D
Q. Yue et al.
Letter
Synlett
Acknowledgment
a)
N
N
We are grateful financial support from the National Natural Science
Foundation of China (NSFC) (grant number 81573286, 21472130).
CrO3, HCl, DMSO
O
O
O
O
100 °C, air, 3 h
O
78%
2a
1a
Supporting Information
b)
c)
N
N
Supporting information for this article is available online at
PCC, Et3N, DMSO
100 °C, air, 3 h
O
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
O
not observed
O
2a
1a
References and Notes
N
N
CrO3, HCl, DMSO
100 °C, air, 3 h
(1) Stefano, C.; Patrick, P.; Marc, M.; Véronique, C.; Cleva, C.;
Arrighi, J. F.; Atherall, J.; Macritchie, J.; Martin, T.; Humbert, Y.;
Gaudet, M.; Pupowicz, D.; Maio, M.; Pittet, P. A.; Golzio, L.;
Giachetti, C.; Rocha, C.; Bernardinelli, G.; Filinchuk, Y.; Scheer,
A.; Schwarz, M. K.; Chollet, A. J. Med. Chem. 2008, 51, 2227.
(2) Romagnoli, R.; Baraldi, P. G.; Sarkar, T.; Carrion, M. D.; Cruz-
Lopez, O.; Cara, C. L.; Tolomeo, M.; Grimaudo, S.; Cristina, A. D.;
Pipitone, M. R.; Balzarini, J.; Gambari, R.; Ilaria, L.; Saletti, R.;
Brancale, A.; Hamel, E. Bioorg. Med. Chem. 2008, 16, 8419.
(3) Moore, P. F.; Larson, D. L.; Otterness, I. G.; Weissman, A.; Kadin,
S. B.; Sweeney, F. J.; Eskara, J. D.; Nagahisa, A.; Sakakibara, M.;
Carty, T. J. Inflammation Res. 1996, 45, 54.
O
O
OH
O
2a
5a
95%
Scheme 3 Control experiments
thylindolin-2-one (5a) via HCl catalysis. Subsequently, in-
termediate 5a was further converted into N-methylindo-
line-2,3-dione (2a) with the assistance of PCC.
(4) Hoessel, R.; Leclerc, S.; Endicott, J. A.; Nobel, M. E.; Lawrie, A.;
Tunnah, P.; Leost, M.; Damiens, E.; Marie, D.; Marko, D.;
Niederberger, E.; Tang, W.; Eisenbrand, G.; Meijer, L. Nat. Cell
Biol. 1999, 1, 60.
(5) (a) Bridges, T. M.; Kennedy, J. P.; Noetzel, M. J.; Breininger, M. L.;
Gentry, P. R.; Conn, P. J.; Lindsley, C. W. Bioorg. Med. Chem. Lett.
2010, 20, 1972. (b) Bridges, T. M.; Kennedy, J. P.; Cho, H. P.
Bioorg. Med. Chem. Lett. 2010, 20, 558.
O
N
PCC, DMSO, 100 °C
air, 3 h
N
H
O
O
1a
2a
O
H+
(6) For selected examples, see (a) Liu, Y.; Wang, H.; Wan, J. Asian J.
Org. Chem. 2013, 2, 374. (b) Singh, G. S.; Desta, Z. Y. Chem. Rev.
2012, 112, 6104. (c) Borad, M. A.; Bhoi, M. N.; Prajapati, N. P.;
Patel, H. D. Synth. Commun. 2014, 44, 897. (d) Pakravan, P.;
Kashanian, S.; Khodaei, M. M.; Harding, F. J. Pharmacol. Rep.
2013, 65, 313. (e) da Silva, J. F. M.; Garden, S. J.; Pinto, A. C. J.
Braz. Chem. Soc. 2001, 12, 273.
(7) For selected examples, see (a) Krishnegowda, G.; Gowda, A. S.
P.; Tagaram, H. R. S.; Carroll, K. F. S. O.; Irby, R. B.; Sharma, A. K.;
Amin, S. Bioorg. Med. Chem. 2011, 19, 6006. (b) Shang, J. L.; Guo,
H.; Li, Z. S.; Ren, B.; Li, Z. M.; Dai, H. Q.; Zhang, L. X.; Wang, J. G.
Bioorg. Med. Chem. Lett. 2013, 23, 724. (c) Beauchard, A.;
Laborie, H.; Rouillard, H.; Lozach, O.; Ferandin, Y.; Le Guével, R.;
Guguen-Guillouzo, C.; Meijer, L.; Besson, T.; Thiéry, V. Bioorg.
Med. Chem. 2009, 17, 6257. (d) Limpachayaporn, P.; Wagner, S.;
Kopka, K.; Schober, O.; Schäfers, M.; Haufe, G. J. Med. Chem.
2014, 57, 9383.
PCC
H+
N
H
O
N
+
O
O
H
4a
5a
OH
Scheme 4 Plausible mechanism for this reaction
In summary, a novel and highly efficient protocol to
synthesize isatins has been established via PCC-catalyzed
intramolecular acylation of formyl-N-arylformamides.17,18
The starting materials are cheap and very easy to prepare.
In addition, compared to Li’s work (reacting in a Schlenk
tube, charging with O2, and long reaction time) the reaction
is very simple to run. This atom-economical intramolecular
transformation offers the corresponding products in high
yields and excellent functional-group tolerance. Further ap-
plications of this method to other substrates are in prog-
ress.
(8) Sandmeyer, T. Helv. Chim. Acta 1919, 2, 234.
(9) Stollé, R. Ber. Dtsch. Chem. Ges. 1913, 46, 3915.
(10) Martinet, J. C. R. Hebd. Seances Acad. Sci. 1918, 166, 851.
(11) Lollar, C. T.; Krenek, K. M.; Bruemmer, K. J.; Lippert, A. R. Org.
Biomol. Chem. 2014, 12, 406.
(12) Liu, Y.; Chen, H.; Hu, X.; Zhou, W.; Deng, G. J. Eur. J. Org. Chem.
2013, 4229.
(13) Satish, G.; Polu, A.; Ramar, T.; Ilangovan, A. J. Org. Chem. 2015,
80, 5167.
(14) Huang, P. C.; Parthasarathy, G.; Cheng, C. H. Chem. Commun.
2013, 49, 8540.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E