Interplay between hydrido/dihydrogen and amine/amido ligands in ruthenium-catalyzed transfer hydrogenation of ketones

Article abstract of DOI:10.1021/ic902339j

This work describes the synthesis of three key intermediates of Noyori-type catalytic systems that are active precatalysts for the transfer hydrogenation of acetophenone. Isolation of the cationic chloro(dihydrogen) complex [RuCl(H₂)(H₂NNPP)(PCy₃)][BArf₄] provides a facile synthetic route to the corresponding cationic and neutral hydrido complexes, and the series highlights the links between hydride/dihydrogen and amine/amido ligands in neutral and cationic species.

Full text of DOI:10.1021/ic902339j

1310 Inorg. Chem. 2010, 49, 1310–1312
DOI: 10.1021/ic902339j
Interplay between Hydrido/Dihydrogen and Amine/Amido Ligands in
Ruthenium-Catalyzed Transfer Hydrogenation of Ketones
Alexandre Picot,†,‡ Hellen Dyer,†,‡ Antoine Buchard,§ Audrey Auffrant,§ Laure Vendier,†,‡ Pascal Le Floch,§ and
Sylviane Sabo-Etienne*,†,‡
†CNRS, LCC (Laboratoire de Chimie de Coordination), 205 Route de Narbonne, F-31077 Toulouse, France,
‡
§
ꢀ
ꢀ ꢀ ꢀ ꢀ
Universite de Toulouse, UPS, INPT, F-31077 Toulouse, France, and Laboratoire “Heteroelements et
ꢀ
coordination”, UMR CNRS 7653 (DCPH), Departement de Chimie Ecole Polytechnique,
91128 Palaiseau Cedex, France
Received November 30, 2009
This work describes the synthesis of three key intermediates of
Noyori-type catalytic systems that are active precatalysts for the
transfer hydrogenation of acetophenone. Isolation of the cationic
chloro(dihydrogen) complex [RuCl(H2)(H2NNPP)(PCy3)][BArf4]
provides a facile synthetic route to the corresponding cationic
and neutral hydrido complexes, and the series highlights the links
between hydride/dihydrogen and amine/amido ligands in neutral
and cationic species.
N ligand capable of acting as a hydrogen acceptor and/or
donor, the literature now provides a wide variety of sys-
tems in which the “NH effect” is predominant.1a,2 In this
area, ruthenium is the metal of choice, despite major
advances recently obtained with other metals, most remark-
ably with iron.3 A number of systems aimed at develo-
ping new ligands favoring such a “NH effect” have been
designed. Mechanistic information has been gained over
the years, but the distinction between various pathways
involving hydride or dihydride species and amine or amido
ligands through inner- or outer-sphere mechanisms is still
difficult. Moreover, the intermediacy of dihydrogen species
remains scarce, despite their possible role in transfer hydro-
genation reactions.1a,2n,4
Some of us have previously reported the synthesis of an
aminophosphonium salt [H2NNHPP][Br] (with H2NNHPP=
H2NC6H4NHPPh2CH2PPh2), which after deprotonation
and reaction with RuCl2(PPh3)4 led to the formation of a
dichloride complex incorporating a tridentate iminophos-
phoranephosphineamine ligand.5 The corresponding hydri-
doamido species RuH(HNNPP)(PPh3) could then be obtai-
ned, and the two complexes were found to catalyze the
transfer hydrogenation of acetophenone with moderate acti-
vity. We now describe a system based on the aminophos-
phonium salt, which allows us to isolate three key species that
are active catalyst precursors for the transfer hydrogenation
of ketones but, more importantly, a system highlighting the
Transfer hydrogenation of ketones by using an alcohol,
preferably isopropyl alcohol, is an interesting alternative to
the classical hydrogenation process requiring the use of
dihydrogen gas.1 Following the pioneering work of Noyori
on metal centers having in their coordination sphere a
*To whom correspondence should be addressed. E-mail:sylviane.sabo@
lcc-toulouse.fr.
(1) (a) Clapham, S. E.; Hadzovic, A.; Morris, R. Coord. Chem. Rev. 2004,
248, 2201. (b) Palmer, M. J.; Wills, M. Tetrahedron: Asymmetry 1999, 10, 2045.
(2) (a) Casey, C. P.; Johnson, J. B. J. Org. Chem. 2003, 68, 1998.
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(b) Baratta, W.; Siega, K.; Rigo, P. Chem. Eur. J. 2007, 13, 7479. (c) Carrion,
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M. C.; Sepꢀulveda, F.; Jalon, F. A.; Manzano, B. R.; Rodríguez, A. M.
Organometallics 2009, 28, 3822. (d) Del Zotto, A.; Baratta, W.; Ballico, M.;
Herdtweck, E.; Rigo, P. Organometallics 2007, 26, 5636. (e) Baratta, W.; Ballico,
M.; Del Zotto, A.; Herdtweck, E.; Magnolia, S.; Peloso, R.; Siega, K.; Toniutti,
M.; Zangrando, E.; Rigo, P. Organometallics 2009, 28, 4421. (f) Pannetier, N.;
Sortais, J.-B.; Dieng, P. S.; Barloy, L.; Sirlin, C.; Pfeffer, M. Organometallics
2008, 27, 5852. (g) Ikariya, T.; Blacker, A. J. Acc. Chem. Res. 2007, 40, 1300.
(h) Hems, W. P.; Groarke, M.; Zanotti-Gerosa, A.; Grasa, G. A. Acc. Chem. Res.
2007, 40, 1340. (i) Hadzovic, A.; Song, D.; MacLaughlin, C. M.; Morris, R. H.
Organometallics 2007, 26, 5987. (j) Samec, J. S. M.; Backvall, J.-E.; Andersson,
P. G.; Brandt, P. Chem. Soc. Rev. 2006, 35, 237. (k) Ito, M.; Osaka, A.;
Kobayashi, C.; Shiibashi, A.; Ikariya, T. Organometallics 2009, 28, 390.
(l) Ito, M.; Ikariya, T. Chem. Commun. 2007, 5134. (m) Ito, M.; Sakaguchi,
A.; Kobayashi, O.; Ikariya, T. J. Am. Chem. Soc. 2007, 129, 290. (n) Ohkuma, T.;
Utsumi, N.; Tsutsumi, K.; Murata, K.; Sandoval, C.; Noyori, R. J. Am. Chem.
Soc. 2006, 128, 8724. (o) Noyori, R.; Yamakawa, M.; Hashiguchi, S. J. Org.
Chem. 2001, 66, 7931. (p) 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. (q) Yamakawa, M.; Ito, M.; Noyori, R.
J. Am. Chem. Soc. 2000, 122, 1466. (r) Noyori, R.; Hashiguchi, S. Acc. Chem.
Res. 1997, 30, 97. (s) Hamilton, R. J.; Bergens, S. H. J. Am. Chem. Soc. 2008,
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(3) (a) Mikhailine, A.; Lough, A. J.; Morris, R. H. J. Am. Chem. Soc.
2009, 131, 1394 and references cited therein.(b) Buchard, A.; Heuclin, H.;
Auffrant, A.; Goff, X. F. L.; Le Floch, P. Dalton Trans. 2009, 1659.
(4) (a) Abbel, R.; Abdur-Rashid, K.; Faatz, M.; Hadzovic, A.; Lough,
A. J.; Morris, R. H. J. Am. Chem. Soc. 2005, 127, 1870. (b) Abdur-Rashid, K.;
Clapham, S. E.; Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H. J. Am.
Chem. Soc. 2002, 124, 15104. (c) Amoroso, D.; Jabri, A.; Yap, G. P. A.; Gusev,
D. G.; Dos Santos, E. N.; Fogg, D. E. Organometallics 2004, 23, 4047. (d) Casey,
C. P.; Beetner, S. E.; Johnson, J. B. J. Am. Chem. Soc. 2008, 130, 2285. (e) Chen,
Y.; Tang, Y.; Liu, S.; Lei, M.; Fang, W. Organometallics 2008, 28, 2078.
(f) Hamilton, R. J.; Leong, C. G.; Bigam, G.; Miskolzie, M.; Bergens, S. H.
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Organometallics 2006, 25, 315.
r
pubs.acs.org/IC
Published on Web 01/22/2010
2010 American Chemical Society

Communication
Inorganic Chemistry, Vol. 49, No. 4, 2010 1311
Scheme 1. Synthesis of the Three Catalyst Precursors 3-5
˚
Figure 1. X-ray structures and selected bond distances (A) and angles
links between hydride/dihydrogen and amine/amido ligands
in neutral and cationic species.
(deg) of cationic complexes 3 (left) and 4 (right) (anions omitted for cla-
rity): Ru-N1, 2.1591(19), 2.137(3); Ru-N2, 2.164(2), 2.183(3); Ru-P2,
2.2864(6), 2.2254(9); Ru-P3, 2.3506(7), 2.2935(9); N1-Ru-N2, 77.40(8),
77.25(11); N1-Ru-P2, 85.19(5), 86.32(8); N2-Ru-P2, 161.14(6),
162.94(9); N1-Ru-P3, 173.11(5), 170.15(8); N2-Ru-P3, 96.51(6),
97.10(8); P2-Ru-P3, 101.22(2), 99.80(3).
The aminophosphonium BArf4 salt [H2NNHPP][BArf4]
(1) was simply prepared from the bromine salt by anion
exchange with NaBArf4 (BArf4 = B(3,5-C6H3(CF3)2)4). 1
was deprotonated in situ by addition to the hydridochloro-
(dihydrogen) complex RuHCl(H2)(PCy3)2 (2).6 Dihydro-
gen evolution was observed, and the new cationic chloro-
(dihydrogen) complex [RuCl(H2)(H2NNPP)(PCy3)][BArf4]
(3) was isolated in very good yield (Scheme 1).
It should be noted that the hydride Hy1 and the nitrogen
proton Hy2 are pointing in the same direction and the dis-
˚
tance of 2.61 A could favor a subsequent concerted transfer.
Finally, the neutral hydrido(amido) complex RuH(HN-
NPP)(PCy3) (5) could be obtained as a red powder by three
synthetic pathways: either by adding 1 or 2 equiv of KOtBu to
4 or 3, respectively, or by passing a Et2O solution of 3 through
an aluminum oxide column and using THF as the final
eluent. 5 is analogous to the PPh3 complex previously
reported,5 with, in particular, a doublet of doublets in the
hydride region at δ -24.00 and a singlet at δ 6.00 for the
amido group. The PPh3 complex was previously character-
ized by X-ray diffraction, and we propose a similar structure
for our PCy3 complex 5.
3 was characterized by elemental analysis, NMR, and
X-ray crystallography. The dihydrogen ligand resonates at
δ -10.23 with a T1 min value of 28 ms at 500 MHz at 278 K.
The amineligand appears asan AB pattern at δ 5.99 and 4.72.
The X-ray structure confirms the deprotonation of the initial
NH group and shows a ruthenium in a pseudooctahedral
geometry with a dihydrogen ligand trans to a chloride (Figure 1).
The dihydrogen ligand displays a short Hy1-Hy2 distance
˚
of 0.75(7) A; however, the quality of the data is not sufficient
to rely on such a short distance. Better evaluation can be
obtained in such a case from the T1 min NMR value, leading
Complexes 3-5 were found to be active precatalysts for the
transfer hydrogenation of acetophenone using an isopropyl
alcohol solution at 80 °C. The main results are summarized in
Table 1.
7
˚
to an estimated distance of 0.90 A in a fast-rotation regime.
There are very few chloro(dihydrogen) ruthenium complexes
that have been characterized by X-ray diffraction.8 In a very
qualitative way, it seems reasonable to propose that 3 dis-
plays a dihydrogen acidity similar to that found in other
[RuCl(H2)(P2N2)][X] compounds, as reported by Morris
et al.8a As observed in other chlororuthenium complexes
incorporating amino ligands,8a there is an intramolecular
Cl1 Hy3N2 hydrogen bond with a Cl1 Hy3 distance of
Similar activities were observed at 80 °C for the three
complexes tested under the same conditions (entries 1-3).
Catalytic experiments carried out with compounds 3-5
always led to precipitation of a large quantity of 5 a few
minutes after immersion of the reaction vessel into the 80 °C
preheated oil bath. Conversions were high and reproducible
(turnover frequency of around 9.3 ꢀ 10-3 s-1 at 50% con-
version), although the concentration of the active species was
significantly lower than that represented by the quantity of
3-5 used because of the insolubility of precipitated 5. 96%
conversion of acetophenone was observed reproducibly with
all initiators 3-5. In the absence of compounds 3-5, transfer
hydrogenation was still observed, but the activity was lower,
with 29% conversion being obtained after 24 h (entry 4).
Base-catalyzed hydrogenation of ketones is well documented.9
Compounds 4 and 5 are even active in the absence of
sodium, although conversion is significantly lower (entries 5
and 6). A basic medium is required for hydride formation
from compound 3. However, any further role of the base
remains so far unclear but might affect the acidity of the
hydrogen atoms and thus hydrogen transfer. Conversion
after 3 h was not improved by the presence of a dynamic
3 3 3
3 3 3
˚
2.63 A.
Passing a tetrahydrofuran (THF) solution of 3 through an
aluminum oxide column or adding 1 equiv of KOtBu led to
the isolation of a red solid [RuH(H2NNPP)(PCy3)][BArf4]
(4), characterized as an unsaturated cationic hydrido com-
plex by elemental analysis, NMR, and X-ray diffraction. The
1H NMR spectrum shows a very shielded doublet of doublets
at δ -31.15, in agreement with a hydride trans to a vacant site
(see the Supporting Information). As depicted in Figure 1,
the X-ray structure of 4 shows a square-pyramidal ruthenium
center with a hydride in the apical position. 4 results from
dehydrochlorination of 3, and the geometrical parameters
of the H2NNPP ligand are very similar in the two complexes.
(6) Christ, M. L.; Sabo-Etienne, S.; Chaudret, B. Organometallics 1994,
13, 3800.
(7) Kubas, G. J. Metal Dihydrogen and σ-Bond Complexes; Kluwer
Academic/Plenum Publishers: New York, 2001.
(8) (a) Li, T.; Lough, A. J.; Zuccaccia, C.; Macchioni, A.; Morris, R. H.
Can. J. Chem. 2006, 84, 164. (b) Lachaize, S.; Caballero, A.; Vendier, L.; Sabo-
Etienne, S. Organometallics 2007, 26, 3713. (c) Dutta, S.; Jagirdar, B. R.; Nethaji,
M. Inorg. Chem. 2008, 47, 548.
(9) (a) Walling, C.; Bollyky, L. J. Am. Chem. Soc. 1964, 86, 3750.
(b) Berkessel, A.; Schubert, T. J. S.; Muller, T. N. J. Am. Chem. Soc. 2002,
ꢀ
ꢀ
124, 8693. (c) Carrion, M. C.; Jalon, F. A.; Manzano, B. R.; Rodríguez, A. M.;
Sepꢀulveda, F.; Maestro, M. Eur. J. Inorg. Chem. 2007, 3961.

1312 Inorganic Chemistry, Vol. 49, No. 4, 2010
Picot et al.
Table 1. Catalytic Transfer Hydrogenation of Acetophenone with Complexes
3-5 at 80 °C
in place of [BArf4]-, was readily formed upon the addition of
isopropyl alcohol to 5, as shown by 1H and 31P NMR data.
Compound 5 also yields compound 4 upon reaction with
1 equiv of HBArf4 [HBArf4=Arf4B-(Et2O)2Hþ] at ambient
temperature. 4 is stable with excess HBArf4 after prolonged
time periods in solution. Notably, compounds 4 and 5 did not
react with acetophenone in THF-d8 at ambient temperature
or at 55 °C. No change in the 1H and 31P NMR spectra could
be seen when monitoring the reaction of 4 in the presence of
acetophenone, isopropyl alcohol, and sodium at ambient
temperature or 55 °C over a period of 1.5 h, but phenylethyl-
ethanol was produced (1H NMR and GC). Notably also, 5 is
conversion (%)
entry
catalyst
3 h
6 h
24 h
1a
2a
3a
4b
5c
6c
7d
8e
3
4
5
84
83
80
4
94
93
91
9
96
95
96
29
79
84
82
96
4
5
4
4
4
8
18
22
52
30
40
84
i
stable in the presence of PrONa, whereas 4 leads to the
a Conditions: 100 equiv of acetophenone (146 μL, 1.25 mmol),10
equiv of sodium (2.9 mg, 0.125 mmol), 100 equiv of veratrole internal
standard (160 μL, 1.25 mmol), and 1 equiv of precatalyst (0.0125 mmol)
in 5 mL of iPrOH at 80 °C. b Conditions: same as those for footnote a but
in the absence of compounds 3-5. c Conditions: same as those for foot-
note a but in the absence of sodium. d Conditions: same as those for
footnote a but with 6.25 mmol of acetophenone. e Conditions: same as
those for footnote a but with the addition of PCy3 (0.125 mmol).
i
formation of 5 when exposed to PrONa, both at room
temperature and at 55 °C. No evidence for the intermediacy
of an alkoxide species could be demonstrated during all of
our mechanistic investigations. Finally, an aliquot of the
catalytic mixture with compound 4 as the catalyst precursor
was taken after 2 h and analyzed by NMR at ambient
temperature. A large quantity of 5 was observed as a
precipitate, and no other species could be detected by 31P
NMR.
dihydrogen atmosphere (3 bar). Conversions obtained over a
24 h period with 4 upon the addition of 500 equiv of aceto-
phenone are shown in entry 7. The kinetics with precatalyst 4
were investigated, under the standard experimental condi-
tions discussed. A semilogarithmic plot of ln [acetophenone]
vs time (s) highlights a first-order dependence on the sub-
strate concentration with no induction period (kapp =1.44ꢀ
10-4 s-1; linear fit R2 = 0.997). Temperature-dependent
studies between 60 and 80 °C allow for extraction of the
activation parameters ΔHq = 71(3) kJ mol-1 and ΔSq =
-121(9) J K-1 mol-1 from the Eyring plot for the hydro-
genation of acetophenone with 4 (see the Supporting Infor-
mation). In addition, ΔGq298=107(6) kJ mol-1 was obtained.
The negative entropy indicates a highly ordered transition
state with association of the complex and the substrate. The
addition of PCy3 (1 equiv or excess) only lowers the initial
rate of hydrogenation, and high conversion is finally obtai-
ned after 24 h (96%; entry 8), thus ruling out the dissociation
of PCy3 as a key event in the catalysis. In order to gain
some information on chemoselectivity, the hydrogenation of
5-hexene-2-one was tested by using complex 4 as a precatalyst
in an isopropyl alcohol solution at 80 °C, under conditions
analogous to those discussed in Table 1, footnote a. A mix-
ture of hydrogenation products was obtained after 6 h (eq 1).
The predominant species, 5-hexen-2-ol, as characterized by
1H and 13C NMR, gas chromatography-mass spectrometry
(GC-MS), and GC indicates preferential hydrogenation of
the ketone functionality with 4.
In conclusion, isolation of the chloro(dihydrogen)amino
cationic complex 3 prior to formation of the hydridoamino
cationic complex 4 and finally the neutral hydridoamido
complex 5 provides useful insight into key intermediates of
Noyori-type catalytic systems. The three complexes act as
active precursors for the transfer hydrogenation of acetophe-
none. All of our observations are consistent with a transfer
hydrogenation pathway and rule out a dihydrogen hydro-
genation pathway, as quoted by Morris et al.1a We have
shown that dehydrochlorination is readily achieved from the
dihydrogen complex 3. In this chloro(dihydrogen) complex,
the dihydrogen ligand is more acidic than that in a corre-
sponding hydrido(dihydrogen) species because the acidity of
the dihydrogen ligand is highly dependent on the withdraw-
ing properties of the trans ligand.7 In contrast, subsequent
deprotonation of the amino ligand in4 is preferred, leading to
formation of the neutral amido complex 5. Remarkably,
reprotonation of 5 to 4 is easily achieved in the presence of
isopropyl alcohol, a key event related to the catalytic transfer
hydrogenation system. Noother intermediate could beobser-
ved during the course of the catalytic reaction. All of the
experimental data that we have are in favor of a TOL mecha-
nism,1a transfer hydrogenation with outer-sphere hydride
transfer assisted by the ligand.
Acknowledgment. We thank the ANR (Programme
blanc “In-Out Tuning” ANR-06-BLAN-0060) and the
CNRS for support.
Supporting Information Available: Full details of the synthesis
and characterization of 3-5, standard catalytic procedures,
kinetic data, and X-ray crystallographic data in CIF format
for 3 and 4. This material is available free of charge via the
Internet at http://pubs.acs.org.
We have performed a few stoichiometric reactions on the
NMR scale in order to gain some more mechanistic informa-
tion. We found that a species analogous to 4, but with [OiPr]-