Communications
DOI: 10.1002/anie.200805307
Catalytic Hydrogenation
Hydrogenation of N-Acylcarbamates and N-Acylsulfonamides
Catalyzed by a Bifunctional [Cp*Ru(PN)] Complex**
Masato Ito, Lee Wei Koo, Akio Himizu, Chika Kobayashi, Ayaka Sakaguchi, and Takao Ikariya*
The development of well-designed molecular catalysts for the
hydrogenation of polar organic functionalities continues to be
an important challenge, because it would provide a solution to
reducing the energy required and waste generated for such a
reactions. It would also provide direct access to stereochem-
ically well-defined molecules through a structural modifica-
tion of the catalyst molecule.[1] The difficulty with this issue is
the discovery of an appropriate catalyst which can generate a
more hydridic species from molecular dihydrogen (H2) with
concomitant release of a more protic product by a formal
heterolytic H2 cleavage. Over a decade ago, an intriguing clue
was offered by a Noyoriꢀs bifunctional catalyst, consisting of
[RuCl2(diphosphane)(diamine)] and a base, for the hydro-
genation of ketones, which promotes this energetically
disfavored process with an aid of alcoholic solvents.[2,3] We
also successfully developed new bifunctional catalyst systems
comprised of [Cp*RuCl{L(CH2)2NH2-k2-L,N}] complexes
Scheme 1. A possible catalytic cycle for the hydrogenation of polar
functionalities with [Cp*Ru(LN)] catalysts.
and a base for the highly efficient hydrogenation of polar
organic functionalities (Cp* = h5-C5(CH3)5; L = (CH3)2N, or
(C6H5)2P).[4] The nucleophilicity of the RuH moiety as well as
the electrophilicity of the NH moiety in the catalytically
active [Cp*RuH{L(CH2)2NH2-k2-L,N}] complexes are suita-
bly controlled by the electronic nature of L in the ligand
(Scheme 1).
[Cp*Ru(PN)] in the hydrogenation of polar organic function-
alities and we found the unprecedented hydrogenation of
N-acylcarbamates and N-acylsulfonamides. Herein, we dis-
close the details of the reactions and their synthetic applica-
tions.
For example, both [Cp*Ru(NN)] (N = tertiary amine) and
[Cp*Ru(PN)] (P = tertiary phosphane) catalysts are capable
Initial experiments focused on the effect of alcoholic
solvents upon the chemoselectivity in the hydrogenation of
N-Boc-pyrrolidinone (2a; Boc = CO2tBu) as a model sub-
strate. The reaction was carried out at 808C under 3 MPa of
H2 in an alcoholic solvent containing 2a, [Cp*RuCl{(C6H5)2P-
(CH2)2NH2-k2-P,N}] (1), and KOtBu (2a/Ru/KOtBu =
100:1:1, [2a] = 0.2m). Substrate 2a was smoothly consumed
in a variety of alcoholic solvents, but the reaction course was
delicately influenced by the sterics of the alcohol employed.
In fact, the use of methanol or 2-propanol significantly caused
alcoholysis in addition to the hydrogenation of 2a to result in
the formation of a mixture of BocNH(CH2)4OH (2ax) and
BocNH(CH2)3CO2R (2ay: R = CH3, 2az: R = CH(CH3)2) in
ratios of 66:34 in methanol and 82:18 in 2-propanol,
respectively. However, the use of tert-butyl alcohol sup-
pressed the undesired alcoholysis to give 2ax as a sole
product. The effect of the base turned out to be negligible
since the use of other bases such as nBu4NOH and KOH
instead of KOtBu gave the similar results (Scheme 2).
Next, the scope of the present hydrogenation with a
binary catalyst system of 1 and KOtBu was examined in tert-
butyl alcohol using a variety of N-acylcarbamates and
N-acylsulfonamides. Table 1 lists the selected examples. In
addition to the Boc group (2a), a range of electron-with-
drawing groups on the nitrogen atom of the pyrrolidinone
À
of heterolytic H H bond cleavage, wherein the increased
p-accepting property of the tertiary phosphane enhances the
Brønsted acidity of the ligated NH group to facilitate the
activation of polar functional groups. Accordingly,
[Cp*Ru(NN)] favorably promotes the hydrogenation of
ketones,[4a] whereas [Cp*Ru(PN)] effects the hydrogenation
of epoxides[4b] and imides[4c] as well as ketones. This successful
expansion of the Ru/NH bifunctionality[5] has led us to
additionally examine the catalytic performance of
[*] Prof. Dr. M. Ito, L.-W. Koo, A. Himizu, C. Kobayashi, A. Sakaguchi,
Prof. Dr. T. Ikariya
Department of Applied Chemistry, Graduate School of Science and
Engineering, Tokyo Institute of Technology
2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552 (Japan)
Fax: (+81)357-342-637
E-mail: tikariya@apc.titech.ac.jp
[**] This work was financially supported by a Grant-in-Aid from MEXT
(Nos. 16750073 and 18065007) and partially supported by the G-
COE program and the Asahi Glass Foundation (M.I.). A part of this
work was presented in 2002 on the 49th symposium on organo-
metallic chemistry at Kobe (Japan) (PB143).Cp*=h5-pentamethyl-
cyclopentadienyl (h5-C5(CH3)5).
Supporting information for this article is available on the WWW
1324
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 1324 –1327