2
898
W. Chen, J. Xiao / Tetrahedron Letters 42 (2001) 2897–2899
thol and the ligands so generated are effective in the
asymmetric hydrogenation of unsaturated carboxylic
acid derivatives.
although it is lower than the value of 97.6% when using
isopropyl binaphthylphosphite. Switching from ligand
1 to 2, the opposite enantiomer was obtained, at 90.5%
ee, indicating that the binaphthyl moiety is decisive for
enantioselectivity and the combination of (S)-binaph-
5
Our approach is based on the observation that racemic
binaphthol readily forms separable phosphite
thol with
L-menthol represents the matched case for
diastereoisomers upon treatment with PCl and one of
this substrate.
3
the cheapest chiral alcohols,
are industrial products. Thus, the reaction of PCl with
L
-menthol, both of which
H2
8
[Rh(COD)2]BF4/1 or 2
3
CO2Me
CO2Me
1
equiv. of (1R,2S,5R)-(−)-menthol in THF yields
MeO2C
MeO2C
*
solvent
rt
quantitatively menthyl phosphorodichloridite, and the
addition of racemic 1,1%-binaphthalene-2,2%-diol to a
THF solution of the menthol derivative in the presence
(1)
of NEt affords the diastereomerically pure phosphites
Table 1 also shows that solvents play an important role
in affecting the enantioselectivity. Thus, when carried
3
1
and 2 upon fractional crystallisation in diethyl ether,
with 1 derived from (S)-binaphthol and 2 from (R)-
out in solvents other than CH Cl , not only were the ee
2 2
9
binaphthol (Scheme 1). This reaction sequence was
values lowered substantially but the conversions
decreased as well. For example, the hydrogenation in
THF afforded a conversion of 42.5% and an ee value of
only 31.1% under conditions otherwise identical to
originally designed by Buono for the optical resolution
of binaphthol; the two enantiomerically pure binaph-
thols were obtained on the oxidation of 1 and 2 fol-
8
,10
lowed by reduction.
Ligands 1 and 2 are surprisingly
those with CH Cl . The dramatic effect of MeOH on
2 2
resistant towards oxidation. Thus, leaving a chloroform
both the conversion and ee may suggest that phosphite
dissociation takes place during the hydrogenation. Sim-
ilar solvent effect on ee was noted with the monoden-
solution of 1 in air for one week resulted in less than
10% oxidation.
7
tate phosphoramidite, albeit to a lesser degree.
The two ligands have been found to be good ligands in
the rhodium-catalysed asymmetric hydrogenation of
prochiral olefins such as itaconic acid dimethyl ester
and methyl-2-acetamido acrylate. The rhodium catalyst
was formed in situ by combining [Rh(COD) ][BF ] with
Pressure appears to have little effect on the enantio-
selectivity. As can be seen from the table, increasing the
hydrogen pressure from 10 to 50 or 100 bar was
accompanied only by a slight decrease in ee, from 95.2
to 94.6 or 93.6%. However, higher pressure favours
faster reactions. Thus, at 100 bar, the hydrogenation
was complete within 2 h reaction time. The aforemen-
tioned phosphoramidite appears to behave similarly in
the hydrogenation of dehydroamino acids. Of practical
interest, the S/C ratios can be substantially increased
without much detrimental effect on ee values when high
pressure is applied. For example, at S/C=10000 and 50
2
4
1
or 2 in a chosen solvent. In a typical hydrogenation
reaction involving itaconic acid dimethyl ester (Eq. (1)),
[
Rh(COD) ][BF ], 2 equiv. of 1 and the olefinic sub-
2
4
strate, with olefin/Rh (S/C) molar ratio=2000, were
mixed under an atmosphere of argon in CH Cl . The
2
2
hydrogenation was started by replacing the argon with
1
1
1
0 bar H2. Pre-generation of the active catalyst in the
absence of the substrate is unnecessary, as it appears to
have little effect on the enantioselectivity. Table 1 sum-
marises the results obtained. As can be seen, overnight
hydrogenation afforded 100% conversion of the olefin
and an ee value of 95.2% in favour of the S-configured
product. This value compares favourably with those
obtained with the monodentate phosphoramidite
bar H with 1 as ligand, a complete conversion was
2
achieved after overnight hydrogenation, with an ee
value of 94.4%, which is only slightly lower than that
observed at S/C=2000 and 10 bar H and about the
2
same as that observed at S/C=2000 and 50 bar H2.
7
4,6
ligand
and the analogous phosphonites,
or
We also examined the ligands 1 and 2 for the hydro-
genation of methyl 2-acetamido acrylate (Eqs. (2) and
(3)). Under conditions identical to those for the itaconic
5
phosphites in which the menthyl in 1 is replaced with
such groups as methyl and substituted phenyls,
a
Table 1. Rh-catalysed asymmetric hydrogenation of itaconic acid ester in the presence of the ligand 1 or 2
Ligand
Solvent
CH Cl
S/C
PH2 (bar)
Time (h)
Conversion (%)
% Ee
1
2
1
1
1
1
1
1
1
2000
10
10
10
10
10
10
50
100
50
12
12
12
12
12
12
5
100
100
55.2
40.5
42.5
9.0
100
100
100
95.2 (S)
90.5 (R)
78.9 (S)
67.5 (S)
31.1 (S)
7.6 (S)
94.6 (S)
93.6 (S)
94.4 (S)
2
2
2
CH Cl
2000
2000
2000
2000
2000
2000
2000
10000
2
Toluene
EtOAc
THF
MeOH
CH Cl
2
2
2
2
CH Cl
2
12
2
CH Cl
2
a
Reactions were carried out at room temperature, with conversion and ee values determined by GC.