Enantioselective catalysis. Part 156 [1]. Ruthenium procatalysts and 2-pyridinealdehyde/(S)-NOBIN-derived cocatalysts in the transfer hydrogenation of acetophenone with 2-propanol

Article abstract of DOI:10.1007/s00706-003-0162-6

Several ruthenium procatalysts were tested in the transfer hydrogenation of acetophenone with 2-propanol using the chiral imine ligand (S)-2-(2- pyridinylmethyleneamino)-2′-hydroxy-1,1′-binaphthyl and the corresponding amine (S)-2-(2-pyridinylmethylamino)

Full text of DOI:10.1007/s00706-003-0162-6

Monatshefte f€ur Chemie 135, 885–897 (2004)
DOI 10.1007/s00706-003-0162-6
Enantioselective Catalysis. Part 156 [1].
Ruthenium Procatalysts and 2-
Pyridinealdehyde=(S)-NOBIN-Derived
Cocatalysts in the Transfer Hydrogenation
of Acetophenone with 2-Propanol
ꢀ
Henri Brunner and Frauke Henning
€
€
Institut fur Anorganische Chemie, Universitat Regensburg, D-93040 Regensburg, Germany
Received December 1, 2003; accepted December 5, 2003
Published online April 9, 2004 # Springer-Verlag 2004
Summary. Several ruthenium procatalysts were tested in the transfer hydrogenation of acetophenone
with 2-propanol using the chiral imine ligand (S)-2-(2-pyridinylmethyleneamino)-20-hydroxy-1,10-
binaphthyl and the corresponding amine (S)-2-(2-pyridinylmethylamino)-20-hydroxy-1,10-binaphthyl.
Ru(PPh3)3Cl2 was the best procatalyst. Its triphenylphosphane ligands were crucial for the catalytic
activity and take part in the chirality transfer. Triphenylphosphane removing reagents such as copper(I)
chloride, TEMPO, or TMAO improved the catalytic performance to enantioselectivities up to 99% ee.
The findings led to a mechanistic proposal including dissociation equilibria of triphenylphosphane and
chelate ring opening of the tridentate chiral binaphthyl ligand. New ligands with an additional chiral
center were synthesized and tested as cocatalysts. The nature of catalytically active intermediates was
examined by MS and NMR spectroscopy.
Keywords. Binaphthyl ligands; Ruthenium complexes; Chirality; Enantioselective catalysis;
Hydrogen transfer.
Introduction
The enantioselective transfer hydrogenation with 2-propanol or formic acid as
hydrogen donors has received wide interest in the last ten years [2]. After the
development of earlier successful catalysts [3, 4], Noyori’s complex [(p-cymene)-
Ru(TsDPEN)Cl] led to increased research in this field [5]. Up to date a large
number of active catalysts has been discovered. Among these Andersson’s azanor-
bornane ligands achieve in situ with [(p-cymene)RuCl2]2 excellent results with
turnover numbers of 8500 sꢁ1 and 96% ee [6]. Our tridentate imine and amine
ꢀ
Corresponding author. E-mail: henri.brunner@chemie.uni-regensburg.de

886
H. Brunner and F. Henning
ligands (S)-1 and (S)-2, derived from (S)-NOBIN and 2-pyridinecarbaldehyde, yield
equally high enantiomeric excesses of up to 97% [7]. Recently, an enantioselective
aluminum catalyst was found for the Meerwein-Schmidt-Ponndorf-Verley reduction
(MPV reduction) of prochiral ketones with up to 83% ee [8].
The difference between the transition metal catalysed transfer hydrogenation
and the aluminum-catalysed MPV reduction lies in the mechanism. Oxophilic,
Lewis acidic aluminum catalysts bind the substrate and the hydrogen donor by
their oxygen atoms and thus enable an intramolecular hydride transfer between
both organic molecules without metal contact. Transition metal catalysts favour the
formation of hydride complexes, which are the catalytically active species and can
transfer a hydride ligand to the substrate by two possible pathways, a stepwise
hydridic route and a concerted metal-ligand bifunctional mechanism [2, 3c, 5b,
9–11].
The substrates of the enantioselective transfer hydrogenation can be olefins,
ketones, and imines. Acetophenone is a common substrate for the testing of cat-
alysts in standard reactions. Avoiding the handling of hydrogen gas and mild
reaction conditions are the advantageous aspects of this reaction, when it is com-
pared to conventional hydrogenation. It has been applied successfully to pharma-
ceutically relevant substrates and a growing number of patents shows the interest of
the chemical industry [12]. In order to facilitate the separation and recycling some
catalysts have been immobilised on solid phases [13] or attached to dendrimers
[14]. Biphasic systems were explored as well as the use of ionic liquids or water as
solvents [15]. Furthermore, biocatalysts were found for the enantioselective trans-
fer hydrogenation [16].
So far the range of transition metal procatalysts that can be used with chiral
ligands to generate the catalytically active species in situ is limited to ruthenium,
rhodium, or iridium. Less common is the use of nickel, cobalt, and samarium
complexes [17]. For halfsandwich complexes containing bidentate chiral ligands
ꢀ
ꢀ
[(p-cymene)RuCl2]2, [Cp RhCl2]2, and [Cp IrCl2]2 are appropriate procatalysts.
For ligands with a higher coordination number Ru(PPh3)3Cl2 or Ru(DMSO)4Cl2
are generally used. In this article we report new investigations into the catalytic
properties of our transfer hydrogenation system with imine and amine ligands (S)-1
and (S)-2 [18]: (i) A series of ruthenium complexes was tested with (S)-1 and (S)-2
to elucidate the role of the procatalyst and to obtain information about the catalyt-
ically active species. (ii) We explored the effects of additives in order to further
improve the catalytic performance. (iii) A yellow precipitate that formed during the
catalytic experiments was analysed by spectroscopic methods. (iv) A methyl group
was introduced into imine ligand (S)-1 generating a chiral carbon atom in addition
to the chiral axis with the aim of increasing the enantioselectivity by fine tuning.
Results and Discussion
In a preceeding paper we had published the imine ligand (S)-2-(2-pyridinylmethy-
leneamino)-20-hydroxy-1,10-binaphthyl ((S)-1), the corresponding amine (S)-2-(2-
pyridinylmethylamino)-20-hydroxy-1,10-binaphthyl ((S)-2), and their use as
cocatalysts in situ with Ru(PPh3)3Cl2 in the transfer hydrogenation of acetophe-
none with 2-propanol, yielding (S)-1-phenylethanol with 94% conversion and 97%

Enantioselective Catalysis. Part 156
887
Scheme 1
ee in 15 h reaction time at 28ꢂC reaction temperature and with a substrate=catalyst
ratio of 100=1 (Scheme 1) [7]. In the present study the standard substrate=catalyst
ratio was 200=1.
Both ligands were tested in the catalytic standard reaction employing the
following procatalysts: Ru(PPh3)3Cl2, Ru(DMSO)4Cl2, Ru2((R,R)-DIOP)2Cl4,
and [(p-cymene)RuCl2]2 (Fig. 1, bars 2 and 3). These ruthenium complexes were
also tested without the addition of the chiral ligands (S)-1 and (S)-2 (bars 1). In the
case of the standard procatalyst Ru(PPh3)3Cl2 the ligand accelerating effect is
clearly visible. The complex Ru(DMSO)4Cl2 with DMSO instead of triphenylphos-
phane hardly displayed any catalytic activity of its own and the reaction rates could
not be improved much by adding the chiral ligands. However, a significant
enantiomeric excess was observed. The procatalyst Ru2((R,R)-DIOP)2Cl4
Fig. 1. Enantioselective transfer hydrogenation of acetophenone in the presence of different ruthe-
nium procatalysts and the ligands (S)-1 and (S)-2 (standard reaction conditions)

888
H. Brunner and F. Henning
contained (R,R)-DIOP as a chiral bisphosphane. It showed some catalytic activity
and low enantioselectivity with 1.3% ee (S). Upon addition of the chiral ligands the
enantiomeric excess increased, but the conversion was reduced to less than 1%. As
for the procatalyst [(p-cymene)RuCl2]2 we refer to published results, that were
obtained with the preformed complex [19]. Conversions and enantiomeric excesses
were below 5% in either case. Thus, phosphane ligands in the procatalyst led to
good catalytic activity, whereas DMSO did not. It must be assumed that many of
the species formed in situ from the procatalysts and cocatalysts in Fig. 1 do not
provide enough empty coordination sites to bind the reactants. Obviously, in the
case of Ru(PPh3)3Cl2 and its reaction products with (S)-1 and (S)-2 these open sites
can be generated by dissociation of the monodentate phosphane, whereas chelation
of the bisphosphane ligand in Ru2((R,R)-DIOP)2Cl4 and its derivatives prevents
ligand dissociation. Thus, out of four easily accessible ruthenium procatalysts only
Ru(PPh3)3Cl2 is suitable for good catalytic results.
To further elucidate the crucial role of the triphenylphosphane ligand we per-
formed cross experiments with Ru(PPh3)3Cl2=(S)-1 and Ru(DMSO)4Cl2=(S)-1 by
adding the missing monodentate ligand, DMSO or PPh3 (Table 1).
The results show that an addition of DMSO to the complex formed from
Ru(PPh3)3Cl2 and (S)-1 does not change the enantioselectivity of the reaction.
The catalytically active species remains unaltered (entries 1–3). The diminishing
conversion may be attributed to a competition between DMSO and the substrate
acetophenone, with DMSO partially blocking the active coordination sites of the
catalyst (see below). On the contrary, upon addition of two or six equivalents of
PPh3 to the complex derived from Ru(DMSO)4Cl2 and (S)-1 the enantiomeric
excess of the product increases from an average of 68% to values close to those
obtained with the catalyst Ru(PPh3)3Cl2=(S)-1 (entries 4–6). These findings indi-
cate an exchange of the DMSO ligand by PPh3 and the formation of the catalyti-
cally active triphenylphosphane-containing species.
Given that one or two equivalents of triphenylphosphane are required for good
catalytic results, we investigated the effect of an excess amount of PPh3 (Table 1).
The addition of three or ten equivalents of additional PPh3 to Ru(PPh3)3Cl2=(S)-1
Table 1. Ligand exchange and excess experiments of the transfer hydrogenation catalysts
Ru(PPh3)3Cl2=(S)-1 and Ru(DMSO)4Cl2=(S)-1 with DMSO and PPh3 (standard conditions)
Entry
Ligand
Procatalyst
Additive
Yield=%
ee=% (S)
1
2
(S)-1
(S)-1
(S)-1
(S)-1
(S)-1
(S)-1
(S)-1
(S)-1
(S)-2
(S)-2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(DMSO)4Cl2
Ru(DMSO)4Cl2
Ru(DMSO)4Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
–
22.8, 22.6, 25.1
14.4
97.1, 97.2, 96.6
97.2
20 eq DMSO
40 eq DMSO
–
3
7.5
97.9
4
0.6, 2.5
3.8, 2.9
4.4
64.7, 72.1
98.0, 92.7
98.3
5
2 eq PPh3
6 eq PPh3
3 eq PPh3
10 eq PPh3
3 eq PPh3
10 eq PPh3
6
7
48.9, 49.8
21.1, 27.2
53.4, 54.7
20.6, 23.6
84.4, 90.5
70.4, 78.5
90.4, 95.0
92.8, 87.9
8
9
10

Enantioselective Catalysis. Part 156
889
leads to a decreasing catalytic activity and enantioselectivity (entries 7–8). The
same trend can be observed for the catalyst Ru(PPh3)3Cl2=(S)-2 (entries 9–10).
Therefore, the amount of triphenylphosphane is not only contributing to the activ-
ity of the catalyst, but also plays a role in the chirality transfer.
The procatalyst Ru(PPh3)3Cl2 contains three phosphane ligands, whereas the
experimentally determined optimum quantity lies in the range of one or two
equivalents. Taking into account that the chiral binaphthyl ligand may bind in a
bidentate or tridentate way and that two further coordination sites are needed for
binding the substrates, a dissociation of triphenylphosphane from Ru(PPh3)3Cl2
must occur in order to enable the complex to enter the catalytic cycle (first step
in Scheme 2).
S in Scheme 2 may stand for a hydride or a hydrogen donor, such as 2-pro-
panol, resulting in a neutral species in the first case or a cationic species in the
latter case. The position of the open site (&) is chosen arbitrarily as well as the
arrangement of the various ligands around the metal center. Chelate ring opening of
the chiral tridentate ligand may occur at the pyridine or at the phenolate side.
Whether the rate limiting step, designated fast for the horizontal branch and slow
Scheme 2

890
H. Brunner and F. Henning
Table 2. Effects of additives on the transfer hydrogenation with the catalysts Ru(PPh3)3Cl2=(S)-1 and
Ru(PPh3)3Cl2=(S)-2 (standard conditions)
Entry
Ligand
Procatalyst
Additive
Yield=%
ee=% (S)
1
2
3
4
5
6
(S)-1
(S)-1
(S)-1
(S)-2
(S)-2
(S)-2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
30 eq CuCl
2 eq TEMPO
2 eq TMAO
30 eq CuCl
2 eq TEMPO
2 eq TMAO
73.7, 70.6
91.1, 94.8
90.2, 92.0
58.1, 59.2
95.5, 95.0
60.1, 48.7
99.1, 99.0
98.5, 97.6
97.8, 97.7
96.1, 98.5
96.4, 97.3
96.5, 94.8
for the perpendicular branch, are at the positions indicated in Scheme 2 remains an
open question.
The horizontal branch of Scheme 2 shows how an open site is formed by
dissociation of triphenylphosphane. Either DMSO (decreasing the conversion) or
the substrate can subsequently bind to the metal center reacting rapidly with high
enantiomeric excess. In the perpendicular branch an open site is generated by
chelate ring opening, the consequence of which is a change in the chiral environ-
ment of the metal center lowering the enantiomeric excess in a slower reaction.
Copper(I) chloride was not soluble in 2-propanol, but it is known to be able to
absorb free phosphane ligands [20]. An excess of 30 equivalents of copper(I)
chloride increased the yield of the standard reaction with the catalyst
Ru(PPh3)3Cl2=(S)-1 from 25% to 70% and the enantiomeric excess from 97% to
99% (Table 2, entry 1), obviously favouring the horizontal branch in Scheme 2.
Reactions employing copper(I) chloride alone or with (S)-1 did not show any
product formation. The salts Cu(OTf)2, NiBr2, and CoCl2 were soluble in 2-pro-
panol but did not show any sign of catalytic activity.
2,2,6,6-Tetramethylpiperidin-1-oxyl (TEMPO) and trimethylamineoxide
(TMAO) oxidize free triphenylphosphane in solution and thus shift the dissociation
equilibria of Scheme 2 to the desired side of the mono-PPh3 species. Using these
two additives in the standard transfer hydrogenation of acetophenone with 2-pro-
panol more than 90% conversion and 98% ee were obtained with the imine ligand
(S)-1 (Table 2, entries 2–3). The catalytic activity observed with 2 equivalents of
TEMPO added was equivalent to that with twice the catalyst concentration [7],
while the enantiomeric excess maintained on a higher level with 98% rather than
94%. The favourable effect of the phosphane removing additives TEMPO and
TMAO was less clear in the case of the amine ligand (S)-2 only TEMPO giving
a measurable improvement (entries 4–6). The addition of TEMPO stabilizes the
catalytically active species in the Ru(PPh3)3Cl2=(S)-1 system resulting in an
increased and highly selective product formation (Fig. 2).
During the catalysis experiments with the ligands (S)-1 and (S)-2 and
Ru(PPh3)3Cl2 the formation of a yellow precipitate was observed. In the case of
the imine ligand (S)-1 it occurred at the end of the reaction, whereas with the amine
ligand (S)-2 the precipitate formed while the catalyst was generated in situ. The
isolated precipitate showed catalytic activity in the transfer hydrogenation of
acetophenone yielding 67% (S)-1-phenylethanol in 70% ee (standard conditions).
Thus, the isolated intermediate is an active and selective catalyst but not the highly

Enantioselective Catalysis. Part 156
891
Fig. 2. Reaction profile of the transfer hydrogenation of acetophenone with 2-propanol (standard
conditions) employing the in situ catalyst Ru(PPh3)3Cl2=(S)-1: ~ conversion without any additive,
& conversion with 2 eq of TEMPO added, ꢂ enantiomeric excess with 2 eq of TEMPO added
enantioselective catalyst in the Ru(PPh3)3Cl2=(S)-1 and Ru(PPh3)3Cl2=(S)-2 sys-
tems. Since the precipitate occurred at the end of the reaction with catalyst
Ru(PPh3)3Cl2=(S)-1 it may be a reduction product (imine ! amine) of the initial
catalyst. In accord with this assumption an ESI-MS of the isolated yellow powder
displayed the fragments of mononuclear complexes containing the tridentate amine
ligand (S)-2 and one or two PPh3 ligands (Fig. 3).
Fig. 3. ESI-MS fragments of the isolated catalytically active intermediate; detected were MHþ ions;
enclosing line ¼ measurement; single line pattern ¼ simulation

892
H. Brunner and F. Henning
1
Fig. 4. Hydride region of the H NMR spectrum (400 MHz, C6D6) of the yellow precipitate at
different temperatures and time intervals
1
The H NMR spectrum of the yellow precipitate showed two signals in the
hydride region at ꢁ7.1 (A) and ꢁ10.2 ppm (B) indicating the presence of two
hydride species in solution. Upon heating to 65ꢂC these peaks broadened due to
an exchange reaction. After cooling down the same sharp signals were obtained,
but the ratio of the integrals had changed in favour of complex A (Fig. 4). After
72 h the initial ratio had reestablished.
In the 400 MHz 31P NMR spectrum a singlet was observed at 58.36 ppm for
complex A and two pseudo triplets for complex B at 49.91 and 41.74 ppm. The
31P NMR spectrum also showed temperature dependence of the signals due to an

Enantioselective Catalysis. Part 156
893
Scheme 3
1
exchange reaction. A H=31P-HMQC spectrum confirmed the coupling of the two
phosphorus groups in B with the hydrides in B [18].
Furthermore, the complex multiplet of the hydride signal B is highly sym-
metric, which is typical for AA’BB’ systems, and it has identical peak distances
at 400 and 600 MHz. Signal B is not an accidental overlap of two hydride signals,
but it represents a genuine spin system, which can be described as AA’MM’X2.
Keeping in mind that a possibly tridentate chiral ligand is bound to the metal center
one can exclude monomeric species. Since Ru(PPh3)3Cl2 is known to dimerize in
solution [21], we suggest that dimerization occurs also with the chiral ligand pres-
ent in the complex. Since the hydride ligands are inequivalent, two structure
proposals can be made that have the corresponding symmetry (Scheme 3). The
1H and 31P NMR peaks of complex A support a monomeric structure in accord
with the MS spectrum. We suggest that the chemical exchange observed in solution
is a dimerization reaction accompanied by a phosphane dissociation and=or a
chelate ring opening.
We introduced a further chiral center into the binaphthyl ligand by reacting the
imine (S)-1 with methyllithium (Scheme 4). The diastereomer ratio of the crude
product was 62:38 in favour of (þ)-3. The diastereomers were seperated by
repeated column chromatography. Since no suitable crystals were obtained, the
assignment of the absolute configuration remains open. Both diastereomers were
tested in situ with Ru(PPh3)3Cl2 in the transfer hydrogenation of acetophenone
with 2-propanol (Table 3).
Ligand (þ)-3 achieved up to 93% conversion and 92% ee (S), whereas (ꢁ)-3
resulted in up to 83% conversion and 85% ee (S). Thus, derivatives (þ)-3 and (ꢁ)-3
with an additional chiral center are matched and mismatched combinations. How-
ever, they did not improve the enantioselectivity of the parent ligand (S)-2.
Comparing the catalytic performance of all four ligands (S)-1, (S)-2, (þ)-3,
(ꢁ)-3 we did not observe any NH effect indicating a bifunctional mechanism
[22]. Instead, inclusion of the OMe derivatives (S)-4 and (S)-5 showed that the
phenolic OH function is crucial for the catalytic activity and enantioselectivity
(Table 3). Two reasons may account for this OH effect. Upon addition of base
the hydroxy group is deprotonated and then binds the chiral part of the ligand to the
ruthenium center. Methylation of the hydroxy group does not allow this bond to
form and thus the enantiomeric excess drops [8]. On the other hand the ligand
could bind in a bidentate way via both nitrogen atoms leaving the hydroxy group in
a fixed position. The hydrogen atom of the hydroxy group then could participate in
a bifunctional mechanism strongly favouring one substrate orientation.

894
H. Brunner and F. Henning
Scheme 4
Table 3. Enantioselective transfer hydrogenation of acetophenone with 2-propanol (standard con-
ditions) in the presence of different (S)-NOBIN-derived ligands
Entry
Ligand
Procatalyst
Yield=%
ee=% (S)
1
2
3
4
5
6
(S)-1
(S)-2
(þ)-3
(ꢁ)-3
(S)-4
(S)-5
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
22.8, 22.6, 25.1
85.7, 77.2
89.1, 93.1
83.0, 42.9
2.3, 3.7
97.1, 97.2, 96.6
96.3, 94.1
92.8, 91.8
85.9, 84.5
rac.
38.2, 11.1
2.4, 2.6
Experimental
1H NMR spectra: Bruker Avance 400 (400MHz) and Bruker Avance 600 (600 MHz) with TMS or
solvent as internal standard. 31P NMR spectra: Bruker Avance 400 (162 MHz) and Bruker Avance 600
(243 MHz) with H3PO4 as external reference. MS spectra: ThermoQuest Finnigan TSQ 7000. (S)-1,
(S)-2, (S)-4, and (S)-5 were prepared as described in previous communications [7, 19]. Ru(PPh3)3Cl2
was purchased from Merck. Ru(DMSO)4Cl2 [23], Ru2((R,R)-DIOP)2Cl4 [24], and [(p-cymene)RuCl2]2
[25] were synthesised according to literature procedures. The catalytic experiments and the synthesis of
(S)-3 were conducted in an inert atmosphere using standard Schlenk techniques. Solvents were dried

Enantioselective Catalysis. Part 156
895
and distilled under inert gas according to standard procedures. Acetophenone was dried with
Siccapent+ and distilled under nitrogen prior to use.
(S)-2-[1-(2-Pyridinyl)ethylamino]-20-hydroxy-1,10-binaphthyl ((ꢃ)-3, C27H22N2O)
Ligand (S)-1 (374.0mg, 1.0mmol) was dissolved in 80cm3 of toluene and cooled to ꢁ78ꢂC.
BF3ꢄOEt2 (0.2cm3, 1.6 mmol) and 1.9 cm3 (3.0mmol) of a 1.6 M MeLi solution in ether were added
with a syringe. After stirring for 5 h at ꢁ78ꢂC the reaction mixture was warmed to room temperature
and hydrolysed with 20 cm3 of a saturated NaHCO3 solution. The pH was adjusted to 10 with KOH
and the mixture was extracted with 5ꢄ20cm3 of ethyl acetate. The organic phase was dried over
Na2SO4, filtered, and the solvent was evaporated. Thus, 315.0mg (81%) of the crude product, a
colourless residue, were obtained. It was purified by column chromatography on silica with ethyl
acetate=petroleum ether 40–60 (1=1). The second fraction (Rf ¼ 0.68, (ꢁ)-3) and the third fraction
(Rf ¼ 0.52, (þ)-3) were collected and subjected to repeated chromatography for purification (2ꢄ).
Dissolving the residues in a minimum of CH2Cl2 and stirring with an excess of n-hexane yielded
colourless powders.
(þ)-3: Yield 190 mg (49%); mp 180ꢂC; ESI MS (CH2Cl2): m=z ¼ 390.0 (M, 100), 375.0 (M–CH3,
70); 1H NMR (400 MHz, CDCl3, TMS): ꢀ ¼ 1.34 (d, J ¼ 6.7 Hz, CH3), 4.24 (b, NH), 4.79 (bq,
J ¼ 6.7 Hz, CH), 5.25 (b, OH), 6.81–8.00 (m, Ar–H), 8.43 (ddd, J ¼ 5.0, 1.7, 0.9Hz, o–Py–H)
ppm; 13C NMR (75.5 MHz, CDCl3): ꢀ ¼ 23.17 (CH3), 55.12 (CH), 108.58 (Cq), 114.07 (Cq), 114.95
(CH), 117.79 (CH), 119.58 (CH), 121.93 (CH), 122.36 (CH), 123.64 (CH), 124.72 (CH), 125.09 (CH),
126.72 (CH), 127.15 (CH), 127.61 (Cq), 128.14 (CH), 128.36 (CH), 129.63 (Cq), 130.51 (CH), 130.55
(CH), 133.53 (Cq), 134.08 (Cq), 136.80 (CH), 144.22 (Cq), 149.06 (CH), 152.16 (Cq), 164.12 (Cq) ppm;
IR (KBr): ꢁꢀ¼ 3350 (b), 3060 (w), 3040 (m), 3020 (w), 2960 (w), 1610 (s), 1590 (s), 1555 (m), 1510
(m), 1480 (s), 1460 (m), 1430 (m), 1340 (s), 1275 (m), 1210 (m), 1150 (m), 820 (s), 755 (s) cmꢁ1
;
26
½ꢂꢅD ¼ þ217ꢂcm2 gꢁ1 (c ¼ 0.4, CHCl3).
(ꢁ)-3: Yield 100 mg (26%); mp 70ꢂC; ESI MS (CH2Cl2): m=z ¼ 390.0 (M, 100), 375.0 (M–CH3,
67); 1H NMR (400 MHz, CDCl3, TMS): ꢀ ¼ 1.35 (d, J ¼ 6.7 Hz, CH3), 4.29 (b, NH), 4.96 (bq,
J ¼ 6.7 Hz, CH), 6.81–8.00 (m, Ar–H), 8.37 (ddd, J ¼ 5.0, 1.7, 0.9Hz, o–Py–H) ppm; 13C NMR
(75.5MHz, CDCl3): ꢀ ¼ 23.56 (CH3), 54.48 (CH), 112.12 (Cq), 115.32 (CH), 118.16 (Cq), 119.77
(CH), 121.73 (CH), 122.05 (CH), 122.32 (CH), 123.49 (CH), 123.72 (CH), 124.35 (CH), 125.09 (CH),
126.71 (CH), 127.30 (Cq), 127.68 (Cq), 127.90 (CH), 128.06 (CH), 129.75 (CH), 130.22 (CH), 130.34
(Cq), 134.38 (Cq), 137.30 (CH), 144.10 (Cq), 148.61 (CH), 152.77 (Cq), 163.47 (Cq) ppm; IR (KBr):
ꢁꢀ¼ 3480 (b), 3400 (b), 3060 (w), 2970 (w), 2930 (w), 2870 (w), 1620 (s), 1590 (s), 1570 (m), 1510 (s),
1490 (s), 1440 (m), 1430 (m), 1350 (m), 1270 (m), 1225 (m), 1155 (m), 825 (s), 760 (s) cmꢁ1
;
26
½ꢂꢅD ¼ ꢁ265ꢂcm2 gꢁ1 (c ¼ 0.4, CHCl3).
General Procedure for the Catalytic Transfer Hydrogenation
Ligand (S)-1 (3.53 mg, 9.43mmol) was dissolved in 15.3 cm3 (14.4 cm3 for amine ligands) of 2-propanol.
0.94cm3 (9.40 mmol) of 0.01 M KOtBu in 2-propanol were added (1.88 cm3 (18.80 mmol) for amine
ligands). After 5 min 8.57 mmol of the ruthenium procatalyst were added (8.22 mg Ru(PPh3)3Cl2,
4.15mg Ru(DMSO)4Cl2, 5.75mg (4.29 mmol) Ru2((R,R)-DIOP)2Cl4). The solution was stirred
for 1 h at 28ꢂC. Acetophenone (0.20 cm3, 1.72 mmol) was added and the reaction was started with
0.86cm3 (8.60 mmol) of the 0.01 M KOtBu solution. When necessary additional reagents, such as
PPh3, DMSO, CuCl, TEMPO, or TMAO, were added before starting the catalysis. After stirring for
15h at 28ꢂC the reaction was stopped with 0.30cm3 (0.03 mmol) of 0.1 M acetic acid in 2-propanol.
The solvent was removed under reduced pressure and the products were isolated by bulb-to-bulb
distillation. Conversion and enantiomeric excess were analysed by quantitative GC with biphenyl as
internal standard (Fisons 8130, CP-Chirasil-Dex-CB-column (25 mꢄ0.25mm), 113ꢂC, 123 kPa, He
2.56cm3=min).

896
H. Brunner and F. Henning
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