New chiral N-(N,N-dialkylamino)sulfamoyl-1,2-diamine ligands for highly enantioselective transfer hydrogenation of ketones

Article abstract of DOI:10.1016/S0957-4166(02)00659-6

Chiral Ru(II) and Rh(III) complexes of N-(N,N-dialkylamino)sulfamoyl-1,2-diamine catalyze the transfer hydrogenation of various classes of aromatic ketones with high activity and excellent enantioselectivity.

Full text of DOI:10.1016/S0957-4166(02)00659-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2605–2608
New chiral N-(N,N-dialkylamino)sulfamoyl-1,2-diamine ligands
for highly enantioselective transfer hydrogenation of ketones
a
b
a,
&
Damjan Sterk, Massoud S. Stephan and Barbara Mohar *
aNational Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia
bPhosPhoenix SARL, 115 rue de l’Abbe´ Groult, F-75015 Paris, France
Received 12 October 2002; accepted 16 October 2002
Abstract—Chiral Ru(II) and Rh(III) complexes of N-(N,N-dialkylamino)sulfamoyl-1,2-diamine catalyze the transfer hydrogena-
tion of various classes of aromatic ketones with high activity and excellent enantioselectivity. © 2002 Elsevier Science Ltd. All
rights reserved.
1. Introduction
Herein, we disclose the preparation of new N-(N,N-
dialkylamino)sulfamoyl-1,2-diamine type ligands and
their application in Ru(II) and Rh(III)-catalysed asym-
metric transfer hydrogenation of aromatic ketones.
The search for economic industrial routes towards the
preparation of enantiomerically pure alcohols still con-
tinues owing to their use in the production of pharma-
ceuticals and agrochemicals. A direct access to single
enantiomer alcohols via catalytic reduction of ketones
appears to be the most attractive, and various methods
have been introduced.1–3 Transfer hydrogenation with
propan-2-ol or HCO2H–Et3N azeotrope is a very con-
venient process eliminating high hydrogen pressure or
the need for hazardous reducing reagents.4 Amongst
some notable achievements for the reduction of aro-
matic ketones, Noyori et al. chiral Ru(II)-N-tosyl-1,2-
diphenylethylenediamine catalyst (Ru(II)-Ts-DPEN)
displays high enantioselectivity.5 The reduction takes
place through a pericyclic mechanism involving a Ru
hydride.6
2. Results and discussion
We prepared two series of N-(N,N-dialkyl-
amino)sulfamoyl-1,2-diamine ligands 1a–d and 2a–c by
reacting a dialkylsulfamoylchloride with DPEN and
trans-1,2-diaminocyclohexane (CYDA), respectively
(Scheme 1).
Their Ru(II) and Rh(III) complexes were prepared and
tested against various models of aromatic ketones10
under transfer hydrogenation conditions at 25°C using
In our quest to optimize the Ru(II)-TsDPEN system
for the reduction of various classes of ketones, we
thought to modify the sulfonamide residue maintaining
the NH2 terminus unchanged. As a matter of fact, the
polystyrene supported Ru(II)-TsDPEN of Bayston et
al.7 and the Ru(II)-N-perfluorosulfonyl-DPEN of
Mioskowski et al.8 showed in some cases higher
enantioselectivities.
Various RSO2-DPEN ligands for transfer hydrogena-
tion were already prepared5,8,9 with R=Ar, CF3, RF,
but to our knowledge, R%N ligands have not been
2
mentioned.
Scheme 1. N-(N,N-Dialkylamino)sulfamoyl-1,2-diamine lig-
ands.
* Corresponding author. Tel.: +386-14760250; fax: +386-14760300;
e-mail: barbara.mohar@ki.si
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00659-6

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D. Sterk et al. / Tetrahedron: Asymmetry 13 (2002) 2605–2608
2606
HCO2H–Et3N azeotrope (Table 1). The metal com-
plexes were prepared by heating the metal precursor
with the ligand (1.2 equiv. to the metal) at 80°C in the
reaction solvent. Enantioselectivity and conversion were
better in highly polar solvents such as DMF, DMA,
NMP, 1,3-dimethyl-2-imidazolidinone, TMU compared
to MeCN, CH2Cl2 and toluene. Increasing the tempera-
ture from rt to 50°C accelerated the reduction but gave
lower enantioselectivity, while at 0°C prolonged reac-
tion time was required and resulted in 1–2% higher ee.
amine ligands and their use in transfer hydrogenation
of various classes of aryl ketones. In particular, the
chiral Ru complex of N-(N,N-dimethylamino)-sulfa-
moyl-1,2-diphenylethyl-enediamine 1a is an effective
catalyst for the transfer hydrogenation of methylben-
zoylformate, ethyl benzoylacetate and 2-carbomethoxy-
1-indanone using HCO2H–Et3N azeotrope.
3. Experimental
3.1. General
Ligand 1c gave up to 85% ee and 100% conversion for
the reduction of methylbenzoylformate. In the case of
ethyl benzoylacetate, ligand 1a led to 98% ee and 100%
conversion. Reduction of 2-carbomethoxy-1-indanone
using the ligand 1a led to the anti-product (>99% de) in
>99% ee and 87% conversion. In the case of acetophe-
none, the reduction with the various ligands resulted in
up to 96% ee but with moderate conversions.
(1S,2S)-Diphenylethylenediamine, (1S,2S)-diaminocy-
clohexane and dimethylsulfamoylchloride are commer-
cially available; N-chlorosulfonylpiperidine was
prepared according to Denivelle;11 dicyclohexyl and
diisopropylsulfamoylchlorides were prepared according
to Nakashima et al.12 1H NMR (300 MHz, internal
Me4Si) spectra were recorded using a Varian VXR-300
instrument for solutions in CDCl3.
The analysis of the above data with the different sulfa-
moyldiamine ligands does not show a specific trend in
relation to the dialkylsulfamoyl residue bulkiness. How-
ever, ligands with the DPEN skeleton gave better
results than the ones with CYDA ligands and the Ru
complexes were found to give better results than the Rh
complexes.
3.2. General procedure for the preparation of ligands
1a–d and 2a–c
To a cold (0°C) solution of (1S,2S)-diphenylethylene-
diamine (212 mg, 1.0 mmol) in DCM (25 mL) was
added dropwise dialkylsulfamoyl chloride (1.0 mmol).
The mixture was stirred at rt overnight, washed with
satd. aq. Na2CO3 (2×10 mL) and the organic layer
dried over Na2SO4. The concentrated residue was
In summary, this work presents new chiral N-(N,N-
dialkylamino)sulfamoyl - 1,2 - diphenylethylenediamine
and N-(N,N-dialkylamino)sulfamoyl-1,2-cyclohexyldi-
Table 1. Asymmetric transfer hydrogenation of various classes of ketonesa
Ketone
Ligand
Metal precursor
S/C ratio
Time (h)
Conv. (%)b
E.e. (%)b
Conf.c
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
1a
1a
1b
2a
1a
1a
1a
1c
2a
1a
1a
1b
1d
2a
1a
1a
[RuCl2(cym)]2
[RuCl2(cym)]2
[RuCl2(cym)]2
[RuCl2(cym)]2
[RuCl2(cym)]2
[RuCl2(cym)]2
[RhCl2Cp*]2
[RuCl2(cym)]2
[RuCl2(C6H6)]2
[RuCl2(cym)]2
[RhCl2Cp*]2
[RuCl2(C6H6)]2
[RuCl2(cym)]2
[RuCl2(cym)]2
[RuCl2(C6H6)]2
[RuCl2(cym)]2
100
100
100
100
200
200d
200
200
200
200
200
200
200
200
200
200
48
72
24
24
2
2
1
3
5
24
24
24
24
24
24
48
67
80
51
96
96
95
94
72
81
72
85
33
98
79
96
65
S
S
S
S
R
R
R
R
R
S
S
S
S
S
anti
anti
25
100
100
100
100
100
100
70
100
24
75
80
85
87
95
\99e
a Reactions were carried out with HCO2H/Et3N azeotrope in DMF at 25°C, unless otherwise noted.
b Determined by GC analysis using a Chirasil-DEX CB (25 m).
c Determined by comparison with available references.
d Reaction in TMU.
e >99% de.

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D. Sterk et al. / Tetrahedron: Asymmetry 13 (2002) 2605–2608
2607
purified by chromatography (DCM/EtOAc, 2:1) and
the product was recrystallized from Pr2O.
3.3. General procedure for asymmetric transfer
hydrogenation
i
Similar reaction conditions were adopted for (1S,2S)-
diaminocyclohexane (500 mg, 4.38 mmol) and the con-
centrated residue was purified by chromatography
(DCM/iPrOH/Et3N, 6:1:0.01) and recrystallized from
iPr2O.
A mixture of the metal precursor ([RuCl2(h6-arene)]2 or
[RhCl2Cp*]2) and the chiral ligand (1.2 equiv. to the
metal atom) was heated in DMF (0.5 mL) at 80°C for
20 min. The solution was cooled to 25°C and HCO2H–
Et3N, 5:2 (0.44 g, 5 mmol HCO2H) and the substrate (1
mmol) were subsequently added. The reaction mixture
was stirred at 25°C for the time indicated in Table 1.
Aliquots were diluted with iPr2O and analyzed by chiral
GC on Chirasil-DEX CB (25 m) column.
3.2.1. (1S,2S)-N-(N,N-Dimethylsulfamoyl)-1,2-diphenyl-
ethylenediamine, 1a. White powder (166 mg, 52%). Mp
94–96°C. [h]25406=−12.6 (c 1.0, CHCl3). 1H NMR: l 2.33
(s, 6H, 2×CH3), 4.15 (d, 1H, CH
(d, 1H, CHNH; J 5.9 Hz), 7.21–7.33 (m, 10H, 2×Ph).
MS (FAB) m/z 320 (M+H)+.
6 NH2; J 5.9 Hz), 4.44
6
3.3.1. 1-Phenylethanol. GC, 120°C: 9.0 min (R), 9.6 min
(S). The stereochemistry was assigned by comparison
with commercially available (S)-1-phenylethanol
(Aldrich).
3.2.2.
(1S,2S)-N-(Piperidyl-N-sulfonyl)-1,2-diphenyl-
ethylenediamine, 1b. White powder (197 mg, 55%). Mp
136–138°C. [h]52406=−5.0 (c 1.0, CHCl3). 1H NMR: l
3.3.2. Methyl mandelate. GC, 135°C: 12.0 min (R), 12.5
min (S). The stereochemistry was assigned by compari-
son with commercially available methyl (R)-mandelate
(Aldrich).
1.24 (m, 6H, CH
CH2NCH2), 4.16 (d, 1H, CH
1H, CHNH; J 5.7 Hz), 7.19–7.35 (m, 10H, 2×Ph). MS
(FAB) m/z 360 (M+H)+.
6
2CH2NCH2CH2
6 CH6 2), 2.70 (m, 4H,
6
NH2; J 5.7 Hz), 4.43 (d,
6
3.3.3. Ethyl 3-hydroxy-3-phenylpropanoate. GC, 140°C:
22.1 min (R), 23.0 min (S). The stereochemistry was
assigned by comparing the specific rotation value with
the literature data.13
3.2.3.
(1S,2S)-N-(N,N-Dicyclohexylsulfamoyl)-1,2-
diphenylethylenediamine, 1c. White powder (160 mg,
1
35%). Mp 145–147°C. [h]25406=−5.4 (c 1.0, CHCl3). H
NMR: l 0.95–1.29 and 1.44–1.72 (2m, 20H, 2×
CH2
1H, CH
Hz), 5.58 (br d, 1H, CHNH
10H, 2×Ph). MS (FAB) m/z 456 (M+H)+.
6
CH2
NH2; J 6.0 Hz), 4.40 (%br t%, 1H, CH
; J 5.7 Hz), 7.10–7.31 (m,
6
CH(CH2 3
6
) ), 2.96 (m, 2H, 2×CH
6
CH2), 4.06 (d,
3.3.4. 2-Carbomethoxy-1-indanol. GC, 160°C: 14.5 min
and 14.8 min (anti), 17.9 and 19.2 (syn). A mixture of
racemic anti- and syn-diastereomers was obtained by
NaBH4 reduction of 2-carbomethoxy-1-indanone.
6
6
NH; J 5.1
6
3.2.4.
(1S,2S)-N-(N,N-Diisopropylsulfamoyl)-1,2-
diphenylethylenediamine, 1d. White powder (184 mg,
Acknowledgements
1
49%). Mp 112–114°C. [h]25406=−3.2 (c 1.0, CHCl3). H
NMR: l 0.97 and 1.11 (2d, 12H, 2×CH(CH3 2
Hz), 3.40 (hept., 2H, 2×CH(CH3)2), 4.10 (d, 1H,
CHNH2; J 5.4 Hz), 4.39 (%t%, 1H, CHNH; J 5.7 Hz),
5.65 (br d, 1H, CHNH; J 6.3 Hz), 7.16–7.32 (m, 10H,
2×Ph). MS (FAB) m/z 376 (M+H)+.
6 ) ; J 6.9
6
We thank the Ministry of Education, Science and Tech-
nology of the Republic of Slovenia for research grant
Z1-3374-0104.
6
6
6
3.2.5.
(1S,2S)-N-(N,N-Dimethylsulfamoyl)-1,2-cyclo-
References
hexanediamine, 2a. Light yellowish powder (269 mg,
1
42%). Mp 97–98°C. [h]25406=+55.1 (c 1.0, CHCl3). H
NMR: l 1.09–1.33 (m, 4H), 1.71 (m, 2H), 1.95 (m, 1H),
2.23 (m, 1H), 2.37 (dt, 1H, CH
2.83 (m, 7H, 2×CH3, CHNH). MS (FAB) m/z 222
(M+H)+.
1. Hydrogenation: Noyori, R.; Ohkuma, T. Angew. Chem.,
Int. Ed. Engl. 2001, 40, 40 and references cited therein.
2. Hydrosilylation: (a) Brunner, H.; Nishiyama, H.; Itoh, K.
In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH:
New York, 1993; Chapter 6; (b) Sun, J.; Buchwald, S. L.
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6 NH2; J 10.5, 3.6 Hz),
6
3.2.6. (1S,2S)-N-(Piperidyl-N-sulfonyl)-1,2-cyclohexane-
diamine, 2b. White powder (356 mg, 47%). Mp 85–
87°C. [h]25406=+43.6 (c 1.0, CHCl3). 1H NMR: l
1.09–1.32, 1.49–1.78 (2m, 12H), 1.96 (m, 1H), 2.22 (m,
1H), 2.37 (dt, 1H, CH
1H, CHNH; J 10.3, 3.9 Hz), 3.20 (t, 4H, CH
5.4 Hz). MS (FAB) m/z 262 (M+H)+.
3. Hydroboration: (a) Singh, V. K. Synthesis 1991, 605; (b)
Brown, J. M.; Hulmes, D. I.; Layzell, T. P. J. Chem. Soc.,
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6
NH2; J 10.3, 3.9 Hz), 2.80 (dt,
6
6
2NCH2; J
6
4. For reviews, see: (a) Zassinovich, G.; Mestroni, G.; Glad-
iali, S. Chem. Rev. 1992, 92, 1051; (b) Noyori, R.;
Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97; (c) Palmer,
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Noyori, R. J. Am. Chem. Soc. 1995, 117, 7562; (b) Fujii,
A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.; Noyori, R.
J. Am. Chem. Soc. 1996, 118, 2521.
3.2.7.
(1S,2S)-N-(N,N-Dicyclohexylsulfamoyl)-1,2-
cyclohexanediamine, 2c. White powder (674 mg, 65%).
1
Mp 151–153°C. [h]52406=+37.4 (c 1.0, CHCl3). H NMR:
l 1.00–1.96 (m, 27H), 2.25–2.39 (m, 2H), 2.78 (m, 1H,
CH
6 NH), 3.20 (m, 2H, 2×NCH), 4.49 (br d, 1H, NH, J
5.1 Hz). MS (FAB) m/z 358 (M+H)+.

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D. Sterk et al. / Tetrahedron: Asymmetry 13 (2002) 2605–2608
2608
6. Yamakawa, M.; Ito, H.; Noyori, R. J. Am. Chem. Soc.
2000, 122, 1466.
7. Bayston, D. J.; Travers, C. B.; Polywka, M. E. C. Tetra-
TsDPEN:
-with acetophenone:5b 98% ee, >99% conversion;
-with methyl benzoylformate: 63% ee, >99% conversion
(this work);
hedron: Asymmetry 1998, 9, 2015.
-with ethyl benzoylacetate:13 94% ee, >99% conversion;
-with 2-carbomethoxy-1-indanone: >99% ee, >99% de,
48% conversion after 48 h (this work).
8. (a) Mohar, B.; Valleix, A.; Desmurs, J.-R.; Felemez, M.;
Wagner, A.; Mioskowski, C. J. Chem. Soc., Chem. Com-
mun. 2001, 2572; (b) Wagner, A.; Mioskowski, C.;
Mohar, B.; Desmurs, J.-R.; Le Guyader, F.; Schlama, T.
WO 00/76942, 2000.
9. We have prepared various ArSO2-DPEN ligands and
their results will be communicated in due course.
10. The best results for transfer hydrogenation using Ru(II)-
11. Denivelle, L. Bull. Soc. Chim. Fr. 1936, 3, 2143.
12. Nakashima, K.; Tsukada, T.; Hibasami, H.; Maekawa, S.
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