A
CuI significantly improved the yield to 88% (Table 1, entry 8). methanola
Increasing the amount of CuI (10 mol%) had no obvious effect
on the yield of 2a. However, Cu(OTf)2 resulted in lower yields
(Table 1, entry 10). In control experiments, there was no
reaction occurred in the absence of catalyst, light and Base,
indicates their crucial roles in the current protocol (Table 1,
entries 12 and 14).
Table 1: Optimization table for quinazolinone 2a from o-Amino
benzamide1a and methanola
Entry
Catalyst
Base (equiv.)
Time (h)
Yield (%)b
1
2
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuBr
CuI
K2CO3 (1)
Cs2CO3 (1)
NaH (1)
24
24
24
24
24
24
24
16
16
24
16
16
16
16
65
70
3
n.r.
n.r.
80
4
Et3N (1)
5
Cs2CO3 (2)
Cs2CO3 (2.5)
Cs2CO3 (2)
CS2CO3 (2)
CS2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
-
6
80
7
82
8
88
9c
10
11d
12
13
14e
CuI
88
Cu(OTf)2
CuI
20
aStandard condition. Yields were determined after purification of
the compound.
55
CuI
n.r.
n.r.
n.r.
Next, we investigate the scope of the o-aminobenzamide
with ethanol and results are shown in Table 3. All the
substituted o-aminobenzamides derivatives were effecitively
coupled with ethanol under this protocol.
-
Cs2CO3 (2)
Cs2CO3 (2)
CuI
aReaction conditions: 0.36 mmol (1a), MeOH (2 mL), and 5
mol% of CuI. The solution was irradiated with blue light in
presence of O2 atmosphere. bYields were determined after
purification of the compound. C10 mol % of CuI used. dReaction
Table 3: Substrate scope of o-amino benzamides with ethanola
e
performed in open air. Reaction performed in dark. n.r. = no
reaction.
Encouraged by these promising results, a diverse array of
anthranilamide derivatives were explored by using methanol
under optimized conditions shown in Table 2. Methyl
substituted anthranilamide 1b and 1c afforded corresponding
quinazolinone 2b and 2c with 85% and 80% yield respectively.
Halogen (F, Cl and Br) substituted anthranilamide 1d-1f reacts
smoothly with methanol resulted in the best yield of 80-88%.
The nitro substituted anthranilamide 1g also afforded
corresponding quinazolinone 2g with 77% yield. Phenyl and
napthyl bearing anthranilamide 1h-j also effectively coupled
with methanol afforded the corresponding product 2h-j in
good yields. Next, the phenylethynyl, 2-etynyl pyridine and 1-
octyne substituted anthranilamide 1k-n also well suited for
this new catalytic protocol leads to the corresponding products
2k-n in 65-75% yields.
aStandard condition. Yields were determined after purification of
the compound.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 6
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
COMMUNICATION
To show the practical utility of this new protocol, we
View Article Online
All the derivatives resulted to the corresponding synthesized the quinazolinones intermDeOdiIa: 1t0e.1063a9/Do0fOEBr0l2o2t3in4bA
quinazolinones 3a-i in 55-65% yield, respectively. In contrast, (Anti-cancer agent) and depicted in scheme 2. The reaction of
2-amino-6-methylbenzamide 1d afforded the trace amount of 2-amino-4,5-bis(3-methoxypropyl)benzamide
1n
with
3d. Notably, ethanol shows less reactivity and takes longer methanol under optimized reaction conditions afforded the
times up to 36 h towards this new catalytic protocol and also quinazolinones intermediate 6a in 82% yield. According to the
produces slightly lower yields than methanol.
literature, further chlorination reaction followed by amination
Further, we screened the reactivity of o-amino-N- with 3-ethynylaniline could afforded the Erlotinib.
substituted benzamides with methanol and ethanol for the
protocol and results are shown in Table 4. All the Scheme 3: Synthetic transformations of quinazoline 2a.
2-amino-N-substiturtedbenzamide derivatives were reacted
smoothly with methanol and ethanol afforded corresponding
products 5a-f in 75-91% yield. Interestingly, o-amino-N-
substituted benzamides shows higher reactivity towards the
coupling with methanol and ethanol, than o-aminobenzamide.
Table 4: Substrate scope of o-amino-N-substituted benzamides
with methanol and ethanola
Reagents and condition: (a) BnBr, 7 (1.1 equiv.), K2CO3 (2.1
equiv.), THF, 12 h, rt; (b) allyl bromide, 8 (1.1 equiv.), K2CO3
(2.1 equiv.), THF, 12 h, rt; (c) propargyl bromide, 9 (1.1 equiv.),
K2CO3 (2.1 equiv.), THF, 12 h, rt.
Due
to
biological
importance
of
N-alkylated
quinazolinones, the synthetic utility of N-alkylation reactions
on quinazolinone 2a were shown in scheme 3. Quinazolinone
2a was treated with various alkyl bromides 7-9 in presence of
K2CO3, afforded corresponding N-alkylated compounds 10-12
with 80-85% yields.
Several control experiments were carried out to investigate
the reaction mechanism as shown in Scheme 4. The other
higher alkyl alcohols (e.g. propayl alcohol, butyl alcohol and
benzyl alcohols) instead of methanol/ethanol were used to
react with o-aminobenzamide 1a (Scheme 4a), but no reaction
was observed. However, the reaction of acetaldehyde 1a’ with
o-aminobenzamide 1a afforded 2a in 60% yield (Scheme 4b).
The results indicate that higher order alcohols were failed to
give desired product and aldehyde may be one of the reaction
intermediate. 2,3-dihydroquinazolin-4(1H)-one 2a’ was treated
under the standard reaction conditions afforded the desired
product 2a in 91% yield within 10 hours (Scheme 4c), it reveals
that 2,3-dihydroquinazolin-4(1H)-one 2a’ is one of the
intermediate in oxidative cyclization. Furthermore, the
reaction with 2a’ was carried out in the absence of base and
CuI resulted in trace and 0% yield of 2a, respectively (Scheme
4d and 4e). These experiments clearly showed the needs of
base and catalyst in the dehydrogenation of quinazolinone 2a.
In trapping and quenching experiments, the reaction was
performed with addition of TEMPO afforded 92% yield of 2a
aStandard condition. Yields were determined after purification
of the compound.
Scheme 2: Synthesis of Erlotinib (Anti-cancer agent)
intermediate
(Scheme 4f). Based on ttheoretical study of H-atom abstraction
30
by TEMPO in alcohol oxidation,
It clearly reveals that the
presence of TEMPO radical does not affect the yield of
benzaldehyde in the catalytic oxidation, suggesting the
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 6
COMMUNICATION
involvement of an intramolecular H-atom abstraction. Further
Journal Name
The reaction of 1a with methanol-d4 under the optimized
View Article Online
quenching experiments for superoxo radical and singlet conditions, afforded corresponding deDutOeI:ra10t.e1d039p/Dro0dOuBc0t22234aAd
oxygen,31 the reaction were performed with addition of with 46% yield (Scheme 5b). This experiment has confirmed
benzoquinone (BQ) and 1,4-diazabicyclo[2.2.2]octane (DABCO) that C-2 carbon source of 2a was methanol. A KIE value of 1.91
afforded 2a in 0% and 81% yield, respectively (Scheme 4g and was determined from two parallel reactions (Scheme 5a and
4h), implies that the involvement of superoxo radical in 5b), and KIE value of 1.86 was also determined from
reaction.
competition reaction of 1a with 1:1 ratio of methanol and
methanol-d4 (Scheme 5c). The moderate KIE value implies that
the activation of methanol is one of the kinetically important
steps in the oxidative cyclization of o-aminobenzamides.32
Scheme 4: Control experiments
Figure 1. UV-visible absorption spectra of CuI in MeOH (red);
CuI and substrate 1a (black); CuI, substrate 1a and base
(green) and after irradiation MeOH solvent (purple).
Based on the experimental studies, UV-vis absorption spectra
and literature report,33 a possible reaction mechanism is proposed
in Scheme 6. In this scenario, the Cu(I)I coordinated with 1a and
molecular oxygen to form Ligand-Cu(II) superoxo complexes A.
These Ligand-Cu(II) superoxo complexes A has absorbed Visible light
(λmax = 473 nm) and produces excited state of Cu(II) superoxo
complexes B as shown in figure 1.34 The excited state of B
undergoes coordination with alcohol to form a complex C. The
resulted complex C is implicated to initiate the oxidation reaction
via hydrogen atom transferred from alpha C(sp3)-H of alcohol to
furnish Cu(II)hydroperoxo complex D and aldehyde 1a’’. The
theoretical study of H-atom abstraction by TEMPO in alcohol
oxidation suggest a pathway where the overlap of HOMO of
alkoxide to π* LUMO of TEMPO.30 Similarly, a copper(II)-superoxide
orbital is proposed to interact with an accessible HOMO of alkoxide
in the abstraction of α-H atom. Further, EPR measurements showed
signals for the formation of Cu(II)hydroperoxo complex (L-
Cu(II)OOH) D (Fig. S1, ESI†).35 Next, complex D can undergo
reductive elimination to form a recycle Cu(I) system and 1a. The
resulted 1a’’ undergoes condensation reaction with o-
aminobenzamide 1a to produce quinazolinone 2a’’, followed by
reaction of CuI and Cs2CO3 under molecular oxygen afforded the
desired quinazolinone 2a.
Scheme 5: Kinetic Isotope Effect (KIE)
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 6
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
COMMUNICATION
15 C. Huang, Y. Fu, H. Fu, Y. Jiang and Y. Zhao, Chem. Commun.,
View Article Online
2008, 47, 6333.
16 Q. Xia, Z. Shi, J. Yuan, Q. Bian, Y. Xu, BD. OLiIu: 1,0Y.1.0H3u9/aDn0gO,BX0.2Y2a3n4Ag
and H. Xu, Asian J. Org. Chem., 2019, 8, 1933.
17 M. Nielsen, E. Alberico, W. Baumann, H. J. Drexler, H. Junge,
S. Gladiali and M. Beller, Nature, 2013, 495, 85.
Scheme 6: Plausible Mechanism.
Conclusions
18 The Methanol Institute: http://www.methanol.org.
19 K. Natte, H. Neumann, M. Beller and R. V. Jagadeesh, Angew.
Chem. Int. Ed., 2017, 56, 6384.
In conclusion, we have investigated the visible light-
mediated Cu(I) catalysed oxidative cyclization of aliphatic
alcohols with cyclization partner of o-aminobenzamides to
synthesize quinazolinones in the presence of molecular
oxygen. This method is only limited to MeOH and EtOH. The in-
situ formation of Ligand-Copper superoxo complex with visible
light (λmax=473 nm) has activated the aliphatic alpha C(sp3)–H
alcohol to aldehyde via hydrogen atom transfer (HAT). The
synthetic utility of this method offers an efficient synthesis of
quinazolinone intermediate for Erlotinb (Anti-cancer agent).
20 B. Paul, M. Maji, and S. Kundu, ACS Catal., 2019, 9, 10469.
21 F. Li, L. Lu and P. Liu, Org. Lett., 2016, 18, 2580.
22 J. Sun, T. Tao, D. Xu, H. Cao, Q. Kong, X. Wang, Y. Liu, J. Zhao,
Y. Wang and Y. Pan, Tetrahedron Lett., 2018, 59, 2099.
23 S. Kerdphon,
Choommongkol,
P, Sanghong, J. Chatwichien,
V.
P. Rithchumpon, T. Singh and P.
Meepowpan, Eur. J. Org. Chem., 2020, 18, 2730.
24 J. L. Jeffrey, J. A. Terrett and D. W. C. MacMillan, Science,
2015, 349, 1532.
25 M. Milan, M. Salamone, M. Costas and M. Bietti, Acc. Chem.
Res., 2018, 51, 1984.
26 J. Twilton, M. Christensen, D. A. DiRocco, R. T. Ruck, I. W.
Davies and D. W. C. MacMillan, Angew. Chem. Int. Ed., 2018,
57, 5369.
Acknowledgments
27 J. Jin and D. W. C. MacMillan, Nature, 2015, 525, 87.
28 A. Sagadevan, V. K. K. Pampana and K. C. Hwang, Angew.
Chem. Int. Ed., 2019, 58, 3838.
The authors thank DST-SERB for a research grant (vide Grant No:
EMEQ/2018/001129) and DST-FIST for providing NMR and HRMS
facilities to the Department of Organic Chemistry. The authors
thank also to SAIF, IIT Madras for EPR analysis. MBR acknowledges
DST-SERB, New Delhi, for fellowship.
29 M. B. Reddy and R. Anandhan, Chem. commun., 2020, 56,
3761.
30 (a) O. Das and T. K. Paine, Dalton Trans., 2012, 41, 11476. (b)
C. Michel, P. Belanzoni, P. Gamez, J. Reedijk and E. J.
Baerends, Inorg. Chem., 2009, 48, 11909. (c) B. Kim, D.
Jeong, T. Ohta and J. Cho, Commun. Chem., 2019, 2, 81.
31 Y. Zhang, D. Riemer, W. Schilling, J. Kollmann and S. Das, ACS
Catal., 2018, 8, 6659.
Conflicts of interest
32 B. C. Roy, S. A. Samim, D. Panja and S. Kundu, Catal. Sci.
Technol., 2019, 9, 6002.
There are no conflicts to declare.
33 (a) S. D. Mccann and S. S. Stahl, Acc. Chem. Res., 2015, 48,
1756. (b) M. Rolff and F. Tuczek, Angew. Chem. Int. Ed.,
2008, 47, 2344. (c) K. K. Toh, Y. F. Wang, E. P. J. Ng and S.
Chiba, J. Am. Chem. Soc., 2011, 133, 13942. (d) A. Ragupathi,
A. Sagadevan, C-C. Lin, J-R Hwu and K.C. Hwang, Chem.
Commun., 2016, 52, 11756. (e) D. Das, P. V. Kishore Kumar
and K. C. Hwang, Chem. Sci., 2018, 9, 7318. (e) A. Modak, U.
Dutta, R. Kancherla, S. Maity, M. Bhadra, S. M. Mobin and D.
Maity, Org. Lett., 2014, 16, 2602.
Notes and references
1
I. Khan, A. Ibrar, N. Abbas and A. Saeed, Eur. J. Med. Chem.,
2014, 76, 193.
J. P. Michael, Nat. Prod. Rep., 2008, 25, 166.
L. Chen, X. Wang, X. Tang, R. Xia, T. Guo, C. Zhang, X. Li and
W. Xue, BMC Chem., 2019, 13, 1.
2
3
34 V. P. Charpe, A. Sagadevan and K. C. Hwang, Green Chem.,
2020, 22, 4426.
4
5
6
7
8
9
X. Wang, H. Hu, X. Zhao, M. Chen, T. Zhang, C. Geng, Y. Mei,
A. Lu and C. Yang, J. Saudi Chem. Soc., 2019, 23, 1144.
R. J. Abdel-Jalil, W. Voelter and M. Saeed, Tetrahedron Lett.,
2004, 45, 3475.
35 (a) T. Tano, Y. Okubo, A. Kunishita, M. Kubo, H.Sugimoto, N.
Fujieda, T. Ogura and S. Itoh, Inorg. Chem., 2013, 52, 10431.
(b) S. Biswas, A. Dutta, M. Debnath, M. Dolai, K. K. Das and
M. Ali, Dalton Trans., 2013, 42, 13210. (c) K. Sobanska, A.
Krasowska, T. Mazur, K. Podolska-Serafin, P. Pietrzyk and Z.
Sojka, Top Catal., 2015, 58, 796.
F. C. Jia, Z. W. Zhou, C. Xu, Y. D. Wu and A. X. Wu, Org. Lett.,
2016, 18, 2942.
A. V. Dubey and A. V. Kumar, ACS Sustain. Chem. Eng., 2018,
6, 14283.
P. T. Kirinde Arachchige and C. S. Yi, Org. Lett., 2019, 21,
3337.
M. Novanna, K. Sathananthan and P. Shanmugam,
Tetrahedron Lett., 2019, 60, 201.
10 W. Zhang, C. Meng, Y. Liu, Y. Tang and F. Li, Adv. Synth.
Catal., 2018, 360, 3751.
11 S. Parua, S. Das, R. Sikari, S. Sinha and N. D. Paul, J. Org.
Chem., 2017, 82, 7165.
12 Z. Zhang, M. Wang, C. Zhang, Z. Zhang, J. Lu and F. Wang,
Chem. Commun., 2015, 51, 9205.
13 Z. Bie, G. Li, L. Wang, Y. Lv, J. Niu and S. Ga, Tetrahedron
Lett., 2016, 57, 4935.
14 Y. Hu, L. Chen and B. Li, RSC Adv., 2016, 6, 65196.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Organic & Biomolecular Chemistry
Page 6 of 6
View Article Online
DOI: 10.1039/D0OB02234A
Table of Contents
O
O
O
R2
CuI
MeOH/EtOH
R2
O
N
N
H3CO
H3CO
NH
R1
R1
H
Cs2CO3, O2,
blue LED
16-36 h
N
H/CH3
NH2
O
N
Up to 91% yield
30 examples
Intermediate of Erlonitib
Anti-Cancer agent
Oxidant free
Green Approach
No chemical wastage
Good functional group tolerance
The activation the C(SP3)-H of MeOH via HAT for synthesis of quinazolinones has been
achieved by in-situ generated Ligand-copper-superoxo complex under visible-light.