Highly Enantioselective Hydrogenation of α-Dehydroamino Acids by Rhodium Complexes with New Unsymmetric P-Chirogenic Bisphosphine Ligands

Article abstract of DOI:10.1021/ol006876s

(Matrix Presented) New rhodium catalysts with unsymmetric P-chirogenic bis(phosphino)ethanes, BisP*-Rh, exhibited very high enantioselectivity (98-99%) in the hydrogenation of α-dehydroamino acid derivatives. Such high enantioselectivity should result fro

Full text of DOI:10.1021/ol006876s

ORGANIC
LETTERS
2001
Vol. 3, No. 3
373-375
Highly Enantioselective Hydrogenation
of r-Dehydroamino Acids by Rhodium
Complexes with New Unsymmetric
P−Chirogenic Bisphosphine Ligands
Atsushi Ohashi* and Tsuneo Imamoto*
Department of Chemistry, Faculty of Science, Chiba UniVersity,
Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
imamoto@scichem.s.chiba-u.ac.jp
Received November 15, 2000
ABSTRACT
New rhodium catalysts with unsymmetric P−chirogenic bis(phosphino)ethanes, BisP*−Rh, exhibited very high enantioselectivity (98−99%) in
the hydrogenation of r-dehydroamino acid derivatives. Such high enantioselectivity should result from the asymmetric environment around
the Rh atom, as was shown in the molecular structure of the catalyst analyzed by X-rays. The asymmetry can be controlled by the combination
of the alkyl groups on the two phosphorus atoms.
Optically active phosphine-transition metal complexes have
played an important role in catalytic asymmetric synthesis.1
Since a C2 symmetric bisphosphine ligand, DIOP, showed
high enantioselectivity, it has been considered that C2
symmetric bisphosphine ligands are endowed with superior
catalytic properties.2 The C2 symmetric ligands such as
DIPAMP,3 BINAP,4 DuPHOS,5 BIPNOR,6 and PennPHOS7
have exhibited high enantioselectivity over a broad range.
On the other hand, it has been shown that unsymmetric
bisphosphine ligands,8 which have different groups on the
two phosphorus atoms, have also been shown to be effective
in some cases of asymmetric hydrogenation. However, an
unsymmetric bis(trialkylphosphine) ligand has not yet been
reported. We also reported previously that (S,S)-1,2-bis-
(alkylmethylphosphino)ethane (alkyl ) 1-adamantyl, tert-
butyl, cyclohexyl, cyclopentyl, 1,1-diethylpropyl; abbreviated
as BisP*) effected highly enantioselective hydrogenation of
R-dehydroamino acids.9
(1) Reviews: (a) Ojima, I., Ed. Catalytic Asymmetric Synthesis, 2nd ed.;
VCH publishers: Wheinheim, 2000. (b) Noyori, R. Asymmetric Catalysis
in Organic Synthesis; Wiley & Sons: New York, 1994. (c) Hayashi, T.;
Tomioka, K.; Yonemitsu, O. Asymmetric Synthesis; Kodansha: Tokyo,
1998. (d) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. ComprehensiVe
Asymmetric Catalysis; Springer: Berlin, 1999. (e) Kagan, H. B. Asymmetric
Synthesis; Morrison, J. D., Ed.; Academic Press: Orlando, 1985; Vol. 5,
Chapter 1.
(2) Kagan, H. B.; Dang, T.-P. J. Am. Chem. Soc. 1972, 94, 6429.
(3) Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J.; Bachman, G. L.;
Weinkauff, D. J. J. Am. Chem. Soc. 1977, 99, 5946.
(4) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi,
T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932.
(7) Jiang, Q.; Jiang, Y.; Xiao, D.; Cao, P.; Zhang, X. Angew. Chem.,
Int. Ed. 1998, 37, 1100.
(8) (a) Yoshikawa, K.; Yamamoto, N.; Murata, M.; Awano, K.;
Morimoto, T.; Achiwa, K. Tetrahedron; Asymmetry 1992, 3, 13. (b) Togni,
A.; Breutel, C.; Schnyder, A.; Spindler, F.; Landert, H.; Tijani, A. J. Am.
Chem. Soc. 1994, 116, 4062. (c) Carmichael, D.; Doucet H.; Brown, J. M.
Chem. Commun. 1999, 261.
(9) Imamoto, T.; Watanabe, J.; Wada, Y.; Masuda, H.; Yamada, H.;
Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J. Am. Chem. Soc. 1998, 120,
1635.
(5) (a) Burk, M. J. J. Am. Chem. Soc. 1991, 113, 8518. (b) Burk, M. J.
Angew. Chem., Int. Ed. 1998, 37, 1931.
(6) Robin, F.; Mercier, F.; Richard, L.; Mathey, F.; Spagnol, M. Chem.
Eur. J. 1997, 3, 1365.
10.1021/ol006876s CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/11/2001

Scheme 1
Recently, we prepared rhodium complexes coordinated
with new unsymmetric BisP* ligands (1a-c) which have
The preliminary hydrogenation with dehydro-N-acetyl-
phenylalanine methyl ester 4 in the presence of rhodium
complex 2a provided a quantitative yield of N-acetyl-
phenylalanine methyl ester 7 with 99.2% ee (R) (Scheme
2).
Scheme 2
different alkyl groups on the two P* atoms in order to
introduce an asymmetric environment around the Rh atom
more effectively.10 This Letter reports a series of enantio-
selective hydrogenations of R-dehydroamino acid derivatives
using the newly designed unsymmetric BisP*-Rh catalysts
and proposes a design concept to obtain high enantioselec-
tivity.
The synthetic route to obtain the unsymmetric BisP*-Rh
is shown in Scheme 1. The bisphosphine-borane precursors,
(R)-1-boranato[alkyl(methyl)phosphino]ethanol 2-tosylates or
(R)-1-boranato[alkyl(methyl)phosphino]ethanol 2-mesylates,
were synthesized from alkyl(dimethyl)phosphine-boranes
in three steps. The tosylates and mesylates were coupled with
lithiated (S)-alkylmethylphosphine-boranes11 to provide
(S,S)-unsymmetric BisP*-BH3, which were converted into
the corresponding cationic rhodium complexes according to
the reported procedure.12
Encouraged by this result, various R-dehydroamino acid
derivatives were applied as reagents (Table 1). Asymmetric
hydrogenation of di- or trisubstituted dehydroamino acid
derivatives 4 and 5 with 1a showed very high enantioselec-
tivity (entries 3 and 8), although 1b and 1c provided 4 and
5 with considerably lower enantioselectivity (entries 4, 5, 9,
and 10).
It has been considered difficult to achieve high enantio-
selectivity in the hydrogenation of tetrasubstituted R-dehy-
droamino acid derivatives.13 The symmetric BisP*-Rh’s also
gave low enantiomeric excesses (entries 11, 12, 16, and 17),
although they showed somewhat higher values for 6c (entries
21 and 22). However, 1b and 1c showed very high enantio-
selectivity for the valine derivative 6a (entries 14 and 15),
although 1a gave a low value for 6a (entry 13). A similar
tendency of enantioselectivity was observed for 6b (entries
18-20) and 6c (entries 23-25), although remarkable dif-
ference was observed between 1b and 1c in the hydrogena-
tion of 6c.
(10) Ohashi, A.; Imamoto, T. Tetrahedron Lett., in press.
(11) Nagata, K.; Matsukawa, S.; Imamoto, T. J. Org. Chem. 2000, 65,
4185.
(12) (a) McKinstry, L.; Livinghouse, T. Tetrahedron Lett. 1994, 35, 9319.
(b) Mckinstry, L.; Livinghouse, T. Tetrahedron 1994, 50, 6145.
(13) (a) Burk, M. J.; Gross, M. F.; Martinez, J. P. J. Am. Chem. Soc.
1995, 117, 9375. (b) Sawamura, M.; Kuwano, R.; Ito, Y. J. Am. Chem.
Soc. 1995, 117, 9602.
(14) Complex 2a: monoclinic P21 (No. 4); a ) 11.045(6) Å, b )
13.512(9) Å, c ) 17.94(2) Å, â ) 91.98(3)°, V ) 2031 Å3, Z ) 2, R )
0.055; Rw ) 0.075; GOF ) 1.75; bond lengths Rh1-P1 2.315(3) Å, Rh1-
P2 2.316(3) Å, Rh1-nbd ca. 2.2 Å, bond angles P1-Rh1-P2 82.9(1)°,
1-Ad-P1-Me 106.3(6)°, t-Bu-P2-Me 104.8°, torsion angle P1-C-C-
P2 48.2(9)°.
To examine the asymmetric environment around the rho-
dium atom, crystallizations of 2a-c were performed. After
many trials, only 2a gave crystals suitable for X-ray work.
The molecular structure of 2a is depicted in Figure 1.14
The bond distances, bond angles, and torsion angles around
374
Org. Lett., Vol. 3, No. 3, 2001

Table 1. Rh-Catalyzed Enantioselective Hydrogenation of
R-Dehydroamino Acid Derivativesa
Figure 1. ORTEP drawing of rhodium complex (30% probability)
[Rh((S,S)-AdtBu-BisP*)(nbd)]BF4 (2a): the hydrogen atoms and the
BF4 anion are omitted for clarity. Dihedral angles C1-P1-Rh-
P2 46.9°, C2-P2-Rh-P1 26.7°.
the symmetric BisP*-Rh since steric repulsion of the
1-adamanyl group on P1 with the neighboring atoms is
different from that of the tert-butyl group. The distortion is
well explained by the dihedral angles between the planes of
P1-Rh-P2 and Rh-P1-C1, and between the planes of P1-
Rh-P2 and Rh-P2-C2. The former dihedral angle of the
1-adamantyl group is 46.9° whereas the latter one of the tert-
butyl group is 26.7°. These values are nearly the same for
the symmetric BisP*-Rh complex. Such a difference should
cause a further asymmetric environment around the Rh atom.
The asymmetry should be introduced when the substrate
molecule comes close to the Rh atom at the transition state.
In summary, catalytic asymmetric hydrogenation of di-,
tri-, or tetrasubstituted R-dehydroamino acid derivatives by
the unsymmetric BisP*-Rh 2a-c gave high reactivity and
enantioselectivity. X-ray crystallographic analysis of 2a
exhibited a distorted chelation ring structure compared with
the corresponding ones of the symmetric BisP*-Rh com-
plexes. This suggests that the asymmetric environment is
effectively controlled by choosing the alkyl groups on the
phosphorus atoms.
Acknowledgment. The authors thank Kosuke Katagiri
for X-ray analysis. This work was supported by a Grant-in-
Aid from The Ministry of Education, Science, Culture and
Sport, Japan.
Supporting Information Available: Experimental pro-
cedures for the preparation of unsymmetric BisP*-BH3 (3a-
c), a general experimental procedure for the enantioselective
hydrogenation, and characterization data for compounds 1-3.
This material is available free of charge via the Internet at
http://pubs.acs.org.
the Rh and two phosphorus atoms are approximately the
same as the corresponding ones of the symmetric BisP*-
Rh. However, the conformation of the five-membered
chelation ring is strongly distorted compared with that of
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