Optically pure 1,2-bis[(o-alkylphenyl)phenylphosphino]ethanes and their use in rhodium-catalyzed asymmetric hydrogenations of α-(acylamino)acrylic derivatives

Article abstract of DOI:10.1002/adsc.200404043

Optically pure (S,S)-1,2-bis[(o-alkylphenyl)-phenylphosphino]ethanes 1a-d were prepared in four steps from phenyldichlorophosphine via phosphine-boranes as the intermediates. The rhodium complexes 5a-d of these diphosphines were used for the asymmetric hydrogenations of α-(acylamino)-acrylic derivatives including β-disubstituted derivatives. Markedly high enantioselectivity (78→99%) was observed for the reduction of β-monosubstituted derivatives. β-Disubstituted derivatives were also reduced in considerably high enantioselectivity (up to 90%). The single crystal X-ray analysis of the rhodium complex 5c of (S,S)-1,2-bis[phenyl(5′,6′,7′,8′- tetrahydronaphthyl)phosphino]ethane (1c) revealed its δ-type structure with face orientation of the two tetrahydronaphthyl groups and edge orientation of the two phenyl groups. This conformation corresponds to that of the rhodium complex of 1,2-bis[(o-methoxyphenyl)phenylphosphino]ethane (DIPAMP); the rhodium complex of (R,R)-DIPAMP, whose chirality at phosphorus is opposite that of 5c, exhibits a λ-type structure with the face orientation of the two o-methoxyphenyl groups and the edge orientation of the two phenyl groups. The conformational similarity of these rhodium complexes as well as the stereochemical outcome in the asymmetric hydrogenations means that the coordinative interaction of the methoxy group of DIPAMP with rhodium metal is not the main factor that affects asymmetric induction.

Full text of DOI:10.1002/adsc.200404043

FULL PAPERS
Optically Pure 1,2-Bis[(o-alkylphenyl)phenylphosphino]ethanes
and Their Use in Rhodium-Catalyzed Asymmetric
Hydrogenations of a-(Acylamino)acrylic Derivatives
Yoshiyuki Wada,a, b Tsuneo Imamoto,a,* Hideyuki Tsuruta,a Kentaro Yamaguchi,c
Ilya D. Gridnevd
a
Department ofChemistry, Faculty ofScience, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Fax: (þ81)-43-290-2791, e-mail: imamoto@faculty.chiba-u.jp
b
Material R & D Laboratory, Ogawa & Co., Ltd., Chidori-cho, Urayasu 279-0032, Japan
c
Chemical Analysis Center, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
COE Laboratory, Graduate School ofScience, Tohoku University, Sendai 980-8578, Japan
d
Received: February 14, 2004; Accepted: May 14, 2004
th
This paper is dedicated to Dr. Joe P. Richmond on the occasion ofhis 60 birthday.
Abstract: Optically pure (S,S)-1,2-bis[(o-alkylphenyl)- to that ofthe rhodium complex of1,2-bis[( o-methoxy-
phenylphosphino]ethanes 1a d were prepared in phenyl)phenylphosphino]ethane (DIPAMP); the rho-
four steps from phenyldichlorophosphine via phos- dium complex of( R,R)-DIPAMP, whose chirality at
phine-boranes as the intermediates. The rhodium phosphorus is opposite that of 5c, exhibits a l-type
complexes 5a d ofthese diphosphines were used
structure with the face orientation of the two o-me-
for the asymmetric hydrogenations of a-(acylamino)- thoxyphenyl groups and the edge orientation ofthe
acrylic derivatives including b-disubstituted deriva- two phenyl groups. The conformational similarity of
tives. Markedly high enantioselectivity (78 >99%) these rhodium complexes as well as the stereochemi-
was observed for the reduction of b-monosubstituted cal outcome in the asymmetric hydrogenations means
derivatives. b-Disubstituted derivatives were also re- that the coordinative interaction ofthe methoxy
duced in considerably high enantioselectivity (up to group ofDIPAMP with rhodium metal is not the
90%). The single crystal X-ray analysis ofthe rhodium
complex 5c of( S,S)-1,2-bis[phenyl(5’,6’,7’,8’-tetrahy-
dronaphthyl)phosphino]ethane (1c) revealed its d-
main factor that affects asymmetric induction.
type structure with face orientation of the two tetra- Keywords: asymmetric catalysis; asymmetric hydroge-
hydronaphthyl groups and edge orientation ofthe nation; enantioselectivity; rhodium catalysts; P-ster-
two phenyl groups. This conformation corresponds eogenic ligands
Introduction
useful in catalytic asymmetric syntheses. For example,
9]
PAMP,[5] CAMP,[5] DIPAMP,[6
1,3-bis[(o-methoxy-
Optically active phosphine ligands have played an im- phenyl)phenylphosphino]propane,[10] DIPAMP-PYR-
portant role in various catalytic asymmetric reactions, PHOS[11], and 1,1-bis[(o-methoxyphenyl)phenylphos-
and numerous chiral phosphines have been designed phino]ferrocene[12
are known to provide high enan-
14]
and synthesized over the past three decades.[1,2] Most tiomeric excesses ofproducts in the asymmetric hydro-
chiral phosphine ligands hitherto reported possess their genation of a-(acylamino)acrylic derivatives.[15] It is
chiral centers not at the phosphorus atoms but at the car- noteworthy that these ligands possess an o-methoxy-
bon backbones. On the other hand, a relatively small phenyl group at the phosphorus atoms. The role ofthe
number ofP-stereogenic phosphines has been reported
so far, and some of them played an important role in the clear, but a weak interaction ofthe methoxy oxygen
early stages ofthe history ofhomogeneous asymmetric with a metal center is suggested as one ofthe afctors
hydrogenation.[3 This is largely ascribed to the fact that effects the enantioselectivity of the hydrogena-
methoxy group in asymmetric induction remains un-
8]
that the phosphines ofthis class are not easily available
tion.[16] We questioned this explanation and decided to
using earlier methods.[2j] Apart from the synthetic diffi- investigate the role ofthe methoxy group in the DI-
culties, some P-stereogenic phosphines are potentially PAMP ligand.
Adv. Synth. Catal. 2004, 346, 777 788
DOI: 10.1002/adsc.200404043
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Tsuneo Imamoto et al.
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Scheme 1.
crystallization or preparative HPLC. The absolute con-
figurations at asymmetric phosphorus atom of the four
diastereomers (SP)-2a d were determined by single
crystal X-ray analysis. Compounds (SP)-2a d were re-
duced by treatment with a large excess oflithium 4,4 ’-
di-t-butylbiphenylide (LDBB)[20] at À988C, followed
by reaction with iodomethane, to furnish (S)-3a d
with about 90% ee.[21] Without further purification,
(S)-3a d were converted to dimerization products via
successive reactions with s-butyllithium and copper(II)
chloride, and the resulting products were recrystallized
to afford enantiomerically pure phosphine-boranes
Figure 1. (S,S)-DIPAMP and (S,S)-bis[(o-alkylphenyl)phenyl-
phosphino]ethanes.
In this paper we report the synthesis ofa series of
structurally similar diphosphines containing alkyl (S,S)-4a d. The two boranato groups ofthese com-
groups ofvarious sizes in one ofthe two phenyl rings pounds were removed by reaction with 1,4-diazabicy-
bonded to each phosphorus atom (Figure 1) as well as clo[2.2.2]octane (DABCO) in toluene at 508C f or
the comparison ofthe sense and order ofenantioselec-
tion oftheir reactions with those catalyzed by Rh-DI-
PAMP.[17]
30 min to furnish the desired phosphine ligands (S,S)-
1a d in an almost quantitative yield.
These ligands were reacted with [RhCl(cod)]2, fol-
lowed by treatment with NaBF4, to afford the corre-
sponding rhodium cationic complexes 5a d as air-stable
orange powders.
Results and Discussion
Synthesis of Optically Pure 1,2-Bis[(o-
alkylphenyl)phenylphosphino]ethanes
Asymmetric Hydrogenation of a-(Acylamino)acrylic
Derivatives
Previously, we reported that the optically pure bidentate Rhodium complexes 5a d were used in the catalytic
P-stereogenic phosphine ligands can be prepared by asymmetric hydrogenation of a-(acylamino)acrylic de-
using phosphine-boranes as the intermediates rivatives (Eq. 1). In order to compare the hydrogenation
(Scheme 1).[18] The method involves the following char- results, the reactions were carried out under the same
acteristic features: (1) The dimerization products, conditions as those employed by Knowles et al. in the
di(phosphine-boranes), are obtained as almost enantio- experiments using DIPAMP.[6.7] The results are summar-
merically pure compounds, even though the enantiopur- ized with reported results in Table 1. It should be noted
ities ofthe starting phosphine-boranes are not very high,
that the use ofcomplex 5a with the o-ethyl group as a
since the meso-isomers can be removed by recrystalliza- catalyst provided remarkably high ees ofthe products,
tion or chromatography. (2) Intermediate phosphine- and the overall performance of this complex is compara-
boranes are stable in air and moisture and can be han- ble to that ofRh-DIPAMP. These results indicate that
dled easily. (3) The final step of removing the boranato the o-ethyl group of 5a is not less effective as a stereodis-
group proceeds under mild conditions without any race- criminating factor than the o-methoxy group ofDI-
mization ofthe diphosphines. [19]
PAMP. Fairly high enantioselectivity with up to 92%
This methodology was applied to the preparation of ee was observed even when the least sterically congested
the desired optically active bidentate phosphines. The ligand 1b bearing an o-methylphenyl group was em-
overall reaction sequence is shown in Scheme 2.
ployed.[22] The ligands with larger alkyl substituents
Dichlorophenylphosphine was allowed to react se- (1c, d) provided almost perfect enantioselectivity (>
quentially with o-alkylphenylmagnesium bromide, lith- 99% ee). Another significant fact is that the catalysts
ium l-menthoxide, and borane-THF to afford a mixture prepared from 1a d, whose chirality at phosphorus
oftwo diastereomers, (SP)-2a d and (RP)-2a d, in good atoms is (S,S), provided hydrogenation products with
yields. Each diastereomer was obtained by fractional re- R configuration. This indicates the same sense of enan-
778
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Rh-Catalyzed Asymmetric Hydrogenation of a-(Acylamino)acrylic Derivatives
FULL PAPERS
Scheme 2. Synthesis ofoptically active 1,2-bis[( o-alkylphenyl)phenylphosphino]ethanes and their rhodium complexes.
Table 1. Asymmetric hydrogenation of b-monosubstituted a-(acylamino)acrylic acids catalyzed by rhodium complexes of
(S,S )-1,2-bis[(o-substituted phenyl)phenylphosphine]ethanes.
[a]
R1
R2
R3
Solvent
Temperature
ee [%] ofproduct
[b]
À
5a
5b
5c
5d
Rh DIPAMP
Ph
Ph
Ph
Ar[c]
H
H
H
CH3
H
H
CH3
Ph
CH3
CH3
CH3
CH3
i-PrOH
i-PrOH
i-PrOH
i-PrOH/H2O (88/12)
EtOH
508C
508C
508C
508C
258C
258C
90
86
97
91
93
91
89
91
92
90
90
84
93
93
>99
92
94
90
92
93
>99
91
96
78
96
93
97
94
90
95
H
CH3
MeOH
[a]
All hydrogenations using rhodium complexes 5a d prepared from ligands 1a d possessing (S,S )-configuration afforded
(R)-amino acid derivatives.
[b]
[c]
The original paper ofKnowles et al. described that ( S)-products were produced by the use of( R,R)-DIPAMP.[6,7] Therefore,
the use of( S,S )-DIPAMP produces (R)-products.
Ar¼4-AcO-3-MeOC6H3.
tioselection as in the case ofDIPAMP [ S products from We also tried the asymmetric hydrogenations of b,b-dis-
(R,R)-DIPAMP]. Thus, the enantioselection ofthe same ubstituted a-(acylamino)acrylates to clarify the poten-
sense and comparable degree is observed for DIPAMP tial synthetic utility of 1a d (Eq. 2). While asymmetric
and 1a d. This means that the donating ability ofthe
methoxy group ofDIPAMP is not the main factor that
effects the asymmetric induction.
hydrogenations of b-monosubstituted a-(acylamino)-
acrylates usually give good results, the reduction of
b,b-disubstituted a-(acylamino)acrylates in high enan-
tioselectivity has been notoriously difficult with the ex-
ception ofrecent studies by several research groups. [23]
For example, methyl b,b-dimethyl-a-(N-acetylamino)-
acrylate has been reported with 55% ee by using the DI-
PAMP-Rh complex.[28] The results ofusing the rhodium
complexes 5c, d are summarized in Table 2. It is note-
ð1Þ
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Tsuneo Imamoto et al.
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worthy that higher enantioselectivities ofup to 89%
ic distances and angles are listed in Table 3. The rhodium
À
À
were obtained. These results indicate that it is possible atom is nearly square planar, and the P Rh P angle of
to improve or tune enantioselectivity by changing the 83.68 is comparable to the values observed in DI-
o-methoxy group to an alkyl group in the structure of PAMP-Rh complex (838).[7] The distance between the
P-stereogenic ligands.
rhodium and the benzylic carbon is 3.73 ä. This value
is almost equal to the reported distance (3.7 ä) between
the rhodium and the methoxy oxygen in the DIPAMP-
Rh complex. This is particularly interesting because
the distances do not change despite the lack ofthe coor-
dination ability in 5c.
ð2Þ
Rhodium complex 5c exhibits a d-type conformation
ofthe hydrocarbon backbone in the solid state. The rho-
dium complex of( R,R)-DIPAMP, whose chirality at
phosphorus is opposite tothat of 1c, forms a l-type struc-
ture. In both structures, the o-substituted phenyl groups
are face-oriented and occupy the equatorial positions,
X-Ray Crystallographic Analysis of the Rhodium
Complex 5c
The most attractive compound for this X-ray study and the edge-oriented phenyl groups are located at the
would be the rhodium complex 5a, since its molecular
structure closely resembles that ofDIPAMP. However,
we failed to obtain good single crystals of 5a for the X-
ray analysis. Instead, we succeeded in the X-ray analysis
ofthe complex 5c. The ORTEP drawing is shown in Fig-
ure 2. The molecular structure is compared with the re-
ported structure ofthe DIPAMP-Rh complex. Both
structures possess C2 symmetry, they closely resemble
each other except for the opposite absolute configura-
tion at the chiral phosphorus atoms. Selected interatom-
Table 2. Asymmetric hydrogenation ofmethyl b,b-disubstitut-
ed a-(acetylamino)acrylates by the use of 5c or 5d.[a]
Figure 2. Molecular structure ofcation complex 5c (OR-
TEP). Coordinated cyclooctadiene and counter anion
(BF4À) are omitted for clarity.
Table 3. Selected interatomic distances and intramolecular
angles for 5c {[Rh(cod)(1c)]þ[BF4À ]}.
Interatomic distances (ä)
Rh(1) P(1)
P(1) C(1)
P(1) C(17)
P(2) C(29)
2.290(5) Rh(1) P(2)
1.79(2) P(1) C(11)
1.83(2) P(2) C(19)
1.85(2) P(2) C(18)
2.274(5)
1.82(2)
1.84(2)
1.82(2)
[a]
All reactions were carried out at 508C and an initial H2
pressure of6 atm for 12 24 h with a substrate/catalyst ra-
tio of100.
Enantiomeric excesses were determined by chiral capillary
GC using a Chrompack Chirasil-L-Val column (25 m).
Absolute configurations were assigned by comparison of
chiral GC elution order with the one described in the lit-
erature.[24]
Intramolecular angles (deg)
P(1) Rh(1) P(2) 83.6(2) Rh(1) P(1) C(1) 118.6(6)
Rh(1) P(1) C(11) 113.8(6) Rh(1) P(1) C(17) 108.0(5)
Rh(1) P(2) C(19) 116.5(5) Rh(1) P(2) C(29) 111.1(6)
Rh(1) P(2) C(18) 110.0(6)
Intramolecular non-bonding distances (ä)
Rh(1) C(9)
[b]
[c]
3.68
Rh(1) C(27)
3.77
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Rh-Catalyzed Asymmetric Hydrogenation of a-(Acylamino)acrylic Derivatives
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Figure 3. Quadrant diagrams.
Figure 4. Schematic illustration ofthe possibility to regard
unsubstituted phenyls of 5c as ™bulky∫ substituents. The X-
ray-based structure of 5c shown in the upper left corner is
conformationally modified by rotation around two P C
bonds producing ™pockets∫ appropriate for the coordination
ofa substrate in the upper right and lower letf quadrants.
axial positions. The structural similarity ofthe rhodium
complexes of 5c and DIPAMP also demonstrates that a
coordinative interaction ofthe methoxy group ofDI-
PAMP with rhodium metal is not a main factor that ef-
fects the asymmetric induction.
À
may be quite different from the solid-state conformation
ofthe catalyst precursor.
Sense of Enantioselection in Asymmetric
Hydrogenations with DIPAMP-Type Ligands and
Other P-Stereogenic Diphosphines
In particular, the hindrance arising from the relatively
bulky equatorial ligands can be almost eliminated by ro-
À
tation around the P C bonds, leaving in the correspond-
The data described above demonstrate that even a min- ing quadrant a ™pocket∫ appropriate for the coordina-
imal difference in size ofthe substituents ofphosphorus
(e.g., in the complex 5b) is sufficient to secure enantiose- stituents hinder the access to the rhodium atom from
lectivities up to 92% ee, and increasing the size ofthe al- above in any conformation of the phenyl ring. Thus,
tion ofthe substrate (Fig. 4). However, the axial sub-
kyl substituents results in the improved performance of the hindrance from the unsubstituted phenyls in DI-
the corresponding rhodium complexes. This clearly indi- PAMP-like ligands can be rationalized, and the quad-
cates the spatial control ofthe enantioselection. Howev-
er, ifthe sense ofenantioselection obtained with Rh-DI-
PAMP and 5a d is compared with that observed in
rant rule becomes generally applicable.
asymmetric hydrogenations catalyzed with rhodium Conclusions
complexes ofsuch ligands as DuPHOS, BisP*, Mini-
PHOS, BPE, BIPNOR, TangPHOS, etc., conclusions Synthesis ofvarious C2-symmetrical diphosphines 1a d
on the exact mechanism ofstereoregulation become
has been accomplished via the phosphine-borane syn-
complicated. Indeed, a straightforward application of thetic route. Testing their rhodium complexes as the cat-
the quadrant diagrams would lead to the opposite con- alysts for the asymmetric hydrogenation of representa-
clusions for these two groups of ligands (Fig. 3).
tive dehydroamino acids demonstrated that the alkyl
In order to explain this contradiction, we suggest con- groups in the substituted phenyl rings of 1a d provide
sidering the difference in the conformational properties the same services in the asymmetric hydrogenations cat-
ofthese two groups. The aryl substituents ofthe DI-
alyzed by their rhodium complexes as the methoxy
PAMP-like ligands are conformationally flexible; the group in the o-methoxyphenyl rings ofDIPAMP. Hence,
À
free rotation around the P C bond can significantly the donating properties ofthe methoxy group in DI-
change the asymmetric environment important for the PAMP are an unlikely reason for its high efficiency,
enantioselectivity ofhydrogenation. On the other
and the enantioselection in the asymmetric hydrogena-
hand, the asymmetric environment does not change tions catalyzed by the rhodium complexes ofDIPAMP
upon any conformational change in the complexes of and 1a d is induced by the spatial properties ofthe li-
the ligands ofthe BisP* type. Hence, we suggest that
the X-ray structures ofthe Rh complexes are not useful
gands. Comparing the sense ofenantioselection provid-
ed by 5a d and Rh-DIPAMP with that observed in the
for the evaluation of the stereoregulating factors in the asymmetric hydrogenations catalyzed by the rhodium
DIPAMP-like ligands, since, in solution, a favorable complexes ofthe ligands with a conformationally stable
conformation acquired for any particular intermediate asymmetric environment (BisP*, DuPHOS, etc.), we
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Tsuneo Imamoto et al.
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substrate was determined by single crystal X-ray analysis.
The X-ray crystallographic data are as follows: prismatic. P21
(#4), a¼14.733(2), b¼8.4430(6), c¼19.109(2) ä, b¼
94.49(1)8, V¼2369.7 ä3, Z¼4, Dcalc ¼1.072 g/cm3, tempera-
ture ofdata collection 296 K, 3180 observed relfections ( I>
3.00s(I)), R¼0.065, RW ¼0.062. Separation ofeach diaster-
eomer was accomplished by preparative HPLC (ODS,
MeOH).
conclude that the unsubstituted phenyls ofRh-DI-
PAMP and the rhodium complexes of 1a d actually hin-
der the substrate coordination.
Experimental Section
(SP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(o-ethylphenyl)phenylphosphine-borane [(SP)-2a]: Colorless
prisms; mp 80.0 80.58C (MeOH); [a]2D6: À103 (c 0.97,
CHCl3); 1H NMR (CDCl3): d¼0.48 (d, J¼6.9 Hz, 3H), 0.63
1.72 (m, 11H), 0.75 (d, J¼6.9 Hz, 3H), 0.78 (t, J¼7.7 Hz,
3H), 0.89 (d, J¼6.5 Hz, 3H), 2.14 2.17 (m, 1H), 2.51 2.58
(m, 2H), 4.33 4.40 (m, 1H), 7.24 7.26 (m, 1H), 7.29 7.33
(m, 1H), 7.37 7.50 (m, 4H), 7.55 7.60 (m, 2H), 8.11 (ddd,
J¼13.7, 7.7, 1.2 Hz, 1H); 13C NMR (CDCl3): d¼14.4 (d, J¼
6.6 Hz), 15.2 (s), 20.9 (d, J¼5.7 Hz), 22.1 (d, J¼8.2 Hz), 22.6
(s), 25.4 (d, J¼8.2 Hz), 26.5 (d, J¼4.1 Hz), 31.5 (s), 34.1 (s),
43.6 (s), 48.9 (s), 80.4 80.5 (m), 125.3 (d, J¼13.1 Hz), 128.3
(d, J¼10.7 Hz), 129.5 (d, J¼7.4 Hz), 130.4 (d, J¼61.5 Hz),
130.4 (d, J¼11.5 Hz), 130.8 (s), 132.3 (s), 134.1 (d, J¼
9.8 Hz), 135.3 (d, J¼68.1 Hz), 147.7 (d, J¼4.9 Hz); 11B NMR
(CDCl3): d À55.4 (d, J¼62.4 Hz); 31P NMR (CDCl3): d¼
105.6 (m); IR (KBr): n¼3040, 2920, 2370, 1585, 1445, 1085,
General Procedures
The NMR spectra were recorded on JEOL JNM-GSX-400 and
JEOL JNM-GSX-500 spectrometers. The IR spectra were re-
corded on a JASCO FT/IR-200 spectrophotometer. Optical ro-
tations were measured with a JASCO DIP-370 digital polarim-
eter with a 10-cm long cell. Analytical high-performance liquid
chromatography (HPLC) was performed on a Shimazu LC-
10AD pump and a Shimazu SPD-10AUV-VIS detector. Prep-
arative HPLC was performed on a JAI LC-908 recycling prep-
arative HPLC. Mass spectra were obtained on JEOL JMS-
HX110 and JEOL JMS-DX-300 (FD-Mass) instruments. Mi-
croanalysis was performed on a Perkin-Elmer 240B instrument
at the Chemical Analysis Center ofChiba University. GC anal-
ysis was performed using a Hewlett-Packard Model HP5890
series II and Shimadzu GC-8A. All reactions were performed
under argon atmosphere. Dry THF was purchased from Kanto
Chemical Co. Inc. and used without further purification. Hy-
drogenation reactions were performed using reagent grade sol-
vents without further purification.
975, 885 cmÀ1; FAB-MS: m/z (rel intensity)¼369 (Mþ BH3,
À
25), 379 (Mþ 3H, 51); anal. calcd. for C24H36BOP: C 75.40, H
À
9.49; found: C 75.66, H 9.69.
The absolute configuration at the asymmetric phosphorus
atom ofthis diastereomer was determined to be S by single
crystal X-ray analysis.
(SP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(o-ethylphenyl)phenylphosphine-borane [(SP)-2a] and
(RP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(o-ethylphenyl)phenylphosphine-borane [(RP)-2a]
X-Ray Crystallographic Data: FW¼382.33, prismatic
P212121 (#19), a¼14.368(2), b¼17.042(1), c¼9.8810(8) ä,
V¼2419.4(4) ä3, Z¼4, Dcalc ¼1.050 g/cm3, temperature of
data collection 196 K, 1428 observed reflections (I>3.00s(I)),
R¼0.064, RW ¼0.069.
o-Ethylphenylmagnesium bromide (35.8 mL ofa 1.40 mol/L
THF solution, 50 mmol) was added dropwise over 30 min
into a solution ofrfeshly distilled dichlorophenylphosphine
(6.8 mL, 50 mmol) in THF (50 mL) with vigorous stirring at
À788C under argon. After addition, the cooling bath was re-
moved, and temperature was elevated gradually to room tem-
perature over 30 min, and stirring was continued for an addi-
tional 1.5 h. The mixture was cooled to 08C, and lithium l-
menthoxide [prepared from l-menthol (7.83 g, 50 mmol) in
THF (50 mL) and n-BuLi (29.6 mL ofa 1.69 mol/L hexane sol-
ution) at 08C] was added dropwise over 30 min, then warmed
to 508C for 1 h. The mixture was again cooled to 08C and a bor-
ane-THF complex (65 mL ofa 1.0 mol/L solution) was added.
The reaction mixture was poured into a mixture ofice/water
and hexane. The organic layer was separated, and the aqueous
layer was extracted with hexane. The combined extracts were
washed with brine and dried (Na2SO4) and then concentrated
under vacuum. The residual oil was subjected to column chro-
matography (silica gel, toluene:hexane, 1:4) as the eluent to
give a mixture of( SP,1’R,2’S,5’R)-(2’-isopropyl-5’-methyl-
cyclohexyloxy)(o-ethylphenyl)phenylphosphine-borane and
(RP,1’R,2’S,5’R)-(2’-isopropyl-5’-methylcyclohexyloxy)(o-ethyl-
phenyl)phenylphosphine-borane (ca. 5:2) as colorless crystals;
yield: 13.4 g (70%). Attempts to separate each diastereomer by
recrystallization from methanol resulted in the formation of
colorless needles (mp 74 758C) consisting of( SP)-2a and
(RP)-2a in a 1:1 molar ratio. The molecular structure ofthis
(RP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(o-ethylphenyl)phenylphosphine-borane [(RP)-2a]: Colorless
crystals; mp 57.5 58.58C; [a]2D4: À25.0 (c 1.05, CHCl3);
1H NMR (CDCl3): d¼0.67 (d, J¼6.9 Hz, 3H), 0.67 1.42 (m,
8H), 0.80 (d, J¼6.3 Hz, 3H), 0.86 (d, J¼7.3, 3H), 0.86 (t, J¼
7.4 Hz, 3H), 1.63 1.66 (m, 2H), 2.00 2.03 (m, 2H), 2.53
2.64 (m, 2H), 4.30 4.40 (m, 1H), 7.26 7.69 (m, 8H), 8.07 (dd,
J¼11.7, 7.8 Hz, 1H); 13C NMR (CDCl3): d¼14.8 (d, J¼
7.4 Hz), 15.4 (d, J¼4.1 Hz), 21.0 (d, J¼7.4 Hz), 22.0 (d, J¼
6.6 Hz), 22.7 (s), 25.5 (d, J¼4.9 Hz), 26.7 (d, J¼4.1 Hz), 31.4
(s), 34.1 (s), 43.2 (s), 49.1 (s), 79.6 79.7 (m), 125.5 (d, J¼
11.5 Hz), 128.3 (d, J¼10.7 Hz), 129.6 (d, J¼9.0 Hz), 130.8 (d,
J¼11.5 Hz), 130.9 (d, J¼55.0 Hz), 131.1 (s), 132.1 (s), 133.4
(d, J¼8.2 Hz), 133.5 (d, J¼9.0 Hz), 134.3 (d, J¼68.9 Hz),
147.7 (d, J¼8.2 Hz); 11B NMR (CDCl3): d¼ À60.4 (d, J¼
62.2 Hz); 31P NMR (CDCl3): d¼103.0 (m); IR (KBr): n¼
3020, 2915, 2360, 1580, 1430, 1060, 960 cmÀþ1; FAB-MS: m/z
(rel intensity)¼369 (Mþ BH3, 25), 379 (M 3H, 48); anal.
À
À
calcd. for C24H36BOP: C 75.40, H 9.49; found: C 75.22, H 9.47.
(S)-o-Ethylphenyl(methyl)phenylphosphine-borane (3a)
A solution of( SP,1’R,2’S,5’R)-(2’-isopropyl-5’-methylcyclo-
hexyloxy)(o-ethylphenyl)phenylphosphine-borane
(2.68 g,
7.0 mmol) in THF (15 mL) was added to a solution oflithium
782
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 777 788

Rh-Catalyzed Asymmetric Hydrogenation of a-(Acylamino)acrylic Derivatives
FULL PAPERS
þ
þ
À
À
À
À
BH3 H, 90), 477 (M 5H, 54), 481 (M H, 45); anal. calcd.
for C30H38B2P2: C 74.73, H 7.94; found: C 74.47, H 7.88.
4,4’-di-tert-butylbiphenylide [prepared from 4,4’-di-tert-butyl-
biphenyl (7.47 g, 28 mmol) and lithium (218 mg, 31 mmol) in
THF (130 mL) at 08C] with vigorous stirring at À988C under
argon. After 5 min, iodomethane (2.0 mL, 32 mmol) was add-
ed at the same temperature, and stirring was continued for
10 min. The reaction was quenched with methanol, and the
mixture was partitioned between hexane and brine. The organ-
ic layer was separated, and the aqueous layer was extracted
with hexane. The combined extracts were washed with brine
and dried (Na2SO4) and concentrated under vacuum. The res-
idue was passed through a short column (silica gel, hexane) to
remove 4,4’-di-tert-butylbiphenyl. The product was isolated by
column chromatography (silica gel, toluene) to afford (S)-o-
ethylphenyl(methyl)phenylphosphine-borane; yield: 1.55 g
(91%). The enantiomeric excess ofthe product was determined
to be 88% ee by HPLC analysis [DAICEL CHIRALCEL OJ,
hexane:2-propanol¼9:1, 1.0 mL/min, (R) t1 ¼10.4 min, (S)
t2 ¼12.3 min]. Colorless oil; [a]2D6: þ21.2 (c 1.04, CHCl3);
1H NMR (CDCl3): d¼0.72 1.59 (m, 3H), 0.91 (t, J¼7.2 Hz,
3H), 1.86 (d, J¼9.7 Hz, 3H), 2.48 2.72 (m, 2H), 7.25 7.33
(m, 2H), 7.34 7.47 (m ,4H), 7.57 7.62 (m, 2H), 7.67 (dd, J¼
13.5, 7.7 Hz); 13C NMR (CDCl3): d¼13.2 13.8 (m), 14.9 (d,
J¼6.6 Hz), 27.1 (d, J¼5.7 Hz), 125.9 126.0 (m), 127.5 (d,
J¼55.0 Hz), 128.8 (d, J¼9.8 Hz), 129.9 (brs), 130.9 (s), 131.5
(s), 131.6 (s), 131.7 (s), 131.8 (d, J¼54.9 Hz), 131.5 (s), 132.2
(S,S)-1,2-Bis[(o-ethylphenyl)phenylphosphino]ethane
(1a)
(S,S)-1,2-Bis[boranato(o-ethylphenyl)phenylphosphino]ethane
(72 mg, 0.15 mmol) and DABCO (67 mg, 0.60 mmol) was
dissolved in 1 mL ofdegassed toluene and the solution was
maintained at 508C for 30 min. The mixture was subjected to
a short column (silica gel, degassed toluene) under argon to
give (S,S)-1,2-bis[(o-ethylphenyl)phenylphosphino]ethane di-
phosphine in almost quantitative yield. Colorless oil; [a]2D4:
1
À10.88 (c 0.50, toluene); H NMR (CDCl3): d¼1.13 (t, J¼
7.5 Hz, 6H), 2.07 2.09 (m, 4H), 2.80 2.95 (m, 4H), 7.10
7.30 (m, 18H); IR (neat): n¼3020, 2925, 1575, 1460, 1425,
1260, 1025 cmÀ1; HRMS (FAB): calcd. for C30H33P2 (MþHþ):
455.2050; found: 455.2068.
(SP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(o-methylphenyl)phenylphosphine-borane [(SP)-2b]
and (RP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclo-
(d, J¼9.8 Hz), 148.5 (d, J¼9.0 Hz); 11B NMR (CDCl3): d¼ hexyloxy)(o-methylphenyl)phenylphosphine-borane
À58.1 (d, J¼54.6 Hz); 31P NMR (CDCl3): d¼10.1 (m); IR
[(RP)-2b]
(neat): n¼3025, 2940, 2360, 1585, 1435, 1085, 895 cmÀ1
;
HRMS (FAB): calcd. for C15H20BKP (MþKþ): 281.1028;
o-Methylphenylmagnesium bromide (47 mL of1.06 M/LTHF
solution, 50 mmol) was added dropwise over 30 min into a sol-
ution ofrfeshly distilled dichlorophenylphosphine (6.8 mL,
50 mmol) in THF (50 mL) with vigorous stirring at À788C un-
der argon. After addition, the cooling bath was removed, the
mixture was warmed to room temperature over ca. 30 min,
and stirring was continued for an additional 1.5 h. The flask
was immersed in an ice bath, and a solution oflithium menth-
oxide [prepared from l-menthol (7.83 g, 50 mmol) in THF
(50 mL) and n-BuLi (29.6 mL of1.69 mol/L hexane solution
at 08C) was added dropwise over 30 min, and the mixture
was warmed to 508C and stirring was continued for 1 h. The
flask was again immersed in an ice-water bath, and borane-
THF complex (65 mL of1.0 mol/L) was added. The reaction
mixture was poured into a mixture ofice/water and hexane.
The organic layer was separated, and the aqueous layer was ex-
tracted with hexane. The combined extracts were washed with
brine and dried (Na2SO4), and the solvents were removed
under vacuum to leave a crystalline solid (yield: 16.1 g) consist-
ing of( SP,1’R,2’S,5’R)-(2’-isopropyl-5’-methylcyclohexyloxy)
(o-methylphenyl)phenylphosphine-borane and (RP,1’R,2’S,5’R)-
(2’-isopropyl-5’-methylcyclohexyloxy)(o-methylphenyl)phenyl-
phosphine-borane (88:12). Each diastereomer was separated
by fractional crystallization or preparative HPLC (ODS,
MeOH).
(SP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(o-methylphenyl)phenylphosphine-borane [(SP)-2b]: Color-
less prisms; mp 85.5 86.58C (MeOH); [a]2D6: À112 (c 0.92,
CHCl3); 1H NMR (CDCl3): d¼0.47 (d, J¼6.8 Hz, 3H), 0.68
1.71 (m, 11H), 0.76 (d, J¼7.0 Hz, 3H), 0.89 (d, J¼6.5 Hz,
3H), 2.10 (s, 3H), 2.15 2.26 (m, 1H), 4.31 4.39 (m, 1H),
7.13 7.20 (m, 1H), 7.30 7.46 (m, 5H), 7.54 7.59 (m, 2H),
8.12 (ddd, J¼13.8 7.7 1.3 Hz, 1H); 13C NMR (CDCl3): d¼
15.2 (s), 21.0 (d, J¼5.4 Hz), 21.2 21.3 (m), 22.1 (d, J¼
7.4 Hz), 25.5 (d, J¼8.2 Hz), 31.5 (s), 34.1 (s), 43.7 (s), 49.0
found: 281.1037.
(S,S)-1,2-Bis[boranato(o-ethylphenyl)-
phenylphosphino]ethane (4a)
A solution of( S)-o-ethylphenyl(methyl)phenylphosphine-
borane (90% ee) (324 mg, 1.34 mmol) was dissolved in THF
(7 mL) was cooled to À788C under argon. To this solution
sec-BuLi (1.4 mL of1.05 M/L cyclohexane solution) was add-
ed, and stirring was continued for 2 h. Freshly dried, well-pow-
dered anhydrous copper(II) chloride (270 mg, 2.0 mmol) was
added with vigorous stirring. The temperature was kept at
this level for 30 min, and then elevated over 2 h to room tem-
perature. After stirring for an additional 1 h, water and ethyl
acetate were added and the mixture was passed through Celite.
The organic layer was separated and the aqueous layer was ex-
tracted with ethyl acetate. The combined extracts were washed
with 5% ammonia and brine, dried (Na2SO4), and concentrat-
ed under vacuum. The product was isolated by preparative
TLC (silica gel, hexane:AcOEt¼5:1) to give (S,S)-1,2-
bis[boranato(o-ethylphenyl)phenylphosphino]ethane; yield:
255 mg (79%); colorless needles; mp 151.5 152.58C (hex-
ane:CH2Cl2 ¼5:1); [a]2D6: þ51.8 (c 1.19, CHCl3); 1H NMR
(CDCl3): d¼0.84 1.61 (m, 6H), 0.86 (t, J¼8.2 Hz, 6H),
2.21 2.28 (m, 2H), 2.46 2.68 (m, 6H), 7.26 7.60 (m, 18H);
13C NMR (CDCl3): d¼14.8 14.9 (m), 19.9 20.3 (m), 27.0
(s), 125.8 (d, J¼54.1 Hz), 126.1 (s), 128.9 (d), 129.4 (d, J¼
55.0 Hz), 130.2 (s), 131.2 (s), 131.8 (s), 132.0 (s), 132.5 (s),
148.8 (d, J¼4.3 Hz), 148.8 (d, J¼4.3 Hz); 11B NMR (CDCl3):
d¼ À59.9 (brs); 31P NMR (CDCl3): d¼18.0 (m); IR (KBr):
n¼3040, 2935, 2360, 1585, 1430, 1185, 1115, 1070 cmÀ1; FAB
þ
MS (rel intensity): m/z¼455 (Mþ 2BH3 þH, 31), 467 (M
À
Adv. Synth. Catal. 2004, 346, 777 788
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783

Tsuneo Imamoto et al.
FULL PAPERS
(s), 80.4 80.5 (m), 125.5 (d, J¼13.1 Hz), 128.3 (d, J¼10.7 Hz),
130.4 (d, J¼11.5 Hz), 130.6 (d, J¼60.7 Hz), 130.9 (s), 131.3
131.4 (m), 132.2 (s), 134.1 134.4 (m), 134.6 (d, J¼58.2 Hz),
141.7 (d, J¼4.9 Hz); 11B NMR (CDCl3): d¼ À60.7 (d, J¼
62.8 Hz); 31P NMR (CDCl3): d¼105.6 (m); IR (KBr): n¼
3050, 2920, 2380, 1585, 1445, 1085, 990, 885 cmÀþ1; FAB MS
1H), 7.30 7.34 (m, 1H), 7.39 7.49 (m, 4H), 7.56 7.61 (m,
2H), 7.69 (ddd, J¼12.1, 7.7, 1.2 Hz, 1H); 13C NMR (CDCl3):
d¼12.7 13.2 (m), 21.7 (d, J¼4.9 Hz), 126.0 (d, J¼11.5 Hz),
127.8 (d, J¼55.0 Hz), 128.8 (d, J¼10.7 Hz), 130.9 (s), 131.0
(d, J¼55.8 Hz), 131.4 (s), 131.5 (s), 131.7 (d, J¼8.2 Hz),
132.3 (d, J¼10.7 Hz), 142.4 (d, J¼8.2 Hz); 11B NMR
(CDCl3): d¼ À58.7 (d, J¼56.3 Hz); 31P NMR (CDCl3): d¼
(rel intensity): m/z¼365 (Mþ 3H, 37), 355 (M BH3, 22);
anal. calcd. for C23H34BOP: C 75.01, H 9.31; found: C 74.79,
H, 9.22. The absolute configuration at the asymmetric phos-
phorus atom ofthis diastereomer was determined to be S by
single crystal X-ray analysis.
À
À
10.9 (m); IR (neat): n¼3020, 2350, 1580, 1430, 1060, 895 cmÀ1
;
HRMS (FAB): calcd. for C14H18BKP (MþKþ): 267.0876;
found: 267.0879.
X-Ray Crystallographic Data: FW¼368.30, prismatic
P212121 (#19), a¼13.283(1), b¼17.079(2), c¼10.026(1) ä,
V¼2274.4(4) ä3, Z¼4, Dcalc ¼1.076 g/cm3, temperature of
data collection 296 K, 1615 observed reflection (I>2.00s(I)),
R¼0.060, RW ¼0.067.
(S,S)-1,2-Bis[boranato(o-methylphenyl)-
phenylphosphino]ethane (4b)
To a solution of( S)-o-methylphenyl(methyl)phenylphos-
phine-borane (77% ee) (1.30 g, 5.7 mmol) in THF (23 mL)
was added sec-BuLi (6.5 mL of0.96 mol/L cyclohexane solu-
tion) at À788C with stirring. After 2 h, freshly dried, well-pow-
dered anhydrous copper(II) chloride (1.15 g, 8.6 mmol) was
added with vigorous stirring and the mixture was gradually
warmed to room temperature over 2 h. After stirring for an ad-
ditional 1 h, water and ethyl acetate were added and the mix-
ture was passed through Celite. The organic layer was separat-
ed and the aqueous layer was extracted with ethyl acetate. The
combined extracts were washed with 5% ammonia and brine,
and dried (Na2SO4). Purification by column chromatography
(silica gel, toluene) and by subsequent recrystallization (tol-
uene-hexane) afforded (S,S)-1,2-bis[boranato(o-methylphe-
nyl)phenylphosphino]ethane; yield: 773 mg (57%); colorless
crystals; mp 152.0 153.08C (toluene:hexane¼1:2); [a]2D3: þ
(RP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(o-methylphenyl)phenylphosphine-borane [(RP)-2b]: Color-
less prisms; mp 73.5 74.58C (hexane); [a]2D6: À23.2 (c 1.0,
CHCl3); 1H NMR (CDCl3): d¼0.69 (d, J¼6.8 Hz, 3H), 0.69
1.67 (m, 10H), 0.79 (d, J¼6.5 Hz, 3H), 0.87 (d, J¼7.0 Hz,
3H), 1.95 2.08 (m, 2H), 2.16 (s, 3H), 4.32 4.35 (m, 1H),
7.15 7.18 (m, 1H), 7.32 7.46 (m, 5H), 7.53 7.58 (m, 2H),
8.09 (ddd, J¼13.0, 7.5, 1.0 Hz, 1H); 13C NMR (CDCl3): d¼
15.4 (s), 21.1 (d, J¼6.6 Hz), 21.4 (s), 22.0 (s), 22.7 (s), 25.5
(s), 31.3 (s), 34.1 (s), 42.9 (s), 49.1 (s), 79.7 (d, J¼2.5 Hz),
125.6 (d, J¼10.7 Hz), 128.3 (d, J¼9.8 Hz), 130.8 (d, J¼
11.5 Hz), 131.1 (s), 131.2 (d, J¼50.0 Hz), 131.5 (s), 131.9 (s),
133.5 (s, J¼69.7 Hz), 133.7 133.8 (m), 141.6 (d, J¼6.6 Hz);
11B NMR (CDCl3): d À60.8 (d, J¼57.5 Hz); 31P NMR
(CDCl3): d¼103.6 (m); IR (KBr): n¼3020, 2915, 2375, 1580,
1440, 1075, 980 cmÀ1; FAB MS (rel intensity): m/z¼365 (Mþ
1
57.0 (c 1.04, CHCl3); H NMR (CDCl3): d¼0.55 1.63 (m,
þ
À
À
3H, 56), 355 (M BH3, 33); anal. calcd. for C23H34BOP: C
75.01, H 9.31; found: C 74.95, H 9.04.
6H), 2.11 (s, 6H), 2.22 2.30 (m, 2H), 2.50 2.57 (m, 2H),
7.18 7.20 (m, 2H), 7.28 7.32 (m, 2H), 7.37 7.54 (m, 12H),
7.63 (dd, J¼11.8, 6.5 Hz, 2H); 13C NMR (CDCl3): d¼19.1
19.5 (m), 21.7 (brs), 126.0 (d, J¼53.3 Hz), 126.2 (brs), 128.7
(d, J¼54.1 Hz), 129.0 (s), 131.3 (s), 131.8 132.0 (m), 132.9
133.4 (m), 142.6 (d, J¼4.1 Hz), 142.7 (d, J¼4.1 Hz);
11B NMR (CDCl3): d¼ À60.4 (brs); 31P NMR (CDCl3): d¼
19.1 (brs); IR (KBr): n¼3020, 2885, 2340, 1575, 1430, 1185,
1105, 1055 cmÀ1; FAB MS (rel intensity): m/z¼427 (Mþ
(S)-o-Methylphenyl(methyl)phenylphosphine-borane
(3b)
A solution of( SP,1’R,2’S,5’R)-(2’-isopropyl-5’-methylcyclohex-
yloxy)(o-methylphenyl)phenylphosphine-borane
(3.68 g,
þ
þ
À
À
À
À
2BH3 þH, 18), 439 (M BH3 H, 52), 449 (M 5H, 30),
10 mmol) in THF (20 mL) was added into a solution oflithium
4,4’-di-tert-butylbiphenylide [prepared from 4,4’-di-tert-butyl-
biphenyl (10.7 g, 40 mmol) and lithium (305 mg, 44 mmol)
and THF (150 mL)] with vigorous stirring at À988C under ar-
gon. After 5 min, iodomethane (3.1 mL, 50 mmol) was added
and stirring was continued at the same temperature for
10 min. The reaction was quenched by the addition ofmetha-
nol and the mixture was partitioned between hexane and brine.
The aqueous layer was extracted with hexane, and the com-
bined organic layers were washed with brine and dried over so-
dium sulfate. The solvents were evaporated, and the residue
was passed through a short column ofsilica gel to remove
4,4’-di-tert-butylbiphenyl using hexane as the eluent. The prod-
uct was isolated by column chromatography (silica gel, tol-
uene) to afford (S)-o-methylphenyl(methyl)phenylphos-
phine-borane; yield: 1.85 g (81%). The enantiomeric excess of
the product was determined to be 77% ee by HPLC analysis
[DAICEL CHIRALPAK AS, hexane:2-propanol¼9:1,
1.0 mL/min, (R) t1 ¼7.4 min, (S) t2 ¼10.0 min]. Colorless oil;
[a]2D3: þ27.8 (c 1.05, CHCl3); 1H NMR (CDCl3): d¼0.86
1.58 (m, 3H), 1.87 (t, J¼9.9 Hz, 3H), 2.19 (s), 7.19 7.22 (m,
453 (Mþ H , 19); anal. calcd. for C28H34B2P2: C 74.05, H 7.55;
À
found: C 74.00, H 7.61.
(S,S)-1,2-Bis[(o-methylphenyl)phenylphosphino]ethane
1
(1b): H NMR (CDCl3): d¼1.95 2.20 (m, 4H), 2.37 (s, 6H),
7.1 7.3 (m, 18H); IR (KBr): n¼3020, 2940, 1430, 760 cmÀ1
;
HRMS (FAB): calcd. for C28H28P2 (Mþ): 426.1708; found:
426.1664.
(SP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(phenyl)(5’’,6’’,7’’,8’’-tetrahydro-1’’-naphthyl)-
phosphine-borane [(SP)-2c] and (RP,1’R,2’S,5’R)-
(2’-Isopropyl-5’-methylcyclohexyloxy)(phenyl)-
(5’’,6’’,7’’,8’’-tetrahydro-1’’-naphthyl)phosphine-borane
[(RP)-2c]
Dichlorophenylphosphine (7.4 mL, 54 mmol) was subsequent-
ly reacted with 5,6,7,8-tetrahydro-1-naphthylmagnesium bro-
mide (56 mL of0.97 mol/L THF solution, 54 mmol), lithium
menthoxide (54 mmol), and borane-THF complex (70 mL of
784
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Adv. Synth. Catal. 2004, 346, 777 788

Rh-Catalyzed Asymmetric Hydrogenation of a-(Acylamino)acrylic Derivatives
FULL PAPERS
1.0 mol/L) in a similar manner to that described above to give a
mixture of( SP)-diastereomer and (RP)-diastereomer (ca. 3:1)
as colorless crystals; yield: 17.7 g (80%). Each diastereomer
was separated by recrystallization from hexane or preparative
HPLC (ODS, MeOH).
tion ofLDBB (210 mL of0.3 M THF solution, 64 mmol) at
À988C. After 5 min, diiodomethane (6.0 mL, 96 mmol) was
added. The product was isolated by column chromatography
(silica gel, toluene) to afford (S)-methylphenyl(5’,6’,7’,8’-tetra-
hydro-1’-naphthyl)phosphine-borane; yield: 4.22 g (98%). The
enantiomeric excess ofthe product was determined to be 84%
ee by HPLC analysis [DAICEL CHIRALCEL OJ, hexane:
2-propanol¼9:1, 0.25 mL/min, (R) t1 ¼41.3 min, (S) t2 ¼
44.8 min]. Colorless oil; [a]2D6: þ10.8 (c 0.88, CHCl3);
1H NMR (CDCl3): d¼0.70 1.42 (m, 3H), 1.58 1.85 (m, 4H),
1.84 (t, J¼9.9 Hz, 3H), 2.17 2.21 (m, 1H), 2.76 2.78 (m,
2H), 2.88 2.92 (m, 1H), 7.22 7.26 (m, 2H), 7.38 7.52 (m,
4H), 7.57 7.62 (m, 2H); 13C NMR (CDCl3): d¼13.7 (d, J¼
41.8 Hz), 22.2 (s), 22.5 (s), 28.6 (d, J¼5.7 Hz), 125.6 (d, J¼
10.7 Hz), 127.6 (d, J¼54.1 Hz), 128.8 (d, J¼9.78 Hz), 129.9
(d, J¼9.8 Hz), 130.9 (d, J¼2.5 Hz), 131.4 (d, J¼9.8 Hz),
131.5 (d, J¼55.0 Hz), 132.8 (d, J¼2.5 Hz), 138.8 (d, J¼
9.0 Hz), 141.6 (d, J¼9.0 Hz); 11B NMR (CDCl3): d À53.6 (d,
J¼52.8 Hz); 31P NMR (CDCl3): d¼10.6 (m); IR (neat): n¼
3055, 2935, 2370, 1435, 1065, 890 cmÀ1; HRMS (FAB): calcd.
for C17H22BKP (MþKþ): 307.1189; found: 307.1182.
(SP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(phenyl)(5’’,6’’,7’’,8’’-tetrahydro-1’’-naphthyl)phosphine-bor-
ane [(SP)-2c]: Colorless prisms; mp 143.5 144.58C (hexane);
1
[a]2D6: À103 (c 0.92, CHCl3); H NMR (CDCl3): d¼0.42 (d,
J¼6.8 Hz, 3H), 0.76 1.69 (m, 15H), 0.76 (d, J¼7.2 Hz, 3H),
0.90 (d, J¼6.5 Hz, 3H), 2.18 2.28 (m, 2H), 2.70 2.77 (m,
3H), 4.28 4.37 (m, 1H), 7.20 7.26 (m, 2H), 7.37 7.46 (m,
3H), 7.53 7.59 (m, 2H), 7.98 (ddd, J¼14.5, 8.0, 2.7 Hz, 1H);
13C NMR (CDCl3): d¼15.2 (s), 21.1 (s), 22.2 (s), 22.4 (s), 22.6
(s), 22.7 (s), 25.6 (s), 28.2 (d, J¼4.1 Hz), 30.0 (s), 31.6 (s),
34.2 (s), 43.8 (s), 49.1 (d, J¼4.9 Hz), 80.3 (d, J¼3.3 Hz),
125.2 (d, J¼14.8 Hz), 128.4 (d, J¼10.7 Hz), 129.9 (d, J¼
59.1 Hz), 130.3 (s), 130.8 (d, J¼2.5 Hz), 132.6 (d, J¼
19.7 Hz), 133.7 (d, J¼2.5 Hz), 134.9 (d, J¼68.9 Hz), 138.3 (d,
J¼7.4 Hz), 141.0 (d, J¼4.9 Hz); 11B NMR (CDCl3): d¼ À
60.2 (d, J¼56.9 Hz); 31P NMR (CDCl3): d¼106.0 (m); IR
(KBr): n¼2925, 2380, 1435, 1200, 1155, 1135, 1065, 980, 830,
755 cmÀ1; FAB MS (rel intensity): m/z¼395 (Mþ BH3, 10),
À
405 (Mþ 3H, 36); HRMS (FAB): calcd. for C26H37BOP
À
(S,S)-1,2-Bis[boranatophenyl(5’,6’,7’,8’-tetrahydro-1’-
naphthyl)phosphino]ethane (4c)
(Mþ H): 407.2677; found: 407.3087; anal. calcd. for C26H38
À
BOP: C 76.47, H 9.38; found: C 76.08, H 9.49. The absolute con-
figuration at the asymmetric phosphorus atom of this diaster-
eomer was determined to be S by single crystal X-ray analysis.
X-Ray Crystallographic Data: FW¼408.37, monoclinic P21
(#4), a¼8.089(1), b¼15.658(9), c¼10.125(3) ä, b¼
109.88(2)8, V¼1206.1100 ä3, Z¼2, Dcalc ¼1.124 g/cm3, tem-
perature ofdata collection 288 K, 1426 observed relfection
(I>3.00s(I)), R¼0.053, RW ¼0.058.
(S)-Methylphenyl(5’,6’,7’,8’-tetrahydro-1’-naphthyl)phosphine-
borane (84% ee) (2.98 g, 11.1 mmol) was subsequently treated
with sec-BuLi (12 mL of1.0 mol/L cyclohexane-hexane solu-
tion) and anhydrous copper(II) chloride (2.4 g, 18 mmol) in
the same procedure as described above. Purification by column
chromatography (silica gel, toluene) and recrystallization (tol-
uene-hexane) afforded (S,S)-1,2-bis[boranatophenyl(5’,6’,7’,8’-
tetrahydro-1’-naphthyl)phosphino]ethane; yield: 1.62 g (55%);
colorless crystals; mp 195.0 195.58C (toluene:hexane¼2:3);
[a]2D3: þ36.6 (c 0.80, CHCl3); 1H NMR (CDCl3): d¼0.77
1.50 (m, 6H), 1.51 1.85 (m, 8H), 2.15 2.22 (m, 4H), 2.50
2.57 (m, 2H), 2.71 2.85 (m, 6H), 7.18 7.25 (m, 4H), 7.36
7.58 (m, 12H); 13C NMR (CDCl3): d¼19.8 20.2 (m), 22.1 (s),
22.4 (s), 28.6 (s), 29.9 (s), 125.7 (d, J¼4.9 Hz), 125.7 (d, J¼
5.7 Hz), 125.8 (d, J¼53.3 Hz), 128.6 129.4 (m), 130.5 (brs),
131.2 (s), 131.8 (d, J¼4.1 Hz), 131.9 (d, J¼4.9 Hz), 139.0 (d,
J¼4.1 Hz), 139.1 (d, J¼4.1 Hz), 141.9 (d, J¼4.1 Hz), 141.9
(d, J¼4.9 Hz); 11B NMR (CDCl3): d¼ À60.0 (brs); 31P NMR
(CDCl3): d¼18.2 (brs); IR (KBr): n¼2935, 2370, 1435, 1060,
(RP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(phenyl)(5’’,6’’,7’’,8’’-tetrahydro-1’’-naphthyl)phosphine-bor-
ane [(RP)-2c]: Colorless crystals; mp 103.0 103.58C; [a]2D5:
1
À21.5 (c 1.02, CHCl3); H NMR (CDCl3): d¼0.67 (d, J¼
7.1 Hz, 3H), 0.71 1.70 (m, 14H), 0.80 (d, J¼6.6 Hz, 3H),
0.86 (d, J¼7.1 Hz, 3H), 1.97 2.06 (m, 2H), 2.53 (t, J¼
6.3 Hz, 2H), 2.77 (t, J¼6.3 Hz, 2H), 4.29 4.38 (m, 1H),
7.24 7.25 (m, 2H), 7.35 7.46 (m, 3H), 7.55 7.58 (m, 2H),
7.94 (ddd, J¼16.8, 9.3, 4.4 Hz, 1H); 13C NMR (CDCl3): d¼
15.5 (s), 21.1 (s), 22.1 (s), 22.3 (s), 22.5 (s), 22.7 (s), 28.2 (d,
J¼4.1 Hz), 29.2 (s), 31.4 (s), 34.2 (s), 43.0 (s), 49.1 (d, J¼
5.8 Hz), 79.6 (d, J¼4.1 Hz), 125.2 (d, J¼12.4 Hz), 128.3 (d,
J¼9.9 Hz), 130.7 (d, J¼11.6 Hz), 130.8 (d, J¼56.2 Hz), 131.1
(s), 131.6 (d, J¼16.5 Hz), 133.3 (d, J¼2.5 Hz), 133.9 (d, J¼
68.6 Hz), 138.3 (d, J¼8.3 Hz), 140.9 (d, J¼7.4 Hz); 11B NMR
(CDCl3): d¼ À60.5 (d, J¼55.8 Hz); 31P NMR (CDCl3): d¼
103.5 (m); IR (KBr): n¼3050, 2930, 2380, 1570, 1440, 1230,
845 cmÀ1; FAB MS (rel intensity): m/z¼507 (Mþ 2BH3 þH,
À
2), 519 (Mþ BH3 H, 6); anal. calcd. for C34H42B2P2: C 76.43,
H 7.92; found: C 76.26, H 7.92.
À
À
1065, 990, 750 cmÀ1; FAB MS (rel intensity): m/z¼395 (Mþ
þ
(SP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(o-isopropylphenyl)phenylphosphine-borane [(SP)-2d]
and (RP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclo-
hexyloxy)(o-isopropylphenyl)phenylphosphine-borane
[(RP)-2d]
À
À
BH3, 15), 405 (M 3H, 46); HRMS (FAB): calcd. for C26
À
H37BOP (M H): 407.2677; found: 407.3121; anal. calcd. for
C26H38BOP: C 76.47, H 9.38; found: C 76.32, H 9.46.
Dichlorophenylphosphine (19 mL, 140 mmol) was successive-
ly reacted with o-isopropylphenylmagnesium bromide
(140 mL of1.0 M/L THF solution, 140 mmol), lithium menth-
oxide (140 mmol), and borane-THF complex (182 mL of
1.0 mol/L) in a similar manner to that described above to
give a mixture of( SP)-diastereomer and (RP)-diastereomer as
(S)-Methylphenyl(5’,6’,7’,8’-tetrahydro-1’-naphthyl)-
phosphine-borane (3c)
A solution of( SP,1’R,2’S,5’R)-(2’-isopropyl-5’-methylcyclohex-
yloxy)(phenyl)(5’’,6’’,7’’,8’’-tetrahydro-1’’-naphthyl)phosphine-
borane (6.53 g, 16 mmol) in THF (80 mL) was added to a solu-
Adv. Synth. Catal. 2004, 346, 777 788
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
785

Tsuneo Imamoto et al.
FULL PAPERS
colorless crystals; yield: 46.6 g (84%). Each diastereomer was
separated by fractional crystallization from hexane.
gel, toluene) to afford (S)-(o-isopropylphenyl)phenylmethyl-
phosphine-borane; yield: 5.06 g (99%). The enantiomeric ex-
cess ofthe product was determined to be 94% ee by HPLC
analysis [DAICEL CHIRALPAK AS, hexane:2-propanol¼
30:1, 0.5 mL/min, (R) t1 ¼14.1 min, (S) t2 ¼18.4 min]. Color-
less plates; mp 80.5 81.58C (toluene-hexane); [a]1D8: þ8.7 (c
(SP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(o-isopropylphenyl)phenylphosphine-borane [(SP)-2d]: Col-
orless prisms; mp 134.5 135.08C (hexane); [a]1D8: À82.6 (c
1.39, CHCl3); 1H NMR (CDCl3): d¼0.52 1.80 (m, 11H), 0.61
(d, J¼7.0 Hz, 3H), 0.67 (d, J¼6.8 Hz, 3H), 0.76 (d, J¼
7.3 Hz, 3H), 0.87 (d, J¼6.8 Hz, 3H), 0.89 (d, J¼6.8 Hz, 3H),
2.05 2.08 (m, 1H), 3.12 3.18 (m, 1H), 4.38 4.47 (m, 1H),
7.28 7.32 (m, 2H), 7.35 7.44 (m, 3H), 7.47 7.51 (m, 1H),
7.55 7.61 (m, 2H), 8.10 (ddd, J¼9.4, 7.7, 1.2 Hz, 1H);
13C NMR (CDCl3): d¼15.3 (d, J¼4.1 Hz), 21.0 (d, J¼
5.7 Hz), 22.1 (d, J¼8.2 Hz), 22.5 (brs), 23.3 (d, J¼8.2 Hz),
23.4 (d, J¼4.9 Hz), 25.4 (d, J¼8.2 Hz), 31.0 (dd, J¼4.9,
4.9 Hz), 31.5 (brs), 34.1 (brs), 43.6 (s), 48.9 (s), 80.5 80.6 (m),
125.4 (d, J¼12.3 Hz), 127.1 (d, J¼8.2 Hz), 128.2 (d, J¼
10.2 Hz), 130.1 (d, J¼75.5 Hz), 130.4 (s), 130.8 (s), 132.4 (s),
133.2 (d, J¼9.8 Hz), 133.4 (d, J¼9.8 Hz), 135.9 (d, J¼
66.5 Hz), 152.6 (d, J¼6.6 Hz); 11B NMR (CDCl3): d À60.4
(d, J¼45.8 Hz); 31P NMR (CDCl3): d¼104.3 (m); IR (KBr):
1
2.30, CHCl3); H NMR (CDCl3): d¼0.73 (d, J¼6.8 Hz, 3H),
0.88 1.56 (m, 3H), 1.08 (d, J¼6.83, 3H), 1.86 (d, J¼9.8 Hz,
3H), 3.13 3.19 (m, 1H), 7.29 7.53 (m, 6H), 7.57 7.67 (m,
3H) 2.19 (s); 13C NMR (CDCl3): d¼13.7 (d, J¼41.4 Hz), 23.3
(s), 24.1 (s), 31.7 (d, J¼6.6 Hz), 126.1 (d, J¼9.9 Hz), 127.1
(d, J¼55.4 Hz), 127.6 (d, J¼8.3 Hz), 128.8 (d, J¼9.9 Hz),
130.9 (d, J¼2.5 Hz), 131.6 (d, J¼9.1 Hz), 131.8 (d, J¼
9.9 Hz), 131.9 (d, J¼1.7 Hz), 132.2 (d, J¼55.4 Hz), 153.6 (d,
J¼9.1 Hz); 11B NMR (CDCl3): d¼ À58.1 (d, J¼45.7 Hz);
31P NMR (CDCl3): d 9.7 (m); IR (KBr): n¼3020, 2935, 2380,
1580, 1470, 1430, 1070, 910, 895 cmÀ1;þFAB MS (rel intensity):
m/z¼242 (Mþ BH3 H, 46), 253 (M 3H, 100); anal. calcd.
À
À
À
for C16H22BP: C 75.03, H 8.66; found: C 75.14, H 8.75.
n¼3055, 2950, 2390, 1590, 1570, 1435, 1060, 990, 765 cmÀ1
;
þ
FAB MS (rel intensity): m/z¼393 (Mþ 3H, 23), 395 (M
À
À
H, 10); anal. calcd. for C25H38BOP: C 75.76, H 9.66; found:
C 75.80, H 9.72. The absolute configuration at the asymmetric
phosphorus atom ofthis diastereomer was determined to be S
by single crystal X-ray analysis.
(S,S)-1,2-Bis[boranato(o-isopropylphenyl)-
phenylphosphino]ethane (4d)
X-Ray Crystallographic Data: FW¼396.36, monoclinic P21
(#4), a¼8.4609(6), b¼10.761(1), c¼13.858(1) ä, b¼
98.473(7)8, V¼1248.0(2) ä3, Z¼2, Dcalc ¼1.055 g/cm3, temper-
ature ofdata collection 296 K, 1609 observed relfection ( I>
3.00s(I)), R¼0.065, RW ¼0.065.
(S)-(o-Isopropylphenyl)phenylmethylphosphine-borane (94%
ee) (2.56 g, 10 mmol) was subsequently treated with sec-BuLi
(10.6 mL of0.96 mol/L cyclohexane-hexane solution) and an-
hydrous copper(II) chloride (2.0 g, 15 mmol) using the same
procedure as described above. Purification by column chroma-
tography (silica gel, toluene) and recrystallization (toluene-
hexane) afforded (S,S)-1,2-bis[boranato(o-isopropylphenyl)-
phenylphosphino]ethane; yield: 1.64 g (64%); colorless crys-
tals; mp 160.5 161.58C (hexane:toluene¼10:1); [a]1D8: þ
55.5 (c 1.0, CHCl3); 1H NMR (CDCl3): d¼0.68 (d, J¼6.8 Hz,
6H), 0.71 1.55 (m, 6H), 1.05 (d, J¼6.5 Hz, 6H), 2.19 2.27
(m, 2H), 2.55 2.63 (m, 6H), 3.12 3.19 (m, 6H), 7.26 7.30
(m, 2H), 7.33 7.40 (m, 5H), 7.43 7.53 (m, 7H), 7.58 (dd, J¼
11.4, 6.5 Hz, 2H); 13C NMR (CDCl3): d¼20.1 20.4 (m), 23.2
(s), 24.0 (s), 31.6 (d, J¼3.3 Hz), 31.6 (d, J¼3.3, Hz), 125.6 (d,
J¼55.0 Hz), 126.2 (d, J¼4.9 Hz), 126.2 (d, J¼4.9 Hz), 127.7
(d, J¼4.1 Hz), 127.8 (d, J¼4.1 Hz), 128.8 (d, J¼4.9 Hz),
128.9 (d, J¼4.9 Hz), 129.7 (d, J¼55.0 Hz), 131.2 (s), 131.9
132.1 (m) , 153.7 (d, J¼4.9 Hz) , 153.7 (d, J¼4.9 Hz);
11B NMR (CDCl3): d¼ À59.9 (brs); 31P NMR (CDCl3): d¼
17.4 (m); IR (KBr): n¼3020, 2935, 2340, 1580, 1470, 1430,
(RP,1’R,2’S,5’R)-(2’-Isopropyl-5’-methylcyclohexyloxy)-
(o-isopropylphenyl)phenylphosphine-borane [(RP)-2d]: Col-
orless needles; mp 116.0 116.58C (hexane); [a]2D4: À29.6 (c
0.99, CHCl3); 1H NMR (CDCl3): d¼0.43 1.66 (m, 10H), 0.64
(d, J¼6.8 Hz, 3H), 0.81 0.86 (m, 12H), 1.93 2.00 (m, 1H),
2.07 2.17 (m, 1H), 3.11 3.20 (m, 1H), 4.28 4.40 (m, 1H);
7.31 7.46 (m, 5H), 7.49 7.59 (m, 3H), 8.06 (dd, J¼10.9,
7.5 Hz, 1H); 13C NMR (CDCl3): d¼15.4 (s), 21.1 (d, J¼
7.4 Hz), 22.0 (d, J¼5.4 Hz), 22.7 (brs), 23.3 (d, J¼9.0 Hz),
23.6 (d, J¼8.2 Hz), 25.5 (d, J¼5.7 Hz), 30.9 (dd, J¼5.7,
5.7 Hz), 31.4 (s), 34.2 (s), 43.5 (s), 49.1 (s), 79.8 (brs), 125.6
(d, J¼11.5 Hz), 127.1 (d, J¼7.4 Hz), 128.2 (d, J¼10.7 Hz),
130.5 (d, J¼73.0 Hz), 130.7 (s), 131.1 (s), 132.2 (s), 132.9 (d,
J¼9.8 Hz), 133.0 (d, J¼9.0 Hz), 134.7 (d, J¼68.0 Hz), 152.6
(d, J¼8.2 Hz); 11B NMR (CDCl3): d¼ À60.4 (d, J¼56.4 Hz);
31P NMR (CDCl3): d¼102.3 (m); IR (KBr): n¼3020, 2920,
2390, 1580, 1560, 1435, 1120, 1070, 985, 960, 930, 870,
770 cmÀ1; FAB MS (rel intensity): m/z¼393 (Mþ 3H, 38),
À
1165 cmÀ1; FAB MS (rel intensity): m/z¼483 (Mþ 2BH3 þ
À
395 (Mþ H, 14); anal. calcd for C25H38BOP: C 75.76, H 9.66;
À
þ
þ
H, 27), 495 (Mþ BH3 H, 100), 505 (M 5H, 40), 509 (M
À
À
À
found: C 75.78, H 9.84.
þ
þ
À
H, 25), 510 (M , 14), 511 (M þH, 28); anal. calcd. for C32
H42B2P2: C 75.33, H 8.30; found: C 75.19, H 8.36.
(S,S)-1,2-Bis[(o-isopropylphenyl)phenylphosphino]ethane
1
(1d): Mp 106 1078C; [a]2D5: À10.0 (c 1.0, toluene); H NMR
(S)-(o-Isopropylphenyl)phenylmethylphosphine-
borane (3d)
(CDCl3): d¼0.98 (d, J¼6.8 Hz, 6H), 1.22 (d, J¼6.8 Hz, 6H),
2.06 2.09 (m, 4H), 3.73 3.81 (m, 2H), 7.1 7.3 (m, 18H); 13C
NMR (CDCl3): d¼23.96, 23.99, 24.06, 24.11, 30.76, 30.89,
31.02, 125.49, 125.51, 125.97, 128.29, 128.34, 128.37, 129.19,
131.11, 132.49, 132.58, 132.68, 134.65, 134.70, 134.77, 138.98,
139.05, 139.12, 153.65, 153.76, 153.88 cmÀ1; IR (KBr): n¼
3050, 2960, 1470, 1435, 745, 695 cmÀ1; HRMS (FAB): calcd
for C32H37P2 (M H): 438.2371; found: 483.2354.
A solution of( SP,1’R,2’S,5’R)-(2’-isopropyl-5’-methylcyclohex-
yloxy)(o-isopropylphenyl)phenylphosphine-borane (7.93 g,
20 mmol) in THF (100 mL) was added to a solution of
LDBB (270 mL of0.3 M THF solution, 80 mmol) at À988C.
After 5 min, diiodomethane (7.0 mL, 112 mmol) was added.
The product was isolated by column chromatography (silica
786
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 777 788

Rh-Catalyzed Asymmetric Hydrogenation of a-(Acylamino)acrylic Derivatives
FULL PAPERS
229, 1; c) M. Ohff, J. Holz, M. Quirmbach, A. Bˆrner,
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Morrison, J. W. Scott), Academic Press, New York, 19
84, Vol. 4, Chap. 3.
Preparation of Rhodium Complexes 5a d
Complexes 5a d were obtained as orange powders using the
procedure described in the literature.[7] Single crystals of 5c
for X-ray analysis were prepared by recrystallization from di-
chloromethane.
X-Ray Crystallographic Data for 5c: Empirical formula¼
C42.5H53BF4P2RhClO2 {[Rh(1c)(cod)]BF4 ¥1/2 CH2Cl2 ¥2 H2)},
FW¼881.99, monoclinic P21 (#4), a¼11.558(2), b¼22.07(2),
c¼16.671(4) ä, b¼93.51(2)8, V¼4244.54 ä3, Z¼2, Dcalc
¼
1.380 g/cm3, temperature ofdata collection 173 K, 4217 ob-
served reflection (I>4.50s(I)), R¼0.066, RW ¼0.082.
[3] W. S. Knowles, M. J. Sabacky, J. Chem. Soc. Chem. Com-
mun. 1968, 1445.
[4] L. Horner, Siegel, H. Buthe, Angew. Chem. Int. Ed. Engl.
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[5] W. S. Knowles, M. J. Sabacky, B. D. Vineyard, J. Chem.
Soc. Chem. Commun. 1972, 10.
[6] W. S. Knowles, M. J. Sabacky, B. D. Vineyard, D. J. Wein-
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[7] B. D. Vineyard, W. S. Knowles, M. J. Sabacky, G. L.
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[8] W. S. Knowles, Acc. Chem. Res. 1983, 16, 106.
[9] W. S. Knowles, Angew. Chem. Int. Ed. 2002, 41, 1998;
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[11] U. Nagel, T. Krink, Angew. Chem. Int. Ed. Engl. 1993, 32,
1052.
General Procedure for Asymmetric Hydrogenation of
a-Acylaminoacrylic Derivatives
A 50-mL Fischer Porter tube was charged with the substrate
(1 mmol) and the catalyst precursor (0.002 mmol or
0.001 mmol). The tube was connected to the hydrogen tank
via stainless steel tubing. The vessel was evacuated and filled
with hydrogen gas (Nippon Sanso, 99.9999%) to a pressure of
about 2 atm. This operation was repeated and the bottle was
immersed in a dry ice-ethanol bath. The upper cock ofthe bot-
tle was opened and degassed solvent was added quickly using a
syringe. After four vacuum/H2 cycles, the tube was pressurized
to the desired initial pressure and immersed in a constant-tem-
perature bath. The solution or suspension was magnetically
stirred at 508C until no further hydrogen uptake was observed.
The resulting solution was passed through silica gel using ethyl
acetate as the eluent, and the filtrate was submitted to direct
analysis ofthe ee values by HPLC or GC.
[12] U. Nettekoven, M. Widhalm, P. C. J. Kamer, P. W. N. M.
Van Leeuwen, Tetrahedron: Asymmetry 1997, 8, 3185.
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M. Widhalm, A. L. Spek, M. Lutz, J. Org. Chem. 1999,
64, 3996.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific re-
search from the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
[14] F. Maienza, M. Wˆrle, P. Steffanut, A. Mezzetti, Organo-
metallics 1999, 18, 1041.
[15] For other representative P-stereogenic phosphine ligands
used for asymmetric catalysis, see: a) L. Horner, B.
Schlotthauer, Phosphorus Sulfur 1978, 4, 155; b) J. W.
Scott, D. D. Keith, G. Nix, Jr., D. R. Parrish, S. Reming-
ton, G. P. Roth, J. M. Townsend, D. Valentine, Jr., R.
Yang, J. Org. Chem. 1981, 46, 5086; c) F. Robin, F. Mer-
cier, L. Ricard, F. Mathey, M. Spagnol, Chem. Eur. J. 199
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mada, H. Tsuruta, S. Matsukawa, K. Yamaguchi, J. Am.
Chem. Soc. 1998, 120, 1635; e) Y. Yamanoi, T. Imamoto,
J. Org. Chem. 1999, 64, 2988; f) T. Miura, T. Imamoto,
Tetrahedron Lett. 1999, 40, 4833; g) I. D. Gridnev, Y. Ya-
manoi, N. Higashi, H. Tsuruta, M. Yasutake, T. Imamoto,
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References and Notes
[1] For representative reviews, see: a) W. Tang, X. Zhang,
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[2] For representative reviews dealing with optically active
[16] The X-ray data ofsingle crystals ofrhodium-DIPAMP
complexes suggest the possibility ofweak interaction of
the methoxy oxygen atom with the rhodium atom; see
phosphine ligands as the main subject, see: a) G. Cheluc-
¡
ci, G. Orru, G. A. Pinna, Tetrahedron 2003, 59, 9471;
¬
b) K. V. L. Crepy, T. Imamoto, Top. Curr. Chem. 2003,
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¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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[17] A preliminary account ofa portion ofthis work has been
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[19] The removal ofthe boranato group from phosphine-bor-
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[23] The following are the highest ee values for the enantio-
selective hydrogenation of b,b-disubstituted derivatives:
Me-DuPHOS: 99.4% ee;[24] Me-BPE: 98.6% ee;[24] un-
symmetric BisP*: 98.2% ee;[25] MiniPHOS: 97% ee:[15e, g]
BisP*: 93.0% ee;[15d, g] (S,S)-bis(isopropylmethylphosphi-
no)benzene: 89% ee;[26] BuTRAP: 88% ee.[27]
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Matsuo, T. Hikosaka, M. Yanagawa, Heteroatom Chem.
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788
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 777 788