Asymmetric hydrogenation of cyclic N-sulfonylimines with phosphine-free chiral cationic Ru-MsDPEN catalysts

Article abstract of DOI:10.1002/cjoc.201090260

Phosphine-free chiral cationic Ru/diamine complexes are effective catalysts for the asymmetric hydrogenation of a range of cyclic N-sulfonylimines, affording chiral sultam derivatives with good to excellent enantioselectivity (up to 94% ee).

Full text of DOI:10.1002/cjoc.201090260

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Asymmetric Hydrogenation of Cyclic N-Sulfonylimines with
Phosphine-Free Chiral Cationic Ru-MsDPEN Catalysts†
Chen, Fei(陈飞)
Li, Zhiwei(李志伟)
He, Yanmei(何艳梅)
Fan, Qinghua*(范青华)
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function,
Institute of Chemistry and Graduate School, Chinese Academy of Sciences, Beijing 100190, China
Phosphine-free chiral cationic Ru/diamine complexes are effective catalysts for the asymmetric hydrogenation
of a range of cyclic N-sulfonylimines, affording chiral sultam derivatives with good to excellent enantioselectivity
(up to 94% ee).
Keywords asymmetric catalysis, hydrogenation, ruthenium, diamine ligand, cyclic N-sulfonylimines, sultams
Introduction
asymmetric hydrogenation of a variety of acyclic N-aryl
imines with excellent enantioselectivities.8b,8c Ikariya et
al.8d also reported that Ir complexes of N-sulfonylated
diamine could efficiently catalyze asymmetric hydro-
genation of acyclic ketimines in the presence of silver
salts with up to 78% ee. Considering no report on
asymmetric hydrogenation of activated imines with such
promising catalytic systems and as a continuation of our
ongoing endeavor to develop effective catalysts for
asymmetric hydrogenation of heteroaromatic com-
pounds and imines,6,9 we herein report the use of chiral
cationic Ru-MsDPEN complexes for asymmetric hy-
drogenation of cyclic N-sulfonylimines, affording chiral
sultam derivatives with up to 94% ee.
The chiral cyclic sulfonamides, sultams, are one type
of most practical synthetic intermediates and chiral aux-
iliaries which have been successfully applied to a num-
ber of asymmetric transformations.1 Among the various
methods for sultams preparation, including classical
cyclization protocols2 and metal-catalyzed transfer hy-
drogenation,3 asymmetric hydrogenation of the corre-
sponding cyclic N-sulfonylimines represents one of the
most direct, atom-economic and efficient approaches for
attaining optically active sultams. In 1990, Oppolzer et
al.1a first reported the asymmetric hydrogenation of cy-
clic N-sulfonylimines by using Ru catalysts with up to
99% ee after crystallization. Recently, Zhang et al.4 de-
scribed a Pd-catalyzed asymmetric hydrogenation of a
cyclic N-sulfonylimine with high enantioselectivity.
However, for the above-reported catalytic systems, only
one substrate derived from saccharin was reported. One
of the most notable examples was recently reported by
Zhou et al.5 in the hydrogenation of a variety of cyclic
N-sulfonylimines with up to ＞ 99% ee by using
Pd/diphosphine catalysts.
Results and discussion
3-Methyl-1,2-benzisothiazole 1,1-dioxide (5a) was
selected as the model substrate for the condition opti-
mization. The initial hydrogenation was carried out in
methanol in the presence of 1 mol% (R,R)-1.10 To our
delight, the reaction proceeded smoothly, affording
(R)-3-methyl-1,2-benzisothiazoline 1,1-dioxide (6a) in
quantatitive yield with 87% ee (Table 1, Entry 1). Based
on this promising result, the solvent effect was then
studied. It was found that alcoholic solvents were suit-
able for obtaining high enantioselectivities (Table 1,
Entries 1—3). In contrast, low reactivities and enanti-
oselectivities were observed in THF and dichloro-
methane (DCM) (Table 1, Entries 5 and 6). Interestingly,
when mixture of MeOH/DCM was used as the solvent,
higher enantioselectivity was observed (Table 1, Entries
7—9). In addition, the effect of hydrogen pressure and
temperature were also tested. Slightly low enantioselec-
tivities were observed when reaction was performed
Most recently, we have demonstrated the effective-
ness of the air-stable Ru and Ir complexes of chiral
N-sulfonylated diamine,6 which are powerful catalysts
for asymmetric transfer hydrogenation of aromatic ke-
tones and imines,7 in the asymmetric hydrogenation of
quinolines with excellent enantioselectivities and reac-
tivities. At the same time, Xiao et al.8a demonstrated
that a Rh complex of N-sulfonylated diamine could effi-
ciently catalyze the asymmetric hydrogenation of cyclic
imines in the presence of AgSbF6. Later, they found that
a combination of the Ir-diamine complex together with a
chiral phosphate anion was an efficient catalyst for the
*
E-mail: fanqh@iccas.ac.cn; Tel.: 0086-010-62554472; Fax: 0086-010-62554472
Received July 21, 2010; revised and accepted August 23, 2010.
Project supported by the National Natural Science Foundation of China (No. 20973178), the National Basic Research Program of China (973 Pro-
gram, No. 2010CB833300), the Ministry of Health (No. 2009ZX09501-017) and the Chinese Academy of Sciences.
† Dedicated to the 60th Anniversary of Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.
Chin. J. Chem. 2010, 28, 1529— 1532
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1529

Chen et al.
COMMUNICATION
under lower hydrogen pressure or higher temperature
(Table 1, Entries 10—13).
obtained for imine bearing an electron-donating meth-
oxyl group (Table 2, Entry 10). Gratifyingly, this
Ru-complex was also found to be an effective catalyst
for the asymmetric hydrogenation of cyclic N-sulfonyl-
imines 7a—7c. The electronic and steric characteristic
of substituents in the substrates has significant influence
on the enantioselectivity and reactivity (Table 2, Entries
12—14). Notably, phenyl-substituted imine 7a gave the
highest enantioselectivity (94% ee, Table 2, Entry 13).
Under the optimized reaction conditions, we subse-
quently investigated the effect of catalysts on this reac-
tion. After a survey of different catalysts in the hydro-
genation of 5a (Table 2, Entries 1—4), catalyst 2 turned
out to be optimal in terms of both reactivity and enantio-
selectivity (Table 2, Entry 2). Notably, both the Ir- and
Rh-catalysts showed lower enantioselectivities under
otherwise the same reaction conditions (Table 2, Entries
3 and 4).
In
contrast,
hydrogenation
of
imine
with
o-methylphenyl group (7c) offered much lower enantio-
selectivity and reactivity (Table 2, Entry 13 vs. Entry
14).
With the optimal catalyst (R,R)-2 in hand, a variety
of cyclic N-sulfonylimines (5 and 7), which can be
conveniently prepared from commercially available
materials according to the reported procedure,5 were
efficiently hydrogenated to afford the corresponding
chiral sultam derivatives with up to 94% ee (Table 2).
For alkyl-substituted benzofused imines 5a—5c, excel-
lent enantioselectivity and full conversion were ob-
served using mixture of MeOH/DCM as solvent (92%
—93% ee, Table 2, Entries 2, 5 and 6), which are com-
parable to those obtained from Pd/(S)-SegPhos.5a How-
ever, for aryl-substituted benzofused imines (5d—5f),
slightly higher enantioselectivities were obtained using
neat methanol as solvent (Table 2, Entry 7 vs. Entry 8),
which are much lower than those of alkyl-substituted
sultams. It was noted that good enantioselectivity was
On the basis of our successful asymmetric hydro-
genation of cyclic N-sulfonylimines, some other acti-
vated imines were futher hydrogenated under the fol-
lowing conditions: 2 mol% (R,R)-2, 5.05×106 Pa of H2
and 50 ℃ for 24 h (Figure 1). The preliminary results
showed that this Ru-catalyst system was not effective
for asymmetric hydrogenation of the strong elec-
tron-withdrawing N-substituent imines. It was found
that hydrogenation of acyclic N-tosyl ketimine 9 re-
sulted in complete decomposition. Although
N-diphenylphosphinyl ketimine 11 and exocyclic
N-tosyl ketimine 10 could be hydrogenated, low con-
versions and enantioselectivities were observed (Figure
1).
Table 1 Optimization of the reaction conditions for asymmetric hydrogenation of 3-methyl-1,2-benzisothiazole 1,1-dioxide (5a)a
Entry
1
p(H2)/(106 Pa)
5.05
Temp./℃
25
Solvent
MeOH
Convn.b/%
＞99
＞99
＞99
＞99
70
eec/%
87
86
86
80
34
28
89
92
91
92
85
88
91
2
5.05
25
EtOH
3
5.05
25
IPA
4
5.05
25
Acetone
5
5.05
25
THF
6
5.05
25
DCM
70
7
5.05
25
V(MeOH)/V(DCM)＝1/1
V(MeOH)/V(DCM)＝1/3
V(MeOH)/V(DCM)＝1/4
V(MeOH)/V(DCM)＝1/3
V(MeOH)/V(DCM)＝1/3
V(MeOH)/V(DCM)＝1/3
V(MeOH)/V(DCM)＝1/3
＞99
＞99
95
8
5.05
25
9
5.05
25
10
11
12
13
7.58
25
＞99
＞99
＞99
95
1.01
25
5.05
50
5.05
0
a Reaction conditions: 0.2 mmol substrate in 1 mL solvent, 1 mol% catalyst, 24 h. b Determined by 1H NMR of the crude reaction mixture.
c Determined by HPLC with chiral OD-H column.
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Chin. J. Chem. 2010, 28, 1529— 1532

Asymmetric Hydrogenation of Cyclic N-Sulfonylimines
Table 2 Asymmetric hydrogenation of cyclic N-sulfonyliminesa
Entry
1
Substrate
5a
Catalyst
(R,R)-1
(R,R)-2
(R,R)-3
(R,R)-4
(R,R)-2
(R,R)-2
(R,R)-2
(R,R)-2
(R,R)-2
(R,R)-2
(R,R)-2
(R,R)-2
(R,R)-2
(R,R)-2
Solvent
V(MeOH)/V(DCM)＝1/3
V(MeOH)/V(DCM)＝1/3
V(MeOH)/V(DCM)＝1/3
V(MeOH)/V(DCM)＝1/3
V(MeOH)/V(DCM)＝1/3
V(MeOH)/V(DCM)＝1/3
V(MeOH)/V(DCM)＝1/3
MeOH
Convn.b/%
＞99
＞99
＞99
＞99
＞99
＞99
＞99
＞99
＞99
＞99
＞99
＞99
＞99
67
eec/%
92 (R)
93 (R)
83 (R)
58 (R)
93 (R)
92 (R)
44 (R)
49 (R)
20 (R)
78 (R)
62 (R)
72 (R)
94 (R)
76 (R)
2
5a
3
5a
4
5a
5
5b
6
5c
7
5e
8
5e
9
5d
MeOH
10
11d
12d
13
14d,e
5f
MeOH
7b
V(MeOH)/V(DCM)＝1/3
7b
MeOH
7a
MeOH
7c
MeOH
a Reaction conditions: 0.2 mmol substrate in 1 mL solvent, 1 mol% catalyst, 5.05×106 Pa of H2, stirred at 25 ℃ for 24 h. b Determined
by 1H NMR of the crude reaction mixture. c Determined by HPLC with chiral OD-H column, and the configurations were determined by
comparison of rotation sign with literature data.5c d 2 mol% catalyst. e Stirred at 40 ℃.
mechanism of the reaction.
Acknowledgements
We thank Professor Zhou, Yonggui for a generous
gift of some imine substates and for many fruitful
discussions.
Figure 1 Asymmetric hydrogenation of other activated imines.
References and note
1
(a) Oppolzer, W.; Wills, M.; Starkemann, C.; Bernardinelli,
G. Tetrahedron Lett. 1990, 31, 4117.
Conclusion
In summary, the phosphine-free chiral cationic
Ru-MsDPEN catalytic system has been successfully
applied in the asymmetric hydrogenation of a range of
cyclic N-sulfonylimines with good to excellent enanti-
oselectivity. Further work will be directed toward ex-
panding the scope of those cyclic N-sulfonylimines and
(b) Wills, M.; Oppolzer, W.; Kelly, M. J.; Signer, M.; Blagg,
J. Tetrahedron Lett. 1990, 31, 5015.
(c) Oppolzer, W.; Rodriguez, I.; Starkeman, C.; Walther, E.
Tetrahedron Lett. 1990, 31, 5019.
(d) Ahn, K. H.; Kim, S.-K.; Ham, C. Tetrahedron Lett. 1998,
Chin. J. Chem. 2010, 28, 1529— 1532
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chen et al.
COMMUNICATION
39, 6321.
Noyori, R. J. Am. Chem. Soc. 1996, 118, 4916.
2
For selected examples of classical cyclization protocols, see:
(a) Merten, S.; Frohlich, R.; Kataeva, O.; Metz, P. Adv.
Synth. Catal. 2005, 347, 754.
(c) Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.;
Sandoval, C. A.; Noyori, R. J. Am. Chem. Soc. 2006, 128,
8724.
(b) Hopking, M. J.; Hanson, P. R. Org. Lett. 2008, 10, 2223.
(c) Zeng, W.; Chemler, S. R. J. Am. Chem. Soc. 2007, 129,
12948.
(a) Ahn, K. H.; Ham, C.; Kim, S. K.; Cho, C. W. J. Org.
Chem. 1997, 62, 7047.
(b) Mao, J. M.; Baker, D. C. Org. Lett. 1999, 1, 841.
(c) Chen, Y.-C.; Wu, T.-F.; Deng, J.-G.; Liu, H.; Cui, X.;
Zhu, J.; Jiang, Y.-Z.; Choi, M. C. K.; Chan, A. S. C. J. Org.
Chem. 2002, 67, 5301.
(d) Liu, P.-N.; Gu, P.-M.; Deng, J.-G.; Tu, Y.-Q.; Ma, Y.-P.
Eur. J. Org. Chem. 2005, 3221.
(d) Sandoval, C. A.; Ohkuma, T.; Utsumi, N.; Tsutsumi, K.;
Murata, K.; Noyori, R. Chem. Asian J. 2006, 1, 102.
(a) Li, C.; Xiao, J. J. Am. Chem. Soc. 2008, 130, 13208.
(b) Li, C.; Wang, C.; Villa-Marcos, B.; Xiao, J. J. Am.
Chem. Soc. 2008, 130, 14450.
(c) Li, C.; Villa-Marcos, B.; Xiao, J. J. Am. Chem. Soc.
2009, 131, 6967.
(d) Shirai, S.; Nara, H.; Kayaki, Y.; Ikariya, T. Organo-
metallics 2009, 28, 802.
8
9
3
(a) He, Y.-M.; Fan, Q.-H. Org. Biomol. Chem. 2010, 8,
2497.
(e) Wu, J.-S.; Wang, F.; Ma, Y.-P.; Cui, X.; Cun, L.-F.; Zhu,
J.; Deng, J.-G.; Yu, B.-L. Chem. Commun. 2006, 1766.
Yang, Q.; Shang, G.; Gao, W.-Z.; Deng, J.-G.; Zhang, X.-M.
Angew. Chem., Int. Ed. 2006, 45, 3832.
(a) Wang, Y.-Q.; Lu, S.-M.; Zhou, Y.-G. J. Org. Chem.
2007, 72, 3729.
(b) Wang, Y.-Q.; Yu, C.-B.; Wang, D.-W.; Wang, X.-B.;
Zhou, Y.-G. Org. Lett. 2008, 10, 2071.
(c) Yu, C.-B.; Wang, D.-W.; Zhou, Y.-G. J. Org. Chem.
2009, 74, 5633.
(a) Zhou, H.; Li, Z.; Wang, Z.; Wang, T.; Xu, L.; He, Y.;
Fan, Q.-H.; Pan, J.; Gu, L.; Chan, A. S. C. Angew. Chem.,
Int. Ed. 2008, 47, 8464.
(b) Li, Z.-W.; Wang, T.-L.; He, Y.-M.; Wang, Z.-J.; Fan,
Q.-H.; Pan, J.; Xu, L.-J. Org. Lett. 2008, 10, 5265.
(c) Wang, Z.-J.; Zhou, H.-F.; Wang, T.-L.; He, Y.-M.; Fan,
Q.-H. Green Chem. 2009, 11, 767.
(b) Wang, Z.-J.; Deng, G.-J.; Li, Y.; He, Y.-M.; Tang, W.-J.;
Fan, Q.-H. Org. Lett. 2007, 9, 1243.
(c) Tang, W.; Xu, L.; Fan, Q.-H.; Wang, J.; Fan, B.; Zhou,
Z.; Lam, K.-H.; Chan, A. S. C. Angew. Chem., Int. Ed. 2009,
48, 9135.
4
5
10 Typical procedure for the asymmetric hydrogenation of cy-
clic N-sulfonylimines: A 30 mL glass-lined stainless-steel
reactor equipped with a magnetic stirrer bar was charged
with (R,R)-2 (1.4 mg, 0.002 mmol), imine (0.2 mmol) in
methanol (1 mL) under nitrogen atmosphere in a glove box.
The autoclave was closed, and the final pressure of the hy-
drogen gas was adjusted to 5.05×106 Pa after purging the
autoclave with hydrogen gas several times. The reaction
mixture was stirred at 25 ℃ for 24 h. Then the hydrogen
gas was carefully released and the conversion was deter-
mined by 1H NMR. The reaction mixture was filtered
through a short pad of silica and eluted with dichloro-
methane to give the pure products. The ee of the product
was determined by HPLC with chiral OD-H column.
6
7
(a) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97.
(b) Uematsu, N.; Fujii, A.; Hashiguchi, S.; Ikariya, T.;
(E1007212 Zhao, C.)
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