Efficient rhodium and iridium-catalysed asymmetric transfer hydrogenation using water-soluble aminosulfonamide ligands

Article abstract of DOI:10.1016/S0040-4039(01)00624-4

A range of aromatic ketones was reduced asymmetrically under transfer hydrogenation conditions using enantiomerically pure catalysts derived from water-soluble diamine ligands and [Cp*MCl₂]₂ (Cp* = pentamethylcyclopentadienyl, M = Rh

Full text of DOI:10.1016/S0040-4039(01)00624-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4041–4043
Efficient rhodium and iridium-catalysed asymmetric transfer
hydrogenation using water-soluble aminosulfonamide ligands
Tim Thorpe,a John Blacker,b Stephen M. Brown,b Christian Bubert,a John Crosby,c Steven Fitzjohn,d
James P. Muxworthyb and Jonathan M. J. Williamsa,*
aDepartment of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK
bAvecia, Huddersfield Works, PO Box A38, Leeds Road, Huddersfield HD2 1FF, UK
cAstraZeneca, Process R&D, Silk Road Business Park, Charter Way, Macclesfield, Cheshire SK10 2NA, UK
dZeneca Agrochemicals, Jealott’s Hill International Research Station, Bracknell, Berkshire RG42 6ET, UK
Received 1 February 2001; accepted 11 April 2001
Abstract—A range of aromatic ketones was reduced asymmetrically under transfer hydrogenation conditions using enantiomeri-
cally pure catalysts derived from water-soluble diamine ligands and [Cp*MCl2]2 (Cp*=pentamethylcyclopentadienyl, M=Rh, Ir).
High catalytic activity and enantioselectivity were observed in systems containing up to 51% water. © 2001 Elsevier Science Ltd.
All rights reserved.
1. Introduction
ported liquid phase (SLP) catalysis7 and this work is a
step further in the development of a SLP transfer
hydrogenation catalyst.
Asymmetric catalytic transfer hydrogenation using 2-
propanol as a source of hydrogen is an attractive
method for the preparation of chiral alcohols and
amines.1 The majority of work carried out in this area
has used ruthenium catalysts in combination with a
variety of phosphine and amine ligands.2 Of these, the
most notable transfer hydrogenation system incorpo-
rates the Ru(II)–TsDPEN (TsDPEN=N-(p-toluenesul-
fonyl)-1,2-diphenylethylenediamine)
catalyst,
first
reported by Noyori et al.3 More recently, the synthesis
and application of efficient rhodium-based catalysts has
been reported in the literature.4 Whilst the utility of
irridium catalysts for transfer hydrogenation has been
documented, there are few results that compare with
those obtained from ruthenium or rhodium-based
systems.4b,5
2. Results and discussion
The chiral rhodium or iridium complexes were prepared
by reacting [Cp*MCl2]2 (M=Rh, Ir) with ligands 1 or 2
in the presence of base at 40°C ([Cp*MCl2]2/diamine/
Recently, we have used the water-soluble aminosulfonic
acid ligands 1 and 2 with ruthenium for the transfer
reduction of various aromatic ketones.6 Herein, we
report on the synthesis and application of efficient
water-soluble rhodium and iridium-based catalysts for
asymmetric transfer hydrogenation under aqueous con-
ditions. Our research interests lie in the area of sup-
* Corresponding author.
Scheme 1.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00624-4

4042
T. Thorpe et al. / Tetrahedron Letters 42 (2001) 4041–4043
Table 1. Asymmetric transfer hydrogenation of acetophenones catalysed by polar rhodium complexes
Ketone
Ligand
Reaction time (h)
Conversion (%)
Enantiomeric excess (%)
Configuration
3
4
6
8
1
2
1
2
1
2
1
2
24
18
18
4
42
42
64
48
92
94
98
99
9
65
81
95
97
95
95
94
94
95
82
96
R
R
R
R
R
R
R
R
Table 2. Asymmetric transfer hydrogenation of acetophenones catalysed by polar iridium complexes
Ketone
Ligand
Reaction time (h)
Conversion (%)
Enantiomeric excess (%)
Configuration
3
4
5
6
7
8
9
1
2
1
2
1
2
1
2
1
2
1
2
1
2
140
26
43
4
51
90
88
95
98
83
99
22
80
93
99
77
96
41
55
82
96
86
93
85
94
78
95
76
95
73
96
91
97
R
R
R
R
R
R
R
R
R
R
R
R
R
R
26
150
141
91
20
139
45
139
45
base=1:8:8) and were used immediately without isola-
tion.8 A range of aromatic ketones was reduced at
room temperature under transfer hydrogenation condi-
tions (Scheme 1). Tables 1 and 2 show the results from
systems containing 15% water.
The results (Table 3) were quite surprising. An expected
rate decrease relating to the lower concentration of
2-propanol was not seen. Instead, a significant rate
increase was noted for both systems. In addition to this,
a large increase in enantiomeric excess was observed for
ligand 1 systems when the concentration of water was
increased from 15 to 34%. The reason for these results
is not clear at this time.
Both the choice of metal and ligand affected the rate
and enantioselectivity of the reaction in the expected
manner.2 Rhodium-based complexes proved to be super-
ior catalysts in terms of rate and enantioselectivity, with
ligand 2 systems providing higher reactivity. The elec-
tronic properties of the substrate had a significant effect
on the outcome of the reaction. Electron deficient
ketones were reduced rapidly to the corresponding
alcohols with high conversion and enantioselectivity.
Electron-rich ketones were reduced more slowly but
also with high enantioselectivity.
In conclusion, we have used water-soluble rhodium and
iridium complexes to efficiently catalyse the asymmetric
reduction of various aromatic ketones. Our future work
will concentrate on the development of biphasic and
supported liquid phase systems that utilise these
catalysts.
In order to determine the effect of an increase in water
concentration, the iridium-catalysed transfer hydro-
genation experiments were carried out in a 2-propanol–
water mixture containing 34 and 51% water. The
overall volume of reaction solvent remained unchanged.
Acknowledgements
We wish to thank AstraZeneca for the funding for this
project through the strategic research fund.

T. Thorpe et al. / Tetrahedron Letters 42 (2001) 4041–4043
4043
Table 3. Transfer hydrogenation using iridium catalysts in systems containing (i) 34% and (ii) 51% water
Ketone
Ligand
Reaction time (h)
Conversion (%)
Enantiomeric excess (%)
5
5
6
6
8
8
1
2
1
2
1
2
22
2.5
115
116
42
(i)
(ii)
(i)
(ii)
(i)
(ii)
(i)
(ii)
(i)
(ii)
(i)
74
90
82
94
20
33
76
89
47
66
92
92
92
92
94
93
91
92
92
87
91
93
95
94
18
(ii)
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