J. Am. Chem. Soc. 1997, 119, 1799-1800
Highly Enantioselective Rh-Catalyzed
1799
Hydrogenations with a New Chiral 1,4-Bisphosphine
Containing a Cyclic Backbone
Guoxin Zhu, Ping Cao, Qiongzhong Jiang, and
Xumu Zhang*
Department of Chemistry
The PennsylVania State UniVersity
UniVersity Park, PennsylVania 16802
ReceiVed October 1, 1996
The design and synthesis of chiral phosphine ligands have
played a significant role in the development of transition metal
catalyzed asymmetric reactions.1 Over 1000 chiral bisphos-
phines2 have been made, and several industrial processes have
used their transition metal complexes as catalysts for the
production of enantiomerically pure compounds (e.g., syntheses
of L-DOPA,3 L-menthol,4 and carbapenems4). While high
selectivities were observed in many reactions using chiral
bisphosphines, such as DIPAMP,5 DIOP,6 Chiraphos,7 Skew-
phos,8 BPPM,9 DEGphos,10 BINAP,11 Duphos,12 BPE,12 and
others,13 there are a variety of reactions where these ligands
are not efficient in their activity and selectivity. The search
for new well-designed chiral ligands is therefore still an
important goal in the field of asymmetric catalysis. Herein we
report the synthesis and application of a new chiral 1,4-
bisphosphine, (2R,2′R)-bis(diphenylphosphino)-(1R,1′R)-dicy-
clopentane (1) (abbreviated (R,R)-BICP) (Figure 1) in the
rhodium-catalyzed asymmetric hydrogenation of R-(acylamino)-
acrylic acids. The key feature of this ligand is that it contains
two cyclopentane rings in its backbone which are present to
restrict its conformational flexibility. We hypothesize this
conformational rigidity leads to high enantioselectivity in
asymmetric reactions. The four stereogenic carbon centers in
the backbone of this phosphine dictate the orientation of
P-phenyl groups. This structure is fundamentally different from
Figure 1.
Figure 2.
Figure 3.
either axially dissymmetric BINAP or bisphosphines with two
stereogenic carbon centers in their backbones such as Chiraphos
and BPPM.
The enantioselectivity achieved with many asymmetric transi-
tion metal catalysts bearing chiral C2 symmetric bisphosphines
can be rationalized by using a simple quadrant diagram (Figure
2).3 Good asymmetric catalysts generally have their ligands
effectively shielding two diagonal quadrants. The absolute
configuration of the ligand dictates which two quadrants are
blocked. The extent to which the quadrants are blocked has a
strong influence on the reaction enantioselectivity.
(1) (a) Morrison, J. D., Ed. Asymmetric Synthesis; Academic Press: New
York, 1985; Vol. 5. (b) Bosnich, B., Ed. Asymmetric Catalysis; Martinus
Nijhoff Publishers: Dordrecht, The Netherlands, 1986. (c) Brunner, H.
Synthesis 1988, 645. (d) Noyori, R.; Kitamura, M. In Modern Synthetic
Methods; Scheffold, R., Ed.; Springer-Verlag: Berlin, Heidelberg, 1989;
Vol. 5, p 115. (e) Nugent, W. A., RajanBabu, T. V., Burk, M. J. Science
1993, 259, 479. (f) Ojima, I., Ed. Catalytic Asymmetric Synthesis; VCH:
New York, 1993. (g) Sheldon, R. A. Chirotechnology; Marcel Dekker: New
York, 1993. (h) Noyori, R. Asymmetric Catalysis In Organic Synthesis;
John Wiley & Sons: New York, 1994.
(2) (a) Brunner, H. In Topics in Stereochemistry; Interscience: New York,
1988; Vol. 18, p 129. (b) Brunner, H., Zettlmeier W., Eds. Handbook of
EnantioselectiVe Catalysis; VCH: New York, 1993; Vol. 2.
(3) Knowles, W. S. Acc. Chem. Res. 1983, 16, 106.
A breakthrough in asymmetric catalysis came with DIOP, a
C2 symmetric chiral bisphosphine prepared from tartaric acid.6
This landmark ligand has been used in a number of transition
metal catalyzed asymmetric reactions.1 The enantioselectivity
with DIOP, however, is not as good in many asymmetric
reactions as some other chiral bisphosphines (e.g., BINAP4). A
possible explanation for this observation is that the seven-
membered chelate ring of DIOP bound to a transition metal is
too conformationally flexible (the transfer of backbone chirality
to the phenyl groups on the phosphine goes through a methylene
group). Figure 3 illustrates the conformational ambiguities in
DIOP metal complexes which could result in the erosion of
enantioselectivities.14
(4) (a) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345. (b) Noyori,
R. Science 1990, 248, 1194.
(5) (a) Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. J. Chem. Soc.,
Chem. Commun. 1972, 10. (b) Vineyard, B. D.; Knowles, W. S.; Sabacky,
M. J.; Bachman, G. L.; Weinkauff, D. J. J. Am. Chem. Soc. 1977, 99, 5946.
(6) Kagan, H. B.; Dang, T.-P. J. Am. Chem. Soc. 1972, 94, 6429.
(7) Fryzuk, M. D.; Bosnich, B. J. Am. Chem. Soc. 1977, 99, 6262.
(8) MacNeil, P. A.; Roberts, N. K.; Bosnich, B. J. Am. Chem. Soc. 1981,
103, 2273.
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Yoda, N. Tetrahedron Lett. 1980, 21, 1051.
(10) Nagel, U.; Kinzel, E.; Andrade, J.; Prescher, G. Chem. Ber. 1986,
119, 3326.
(11) (a) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.;
Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932. (b) Miyashita,
A.; Takaya, H.; Souchi, T.; Noyori, R. Tetrahedron 1984, 40, 1245. (c)
Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.;
Takemomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629.
(d) Takaya, H.; Akutagawa, S.; Noyori, R. Org. Synth. 1988, 67, 20.
(12) (a) Burk, M. J.; Feaster, J. E.; Harlow, R. L. Organometallics 1990,
9, 2653. (b) Burk, M. J. J. Am. Chem. Soc. 1991, 113, 8518. (c) Burk, M.
J.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am. Chem. Soc. 1993,
115, 10125. (d) Burk, M. J.; Lee, J. R.; Martinez, J. P. J. Am. Chem. Soc.
1994, 116, 10847.
Since achieving conformationally unambiguous coordination
geometry between transition metals and chiral ligands is
important in the development of efficient ligand systems, we
have designed the chiral 1,4-bisphosphine 1 by introducing rings
into the backbone. Molecular modeling (MM2 calculations
based on the CAChe program) shows that the preferred
conformation of transition metal complexes of 1 is a highly
skewed seven-membered ring (Figure 1). The two axial phenyls
stay back and parallel to two methylene groups. The two
equatorial phenyls protrude into the P-M-P in-plane coordina-
(13) (a) Sawamura, M.; Kuwano, R.; Ito, Y. J. Am. Chem. Soc. 1995,
117, 9602. (b) Rajanbabu, T. V.; Ayers, T. A.; Casalnuovo, A. L. J. Am.
Chem. Soc. 1994, 116, 4101. (c) Inoguchi, K.; Achiwa, K. Synlett 1991,
49.
(14) See: ref 1g, p 284.
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