Recent developments in the area of asymmetric transfer hydrogenation

Article abstract of DOI:10.3390/50100004

The use of an enantiomerically pure amino alcohol, coupled to a transfer hydrogenation process, in the asymmetric catalysis of the reduction of ketones to alcohols, is described. The process works well for unfunctionalised ketones, affording e.e.s of up to 98%, and excellent conversions. We have recently extended, for the first time in this application, the scope of the methodology to the reductions of α-heteroatom substituted substrates, through the use of the appropriate protecting groups on each atom.

Full text of DOI:10.3390/50100004

Molecules 2000, 5, 4-18
molecules
ISSN 1420-3049
http://www.mdpi.org
Recent Developments in the Area of Asymmetric Transfer
Hydrogenation
Martin Willsa,*, Matthew Palmera, Athene Smitha, Jennifer Kennya and Tim Walsgroveb
aDepartment of Chemistry, University of Warwick, Coventry, CV4 7AL, UK
Tel.: (024) 7652 3260, Fax: (024) 7652 4112, E-mail: M.Wills@warwick.ac.uk
http://www.warwick.ac.uk/fac/sci/Chemistry/astaff/wills/
bSmithKline Beecham Pharmaceuticals, Old Powder Mills, Nr Leigh, Tonbridge, Kent, TN11 9AN,
UK
*Author to whom correspondence should be addressed.
Received: 14 September 1999 / Accepted: 15 November 1999 / Published: 21 January 2000
Abstract: The use of an enantiomerically pure amino alcohol, coupled to a transfer hydro-
genation process, in the asymmetric catalysis of the reduction of ketones to alcohols, is de-
scribed. The process works well for unfunctionalised ketones, affording e.e.s of up to 98%,
and excellent conversions. We have recently extended, for the first time in this application,
the scope of the methodology to the reductions of α-heteroatom substituted substrates,
through the use of the appropriate protecting groups on each atom.
Keywords: asymmetric, transfer, hydrogenation, catalysis, ruthenium.
Introduction
The asymmetric reduction of ketones to enantiomerically enriched alcohols remains a pivotal trans-
formation in organic synthesis [1,2]. Of the methods available to achieve this reaction in a catalytic
sense the most established are those based on either hydrogenation [3-7] or the use of oxazaboroli-
dines for the catalysis of ketone reduction by borane [8,9].
Catalytic hydrogenation using a homochiral phosphine in conjunction with an appropriate metal,
usually rhodium or ruthenium, is a versatile method which requires only very low levels of catalyst. In
© 2000 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.

5
Molecules 2000, 5
general, however, the method is most suitable for ketones which bear a proximal co-ordinating group
[3-7]. There are however a number of recent notable examples of reductions of simple ketones
through the use of additives [10-13] and a remarkable system for the asymmetric hydrogenation of
simple ketones using a combination of a Rh(I) complex of a chiral phosphine with lutidine and KBr as
additives has been reported very recently [14].
The oxazaborolidine-catalysed borane reduction process is complementary to hydrogenation and is
ideally suited to the reduction of unfunctionalised ketones and enones [8,9]. The drawback of this
method is the requirement for a relatively large quantity (usually at least 10 mol%) of catalyst and the
non-compatibility of certain functional groups with borane.
In this paper the combination of a homochiral amino alcohol with ruthenium(II) is demonstrated to
form an effective new system for the asymmetric catalysis of the transfer of hydrogen from isopropa-
nol to acetophenone.
Transfer Hydrogenation of Ketones
Asymmetric transfer hydrogenation with Ru(II) complexes, in which we have recently commenced
a programme of research, has recently emerged as an effective approach to asymmetric carbonyl re-
duction [15].
A particular advantage of transfer hydrogenation methodology is the requirement for only very low
quantities of catalysts; typically less than 1 mol%. Furthermore the ligands employed are often are in-
definitely stable to the reaction conditions and may be recovered after use.
We have recently discovered that (1R,2S)-(+)-1 is an excellent ligand for asymmetric transfer hy-
drogenation of ketones (Scheme 1) [16]. The use of 1 mol% of 1 in conjunction with 0.25 mol% of the
ruthenium complex [RuCl (p-cymene)] and 2.5 mol% of KOH in propan-2-ol ([ketone]=0.1M) at
2
2
room temperature resulted in reduction of acetophenone to S-(-)-1-phenethanol in 70% isolated yield
and 91% e.e. after 90 minutes. Of a series of aromatic groups in the catalyst, p-cymene proved to be
superior to benzene and 1,3,5-trimethylbenzene. The reaction does not require exclusion of water or
air and may be worked up simply by filtration of the reaction mixture through a plug of silica followed
by removal of solvent.
OH
NH2
1 mol%
(1R,2S)-
O
OH
Me
H
1
72% isolated yield
91% enantiomeric excess
Ph
Me
Ph
0.25 mol% [RuCl(p-cymene)]
S
2
2
o
(49% yield, 93% e.e. at 0C)
2.5 mol% KOH, i-PrOH solvent, 4 hrs
room temperature
Scheme 1. Asymmetric transfer hydrogenation of acetophenone using (1R,2S)-1.
The presence of a primary amine function on the ligand appears to be crucial; use of the methylated
amine gave a product of only 20% e.e. In order to determine the importance of the rigid structure of the

6
Molecules 2000, 5
ligand we repeated the reaction under identical conditions using R-phenylglycinol 2. In this reaction S-
(-)-phenethanol was obtained in 95% yield but only 23% enantiomeric excess (Scheme 2). Although
we have not yet investigated a systematic series of ligand modifications, it appears that a primary
amine function in the ligand is essential. We have also established that the relationship between the
enantiomeric purity of the ligand and the e.e. of the product is linear, suggesting that the active catalyst
contains a 1:1 ligand:Ru ratio [17].
1 mol%
OH
NH2
O
OH
H
R-
2
95% yield
23% enantiomeric excess
Ph
Me
Ph
Me
0.25 mol% [RuCl2(p-cymene)]2
S
2.5 mol% KOH, i-PrOH solvent, 4 hrs
room temperature
Scheme 2. Asymmetric transfer hydrogenation of acetophenone using (R)-2.
Reduction of a series of aromatic ketones under identical conditions using ligand 1 resulted in for-
mation of the corresponding alcohols in good to excellent yields and enantiomeric excesses (Figure 1).
The reduction of 1-tetralone gave the most remarkable result; up to 98% enantiomeric excess under the
room temperature reduction conditions. Extended reaction times resulted in loss of selectivity due to he
reversibility of the reaction. Isolated yields of only 39 to 63% were obtained however when account
was taken of the quantity of recovered starting material the mass balance is generally excellent. In all
instances where e.e.s are observed to reduce over extended times it is likely that this is a result of the
slow reversibility of the reaction.
Although aromatic/alkyl ketones were generally good substrates, alkyl/alkyl ketones gave products
of lower enantiomeric excess. An exception to this trend was observed for 2-tetralone, which gave a
product of 81% e.e., which represents a result competitive with any of the best alternative methods.
H
OH
H
OH
H
OH
S
Ph
Ph
H OH
S
S
S
84% yield
86% e.e.
90% yield
43% e.e.
85% yield
81% e.e.
48 hours: 60% yield
67% e.e.
OH
OH
H
H
OH
H
4 hours: 40% yield,
98% e.e.
S
S
S
MeO
94% yield
85% e.e.
56% yield
84% e.e.
79% yield
95% e.e.
Figure 1. Asymmetric transfer hydrogenation of ketones using 1 mol% (1R,2S)-1,
0.25% [RuCl2(p-cymene)]2, 2.5 mol% KOH, i-PrOH solvent, 1,5 hrs, room temperature.

7
Molecules 2000, 5
Our speculation on the mechanism of the reaction follows on from the suggestion by Noyori that
hydrogen bonding may play a key role in the catalytic process [18]. This speculation has been sup-
ported by a series of enlightening X-ray crystallographic studies [19]. We have obtained results which
suggest a 1:1 relationship between the ligand and the metal and have observed that the nature of the
aryl group has an effect on the enantiomeric excess [16]. This leads us to suggest that the ‘pro-
catalyst’ is probably an 18 electron compound such as 3, which forms upon treatment of the ligand 1
and the ruthenium complex precursor with base. Further elimination of HCl allows the active catalyst
to form and enter the catalytic cycle of hydrogen transfer (Scheme 3) in a process analogous to that
proposed by Noyori.
H
KOH
H O
Ph Me
PRODUCT
O
O
(-HCl)
Ru
Ru
Cl
H
H O
N
N
H
H2
3
Me
Me
O
O
O
Me
Me
Ph
Me
Ru
NH
H
H
Scheme 3. Proposed catalytic cyclic for transfer hydrogenation using (1R,2S)-1 as catalyst.
The origin of the asymmetric induction is less clear, however the highly rigid nature of the amino
indanol ligand ensures that any complex will be well defined. In this the hydrogenated ligand will
have a choice of two geometries for complexation (Figure 2), one of which is likely to be rather more
congested than the other and thus disfavoured.
Ru
NH
H
H O
H
H
NH
Ru
O
H
H
H
H
Favoured
Disfavoured
Figure 2. Possible diastereomeric complexes of 1 and rutheniu(arene)C.

8
Molecules 2000, 5
Having thus generated a rigid and well defined chiral environment in the complex, the hydrogen
transfer, which may involve a hydrogen bond from the amine nitrogen atom to the carbonyl oxygen,
will take place in a stereochemically predictable manner (Figure 3). We have no direct evidence, how-
ever, for the structure shown in Figure 3, which is our present speculation and the subject of ongoing
investigations [17].
Ru
Me
H
O
H O
H
NH
H
Figure 3. Proposed transition state for asymmetric reduction.
With a view to extending the transfer hydrogenation methodology to a variety of substrates we have
studied the reductions of a series of α-heteroatom substituted ketones (the results are summarised in
Figure 4). The reaction of α−chloro acetophenone 4 failed to give any product, a result which we ini-
tially explained by assuming in-situ cyclisation to the epoxide and thus deactivation of catalyst by
neutralisation of the base. However we were most surprised by the same lack of reactivity of both
α−methoxy and α−amino substituted ketones 5 and 6. It was clearly the case either these ketones were
poor substrates or that some form of product inhibition was terminating the catalytic process.
O
O
O
NMe2
Cl
OMe
O
Ph
Ph
Ph
6
4
5
R
Ph
no reduction
no reduction
O
no reduction
O
50:50 mixture of
R=Me and R=OMe
O
OMe
O
no reduction of
either ketone
Ph
OMe
Ph
Ph
Ph
7
8
9
38% yield (48 hrs)
58% yield (48 hrs)
84% e.e. (S)
97% yield
88% e.e. (R)
84% e.e. (S)
Figure 4. Results of asymmetric transfer hydrogenation substrates bearing α-heteroatom functions
(1 mol% (1R,2S)-1, 0.25 mol% [RuCl2(p-cymene)]2, 2.5 mol% KOH, i-PrOH solvent, 1,5 hrs,
room temperature).

9
Molecules 2000, 5
In order to test this we examined the transfer hydrogenation of a 1:1 mixture of propiophenone
(which is known to be a good substrate) and α-methoxyacetophenone. In the event neither ketone was
reduced, thus confirming that the catalyst is clearly inhibited by certain substrates or their reduction
products. Our present speculation is that the formation of a chelating product results in inhibitory
complexation and ultimately decomposition of the catalytic species (Figure 5) [20]. The proposed
complex is a 20-electron complex and is likely to undergo rapid decomposition through loss of the
aromatic ring.
Ru
X
O
H O
H
H
NH
2
(X=OMe, Cl, NMe )
2
Figure 5. Proposed intermediate leading to catalyst inactivation by a chelating product.
Further investigations have added support to the product inhibition theory. Reduction of β-methoxy
substituted ketone 7 proceeds rather more slowly than the acetophenone reaction whilst reduction of γ-
methoxy substituted ketone 8 is once again a rapid process. These results suggest that, as one would
predict, an increase in the distance between the potential chelating groups in the product causes the in-
hibitory effect to decrease sharply. Furthermore the reduction of α−phenoxy substituted acetophenone
9 proceeds rapidly and with high selectivity; a valuable and noteworthy result [20]. In the latter case
the lone pair of the oxygen atom adjacent to phenyl is delocalised with the aromatic group and is thus
unavailable to contribute to a strongly chelating product.
Armed with a realistic hypothesis for the mechanism of inhibition we have been able to design
functionalised systems which are compatible with transfer hydrogenation reactions under our condi-
tions. Mindful of the need to deactivate the electron-donating ability of the alkoxy substituted sub-
strates we have discovered that the acylation of the adjacent hydroxy group gives a substrate which is
both rapidly and selectivity reduced to the acylated diol (Scheme 4). Although some product of acyl
transfer is isolated, both products are of essentially identical e.e. and we have therefore assumed that
the isomerisation process follows the reduction reaction. To our knowledge this is the first example of
the reduction of an α−alkoxy functionised substrate containing a removable protecting group under
these conditions of transfer hydrogenation [20].

10
Molecules 2000, 5
O
OH
NH2
1 mol%
O
OH
Ph
OH
H
O
H
(1R,2S)-
1
O
Ph
O
Ph
76:24
+
Ph
Ph
Ph
R
0.25 mol% [RuCl2(p-cymene)]2
R
O
O
2.5 mol% KOH, i-PrOH, 2 hrs
room temperature 51% conversion
84% e.e.
90% e.e.
Scheme 4. Asymmetric transfer hydrogenation of α-acyloxy substrates using (1R,2S)-1.
In a similar manner we have demonstrated that α-amino substituted substrates bearing an electron-
withdrawing group on the nitrogen atom are valuable reagents for our process (Scheme 5) [20]. In our
example the use of an acylated primary amine function gave no reduction, however Noyori has re-
ported one example of the reduction of a substrate containing such a functional group [15s].
OH
NH2
1 mol%
OH
H
O
Me
Me
(1R,2S)-
1
N
OtBu
N
OtBu
Ph
Ph
R
0.25 mol% [RuCl2(p-cymene)]2
O
O
2.5 mol% KOH, i-PrOH, 2 hrs
room temperature
86% yield
79% e.e.
Scheme 5. Asymmetric transfer hydrogenation of α-acylamino substrates using (1R,2S)-1.
It is also noteworthy that, since our own studies, the highly enantioselective asymmetric reduction
of α-chloroacetophenone using a combination of formic acid/triethylamine in conjunction with a ru-
thenium(II)/monotosylated diamine system has recently been reported [21].
In conclusion it has been demonstrated that transfer hydrogenation using stereochemically rigid
amino alcohols is a versatile and practical method for the synthesis of enantiomerically enriched sec-
ondary alcohols. Recent developments have extended the scope of the reaction system to substrates
containing heteroatoms adjacent to the ketone, thus greatly increasing the applicability of the system.
Our current research portfolio in this area is focused at the extension of the methodology to related
systems, the reduction of C=N bonds [22], the solid phase support of our reagents [23], [15l] and the
reverse process, which allows kinetic resolution of alcohols through an enantioselective oxidation [24].
Acknowledgements: I wish to extend my thanks to the organisers of this online conference for the in-
vitation to contribute a paper. I am indebted to the EPSRC and SmithKline Beecham (Tonbridge) for
funding through CASE awards to Matthew Palmer and Jennifer Kenny. Oxford Asymmetry interna-
tional have provided some very generous recent funding to extend the transfer hydrogenation work
further.

11
Molecules 2000, 5
References and Notes
1. Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley and Sons Ltd: NY, 1994.
2. Ojima, I. Catalytic Asymmetric Synthesis; VCH Press: Berlin, 1993.
3. Noyori, R. Chemical multiplication of chirality - science and applications. Chem. Soc. Rev. 1989,
18, 187-208.
4. Noyori, R.; Takaya, H. BINAP - An efficient chiral element for asymmetric catalysis. Acc. Chem.
Res. 1990, 23, 345-350.
5. Takaya, H.; Ohno, T.; Noyori, R. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New
York, 1993, Chapter 1.
6. Noyori, R. Organometallic ways for the multiplication of chirality. Tetrahedron 1994, 50, 4259-
4292.
7. Wills, M. in Supplement A3: The chemistry of double-bonded functional groups; Patai, S., Ed.;
John Wiley and Sons Ltd, 1997, pp 781-842.
8. Deloux, L.; Srebnik, M. Asymmetric boron-catalyzed reactions. Chem. Rev. 1993, 93, 763-784.
9. Wallbaum, S.; Martens, J. Asymmetric syntheses with chiral oxazaborolidines. Tetrahedron
Asymmetry 1992, 3, 1475-1504.
10. Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. Practical enantioselective hydro-
genation of aromatic ketones. J. Am. Chem. Soc. 1995, 117, 2675-2676.
11. Ohkuma, T.; Ooka, H.; Yamakawa, M.; Ikariya, T.; Noyori, R. Stereoselective hydrogenation of
simple ketones catalyzed by Ruthenium(II) complexes. J. Org. Chem. 1996, 61, 4872-4873.
12. Ohkuma, T.; Ikehira, H.; Ikariya, T.; Noyori, R. Asymmetric hydrogenation of cyclic alpha,beta-
unsaturated ketones to chiral allylic alcohols. Synlett 1997, 467-469.
13. Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. Preferential hydrogenation of aldehydes and ke-
tones. J. Am. Chem. Soc. 1995, 117, 10417-10418.
14. Jiang, Q.; Jiang, Y.; Xiao, D.; Cao, P.; Zhang, X. Highly enantioselective hydrogenation of simple
ketones catalyzed by a Rh-PennPhos complex. Angew. Chem., Int. Edn. Engl. 1998, 37, 1100-
1103.
15. A summary of ligands (including our own) which have recently been reported for the asymmetric
transfer hydrogenation of ketones are given below. For reasons of space the comparison is limited
to the reduction of acetophenone.

12
Molecules 2000, 5
Me
*
H
O
PPh
Fe
2
PPh
PPh
Me
PPh
PPh
2
2
2
2
P
PPh
2
O
H
*
Fe
i
Pr
Ph P
2
MDPP
3
(pigiphos)
4
(R,R)-DIOP
(R)-PROPHOS
2
1
Me
Ph
Me
N
N
N
N
t
Et
N
N
Bu
7
5
6
O
O
O
N
Bn
N
N
Ph
Ph
Ph
Ph
NH
N
N
OH
OH
8
10
O
9
Ph
Ph
Ph
Ph
Ph
Ph
NHCH
O
S
O
S
NH HN
NH HN
H CHN
3
3
NHPh
PhHN
NHPh
PhHN
11
12
14
13
(poly(urea) of
)
11
NHMe
Ph
Ph
Ph
Ph
S
An
An
Fe
Ph
MeHN
HN
H N
NH
2
2
NHPh
NHMe
(An = p(MeO)C H )
15p
17
6 4
15
16
Se
2
Ph
H N
Ph
NMe
2
N
N
Fe
NHTs
2
Ar
Ar
15ff
(Ar = 1-naphthyl)
19
18
20

13
Molecules 2000, 5
NHTs
Ph
NHSO Ar
2
Ph
Ph
Fe
Ph
HO
NHCH
3
NH
2
23
22
(Ar = 1-naphthyl)
NH
21
2
O
OH
NH
OH
N
NH
2
Ph P
2
25
24
26
PPh
2
O
NH
Ph P
Me
Me
PPh
H
N
N
Fe
N
PPh
2
2
29
Ph
27
28
O
Ph
Ph
N
N
NH HN
H
Ph P
PPh
2
PPh
N
2
Ph P
2
O(-)Men
O
30
31
32

14
Molecules 2000, 5
Table. Asymmetric transfer hydrogenation of acetophenone
(hydride source / solvent is isopropanol unless otherwise indicated).
Entry Ligand Metal Time, h
Yleld, % e.e., % Ref
Temp, °C
120
82
82
100
82
68
82
82
82
80
82
rt
1
2
3
Ru(II)
Rh(I)
Ir(I)
111
3.5
23
35
60
71
80
87
99
-
4(S)
9(R)
a
b
b
b
c
1
2
2
58(S)
52(S)
42(S)
72(R)
7(R)
4
Ru(II) 0.03
2
5
6
7
8
Ir(I)
Ru(II)
Rh(I)
Rh(I)
Ir(I)
3
120
-
4
-
3
4
5
6
d
e
89
89
89
91
74
100
100
97
98
98
74
89
95
99
97
42
99
94
70
95
74
80
91
96
72
60
93
63(S)
37(S)
58(R)
97(S)
96(R)
67(R)
60(S)
43(R)
87(S)
30(R)
78(R)
28(S)
97(S)
98(S)
56(R)
83(R)
96(R)
92(S)
91(S)
95(S)
86(R)
94(R)
35(R)
20(R)
79(R)
60(R)
97(R)
f
g
h
i
j
k
1
m
n/o
p
q
r
s
t
u
u
9
7
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
Ir(I)
Ru(II) 0.17
Sm(III)
Rh(I)
Rh(I)
3
8
9
2
168
24
163
9
120
12
2-8
15
20
24
120
24
1
1.5
5
0.5
7
24
24
0.2
1
10
11
12
13
I4
16
17
19
20
20*
21
21*
22*
23
24
25
26
27
28
29
30
31
32
rt
70
60
82
-30
rt
82
rt
rt
rt
rt
30
rt
rt
Rh(I)
Ru(II)
Ru(II)
Ir(I)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
u
v
w
x
y
83
82
28
rt
z
aa
bb
cc
dd
ee
rt
80
45
45
7
aFormic acid / triethylamine 5/2 used as solvent and hydride source
a. Bianchi, M.; Matteoli, U.; Menchi, G.; Frediani, P.; Pratesi, S.; Piacenti, F.; Botteghi, C. Use of
DIOP in asymmetric transfer hydrogenation. J. Organomet. Chem. 1980, 198, 73.
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ketones catalyzed by phosphine-rhodium(I) and phosphine-iridium(I) complexes. J. Organomet.

15
Molecules 2000, 5
Chem. 1986, 306, 407-412; b) Genêt, J.- P.; Ratovelomanana-Vidal, V.; Pinel, C. Asymmetric hy-
drogen transfer reaction of aryl ketones with chiral diphosphine-ruthenium(II) catalysts. Synlett
1993, 478-480.
c. Krause, H. W.; Bhatnagar, A. K. Asymmetric transfer hydrogenation of ketones catalyzed by chi-
ral phosphineiridium complexes. J. Organomet. Chem. 1986, 302, 265-267.
d. Barbaro, P.; Bianchini, C.; Togni, A. Synthesis and chracterisation of ruthenium(II) complexes
containing chiral bis(ferrocenyl) P3 or P2S ligands. Asymmetric transfer hydrogenation of aceto-
phenone. Organometallics 1997, 16, 3004-3014.
e. Botteghi, C.; Chelucci, G.; Chessa, G.; Delogu, G.; Gladiali, S.; Soccolini, F. Optically-active ni-
trogen ligands. 3. enantioface-discriminating transfer hydrogenation of acetophenone catalyzed by
rhodium(I) complexes with chiral 2-(2'-pyridyl)pyridines. J. Organomet. Chem. 1986, 304, 217-
225.
f. Gladiali, S.; Pinna, L.; Delogu, G.; De Martin, S.; Zassinovich, G.; Mestroni, G. Optically active
phenanthrolines in asymmetric catalysis III. Highly efficient enantioselective transfere hydro-
genation of acetophenone by chiral Rh(/3-alkyl phenanthroline catalysts. Tetrahedron Asymmetry
1990, 1, 635-648.
g. Zassinovich, G.; Bettella, R.; Mestroni, G.; Bresciani-Pahor, N.; Geremia, S.; Randaccio, L. En-
antioselective hydrogen transfer-reactions from propan-2-ol to ketones catalyzed by pentacoordi-
nate iridium(I) complexes with chiral schiff-bases. J. Organomet. Chem. 1989, 370, 187-202.
h. Müller, D.; Umbricht, G.; Weber, B.; Pfaltz, A. C2 Symmetric 4,4’,5,5’-tetrahydro(oxazoles) and
4,4’,5,5’-tetrahydro-2,2’-methylenebis(oxazoles) as chiral ligands for enantioselective catalysis.
Helv. Chim. Acta 1991, 74, 232-240.
i. Jiang, Y.; Jiang, Q.; Zhang, X. A new chiral bis(oxazolinylmethyl)amine ligand for Ru-catalysed
asymmetric transfer hydrogenation of ketones. J. Am. Chem. Soc. 1998, 120, 3817-3818.
j. Evans, D. A.; Nelson, S. G.; Gagné, M. R.; Muci, A. R. A chiral samarium-based catalyst for the
asymmetric Meerwein-Ponndorf-Verley reduction. J. Am. Chem. Soc. 1993, 115, 9800-9801.
k. a) Gamez,P.; Fache, F.; Mangeney, P.; Lemaire, M. Enantioselective catalytic reduction of ke-
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Samples Availability: available from the authors.
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