9020
J . Org. Chem. 2001, 66, 9020-9022
Notes
Sch em e 1
An Un u su a l Typ e of Ru th en iu m -Ca ta lyzed
Tr a n sfer Hyd r ogen a tion of Keton es w ith
Alcoh ols Accom p a n ied by C-C Cou p lin g
Chan Sik Cho,* Bok Tae Kim, Tae-J eong Kim, and
Sang Chul Shim*
Department of Industrial Chemistry, College of Engineering,
Kyungpook National University, Taegu 702-701, Korea
Ta ble 1. Op tim iza tion of Con d ition s for th e Rea ction of
1a w ith 2a a
scshim@kyungpook.ac.kr
Received August 20, 2001
entry
ruthenium catalyst
temp (°C) yieldb (%) 4a /5a
1
2
3
4c
5
6
7
8
9
RuCl2(PPh3)3
RuCl2(PPh3)3
RuCl2(PPh3)3
RuCl2(PPh3)3
RuCl3‚nH2O/3PPh3
RuH2(PPh3)4
RuCl2(dCHPh)(PCy3)2
Cp*RuCl2(CO)d
Ru3(CO)12
80
50
25
80
80
80
80
80
80
92
76
52
76
32
81
70
78
0
97/3
86/14
81/19
63/37
97/3
97/3
98/2
Transition metal-catalyzed transfer hydrogenation of
hydrogen acceptors by hydrogen donors has been recog-
nized to be of importance in reduction chemistry.1 In
contrast to conventional reduction routes, which fre-
quently require a high hydrogen pressure and hazardous
reducing reagents,2 the transfer hydrogenation has some
unique advantages in its simplicity and avoidance of
cumbersome reducing agents. Of various hydrogen do-
nors so far employed, a primary or secondary alcohol is
the choice of preference for various reasons.3 In conven-
tional transfer hydrogenation, the alcohol is oxidized to
the corresponding ketone (or aldehyde) depending on the
nature of the alcohol (Scheme 1, route a).
90/10
a
Reaction conditions: 1a (1 mmol), 2a (3 mmol), ruthenium
catalyst (5 mol %), KOH (3 mmol), dioxane (3 mL), under argon,
b
d
for 40 h. Determined by GLC based on 1a . c [2a ]/[1a ] ) 1. Cp*
) η5-C5Me5.
the transfer hydrogenation of ketones by alcohols only
to discover the formation of unconventional transfer
hydrogenation products (Scheme 1, route b). Here we are
pleased to report our new findings.
Table 1 shows optimization of the conditions for the
transfer hydrogenation of acetophenone (1a ) with butanol
(2a ) (eq 1).7 Under all circumstances, the reaction gives
We have recently been engaged in ruthenium-catalyzed
reactions and developed some novel reactions.4-6 Prompted
by these findings and intrigued by diverse reactivities of
ruthenium catalysts, we have directed our attention to
(1) For reviews, see: (a) Brieger, G.; Nestrick, T. J . Chem. Rev. 1974,
74, 567. (b) Matteoli, U.; Frediani, P.; Bianchi, M.; Botteghi, C.;
Gladiali, S. J . Mol. Catal. 1981, 12, 265. (c) Bennet, M. A.; Matheson,
T. W. In Comprehensive Organometallic Chemistry; Wilkinson, G.,
Stone, F. G. A., Abel, E. W., Eds.; Pergamon Press: Oxford, 1984; Vol.
4, pp 945-953. (d) J ohnstone, R. W.; Wilby, A. H.; Entwistle, I. D.
Chem. Rev. 1985, 85, 129. (e) Zassinovich, G.; Mestroni, G.; Gladiali,
S. Chem. Rev. 1992, 92, 1051. (f) Ba¨ckvall, J .-E.; Chowdhury, R. L.;
Karlsson, U.; Wang G. In Perspectives in Coordination Chemistry;
Williams, A. F., Floriani, C., Merbach, A. E., Eds.; VCH: New York,
1992; pp 463-486. (g) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997,
30, 97. (h) Naota, T.; Takaya, H.; Murahashi, S.-I. Chem. Rev. 1998,
98, 2599. (i) Palmer, M.; Wills, M. Tetrahedron: Asymmetry 1999, 10,
2045.
rise to unconventional alkylated products, 1-phenyl-
hexan-1-ol (4a ) and 1-phenylhexan-1-one (5a ), rather
than the expected direct transfer hydrogenation product,
1-phenylethanol, the yield of which remains less than
5%.8 The best result in terms of both overall yield and
the relative amount of 4a to 5a is best accomplished by
RuCl2(PPh3)3 under the standard set of reaction condi-
tions (entry 1). The ratio 4a /5a increases with an increase
in the reaction temperature (entries 1-3). To account for
(2) (a) In Comprehensive Organometallic Chemistry; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 8. (b) Hudlicky, M.
Reductions in Organic Chemistry; American Chemical Society: Wash-
ington, DC, 1996.
(3) Besides primary and secondary alcohols, various hydrogen
donors have been explored for transition metal-catalyzed transfer
hydrogenation. Formic acid/trialkylamines and alkyl formates: (a)
Vol’pin, M. E.; Kukolev, V. P.; Chernyshev, V. O.; Kolomnikov, I. S.
Tetrahedron Lett. 1971, 4435. (b) Khai, B. T.; Arcelli, A. Tetrahedron
Lett. 1985, 26, 3365. (c) Brunner, H.; Kunz, M. Chem. Ber. 1986, 119,
2868. (d) Leitner, W.; Brown, J . M.; Brunner, H. J . Am. Chem. Soc.
1993, 115, 152. (e) Yamada, I.; Noyori, R. Org. Lett. 2000, 2, 3425.
Aldehydes: Blum, J .; Sasson, Y.; Iflah, S. Tetrahedron Lett. 1972,
1015. Amines, ethers, and hydroaromatic compounds: Nishiguchi, T.;
Tachi, K.; Fukuzumi, K. J . Org. Chem. 1975, 40, 237 and references
therein.
(4) Formation of indoles by ruthenium-catalyzed amine exchange
reaction between anilines and alkanolamines: (a) Cho, C. S.; Lim, H.
K.; Shim, S. C.; Kim, T. J .; Choi, H.-J . Chem. Commun. 1998, 995. (b)
Cho, C. S.; Kim, J . H.; Shim, S. C. Tetrahedron Lett. 2000, 41, 1811.
(c) Cho, C. S.; Kim, J . H.; Kim, T.-J .; Shim, S. C. Tetrahedron 2001,
57, 3321.
(5) Formation of quinolines by ruthenium-catalyzed amine exchange
reaction between anilines and alkylamines: (a) Cho, C. S.; Oh, B. H.;
Shim, S. C. Tetrahedron Lett. 1999, 40, 1499. (b) Cho, C. S.; Kim, J .
S.; Oh, B. H.; Kim, T.-J .; Shim, S. C.; Yoon, N. S. Tetrahedron 2000,
56, 7747. (c) Cho, C. S.; Oh, B. H.; Kim, J . S.; Kim, T.-J .; Shim, S. C.
Chem. Commun. 2000, 1885.
(6) Ruthenium-catalyzed regioselective R-alkylation of ketones with
trialkylamines: Cho, C. S.; Kim, B. T.; Lee, M. J .; Kim, T.-J .; Shim, S.
C. Angew. Chem., Int. Ed. 2001, 40, 958.
(7) Strong bases are frequently used as cocatalysts to promote
transition metal-catalyzed transfer hydrogenation: see ref 1.
10.1021/jo0108459 CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/22/2001