Synthesis of water-soluble aminosulfonamide ligands and their application in enantioselective transfer hydrogenation

Article abstract of DOI:10.1016/S0040-4039(01)00623-2

Water-soluble analogues of Noyori's (1S,2S)-N-(p-tolylsulfonyl)-1,2-diphenylethylenediamine and Knochel's (1R,2R)-N-(p-tolylsulfonyl)-1,2-diaminocyclohexane, containing an additional sulfonic acid group, have been synthesised. The ruthenium catalysed reduction of aromatic ketones using enantiomerically pure catalyst derived from water soluble ligands and [RuCl₂(p-cymene)]₂ has been examined. High enantioselectivity and moderate activity were observed in the 2-propanol/base system. The addition of water is necessary to stabilise the catalyst.

Full text of DOI:10.1016/S0040-4039(01)00623-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4037–4039
Synthesis of water-soluble aminosulfonamide ligands and their
application in enantioselective transfer hydrogenation
Christian Bubert,a John Blacker,b Stephen M. Brown,b John Crosby,c Steven Fitzjohn,d
James P. Muxworthy,b Tim Thorpea 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—Water-soluble analogues of Noyori’s (1S,2S)-N-(p-tolylsulfonyl)-1,2-diphenylethylenediamine and Knochel’s (1R,2R)-
N-(p-tolylsulfonyl)-1,2-diaminocyclohexane, containing an additional sulfonic acid group, have been synthesised. The ruthenium
catalysed reduction of aromatic ketones using enantiomerically pure catalyst derived from water soluble ligands and [RuCl2(p-
cymene)]2 has been examined. High enantioselectivity and moderate activity were observed in the 2-propanol/base system. The
addition of water is necessary to stabilise the catalyst. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
ligands 1, 2 and 3 and their use in asymmetric
catalysis.
Enantioselective transfer hydrogenation reactions of
prochiral ketones have been achieved using a range of
catalysts.1 Amongst the best catalysts for these reac-
tions are ruthenium complexes developed by Noyori2
and Knochel.3
2. Results and discussion
Ligand 1 was prepared as shown in Scheme 1. Sulfanilic
acid 4 was first converted to the sodium salt of 4,4-
dithiobisbenzenesulfonic acid 5 using a procedure previ-
ously described by Smith et al.8 via diazotisation
followed by quenching with disodium disulfide. The
conversion of compound 5 into bissulfochloride 6 was
effected using a mixture of PCl5 and POCl3 at reflux.
Addition of (1S,2S)-diphenylethylenediamine (DPEN)
7 to a solution of 6 in (10:1) dichloromethane/triethyl-
amine gave bissulfonamide 8 in high yield. Oxidation of
There has been considerable interest in the develop-
ment of water-soluble ligands,4 which allow metal
catalysed reactions to take place in water,5 other polar
solvents, biphasic systems6 and in supported polar
phase catalysis.7 We are interested in preparing water-
soluble ligands, which would be effective in the enan-
tioselective transfer hydrogenation of ketones. In
this Letter, we report the successful synthesis of
O
O
NH S
O
O
H2N
NH S
O
SO3H
H2N
H2N
NH S
O
SO3H
SO3H
1
2
3
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00623-2

4038
C. Bubert et al. / Tetrahedron Letters 42 (2001) 4037–4039
Scheme 1.
Scheme 2.
the disulfide bond with basic hydrogen peroxide pro-
duced ligand 1 in good yield. Ligand 2 was prepared in
a similar manner using (1R,2R)-diaminocyclohexane in
place of DPEN. As expected, ligand 2 has a higher
water-solubility than ligand 1. As a result of this a
slightly lower yield was isolated.
Scheme 3.
Table 1. Asymmetric transfer hydrogenation of aromatic ketones catalysed by polar ruthenium complexes
Ketone
Ligand
Reaction time (h)
Conversion (%)
Enantiomeric excess (%)
Configuration
10
10
10
12
12
13
13
14
14
15
15
1
2
3
1
2
1
2
1
2
1
2
48
48
48
72
48
4
96
91
11
94
87
100
100
90
91
31
94
88
91
95
90
81
88
87
81
91
83
S
R
S
S
R
S
R
S
R
S
R
4
24
24
42
42
35

C. Bubert et al. / Tetrahedron Letters 42 (2001) 4037–4039
4039
Ligand 3 was prepared in one-step by the reaction of
References
(1S,2S)-diphenylethylenediamine 7 with benzene-1,2-
disulfonic acid anhydride9 9 as shown in Scheme 2.
1. For reviews on transfer hydrogenation, see: (a) Palmer,
M. J.; Wills, M. Tetrahedron: Asymmetry 1999, 10,
2045–2061; (b) Zassinovich, G.; Mestroni, G. Chem.
Rev. 1992, 92, 1051–1069.
2. (a) Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.;
Noyori, R. J. Am. Chem. Soc. 1996, 118, 2521–2522; (b)
Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noy-
ori, R. J. Am. Chem. Soc. 1995, 117, 7562–7563; (c)
Matsumura, K.; Hashiguchi, S.; Ikariya, T.; Noyori, R.
J. Am. Chem. Soc. 1997, 119, 8738–8739.
The water-soluble amino sulfonic acid ligands 1, 2 and
3 were tested in the ruthenium catalysed transfer hydro-
genation using 2-propanol as the source of hydrogen.
The enantiomerically pure ruthenium catalyst was pre-
pared by reacting [RuCl2(p-cymene)]2 with the required
ligand in the presence of base at 40°C. Under standard
conditions,10 acetophenone 10 was converted into
phenethyl alcohol 11 (Scheme 3). The aromatic ketones
12, 13, 14 and 15 were also reduced to the correspond-
ing alcohols under identical conditions (Table 1).
3. Pu¨ntener, K.; Schwink, L.; Knochel, P. Tetrahedron
Lett. 1996, 37, 8165–8168.
4. (a) Thorpe, T.; Brown, S. M.; Crosby, J.; Fitzjohn, S.;
Muxworthy, J. P.; Williams, J. M. J. Tetrahedron Lett.
2000, 41, 4503–4505; (b) Darensbourg, M. Y. Inorg.
Synth. 1998, 32, 14–16; (c) Herrmann, W. A.;
Kohlpainter, C. W. Angew. Chem., Int. Ed. Engl. 1993,
32, 1524–1544.
5. For a review on aqueous organometallic chemistry, see:
Joo´, F.; Katho´, A. J. Mol. Catal. 1997, 116, 3–26.
6. Bhanage, B. M.; Zhao, F.-G.; Shirai, M.; Arai, M. Tetra-
hedron Lett. 1998, 39, 9509–9512.
Preliminary results indicate that ruthenium ligand 1
systems give rise to a higher enantioselectivity, whilst
ruthenium ligand 2 systems demonstrate higher activity.
As yet, little work has been carried out using ligand 3;
however, crystalline transition metal complexes of this
ligand have been isolated and characterised by X-ray
crystallography. As expected, electron deficient ketones
13 and 14 were reduced more rapidly than the electron
rich ketone 15.
7. (a) For a review on supported polar phase catalysis, see:
Anson, M. S.; Leese, M. P.; Tonks, L.; Williams, J. M.
J. J. Chem. Soc., Dalton Trans. 1998, 21, 3529–3538; (b)
Tonks, L.; Anson, M. S.; Hellgardt, K.; Mirza, A. R.;
Thompson, D. F.; Williams, J. M. J. Tetrahedron Lett.
1997, 38, 4319–4322; (c) Mirza, A. R.; Anson, M. S.;
Hellgardt, K.; Leese, M. P.; Thompson, D. F.; Tonks,
L.; Williams, J. M. J. Org. Proc. Res. Dev. 1998, 2,
325–331; (d) Tonks, L.; Anson, M. S.; Hellgardt, K.;
Mirza, A. R.; Thompson, D. F.; Williams, J. M. J.
Tetrahedron Lett. 1997, 38, 4319–4322.
In summary, the preparation of three new water-soluble
ligands has been achieved. Initial experiments demon-
strate that these function are effective chiral ligands in
the reduction of various aromatic ketones under trans-
fer hydrogenation conditions. It is anticipated that
these ligands will enable the development of biphasic
systems and ultimately, supported liquid phase cata-
lysts. Our attention will now turn to this chemistry and
results will be reported in due course.
8. Smith, H. A.; Doughty, G.; Gorin, G. J. Org. Chem.
Acknowledgements
1964, 29, 1484–1488.
9. Hurtley, W. R.; Smiles, S. J. Chem. Soc. 1926, 1821–
1828.
We wish to thank AstraZeneca for the funding for this
project through the strategic research fund.
10. For a typical method, see the following paper. Tetra-
hedron Lett. 2001, 42, 4041–4043.
.