ORGANIC
LETTERS
2006
Vol. 8, No. 15
3279-3281
Pd/C-Catalyzed Chemoselective
Hydrogenation in the Presence of
Diphenylsulfide
Akinori Mori, Yumi Miyakawa, Eri Ohashi, Tomoko Haga,
Tomohiro Maegawa, and Hironao Sajiki*
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical UniVersity,
Mitahora-higashi, Gifu 502-8585, Japan
Received May 11, 2006
ABSTRACT
A Pd/C-catalyzed chemoselective hydrogenation using diphenylsulfide as a catalyst poison has been developed. This methodology selectively
hydrogenates olefin and acetylene functionalities without hydrogenolysis of aromatic carbonyls and halogens, benzyl esters, and N-Cbz protective
groups.
Transition-metal-catalyzed hydrogenation methods have been
applied to a number of chemical transformations of functional
groups.1 Chemoselective hydrogenation among some reduc-
ible functionalities has been one of the most important
subjects in the field of synthetic chemistry. Catalytic
hydrogenations are usually suppressed or degraded by
catalyst poisons, such as sulfur or nitrogen-containing
molecules.1,2 Several applications of catalyst poisons have
been studied to develop a chemoselective hydrogenation
method; such methods usually lack generality except for a
few examples, such as the Lindlar catalyst3 and Rosenmund’s
reduction.4 Although Pd/C is known as the most universal
catalyst for hydrogenation, it has poor selectivity due to its
efficient catalytic activity.1 Recently, we have reported that
the addition of a nitrogen-containing base to a Pd/C-catalyzed
hydrogenation system selectively suppressed the hydro-
genolysis of benzyl ether in the presence of other reducible
functionalities, such as olefin, benzyl ester, and so on.5,6
However, aromatic N-Cbz (benzyloxycarbonyl) and aromatic
halogen functionalities are hydrogenated under those reaction
conditions.5 During our efforts to solve the problem, we
found that the addition of a sulfur-atom-containing catalyst
(4) (a) Rosenmund, K. W. Ber. Dtsch. Chem. Ges. 1918, 51, 585. (b)
Rosenmund, K. W.; Zetzsche, F. Ber. Dtsch. Chem. Ges. 1921, 54, 425.
(c) Mosettig, E.; Mozingo, R. Org. React. 1948, 4, 362. (d) Brown, H. C.;
Rao, B. C. S. J. Am. Chem. Soc. 1958, 80, 5377.
(5) (a) Sajiki, H. Tetrahedron Lett. 1995, 36, 3465. (b) Sajiki, H.; Kuno,
H.; Hirota, K. Tetrahedron Lett. 1997, 38, 399. (c) Sajiki, H.; Kuno, H.;
Hirota, K. Tetrahedon Lett. 1998, 39, 7127. (d) Sajiki, H.; Hirota, K.
Tetrahedron 1998, 54, 13981. (e) Sajiki, H. Yakugaku Zasshi 2000, 120,
1091. (f) Sajiki, H.; Hirota, K. Chem. Pharm. Bull. 2003, 51, 320.
(6) (a) Sajiki, H.; Hattori, K.; Hirota, K. J. Org. Chem. 1998, 63, 7990.
(b) Sajiki, H.; Hattori, K.; Hirota, K. J. Chem. Soc., Perkin Trans. 1 1998,
4043. (c) Sajiki, H.; Hattori, K.; Hirota, K. Chem. Commun. 1999, 1041.
(d) Sajiki, H.; Hattori, K.; Hirota, K. Chem.sEur. J. 2000, 6, 2200. (e)
Hattori, K.; Sajiki, H.; Hirota, K. Tetrahedron 2000, 56, 8433. (f) Hattori,
K.; Sajiki, H.; Hirota, K. Tetrahedron 2001, 57, 4817. (g) Sajiki, H.; Hirota,
K. J. Org. Synth. Chem. Jpn. 2001, 59, 109.
(1) (a) Larock, R. C. ComprehensiVe Organic Transformations, 2nd ed.;
Wiley-VCH: New York, 1999. (b) Nishimura, S. Handbook of Heteroge-
neous Catalytic Hydrogenation for Organic Synthesis; Wiley-Interscience:
New York, 2001. (c) Hudlickey, M. Reductions in Organic Chemistry, 2nd
ed.; American Chemical Society: Washington, DC, 1996. (d) Rylander, P.
N. Hydrogenation Methods; Academic: New York, 1985.
(2) (a) Baltzly, R. J. Am. Chem. Soc. 1952, 74, 4586. (b) Horner, L.;
Reuter, H.; Herrmann, E. Justus Liebigs Ann. Chem. 1962, 660, 1. (c)
Baltzly, R. J. Org. Chem. 1976, 41, 928.
(3) Lindlar, H.; Dubuis, R. Organic Syntheses; John Wiley & Sons: New
York, 1973; Collect. Vol. 5, p 880.
10.1021/ol061147j CCC: $33.50
© 2006 American Chemical Society
Published on Web 06/28/2006