CeCl3 ·7H2O in Hydrogenation of Aromatic R-Ketoesters
R-hydroxy ester,9 hydrogen mediated C-C bond formation,10
and synthesis of chiral cyanohydrins as precursors via metal
catalysts and organocatalysts11) available for the preparation of
these compounds, transition metal catalyzed enantioselective
hydrogenation proved most efficient. However,asymmetric
hydrogenation of R-ketoesters has received much less attention
than the hydrogenation of dehydroamino acid derivatives and
ꢀ-ketoesters, and there are only a few ligands that afford high
enantioselectivities for this substrate class.6m–o Therefore, the
search for effective, high enantioselective, and universal ap-
proaches to R-hydroxy acids or esters is still of significance.
We have reported that aromatic R-ketoesters were hydroge-
nated efficiently with high enantioselectivities by employing
Lewis acid additives and our chiral diphosphines.12 We extended
these studies to a variety of aromatic R-ketoesters, and here we
report the effect of different substituents of aryls on the catalyst
performances and the function of the additives.
Results and Discussion
In our previous letter, with the use of methyl benzoylformate
as the model substrate, the effect of ligands, solvents, and the
additives on reactivity and enantioselectivity was screened.12
In general, both Brønsted acids and Lewis acids could be used
as additives to improve enantioselectivities in the asymmetric
hydrogenations, but when Lewis acids were used as additives
in the hydrogenation of our model substrate with [RuCl(ben-
zene)(S)-SunPhos]Cl (4) as the catalyst, dramatically improved
enantioselectivities (90-96% ee vs 85-89% ee) were obtained.
A variety of lanthanide (LnCl3 ·XH2O) salts proved effective,
and for reasons of simplicity, CeCl3 ·7H2O was chosen as the
preferred additive.
Based on the initial success of asymmetric hydrogenation of
R-ketoesters with 4 and CeCl3 ·7H2O as the additive, we
employed ethyl benzoylformate as the model substrate to study
the effect of Ru catalyst precursors. Toward this end, [Ru-
Cl(benzene)(S)-SunPhos]Cl (4),6c RuCl2[(S)-SunPhos](DMF)m
(5),13 and [NH2Me2]+[{RuCl [(S)-SunPhos]}2(µ-Cl3)] (6)14 were
tested across a range of reaction temperatures and concentrations
for enantioselectivity, and the results are summarized in Table
1. In the presence of CeCl3 ·7H2O, all Ru precursors led to complete
conversion with comparable enantioselectivities, and the results are
superior to those obtained without addition of CeCl3 ·7H2O (Table
1, entries 2, 4, 6 vs entries 1, 3, 5). Increasing the reaction
temperature improved the reaction rate; however, a slight
decrease in ee was observed. Lowering the substrate concentra-
tion from 0.5 to 0.1 M increased the ee value from 96.3% to
97.5% (Table 1, entry 2 vs entry 8). Some other atropisomer
ligands (L1, L2, L4, L5) were also tested for the asymmetric
hydrogenation of ethyl benzoylformate. Although the enanti-
oselectivities were greatly dependent on ligands, the addition
of CeCl3 ·7H2O was proved efficient in improving the enanti-
oselectivities (Table 1, entries 9, 11, 13, 15 vs entries 10, 12,
14, 16). Because both ruthenium complex 5 and 6 were prepared
from complex 4, for simplicity and convenience the optimized
reaction conditions were therefore set as the following: 1 mol
% of [RuCl(benzene)(S)-SunPhos]Cl (4) as the catalyst, 5 mol
% of CeCl3 ·7H2O as the additive, ethanol as the solvent with
the substrate concentration of 0.5 M, and 50 bar of H2 at
50 °C.
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The results for asymmetric hydrogenation of aromatic R-ke-
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summarized in Table 2. Column A illustrates the results of
hydrogenation without additive. As a matter of fact, without
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entries 1-6) and meta- (column A, entry 10) monosubstituted
and para and meta-polysubstituted phenylglyoxylate (column
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