A formally zwitterionic ruthenium catalyst precursor for the transfer hydrogenation of ketones that does not feature an ancillary ligand N-H dunctionality

Article abstract of DOI:10.1002/anie.200700345

Fast and furious: Even without the assistance of an N-H donor ligand, the Ra complex shown in the scheme is a remarkably active precatalyst for the transfer hydrogenation of ketones in basic iPrOH (R,R′ = alkyl oraryl), providing near-quantitative yields within minutes and exhibiting consistently high turnover frequencies (10⁴ to 10⁵ h^-1) for a diverse range of substrates. (Chemical Equation Presented).

Full text of DOI:10.1002/anie.200700345

Communications
DOI: 10.1002/anie.200700345
Transfer Hydrogenation
A Formally Zwitterionic Ruthenium Catalyst Precursor for the
Transfer Hydrogenation of Ketones that Does Not Feature an Ancillary
À
Ligand N H Functionality**
Rylan J. Lundgren, Matthew A. Rankin, Robert McDonald, Gabriele Schatte, and
Mark Stradiotto*
The ruthenium-mediated transfer hydrogenation (TH) of
ketones under basic conditions employing iPrOH or other H2-
donor solvents has emerged as an atom-economical method-
ology for the synthesis of secondary alcohols.[1] Although the
catalytic abilities of Ru complexes supported by a range of
structurally diverse ancillary ligands have been evaluated,
enabled through the development of ancillary ligands featur-
À
ing N H donors, such a structural prerequisite limits the
future design of alternative classes of Ru-based TH catalysts
for use in mediating new and increasingly challenging
substrate transformations. In this context, the identification
À
of novel ligation strategies that do not rely on the N H effect
À
precatalysts featuring a Ru NH linkage commonly offer the
and which give rise to highly active and selective Ru-based
TH catalysts represents an important goal in modern catalysis
research.[1,2]
highest levels of activity and selectivity in the TH of
ketones.[1,2] In the case of the landmark {(h6-arene)Ru}
catalysts featuring chiral diamido ligands developed by
Encouraged by the catalytic abilities of Noyoriꢀs [(h6-
arene)Ru(diamido)] complexes,[3] and in light of the obser-
vation that the pairing of P- and N-donor ligands is a common
feature in several highly effective Ru-based TH cata-
Noyori and co-workers,[3] this now well-established N H
À
effect has been rationalized in terms of an outer-sphere TH
mechanism involving the concerted transfer of H2 from a
{(H)Ru NH2R} intermediate to a ketone substrate.[1c,3] More
lysts,[1c,2b,4] we became interested in developing new non-N
À
À
recently, Baratta and co-workers have reported an alternative
class of precatalysts supported by 2-(aminomethyl)pyridine
(ampy) coligands that give rise to the most active catalysts
known for the TH of ketones.[4] For both of these prominent
Ru-based TH catalyst systems, the inferior performance
H [(h6-arene)Ru(k2-P,N)(Cl)] precatalysts for use in the TH
of ketones. In the context of our research comparing the
reactivity properties of late-transition-metal cations and
zwitterions derived from 1-H,[5] we identified the cationic
complexes 2+XÀ and the zwitterion 3 as being worthwhile
candidates for catalytic studies (Scheme 1). Herein, we report
À
exhibited by the analogous {Ru NMe2R} species underscores
the crucial role that the ancillary ligand NH2 terminus plays in
enhancing catalyst activity and selectivity.[3c,4] Notwithstand-
ing the advancements in Ru-mediated TH that have been
[*] R. J. Lundgren,[+] M. A. Rankin,[+] Prof. Dr. M. Stradiotto
Department of Chemistry
Dalhousie University
Halifax, NS B3H4J3 (Canada)
Fax: (+1)902-494-1310
E-mail: mark.stradiotto@dal.ca
Scheme 1. Synthesis of 2+XÀ and 3. a) 0.5 [{h6-p-cymene)RuCl2}2] in
CH2Cl2 (X=Cl), or 0.5 [{h6-p-cymene)RuCl2}2] with AgX (X=BF4,
SO3CF3) or Li(Et2O)2.5B(C6F5)4 (X=B(C6F5)4) in MeCN; b) 1) 0.5 [{h6-p-
cymene)RuCl2}2] in CH2Cl2, 2) K2CO3 in THF.
Dr. R. McDonald
X-Ray Crystallography Laboratory
Department of Chemistry
University of Alberta
Edmonton, AB T6G2G2 (Canada)
Dr. G. Schatte
Saskatchewan Structural Sciences Centre
University of Saskatchewan
Saskatoon, SK S7N5C9 (Canada)
the synthesis and characterization of 2+XÀ and 3 as well as
their application as precatalysts in the TH of ketones. Despite
À
lacking an ancillary ligand N H functionality, complex 3 is
[+] These co-authors contributed equally to this work.
among the most active ketone TH precatalysts known,
providing near-quantitative conversions and exhibiting con-
sistently high turnover frequencies (TOFs; up to 220000 hÀ1)
for a diversity of alkyl and aryl ketone substrates at low
catalyst loadings. Furthermore, while the anticipated zwitter-
ionic hydrido complex 4 is formed quantitatively upon
treatment of 3 with KOtBu in iPrOH, reactivity studies
confirm that this hydrido species is not the active catalyst in
TH reactions employing 3 as a precatalyst.
[**] Acknowledgment is made to the Natural Sciences and Engineering
Research Council of Canada (including a Postgraduate Scholarship
for M.A.R.), the Canada Foundation for Innovation, the Nova Scotia
Research and Innovation Trust Fund, and Dalhousie University for
their generous support of this work. We also thank Dr. Michael
Lumsden (AtlanticRegion MagneticResonance Center, Dalhousie)
for assistance in the acquisition of NMR data.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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The reduction of acetophenone in refluxing iPrOH in the
presence of KOtBu was selected to assess the catalytic utility
of 2+XÀ and 3 (0.05 mol%, denoted [Ru]) for the TH of
ketones [Eq. (1)].[6d] The cations 2+XÀ (X = Cl, BF4, SO3CF3,
or B(C6F5)4) exhibited modest activity, with conversions of
acetophenone to 1-phenylethanol ranging between 4 and
23% after 15 min.[6b] In contrast, the zwitterion 3 proved to be
an extremely active precatalyst for this reaction, providing
99% conversion into 1-phenylethanol after only 5 min
(Table 1, entry 1), and with a TOF value (180000 hÀ1) that is
among the highest reported for the TH of ketones.[2c–e,4]
Excellent catalytic performance was also observed when
employing 0.025 mol% 3 in refluxing iPrOH (93%, 15 min,
TOF = 170000 hÀ1) or by use of 0.2 mol% 3 at 458C (97%,
15 h).
Figure 1. ORTEP diagrams for 2+BF4À, 3·(OC4H8)2, and 4; thermal
ellipsoids set at 50% probability, selected hydrogen atoms and the
THF solvates have been omitted for clarity. Selected bond lengths [Š]
for 2+BF4À and 3·(OC4H8)2 (the latter given in parentheses): Ru-P
2.3503(8) (2.374(1)), Ru-N 2.228(2) (2.218(4)), Ru-Cl 2.3909(8)
(2.390(1)), P-C3 1.810(3) (1.755(5)), N-C2 1.450(4) (1.473(6)), C1-C2
1.501(4) (1.383(7)), C2-C3 1.341(4) (1.413(7)). Selected bond
lengths [Š] for 4: Ru-P 2.297(1), Ru-N 2.206(3), P-C3 1.757(4), N-C2
1.475(5), C1-C2 1.379(5), C2-C3 1.408(5).
Addition of 1-H[6a] to 0.5 equiv-
alents of [{(h6-p-cymene)RuCl2}2]
afforded 2+ClÀ, isolated in 93%
yield, while the corresponding
2+XÀ (X = BF4, SO3CF3, or B-
(C6F5)4) complexes were prepared
and isolated in 88–91% yield by
Table 1: Transfer hydrogenation of ketones (0.1m) with 3 (0.05 mol%) and KOtBu (1 mol%) in iPrOH.[a]
Entry
Ketone
t [min]
Conversion [%][b]
TOF [hÀ1 [c]
]
1
5
99
180000
220000
2
3
5
98[d]
94
treatment
of
[(h6-p-cymene)-
(CH3CN)2RuCl]+XÀ
(formed
in situ) with 1-H.[6b] As well, 2+ClÀ
15
180000
was transformed cleanly into the
zwitterion
3 upon exposure to
K2CO3, thereby allowing for the
isolation of 3 in 81% yield follow-
ing workup. The k2-P,N connectiv-
ity in both 2+XÀ and 3, which was
determined initially on the basis of
solution NMR spectroscopy data,
was confirmed by use of X-ray
diffraction techniques;[6c] the crys-
4
5
6
7
8
5
15
15
5
97
95
99
97
99
180000
125000
57000
À
tal structures of 2+BF4 and 3·-
(OC4H8)2 (Figure 1) can be com-
pared with those of other [(h6-
arene)Ru(k2-P,N)(Cl)] complex-
es.[2d,7] Whereas the Ru coordina-
tion environments in 2+BF4À and 3
are similar, the interatomic distan-
ces within the backbone of the
P,N ligands differ significantly;
pronounced bond-length alterna-
120000
54000
5
9
5
99
99
91000
10
15
150000
tion is observed within the indene
fragment of 2+BF4
, while the
À
[a] 0.8 mmol scale (ketones (0.1m), 3 (0.05 mol%), KOtBu (1 mol%)) in refluxing iPrOH. [b] Con-
version to the secondary alcohol determined on the basis of GC-FID data at time t stated in column 3.
[c] Turnover frequency (mole of ketone converted into alcohol per mole of catalyst per hour) measured at
20 seconds (50% conversion for entry 1). [d] When the reaction was conducted on a 2.0 mmol scale,
Ph2CH(OH) was isolated with 96% yield.
indenide unit in 3 exhibits a more
delocalized structure, in keeping
with
a
10p electron indenide
framework.[5]
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Communications
Complex 3 also proved to be an effective precatalyst for
Ru species for the TH of ketones in basic iPrOH. In fact, 3 is
the TH of other diaryl (Table 1, entries 2 to 4), aryl alkyl
(Table 1, entries 5 to 7), and dialkyl (Table 1, entries 8 to 10)
ketones. Notably, the ability of 3 to mediate the rapid (5–
15 min) reduction of such structurally diverse ketones with
high conversions (94–99%) and with remarkably high TOF
values (54000–220000 hÀ1) is unprecedented for a precatalyst
the most active in a limited series of precatalysts for ketone
À
TH that do not exploit Ru NH interactions, providing near-
quantitative conversions in minutes for a range of ketone
substrates at low catalyst loading and with TOF values as high
as 220000 hÀ1. Interestingly, all previously reported cationic
ketone TH precatalysts of the type [(h6-arene)Ru(k2-
P,N)(Cl)]+XÀ feature neutral P,N ligands, and are commonly
102 to 103 times less active than 3.[10] Such observations, when
considered in the context of the diminished catalytic abilities
of 2+XÀ relative to 3, suggest that the anionic nature of the
P,N ligand 1 may play an important role in engendering
desirable reactivity properties to ketone TH catalysts formed
in situ from 3. Experimentation directed toward elucidating
the source of the observed reactivity differences between
2+XÀ and 3, as well as identifying the catalytically active
intermediates that are generated in ketone TH reactions
featuring these precatalysts, is ongoing.
À
not featuring a Ru NH linkage. To our knowledge, the
activity afforded by 3 in ketone TH is surpassed only by a
À
selection of N H-containing {Ru(ampy)} complexes reported
recently by Baratta and co-workers.[4] The practical utility of 3
(0.01mol%) was demonstrated through the 0.91g scale
reduction of benzophenone to afford benzhydrol (91%
conversion by GC-FID (gas chromatography–flame ioniza-
tion detector); isolated in 82% yield).
To gain insight into the divergent catalytic performance of
2+XÀ and 3 in the TH of acetophenone, we sought to
determine the fate of 2+ClÀ and 3 upon heating at reflux for
10 min in an iPrOH solution containing 20 equivalents of
KOtBu; in both cases, quantitative conversion into a single,
phosphorus-containing, product 4 was detected spectroscopi-
cally [Eq. (2)]. Complex 4 was prepared rationally from 3
Received: January 25, 2007
Revised: March 30, 2007
Published online: May 16, 2007
Keywords: homogeneous catalysis · ketones · ruthenium ·
.
transfer hydrogenation · zwitterions
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À
feature Ru NH2R linkages, see: a) M. T. Reetz, X. Li, J. Am.
(employing 1equiv of KO tBu in iPrOH) and isolated in 71%
yield; both NMR spectroscopy and X-ray diffraction data
support the identity of 4 as the hydrido analogue of 3
(Figure 1). We have confirmed independently that 2+ClÀ is
transformed cleanly into 3 upon net extrusion of HCl with
1equivalent of KO tBu in THF, and the conversion of 3 to 4 in
basic iPrOH can be viewed as arising from the reaction of
KOiPr with 3 to give [(h6-p-cymene)Ru(k2-P,N-1)(OiPr)]
with subsequent b-H elimination and loss of acetone. The
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[6] a) The ligand 1-H is available from Strem Chemicals Inc; b) The
Supporting Information contains experimental procedures and
characterization data for all new compounds; c) CCDC-630880
(2+BF4À), CCDC-630881( 3·(OC4H8)2), and CCDC-630879 (4)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
À
À
formation of Ru H complexes from {Ru Cl} precursors
under such conditions is well-established,[8] and the prepon-
derance of empirical and theoretical evidence points to
hydrido species as the active catalysts formed in situ from
À
Ru Cl precatalysts during the course of ketone TH reactions
conducted in basic iPrOH.[1,9] In this regard, our observation
that 4 (0.05 or 0.2 mol%) is completely inactive for ketone
TH, both in the presence and absence of added KOtBu, is
surprising. Evidently, the formation of 4 represents a catalyst
deactivation pathway in ketone TH reactions employing 2+XÀ
or 3 as precatalysts. However, such an observation does not
rule out the involvement of alternative hydrido species as
catalysts in reactions employing precatalysts 2+XÀ or 3,
À
including species that might arise from intramolecular C H
activation involving a ligand NMe fragment.[5a]
In summary, donor-substituted indenides, such as 1 in the
zwitterion 3, are established as a promising new class of non-
À
N H ancillary ligands for use in constructing highly active
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Angewandte
Chemie
À
request/cif. d) Precatalyst 3 exhibited no activity in the absence
of KOtBu.
[7] For example, see: a) C. Standfest-Hauser, C. Slugovc, K.
Mereiter, R. Schmid, K. Kirchner, L. Xiao, W. Weissensteiner,
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Naud, S. J. Rettig, New J. Chem. 2001, 25, 32.
[9] {Ru H} species have proven capable of mediating the TH of
ketones in the absence of base, see: V. Cadierno, P. Crochet, J.
Dꢁez, S. E. Garcꢁa-Garrido, J. Gimeno, Organometallics 2004, 23,
4836, and references therein.
[10] For selected examples, see: a) V. Cadierno, P. Crochet, J. Garcꢁa-
ꢂlvarez, S. E. Garcꢁa-Garrido, J. Gimeno, J. Organomet. Chem.
2002, 663, 32; b) Ref. [7].
[8] S. P. Nolan, T. R. Belderrain, R. H. Grubbs, Organometallics
1997, 16, 5569.
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