The use of new chiral phosphite and amidophosphite ligands in the Rh-catalyzed hydrogenation of dehydro-β-amino acid derivatives

Article abstract of DOI:10.1007/s11172-011-0315-4

New chiral phosphite-type ligands were synthesized. The tests of these ligands in the asymmetric Rh-catalyzed hydrogenation of N-acetyl derivatives of dehydro-β-amino acid esters showed their high enantioselectivity (up to 75% ee). The reaction of nucleop

Full text of DOI:10.1007/s11172-011-0315-4

Russian Chemical Bulletin, International Edition, Vol. 60, No. 10, pp. 2068—2073, October, 2011
2068
The use of new chiral phosphite and amidophosphite ligands
in the Rhꢀcatalyzed hydrogenation of dehydroꢀβꢀamino acid derivatives
S. E. Lyubimov, E. A. Rastorguev, P. V. Petrovskii, and V. A. Davankov
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (495) 135 6471. Eꢀmail: lssp452@mail.ru
New chiral phosphiteꢀtype ligands were synthesized. The tests of these ligands in the
asymmetric Rhꢀcatalyzed hydrogenation of Nꢀacetyl derivatives of dehydroꢀβꢀamino acid esꢀ
ters showed their high enantioselectivity (up to 75% ee). The reaction of nucleophilic addition
of phthalimide to disubstituted alkynes offering access to esters of Nꢀphthaloyldehydroꢀβꢀamino
acids was discovered. Higher conversion and enantioselectivity in the hydrogenation of Nꢀacetyl
and Nꢀphtaloyl derivatives of dehydroꢀβꢀamino acids were observed in fluorinated alcohols as
compared to common organic solvents.
Key words: hydrogenation, rhodium, enamides, alkynes, nucleophilic addition.
hydrogenation needs fairly drastic conditions,7,8 which can
induce undesirable processes. Unsaturated compounds
containing the phthalimide protection group, which are
characterized by considerably milder conditions of prepaꢀ
ration of target βꢀamino acids, are more attractive initial
components for organic synthesis.9—11
In the present work, we report a new reaction of nucleoꢀ
philic addition of phthalimide to substituted alkynes yieldꢀ
ing dehydroamino acid derivatives and the use of new chiral
phosphiteꢀtype ligands in the Rhꢀcatalyzed hydrogenaꢀ
tion of Nꢀacetylꢀ and Nꢀphthaloylacrylates.
Chiral βꢀamino acids and their derivatives are valuable
objects for the synthesis of βꢀpeptides, βꢀlactams, antiꢀ
allergic and antifungal drugs.1—3 Among reactions leading
to the formation of βꢀamino acids, asymmetric metalloꢀ
complex hydrogenation is the most economically reasonꢀ
able choice due to cheapness of hydrogen and low catalyst
loading. The known examples for the metallocomplex
hydrogenation of unsaturated precursors of βꢀamino acids
are mainly associated with the use of expensive chiral phosꢀ
phine ligands.4 Poor attention is given to the use of synꢀ
thetically more accessible ligands of the phosphite type in
this process.5 Therefore, search for simple and efficient
metallocomplex catalysts containing phosphite or amiꢀ
dophosphite ligands for the asymmetric hydrogenation of
unsaturated precursors of βꢀamino acids is an urgent probꢀ
lem. The predominant number of works on the asymmetꢀ
ric hydrogenation of enamides is related to the involveꢀ
ment of Nꢀacetylꢀsubstituted unsaturated substrates in the
reaction.6 Removal of the acetyl protection group after
Results and Discussion
The reactions of phosphorylating agent 1 with methꢀ
oxyphenyl (2) and oꢀtoluidine (3) in benzene afforded new
phosphite 4 and amidophosphite 5 ligands (Scheme 1).
Compounds 4 and 5 are easily soluble in the majority of
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2031—2036, October, 2011.
1066ꢀ5285/11/6010ꢀ2068 © 2011 Springer Science+Business Media, Inc.

Phosphiteꢀtype ligands
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2069
organic solvents and stable under dry atmosphere on proꢀ
long storage.
When the reaction was carried out at 40 °С and an H2
pressure of 35 atm, the complete conversion was achieved
within 4 h; however, enantioselectivity was low. In order
to increase the enantiomeric excess of product 9a in this
reaction, we used the fluorinated analog of isopropanol,
namely, 1,1,1,3,3,3ꢀhexafluoropropanꢀ2ꢀol (hexafluoroꢀ
isopropanol). We succeeded in obtaining already up to
63% ее at the complete conversion of the initial substrate
8a in hexafluoroisopropanol under other equal reaction
conditions (see Table 1, entries 3 and 4). The use of fluorꢀ
inated alcohols in combination with the metallocomplex
catalysts containing the chiral phosphine ligands can favor
an increase in enantioselectivity in the hydrogenation of
enamides and dimethyl itaconate compared to traditional
organic solvents.12—15 Similar increase in enantioselectivity
has earlier been observed in the Rhꢀcatalyzed hydrogenaꢀ
tion of enamides16 with the amidophosphite ligand conꢀ
taining the carborane substituent. In order to optimize
enantioselectivity, we decreased the hydrogenation temꢀ
perature from 40 to 20 °С. In the case of Rh complex 6
containing the phosphite ligand, the enantiomeric excess
of the reaction product decreases (see Table 1, entries 3
and 5), whereas complex 7 with the amidophosphite ligand
at a lower temperature provides a higher enantioselectivity
(see Table 1, entries 4 and 6). Interestingly, using considꢀ
erably more accessible fluorinated alcohol (2,2,2ꢀtrifluoroꢀ
ethanol) as a solvent a further increase in the enantiomeric
excess of the reaction product in the case of complex 7 can
be recorded (see Table 1, entries 6 and 8). However, when
using trifluoroethanol in the case of complex 6, a little
lower enantioselectivity compared to that for hexafluoroꢀ
isopropanol is observed (see Table 1, entries 5 and 7). The
use of catalyst 7 at higher temperature (40 °С) considerꢀ
ably accelerates hydrogenation, although a small decrease
in the enantiomeric excess of the reaction product is obꢀ
served in this case (see Table 1, entries 8 and 9).
The study of the coordination behavior of ligands 4
and 5 with [Rh(COD)2]BF4 (COD is cyclooctaꢀ1,5ꢀdiꢀ
ene) indicates the monodentate coordination of the ligands
and formation of complexes [Rh(COD)L2]BF4 (Scheme 2),
which was confirmed by the data of 31P NMR spectroꢀ
scopy and elemental analysis.
Scheme 2
The efficiency of complexes 6 and 7 was primarily
tested in the Rhꢀcatalyzed hydrogenation of (Z)ꢀethyl
3ꢀacetamidoꢀ2ꢀbutenoate (8a) (Scheme 3) in isopropanol
(Table 1, entries 1 and 2).
Scheme 3
R = Me (a), Ph (b)
Table 1. Asymmetric hydrogenation of substrates 8a,b
Entry
Substrate
Catalyst
Solvent
T/°C
t/h
Conversion of
ee (%)*
compound 8 (%)
1
2
3
4
5
6
7
8
8a
8a
8a
8a
8a
8a
8a
8a
8a
8b
8b
8b
8b
6
7
6
7
6
7
6
7
6
6
7
6
7
HOCHMe2
HOCHMe2
40
40
40
40
20
20
20
20
40
20
20
20
20
4
4
4
100
100
100
100
100
100
100
100
100
60
5 (R)
7 (R)
HOCH(CF3)2
HOCH(CF3)2
HOCH(CF3)2
HOCH(CF3)2
HOCH2CF3
HOCH2CF3
HOCH2CF3
HOCH(CF3)2
HOCH(CF3)2
HOCH2CF3
HOCH2CF3
61 (R)
63 (R)
50 (R)
65 (R)
46 (R)
75 (R)
71 (R)
5 (S)
4
16
16
16
16
4
16
16
16
16
9
10
11
12
13
73
100
100
38 (S)
31 (S)
33 (S)
* The configuration of the corresponding product 9 is indicated in parentheses.

2070
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
Lyubimov et al.
Rhodium complexes 6 and 7 were also studied in the
hydrogenation of sterically more bulky substrate (Z)ꢀethyl
3ꢀacetamidoꢀ3ꢀphenylacrylate (8b) (see Scheme 3). When
complex 6 containing the phosphite ligand is used, the
conversion and enantioselectivity in hexafluoroisopropanol
were lower than those in trifluoroethanol (see Table 1,
entries 10 and 12). In the case of complex 7, a higher
conversion is achieved in trifluoroethanol and somewhat
higher enantioselectivity is attained in hexafluoroisoproꢀ
panol (see Table 1, entries 11 and 13).
obtained in the pure form neither by multiple crystallizaꢀ
tion nor column chromatography. Higher regiospecificity
of formation of the (Z)ꢀisomer (Z : E = 50 : 1) is observed
when using vinyl bromides (see Scheme 5).
Scheme 5
We also developed an approach to the synthesis of esters
of Nꢀphthaloyldehydroꢀβꢀamino acids by refluxing phthalꢀ
imide with ethyl 3ꢀphenylpropiolate (10) in DMF in the
presence of a catalytic amount of KOH (Scheme 4).
R = Ar, Alk
Scheme 4
The study of the efficiency of hydrogenation of (Z)ꢀ11
and (E)ꢀ11 (Scheme 6) was started from an experiment
with an equimolar mixture of isomers 11 using Pd/C
(3 mol.%) as a catalyst in a MeOH—CH2Cl2 mixture in
order to increase solubility of the substrate (35 atm H2,
30 °С). When the reaction time was 1 h, we found that the
(Z)ꢀisomer was hydrogenated quantitatively, whereas only
the 30% conversion was observed for the (E)ꢀisomer. When
the duration of the experiment was extended to 5 h, the
complete conversion of both the isomers was achieved.
These results indicate a considerably lower reactivity of
the (E)ꢀisomer.
Scheme 6
The only method known for the synthesis of substrates
of this type is the reaction of poorly accessible substituted
vinyl bromides and vinyl tosylates with potassium phthalꢀ
imide (Scheme 5). Regardless of the position of the leavꢀ
ing group (Br or OTs) at the double bond, the product
containing the phthalimide group at the βꢀC carbon atom
is formed.11 In our case (see Scheme 4), phthalimide is
also added to the βꢀposition of ethyl 3ꢀphenylpropiolate
to give a similar yield of product (Z)ꢀ11 under compatible
reaction conditions. Therefore, it can be assumed that the
reaction follows Scheme 5 through the initial dehydroꢀ
halogenation (dehydrotosylation) by treatment with highly
basic potassium phthalimide followed by the nucleophilic
addition of phthalimide to alkynes formed rather than
according to the earlier proposed11 mechanism of the tanꢀ
dem Michael addition—elimination. However, there is
a distinction between two proposed synthetic approaches.
We found that reaction product 11 was a mixture of
(Z)ꢀ and (E)ꢀisomers in the ratio 4 : 1. The (Z)ꢀisomer
can be separated from the (E)ꢀisomer by single crystalliꢀ
zation from the mixture, whereas the (E)ꢀisomer can be
Rhodium complexes 6 and 7 were also studied in the
asymmetric hydrogenation of (Z)ꢀ11 (see Scheme 6 and
Table 2). It was shown that complex 7 in methylene
chloride and methanol does not react, whereas the use of
ethyl acetate gave racemic product 12 (see Table 2, enꢀ
tries 1—3). The use of hexafluoroisopropanol as a solvent
gives 51% ее at the 54% conversion within 24 h. Catalysis
by complex 6 containing the phosphite ligand proceeds

Phosphiteꢀtype ligands
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2071
with lower enantioselectivity and conversion (see Table 2,
entries 4 and 5). In the presence of frifluoroethanol, the
results close to those with hexafluoroisopropanol were obꢀ
tained under the same reaction conditions (see Table 2,
cf. pairs of entries 4 and 5, 6 and 7). Increasing the hydroꢀ
gen pressure slightly increases the conversion, and differꢀ
ent enantiodiscriminating behavior of catalysts 6 and 7 are
observed. A lower enantioselectivity resulted from the use
of an enhanced hydrogen pressure in the presence of comꢀ
plex 7 (see Table 2, cf. entries 6 and 8). Catalyst 6 makes it
possible to increase the values of enantiomeric excess of
the reaction product (see Table 2, cf. entries 7 and 9).
Elevated temperature (50 °С) and hydrogen pressure
(50 atm) produced the same enantioselectivity on both the
catalysts and close values of conversion (see Table 2, entries
10 and 11).
In order to increase conversion, we also used superꢀ
critical carbon dioxide (scСО2) as a medium for hydrogeꢀ
nation with trifluoroethanol as a coꢀsolvent. The scСО2
medium in combination with metal complexes containing
the phosphiteꢀtype ligands can significantly accelerate
hydrogenation; this property is due to high values of diffuꢀ
sion coefficient and easy miscibility with reaction gases,
which result in intense mass exchange in the reaction sysꢀ
tem.17—20 Indeed, in scСО2 we achieved high conversion
within 10 h and somewhat higher enantioselectivity comꢀ
pared to that obtained with trifluoroethanol as a solvent
under all other reaction conditions being equal (see Table 2,
cf. entries 12, 13 and 10, 11). The reaction does not occur
in scСО2 without a cosolvent (see Table 2, entries 14 and
15). This is related most likely to the low solubility of
rhodium catalysts 6 and 7 in scСО2, whose dielectric conꢀ
stant is similar to that of hexane,21 and to easy precipitaꢀ
tion of the catalyst in nonpolar media (see Experimental).
The use of lower temperature (35 °С) for the hydrogenaꢀ
tion of (Z)ꢀ11 in scСО2 containing trifluoroethanol deꢀ
creases the rate of the process and reduces an enantiomerꢀ
ic excess of the reaction product (see Table 2, entries 12
and 16).
Thus, in this work we were able to synthesize new
chiral phosphiteꢀtype ligands, study their coordination
behavior towards [Rh(COD)2]BF4, and examine their acꢀ
tivity in the reactions of the Rhꢀcatalyzed hydrogenation
of Nꢀacetylꢀ and Nꢀphthaloylꢀβꢀdehydroamino acid deꢀ
rivatives. The new approach to the synthesis of esters of
Nꢀphthaloylꢀβꢀdehydroamino acids was developed that
includes the nucleophilic addition of phthalimide to disꢀ
ubstituted alkynes. It was shown that higher enantioselecꢀ
tivities were observed in fluorinated alcohols compared to
common organic solvents and, in several cases, higher
conversions were observed for the hydrogenation of unsatꢀ
urated derivatives of dehydroꢀβꢀamino acids.
Experimental
1
H and 31Р NMR spectra were recorded on a Bruker Avance
400 instrument (400.13 and 161.98 MHz, respectively) relative
to Me4Si and 85% Н3РО4 in D2О, respectively. Mass spectra
(EI, 70 eV) were measured on a Finnigan Polaris Q instrument.
Elemental analysis was carried out at the Laboratory of Microꢀ
analysis of the A. N. Nesmeyanov Institute of Organoelement
Compounds, Russian Academy of Sciences. All reactions were
carried out under dry argon in anhydrous solvents. The phosꢀ
phorylating agent (Sb)ꢀ4ꢀchlorodinaphtho[2,1ꢀd:1´,2´ꢀf][1,3,2]ꢀ
dioxaphosphepine (1), (Z)ꢀethyl 3ꢀacetamidoꢀ2ꢀbutenoate (8a),
(Z)ꢀethyl 3ꢀacetamidoꢀ3ꢀphenylacrylate (8b), and initial comꢀ
plex [Rh(COD)2]BF4 were synthesized according to published
Table 2. RhꢀCatalyzed hydrogenation of compound (Z)ꢀ11
Entry
Catalyst
Solvent
CH2Cl2
MeOH
EtOAc
Cosolvent
T/°C
PH /atm
t/h
Conversion (%)
ee (%)a
2
1
2
3
4
5
6
7
8
7
7
7
7
6
7
6
7
6
7
6
7
6
7
6
7
—
—
—
—
—
—
—
—
40
40
40
30
30
30
30
30
30
50
50
50
50
50
50
35
35
35
35
35
35
35
35
50
50
50
50
50
50
50
50
50
24
24
5
0
0
—
—
0
31
54
48
50
45
60
52
71
67
89
92
0
HOCH(CF3)2
HOCH(CF3)2
HOCH2CF3
HOCH2CF3
HOCH2CF3
HOCH2CF3
HOCH2CF3
HOCH2CF3
24
24
24
24
24
24
24
24
10
10
10
10
24
51 (+)
37 (+)
50 (+)
37 (+)
37 (+)
40 (+)
30 (+)
30 (+)
37 (+)
34 (+)
—
9
—
—
—
10
11
12
13
14
15
16
b
scСО2b
HOCH2CF3
HOCH2CF3
—
scСО2b
scСО2b
scСО2b
scСО2
—
0
50
—
33 (+)
HOCH2CF3
a The sign of the specific rotation angle of product 12 is indicated in parentheses.
b The total pressure is 100 atm.

2072
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
Lyubimov et al.
procedures.22—24 Ethyl 3ꢀphenylpropiolate (10) is a commerꢀ
cially available compound (Aldrich).
Ethyl 3ꢀ(1,3ꢀdioxoisoindolinꢀ2ꢀyl)ꢀ3ꢀphenylacrylate (11).
Phthalimide (5.15 g, 0.035 mol) and KOH (50 mg) were added
to a solution of ethyl 3ꢀphenylpropiolate (10) (5.53 g, 0.032 mol)
in DMF (40 mL). The mixture was refluxed for 20 h with stirꢀ
ring. After cooling to room temperature, water (60 mL) was
added to the solution and the product was extracted with ethyl
acetate (3×30 mL). The organic layer was washed with water
(3×30 mL), dried with Na2SO4, and the solvent was removed
in vacuo. The obtained light yellow solid product was washed
with diethyl ether (2×5 mL) on the Schott filter to remove DMF
residues, dissolved in 70 mL of CHCl3, and subjected to flash
chromatography on silica gel (CHCl3 as eluent). The product
obtained in a yield of 5.111 g (0.016 mol, 50%) contains, accordꢀ
Synthesis of ligands 4 and 5 (general procedure). A solution of
2ꢀmethoxyphenol or 2ꢀmethylaniline (1.4 mmol) and NEt3
(0.3 mL, 2.1 mmol) in C6H6 (10 mL) were added to a solution of
dioxaphosphepane (1) (0.5 g, 1.4 mmol) in C6H6 (15 mL). The
reaction mixture was heated to boiling and then cooled to room
temperature, and a precipitate of NEt3•HCl was filtered off.
The obtained solution was subjected to flash chromatography on
silica gel (benzene as eluent). The solvent was removed in vacuo.
(Sb)ꢀ4ꢀ(2ꢀMethoxyphenoxy)dinaphtho[2,1ꢀd:1´,2´ꢀf]ꢀ
[1,3,2]dioxaphosphepine (4). The yield was 0.534 g (87%), white
powder, m.p. 95—97 °С. Found (%): C, 74.08; H, 4.40; P, 6.98.
C27H19O4P. Calculated (%): C, 73.97; H, 4.37; P, 7.07. 31P{H}
NMR (CDCl3), δ: 146.68. 1Н NMR (CDCl3), δ: 3.93 (s, 3 H,
OMe); 6.82—7.61 (m, 12 Н, Ar); 7.85—8.03 (m, 4 Н, Ar). MS,
m/z (Irel (%)): 252 (40), 268 (100), 315 (70), 333 (41), 437
(60) [M]+.
(Sb)ꢀ4ꢀ(NꢀоꢀTolylamino)dinaphtho[2,1ꢀd:1´,2´ꢀf][1,3,2]ꢀ
dioxaphosphepine (5). The yield was 0.478 г (81%), white powꢀ
der, m.p. 110—111 °С. Found (%): C, 76.89; H, 4.84; N, 3.39.
C27H20NO2P. Calculated (%): C, 76.95; H, 4.78; N, 3.32. 31P{H}
NMR (CDCl3), δ: 146.92. 1Н NMR (CDCl3), δ: 2.08 (s, 3 H,
Me); 5.01 (br.s, 1 H, NH); 6.91—7.60 (m, 12 Н, Ar); 7.86—8.04
(m, 4 Н, Ar). MS, m/z (Irel (%)): 239 (40), 268 (100), 286 (90),
313 (62), 357 (20), 421 (50) [M]+.
Synthesis of rhodium complexes 6 and 7 (general procedure).
A solution of ligand 4 or 5 (0.2 mmol) in CH2Cl2 (0.5 mL) was
added dropwise for 2 min to a solution of [Rh(COD)2]BF4
(0.04 g, 0.1 mmol) in CH2Cl2 (0.5 mL). Hexane (10 mL) was
added to the obtained mixture, and precipitated complexes 6 or
7 were separated by centrifuging and dried in vacuo (1 Torr).
{Bis[(Sb)ꢀ4ꢀ(2ꢀmethoxyphenoxy)dinaphtho[2,1ꢀd:1´,2´ꢀf]ꢀ
[1,3,2]dioxaphosphepine]}(ηꢀcyclooctaꢀ1,5ꢀdiene)rhodium(I)
tetrafluoroborate (6). The yield was 108 mg (94%), yellow powꢀ
der, m.p. 121—123 °С (with decomp.). Found (%): C, 63.47;
H, 4.23; P, 5.34. C62H50BF4O8P2Rh. Calculated (%): C, 63.39;
H, 4.29; P, 5.27. 31P NMR (CDCl3), δ: 123.9 (d, JP,Rh = 260.0 Hz).
{Bis[(Sb)ꢀ4ꢀ(Nꢀоꢀtolylamino)dinaphtho[2,1ꢀd:1´,2´ꢀf][1,3,2]ꢀ
dioxaphosphepine]}(ηꢀcyclooctaꢀ1,5ꢀdiene)rhodium(I) tetraꢀ
fluoroborate (7). The yield was 103 mg (92%), yellow powder,
m.p. 144—146 °С (with decomp.). Found (%): C, 65.33; H, 4.66;
N, 2.39. C62H52BF4N2O4P2Rh. Calculated (%): C, 65.28; H, 4.59;
N, 2.46. 31P NMR (CDCl3), δ: 131.6 (d, JP,Rh = 238.5 Hz).
Asymmetric hydrogenation of enamides 8a,b (general proceꢀ
dure). A solution of rhodium complex 6 or 7 (0.006 mmol) and
a substrate (0.6 mmol) in 1.5 mL of the corresponding alcohol
were placed in an autoclave. The solution in the closed autoꢀ
clave was purged with argon, and the autoclave was filled with
hydrogen (35 atm) and heated to a required temperature. Experꢀ
iments were carried out with magnetic stirring (see Table 1).
After discharging hydrogen, the reaction mixture was diluted with
CH2Cl2 (2 mL) and purified from the catalyst by filtration through
a thin layer of silica gel. The solvents were removed in vacuo.
The conversion of enamides 8a,b was determined by 1H NMR
spectroscopy. Enantiomeric excesses of reaction products 9a,b
(see Ref. 23) were measured by HPLC on an Agilent HPꢀ1100
chromatograph using the Chiralcel OJꢀH and Chiralcel ODꢀH
columns according to the literature data.16 The absolute configꢀ
uration of the reaction products was established by a comparison
of the signs of optical rotation with the known values.25,26
1
ing to the Н NMR spectrum, 80% of known (Z)ꢀethyl 3ꢀ(1,3ꢀ
dioxoisoindolinꢀ2ꢀyl)ꢀ3ꢀphenylacrylate11 and 20% of its (E)ꢀisoꢀ
mer. 1H NMR for (E)ꢀisomer (CDCl3), δ: 1.13 (t, 3 H, Me,
J = 7.1 Hz); 4.10 (q, 2 H, CH2, J = 7.1 Hz); 6.19 (s, 1 H, CH),
7.30—7.97 (m, 9 H, Ar). Crystallization from ethyl acetate on
cooling the solution to –10 °С gave 3.1 g of the (Z)ꢀisomer of
product 11. If the recrystallized product contains small amounts
(5—7%) of phthalimide, the product should be dissolved in
CHCl3 and subjected to consequent flash chromatography. The
evaporation of the mother liquor results in the product with
approximately equal content of the (Z)ꢀ and (E)ꢀisomers. The
crystallization of the (E)ꢀisomer from ethyl acetate is not reaꢀ
sonable because of the low subsequent enrichment (5—7%); howꢀ
ever, additional 200—300 mg of the pure (Z)ꢀisomer can be obꢀ
tained in this case.
Asymmetric hydrogenation of (Z)ꢀethyl 3ꢀ(1,3ꢀdioxoisoindoꢀ
linꢀ2ꢀyl)ꢀ3ꢀphenylacrylate ((Z)ꢀ11). Substrate (Z)ꢀ11 (96 mg,
0.3 mmol), rhodium complex 6 or 7 (0.003 mmol), and the
corresponding solvent (1.5 mL) were placed in an autoclave (see
Table 2). The solution in the closed autoclave was purged with
argon, and the autoclave was filled with hydrogen to a required presꢀ
sure (in some cases, with carbon dioxide) using a manually operated
pump (High Pressure Equipment). Experiments were carried
out with stirring and heating to a required temperature. After
discharging hydrogen and СО2, the reaction mixture was diluted
with CH2Cl2 (3 mL) and purified from the catalyst by filtration
through a thin layer of silica gel and the solvents were removed
in vacuo. The conversion of (Z)ꢀ11 was determined by 1H NMR
spectroscopy. Enantiomeric excess of reaction product 12 (see
Ref. 11) was determined by HPLC on an Agilent HPꢀ1100
chromatograph using the WhelkꢀO1 column (UV, λ = 219 nm,
hexane—isopropanol (7 : 3), flow rate 0.8 mL min–1). The retenꢀ
tion times for enantiomers 12 were 15.2 min for the (+)ꢀisomer,
17.1 min for the (–)ꢀisomer, and 20.2 min for enamide (Z)ꢀ11.
References
1. H. Hebbache, Z. Hank, C. Bruneau, J.ꢀL. Renaud, Syntheꢀ
sis, 2009, 15, 2627.
2. P. A. Magriotis, Angew. Chem., Int. Ed., 2001, 40, 4377.
3. J. Liu, Y. Wang, Y. Sun, D. Marshall, S. Miao, G. Tonn,
P. Anders, J. Tocker, H. L. Tang, J. Medina, Bioorg. Med.
Chem. Lett., 2009, 19, 6840.
4. B. Weiner, W. Szymanski, D. B. Janssen, A. J. Minnaard,
B. L. Feringa, Chem. Soc. Rev., 2010, 39, 1656.
5. P. van Leeuwen, P. Kamer, C. Claver, O. Pamies, M. Diꢀ
eguez, Chem. Rev., 2011, 111, 2077.

Phosphiteꢀtype ligands
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2073
6. A. Boerner, Phosphorus Ligands in Asymmetric Catalysis,
WileyꢀVCH, Weinheim, 2008, 1506 pp.
7. W. D. Lubell, M. Kitamura, R. Noyori, Tetrahedron: Asymꢀ
metry, 1991, 2, 543.
8. N. W. Boaz, S. E. Large, J. A. Ponasik, M. K. Moore, T. Barꢀ
nette, W. D. Nottingham, Org. Process Res. Dev., 2005, 9, 472.
9. J. Deng, X.ꢀP. Hu, J.ꢀD. Huang, S.ꢀB. Yo, D.ꢀY. Wang,
Z.ꢀC. Duan, Z. Zheng, J. Org. Chem., 2008, 73, 2015.
10. H. Huang, X. Liu, J. Deng, M. Qiu, Z. Zheng, Org. Lett.,
2006, 8, 3359.
17. S. E. Lyubimov, A. A. Tyutyunov, V. N. Kalinin, E. E. Saidꢀ
Galiev, A. R. Khokhlov, P. V. Petrovskii, V. A. Davankov,
Tetrahedron Lett., 2007, 48, 8217.
18. S. E. Lyubimov, V. A. Davankov, E. E. SaidꢀGaliev, A. R.
Khokhlov, Catal. Commun., 2008, 9, 1851.
19. S. E. Lyubimov, I. V. Kuchurov, A. A. Tyutyunov, P. V.
Petrovskii, V. N. Kalinin, S. G. Zlotin, V. A. Davankov,
E. HeyꢀHawkins, Catal. Commun., 2010, 11, 419.
20. S. E. Lyubimov, E. A. Rastorguev, P. V. Petrovskii, E. S.
Kelbysheva, N. M. Loim, V. A. Davankov, Tetrahedron Lett.,
2011, 52, 1395.
21. E. J. Beckman, J. Supercrit. Fluids, 2004, 28, 121.
22. G. Francio, C. G. Arena, F. Faraone, C. Graiff, M. Lanꢀ
franchi, A. Tiripicchio, Eur. J. Inorg. Chem., 1999, 1219.
23. S. Lee, Y. J. Zhang, Org. Lett., 2002, 4, 2429.
24. T. V. RajanBabu, T. A. Ayers, G. A. Halliday, K. K. You,
J. C. Calabrese, J. Org. Chem., 1997, 62, 6012.
11. J. Chen, Q. Liu, W. Zhang, S. Spinella, A. Lei, X. Zhang,
Org. Lett., 2008, 10, 3033.
12. I. A. Shuklov, N. V. Dubrovina, E. Barsch, R. Ludwig,
D. Michalik, A. Borner, Chem. Commun., 2009, 1535.
13. N. V. Dubrovina, I. A. Shuklov, M. Birkholz, D. Michalik,
R. Paciello, A. Borner, Adv. Synth. Catal., 2007, 349, 2183.
14. N. V. Dubrovina, V. I. Tararov, A. Monsees, A. Spannenꢀ
berg, I. D. Kostas, A. Borner, Tetrahedron: Asymmetry, 2005,
16, 3640.
25. G. Zhu, Z. Chen, X. Zhang, J. Org. Chem., 1999, 64, 6907.
26. H. Wu, G. Hoge, Org. Lett., 2004, 6, 3645.
15. N. V. Dubrovina, V. I. Tararov, A. Monsees, R. Kadyrov,
C. Fischer, A. Borner, Tetrahedron: Asymmetry, 2003, 14, 2739.
16. S. E. Lyubimov, E. A. Rastorguev, T. A. Verbitskaya, P. V.
Petrovskii, E. HeyꢀHawkins, V. N. Kalinin, V. A. Davanꢀ
kov, Polyhedron, 2011, 30, 1258.
Received May 12, 2011;
in revised form August 4, 2011