Optically active 1,1′-di-tert-butyl-2,2′-dibenzophosphetenyl: A highly strained P-stereogenic diphosphine ligand

Article abstract of DOI:10.1016/j.tetasy.2004.05.041

Both enantiomers of 1,1′-di-tert-butyl-2,2′-dibenzophosphetenyl were prepared from 2-bromobenzyl chloride and tert-butyldichlorophosphine. These ligands exhibited excellent enantioselectivity in the rhodium catalyzed asymmetric hydrogenation of methyl α-a

Full text of DOI:10.1016/j.tetasy.2004.05.041

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 2213–2218
Optically active 1,10-di-tert-butyl-2,20-dibenzophosphetenyl:
a highly strained P-stereogenic diphosphine ligand
*
ꢀ
Tsuneo Imamoto, Karen V. L. Crepy and Kosuke Katagiri
Department of Chemistry, Faculty of Science, Chiba University, Yayoi-cho 1-333, Inage-ku, Chiba 263-8522, Japan
Received 19 April 2004; accepted 10 May 2004
Abstract—Both enantiomers of 1,10-di-tert-butyl-2,20-dibenzophosphetenyl were prepared from 2-bromobenzyl chloride and tert-
butyldichlorophosphine. These ligands exhibited excellent enantioselectivity in the rhodium catalyzed asymmetric hydrogenation of
methyl a-acetylamidocinnamate.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
H H
H H
Optically active phosphine ligands have played a key
role in transition metal catalyzed asymmetric reactions
with numerous ligands of this class being designed and
synthesized over the past three decades.1 It has been well
recognized that the conformational rigidity of a catalyst
is one of the more important factors to realize excellent
asymmetric induction. Outstanding chiral phosphine
ligands such as DuPHOS,2 PennPHOS,3 BIPNOR,4
MiniPHOS5 and TangPhos6 have been designed to have
maximal conformational rigidity. These ligands have
been successfully employed in asymmetric reactions,
especially in the Rh-catalyzed asymmetric hydrogena-
tions of a-dehydroamino acids and related substrates.
These facts and our continuing studies on the synthesis
and application of P-stereogenic phosphine ligands7 led
us to develop new ligands that are anticipated to form
very rigid metal complexes. The newly designed ligands
are (1S,10S,2R,20-R)-1,10-di-tert-butyl-2,20-dibenzophos-
phetenyl (S,S)-1 and its enantiomer (1R,10R,2S,20S)-1,10-
di-tert-butyl-2,20dibenzophosphetenyl (R,R)-1 (Fig. 1).
P
P
P
P
(S,S)-1
(R,R)-1
Figure 1.
phosphorus atoms might lead to very high enantio-
selection in catalytic asymmetric reactions.8 Herein we
report the preparation of the ligands and their stereo-
differentiation ability in rhodium-catalyzed asymmetric
hydrogenation.
2. Results and discussion
We planned to prepare the designed phosphine ligands
by the oxidative coupling of 1-tert-butylbenzophosphet-
ene oxide. At first, racemic 1-tert-butylbenzophosphet-
ane oxide was prepared from 2-bromobenzyl chloride.
Thus, the dihalide was converted to 1,2-dihydro-1-
magnesacyclobutabenzene by treatment with a large
excess of magnesium in tetrahydrofuran according to
the procedure described.9 The resulting organomagne-
sium reagent was reacted with tert-butyldichlorophos-
phine, followed by oxidation with hydrogen peroxide, to
give the desired phosphine oxide dl-2 in reasonable yield
(Scheme 1).
These ligands are C2-symmetric and consist of two
directly bonded benzophosphetene units containing a
pair of asymmetric phosphorus and carbon atoms. The
conformational rigidity of the metal chelates together
with an ideal asymmetric environment owing to the
existence of two tert-butyl groups at the stereogenic
Attempts to resolve the phosphine oxide by frac-
tional crystallization using (þ)-dibenzoyl-
* Corresponding author. Tel./fax: +81-432902791; e-mail: imamoto@
faculty.chiba-u.jp
D-tartaric acid
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.05.041

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T. Imamoto et al. / Tetrahedron: Asymmetry 15 (2004) 2213–2218
1. t-BuPCl2, THF
Mg, I2, THF
2. H2O2, H2O
Cl
P O
Mg
Br
dl-2
52% yield
Scheme 1.
[(þ)-DBTA] or (1R)-(À)-10-camphorsulfonic acid were
unsuccessful. Alternatively, the direct separation of each
enantiomer in gram scale was easily achieved by using a
simulated moving bed (SMB) system. The respective
optically active phosphine oxides (R)-2 and (S)-2 were
reacted with sec-butyllithium and the resulting organo-
lithium compounds oxidized with copper(II) chloride, to
give the corresponding diphosphine oxides, (R,R)-3 and
(S,S)-3, in moderate yields (Scheme 2).
Similarly, racemic diphosphine oxide dl-3 was prepared
in moderate yield by oxidative dimerization of dl-2. This
compound was resolved using (þ)- and (À)-DBTA to
give enantiomerically pure (S,S)-3 and (R,R)-3, respec-
tively (Scheme 3).
The absolute configurations of the compounds of
interest above were established by single-crystal X-ray
analysis of one of the chiral diphosphine oxides. Thus,
1. s-BuLi/TMEDA, THF
H
H
–78 ˚C to –50 ˚C
P O
2. CuCl2, –50 ˚C to rt
44%
P
O O
P
(S)-2
(S,S)-3
1. s-BuLi/TMEDA, THF
–78 ˚C to –50 ˚C
H H
P O
P
P
2. CuCl2, –50 ˚C to rt
45%
O
O
(R,R)-3
(R)-2
Scheme 2.
1. s-BuLi/TMEDA, THF
H
H
H
H
–78 ˚C to –50 ˚C
+
P O
P
P
P
P
2. CuCl2, –50 ˚C to rt
O O
O O
dl-2
dl-3
meso-3
H H
P
O O
P
(+)-DBTA,
AcOEt
H
H
(S,S)-3
P
P
O O
H H
dl-3
(–)-DBTA,
AcOEt
P
P
O
O
(R,R)-3
Scheme 3.

T. Imamoto et al. / Tetrahedron: Asymmetry 15 (2004) 2213–2218
2215
catalyzed asymmetric hydrogenation of methyl a-ace-
tamidocinnamate (MAC). A markedly high ee (96%) of
the product was observed when complex 4 was used.12
This result was compared with those of hydrogenation
obtained by the use of the rhodium complexes of
structurally resembling chiral diphosphine ligands. Fig-
ure 3 illustrates representative C2-symmetric ligands
bearing tert-butyl groups and their enantioselectivity in
Rh-catalyzed hydrogenation of MAC. It should be
noted that ligand 5, whose molecular structure closely
resembles (S,S)-1, provided only 6.6% enantioselecti-
vity.13 This significantly low enantioselectivity is
responsible for the conformational flexibility of the
benzene ring. Ligands 6–8 afforded excellent to almost
perfect enantioselectivity,5;6;14 while in sharp contrast
ligands 9–11 gave very low selectivity.15;16 These dra-
matic differences are also ascribed to the rigidity/flexi-
bility of the catalyst complexes. The use of ligand 12
resulted in 76% enantioselectivity.17 The X-ray analysis
of the Rh-complex of 12 shows that it is considerably
rigid but not C2-symmetric. The observed fairly good
selectivity can be interpreted by considering these
asymmetric environments around the rhodium metal
centre.
Figure 2.
19
D
one enantiomer {½aŠ ¼ À12:3 (c 1.00, CHCl3)} was
subjected to X-ray analysis by the Flack parameter
method. Figure 2shows its molecular structure with a
(1S,10S,2S,20S)-configuration.
Reduction of (R,R)-3 and (S,S)-3 to the corresponding
optically active diphosphines was attempted using
PhSiH3, HSiCl3/amine, Cl3SiSiCl3, HSi(OEt)3 and
MeOTf/LiAlH4 as the reducing agents. However, the
standard reaction conditions described in the literature
were not effective in this case, even if reagents were used
in large excess. Careful tuning of the reaction conditions
using Cl3SiSiCl3 enabled the isolation of the desired
diphosphines in moderate yields. The reduction of
phosphine oxide with Cl3SiSiCl3 usually proceeds
through inversion of configuration,10 while in the
reduction of four-membered phosphine oxides is known
to occur with retention of configuration.11 Therefore, we
assume that these benzophosphetene oxides were
reduced with retention of configuration.
3. Conclusion
We have prepared both enantiomers of 1,10-di-tert-
butyl-2,20-dibenzophosphetenyl and observed very high
enantioselectivity in their application to Rh-catalyzed
asymmetric hydrogenation of MAC. These results
indicate the importance of the rigid conformation of the
catalyst in highly enantioselective hydrogenation and
suggest the potential utility of these highly strained
ligands in other catalytic asymmetric reactions.
4. Experimental
4.1. General
The two enantiomer diphosphines (S,S)-1 and (R,R)-1
were highly air-sensitive, and hence were converted to
the corresponding rhodium complexes by treatment
with [Rh(nbd)2]BF4 (Scheme 4). The stereodifferentia-
tion ability of the complexes was tested by typical Rh-
All reactions except for the hydrogenation were carried
out under an argon atmosphere. Dehydrated THF and
H H
H H
Si2Cl6, THF, 80 ˚C
P
P
P
P
O
O
(R,R)-3
(S,S)-1
H H
[Rh(nbd)2]BF4
P
P
+
–
BF4
Rh Bu-t
t-Bu
4
Scheme 4.

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T. Imamoto et al. / Tetrahedron: Asymmetry 15 (2004) 2213–2218
CO2Me
Rh-Ligand
MeOH, rt
CO2Me
NHAc
Ph
Ph
+
H2
NHAc
H H
H
H
P
P
P
P
P
P
513
6.3% ee
66
(S,S)-1
96% ee
TangPhos
99% ee
Me
Me
Me
Me
P
P
P
P
Me
P
P Me
714
85,14b
915
14% ee
t-Bu-BisP*
99.9% ee
t-Bu-MiniPHOS
98% ee
Me Me
Si
Fe
Me
P
P Me
Me
P
P Me
Me
P
P Me
1217
76% ee
1015
0% ee
1116
14% ee
Figure 3.
diethyl ether were purchased from Kanto Chemical Co.,
Inc. and Wako Pure Chemical Industries, Ltd, respec-
was stirred for an extra 2h, decanted and transferred in
small portions to a solution of tert-butyldichlorophos-
phine (2.32 g, 14.6 mmol) in dry THF (25 mL) at À50 ꢁC.
This mixture was gradually warmed to room tempera-
ture and stirred overnight. Water (30 mL) and H2O2
(30% aq, 2mL) were successively added and the result-
ing mixture stirred for 1 h at room temperature. A sat-
urated aqueous solution of FeSO4 (40 mL) was added
and the mixture extracted with ethyl acetate (2 · 50 mL).
The combined organic extracts were washed with brine
and dried over Na2SO4. The solvent was removed under
reduced pressure and the residue purified by column
chromatography on silica gel, eluting with ethyl acetate
to give dl-2 as an off-white solid. Yield: 52%.
1
tively, and used as received. H NMR, 13C NMR and
31P NMR spectra were recorded on JNM-LA400 or
JNM-400s spectrometer. In both 1H NMR and 13C
NMR, chemical shifts are reported in parts per million
downfield from TMS. 31P NMR chemical shifts are
relative to 85% H3PO4. FT-IR spectra were performed
with a Hitachi IR 215 spectrometer and recorded in the
form of KBr disks or on NaCl plates. Mass spectra were
obtained by EI at 70 eV or FAB. HPLC analysis was
performed on a Shimadzu LC10AD liquid chromato-
graph system with chiral stationary columns. Optical
rotations were measured using a JASCO P-1020 polari-
meter with a 1 dm cell.
4.3. (S)-tert-Butylbenzophosphetene oxide (S)-2 and
(R)-tert-butylbenzophosphetene oxide (R)-2
4.2. tert-Butylbenzophosphetane oxide dl-2
A solution of o-bromobenzyl chloride (3 g, 14.6 mmol)
in dry THF (150 mL) was added dropwise to a suspen-
sion of dry magnesium turnings (3.5 g, 146 mmol) and a
crystal of iodine in dry THF (30 mL) at room temper-
ature under argon. The reaction mixture was initiated by
the addition of 1,2-dibromoethane (0.1 mL). Once the
reaction had started, the dihalide compound was added
over 4 h. The mixture gradually turned into a light green
milky aspect. The resulting organomagnesium reagent
Racemic tert-butylbenzophosphetene dl-2 was subjected
to HPLC analysis by using several kinds of chiral col-
umns to find optimum resolution conditions. Use of
Chiralcel OJ provided good separation of the two
enantiomers: 0.7 mL/min, 25 ꢁC, 5% 2-propanol/hexane,
17.1 min and 19.9 min. Based on the results, 3 g of dl-2
were separated by preparative HPLC (SMB system) into
1.3 g of each enantiomer. The enantiomer with early
17
D
retention time: mp 39–40 ꢁC, >99.9% ee, ½aŠ ¼ À22:5

T. Imamoto et al. / Tetrahedron: Asymmetry 15 (2004) 2213–2218
2217
(c 1.01, CHCl3). This compound corresponds to (S)-2.
1H NMR (400 MHz, CDCl3): d 1.17 (d, 3JHP 16 Hz, 9H),
3.38–3.58 (m, 2H), 7.30–7.43 (m, 2H), 7.47–7.57 (m,
2H); 13C NMR (100 MHz, CDCl3): d 24.16 (d, JCP
1.7 Hz), 33.18 (d, JCP 56.6 Hz), 36.12(d, JCP 56.6 Hz),
125.59 (d, JCP 25.4 Hz), 127.20, 128.54 (d, JCP 12.4 Hz),
133.91 (d, JCP 3.3 Hz), 141.31 (d, JCP 24.6 Hz), 141.73 (d,
JCP 42.6 Hz); IR (KBr): 3060, 2950, 2900, 2860, 1960,
1920, 1590, 1450 cmÀ1; IR (KBr): 3060, 2950, 2900,
2860, 1960, 1920, 1590, 1450 cmÀ1. Anal. Calcd for
C11H15PO: C, 68.03, H, 7.78. Found: C, 68.13; H, 8.01.
144.76 (m); IR (KBr) 2950, 2860, 2360, 1590, 1480, 1450,
1190 cmÀ1
.
4.5. dl-1,10-Di-tert-butyl-2,20-dibenzophosphetanyl
dioxide dl-3
Compound dl-2 was treated subsequently with s-BuLi
and copper(II) chloride to produce dl-3 and meso-isomer
in 83:17 ratio. Pure dl-3 was obtained by chromatogra-
phy on silica gel using EtOAc as the eluent. Mp 180 ꢁC
3
(decomp.). 1H NMR (100 MHz, CDCl3): d 1.23 (d, JHP
The compound with late retention time: mp 39–41 ꢁC,
1
17
15.9 Hz, 18H), 4.46 (d, JHP 4.1 Hz, 2H), 7.31–7.39 (m,
99.0% ee, ½aŠ ¼ þ21:7 (c 0.98, CHCl3). This compound
D
2H), 7.41–7.52 (m, 6H); 13C NMR (100 MHz, CDCl3): d
24.12, 33.22–33.98 (m), 46.38–47.20 (m), 126.91–127.16
1
corresponds to (R)-2. H NMR (400 MHz, CDCl3): d
3
1.18 (d, JHP 16 Hz, 9H), 3.38–3.58 (m, 2H), 7.30–7.43
(m, 2H), 7.47–7.57 (m, 2H); 13C NMR (100 MHz,
CDCl3): d 24.09 (d, JCP 1.6 Hz), 33.61 (d, JCP 56.6 Hz),
36.05 (d, JCP 56.6 Hz), 125.53 (d, JCP 26.2 Hz), 127.13,
128.48 (d, JCP 11.5 Hz), 133.86 (d, JCP 3.3 Hz), 141.31 (d,
JCP 26.2 Hz), 141.65 (d, JCP 40.2Hz).
(m), 129.05–129.16 (m), 133.77, 140.79–141.61 (m, 2C),
31
144.72–144.76 (m);
60.95. IR (KBr): 2950, 2860, 2360, 1590, 1480, 1450,
P NMR (202 MHz, CDCl3): d
1190 cmÀ1
.
4.6. Optical resolution of dl-3
4.4. (1S,10S,2R,20R)-1,10-di-tert-butyl-2,20-dibenzo-
phosphetenyl dioxide (S,S)-3 and (1R,10R,2S,20S)-1,10-di-
tert-butyl-2,20-dibenzophosphetenyl dioxide (R,R)-3
A mixture of dl-3 (38.6 mg, 0.1 mmol) and (2S,3S)-
(þ)-O,O0-dibenzoyltartaric acid [(þ)-DBTA; 179 mg,
0.5 mmol] was dissolved in hot ethyl acetate (1 mL). The
mixture was gradually cooled to room temperature. The
precipitated crystalline solid was collected by filtration,
washed with ethyl acetate, treated with 1 M NaOH
(2mL). The mixture was extracted with chloroform,
dried over Na2SO4 and concentrated under reduced
pressure to give (S,S)-3 (8.1 mg) as a white powder.
Enantiomeric excess of this product was determined to
be 98.8% by HPLC analysis (Chiralcel OD-H, 0.5 mL,
25 ꢁC, 2-propanol/hexane (1:19), (S,S) t1 ¼ 16:9 min,
(R,R) t2 ¼ 23:3 min, (meso) t3 ¼ 25:3 min).
s-Butyllithium (0.97 M in cyclohexane, 2.9 mL,
2.8 mmol) was added over 5 min to a solution of
N,N,N0,N0-tetramethylethylenediamine (0.42mL, 2.8
mmol) in dry THF (2mL) at À78 ꢁC under argon. After
30 min, a solution of (S)-2 (500 mg, 2.57 mmol) in dry
THF (3 mL) was added dropwise. The bright red mix-
ture was stirred at this temperature for 2h then À50 ꢁC
for 2h. Dry copper(II) chloride (dried at 120–130 ꢁC for
4 h in vacuo, 450 mg, 3.34 mmol) was added in one
portion with vigorous stirring and the mixture then
gradually warmed to room temperature overnight.
Aqueous ammonia (25%, 5 mL) was added and the
layers separated. The aqueous layer was extracted with
ethyl acetate (2 · 10 mL). The combined organic layers
were washed with 1 M HCl, water, and brine and dried
over Na2SO4. The solvents were removed under reduced
pressure and the residual (a yellow solid) was washed
with a small amount of ethyl acetate (ca. 4 mL) to give
4.7. X-ray crystallographic analysis of (S,S)-3
A well shaped orthorhombic crystal of (S,S)-3 was
obtained by recrystallization from ethyl acetate. A col-
ourless prism crystal of C22H28O2P2 having approxi-
mate dimensions of 0.40 · 0.30 · 0.20 mm was mounted
in a glass capillary. All measurements were made on a
Rigaku RAXIS-II Imaging Plate diffractometer
with graphite monochromated Mo Ka radiation
(S,S)-3 (220 mg, 44%). Mp 180 ꢁC (decomp); Rf 0.11
19
(EtOAc); ½aŠ ¼ À12:3 (c 1.00, CHCl3); 1H NMR
D
3
(400 MHz, CDCl3): d 1.23 (d, JHP 16Hz, 18H), 4.46 (d,
ꢁ
(k ¼ 0:71070 A) at 173 K. Crystal data and refinement
1JHP 4 Hz, 2H), 7.31–7.39 (m, 2H), 7.41–7.52 (m, 6H);
13C NMR (100 MHz, CDCl3): d 24.11, 33.22–33.98 (m),
46.38–47.20 (m), 126.91–127.16 (m), 129.05–129.16 (m),
133.77, 140.79–141.61 (m, 2C), 144.72–144.76 (m); IR
ꢁ
details: space group P212121 (#19); a ¼ 9:722ð7Þ A,
3
ꢁ
ꢁ
ꢁ
b ¼ 22:91ð2Þ A, c ¼ 9; 65ð1Þ A; V ¼ 2149ð3Þ A ; Z ¼ 4,
Dcalcd ¼ 1:194 g/cm3;
F ð000Þ ¼ 824;
l(Mo Ka) ¼
2.15 cmÀ1; 1790 reflections measured, 1654 observed
(I > 2:00rðIÞ); 235 variables; R ¼ 0:072, Rw ¼ 0:079,
GOF ¼ 1.40. The absolute configuration was determined
by the Flack parameter method. Cambridge Crystallo-
graphic Data Centre supplementary publication number
CCDC 240727.
(KBr) 2950, 2860, 2360, 1590, 1480, 1450, 1190 cmÀ1
.
Anal. Calcd for C22H28O2P2: C, 68.38; H, 7.30. Found:
C, 68.10; H, 7.49.
In a similar manner, (R)-2 was converted to (R,R)-3
in 45% yield. Mp 180 ꢁC (decomp); Rf 0.11
19
(EtOAc); ½aŠ ¼ þ12:5 (c 0.97, CHCl3); 1H NMR
D
3
(400 MHz, CDCl3): d 1.23 (d, JHP 16 Hz, 18H), 4.45
4.8. Reduction of bis(tert-butylbenzophosphetane)oxide
and preparation of rhodium complex
1
(d, JHP 4 Hz, 2H), 7.32–7.40 (m, 2H), 7.41–7.52
(m, 6H); 13C NMR (100 MHz, CDCl3): d 24.11, 33.21–
33.97 (m), 46.38–47.20 (m), 126.91–127.16 (m), 129.04–
129.16 (m), 133.76, 140.79–141.70 (m, 2C), 144.71–
Hexachlorodisilane (70 lL, 0.39 mmol) was added drop-
wise to a solution of (R,R)-3 (50 mg, 0.13 mmol) in dry,

2218
T. Imamoto et al. / Tetrahedron: Asymmetry 15 (2004) 2213–2218
freshly degassed THF (3.5 mL) at room temperature
under argon. The flask was immersed in a preheated oil
bath (80 ꢁC) and stirring continued for 90 min. The flask
was removed from the oil bath, and hexachlorodisilane
(70 lL, 0.39 mmol) again added. The reaction mixture
was stirred at 80 ꢁC for 70 min. The operation was re-
peated at 70 min interval until 12–15 equiv was used for
disappearance of the starting diphosphine oxide and
intermediate monophosphine oxide (TLC monitoring).
The mixture was cooled to À10 ꢁC. A well degassed
aqueous solution of sodium hydroxide (10%, 3 mL) was
added dropwise under argon and the mixture stirred for
5 min at this temperature and then 10 min at room
temperature. Degassed benzene (2mL) was added and
the organic layer transferred onto Na2SO4 under argon.
The extraction procedure was repeated three times. The
solution was passed through a column of basic alumina
under argon and the column washed using degassed
benzene (15 mL). The eluent was removed under re-
duced pressure, releasing the pressure with argon, to
give a white solid. This was dissolved in dry, degassed
THF (3 mL) and then transferred to a stirred suspension
of [Rh(nbd)2]BF4 (24.2 mg, 0.06 mmol) in THF (2 mL)
under argon. The suspension turned immediately into
an almost clear solution. After overnight stirring, the
insoluble material was filtered off and the filtrate evap-
orated under reduced pressure. The residual solid was
washed with hexane to give an orange powder, which
was dried in vacuo. This product was used without
further purification for the asymmetric hydrogenation of
methyl a-acetamidocinnamate.
phosphine oxide dl-2 by preparative HPLC with SMB
system.
References and notes
1. For representative reviews and accounts, see: (a) Tang,
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Ohkuma, T.; Kitamura, M.; Noyori, R. In Catalytic
Asymmetric Synthesis; 2nd ed.; Ojima, I., Ed.; Wiley-
VCH: Weinheim, 2000, Chapter 1; (c) Brown, J. M. In
Comprehensive Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999;
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8. It should be noted that TangPhos, (1S,10S,2R,20R)-1,10-di-
tert-butyl-2,20-diphospholanyl, is a well designed chiral
phosphine ligand for the formation of a very rigid metal
complex and in fact it is successfully applied in highly
enantioselective Rh-catalyzed hydrogenations. See: Ref. 6.
9. (a) de Boer, H. J. R.; Akkerman, O. S.; Bickelhaupt, F.
J. Organomet. Chem. 1987, 321, 291–306; (b) de Boer, H.
J. R.; van de Heisteeg, B. J. J.; Schat, G.; Akkerman, O.
S.; Bickelhaupt, F. J. Organomet. Chem. 1988, 346, 197–
200; (c) Patzke, B.; Stanger, A. Organometallics 1996, 15,
2633–2639.
In a similar manner, (S,S)-3 was reduced to (R,R)-1 and
converted to the corresponding rhodium complex.
4.9. Asymmetric hydrogenation of methyl a-acetamido-
cinnamate
10. Naumann, K.; Zon, G.; Mislow, K. J. Am. Chem. Soc.
1969, 91, 7012–7023.
The reaction was carried out according to the procedure
described in the literature.2;13 The ee of the product was
determined by HPLC using a chiral column: Daicel
Chiralcel OJ, 1.0 mL/min, hexane/2-propanol ¼ 9:1, (R)
t1 ¼ 13:3 min; (S) t2 ¼ 19:3 min.
11. (a) DeBruin, K. E.; Zon, G.; Naumann, K.; Mislow, K.
J. Am. Chem. Soc. 1969, 91, 7027–7030; (b) Marinetti, A.;
Carmichael, D. Chem. Rev. 2002, 102, 201–230.
12. The enantiomer of complex 4 was also prepared from
(R,R)-1 and used in the hydrogenation of MAC. The
observed enantioselectivity in this case was 94%.
13. Meienza, F.; Spindler, F.; Thommen, M.; Pugin, B.;
Malan, C.; Mezzetti, A. J. Org. Chem. 2002, 67, 5239–
5249.
Acknowledgements
14. (a) Imamoto, T.; Watanabe, J.; Wada, Y.; Masuda, H.;
Yamada, H.; Tsuruta, H.; Matsukawa, S.; Yamaguchi, K.
J. Am. Chem. Soc. 1998, 120, 1635–1636; (b) Gridnev, I.
D.; Yamanoi, Y.; Higashi, N.; Tsuruta, H.; Yasutake, M.;
Imamoto, T. Adv. Synth. Catal. 2001, 343, 118–136.
15. Imamoto, T.; Nagata, K. Unpublished results.
16. Tsuruta, H.; Imamoto, T. Tetrahedron: Asymmetry 1999,
10, 877–882.
The authors are grateful to the European Commission
(European Union Science and Technology Fellowship
Programme in Japan, EU S&T FPJ 15) for the fellow-
ship of K.V.L.C. This work was supported by a Grant-
in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science and Technology,
Japan. We thank Dr. Mitsuru Kawata, Takeda Phar-
maceutical Industries Ltd, for the resolution of racemic
17. Gridnev, I. D.; Higashi, N.; Imamoto, T. Organometallics
2001, 20, 4542–4553.