Mech a n ism of Ru th en iu m -Ca ta lyzed Hyd r ogen Tr a n sfer
Rea ction s. Con cer ted Tr a n sfer of OH a n d CH Hyd r ogen s fr om a n
Alcoh ol to a (Cyclop en ta d ien on e)r u th en iu m Com p lex
J effrey B. J ohnson and J an-E. Ba¨ckvall*
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University,
SE-106 91 Stockholm, Sweden
jeb@organ.su.se
Received May 13, 2003
Kinetic studies of the ruthenium-catalyzed dehydrogenation of 1-(4-fluorophenyl)ethanol (4) by
tetrafluorobenzoquinone (7) using the Shvo catalyst 1 at 70 °C show that the dehydrogenation by
catalytic intermediate 2 is rate-determining with the rate ) k[4][1]1/2 and with ∆Hq ) 17.7 kcal
mol-1 and ∆Sq ) -13.0 eu. The use of specifically deuterated derivative 4-CHOD and 4-CDOH
gave individual isotope effects of kCHOH/kCHOD ) 1.87 ( 0.17 and kCHOH/kCDOH ) 2.57 ( 0.26,
respectively. Dideuterated derivative 4-CDOD gave a combined isotope effect of kCHOH/kCDOD
)
4.61 ( 0.37. These isotope effects are consistent with a concerted transfer of both hydrogens of the
alcohol to ruthenium species 2.
In tr od u ction
coordination sphere of the metal for the arene-Ru(II)-
diamine system, and he and others have provided cal-
culations that support this concerted mechanism.9 Casey
has reported mechanistic evidence based on deuterium
isotope effects that support a concerted transfer of
hydrogen using the Shvo catalyst 1.10
In dynamic kinetic resolution, the Shvo catalyst 1 is
used to racemize a secondary alcohol (Scheme 1).5a An
enzyme, in the presence of an acyl donor, is employed to
acylate one of the enantiomers of the racemic alcohol,
while the other enantiomer is racemized in situ by the
catalyst 1. This process continues until all of the alcohol
has been converted to a single enantiomer of the acylated
product. The racemization proceeds via a dehydrogena-
tion of the alcohol by the catalyst and readdition of the
hydrogens to the intermediate ketone.
To address the mechanistic questions concerning the
transfer of hydrogen and to better understand this
process in dynamic kinetic resolution, we studied the
kinetics of hydrogen transfer from an alcohol to ruthe-
nium complex 2. The results of our mechanistic study,
including kinetic isotope effects, provide direct evidence
for a mechanism involving simultaneous transfer of the
C-H and O-H hydrogens from an alcohol to the unsat-
urated ruthenium catalyst 2.
The use of transition metals that catalyze the transfer
of hydrogen from alcohols has increased dramatically
during the past decade.1,2 Systems such as Noyori’s
arene-Ru(II)-diamine catalyst and Shvo’s hydroxy-
cyclopentadienyl ruthenium(II) catalyst (1) have been
used for the catalytic reduction of polarized unsaturated
species,3,4 and Shvo’s catalyst (1) has also been used for
dynamic kinetic resolution.5,6 Unlike earlier systems,
these hydrogen-transfer catalysts do not require the
presence of base for the transfer of hydrogen from an
alcohol to a ketone and have thus been suggested to
operate through a mechanism different from the metal
hydride mechanism common for transition-metal com-
plexes1,2a or the traditional Meerwein-Ponndorf-Verley
mechanism common for main group elements.7,8 Noyori
has proposed that hydrogen transfer occurs outside the
(1) Gladiali, S.; Mestroni, G. Transition Metals for Organic Synthe-
sis; Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim, 1998; pp 97-
119.
(2) (a) Noyori, R.; Yamakawa, M.; Hashiguchi, S. J . Org. Chem.
2001, 66, 7931. (b) Palmer, M. J .; Wills, M. Tetrahedron Asymmetry
1999, 10, 2045.
(3) Haack, K.-J .; Hashiguchi, S.; Fujii, A.; Noyori, R. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 285.
(4) (a) Shvo, Y.; Czarkie, D.; Rahamim, Y. J . Am. Chem. Soc. 1986,
108, 7400. (b) Samec, J . S. M.; Ba¨ckvall, J .-E. Chem. Eur. J . 2002, 8,
2955-2961.
Resu lts
(5) (a) Larsson, A. L. E.; Persson, B. A.; Ba¨ckvall, J .-E. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1211. (b) Persson, B. A.; Larsson, A.
L. E.; LeRay, M.; Ba¨ckvall, J .-E. J . Am. Chem. Soc. 1999, 121, 1645.
(c) Persson, B. A.; Huerta, F. F.; Ba¨ckvall, J .-E. J . Org. Chem. 1999,
64, 5237. (d) Huerta, F. F.; Laxmi, Y. R. S.; Ba¨ckvall, J .-E. Org. Lett.
2000, 3, 1037. (e) Pamies, O.; Ba¨ckvall, J .-E. J . Org. Chem. 2001, 66,
4022.
(6) (a) Dinh, P. M.; Howarth, J . A.; Hudnott, A. R.; Williams, J . M.
J . Tetrahedron Lett. 1996, 37, 7623. (b) Koh, J . H.; J ung, H. M.; Kim,
M.-J .; Park, J . Tetrahedron Lett. 1999, 40, 6281. (c) J ung, H. M.; Koh,
J . H.; Kim, M.-J .; Park, J . Org. Lett. 2000, 2, 409.
(7) (a) Meerwein, H.; Schmidt, R. J ustus Liebigs Ann. Chem. 1925,
444, 221. (b) Verley, A. Bull. Soc. Chem. Fr. 1925, 37, 537. (c) Ponndorf,
W. Angew. Chem. 1926, 39, 138.
Due to the high temperature necessary to dissociate
the Shvo catalyst 1 and produce the unsaturated species
(8) De Graauw, C. F.; Peters, J . A.; van Bekkum, H.; Huskens, J .
Synthesis 1994, 1007.
(9) (a) Alonso, D. A.; Brandt, P.; Nordin S. J . M.; Andersson, P. G.
J . Am. Chem. Soc. 1999, 121, 9580. (b) Yamakawa, M.; Ito, H.; Noyori,
R. J . Am. Chem. Soc. 2000, 122, 1466. (c) Petra, D. G. I.; Reek, J . N.
H.; Handgraaf, J .-W.; Meijer, E. J .; Dierkes, P.; Kamer, P. C. J .;
Brussee, J .; Schoemaker, H. E.; van Leeuwen, P. W. N. M. Chem. Eur.
J . 2000, 6, 2818.
(10) Casey, C. P.; Singer, S. W.; Powell, D. R.; Hayashi, R. K.;
Kavana, M. J . Am. Chem. Soc. 2001, 123, 1090.
10.1021/jo034634a CCC: $25.00 © 2003 American Chemical Society
Published on Web 08/30/2003
J . Org. Chem. 2003, 68, 7681-7684
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