also showed good enantioselectivity, giving the hydrogenation
product in 91% ee and 100% conversion accompanied by another
dark brown oil, formed after the addition of ether (Table 3, run 4).
These results demonstrate that the MeOPEG-monophosphite
ligands have the advantage of easy recovery and reutilization in
asymmetric hydrogenation, in addition to their facile preparation
and high efficiency.
Table 2 Asymmetric hydrogenation of b-alkyl-b-(acylamino)acry-
lates 6 catalyzed by Rh-MeOPEG-monophosphites 1 in CH2Cl2
a
In conclusion, we have reported the first examples of polymer-
monophosphite ligands, using a PEG structure as the alkoxy
moiety of monophosphites, for use in the highly effective Rh-
catalyzed enantioselective hydrogenation of enamides and
b-(acylamino)acrylates. As well as obtaining higher enantioselec-
tivities than their parent ligands, these polymer-monophosphites
have the advantages of being readily available, air stable, easily
separated and recovered from the reaction mixture, and con-
veniently recyclable several times. Further investigations of other
catalytic asymmetric reactions with these polymer-monophosphite
ligands are under way.
Entry
Ligand
Substrate (R)
Conversion (%)
ee (%)b
1
2
3
4
5
6
7
a
1a
1a
1a
1a
1a
1b
1c
(Z)-6a (Me)
(E)-6a (Me)
(E)-6b (Et)
(E)-6c (iPr)
(E)-6c (iPr)
(E)-6c (iPr)
(E)-6c (iPr)
73
94
97 (S)
96 (S)
98 (S)
99.9 (R)
99.9 (R)c
99.9 (R)c
99.9 (R)c
100
100
100
100
100
Reactions were performed under 10 bar H2 pressure in CH2Cl2 at
room temperature for 20 h. Substrate : Rh(COD)2BF4 : ligand =
50 : 1 : 2.2. Enantiomeric excesses were determined by GC using a
chiral Select 1000 capillary (0.25 mm 6 30 m) column and a Varian
Chirasil-L-Val capillary (0.25 mm 6 30 m) column. Substrate :
Rh(COD)2BF4 : ligand = 100 : 1 : 2.2.
b
c
Notes and references
1 For reviews, see: (a) J. M. Brown, in Comprehensive Asymmetric
Catalysis, ed. E. N. Jacobsen, A. Pfaltz and H. Yamamoto, Springer,
Berlin, 1999, vol. 1, ch. 5.1; (b) T. Ohkuma, M. Kitamura and
R. Noyori, in Catalytic Asymmetric Synthesis, ed. I. Ojima, Wiley-VCH,
New York, 2nd edn, 2000, ch. 1.
2 For reviews, see: (a) H.-U. Blaser, C. Malan, B. Pugin, F. Spindler,
H. Steiner and M. Studer, Adv. Synth. Catal., 2003, 345, 103; (b)
W. Tang and X. Zhang, Chem. Rev., 2003, 103, 3029.
3 (a) C. Claver, E. Fernandez, A. Gillon, K. Heslop, D. J. Hyett,
A. Martorell, A. G. Orpen and P. G. Pringle, Chem. Commun., 2000,
961; (b) M. T. Reetz and G. Mehler, Angew. Chem., Int. Ed., 2000, 39,
3889; (c) M. van den Berg, A. J. Minnaard, E. P. Schudde, J. van Esch,
A. H. M. de Vries, J. G. de Vries and B. L. Feringa, J. Am. Chem. Soc.,
2000, 122, 11539.
4 For reviews of monophosphorus ligands, see: (a) I. V. Komarov and
A. Bo¨rner, Angew. Chem., Int. Ed., 2001, 40, 1197; (b) F. Lagasse and
H. B. Kagan, Chem. Pharm. Bull., 2000, 48, 315; (c) T. Jerphagnon,
J.-L. Renaud and C. Bruneau, Tetrahedron: Asymmetry, 2004, 14, 2101.
For other recent examples, see: (d) Y. Fu, X.-X. Guo, S.-F. Zhu,
A.-G. Hu, J.-H. Xie and Q.-L. Zhou, J. Org. Chem., 2004, 69, 4648; (e)
Y. Fu, G.-H. Hou, J.-H. Xie, L. Xing, L.-X. Wang and Q.-L. Zhou,
J. Org. Chem., 2004, 69, 8157; (f) S. Wu, W. Zhang, Z. Zhang and
X. Zhang, Org. Lett., 2004, 6, 3565; (g) P. N. M. Botman, A. Amore,
R. van Heerbeek, J. W. Back, H. Hiemstra, J. N. H. Reek and J. H. van
Maarseveen, Tetrahedron Lett., 2004, 45, 5999; (h) H. Bernsmann,
M. van den Berg, R. Hoen, A. J. Minnaard, G. Mehler, M. T. Reetz,
J. G. de Vries and B. L. Feringa, J. Org. Chem., 2005, 70, 943; (i)
M. T. Reetz, J.-A. Ma and R. Goddard, Angew. Chem., Int. Ed., 2005,
44, 412.
5 (a) S. Doherty, E. G. Robins, I. Pa´l, C. R. Newman, C. Hardacre,
D. Rooney and D. A. Mooney, Tetrahedron: Asymmetry, 2003,
14, 1517; (b) X. Wang and K. Ding, J. Am. Chem. Soc., 2004,
126, 10524; (c) C. Simons, U. Hanefeld, I. W. C. E. Arends,
A. J. Minnaard, T. Maschmeyer and R. A. Sheldon, Chem.
Commun., 2004, 2830.
6 Q.-H. Fan, Y.-M. Li and A. S. C. Chan, Chem. Rev., 2002, 102, 3385.
7 M. T. Reetz, L. J. Goossen, A. Meiswinkel, J. Paetzold and J. F. Jensen,
Org. Lett., 2003, 5, 3099.
99.9% ee, even at 1.0 mol% catalyst loadings (Table 2, entries 5–7).
To the best of our knowledge, few monophosphite ligands have
been reported as showing such high enantioselectivity and catalytic
activity in this reaction.
As well as the high efficiency observed in the Rh-catalyzed
asymmetric hydrogenation of enamides and b-alkyl-b-(acetyl-
amino)acrylates, another salient and practical feature of these
MeOPEG-monophosphite ligands is that they are easily separated
and recovered from the reaction mixture. After completion of the
hydrogenation, ether was added to the reaction mixture and a
precipitate was formed immediately. Simple filtration under an Ar
atmosphere afforded separation of the precipitated catalyst and
products remaining in solution. An exception was 1a with a low
molecular weight PEG chain, which was separated as a brown oil.
We then examined the reuseability of the recovered Rh complex of
MeOPEG-monophosphite ligand 1b in the hydrogenation of N-(1-
phenylethenyl)acetamide 4a, the results of which are summarized
in Table 3. The recovered catalyst was submitted to the next
catalytic reaction without any further addition of Rh. The
recovered catalyst could be recycled with only a slight loss of
enantioselectivity (from 97% ee in the first run to 91% ee in the
fourth run) (Table 3, runs 1–4). After the completion of the
hydrogenation in the third run, a brown oil was separated. This oil
Table 3 The recycling of Rh/MeOPEG-monophosphite 1b catalyst in
the enantioselective hydrogenation of N-(1-phenylethenyl)acetamide
4aa
Run
Conversion (%)
ee (%)b
8 (a) H. Huang, Z. Zheng, H. Luo, C. Bai, X. Hu and H. Chen, Org.
Lett., 2003, 5, 4137; (b) H. Huang, Z. Zheng, H. Luo, C. Bai, X. Hu and
H. Chen, J. Org. Chem., 2004, 69, 2355.
9 For review of hemilabile ligands, see: A. Bader and E. Lindner, Coord.
Chem. Rev., 1991, 108, 27.
10 M. T. Reetz, G. Mehler, A. Meiswinkel and T. Sell, Tetrahedron Lett.,
2002, 43, 7941.
11 (a) T. Jerphagnon, J.-L. Renaud, P. Demonchaux, A. Ferreira and
C. Bruneau, Adv. Synth. Catal., 2004, 346, 33; (b) M. T. Reetz and X. Li,
Tetrahedron, 2004, 60, 9709; (c) M. T. Reetz and X. Li, Angew. Chem.,
Int. Ed., 2005, 44, 2959.
1
2
3
4
a
100
100
100
100
97 (R)
97 (R)
96 (R)
91 (R)
Reactions were performed in the presence of 5 mmol of substrate
in 10 mL of CH2Cl2 at room temperature and a H2 pressure of
10 bar for 24 h. The molar ratio of 4a : Rh : L = 100 : 1 : 2.2 in the
b
first run. Enantiomeric excesses were determined by GC using a
Chiral Select 1000 capillary (0.25 mm 6 30 m) column.
This journal is ß The Royal Society of Chemistry 2006
Chem. Commun., 2006, 293–295 | 295