S. Lee, Y. J. Zhang / Tetrahedron: Asymmetry 13 (2002) 1039–1042
1041
In the hydrogenation of itaconic acid 4a with BDPMI
4. Experimental
ligands, it was found that the enantioselectivity
decreased as the bulk of the N-substituents increased.
Thus, the NꢀH ligand 1a induced higher enantioselec-
tivity (57.0% ee, entry 8 in Table 2) than the N-substi-
tuted ligands 1b (23.0% ee, entry 9), 1c (42.5% ee, entry
10) and 1d (8.6% ee, entry 11). In contrast with the
BDPMI ligands, the N-substituents in MOD-BDPMI
ligands affected the enantioselectivity positively, i.e. the
enantioselectivity improved with increasing A value of
the substituents.6 Thus, the N-benzylated MOD-
BDPMI ligand 2c exhibited the highest enantioselectiv-
ity (81.5% ee, entry 14) than the N-methylated 2b
(77.7% ee, entry 13) or the unsubstituted amine ligand
2a (68.3% ee, entry 12). However, in the hydrogenation
of dimethyl itaconate 4b (entries 15–20), the N-H
MOD-BDPMI ligand 2a exhibited the highest enan-
tioselectivity (74.4% ee, entry 18). These results indicate
that in the hydrogenation of a,b-unsaturated carboxylic
acids, the MOD-BDPMI ligands with electron-rich and
bulky phosphine groups showed better enantioselectiv-
ity than BDPMI ligands bearing diphenylphosphine
groups.
Unless otherwise noted, all hydrogenations were carried
out in an inert atmosphere. All solvents were degassed
prior to use. NMR spectra were recorded on a Bruker
300 spectrometer. GC analyses were performed using a
Hewlett–Packard 5890 Model. HPLC analyses were
performed using Agilent 1100 interfaced to a HP 71
series computer workstation.
4.1. General procedure for asymmetric hydrogenation
In a glovebox under an inert atmosphere, a reaction
flask was charged with [Rh(cod)2]BF4 (3.8×10−3 mmol)
and chiral ligand (4.7×10−3 mmol) in solvent (1 mL).
The mixture was stirred for 30 min at 20°C. An olefin
(for example, itaconic acid) (0.38 mmol) was added to
the reaction mixture, and hydrogenation was performed
under 1 atm of H2 for 12 h. The reaction mixture was
passed through a short silica gel column to remove the
catalyst. After evaporation of the solvent, the crude
1
reaction mixture was subjected to H NMR analysis to
determine the conversion. In order to determine the
enantiomeric excess, the hydrogenated acid product
was treated with chlorotrimethylsilane in methanol for
1 h to give the corresponding methyl ester. After evap-
oration of the solvent, a sample of the crude mixture
was analyzed by capillary GC or HPLC directly with-
out any further purification.
With respect to enantioselectivity, these are quite differ-
ent ligand effects to those observed in the hydrogena-
tions of electron-rich olefins, such as a-arylenamides, in
which higher enantioselectivities have been achieved
with BDPMI ligands.5 Moreover, it was also found that
the effects of the N-substituents in BDPMI and MOD-
BDPMI on the enantioselectivity are largely dependent
on the structure of the olefin. Consequently, each com-
bination of chiral ligand and prochiral olefin requires
careful optimization in order to obtain the best results.
Obviously a more in-depth study, including the synthe-
sis of MOD-BDPMI ligands having more sterically
demanding N-substituents and less bulky phosphine
N-Acetylphenylalanine methyl ester: HPLC column:
Chiralpack AD; eluent: n-hexane:i-PrOH=88:12; flow
rate: 1.0 mL/min; retention times: (R)-isomer=7.60
min, (S)-isomer=9.48 min.
Methyl dimethylsuccinate: GC column: Chiraldex G-
TA; flow rate of carrier gas (N2): 2 mL/min; column
temp.: 75°C isothermal; retention times: (R)-isomer=
17.54 min, (S)-isomer=18.58 min.
groups (for example,
a
ligand which has (p-
methoxyphenyl)phosphine groups) would be useful to
allow more accurate comparisons and the elucidation
of the key factors influencing the enantioselectivity with
Rh-BDPMI catalysts. In this way a more rational basis
for the design and improvement of such catalysts can
be achieved.
Acknowledgements
We are grateful for financial support from the Ministry
of Science and Technology (National Research Labora-
tory Program, 2N22890), from KIST (2E17512) and
CMDS at KAIST.
3. Conclusion
In summary, we have carried out the asymmetric
hydrogenation of electron deficient olefins, (Z)-a-(N-
acetamido)cinnamic acid 3, itaconic acid 4a and its
dimethyl ester 4b, using the Rh-complexes of the
BDPMI 1a–d and MOD-BDPMI 2a–c as catalysts. In
the hydrogenation of electron-deficient olefins, the
MOD-BDPMI ligands 2a–c bearing both a para-elec-
tron donating and meta-methyl groups proved to be
more efficient ligands than the BDPMI ligands 1a–c.
Therefore, in order to obtain high enantioselectivity
with electron-deficient olefins, ligands having electron-
rich phosphine groups may be required and vice versa.
The design and synthesis of more effective chiral lig-
ands and their applications in asymmetric catalytic
hydrogenation are currently in progress.
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