4
Tetrahedron
5. Rayle, H. L.; Fellmeth, L. Org. Process Res. Dev. 1999, 3, 172-
176.
with the amine to give the amide while releasing PPh3 back into
the catalytic cycle.
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3040.
8. Lahoti, R. J.; Wagle, D. R. Indian J. Chem., Sect. B 1981, 20B,
1007-1008.
Cl
N
PPh3
N
N
Cl
Cl
9. Giacomelli, G.; Porcheddu, A.; Salaris, M. Org. Lett. 2003, 5,
2715-2717.
10. de Luca, L.; Giacomelli, G.; Taddei, M. J. Org. Chem. 2001, 66,
2534-2537.
11. Bandgar, B. P.; Pandit, S. S. Tetrahedron Lett. 2002, 43, 3413-
3414.
Cl
N
N
(cat.)
PPh3
Cl
Cl
N
PPh3
O
II
R2
12. Wet-osot, S.; Duangkamol, C.; Pattarawarapan, M.; Phakhodee,
W. Monatsh. Chem. 2015, 146, 959-963.
13. Rolfe, A.; Probst, D. A.; Volp, K. A.; Omar, I.; Flynn, D. L.;
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15. Kaminski, Z. J. Synthesis 1987, 917-920.
R1
N
R3
O
R1
OH,
Cs2CO3
NHR2R3
Cl
Cl
Cl
PPh3
16. Kunishima, M.; Ujigawa, T.; Nagaoka, Y.; Kawachi, C.; Hioki,
K.; Shiro, M. Chem. - Eur. J. 2012, 18, 15856-15867.
17. Kaminski, Z. J.; Paneth, P.; Rudzinski, J. J. Org. Chem. 1998, 63,
4248-4255.
N
N
N
N
Cl
N
O
Cl
N
O
R1
O
R1
O
Meisenheimer
IV
18. Kunishima, M.; Kitamura, M.; Tanaka, H.; Nakakura, I.; Moriya,
T.; Hioki, K. Chem. Pharm. Bull. 2013, 61, 882-886.
19. Kunishima, M.; Yoshimura, K.; Morigaki, H.; Kawamata, R.;
Terao, K.; Tani, S. J. Am. Chem. Soc. 2001, 123, 10760-10761.
20. Kunishima, M.; Nakanishi, S.; Nishida, J.; Tanaka, H.; Morisaki,
D.; Hioki, K.; Nomoto, H. Chem. Commun. 2009, 5597-5599.
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active ester III
complex
Scheme 2 Proposed mechanism for the TCT/PPh3 mediated
amidation.
In summary, using catalytic amounts of PPh3 or its polymer
bound analog, a series of amides could be readily accessed
through the TCT-mediated amidation of carboxylic acids in the
presence of an inorganic base. Unlike DMT-MM which is
incompatible with CH2Cl2, our reagent system works best in such
media which complements the existing methods. Although a
stepwise procedure was required to avoid competitive side
reactions between TCT and the amines, the reaction can be
conveniently performed in one-pot using inexpensive and readily
available TCT as an acid activator. The reaction conditions are
also mild, allowing optically active dipeptides to be synthesized
without racemization. Additionally, the use of polymer bound
PPh3 greatly simplifies product isolation, and allows its recovery
for reuse.
22. Kunishima, M.; Kawachi, C.; Iwasaki, F.; Terao, K.; Tani, S.
Tetrahedron Lett. 1999, 40, 5327-5330.
23. Kunishima, M.; Kawachi, C.; Morita, J.; Terao, K.; Iwasaki, F.;
Tani, S. Tetrahedron 1999, 55, 13159-13170.
24. Kunishima, M.; Kawachi, C.; Hioki, K.; Terao, K.; Tani, S.
Tetrahedron 2001, 57, 1551-1558.
25. Kolesinska, B.; Kaminski, Z. J. Tetrahedron 2009, 65, 3573-3576.
26. Jaita, S.; Kaewkum, P.; Duangkamol, C.; Phakhodee, W.;
Pattarawarapan, M. RSC Adv. 2014, 46947-46950.
27. Stenger, V. A. J. Chem. Eng. Data 1996, 41, 1111-1113.
Acknowledgements
This work is supported by the National Research University
Project under Thailand's Office of the Higher Education
Commission and the Center of Excellence for Innovation in
Chemistry (PERCH-CIC). Financial support from the Thailand
Research Fund through the Royal Golden Jubilee Ph.D. Program
(Grant No. PHD/0206/2556) to S.W. is also acknowledged.
Supplementary data
Supplementary data (experimental details and spectroscopic data
for the representative products) associated with this article can be
found in the online version, at doi.
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