(R)-binap-mediated asymmetric hydrogenation with a rhodacarborane catalyst in ionic-liquid media

Article abstract of DOI:10.1002/anie.200351273

Unsymmetrical aryl ketones undergo asymmetric hydrogenation in ionic-liquid media in the presence of (R)-binap and a rhodacarborane catalyst derived from the suicide precursor 1 (see scheme). Ketones that are poor substrates for other methods can be hydro

Full text of DOI:10.1002/anie.200351273

Communications
Asymmetric Hydrogenation
(R)-Binap-Mediated Asymmetric Hydrogenation
with a Rhodacarborane Catalyst in Ionic-Liquid
Media**
Zhu Yinghuai,* Keith Carpenter, Ching Chi Bun,
Stefan Bahnmueller, Chan Pek Ke,*
Venugopal Shanmugham Srid, Leong Weng Kee, and
M. Frederick Hawthorne*
The reduction of ketones to alcohols under homogeneous
catalysis is an important synthetic step in the chemical
industry, and recent emphasis placed upon the asymmetric
hydrogenation of prochiral substrates as pharmaceutical
precursors enhances the importance of this chemistry.[1]
Aside from the discovery of new asymmetric hydrogenation
reactions, there remains the challenge of separating the
reaction products from an expensive chiral catalyst[2] for
purposes of recycling. Novel reaction media or polymer-
immobilized catalysts may play an important role in this
regard. More specifically, salts that are liquids at ambient
temperature have received much attention because of their
potential as direct replacements for conventional solvents and
as a means to immobilize transition-metal catalysts in biphasic
processes.[3–5] Many organic reactions have been carried out in
ionic liquids, such as hydrogenation,[6,7] oxidation,[8] epoxida-
tion,[9] and hydroformylation reactions.[10] The use of ionic-
liquid media for other classic transformations, such as
Friedel–Crafts acylation[11] and alkylation[12] reactions, allyla-
tion,[13,14] Diels–Alder,[15] and Heck[16] reactions, as well as
Suzuki[17] and Trost–Tsuji coupling[18] reactions in ionic liquids
have also been reported. In contrast, relatively little attention
has been given to the use of ionic-liquid reaction media in the
catalytic hydrogenation of ketones.
As has been repeatedly demonstrated in the past, ketones
do not easily undergo homogeneous hydrogenation in the
presence of simple transition-metal catalysts. Rhodium was
successfully employed for this purpose under 1 atm of H2, in
[*] Z. Yinghuai, K. Carpenter, C. C. Bun, S. Bahnmueller
Institute of Chemical and Engineering Sciences, Block 28
Ayer Rajah Crescent, #02-08, Singapore 139959 (Singapore)
Fax: (+65)6873-4805
E-mail: zhu_yinghuai@ices.a-star.edu.sg
C. P. Ke, V. S. Srid, L. W. Kee
Department of Chemistry, National University of Singapore
10 Kent Ridge Crescent, Singapore 119260 (Singapore)
Fax: (+65)6779-1691
E-mail: chmlwk@nus.edu.sg
M. F. Hawthorne
Department of Chemistry and Biochemistry
University of California
Los Angeles, CA 90095 (USA)
Fax: (+1)310-825-5490
E-mail: mfh@chem.ucla.edu
[**] This research was generously supported by an ICES grant, A* Star,
Singapore (Z.Y.), and a U.S. National Science Foundation Grant
CHE-0111718 (M.F.H.).
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DOI: 10.1002/anie.200351273
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Angewandte
Chemie
complexes in which the metal center was made electron rich
by using ligands of the fully alkylated bidentate diphosphane
type.[1] In contrast with these results, we describe herein 1) the
hydrogenation of aromatic ketones in the presence of a
catalyst derived from a previously described rhodacarborane
a potential new route to the corresponding alcohols and the
opportunity to include optically active phosphanes, such as 5,
in the rhodacarborane catalyst system as structural compo-
nents. This modification provided effective chiral catalysts
that promoted the asymmetric hydrogenation of prochiral
ketones under mild conditions. Both acetophenone and ethyl
benzoylformate were hydrogenated in the presence of the
catalyst precursor 1[23] and (R)-binap (150 mol% relative to
1), in the reaction media 2, 3, 4, and tetrahydrofuran at 508C
under H2 (12 atm) within 12 h. In 2, 3, and 4, the desired
products (R)-phenylethanol and ethyl (R)-mandelate were
formed in quantitative chemical yields and with very high
ee values. The use of tetrahydrofuran led to both diminished
chemical yields and diminished ee values. Reaction mixtures
were monitored and product mixtures analyzed by GC.[24]
Typical hydrogenation results for acetophenone are reported
in Table 1, for which reaction rates are shown in Figure 1. The
catalyst and (R)-binap were recycled in the ionic-liquid
experiments by volatilization and removal of the reaction
product under high vacuum, followed by the addition of fresh
ketone. Six such cycles were carried out without degradation
of catalyst activity or selectivity.
catalyst[19] precursor with a suicide alkene ligand: [closo-1,3-
2
¼
{m-(h -3-CH2 CHCH2CH2)}-3-H-3-PPh3-3,1,2-RhC2B9H10] (1);
2) the use of ionic-liquid reaction media: 1-methyl-3-octyli-
midazolium tetrafluoroborate (OMIM+ BF4ꢀ, 2), 1-butyl-3-
methylimidazolium hexafluorophosphate (BMIM+ PF6ꢀ, 3),
and the new liquid salt comprised of 1-carbadodecaborate
ions[20] and N-n-butylpyridinium (BP) ions, BP+ CB11H12ꢀ (4);
3) the introduction of molecular asymmetry in the catalytic
hydrogenation by complexation of the rhodium center of the
catalyst with the optically active (R)-binap ligand, (R)-2,2’-
bis(diphenylphosphanyl)-1,1’-binaphthyl (5); and 4) the com-
parison of these ionic liquids with tetrahydrofuran as reaction
media, and comparison of the performance of the catalyst
derived from 1 with that derived from [{Rh(cod)Cl}2] (cod =
1,5-cyclooctadiene) under otherwise identical conditions.
The robust rhodacarborane catalyst systems developed by
Hawthorne and co-workers,[21] such as [closo-3-H-3,3-(Ph3P)2-
3,1,2-RhC2B9H11], are understood mechanistically in the
hydrogenation and isomerization of alkenes, as well as in
the hydrogenolysis and hydrosilanolysis of alkenyl carbox-
Table 1: Rhodium-catalyzed hydrogenation of acetophenone (A) and
ethyl benzoylformate (B).[a]
ylates. The complex 1 stands out among rhodacarborane
Solvent
Conversion [%][b] ee [%][c]
TOF [hꢀ1 [d]
]
2
¼
catalyst precursors because of its h -3-CH2 CH-(CH2)2
alkene ligand, which is linked to the nido-7,8-C2B9H11
OMIM+ BF4
2
100(A,B)
100(A,B)
97.3(A), 99.3(B) 194(A), 201(B)
97.8(A), 98.2(B) 207(A), 213(B)
99.1(A), 99.5(B) 239(A), 306(B)
91.3(A), 85.7(B) 96(A), 107(B)
ꢀ
2ꢀ
BMIM+ PF6ꢀ 3
dicarbollide module at the 7-vertex. Saturation of this alkenyl
ligand under hydrogenation conditions removes it from the
manifold of competitive ligands and creates a catalyst system
that has only one triphenylphosphane ligand per rhodium
atom, which results in its enhanced reactivity with alkene
substrates. This alkene-hydrogenation catalyst is among the
most reactive known.[19] The corresponding closo rhodacar-
borane catalyst systems, which contain two triphenylphos-
phane ligands per rhodium atom, are also quite active and
robust in alkene hydrogenation.[21] As discussed below, 1 was
used in this study because the bidentate ligand (R)-binap
displaces all ligands originally attached to the rhodium center
of 1 other than the hydride and the dicarbollide, in situ, to
generate an active chiral catalyst. Hydrogenation of the
coordinated suicide alkene ligand present in 1 simplifies this
process.
BP+ CB10H12ꢀ 4 100(A,B)
tetrahydrofuran 82(A), 87(B)
[a] Mole ratio of catalyst/(R)-binap/acetophenone=1:1.5:1000; reaction
conditions: H2 (12atm), 50 8C, 12h; [ 1]=8.1”10ꢀ4 m; [5]=1.21”
10ꢀ3 m. [b] Determined by GC. [c] Determined by GC on a Chirasil DEX-
CB column.[24] [d] Turnover frequency (=moles of hydrogenation product
per mole of Rh per hour) was determined after 3 h.
The application of ionic-liquid media in the hydrogena-
tion of aromatic ketones was explored by using the known
liquid salts 2 and 3 as reaction media. The new liquid salt 4
was also prepared for use in this study, as it was thought that a
Figure 1. The course of acetophenone hydrogenation under standard
ꢀ
ꢀ
beneficial interaction of the B H bonds of the closo-CB11H12
conditions in the ionic-liquid media OMIM+ BF4 (2), BMIM+ PF6 (3),
and BP+ CB11H12ꢀ (4), and in tetrahydrofuran.
ꢀ
ꢀ
ion with the rhodium center in the catalyst derived from 1
may occur, and that 4 should otherwise be chemically inert
under the conditions used. The salt 4 was readily prepared by
the metathesis reaction of N-n-butylpyridinium chloride with
The conversion, ee values, and turnover frequency
observed when 1 and [{Rh(cod)Cl}2] were used as catalyst
precursors in the hydrogenation of acetophenone in the
reaction media 2 and tetrahydrofuran are reported in Table 2.
Thus, the replacement of 1 with [{Rh(cod)Cl}2] as the catalyst
precursor caused a severe decrease in performance in both
reaction media examined. These observations strongly sug-
Cs+ closo-CB11H12 as a solution in CH2Cl2. Pure 4 is a
ꢀ
colorless solid that melts at 218C.[22] This novel ionic liquid
will undoubtedly find use in catalytic reactions other than
those described herein.
The use of the catalyst precursor 1 in the hydrogenation of
aromatic ketones in ionic-liquid reaction media provides both
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Table 2: Hydrogenation of acetophenone catalyzed by [{Rh(cod)Cl}2]
and by 1 in the ionic liquid OMIM+ BF4 2 (I) and in THF (II).[a]
ꢀ
Catalyst
Conversion [%][b]
ee [%][c]
TOF [hꢀ1 [d]
]
1
100(I), 82(II)
17(I), 8(II)
97.3(I), 91.3(II)
10.3(I), 5.7(II)
194(I), 96(II)
16(I), 11(II)
[{Rh(cod)Cl}2]
[a] Mole ratio of catalyst/(R)-binap/acetophenone=1:1.5:1000; reaction
conditions: H2 (12atm), 50 8C, 12h. [b] Determined by GC. [c] Deter-
mined by GC on a Chirasil DEX-CB column.[24] [d] Turnover frequency was
determined after 3 h.
gest that the hydrogenation processes in which 1 and
[{Rh(cod)Cl}2] serve as catalyst precursors differ in their
mechanism. We are as yet unable to explain the significant
increase in performance that results from the substitution of
the ionic liquid 2 for tetrahydrofuran as the reaction medium
for rhodacarborane-catalyzed reactions. However, it seems
likely that an ionic medium better supports zwitterionic
intermediates. The most efficient ionic-liquid reaction
medium studied was 4, which has a large number of available
Scheme 2. Proposed mechanism for the asymmetric hydrogenation of
prochiral ketones in the presence of the rhodacarborane catalysts 12
and/or 14.
ꢀ
B H bonds that may be involved in the reaction, as discussed
below.
As previously established, closo-rhodacarborane catalyst
precursors, such as 8, reductively eliminate RhIII to produce
mixtures of RhI exo-nido isomers, such as 9, in which the
[L2Rh]+ center is attached to the nido anion cage by a pair of
If it is assumed that ketone hydrogenation catalyzed by
rhodacarboranes resembles rhodacarborane-catalyzed alkene
hydrogenation and many other reactions that share its
unusual mechanistic features,[21] the mechanisms shown in
Schemes 1 and 2 can be proposed. The established mecha-
nisms of rhodacarborane-catalyzed reactions[21] involve the
presence of equilibrium concentrations of active zwitterionic
[B-RhL2-H] species formed by the oxidative addition of
ꢀ ꢀ
three-center two-electron Rh H B bonds (Scheme 1). These
species do not provide catalysis by dissociation to active
[L2RhX2]+ (X = electron pair donor) ion-pair species 13, but
rather undergo reversible oxidative addition of RhI to the
ꢀ
coordinated terminal B H bonds. The result is a set of
[L2Rh]+ to electron-rich terminal B H bonds of the many
isoelectronic, isomeric, and substituted variants of the parent
nido-7,8-C2B9H12 ion 6.
catalytically active exo-nido RhIII hydride derivatives 14.
Alkene hydrogenation and related reactions have been shown
to proceed by a metathesis mechanism involving species such
as 14, which are regenerated in a separate
ꢀ
ꢀ
catalytic cycle.[21] In reactions in which 4 was
used as the ionic-liquid medium, reaction of the
ꢀ
solvent closo-CB11H12 ion through its B–H
donors with the [L2RhX2]+ could possibly lead to
the conversion of 9, 13, and 14 into the analogues
10, 11, and 12, respectively. Of the latter group,
species 12 would be expected, by analogy, to
exhibit catalytic activity.
A generalized mechanism for the asymmetric
hydrogenation of the aromatic ketones described
in this study is proposed in Scheme 2. Species 12
and 14 are generalized, as shown, and the
coordination of the ketone is followed by hydride
transfer from the rhodium center of the catalyst to
the carbonyl carbon atom of the ketone. Reversal
of this last step is prevented by rapid irreversible
H2 metathesis, which regenerates the rhodium
hydride species (either 12 or 14). This metathesis
step involves the formal addition of a proton to
the complexed oxygen atom of the alkoxy group
and the simultaneous formal addition of a hydride
ion to RhIII. This process is similar to the observed
metathesis of the RhO(CO)CH3 species involved
in catalytic alkenyl acetate hydrogenolysis.[21] The
Scheme 1. Fate of the rhodacarborane catalyst precursor 1 under the reaction conditions and
equilibria leading to the possible catalytic species 12 and 14.
precise stereochemical role of the (R)-binap
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[19] a) M. S. Delaney, C. B. Knobler, M. F. Hawthorne, Inorg. Chem.
ligand in these hydrogenation reactions is not yet understood.
However, its remarkable effect can be seen in the essentially
quantitative chemical yields and superb ee values recorded in
Table 1. The observed reaction rates and ee data show that
ketone hydrogenation is both more rapid and stereochemi-
cally more selective in the ionic liquid 4 than in the other
reaction media studied (Figure 1 and Table 1). This suggests
that 12 may play an important role under hydrogenation
conditions.
In summary, we have synthesized a new carborane-based
room-temperature ionic liquid 4, and used this salt as the
reaction medium in the asymmetric hydrogenation of unsym-
metrical aryl ketones in the presence of the chelating ligand
(R)-binap and a previously known[19] rhodacarborane catalyst.
The extraordinary performance of this catalyst system
warrants further synthetic and mechanistic studies, which
are in progress.
1981, 20, 1341 – 1347; b) M. F. Hawthorne, M. S. Delaney, US
Patent 4363747, 1982.
[20] A. S. Larsen, J. D. Holbrey, F. S. Tham, C. A. Reed, J. Am. Chem.
Soc. 2000, 122, 7264 – 7272.
[21] J. A. Belmont, J. Soto, R. E. King, A. J. Donaldson, J. D. Hewes,
M. F. Hawthorne, J. Am. Chem. Soc. 1989, 111, 7475 – 7486.
[22] 4: A solution of (N-n-butyl-C5H5N)+ Clꢀ (1.40 g, 8.16 mmol) in
dry CH2Cl2ꢀ (30 mL) was added to
a stirred solution of
Cs+ CB11H12 (2.26 g, 8.19 mmol) in dry methanol (120 mL),
and the mixture was stirred at room temperature for 20 h. All
solvents were then evaporated under reduced pressure, and the
resulting viscous residue was dissolved in CH2Cl2 and purified by
column chromatography (SiO2; CH2Cl2/Et2O 4:1). The solvent
was removed under reduced pressure and the product was dried
under high vacuum for 2 days to give (N-n-butylpyridinium)+ -
closo-CB11H12ꢀ (4; 2.10 g, 92%) as a colorless sticky liquid with
the dynamic viscosity m = 250 cP (0.01 gcmꢀ1 sꢀ1; measured on a
CV-100 Caulking Viscometer at 208C; estimated error: ꢁ 2%).
The liquid solidified at 218C to give 4 as a colorless waxy solid.
Elemental analysis: calcd for C10H26B11N(279.246): C 43.01, H
9.39, N5.02; found: C 43.10, H 9.41, N5.08; 1H NMR (400 MHz,
CDCl3): d = 8.92 (m, 2H, N-Cpy-H), 8.18 (m, 1H, Cpy-H), 7.75
(m, 2H; Cpy-H), 4.46 (t, 2H; N-CH2), 2.92 (s, 1H; B-CH), 1.65
(m, 2H; N-C-CH2-), 1.03 (m, 2H; N-C-C-CH2-), 0.56 (t, 3H;
CH3), 0.20–3.60 ppm (m, 11H; BH); 13C NMR (100.6 MHz,
CDCl3): d = 13.37 (C-C-C-C-N), 19.24 (C-C-C-C-N), 33.59 (C-C-
C-C-N), 55.67 (C-B), 61.89 (C-C-C-C-N), 128.58 (Cpy), 144.72
(Cpy), 145.41 ppm (Cpy); IR (KBr): n˜ = 2955 s, 2894 m, 2592 vs
(nBH), 1588 m, 1501 m, 1455 m, 1409 m, 1322 s, 1250 vs, 1086 s,
Received: February 25, 2003 [Z51273]
Keywords: asymmetric catalysis · carboranes · hydrogenation ·
.
ionic liquids · P ligands · rhodium
927 s, 886 s, 835 vs, br, 692 s, 636 s, 518 s, 497 s cmꢀ1
.
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[23] Typical procedure: a solution of the catalyst precursor (8.1 mmol)
in THF (2.53 mL), a solution of (R)-binap (12 mmol, 4.5 mm) in
THF (2.64 mL), and an ionic liquid (10 mL) were placed in a
100-mL glass autoclave equipped with a magnetic stirring bar, a
pressure gauge, and a gas inlet tube to be attached to a hydrogen
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product was determined by GC analysis and the residue was
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ꢀ788C.
Chloro(1,5-cyclooctadiene)rhodium(i)
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[24] GC column: Chirasil-DEX CB, 25 m, CHROMPACK; carrier
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17.8 min, (S)-1-phenylethanol: 20.5 min, acetophenone:
8.3 min, ethyl (R)-mandelate: 25.6 min, ethyl (S)-mandelate:
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