Mechanism of hydrogen transfer to imines from a hydroxycyclopentadienyl ruthenium hydride. Support for a stepwise mechanism

Article abstract of DOI:10.1039/b410698a

The negligible double kinetic deuterium isotope effect (k _HH/k_DD = 1.05) in the reaction where [2,3,4,5-Ph ₄(η⁵-C₄COH)Ru(CO)₂H (2) transfers a hydride and a proton to N-phenyl-[1-(4-methoxyphenyl)ethylidene] amine (4) indicates that no bond to hydrogen is broken or formed in the rate-determining step.

Full text of DOI:10.1039/b410698a

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Mechanism of hydrogen transfer to imines from a
hydroxycyclopentadienyl ruthenium hydride. Support for a stepwise
mechanism{
´
Joseph S. M. Samec, Alida H. Ell and Jan-E. Ba¨ckvall*
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm,
Sweden. E-mail: jeb@organ.su.se; Fax: 146-8-154908; Tel: 146-8-674 7178
Received (in Cambridge, UK) 17th July 2004, Accepted 9th September 2004
First published as an Advance Article on the web 6th October 2004
The negligible double kinetic deuterium isotope effect (kHH
kDD
C4COH)Ru(CO)2H (2) transfers a hydride and a proton to
N-phenyl-[1-(4-methoxyphenyl)ethylidene]amine (4) indicates
that no bond to hydrogen is broken or formed in the rate-
determining step.
/
without coordination of the unsaturated substrate was proposed. A
concerted mechanism was also observed by our group for the
dehydrogenation of alcohols by A.12
We recently reported that transfer dehydrogenation of
N-phenyl-1-phenylethylamine to the corresponding imine by A,
generated from 1 in situ, gave deuterium isotope effects consistent
with a stepwise mechanism.7b Thus, the combined isotope effect
kCHNH/kCDND ~ 3.26 was equal to the individual isotope effect
kCHNH/kCDNH ~ 3.24 and the other individual isotope effect (ND)
was very small.
Here we report on the kinetic deuterium isotope effect for the
reaction of 2 with a ketimine, which shows that the hydrogen
transfer is not involved in the rate-determining step, thus ruling out
the concerted mechanism of Scheme 2 for this imine.11
Hydride 2 was prepared from 3 in THF under hydrogen or
deuterium atmosphere at 120 uC in a microwave oven for 20 min
(Scheme 3).13 The imine was prepared according to a literature
procedure.5
~
1.05) in the reaction where [2,3,4,5-Ph4(g5-
Transition metal-catalyzed hydrogen transfer has attracted con-
siderable attention during the past 10–15 years.1 A variety of new
catalysts have been reported that are highly efficient for transferring
hydrogen from a hydrogen donor (e.g. an alcohol) to a hydrogen
acceptor (e.g. a ketone or an imine). Catalytic hydrogen transfer
reactions have been successfully applied to enantioselective
versions.2
In 1985 Shvo reported on the dimeric catalyst 1 (Scheme 1),3
which since then has been used in a number of hydrogen transfer
reactions4–10 These reactions include disproportion of aldehydes to
esters,4a hydrogenation of carbonyl compounds,4b and Oppenauer-
type oxidations of alcohols1b,6 and amines.7 It has also been shown
that catalyst 1 is efficient for racemization of alcohols and this
was used in combination with lipases for dynamic kinetic resolution
of secondary alcohols.8 Complex 1 has also been used for
racemization of amines.9
Scheme 3
The kinetic deuterium isotope effect in the reaction of 2 with
ketimine 4 in CD2Cl2 was studied at 254 uC using 2 and
dideuterated 2 (OD, Ru–D) (Scheme 4). The reaction showed
second order kinetics with a first-order dependence on imine and 2,
respectively. (For the details of the kinetics see ESI.{) The product
of this reaction at this temperature is the ruthenium amine complex
5. The reaction is readily followed by 1H NMR spectroscopy. The
Scheme 1
Catalyst 1 is in equilibrium with monomers 2 and A (Scheme 1).
The monomer 2 is able to hydrogenate a hydrogen acceptor
whereas the monomer A can dehydrogenate a hydrogen donor.
These processes interconvert 2 and A.
In 2001 Casey and coworkers reported a mechanistic study on
hydrogen transfer to carbonyls and imines from 2’ (Scheme 2).11
From the large combined isotope effect observed for benzaldehyde
(X ~ O, R ~ H) kRuHOH/kRuDOD ~ 3.6 together with individual
isotope effects of 1.5 (RuD) and 2.2 (OD) a concerted mechanism
1
methoxy peak gives a characteristic signal in the H NMR for
imine 4 at d 3.85 and two characteristic signals for the two
diastereoisomers of complex 5 at d 3.62 and 3.55 where the former
is the kinetically favored diastereoisomer. The reactions were run
under pseudo-first-order kinetics with an excess of 2 until over two
half lives were over (24 min) integrating the methoxy peaks of imine
4 versus the two peaks of 5.
Scheme 2 Concerted mechanism proposed in ref. 11.
{ Electronic supplementary information (ESI) available: experimental
procedures and kinetic data. See http://www.rsc.org/suppdata/cc/b4/
b410698a/
Scheme 4
2 7 4 8
C h e m . C o m m u n . , 2 0 0 4 , 2 7 4 8 – 2 7 4 9
T h i s j o u r n a l i s ß T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

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The observed rate constant for the formation of 5 (Scheme 4) for
RuHOH was kobs ~ (1.24 ¡ 0.08) 6 1023 s21 and for RuDOD it
was kobs ~ (1.18 ¡ 0.09) 6 1023 s21 14
. The kinetic isotope effect
calculated from the results is therefore kRuHOH/kRuDOD ~ 1.05 ¡
0.14. This is in sharp contrast to the corresponding kinetic isotope
effect observed for benzaldehyde which was 3.6.11 The latter
isotope effect shows that the transfer of hydrogen from ruthenium
and oxygen to the aldehyde occurs within the rate-determining
step. The low isotope effect of 1.05 for the transfer of hydrogen
from 2 to imine 4 suggests another mechanism where the hydrogen
transfer is not the rate-determining step. It should be noted that
complex 5 is unstable at temperatures above 225 uC in the presence
of hydride 2. The products above 225 uC are the free amine 6 and
dimer 1 (eqn. (1)). The free amine (6) is distinguishable by 1H
NMR at d 3.75.
Scheme 5
(1)
Financial support from the Swedish Research Council is
gratefully acknowledged. We thank Professor Charles P. Casey
and coworkers for fruitful discussions.
The ruthenium-mediated hydrogen transfer of imines appears to
proceed through a mechanism different to that for carbonyl
compounds. Even though there are many similarities between the
two classes of compounds there are important differences. Amines
and imines are more nucleophilic than alcohols and carbonyls.
Therefore it is expected that amines and imines should coordinate
better to ruthenium. This is evident when comparing the electronic
properties of the substrates in transfer hydrogenation of imines,5
transfer dehydrogenations of amines,7a and racemization of
amines9 where electron-rich substrates react faster than electron-
deficient substrates suggesting a mechanism where the coordination
of the substrate to ruthenium comes into the rate expression.{ The
negligible kinetic isotope effect in the reaction of 2 with imines
implies that there is no hydrogen transfer in the rate-determining
step.
Notes and references
{ The presence of imine in the rate expression is also consistent with the
outer sphere mechanism (cf. ref. 11)
1 (a) S. Gladiali and G. Mestroni, in Transition Met. Org. Synth., (Eds.:
M. Beller and C. Bolm), Wiley-VCH, Weinheim, 1998, vol. 2, p. 97; (b)
J.-E. Ba¨ckvall, R. L. Chowdhury, U. Karlsson and G.-Z. Wang, in
Perspectives in Coordination Chemistry, (Eds.: A. F. Williams, C. Floriani
and A. E. Merbach), Verlag Helvetica Chimica Acta, Basel, 1992, p. 463;
(c) O. Pa`mies and J.-E. Ba¨ckvall, Chem. Eur. J., 2001, 7, 5052;
(d) K. Abdur-Rashid, S. E. Clapham, A. Hadzovic, J. N. Harvey,
A. J. Lough and R. H. Morris, J. Am. Chem. Soc., 2002, 124, 15104;
(e) V. Rautenstrauch, X. Hoang-Cong, R. Churlaud, K. Abdur-Rashid
and R. H. Morris, Chem. Eur. J., 2003, 9, 4954.
A mechanism for the hydrogen transfer from 2 to the ketimine is
proposed in Scheme 5. If 18 e2 complex 2 is in equilibrium with
16 e2 complex B via an g5 A g3 ring slippage, the imine can
coordinate to give an 18 e2 intermediate C. Subsequent fast
hydride and proton transfer via p-bound imine would then yield the
g2 complex D, which would rearrange to g4 ruthenium amine
complex 7 (Scheme 5). It is likely that the ring slippage from g5 A
g3to give B is slow compared to the back reaction (B A 2).
If k21 w k2 then 2 and B are in equilibrium. Then the rate
expression for the formation of complex 7 can be formulated as in
eqn. (2):
2 (a) R. Noyori and S. Hashiguchi, Acc. Chem. Res., 1997, 30, 97;
(b) J. Mao and D. C. Baker, Org. Lett., 1999, 6, 841; (c) S. J. M. Nordin,
P. Roth, T. Tarnai, D. A. Alonso, P. Brandt and P. G. Andersson,
Chem. Eur. J., 2001, 7, 1431; (d) D. G. I. Petra, P. C. J. Kamer,
A. L. Spek, H. E. Schoemaker and P. W. N. M. van Leeuwen, J. Org.
Chem., 2000, 65, 3010; (e) A. Bøgevig, I. M. Pastor and H. Adolfsson,
Chem. Eur. J., 2004, 10, 294.
3 Y. Blum, D. Czarkie, Y. Rahamim and Y. Shvo, Organometallics, 1985,
4, 1459.
4 (a) N. Menashe and Y. Shvo, Organometallics, 1991, 10, 3885;
(b) Y. Shvo, D. Czarkie and Y. Rahamim, J. Am. Chem. Soc., 1986,
108, 7400.
5 J. S. M. Samec and J.-E. Ba¨ckvall, Chem. Eur. J., 2002, 8, 2955.
6 (a) G.-Z. Wang, U. Andreasson and J.-E. Ba¨ckvall, J. Chem. Soc., Chem.
Commun., 1994, 1037; (b) M. L. S. Almeida, M. Beller, G-Z. Wang and
d½7ꢀ
~k2½imineꢀ½Bꢀ~k2K½imineꢀ½2ꢀ~const½imineꢀ½2ꢀ (2)
dt
´
J.-E. Ba¨ckvall, Chem. Eur. J., 1996, 2, 1533; (c) G. Csjernyik, A. H. Ell,
L. Fadini, B. Pugin and J.-E. Ba¨ckvall, J. Org. Chem., 2002, 67, 1657.
The rate expression is in agreement with the observed first-order
dependence on both imine and 2 for the formation of the
ruthenium amine complex 7. An alternative mechanism, where a
reversible transfer of a proton from 2 to imine gives protonated
imine and an anionic hydride, followed by ring slippage and
insertion, gives the same kinetics and would also explain the
absence of isotope effect.15 We cannot completely exclude direct
hydride transfer from ruthenium to uncoordinated protonated
imine in the latter mechanism (followed by association of
ruthenium complex and amine) but it does not seem compatible
with the very low isotope effect.
´
7 (a) A. H. Ell, J. S. M. Samec, C. Brasse and J.-E. Ba¨ckvall, Chem.
´
Commun., 2002, 1144; (b) A. H. Ell, J. B. Johnson and J.-E. Ba¨ckvall,
Chem. Commun., 2003, 1652.
8 (a) A. L. E. Larsson, B. A. Persson and J.-E. Ba¨ckvall, Angew. Chem.,
Int. Ed. Engl., 1997, 36, 1211; (b) B. A. Persson, A. L. E. Larsson,
M. L. Ray and J.-E. Ba¨ckvall, J. Am. Chem. Soc., 1999, 121, 1645;
(c) F. F. Huerta, A. Minidis and J.-E. Ba¨ckvall, Chem. Soc. Rev., 2001,
30, 321; (d) O. Pa`mies and J.-E. Ba¨ckvall, Chem. Rev., 2003, 103, 3247;
(e) M. J. Kim, Y. Ahn and J. Park, Curr. Opin. Biotechnol., 2002, 13, 578.
´
9 O. Pa`mies, A. H. Ell, J. S. M. Samec, N. Hermanns and J.-E. Ba¨ckvall,
Tetrahedron Lett., 2002, 43, 4699.
In the dehydrogenation of amines by A (the reverse reaction) a
large isotope effect was previously observed.7b Considering the
microscopic reversibility of Scheme 5 the amine would readily
coordinate to A to give 7. A g4 A g2 ring slip of 7 in an
equilibration process to give D followed by a rate limiting
b-elimination would account for the large isotope effect observed.
In conclusion the low kinetic isotope effect of kRuHOH/kRuDOD
~ 1.05 ¡ 0.14 observed in the hydrogen transfer from 2 to imine 4
shows that the rate-determining step for the reaction does not
involve the hydrogen transfer step, and supports a stepwise
mechanism.
10 J. H. Choi, N. Kim, Y. J. Shin, J. H. Park and J. Park, Tetrahedron Lett.,
2004, 45, 4607.
11 C. P. Casey, S. W. Singer, D. R. Powell, R. K. Hayashi and M. Kavana,
J. Am. Chem. Soc., 2001, 123, 1090.
12 J. B. Johnson and J.-E. Ba¨ckvall, J. Org. Chem., 2003, 68, 7681.
13 Casey and coworkers have reported the same reaction without
microwave assistance (see ref. 11).
14 Six/seven different experiments were run for both RuHOH and RuDOD
individually.
15 Proton transfer to ketones in a pre-equilibrium has been discussed as a
possible mechanism in catalytic ionic hydrogenations: R. M. Bullock,
Chem. Eur. J., 2004, 10, 2366.
C h e m . C o m m u n . , 2 0 0 4 , 2 7 4 8 – 2 7 4 9
2 7 4 9