Chiral Phosphine-Phosphite Ligands
J . Org. Chem., Vol. 66, No. 23, 2001 7629
in reactivity and selectivity between rhodium complexes
containing ligands 4a and 4b is remarkable when
compared to ligands 2a and 2b, which both afforded
similar ee’s of different enantiomers. We suggest that the
small bite angles of the rhodium complexes containing
ligands 4 enhance a cooperative effect between the
stereocenters, which results in a matched combination
for ligand 4b and a mismatched combination for ligand
4
a . Ligands 1-3 have a larger bite angle, and therefore
the substituents of the phosphine moiety and the carbon
stereocenter are not in close proximity.
Table 4 shows the results of the rhodium-catalyzed
hydrogenation of methyl (Z)-(N)-acetylaminocinnamate.
In general, the hydrogenation of methyl (Z)-(N)-acetyl-
aminocinnamate followed the same trend as that of
methyl (N)-acetylaminoacrylate. However, the enantio-
meric excesses were somewhat smaller, and the reaction
rates were lower. Using the same ligand in the hydro-
genation reaction of methyl (N)-acetylaminoacrylate and
methyl (Z)-(N)-acetylaminocinnamate produced the same
configurations for the corresponding products 6 and 8,
respectively, and similar ee’s. The catalyst containing
ligand 1a gave the highest ee of 97% (R) for this series
at a low reaction rate (entry 14). Ligand 4b afforded the
highest reaction rate, and there was a cooperative effect
between the stereogenic phosphine moiety and the ste-
reocenter at the backbone (entry 23). Complexes with
ligands 2 and 4 afforded the highest reaction rates
together with high enantioselectivities of all the ligands
used.
F igu r e 3. Diastereomeric [Rh(P
1
2
-P )(5)] complexes.
Sch em e 2
Ta ble 5. Kin etic Da ta for th e Hyd r ogen a tion of 5
Ca ta lyzed by [Rh (2a )(cod )]BF 4 in Dich lor om eth a n e
PH2a
[Rh(2a )(cod)]BF4b
TOFc
1
2
3
1
1
0.0017
0.0017
0.0017
0.005
42.1
75.3
131.7
117.8
13.2
Mech a n istic Con sid er a tion s. The mechanism of the
enantioselective hydrogenation catalyzed by cationic
diphosphine rhodium complexes has been thoroughly
studied. The widely accepted catalytic cycle, a result from
the work by the groups of Brown, Halpern, Landis, and
Bosnich, involves the reversible binding of the substrate
to the catalyst, followed by the rate-determining oxidative
0.0005
a
Pressure in bar. Concentration in mol‚l-1. c TOF measured
b
-
1
-1
in mol‚molRh ‚h
.
doublets at 136.02 and 35.57 ppm were observed in the
addition of H
2
and the subsequent rapid elimination of
3
1
1
the hydrogenated product.13 Halpern’s classic studies
13a
P{ H} NMR spectrum. These new signals were assigned
+
to the cationic rhodium complex [Rh(2a )(5)] and at-
tributed to the phosphine and phosphite moieties, re-
on hydrogenation have shown that enantioselectivity is
determined by the ratio of the initially formed diastereo-
+
spectively. The P -P coupling constant is 56 Hz, whereas
isomers of [Rh(P
and the respective reactivities of these intermediates
toward H . Since phosphine-phosphite ligands have
1
-P
2
)(substrate)] complexes (Figure 3)
1
2
J {P
1
-Rh} and J {P -Rh} are 241 and 161 Hz, respec-
31 1
2
tively. The shift of the phosphite signal in the P{ H}
2
4
NMR spectrum of complex [Rh(2a )(5)]BF is consistent
different properties compared to diphosphines, the cata-
lytic sequence is not necessarily the same. To learn more
about the catalytic cycle, we monitored the hydrogenation
of methyl acetamidoacrylate ester (5) using ligand 2a by
with a diastereoisomer the phosphite of which is trans
to the CdO fragment and the phosphine of which is trans
to the CdC fragment.1 Variable-temperature P{ H}
NMR spectra between 303 and 193 K showed that only
one diastereoisomer was present. Furthermore, the for-
3a
31
1
3
1
1
P{ H} NMR. We examined a solution of [Rh(2a )(cod)]-
BF in dichloromethane-d at 1 bar of dihydrogen, but a
Rh(2a )(cod)H ] species was not detected. After methyl
acetamidoacrylate ester was added, two new double
4
2
1
mation of hydride species was not observed in the H
NMR spectrum.
These results show that the so-called alkene pathway
[
2
(
pathway A, Scheme 2) seems to be the preferred route.
(
13) (a) Landis, C. R.; Halpern, J . J . Am. Chem. Soc. 1987, 109, 1746.
b) Brown, J . M.; Chaloner, P. A.; Morris, G. A. J . Chem. Soc., Chem.
Commun. 1983, 644. (c) Brown, J . M.; Evans, P. L. Tetrahedron Lett.
988, 44, 4905. (d) Bodgan, P. L.; Irwin, J . J .; Bosnich, B. Organome-
(
Pathway B (Scheme 2), in which a dihydrogen complex
was formed, cannot be excluded, since species [Rh(2a )-
1
2 4
(cod)H ]BF may be present in amounts below the detec-
tallics 1989, 8, 1450. (e) Alcock, N. W.; Brown, J . M.; Derome, A. E.;
Lucy, A. R. J . Chem. Soc., Chem. Commun. 1985, 575. (f) Allen, D. G.;
Wild, S. B.; Wood, D. L. Organometallics 1986, 5, 1009. (g) Brown, J .
M.; Maddox, P. J . J . Chem. Soc., Chem. Commun. 1987, 1278. (h)
Brown, J . M.; Chaloner, P. A.; Morris, G. A. J . Chem. Soc., Perkin
Trans. 2 1987, 1583. (i) McCulloch, B. M.; Halpern, J . T., M. R.; Landis,
C. R. Organometallics 1990, 9, 1392. (j) Brown, J . M. Chem. Soc. Rev.
993, 22, 25. Landis, C. R.; Brauch, T. W. Inorg. Chim. Acta 1998,
70, 285. (k) Kimmich, B. F. M.; Somsook, E.; Landis, C. R. J . Am.
Chem. Soc. 1998, 120, 10115. (l) Landis, C. R.; Hilfenhaus, P.; Feldgus,
S. J . Am. Chem. Soc. 1999, 121, 8741. (m) RajanBabu, T. V.; Radetich,
B.; You, K. K.; Ayers, T. A.; Casalnuovo, A. L.; Calabrese, J . C. J . Org.
Chem. 1999, 64, 3429.
tion limit of the NMR equipment.
To obtain more insight into the sequence of the cycle,
we studied the rate dependence on substrate concentra-
tion, hydrogen pressure, and rhodium concentration. The
data collected in Table 5 indicate that the reaction is first
order in rhodium concentration and hydrogen pressure.
For a typical hydrogenation reaction, performed at
standard conditions, the formation of hydrogenated
product shows a zeroth-order dependency on substrate
1
2
Deerenberg
