Highly enantioselective rhodium-catalyzed hydrogenation of β-dehydroamino acid derivatives using monodentate phosphoramidites

Article abstract of DOI:10.1021/ja028235t

New and very easily accessible monodentate phosphoramidite ligands have been developed that lead to excellent ee's and full conversions in the hydrogenation of (E)- and (Z)-β-dehydroamino acid derivatives with both aliphatic and aromatic side chains. Particularly, two different catalytic systems were established for (E)-β-(acylamino)acrylates (98-99% ee) and (Z)-β-(acylamino)acrylates (92-95% ee) based on phosphoramidites 2 and 3, respectively. Copyright

Full text of DOI:10.1021/ja028235t

Published on Web 11/16/2002
Highly Enantioselective Rhodium-Catalyzed Hydrogenation of
â-Dehydroamino Acid Derivatives Using Monodentate Phosphoramidites
Diego Pe n˜ a, Adriaan J. Minnaard,* Johannes G. de Vries,†,‡ and Ben L. Feringa*,†
†
,†
Department of Organic and Molecular Inorganic Chemistry, Stratingh Institute, UniVersity of Groningen,
Nijenborgh 4, 9747 AG Groningen, The Netherlands, and DSM Research, Life Sciences-Chemistry & Catalysis,
Geleen, The Netherlands
Received August 21, 2002
The asymmetric hydrogenation of prochiral olefins is one of the
most extensively studied reactions in homogeneous catalysis and
is widely applied in the preparation of optically active amino acids,
itaconic acids, and amines.1 Despite the successful use of mono-
phosphanes as chiral ligands in the pioneering studies on asymmetric
,2
3
hydrogenation of R-dehydroamino acid derivatives, the field has
been dominated for three decades by bidentate chiral ligands,1
,4
Figure 1. Monodentate phosphoramidites 1-3.
considered to be essential to achieve high enantioselectivities in
2
these hydrogenations. However, recent breakthroughs have ques-
tioned this common view as chiral monodentate phosphorus ligands
can also lead to high enantioselectivities in a number of asymmetric
4
5a
hydrogenations. In the past three years, monophosphines, mono-
phosphonites,5b monophosphoramidites, and monophosphites5d
have been successfully used in the enantioselective hydrogenation
5c
6
of R-dehydroamino acids and itaconic acid derivatives, and more
Figure 2. (E/Z)-â-(Acylamino)acrylates.
recently enamides.7
To examine the behavior of both ligands, they were first used in
the Rh-catalyzed hydrogenation of a benchmark substrate, methyl
Enantiomerically pure â-amino acid derivatives are important
building blocks in the synthesis of â-peptides and â-lactams. One
8
2
-acetamido cinnamate (N-acetyl-dehydrophenylalanine methyl
of the most facile routes to â-amino acids involves the asymmetric
hydrogenation of the corresponding dehydroamino acid precursors.
Although this approach has been widely used for the preparation
of R-amino acids, the enantioselective metal-catalyzed hydrogena-
tion of â-(acylamino)acrylates has turned out to be more problem-
atic, mainly because the catalytic behavior is highly dependent on
the structure of the substrate (E or Z isomers, aliphatic or aromatic
12
13
ester). Satisfyingly, under standard conditions, high selectivities
were obtained with both ligands. In the case of 2, the reaction was
slightly slower, but the enantioselectivity (95%) was enhanced as
compared to that of MonoPhos (1) under the same conditions (93%
ee). On the contrary, employing ligand 3, we found that the
hydrogenation was dramatically faster, although the enantioselec-
tivity (90%) was somewhat lower as compared to MonoPhos.
Remarkably, the ee of the product when using ligand 3 only depends
on the chirality of the bisnaphthol unit.14
9
side chains). To date, these hydrogenation approaches are based
on bidentate phosphine or phosphinite complexes with rhodium
BDPMI,9 DuPhos,
a
9c,e
9d
9e
9g,h
(
MiniPhos, BICP, and BPPM ) or
9b
9f
Encouraged by these findings, we decided to study monodentate
phosphoramidites 1-3 in the hydrogenation of â-dehydroamino
ruthenium (BINAPO and BINAP ). As far as we know, no
monodentate ligands have been described for the catalytic asym-
metric hydrogenation of â-(acylamino)acrylates.
acids (Figure 2, Table 1). Substrates 4a-f were prepared according
to a known procedure,9
a,b,e,f
allowing the formation of both Z and
We now report the use of new monodentate phosphoramidites
in the rhodium-catalyzed asymmetric hydrogenation of (E/Z)-â-
dehydroamino acid derivatives leading to excellent (up to 99% ee)
enantioselectivities.
E isomers simultaneously (4a-d) or exclusively the Z isomers
4e-f). These isomers can be separated by silica gel column
(
chromatography.
First, the hydrogenation of the Z isomers with aliphatic side
chains was examined. Full conversions and 92-95% ee were
obtained in the hydrogenation of (Z)-4a-d (entries 6-8 and 10),
A systematic optimization of the structure of MonoPhos (1), to
enhance both enantioselectivity and activity with this ligand in the
dehydroamino acid hydrogenation, initially led to the finding that
small R-groups on the amine unit of the ligand (Figure 1) are
necessary to achieve high stereocontrol.5 Further variations of
the amine function were introduced by preparing new phosphora-
midites [(S)-2 and (S,R)-3], readily obtained starting from (S)-
MonoPhos [(S)-1]11 via amine exchange, either with one larger
using 2 mol % of Rh(COD)
of ligand (S,R)-3 with respect to rhodium in i-PrOH under 10 bar
of H . Remarkably, the hydrogenation of (Z)-4e and (Z)-4f under
2 4
BF as catalyst precursor and 2 equiv
c,10
2
these conditions led to 92% and 94% ee (entries 12 and 13). To
the best of our knowledge, this is the highest ee so far reported in
the Rh-catalyzed hydrogenation of â-aryl-â-(acylamino)acrylates.
The best of all previous reported results is 75.6% ee with BDPMI
as ligand.9 Recently, up to 99% ee has been reported in the
ruthenium-catalyzed hydrogenation of â-aryl-â-dehydroamino acids
12
(
2, Bn) or with one smaller (3, H) N-substituent.
a
*
To whom correspondence should be addressed. E-mail: b.l.feringa@chem.rug.nl.
University of Groningen.
DSM Research.
†
‡
9b
using bidentate phosphinite ligands. During the optimization
14552
9
J. AM. CHEM. SOC. 2002, 124, 14552-14553
10.1021/ja028235t CCC: $22.00 © 2002 American Chemical Society

C O MMU N I C A T I O N S
Table 1. Asymmetric Hydrogenation of (E/Z)-4
and (Z)-â-dehydroamino acid derivatives with both aliphatic and
aromatic side chains. Particularly, two different catalytic systems
have been established for E (up to 99% ee) and Z (up to 95% ee)
isomers, based on the very easy fine-tuning of monophosphora-
midites leading to selectivities comparable to or better than those
reached with bidentate ligands reported so far.
cat
p
time
(h)
conv
(%)c
ee
(%)d
entry
4
ligand
solvent
(%)
(bar)
Acknowledgment. We thank Mr. M. B. van Gelder and Mr. E.
P. Schudde for technical support and Mr. M. van den Berg, Dr. J.
A. F. Boogers, and Dr. A. H. M. de Vries for useful discussions.
D.P. also thanks the European Community (IHP Program) for the
award of a Marie Curie Fellowship (contract no. HPMF-CT-2002-
a
1
(Z)-4a
(Z)-4a
(Z)-4a
(Z)-4a
(Z)-4a
(Z)-4a
(Z)-4b
(Z)-4c
(Z)-4c
(Z)-4d
(Z)-4d
(Z)-4e
(Z)-4f
3
3
3
3
3
3
3
3
3
3
3
3
3
EtOAc
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
1
1
1
1
1
2
2
2
0.5
2
2
2
2
1
1
1
24
24
3
16
1
0.3
0.3
0.3
1
0.3
0.05
0.3
0.3
88
98
40
3
20
47
77
94
95
94
94
94
92
92
92
94
a
2
a
3
a
4
10
10
10
10
10
10
10
25
10
10
100
100
100
100
100
100
100
100
100
100
b
5
b
6
7
8
9
0
1
2
3
01612).
b
b
Supporting Information Available: Experimental and chromato-
graphic details (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
b
b
1
1
1
1
b
b
b
References
a
a
a
a
a
b
b
b
b
b
b
14
15
16
17
18
19
20
21
22
23
24
(E)-4a
(E)-4a
(E)-4a
(E)-4a
(E)-4a
(E)-4a
(E)-4b
(E)-4c
(E)-4c
(E)-4c
(E)-4d
3
3
1
1
2
2
2
2
2
2
2
i-PrOH
CH2Cl2
i-PrOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
1
1
1
1
1
2
2
2
10
10
10
10
10
10
10
10
25
25
10
18
52
100
49
100
86
100
100
100
100
100
100
52
83
64
95
98
99
99
98
99
98
99
(1) (a) Knowles, W. S. Angew. Chem., Int. Ed. 2002, 41, 1998. (b) Noyori,
R. Angew. Chem., Int. Ed. 2002, 41, 2008. (c) Chaloner, P. A.; Esteruelas,
M. A.; Jo o´ , F.; Oro, L. A. Homogeneous Hydrogenation; Kluwer:
Dordrecht, 1994. (d) Brown, J. M. In ComprehensiVe Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
Berlin, 1999; Vol. 1, Chapter 5.1.
(2) (a) Zhang, X. Enantiomer 1999, 4, 541. (b) Noyori, R. Asymmetric
Catalysis in Organic Synthesis; Wiley & Sons: New York, 1994; Chapter
2.
18
18
18
18
4
4
4
3
6
(3) (a) Knowles, W. S.; Sabacky, M. J. Chem. Commun. 1968, 1445. (b)
Horner, L.; Siegel, H.; B u¨ the, H. Angew. Chem. 1968, 80, 1034. (c)
Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. Chem. Commun. 1972,
2
0.5
2
4
10. (d) Lagasse, F.; Kagan, H. B. Chem. Pharm. Bull. 2000, 48, 315.
(
4) For a recent rewiew, see: Komarov, I. V.; B o¨ rner, A. Angew. Chem., Int.
a
Ed. 2001, 40, 1197.
The reaction was performed at room temperature by dissolving 4,
b
(5) (a) Guillen, F.; Fiaud, J.-C. Tetrahedron Lett. 1999, 40, 2939. (b) Claver,
C.; Fernandez, E.; Gillon, A.; Heslop, K.; Hyett, D. J.; Martorell, A.;
Orpen, A. G.; Pringle, P. G. Chem. Commun. 2000, 961. (c) van den Berg,
M.; Minnaard, A. J.; Schudde, E. P.; van Esch, J.; de Vries, A. H. M.; de
Vries, J. G.; Feringa, B. L. J. Am. Chem. Soc. 2000, 122, 11539. (d) Reetz,
M. T.; Mehler, G. Angew. Chem., Int. Ed. 2000, 39, 3889.
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Wang, L.-X.; Zhou, Q.-L. Chem. Commun. 2002, 480. (b) Junge, K.;
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Tetrahedron Lett. 2002, 43, 4977. (c) Zeng, Q.; Liu, H.; Cui, X.; Mi, A.;
Jiang, Y.; Li, X.; Choi, M. C. K.; Chan, A. S. C. Tetrahedron: Asymmetry
2002, 13, 115. (d) Chen, W.; Xiao, J. Tetrahedron Lett. 2001, 42, 2897.
Rh(COD)2BF4, and ligand (100:1:2) in the suitable solvent. A solution of
Rh(COD)2BF4 and 2 equiv of ligand in CH2Cl2 (10 mM) was added to the
reaction mixture. Determined by H NMR. Determined by chiral GC.
The configuration of the product is R (5a-d) and S (5e-f). See Supporting
Information for details. For the absolute configuration of the ligands, see
Figure 1.
c
1
d
process, several observations were made: (1) A protic solvent leads
to an important increase in the enantioselectivity (compare entries
and 2).15 (2) At low hydrogen pressure, the ee decreases during
1
(e) Reetz, M. T.; Sell, T. Tetrahedron Lett. 2000, 41, 6333.
the reaction (entries 2 and 3). (3) Higher hydrogen pressure results
in a considerable increase in the enantioselectivity (entries 3 and
(
7) (a) van den Berg, M.; Haak, R. M.; Minnaard, A. J.; de Vries, A. H. M.;
de Vries, J. G.; Feringa, B. L. AdV. Synth. Catal. 2002, 344, 1003. (b)
Hu, A.-G.; Fu, Y.; Xie, J.-H.; Zhou, H.; Wang, L.-X.; Zhou, Q.-L. Angew.
Chem., Int. Ed. 2002, 41, 2348. (c) Jia, X.; Guo, R.; Li, X.; Yao, X.;
Chan, A. S. C. Tetrahedron Lett. 2002, 43, 5541.
8) (a) EnantioselectiVe Synthesis of â-Amino Acids; Juaristi, E., Ed.; Wiley-
VCH: New York, 1997. (b) Gellman, S. H. Acc. Chem. Res. 1998, 31,
173. (c) Cole, D. C. Tetrahedron 1994, 50, 9517.
9) (a) Lee, S.-g.; Zhang, Y. J. Org. Lett. 2002, 4, 2429. (b) Zhou, Y.-G.;
Tang, W.; Wang, W.-B.; Li, W.; Zhang, X. J. Am. Chem. Soc. 2002, 124,
4952. (c) Heller, D.; Holz, J.; Drexler, H.-J.; Lang, J.; Drauz, K.; Krimmer,
H.-P.; B o¨ rner, A. J. Org. Chem. 2001, 66, 6816. (d) Yasutake, M.;
Gridnev, I. D.; Higashi, N.; Imamoto, T. Org. Lett. 2001, 3, 1701. (e)
Zhu, G.; Chen, Z.; Zhang, X. J. Org. Chem. 1999, 64, 6907. (f) Lubell,
W. D.; Kitamura, M.; Noyori, R. Tetrahedron: Asymmetry 1991, 2, 543.
1
6
4
h
). (4) A dramatic increase in the reaction rate (TOF up to 1000
-
1
, entry 11) and in the ee of the product is obtained when a
(
preformed solution of both catalyst precursor and ligand in CH
2
-
Cl is added to the reaction mixture (entries 4 and 5). Under these
2
(
conditions, it is possible to reduce the amount of catalyst while
maintaining the same enantioselectivity (TON ) 200, entry 9).
In contrast to the results with the Z isomers, when studying the
hydrogenation of (E)-4a-d, ligand (S)-2 turned out to be the most
efficient, affording excellent enantioselectivities (98-99% ee,
entries 19-21 and 24) when using 2 mol % of Rh(COD)
catalyst precursor and 2 equiv of ligand 2 with respect to rhodium
in CH Cl under 10 bar of H . In this case, it was observed that by
(
g) Furukawa, M.; Okawara, T.; Noguchi, Y.; Terawaki, Y. Chem. Pharm.
Bull. 1979, 27, 2223. (h) Achiwa, K.; Soga, T. Tetrahedron Lett. 1978,
3, 1119.
2 4
BF as
1
(
10) Other authors (see ref 7b) recently also described the beneficial influence
2
2
2
of small alkyl groups on the nitrogen.
using a nonprotic solvent, better conversion and enantioselectivity
were obtained as compared to a protic solvent (entries 14 vs 15
and 16 vs 17). As in the Z series, the rate of the reaction and the
ee of the product were improved when a preformed solution of
(11) MonoPhos (1) was prepared from bis-â-naphthol and HMPT with excellent
yields: Hulst, R.; de Vries, N. K.; Feringa, B. L. Tetrahedron: Asymmetry
1994, 5, 699.
(12) See Supporting Information.
(
13) With 5% of Rh(COD)
monodentate ligand in EtOAc at room temperature, and 1 bar of H
14) Although the diastereoisomer (S,S)-3 seems to be less stable than (S,R)-
, both led to a similar ee. This result is analogous to one reported by
2 4
BF as the catalyst precursor, 11% of the
2
.
2 2
both catalyst precursor and ligand in CH Cl was added to the
(
3
reaction mixture (entries 18 and 19). Remarkably, at higher
hydrogen pressure, the same ee was reached (entry 21 and 22).16
Under these conditions, it was also possible to reduce the amount
of catalyst while maintaining the same enantioselectivity (entry 23).
In conclusion, new and readily accessible monodentate phos-
phoramidite ligands (2 and 3) have been developed that lead to
excellent ee’s and full conversions in the hydrogenation of (E)-
Reetz and Mehler in the case of monophosphites (see ref 5d).
15) It is known that polar solvents favor the hydrogenation of (Z)-â-
(acylamino)acrylates probably because these solvents can break up the
intramolecular hydrogen bond in the substrate and thus allow a selective
bidentate coordination to the metal (see ref 9a and f).
(
(16) Interestingly, it has been reported that in the case of bidentate phosphines,
the ee decreases upon increasing the pressure (see ref 9a and c).
JA028235T
J. AM. CHEM. SOC.
9
VOL. 124, NO. 49, 2002 14553