Highly enantioselective hydrogenation of α-dehydroamino acids by rhodium complex with H8-MonoPhos

Article abstract of DOI:10.1016/S0957-4166(02)00096-4

H₈-MonoPhos, a new stable and easily prepared monodentate phosphoramidite ligand, has been synthesized from H₈-BINOL. The ligand showed extremely highly enantioselectivity of higher than 99.9% e.e. in the asymmetric Rh-catalyzed hydr

Full text of DOI:10.1016/S0957-4166(02)00096-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 115–117
Highly enantioselective hydrogenation of a-dehydroamino acids
by rhodium complex with H8-MonoPhos
Qingle Zeng,a Hui Liu,a Xin Cui,a Aiqiao Mi,a Yaozhong Jiang,a,* Xingshu Li,b
Michael C. K. Choib and Albert S. C. Chanb
aUnion Laboratory of Asymmetric Synthesis, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu
610041, China
bOpen Laboratory of Chirotechnology and Department of Applied Biology and Chemical Technology, The Hong Kong
Polytechnic University, Hong Kong, China
Received 9 January 2002; accepted 20 February 2002
Abstract—H8-MonoPhos, a new stable and easily prepared monodentate phosphoramidite ligand, has been synthesized from
H8-BINOL. The ligand showed extremely highly enantioselectivity of higher than 99.9% e.e. in the asymmetric Rh-catalyzed
hydrogenation of a-dehydroamino acids. Our study further supports the new concept that there is no gap in efficiency and
enantioselectivity between monodentate and chelating ligands for asymmetric catalysis. © 2002 Elsevier Science Ltd. All rights
reserved.
An important recent breakthrough in asymmetric
hydrogenation is the discovery that monodentate cata-
lytic ligands may induce higher enantioselectivity than
their bidentate analogues. Herein our study further
demonstrates that monodentate ligands may provide
excellent chiral induction, comparable to that of the
best chelating ligands.
thermore, H8-BINOL is somewhat different from
BINOL in conformation and electronic character. Some
ligands based on H8-BINOL show higher asymmetric
induction than those based on BINOL in many asym-
metric transformations such as hydrogenation,4 alkyla-
tion of aldehydes5 and hetero-Diels–Alder reaction.6
Prompted by these results and the facile preparation of
H8-BINOL from BINOL, we synthesized the H8-
Amongst the monodentate phosphorous ligands,1–3
Feringa’s MonoPhos 1 (Fig. 1) derived from 1,1%-bi-2-
naphthol (BINOL) gave the best results.3 However, its
solubility is low in some solvents, which resulted in
decreased rate of hydrogenation.3 We thought that if
the BINOL backbone was replaced by H8-BINOL, the
resulting compound would have better solubility. Fur-
BINOL based monodentate phosphoramidite
2
(shorted as H8-MonoPhos) and investigated its applica-
tion in the enantioselective hydrogenation of a-dehydro-
amino acid derivatives. To our best knowledge, no
H8-BINOL backbone has been used as a monodentate
phosphorous ligand until now.
H8-BINOL was prepared by the reduction of BINOL
with NiꢀAl alloy under strongly basic conditions.7
Treatment of (R)-H8-BINOL with hexamethylphospho-
rous triamide gave (R)-H8-MonoPhos 28 in high yield.
O
O
P
N
1
Its structure was fully characterized by H, 13C and 31P
P
N
O
O
NMR. Unlike MonoPhos 1, H8-MonoPhos 2 is soluble
in most common organic solvents, which provides a
wide scope of solvents for optimizing the reaction con-
ditions for various substrates.
(S)-MonoPhos 1
(R)-H8-MonoPhos 2
Figure 1. (S)-MonoPhos 1 and (R)-H8-MonoPhos 2.
Initially, we screened solvents and hydrogen pressure in
the hydrogenation of dehydro-N-acetylphenylalanine
methyl ester 3a (Table 1). All of the resulting e.e. values
in the tested solvents are higher than or comparable to
* Corresponding author. Tel.: +86-28-5229250; fax: +86-28-5223978;
e-mail: ulas@cioc.ac.cn
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00096-4

116
Q. Zeng et al. / Tetrahedron: Asymmetry 13 (2002) 115–117
Table 1. Enantioselective hydrogenation of a-dehydroamino acid derivatives 3 by H8-MonoPhos-Rh complexa
Entry
Substrates
t (h)
Solvents
E.e.b (%)
Conv.b (%)
1
2
3
4
5
6
7
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
2
Toluene
ClCH2CH2Cl
CH2Cl2
AcOEt
94.9
95.0
94.4
95.7
94.2
95.4
96.0
94.8
95.6
95.6
96.4
94.4
96.0
98.0
92.5
95.9
99.9
99.9
99.1
99.7
99.3
96.9
90.2
99.2
98.9
99.7
96.8
99.6
99.9
95.9
99.9
99.9
98.6
99.9
99.9
99.9
0.5
0.5
0.5
0.5
1
0.5
6
1
0.5
8
0.5
5
5
0.5
2
THF
Acetone
i-PrOH
i-PrOH
i-PrOH
i-PrOH
Acetone
Acetone
CH2Cl2
CH2Cl2
Acetone
Acetone
Acetone
Acetone
8c
9d
10e
11f
12
13g
14g
15
16
17
18f
3g
3g
0.5
8
a Reactions were performed with 0.1 M solutions of substrates at S/C=100/1 at rt and 20 bar initial hydrogen pressure unless otherwise noted.
b E.e. and conversion were determined by GC on a CP-Chirasil-
L-Val column. The configurations of all the predominant products were in S form.
c 1 bar of H2.
d 10 bar of H2.
e 40 bar of H2.
f The substrate to catalyst mole ratio is 500.
g 100 psi of H2.
those of MonoPhos. The effects of solvents on the
chiral induction are minimal (entries 1–7); that is, H8-
MonoPhos is one of the rare ligands that have extensive
adaptation to various solvents. Increased hydrogen
pressure accelerated the reaction but played a minor
role in enantioselectivity (entries 7–10). Interestingly,
when the substrate to catalyst ratio was increased from
100 to 500, the reaction gave consistent e.e. value (entry
11). It is notable that the substrate could not be com-
of
L
-Dopa 3f was reduced completely over 2 h with
excellent e.e. (entry 16). In particular, methyl N-
acetamidoacrylate 3g was hydrogenated to give 4g with
higher than 99.9% e.e. (entries 17 and 18) and quantita-
tive conversion even in the presence of 0.2 mol% cata-
lyst, which is comparable to the results of the best
chelating catalysts.
In summary, a new monodentate phosphoramidite H8-
MonoPhos 2 was designed and synthesized. Excellent
e.e. values are obtained in the H8-MonoPhos–rhodium-
catalyzed hydrogenation of a-dehydroamino acid
derivatives, which demonstrates that H8-MonoPhos is
comparable to the best mono- and bidentate phosphine
ligands.
pletely hydrogenated in toluene with
5 (mol)%
rhodium–MonoPhos complex under ambient H2 pres-
sure for 20 h due to poor solubility of the catalyst;3 but
the reaction did reach completion with 1 mol% H8-
MonoPhos–rhodium complex under 20 bar of H2 for 2
h (entry 1).
We next sought to investigate the hydrogenation of
some other dehydroamino acid substrates. Excellent
enantioselectivities were achieved for the dehy-
drophenylalanines 3b, 3c and 3d with electron-donating
and withdrawing para-substituents on the phenyl
group, but for the ortho-substituted 3e a slightly lower
e.e. value was obtained (entries 12–15). The precursor
Acknowledgements
We are grateful for financial support from the National
Science Foundation of China (29872036) and The
Hong Kong Polytechnic University ASD Fund.

Q. Zeng et al. / Tetrahedron: Asymmetry 13 (2002) 115–117
117
References
5. (a) Chan, A. S. C.; Zhang, F. Y.; Yip, C. W. J. Am. Chem.
Soc. 1997, 119, 4080; (b) Zhang, F. Y.; Yip, C. W.; Cao,
R.; Chan, A. S. C. Tetrahedron: Asymmetry 1997, 8, 585;
(c) Zhang, F. Y.; Chan, A. S. C. Tetrahedron: Asymmetry
1997, 8, 3651.
1. Claver, C.; Fernandez, E.; Gillon, A.; Heslop, K.; Hyett, D.
J.; Martorell, A.; Orpen, A. G.; Pringle, P. G. Chem.
Commun. 2000, 961.
6. Wang, B.; Feng, X. M.; Cui, X.; Liu, H.; Jiang, Y. Z. Chem.
2. (a) Reetz, M. T.; Mehler, G. Angew. Chem., Int. Ed. Engl.
2000, 39, 3889; (b) Reetz, M. T.; Sell, T. Tetrahedron Lett.
2000, 41, 6333.
3. 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.
4. (a) Zhang, X.; Uemura, T.; Matsumura, K.; Kumobayashi,
H.; Sayo, N.; Takaya, H. Synlett 1994, 7, 501; (b) Uemura,
T.; Zhang, X.; Matsumura, K.; Sayo, N.; Kumobayashi, H.;
Ohta, T.; Nozaki, K.; Takaya, H. J. Org. Chem 1996, 61,
5510; (c) Zhang, F. Y.; Pai, C. C.; Chan, A. S. C. J. Am.
Chem. Soc. 1998, 120, 5808; (d) Zhang, F. Y.; Kwok, W.
H.; Chan, A. S. C. Tetrahedron: Asymmetry 2001, 12, 2337.
Commun. 2000, 1605.
7. Guo, H.; Ding, K. L. Tetrahedron Lett. 2000, 41,
10061.
1
8. (R)-H8-MonoPhos 2: [h]3D2−310 (c 0.610, THF); H NMR
(400 MHz, CDCl3) l 1.52–1.62 (m, 2H), 1.74–1.81 (m, 6H),
2.18–2.36 (m, 2H), 2.486 (d, 6H, J=8.8 Hz), 2.56–2.71 (m,
2H), 2.74–2.87 (m, 4H), 6.836 (d, H, J=6.0 Hz), 6.990 (d,
H, J=3.9 Hz), 7.010 (d, H, J=3.9 Hz), 7.068 (d, H, J=6.3
Hz); 13C NMR (75.5 MHz, CDCl3) l 22.5, 22.7, 22.8, 27.6,
27.7, 22.7, 29.0, 29.1, 35.6, 35.9, 118.5, 118.6, 128.2, 128.3,
129.2, 132.9, 137.4, 137.8, 137.9, 148.2, 148.3, 148.6; 31P
NMR (121.5 MHz, CDCl3) l 143.4.