Organic Letters
Letter
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Scheme 7. Plausible Reaction Mechanism
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oxidant.12 Nucleophilic addition of the intermediate A to the
iminium ion intermediate B provided the intermediate C.
Reductive elimination produces intermediate D and Pd(0), and
the latter is oxidized by Ag in the presence of terminal oxidant O2,
thuscompleting thecatalytic cycle. Intermediate Dthenproduces
the product 2a via oxidation and hydrolysis. The formation of
phenanthridinones alsotookplace byfollowingasimilarpathway.
In summary, we have established a cooperative Pd/Ag-
catalyzed carbonylation of C(sp2)−H bonds by employing N,N-
dimethylformamide (DMF) as the carbon source of the carbonyl
group under atmospheric O2. The process is general in delivering
medicinally important pyrido-fused quinazolinones and phenan-
thridinones with challenging substitution patterns. Mechanistic
studiessuggestedthatthisreactionproceededviapalladium/silver
synergisticcatalysis,withthepalladiumspeciesinitiatingtheC−H
activation of substrates to generate a nucleophile and DMF,
providing an electrophile by utilizing the silver salt. With the easy
availability of the substrates, economic DMF as the carbonyl
source, excellent functional group tolerability, and easy to handle
CO-free reaction conditions, this procedure is expected to
complement current methods. Detailed mechanistic studies and
further substrate scope study are underway in our laboratory.
ASSOCIATED CONTENT
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Notes
(10) (a) Khan, I.; Ibrar, A.; Ahmed, W.; Saeed, A. Eur. J. Med. Chem.
2015, 90, 124. (b) Ikuta, A.; Urabe, H.; Nakamura, T. J. Nat. Prod. 1998,
61,1012.(c)Lee,S.H.;Son,J.K.;Jeong,B.S.;Jeong,T.C.;Chang,H.W.;
Lee, E. S.; Jahng, Y. Molecules 2008, 13, 272. (d) Holl, V.; Coelho, D.;
Weltin, D.; Dufour, P.; Bischoff, P. Anticancer Res. 2000, 20, 3233.
(e) Patil, S.; Kamath, S.; Sanchez, T.; Neamati, N.; Schinazi, R. F.;
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(11) Ding, S.-T.; Jiao, N. Angew. Chem., Int. Ed. 2012, 51, 9226.
(12) (a) Youn, S. W.; Ko, T. Y.; Jang, M. J.; Jang, S. S. Adv. Synth. Catal.
2015,357,227.(b)Zeng,Y.−Z.;Tan,D.−H.;Lv,W.−X.;Li,Q.;Wang,
H. Eur. J. Org. Chem. 2015, 2015, 4335. (c) Maji, A.; Hazra, A.; Maiti, D.
Org. Lett. 2014, 16, 4524.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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D.N.R. and Sk.R. thank UGC-New Delhi and CSIR for their
research fellowship. This research work financially supported by
CSIR-New Delhi (BSC0108). IIIM communication no: IIIM/
1908/2016.
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