Y. Suto et al. / Tetrahedron Letters 49 (2008) 5732–5735
5735
R3
References and notes
R3
HO
H
HO
N
O
R1
1. (a) Humphrey, J. M.; Chamberlin, A. R. Chem. Rev. 1997, 97, 2243; (b) Dale, D. J.;
Dunn, P. J.; Golightly, C.; Hughes, M. L.; Levett, P. C.; Pearce, A. K.; Searle, P. M.;
Ward, G.; Wood, A. S. Org. Process Res. Dev. 2000, 4, 17; (c) Mylavarapu, R. K.;
Kondaiah, G. C. M.; Kolla, N.; Veeramalla, R.; Koilkonda, P.; Bhattacharya, A.;
Bandichhor, R. Org. Process Res. Dev. 2007, 11, 1065.
HO
O
Aldehyde
R1
[Pd]
H
+
Amine
+
[Pd]
N
R2
H
2. Torisawa, Y.; Furuta, T.; Nishi, T.; Aki, S.; Minamikawa, J. Bioorg. Med. Chem. Lett.
2007, 17, 6455.
3. A review for oxidative amidation and oxidative esterification Ekoue-Kovi, K.;
Wolf, C. Chem. Eur. J. 2008, as an early view.
R2
R3 = H or Ac
H2O2-AcOH
4. (a) Yoo, W. J.; Li, C.-J. J. Am. Chem. Soc. 2006, 128, 13064; (b) Tillack, A.; Rudloff,
I.; Beller, M. Chem. Eur. J. 2001, 523; (c) Naota, T.; Murahashi, S. Synlett 1991,
693; (d) Tamaru, Y.; Yamada, Y.; Yoshida, Z. Synthesis 1983, 474.
5. (a) Ishihara, K.; Yano, T. Org. Lett. 2004, 6, 1983; (b) Seo, S.; Marks, T. J. Org Lett.
2008, 10, 317.
6. (a) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007, 317, 790; (b)
Owston, N. A.; Parler, A. J.; Williams, J. M. J. Org. Lett. 2007, 9, 73.
7. (a) Ekoue-Kovi, K.; Wolf, C. Org. Lett. 2007, 9, 3429; (b) Gao, J.; Wang, G.-W. J.
Org. Chem. 2008, 73, 2955.
8. For recent reviews on catalytic oxidation using H2O2 as a terminal oxidant, see:
(a) Lane, B. S.; Burgess, K. Chem. Rev. 2003, 103, 2457; (b) ten Brink, G.-J.;
Arends, I. W. C. E.; Sheldon, R. A. Chem. Rev. 2004, 104, 4105.
9. (a) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001,
34, 895; (b) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043; (c) Fujita,
K.; Yamashita, M.; Puschmann, F.; Alvarez-Falcon, M. M.; Incarvito, C. D.;
Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 9044; (d) Shen, Q.; Hartwig, J. F. J. Am.
Chem. Soc. 2007, 129, 7734.
R3
O
OH
NHR2
O
N
O
R1
H
R1
R1
NHR2
[Pd]
R2
H
Scheme 3. Mechanistic speculation.
olefins.14 Thus, Pd-catalyst can transfer OOH moiety to the coordi-
nated imine intermediate to form the key peroxide intermediate as
shown.
Even though we are not quite sure how the peroxide intermedi-
ate can be transformed into the final amide product, a Baeyer–
Villiger type degradation shown in Scheme 3 might be most
plausible. Further mechanistic studies to gain deeper insight into
the key intermediate are in progress and the result will be reported
in due course.15
10. General procedure: A solution of PdCl2 (4.4 mg, 0.025 mmol) and xantphos
(14.9 mg, 0.025 mmol) in MeOH (500
lL) was stirred at 50 °C for 1 h. To the
resulting mixture, AcOH (150 L, ca. 2 equiv to amine), butylamine (120
l
lL,
1.2 mmol), 4-chlroro benzaldehyde (141 mg, 1.0 mmol) and H2O2–urea
(136 mg, 1.4 mmol) were added successively. The mixture was stirred at
50 °C for 20 h. After addition of ca. 20 mL of AcOEt, the organic layer was
washed with saturated NaHCO3 aq two times and NaCl aq and dried over
Na2SO4. Volatiles were removed by evaporation and purification with silica-gel
column chromatography afforded N-butyl-4-chlorobenzamide in 82% yield
(176 mg).
11. Compound 5 was prepared by the reported procedure: Lin, Y.-M.; Miller, M. J. J.
Org. Chem. 1997, 64, 7451. Compound 5: 1H NMR (500 MHz, CDCl3) d 7.45–7.41
(m, 2H), 7.41–7.36 (m, 3H), 4.49 (s, 1H), 2.97 (dt, J = 12.0, 7.5 Hz, 1H), 2.78 (dt,
J = 12.0, 6.5 Hz, 1H), 1.75–1.68 (m, 2H), 1.51–1.42 (m, 2H), 0.96 (t, J = 7.5 Hz,
3H); 13C NMR (126 Hz, CDCl3) d 135.0, 130.1, 128.6, 127.7, 80.7, 62.1, 30.1, 20.7,
14.1; IR (neat) 2959, 2936, 2872, 1460, 1406, 758, 696 cmꢁ1; ESIMS m/z 178
(M+H+).
12. An, G.; Kim, M.; Kim, J. Y.; Rhee, H. Tetrahedron Lett. 2003, 44, 2183.
13. Spectral data of compound 6 are consistent with the reported one: Duhamel,
L.; Tombret, F. J. Organomet. Chem. 1985, 280, 1.
In summary, we have developed a new catalytic oxidative ami-
dation of aldehydes with amines, in which PdCl2/H2O2–urea was a
preferable reagent combination with xantphos as a key supporting
ligand under mild acidic conditions (MeOH/AcOH). Further optimi-
zation of the reagents should be necessary, particularly based on
the careful mechanistic insights into the intermediate involved.
Progress along these lines is under active investigation in our
laboratory for the development of new Pd-mediated synthetic
avenues as well as metal-free conversion.16
14. (a) Roussel, M.; Mimoun, H. J. Org. Chem. 1980, 45, 5387; (b) Mimoun, H.;
Charpentier, R.; Mitschler, A.; Fischer, J.; Weiss, R. J. Am. Chem. Soc. 1980, 102,
1047; (c) Mimoun, H. Angew. Chem., Int. Ed. 1982, 21, 734.
15. In place of PdCl2, similar reactions with CuCl2, NiCl2 and FeCl3 as an alternative
metal salt were examined in the optimized conditions, however, resulting in
very low yields of the amide product, presumably because of facile
decomposition of H2O2. These results indicated PdCl2–xantphos catalyst did
not participate in a decomposition reaction of H2O2. Instead, PdCl2–xantphos
system was interacting with peroxide intermediate and facilitating the
formation of the key peroxide intermediate as shown in Scheme 3.
16. Very recently, Reddy has disclosed a new oxidative amidation reaction with
KI-TBHP as a key oxidant Reddy, K. R.; Maheswari, C. U.; Venkateshwar, M.;
Kantam, M. L. Eur. J. Org. Chem. 2008.
Acknowledgments
We are grateful to Drs. F. Sato and D. Tanaka at Dainippon Sumi-
tomo Pharmaceutical Co., Ltd. for critical literature survey. Thanks
are due to Prof. V. K. Yadav of IIT at Kanpur, for his kind suggestion
in manuscript preparation. We also thank to Dr. M. Yamashita in
our University for his helpful discussions.