ORGANIC
LETTERS
2006
Vol. 8, No. 5
987-990
Pd/C-Catalyzed Deoxygenation of Phenol
Derivatives Using Mg Metal and MeOH
in the Presence of NH4OAc
Hironao Sajiki,* Akinori Mori, Tomoteru Mizusaki, Takashi Ikawa,
Tomohiro Maegawa, and Kosaku Hirota
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical UniVersity,
Mitahora-higashi, Gifu 502-8585, Japan
Received January 8, 2006
ABSTRACT
A Pd/C-catalyzed deoxygenation method of phenolic hydroxyl groups via aryl triflates or mesylates using Mg metal in MeOH at room temperature
was developed. The addition of NH4OAc dramatically affects the reactivity and reaction rate. This method is particularly attractive to provide
an environmentally benign and widely applicable removal method of phenolic alcohols under quite mild reaction conditions.
Many phenolic moiety-containing organic compounds are
well-known as biologically and functionally important
compounds and phenolic hydroxyl groups frequently play
an important role in expressing those activities.1 Therefore,
the development of a simple, efficient, and chemoselective
method of deoxygenation of phenol derivatives is quite
important to prepare the corresponding nonphenolic deriva-
tives as reference compounds and/or biologically active
natural or new synthetic molecules such as angelicin,2
vancomycin,3 and so on. Since a phenolic hydroxyl group
is a quite poor leaving group, it should be activated prior to
the deoxygenation. While a few direct deoxygenation
methods of phenol derivatives have been reported,4 such
conventional procedures require, a vast amount (5-10 equiv)
of the reagents,4a-c leading to low yields,4a and are limited
to the phenolic hydroxyl group of fused aromatics.4b,c The
conversion of the phenolic hydroxyl group to the corre-
sponding sulfonate,2,5,6,7 isourea,5,8 dimethyl thiocarbamate,5
aryl ether,9 5-phenyltetrazolyl ether,10 and phosphate ester11
is employed for activation as a substrate of reductive
deoxygenation. Nevertheless, these conventional methods still
include disadvantages such as lack of stability of the activated
(5) Sebo¨k, P.; Timar, T.; Eszenyi, T.; Patonay, T. J. Org. Chem. 1994,
59, 6318 and references therein.
(6) (a) Rottendorf, H.; Sternhell, S. Aust. J. Chem. 1963, 16, 647. (b)
Clauss, K.; Jensen, H. Angew. Chem., Int. Ed. Engl. 1973, 12, 918. (c)
Lonsky, W.; Traitler, H.; Kratzl, K. J. Chem. Soc., Perkin Trans. 1 1975,
169. (d) Subramanian, L. R. Synthesis 1984, 481. (e) Cacchi, S.; Ciattini,
P. G.; Morera, E.; Orter, G. Tetrahedron Lett. 1986, 27, 5541. (f) Chen,
Q.-Y.; He, Y.-B.; Yang, Z.-Y, J. Chem. Soc., Chem. Commun. 1986, 1452.
(g) Cabri, W.; Bernardinis, S. D.; Francalanci, F.; Penco, S. J. Org. Chem.
1990, 55, 350. (h) Saa, J. M.; Dopico, M.; Martorell, G.; Garcia-Raso, A.
J. Org. Chem. 1990, 55, 991. (i) Sasaki, K.; Sakai, M.; Sakakibara, Y.;
Takagi, K. Chem. Lett. 1991, 2017. (j) Kotsuki, H.; Datta, P. K.; Hayakawa,
H.; Suenaga, H. Synthesis 1995, 1348. (k) Lipshutz, B. H.; Buzard, D. J.;
Vivian, R. W. Tetrahedron Lett. 1999, 40, 6871-6874.
(7) Recently Pd(OAc)2-catalyzed reductive deoxygenation methods of
polymer supported aromatic sulfonates are reported as a quite useful tool
for combinatorial chemistry, while a perfluorated linker, phosphine ligand,
and heating conditions are required; see: (a) Pan, Y.; Holmes, C. P. Org.
Lett. 2001, 3, 2769. (b) Cammidge, A. N.; Ngaini, Z. Chem. Commun. 2004,
1914. (c) Revell, J. D.; Ganesan, A. Chem. Commun, 2004, 1916.
(8) Vowinkel, E.; Wolff, C. Chem. Ber. 1974, 107, 907.
(9) (a) Sartoretto, P. A.; Sowa, F. J. J. Am. Chem. Soc. 1937, 59, 603.
(b) Sawa, Y. K.; Tsuji, N.; Maeda, S. Tetrahedron 1961, 15, 144 and 154.
(c) Pirkle, W. H.; Zabriskie, J. L. J. Org. Chem. 1964, 29, 3124.
(10) (a) Musliner, W. J.; Gates, J. W., Jr. J. Am. Chem. Soc. 1966, 88,
4271. (b) Hussey, J.; Johnstone, R. A. Q. Tetrahedron 1982, 38, 3775.
(11) (a) Pelletier, S. W.; Locke, D. M. J. Org. Chem. 1958, 23, 131. (b)
Kenner, G. W.; Williams, N. R. J. Chem. Soc. 1955, 522. (c) Goldkamo,
A. H.; Hoehn, W. M.; Mikulec, R. A.; Nutting, E. F.; Cook, D. L. J. Med.
Chem. 1965, 8, 409. (d) Rossi, R. A.; Bunnett, J. F. J. Org. Chem. 1973,
38, 2314. (e) Shafer, S. J.; Closson, W. D.; van Dijk, J. M. F.; Piepers, O.;
(1) (a) Okuda, T.; Yoshida, T.; Hatano, T. Planta Med. 1989, 55, 117.
(b) Akiyama, H.; Sakushima, J.; Taniuchi, S.; Kanda, T.; Yanagida, A.;
Kojima, T.; Teshima, R.; Kobayashi, Y.; Goda, Y.; Toyoda, M. Biol. Pharm.
Bull. 2000, 23, 1370.
(2) Peterson, G. A.; Kunng, F.; McCallumg, J. S.; Wulff, W. D.
Tetrahedron Lett. 1987, 28, 1381.
(3) Evans, D. A.; Wood, M. R.; Trotter, B. W.; Richardson, T. I.; Barrow,
J. C.; Katz, J. L. Angew. Chem., Int. Ed. 1998, 37, 2700.
(4) (a) Severin, T.; Ipach, I. Synthesis 1973, 796. (b) Konieczny, M.;
Harvey, R. G. J. Org. Chem. 1979, 44, 4813. (c) Node, M.; Nishide, K.;
Ohta, K.; Fujita, E. Tetrahedron Lett. 1982, 23, 689.
10.1021/ol060045q CCC: $33.50
© 2006 American Chemical Society
Published on Web 02/02/2006