Synthesis of diastereomeric 1,4-diphosphine ligands bearing imidazolidin-2-one backbone and their application in Rh(I)-catalyzed asymmetric hydrogenation of functionalized olefins

Article abstract of DOI:10.1002/adsc.200404286

The diastereomeric 1,4-diphosphine ligands, (S,S,S,S)-1a, (R,S,S,R)-1b and (R,S,S,S)-1c, with the imidazolidin-2-one backbone were synthesized, and utilized for an investigation of the effects of backbone chirality on the enantioselectivity in the Rh(I)-catalyzed hydrogenation of various functionalized olefinic substrates. It was found that the catalytic efficiencies are largely dependent on the configurations of the α-carbons to phosphine. Thus, the Rh complex of the pseudo-C₂-symmetrical diphosphine, (R,S,S,S)-1c, showed excellent enantioselectivities (93.0-98.6% ees) in the hydrogenations of a broad spectrum of substrates, and especially in the hydrogenations of methyl α-(N-acetyamino)-β-arylacrylates (95.3-97.0% ees). However, the enantioselectivities obtained with the C ₂-symmetrical (R,S,S,R)-1b were largely dependent on the substrate (19.8-97.3% ees). The Rh complex of ligand 1a having the (S,S,S,S)-configuration showed the lowest catalytic efficiency for all of the substrates examined (0-84.8% ees).

Full text of DOI:10.1002/adsc.200404286

FULL PAPERS
Synthesis of Diastereomeric 1,4-Diphosphine Ligands Bearing
Imidazolidin-2-one Backbone and Their Application in Rh(I)-
Catalyzed Asymmetric Hydrogenation of Functionalized Olefins
Yong Jian Zhang,a Kee Yong Kim,a Jung Hwan Park,a Choong Eui Song,b,*
Kyungae Lee,c Myoung Soo Lah,c Sang-gi Leea,*
a
Life Sciences Division, Korea Institute of Science and Technology, P. O. Box 131, Cheongryang, Seoul 130-650, Korea
Fax: (þ82)-2-958-5189, e-mail: sanggi@kist.re.kr
b
Institute of Basic Science, Department of Chemistry, Sungkyunkwan University, Suwon, Kyeonggi-do 440-746, Korea
c
Department of Chemistry, College of Science, Hanyang University, Ansan, Kyeonggi-do 426-791, Korea
Received: September 9, 2004; Accepted: January 3, 2005
Dedicated to Professor Yong Hae Kim on the occasion of his retirement.
Abstract: The diastereomeric 1,4-diphosphine ligands, substrates, and especially in the hydrogenations of
(S,S,S,S)-1a, (R,S,S,R)-1b and (R,S,S,S)-1c, with the methyl
a-(N-acetyamino)-b-arylacrylates
(95.3–
imidazolidin-2-one backbone were synthesized, and 97.0% ees). However, the enantioselectivities ob-
utilized for an investigation of the effects of backbone tained with the C2-symmetrical (R,S,S,R)-1b were
chirality on the enantioselectivity in the Rh(I)-cata- largely dependent on the substrate (19.8–97.3% ees).
lyzed hydrogenation of various functionalized olefinic The Rh complex of ligand 1a having the (S,S,S,S)-con-
substrates. It was found that the catalytic efficiencies figuration showed the lowest catalytic efficiency for
are largely dependent on the configurations of the all of the substrates examined (0–84.8% ees).
a-carbons to phosphine. Thus, the Rh complex of
the pseudo-C2-symmetrical diphosphine, (R,S,S,S)-1c,
showed excellent enantioselectivities (93.0–98.6% Keywords: asymmetric hydrogenation; backbone chir-
ees) in the hydrogenations of a broad spectrum of ality; diphosphine ligands; olefins; rhodium
Introduction
ibility of the seven-membered metal chelates by employ-
ment of conformationally rigid backbones such as biscy-
The design and synthesis of new and unique chiral phos- clopentyl (BICP) or 1,4-dioxane (SK-Phos).[3] Zhang[4]
phine ligands with properties superior to their predeces- and RanjaBabu[5] have also independently synthesized
sors are important targets in catalytic asymmetric reac- diastereomeric (S,S,S,S)- and (R,S,S,R)-DIOP* ligands,
tions, and have attracted a great deal of attention from in which new stereogenic centers at the a position to
both academia and industry.[1] Modulation of the steric the diphenylphosphine groups in DIOP were introduced.
and electronic properties of a specific ligand scaffold In Rh-catalyzed asymmetric hydrogenations of a-aryl-
could provide an opportunity for the development of a enamides, it was found that (R,S,S,R)-DIOP* provided
more efficient chiral ligand. Kaganꢀs pioneering work excellent enantioselectivities, whereas its diastereomeric
on the development of the historical DIOP had a signifi- ligand, (S,S,S,S)-DIOP*, which was first synthesized by
cant impact in the design of new efficient chiral ligands Kagan,[6] provided much lower enantioselectivity. Based
for asymmetric hydrogenation.[2] However, due to the on conformational analysis, it has been reasoned that
conformational flexibility of the seven-membered metal the two methyl groups are oriented at pseudoequatorial
chelates (a number of energetically similar conforma- positions in the effective conformer of the (R,S,S,R)-
tions of the chelates are available), the enantioselectivi- DIOP*-metal complex, thereforestabilizing the effective
ties obtained with the metal complexes of the DIOP or conformer to promote high enantioselectivity. On the
its analogous are not always sufficiently high. Recent ef- other hand, the (S,S,S,S)-DIOP* has two methyl groups
forts onthe developmentof DIOP-type 1,4-diphosphines at pseudoaxial positions which destabilize the effective
were mainly focused on the restriction of the conforma- conformer and lead to diminished ees.
tional flexibility of the seven-membered metal chelates.
Recently, we reported a new type of 1,4-diphosphine
Zhang et al. reduced effectively the conformational flex- ligands, BDPMI, with an imidazolidin-2-one back-
Adv. Synth. Catal. 2005, 347, 563–570
DOI: 10.1002/adsc.200404286
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FULL PAPERS
Figure 1. Chiral 1,4-diphosphine ligands.
bone[7]. The gauche steric interaction between the N sub-
stituents and the phosphanylmethyl group of the ligands
may restrict the conformational flexibility of the seven-
membered metal chelate ring. These BDPMI ligands
have been successfully applied in Rh-catalyzed hydro-
genations of a-arylenamides,[7a], acyclic[7b] and cyclic b-
(N-acylamino)acrylates,[7d] and excellent enantioselec-
tivities (up to 99% ees) have been obtained. However,
the Rh complexes of BDPMI ligands furnished only
Figure 2. ORTEP diagram of (R,S,S,R)-6a.
low to moderate enantioselectivities in the hydrogena- (Scheme 1).[8] Selective epimerization of the a-methine
tion of other olefinic substrates such as a-(N-acylami- proton to the ester group in the cis-monoester (R,S)-2
no)cinnamic acid or itaconic acid derivatives.[7c] We as- (optical purity>99.9% ee), followed by hydrolysis and
sumed that the introduction of a-substituents (a to the esterification afforded the trans-dicarboxylic acid di-
diphenylphosphine groups) in the BDPMI ligand could methyl ester (S,S)-3c in high yield (three steps with
beneficially affect the gauche steric interaction between 88% overall yield). The optical purity (>99.9% ee) of
the N substituent and the phosphinomethyl groups, the dimethyl ester (S,S)-3c as determined by HPLC
which may largely depend on the configuration of the analysis (Dicel Chiralpak AD column) indicated that
a-substituent. To investigate the effects of backbone there are no loss of optical purity during these transfor-
configurations on the enantioselectivity, we synthesized mation processes. The trans-diester (S,S)-3c was con-
the new diastereomeric 1,4-diphosphine ligands, verted to the diketone (S,S)-4b through the formation
(4S,5S)-1,3-dibenzyl-4,5-di[(1S,1’S)-(1-diphenylphospha- of the Weinreb amide (S,S)-4a followed by reaction
noethyl)]imidazolidin-2-one (1a) [abbreviated as with methylmagnesium bromide in 84% yield (two
(S,S,S,S)-BDPMI*] and its diasteromeric analogues steps). Reduction of the diketone (S,S)-4b with Dibal-
(R,S,S,R)-BDPMI* (1b) and (R,S,S,S)-BDPMI* (1c). H afforded a mixture of diastereomeric diols 5a–c in
In this paper, we report the synthesis of the diastereo- 93% yield with the ratio of 5a:5b:5c¼68:3:29 (based
meric ligands 1a–c and their application in the Rh-cata- on 1H NMR analysis), which were not separable by silica
lyzed asymmetric hydrogenation of various functional- gel column chromatography. Fortunately, the formation
ized olefins.
of the corresponding p-nitrobenzoates 6a–c allowed the
separation ofeachisomer. Thus, the inseparable mixture
of 5a–c was treated with p-nitrobenzoyl chloride to give
the mixture of dibenzoates 6a–c. Recrystallization from
ethyl acetate/n-hexane (ca. 1/1, v/v) afforded the pure
(R,S,S,R)-6a as single crystals suitable for X-ray analysis
from which the absolute stereochemistries at the newly
generated stereogenic centers of 6a could be assigned
unambiguously as the R configuration. Methanolysis
Results and Discussion
Synthesis of the Diastereomeric Diphosphine Ligands
1a–1c
The N,N’-dibenzylated diastereomeric diphosphine li- of the benzoate 6a provided an optically pure
gands 1a–c could be prepared starting from the optically (R,S,S,R)-5a. From the mother liquor, the second major
pure (4R,5S)-1,3-dibenzylimidazolidin-2-one-4,5-dicar- isomer (S,S,S,R)-6c could be separated by silica gel col-
boxylicacid monocyclohexylester 2, which is a keyinter- umn chromatography. The minor diastereomer
mediate for the commercial production of biotin (S,S,S,S)-6b could be synthesized by Mitsunobu reaction
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FULL PAPERS
Scheme 1. Synthesis of the diastereomeric 1,4-diphosphine ligands 1a–1c. (a) MeONa/MeOH, reflux, 4 h, 98%. (b) 1 M aque-
ous NaOH, reflux, 1 h, 95%. (c) TMSCl/MeOH, rt, 12 h, 95%. (d) HN(OMe)Me, i-PrMgBr, THF. (e) CH3MgBr (two steps:
84%). (f) Dibal-H, THF, ꢀ78 8C, 3 h, 93%. (g) p-NO2-C6H4COCl, Et3N, DMAP, CH2Cl2, rt, 5 h, 94%; recrystallization in
EtOAc/n-hexane; silica-gel column chromatography. (h) K2CO3, MeOH-CH2Cl2 (v/v, 3/1), 96–97%. (i) p-NO2-C6H4COOH,
PPh3, DEAD, THF, rt, 4 h, 91%. (j) MsCl/Et3N, CH2Cl2, 0 8C, 2 h, 97–98%. (k) KPPh2 (0.5 M THF), THF, rt, 18 h, 74%
for 1a, 65% for 1b, 47% for 1c.
of the optically pure (R,S,S,R)-5a with p-nitrobenzoic Asymmetric Hydrogenation
acid. Methanolysis ofthe optically pure 6b and 6c afford-
ed the corresponding diols 5b and 5c quantitatively. To investigate the catalytic efficiency of the novel dia-
Methanesulfonylation of the diols 5a, 5b and 5c, fol- stereomeric diphosphine ligands, various kinds of proto-
lowed by reaction with potassium diphenylphosphide typical olefinic substrates, a-(N-acylamino)cinnamic
afforded the desired diphosphines 1a, 1b and 1c in acid (7) and its methyl ester (8), a-arylenamides 9,
good yields. The sign of optical rotation of 1a {[a]2D5: (E)-(10a)and (Z)-b-(N-acylamino)acrylates (10b), and
þ26.9 (c 0.23 in chloroform)} and 1b {[a]2D5: þ31.7 (c itaconate 11, were hydrogenated using the Rh complex
0.24 in chloroform)} is opposite to that of 1c {[a]2D5: of the diastereomeric BDPMI* 1a–c and with Bn-
ꢀ44.7 (c 0.37 in chloroform)}. The 31P NMR spectra of BDPMI for comparison. All hydrogenations were car-
the C2-symmetrical ligands 1a and 1b showed a single ried out at 208C under 1 atm of H2 pressure in the pres-
resonance at 1.91 and 4.02 ppm, respectively, whereas ence of 1 mol % of Rh complex in situ generated from
two resonance at ꢀ0.04 and 8.85 ppm were shown by Rh(cod)2BF4 and ligand, and the results are summarized
the pseudo-C2-symmetrical 1c.
in Table 1 (data of entries 1,[7c] 10[7a] and 22[7c] from our
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Yong Jian Zhang et al.
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Table 1. Rh(I)-catalyzed asymmetric hydrogenation of func-
tionalized olefins 7–11 using 1a–c and Bn-BDPMI.[a]
previous reports). It was found that the backbone con-
figurations of the ligand profoundly influenced the
enantioselectivity for all substrates examined. In the hy-
drogenations of a-(N-acylamino)cinnamic acid 7, the
enantioselectivities were dramatically changed (from
racemic to 94.9% ee) with changes of the configurations
of the a-stereogenic centers (a to the phosphorus atom)
(entries 2–4). No stereoinductions were observed with
(S,S,S,S)-BDPMI* (1a) (entry 2). Moreover, the enan-
tioselectivity obtained with the C2-symmetrical diphos-
phine ligand (R,S,S,R)-1b was lower than that obtained
with the parent ligand (S,S)-Bn-BDPMI with the oppo-
site sense of stereoinduction (compare entries 1 with 2
and 3). Surprisingly, excellent enantioselectivities
(93.0% ee, entry 4)can be achieved with the non C2-sym-
metrialc ligand (R,S,S,S)-BDPMI* (1c). In the case of a-
(N-acylamino)cinnamic acid methyl esters 8, ligand 1a
exhibited a much higher enantioselectivity (84.8% ee)
than ligand 1b (19.8% ee). Here again, (R,S,S,S)-
BDPMI* (1c) achieved the highest enantioselectivity
(96.0% ee, entry 8). The enantioselectivities in the hy-
drogenation of a-arylenamides 9 were also affected by
the backbone configurations of the ligands, but the ef-
fects were not significantly high (entries 9–12). Both
C2-symmetrical ligands 1a (50.6% ee, entry 10) and 1b
(95.1% ee, entry 11) gave lower enantioselectivities
Entry
Substrate
Ligand
% ee[k]
(confuration)[l]
1[b]
2
7
7
Bn-BDPMI
1a
75.0 (S)
rac (-)
3
7
7
8
8
8
8
9
9
1b
1c
71.4 (S)
93.0 (R)
16.0 (R)
84.8 (R)
19.8 (R)
96.0 (R)
96.2 (R)
50.6 (R)
95.1 (R)
98.6 (R)
91.7 (R)
13.0 (R)[e]
78.2 (R)
95.7 (R)
96.3 (R)[f]
96.2 (R)
50.3 (R)[h]
80.2 (R)[i]
97.2 (R)
42.5 (R)
6.0 (R)
4
5[c]
6
Bn-BDPMI
1a
1b
1c
Bn-BDPMI
1a
1b
1c
Bn-BDPMI
1a
1b
1c
7
8
9[d]
10
11
12
13[d]
14
15
16
17
18[g]
9
9
(E)-10
(E)-10
(E)-10
(E)-10
(E)-10
(Z)-10
(Z)-10
(Z)-10
(Z)-10
11
1c
Bn-BDPMI
1a
1b
1c
than the parent ligand (S,S)-Bn-BDPMI (96.2% ee, en- 19
20
try 9). Again, the highest enantioselectivity could also be
achieved with 1c (98.6% ee, entry 12). Similar trends
21
22[j]
Bn-BDPMI
were observed in the hydrogenation of (E)- and (Z)-b-
(acylamino)acrylates (10), which have recently received
a great deal of attention due to their different stereose-
lectivity.[9] Both ligands 1a (entries 14 and 19) and 1b
(entries 15 and 20) showed much lower enantioselectiv-
ity and reactivity compared with 1c (entries 16 and 21).
In the hydrogenation of (E)-b-(acylamino)acrylate, (E)-
10, using the Rh complex of 1c, the enantioselectivity
obtained in i-PrOH solvent (96.3% ee, entry 17) was
higher than in CH2Cl2 (95.7% ee, entry 16), which is a
rare case, but the reaction did not go to completion
(74% conversion). In contrast to the other substrates,
the same enantioselectivity could be achieved in the hy-
drogenation of methyl itaconate with both ligands 1b
(97.3% ee, entries 24) and 1c (97.3% ee, entry 25), but
the ligand 1a still exhibited a much lower enantioselec-
tivity (6.0% ee, entry 23). Taken together, the enantioin-
duction ability of non C2-symmetrical (R,S,S,S)-
BDPMI* (1c) is clearly superior as compared to the oth-
er C2-symmetrical diastereomeric ligands (S,S,S,S)-
BDPMI* (1a) and (S,S,S,S)-BDPMI* (1b). Most gratify-
ingly, the Rh complex of ligand 1c catalyzed the hydro-
genation of a broad spectrum of functionalized olefins
with excellent enantioselectivity.
23
24
25
11
11
11
1a
1b
1c
97.3 (R)
97.3 (R)
[a]
All hydrogenations were carried out at room temperature
using 1 mol % of Rh complex in situ generated from
Rh(cod)2BF4 and ligand, and achieved 100% conversion
unless otherwise noted.
Reactions for the substrate 7 were carried out in acetone
for 1 h.
Reactions for the substrate 8 were carried in THF for 1 h.
Reactions for the substrates 9 and (E)-10 were carried out
in CH2Cl2 for 12 h.
53% conversion.
Reaction was carried out in i-PrOH for 12 h, 74% conver-
sion.
Reactions for the substrate (Z)-10 were carried out in i-
PrOH for 12 h.
20% conversion.
[b]
[c]
[d]
[e]
[f]
[g]
[h]
[i]
[j]
75% conversion.
Reactions for the substrate 11 were carried out in i-PrOH
for 1 h.
Determined by GC analysis.
Determined by the sign of the optical rotation.
[k]
[l]
Finally, various b-aryl-a-dehydroamino acid methyl of (R,S,S,S)-BDPMI* (1c), and the results are summar-
esters, which are known to be notorious substrates for ized in Table 2. As exemplified by the substrates with
DIOP-type 1,4-diphosphine ligands, were hydrogenated methyl groups in ortho-, meta- and para-positions (en-
with excellent enantioselectivities using the Rh complex tries 2–4), the steric properties of the substrates slightly
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Diastereomeric 1,4-Diphosphine Ligands Bearing Imidazolidin-2-one Backbone
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Table 2. Rh(I)-catalyzed asymmetric hydrogenation of me-
thyl a-(N-acetylamino)-b-arylacrylates using 1c as a ligand.[a]
solvents were distilled prior to use. All purchased reagents
were used without further purification. Anhydrous solvents
were transferred by oven-dried syringes. Flasks were dried
with a flame under a stream of nitrogen. The NMR spectra
were recorded on a Bruker 300 spectrometer at 300 MHz
(1H), 75.5 MHz (13C) and 121 MHz (31P). The chemical shifts
are given in ppm relative to the corresponding reference;
TMS for 1H NMR and P(O)(OPh)3 (as an external reference)
for 31P NMR. GC analyses were performed using a Hewlett-
Packard 5890 Model. HPLC analyses were performed using
Agilent 1100 interfaced to an HP 71 series computer worksta-
tion. The enantiomeric excesses of the hydrogenation products
were determined by chiral capillary GC column using CP-Chir-
asil-Dex-CB (dimensions 30 mꢁ0.32 mm i.d.), CP-Chirasil-L-
Val (dimensions 30 mꢁ0.25 mm i.d.) and g-DEX 225 (dimen-
sions 30 mꢁ0.32 mm i.d.) columns with N2 as carrier gas
(2 mL/min). The racemic products were obtained by hydroge-
nation of substrates with Pd/C or an achiral rhodium catalyst.
Chemical analyses were carried out by the Advanced Anal-
ysis Center at Korea Institute of Science and Technology. The
optically pure cis-monocyclohexyl ester 2 was generously do-
nated by Samcho Biochemical Ltd., Korea.
Entry
Ar
% ee[b]
1
2
3
4
5
6
7
8
9
Ph
96.0
95.4
96.8
97.0
95.8
96.4
96.4
95.3
95.5
95.4
ortho-Me-C6H4
meta-Me-C6H4
para-Me-C6H4
para-F-C6H4
para-Cl-C6H4
para-Br-C6H4
para-OMe-C6H4
3,4-methylenedioxy-C6H3
2-naphthyl
10
[a]
All hydrogenations were carried out in THF at room tem-
perature using 1 mol % of Rh complex in situ generated
from Rh(cod)2BF4 and ligand, and achieved 100% conver-
sion as determined by NMR and GC analysis.
Determined by GC analysis.
[b]
(4S,5S)-1,3-Dibenzylimidazolidin-2-one-4,5-
dicarboxylic Acid Monocyclohexyl Ester [(S,S)-3a]
affected the enantioselectivity. On the other hand, the
enantioselectivities are not much dependent on the elec-
tronic property of the substrates. Both substrates bear-
ing electron-donating and electron-withdrawing groups
at the para-position were hydrogenated with almost the
same enantioselectivities. Although the enantioselectiv-
ities (95.3–97.0% ees) are not extremely high (>99%
ee), it is noteworthy that these are among the highest
enantioselectivities obtained from the Rh-catalyzed hy-
drogenation of a-dehydroamino acid derivatives using
DIOP-type 1,4-diphosphine ligands.[10]
To a solution of sodium methoxide generated from sodium
metal (0.34 g, 14.9 mmol) in methanol (100 mL) was added
cis-monocyclohexyl ester (R,S)-2 (5 g, 11.5 mmol) in one por-
tion. The reaction mixture was refluxed for 4 h, and allowed
to cool to room temperature. The solution was acidified with
3% aqueous HCl solution until the solution had pH¼4. After
evaporation of the methanol on a rotary evaporator, the organ-
ic materials was extracted with ethyl acetate (50 mLꢁ3). The
combined organic layer was dried over anhydrous MgSO4,
and the ethyl acetate was evaporated to give product (S,S)-3a
as a viscous oil; yield: 4.9 g (98%); [a]2D5: ꢀ13.6 (c 2.22,
MeOH); 1H NMR (acetone-d6): d¼1.17–1.31 (m, 6H), 1.54–
1.89 (m, 4H), 3.60 (m, 1H), 4.02–4.25 (m 4H), 4.93 (d, J¼
15.3 Hz, 2H), 5.08 (d, 2H, J¼15.3 Hz, 2H), 7.23–7.35 (m,
10H); 13C NMR (acetone-d6): d¼24.0, 25.2, 34.8, 46.4, 46.7,
56.8, 57.5, 70.7, 127.6, 127.9, 128.0, 128.1, 128.6, 135.7, 159.1,
169.6, 171.0; anal. calcd. for C25H28N2O5: C 68.79, H 6.47, N
6.42; found: C 68.3, H 6.7, N, 6.1.
Conclusion
In conclusion, novel diastereomeric 1,4-diphosphine li-
gands have been synthesized starting from an intermedi-
ate for the commercial production of biotin, and their
catalytic efficiencies were investigated in Rh(I)-cata-
lyzed asymmetric hydrogenations of various functional-
ized olefins. Pronounced effects of the backbone config-
uration on the enantioselectivity, reactivity as well as
substrate scope have been observed. These results
should be very helpful in the design of new efficient chi-
ral ligands. Further studies on the structural variation of
the ligands are in progress.
(4S,5S)-1,3-Dibenzylimidazolidin-2-one-4,5-
dicarboxylic Acid [(S,S)-3b]
A solution of trans-monocyclohexyl ester (S,S)-3a (5 g,
11.5 mmol) in 1 M aqueous NaOH solution (50 mL) was heat-
ed to reflux for 1 h. The reaction mixture was cooled to room
temperature and treated with 3% aqueous HCl until the solu-
tion had pH¼4. The solution was extracted with ethyl acetate
(50 mLꢁ3), and the combined organic layer was dried over an-
hydrous MgSO4, and the solvent removed to give trans-diacid
(S,S)-3b as a white solid; yield: 3.9 g (95%); mp 164–1668C;
Experimental Section
1
[a]2D5: ꢀ16.7 (c 1.11, chloroform); H NMR (acetone-d6): d¼
General Remarks
4.15 (s, 2H), 4.18 (d, J¼15.4 Hz, 2H), 5.02 (d, 2H, J¼
15.4 Hz, 2H), 7.28–7.36 (m, 10H); 13C NMR (75.5 MHz,
CDCl3): d¼46.4, 57.7, 127.8, 128.2, 128.9, 137.5, 159.1, 170.6;
All reactions and manipulations were performed in a nitrogen
atmosphere using standard Schlenk techniques. The reaction
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Yong Jian Zhang et al.
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anal. calcd. for C19H18N2O5: C 64.40, H 5.12, N 7.91; found: C
64.0, H 5.1, N 7.8.
6H), 3.59 (s, 2H), 4.01 (d, J¼14.9 Hz, 2H), 4.99 (d, J¼
14.9 Hz, 2H), 7.18–7.35 (m, 10H); 13C NMR (CDCl3): d¼
25.3, 47.2, 62.6, 128.1, 128.4, 135.6, 159.1, 204.3; anal. calcd.
for C21H22N2O3: C 71.98, H 6.33, N 7.99; found: C 71.9, H 6.3,
N 8.0.
(4S,5S)-1,3-Dibenzylimidazolidin-2-one-4,5-
dicarboxylic Acid Dimethyl Ester [(S,S)-3c]
To a solution of diacid (S,S)-3b (27 g, 80 mmol) in methanol
(200 mL) was added dropwise chlorotrimethylsilane (29 mL,
0.23 mol) at room temperature. The reaction mixture was stir-
red at room temperature for 12 h. The solvent was evaporated,
and the residue was purified by short silica gel column (ethyl
acetate:n-hexane¼1:2) to give diester (S,S)-3c as a white solid;
yield: 27.7 g (95%); mp 66–678C; Rf ¼0.31 (ethyl acetate:n-
hexane¼1:2); [a]2D5: ꢀ5.8 (c 0.49, chloroform); 1H NMR
(CDCl3): d¼3.64 (s, 6H), 4.04 (s, 2H), 4.19 (d, J¼15.3 Hz,
2H), 4.98 (d, 2H, J¼15.3 Hz, 2H), 7.23–7.33 (m, 10H); 13C
NMR (CDCl3): d¼46.7, 52.7, 57.3, 127.7, 128.1, 128.6, 136.1,
158.6, 169.7; anal. calcd. for C21H22N2O5: C 65.96, H 5.80, N
7.33; found: C 65.7, H 5.8, N 7.3.
Mixture of (4S,5S)-1,3-Dibenzyl-4,5-bis(1-
hydroxyethyl)imidazolidin-2-one (5a–c)
To a stirred solution of diketone (S,S)-4b (0.17 g, 0.49 mmol) in
THF was added Dibal-H (1.46 mL of 1 M solution in toluene,
1.46 mmol) at ꢀ788C. The reaction mixture was stirred at
the same temperature for 3 h. To the reaction mixture, metha-
nol (2 mL) was added and stirring at the same temperature was
continued for 30 min, and then water (5 mL) was added. The
mixture was extracted with dichloromethane and dried over
anhydrous MgSO4, filtered, and the solvent was removed.
The residue was purified by column chromatography on silica
gel to give a mixture of 5a–c (yield: 0.16 g, 93%) with the ratio
of 5a:5b:5c¼68:3:29 by 1H NMR analysis.
(4S,5S)-1,3-Dibenzylimidazolidin-2-one-4,5-
dicarboxylic Acid Bis(methoxymethyl)amide [(S,S)-
4a]
(4S,5S)-1,3-Dibenzyl-4,5-bis[(1R,1’R)-p-
nitrobenzoyloxyethyl]imidazolidin-2-one (6a) and
(4S,5S)-1,3-Dibenzyl-4,5-bis[(1S,1’R)-p-
To a suspension of diester (S,S)-3c (1.00 g, 2.61 mmol) and
nitrobenzoyloxyethyl]imidazolidin-2-one (6c)
N,O-dimethylhydroxyamine
hydrochloride
(0.77 g,
7.84 mmol) in THF (30 mL) was added dropwise isopropyl-
magnesium bromide (6.6 mL of 2 M solution in THF,
13.1 mmol) at ꢀ288C. The reaction mixture was stirred at
the same temperature for 20 min, and then, quenched with sa-
turated aqueous NH4Cl solution. The organic materials were
extracted with ethyl acetate (20 mLꢁ3), and the combined or-
ganic layer was dried over anhydrous MgSO4 and filtered.
Evaporation of the solvent afforded viscous oil (1.25 g), which
was crystallized from n-hexane/ethyl acetate to give white sol-
id; mp 86–878C; Rf ¼0.24 (ethyl acetate:n-hexane¼2:1);
To a stirred solution of diol 5 (mixture of 5a–c, 1.5 g,
4.23 mmol), triethylamine (1.9 mL, 12.7 mmol) and DMAP
(0.1 g, 0.85 mmol, 20 mol%) in dichloromethane was added
p-nitrobenzoyl chloride (2.4 g, 12.7 mmol) in one portion at
ice bath temperature. The reaction mixture was stirred at
room temperature for 5 h. The reaction was quenched with wa-
ter and extracted with dichloromethane. The combined organ-
ic layer was washed with 3% aqueous HCl, dried over anhy-
drous MgSO4, and filtered. After evaporation of the solvent,
the residue was purified by short column chromatography on
silica gel to give the diastereomeric mixture 6a–c (yield:
2.6 g, 94%). Recrystallization with ethyl acetate/n-hexane
(ca. 1/1, v/v) afforded the optically pure diastereomer 6a (yield:
1.05 g, 40%).
1
[a]2D5: ꢀ23.1 (c 0.8, chloroform); H NMR (CDCl3): d¼2.99
(s, 6H), 3.18 (s, 6H), 4.15 (d, J¼15.4 Hz, 2H), 4.34 (s, 2H),
5.00 (d, J¼15.4 Hz, 2H), 7.21–7.35 (m, 10H); 13C NMR
(CDCl3): d¼32.5, 46.4, 55.1, 61.0, 127.4, 128.2, 128.5, 136.3,
159.5, 169.8; anal. calcd. for C23H28N4O5: C 62.71, H 6.41, N
12.72; found: C 62.5, H 6.5, N 12.7.
The filtrate was evaporated and optically pure 6c separated
by column chromatography on silica gel (eluent: ethyl
acetate:hexane¼1:4–1:2) (yield: 0.4 g, 16%).
6a: mp 162–1638C; Rf ¼0.19 (ethyl acetate:n-hexane¼1:2);
[a]2D5: ꢀ30.9 (c¼1.10, chloroform); 1H NMR (CDCl3): d¼1.26
(d, J¼6.6 Hz, 6H), 3.59 (s, 2H), 4.13 (d, J¼15.2 Hz, 2H), 5.09
(d, J¼15.2 Hz, 2H), 5.28 (q, J¼6.6 Hz, 2H), 7.09–7.29 (m,
10H), 8.01 (m, 4H), 8.27 (m, 4H); 13C NMR (CDCl3): d¼
14.1, 46.2, 56.4, 71.7, 123.6, 127.8, 128.3, 128.7, 130.7, 134.9,
136.3, 150.6, 159.7, 163.9; anal. calcd. for C35H32N4O9: C
64.41, H 4.94, N 8.58; found: C 64.2, H 4.9, N 8.5.
(4S,5S)-4,5-Diacetyl-1,3-dibenzylimidazolidin-2-one
[(S,S)-4b]
To a solution of Weinreb amide (S,S)-4a (1.0 g, 2.27 mmol) in
THF (30 mL) was added dropwise methylmagnesium bromide
(2.3 mL of 3 M solution in THF, 6.81 mmol) at 08C. The reac-
tion mixture was stirred at room temperature for 12 h, and the
reaction was quenched with saturated aqueous NH4Cl solu-
tion. The organic materials were extracted with ethyl acetate
(20 mLꢁ3), and the combined organic layer was dried over an-
hydrous MgSO4, filtered. After evaporation of the solvent, the
residue was purified by column chromatography (eluent: ethyl
acetate:n-hexane¼1:2) on silica gel to give diketone (S,S)-4b
as a white solid; yield 0.58 g [84% from diester (S,S)-3c]; mp
70–718C; Rf ¼0.28 (ethyl acetate:n-hexane¼1:2); [a]2D5:
þ9.1 (c 0.42, chloroform); 1H NMR (CDCl3): d¼1.94 (s,
Crystal data of 6a: C35H32N4O9, monoclinic, a¼10.5246(11),
b¼22.836(2), c¼13.6412(14) ꢂ, V¼3265.3(6) ꢂ3, Z¼4,
Dcalcd. ¼1.328 g/cm3, F(000)¼1368, Goodness of fit on F2 ¼
1.060, 20037 independent reflections with I/s (I)¼2.0 were
used in the analysis. Data for crystallographic analysis were
measured on an Enraf-Nonius CAD-4 diffractormeter using
graphite-monochromated MoKa (l¼0.71073 ꢂ) and w¯ -2
scans in the range of q; 1.50<q<23.30. Structure was solved
by direct methods and refined by least squares using SHEL-
568
ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 563–570

Diastereomeric 1,4-Diphosphine Ligands Bearing Imidazolidin-2-one Backbone
FULL PAPERS
X. Crystallographic data (excluding structure factors) for the
structure(s) reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplementa-
ry publication no. CCDC-249564. Copies of the data can be ob-
tained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [Fax: int. codeþ44(1223)336–033;
E-mail: deposit@ccdc.cam.ac.uk].
(CDCl3): d¼0.81 (d, J¼6.0 Hz, 6H), 3.08 (bs, 2H), 3.35 (dd,
J¼4.5, 8.4 Hz, 2H), 3.87 (m, 2H), 3.93 (d, J¼15.3 Hz, 2H),
4.84 (d, J¼15.6 Hz, 2H), 7.22–7.32 (m, 10H); 13C NMR
(CDCl3): d¼16.5, 46.7, 55.8, 65.4, 127.7, 128.4, 128.6, 136.5,
160.1.
(4S,5S)-1,3-Dibenzyl-4,5-bis-[(1R,1’S)-(hydroxyethyl)]imi-
dazolidin-2-one (5c): Yield: 96%; mp 158–1598C; Rf ¼0.27
(ethyl acetate:n-hexane¼2:1); [a]2D5: ꢀ14.2 (c 0.45, chloro-
form); 1H NMR (CDCl3): d¼0.77 (d, J¼6.4 Hz, 3H), 0.94 (d,
J¼6.4 Hz, 3H), 2.61 (bs, 1H), 2.68 (bs, 1H), 3.20 (dd, J¼2.4,
4.2 Hz, 1H), 3.24 (dd, J¼4.2, 4.2 Hz, 1H), 3.74 (m, 2H), 4.06
6c: mp 738C; Rf ¼0.23 (ethyl acetate:n-hexane¼1:2); [a]2D5:
ꢀ106.5 (c¼0.61, chloroform); 1H NMR (CDCl3): d¼1.03 (d,
J¼6.6 Hz, 3H), 1.06 (d, J¼6.7 Hz, 3H), 3.54 (dd, J¼4.1,
4.1 Hz, 1H), 3.78 (dd, J¼1.6, 4.1 Hz, 1H), 4.08 (d, J¼
15.1 Hz, 1H), 4.15 (d, J¼14.9 Hz, 1H), 4.93 (d, J¼14.9 Hz,
1H), 5.16 (d, J¼15.2 Hz, 1H), 5.15 (m, 1H), 5.39 (m, 1H),
7.14–7.40 (m, 10H), 8.07 (m, 2H), 8.21–8.32 (m, 6H); 13C
NMR (CDCl3): d¼12.9, 13.7, 46.5, 46.6, 54.9, 55.6, 69.7, 73.0,
123.6, 123.7, 127.8, 128.1, 128.3, 128.6, 128.8, 128.9, 130.7,
131.0, 134.8, 135.0, 136.2, 136.4, 150.7, 159.4, 163.8, 163.8.
¼
(d, J¼13.2 Hz, 1H), 4.12 (d, J 13.1 Hz, 1H), 4.72 (d, J¼
15.2 Hz, 1H), 4.72 (d, J¼15.0 Hz, 1H), 7.21–7.31 (m, 10H);
13C NMR (CDCl3): d¼16.9, 17.2, 46.4, 47.1, 57.6, 57.9, 66.5,
67.5, 127.5, 127.6, 128.2, 128.5, 128.5, 136.9, 160.5.
(4S,5S)-1,3-Dibenzyl-4,5-bis[(1S,1’S)-p-
nitrobenzoyloxyethyl]imidazolidin-2-one (6b)
Typical Procedure for the Methanesulfonylation of
Diol 5a–c
To a stirred solution of diol 5a (0.30 g, 0.85 mmol) obtained by
methanolysis of 6a, triphenylphosphine (0.89 g, 3.39 mmol)
and p-nitrobenzoic acid (0.57 g, 3.39 mmol) in THF (20 mL)
were added DEAD (0.53 mL, 3.39 mmol) at ice bath tempera-
ture. The reaction mixture was stirred at room temperature for
4 h. After quenching the reaction by addition of methanol
(5 mL), the volatiles were evaporated. The residue was puri-
fied by column chromatography on silica gel to give 6b; yield:
0.50 g (91%); mp 186–1878C; Rf ¼0.19 (ethyl acetate:n-
To a stirred solution of diol 5a (56.4 mg, 0.16 mmol) and tri-
ethylamine (0.072 mL, 0.48 mmol) in dichloromethane was
added dropwise methanesulfonyl chloride (0.037 mL,
0.48 mmol) at ice bath. The reaction mixture was stirred at
room temperature for 2 h. The mixture was quenched with wa-
ter and extracted with dichloromethane, dried over anhydrous
MgSO4, and filtered. After evaporation of the solvent, the res-
idue was purified by column chromatography (ethyl acetate:n-
hexane¼1:1) on silica gel to give the corresponding mesylate;
yield: 79 mg (98%).
1
hexane¼1:2); [a]2D5: ꢀ18.7 (c 0.45, chloroform); H NMR
(CDCl3): d¼0.95 (d, J¼7.2 Hz, 6H), 3.79 (d, J¼3.3 Hz, 2H),
4.18 (d, J¼14.7 Hz, 2H), 4.90 (d, J¼14.7 Hz, 2H), 5.23 (dq,
J¼3.9, 6.6 Hz, 2H), 7.27–7.46 (m, 10H), 7.79 (m, 4H), 7.92
(m, 4H); 13C NMR (CDCl3) d 13.1, 46.6, 53.9, 69.9, 99.9,
123.1, 128.0, 128.8, 128.9, 130.4, 134.4, 136.5, 150.3, 158.8, 163.4.
(4S,5S)-1,3-Dibenzyl-4,5-bis[(1R,1’R)-methanesulfonyloxy-
ethyl]imidazolidin-2-one (5a): Rf ¼0.54 (ethyl acetate:n-
1
hexane¼2:1); [a]2D5: þ19.6 (c 0.65, chloroform); H NMR
(CDCl3): d¼1.16 (d, J¼6.6 Hz, 6H), 2.81 (s, 6H), 3.33 (s,
2H), 4.03 (d, J¼15.3 Hz, 2H), 4.75 (q, J¼6.6 Hz, 2H), 5.08
(d, J¼14.7 Hz, 2H), 7.30–7.37 (m, 10H); 13C NMR (CDCl3):
d¼15.8, 38.8, 46.1, 56.7, 76.8, 128.1, 128.9, 129.0, 136.2, 159.3;
anal. calcd. for C23H30N2O7S2: C 54.10, H 5.92, N 5.49; found:
C 53.7, H 5.9, N 5.4.
Typical Procedure for Methanolysis of Dibenzoate
6a–c
To a stirred solution of dibenzoate 6a (1.05 g, 1.61 mmol) in
methanol (30 mL) and dichloromethane (10 mL) was added
anhydrous potassium carbonate (1.10 g, 8.04 mmol) at room
temperature. The reaction mixture was stirred at room temper-
ature for 1 h. The solid was filtered off, and the filtrate was con-
centrated. The residue was purified by column chromatogra-
phy (ethyl acetate:n-hexane¼1:1) on silica gel to give 5a;
yield: 0.55 g (97%).
(4S,5S)-1,3-Dibenzyl-4,5-bis[(1S,1’S)-methanesulfonyloxy-
ethyl]]imidazolidin-2-one (5b): Yield: 97%; Rf ¼0.54 (ethyl
acetate:n-hexane¼2:1); [a]2D5: ꢀ31.2 (c 0.71, chloroform); 1H
NMR (CDCl3): d¼0.93 (d, J¼6.6 Hz, 6H), 2.88 (s, 6H), 3.61
(d, J¼3.3 Hz, 2H), 4.03 (d, J¼14.7 Hz, 2H), 4.71 (dq, J¼3.3,
6.6 Hz, 2H), 4.84 (d, J¼14.7 Hz, 2H), 7.31–7.37 (m, 10H);
13C NMR (CDCl3): d¼13.8, 38.2, 46.6, 54.3, 74.1, 128.3, 128.9,
129.0, 135.9, 158.4.
(4S,5S)-1,3-Dibenzyl-4,5-bis[(1R,1’S)-methanesulfonyloxy-
ethyl]]imidazolidin-2-one (5c): Yield: 98%; Rf ¼0.54 (ethyl
acetate:n-hexane¼2:1); [a]2D5: ꢀ16.8 (c 0.60, chloroform);
1H NMR (CDCl3): d¼0.90 (d, J¼6.6 Hz, 3H), 1.13 (d, J¼
6.5 Hz, 3H), 2.84 (s, 3H), 2.89 (s, 3H), 3.45 (dd, J¼1.6,
3.6 Hz, 1H), 3.49 (dd, J¼4.0, 4.0 Hz, 1H), 3.98 (d, J¼
14.9 Hz, 1H), 4.07 (d, J¼14.8 Hz, 1H), 4.75 (d, J¼14.6 Hz,
1H), 4.71 (m, 1H), 4.80 (m, 1H), 5.11 (d, J¼14.9 Hz, 1H),
7.30–7.38 (m, 10H); 13C NMR (CDCl3): d¼13.6, 15.4, 38.3,
38.5, 46.8, 46.8, 55.2, 55.7, 74.5, 128.0, 128.2, 128.8, 128.9,
139.0, 135.9, 136.0, 158.9.
(4S,5S)-1,3-Dibenzyl-4,5-bis[(1R,1’R)-hydroxyethyl)]imi-
dazolidin-2-one (5a): mp 125–1268C; Rf ¼0.27 (ethyl acetat-
1
e:n-hexane¼2:1); [a]2D5: þ4.0 (c 0.50, chloroform); H NMR
(CDCl3): d¼0.91 (d, J¼6.6 Hz, 6H), 1.96 (bs, 2H), 3.22 (s,
2H), 3.76 (dq, J¼2.7, 6.6 Hz, 2H), 4.30 (d, J¼15.3 Hz, 2H),
4.79 (d, J¼15.3 Hz, 2H), 7.24–7.33 (m, 10H); 13C NMR
(CDCl3) d 17.2, 46.7, 58.3, 66.4, 127.6, 128.1, 128.7, 137.4,
160.7; anal. calcd. for C21H26N2O3: C 71.16, H 7.39, N 7.90;
found: C 70.4, H 7.2, N 7.6.
(4S,5S)-1,3-Dibenzyl-4,5-bis-[(1S,1’S)-(hydroxyethyl)]imi-
dazolidin-2-one (5b): Yield: 97%; Rf ¼0.27 (ethyl acetate:n-
1
hexane¼2:1); [a]2D5: ꢀ20.0 (c 0.57, chloroform); H NMR
Adv. Synth. Catal. 2005, 347, 563–570
asc.wiley-vch.de
ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
569

Yong Jian Zhang et al.
FULL PAPERS
short silica gel column to remove the catalyst. After evapora-
tion of the solvent, the crude reaction mixture was subjected
to 1H NMR and capillary GC analyses to determine the conver-
sion and enantiomeric excess, respectively.
General Procedure for Preparation of Phosphine
Ligands 1a–c
To a stirred solution of (4S,5S)-1,3-dibenzyl-4,5-bis[(1R,1’R)-
methanesulfonyloxyethyl]-imidazolidin-2-one
(60 mg,
0.12 mmol) in THF (10 mL) was added potassium diphenyl-
phosphide (0.7 mL of 0.5 M solution in THF, 0.36 mmol) at
08C. The reaction mixture was stirred at room temperature
for 18 h. The precipitate was filtered off through celite and
washed with toluene, the filtrate was concentrated and the res-
idue was purified by column chromatography (ethyl acetate:n-
hexane¼1:5) on silica gel to give diphosphine 1a; yield: 60 mg
(74%).
Acknowledgements
We thank the National Research Laboratory Program and Cen-
ter for Molecular Design and Synthesis for financial support.
References and Notes
(4S,5S)-1,3-Dibenzyl-4,5-bis[(1S,1’S)-diphenylphosphinoe-
thyl]imidazolidin-2-one (1a): Rf ¼0.14 (ethyl acetate:n-
1
hexane¼1:5); [a]2D5: þ26.9 (c 0.23, chloroform); H NMR
[1] a) R. Noyori, Asymmetric Catalysis in Organic Synthesis,
Wiley, New York, 1994; b) T. Ohkuma, M. Kitamura, R.
Noyori, in: Catalytic Asymmetric Synthesis, (Ed.: I. Oji-
ma), Wiley-VCH, Weinheim, 2000, pp. 1; c) G. Helm-
chen, A. Pfaltz, Acc. Chem. Res. 2000, 33, 336; d) H.-U.
Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner, M.
Studer, Adv. Synth. Catal. 2003, 345, 103; e) W. Tang,
X. Zhang, X. Chem. Rev. 2003, 103, 3029.
[2] a) T. P. Dang, H. B. Kagan, J. Chem. Soc. Chem. Com-
mun. 1971, 481; b) H. B. Kagan, T. P. Dang, J. Am.
Chem. Soc. 1972, 94, 6429.
[3] a) G. Zhu, P. Cao, Q. Jiang, X. Zhang, J. Am. Chem. Soc.
1997, 119, 1799; b) W. Li, J. P. Waldkirch, X. Zhang, J.
Org. Chem. 2002, 67, 7618.
[4] W. Li, X. Zhang, X. J. Org. Chem. 2000, 65, 5871.
[5] Y.-Y.Yan, T. V. RajanBabu, Org. Lett. 2000, 2, 4137.
[6] H. B. Kagan, J. C. Fiaud, C. Hoornaert, D. Meyer, J. C.
Poulin, Bull. Soc. Chim. Belg. 1979, 88, 923.
[7] a) S.-g. Lee, Y. J. Zhang, C. E. Song, J. K. Lee, J. H. Choi,
Angew. Chem. Int. Ed. 2002, 41, 847; b) S.-g. Lee, Y. J.
Zhang, Org. Lett. 2002, 4, 2429; c) S.-g. Lee, Y. J. Zhang,
Tetrahedron: Asymmetry 2002, 13, 1039; d) Y. J. Zhang,
J. H. Park, S.-g. Lee, Tetrahedron: Asymmetry 2004, 15,
2209.
[8] H. P. Bottmingen, C. W. Birsfelden, J.-J. V. Hannut,
(Hoffmann-La Roche), US Patent 4,463,180, 1984.
[9] a) G. Zhu, Z. Chen, X. Zhang, X. J. Org. Chem. 1999, 64,
6907; b) U.-G. Zhou, W. Tang, W.-B. Wang, W. Li, X.
Zhang, J. Am. Chem. Soc. 2002, 124, 4952; c) W. Tang,
(CDCl3): d¼0.69 (dd, J¼7.2, 11.1 Hz, 6H), 2.42 (m, 2H),
3.59 (m, 2H), 3.77 (d, J¼15.0 Hz, 2H), 4.69 (d, J¼14.9 Hz,
2H), 7.04–7.34 (m, 30H); 13C NMR (CDCl3): d¼12.3, 34.3,
46.6, 57.1, 57.3, 57.5, 127.5, 128.1, 128.2, 128.2, 128.3, 128.5,
128.8, 129.1, 132.7, 132.8, 132.9, 134.4, 134.5, 134.7, 135.9,
136.0, 136.1, 136.3, 136.4, 136.4, 137.0, 160.4; 31P NMR
(CDCl3): d¼1.91; HRMS: m/z calcd. for C45H44N2OP2:
691.3007; found: 691.2991.
(4S,5S)-1,3-Dibenzyl-4,5-bis[(1R,1’R)-diphenylphosphi-
noethyl]imidazolidin-2-one (1b): Yield: 63%; Rf ¼0.14 (ethyl
acetate:n-hexane¼1:5); [a]2D5: þ31.7 (c 0.24, chloroform); 1H
NMR (CDCl3): d¼0.64 (dd, J¼7.1, 13.3 Hz, 6H), 1.51 (m,
2H), 3.00 (m, 2H), 4.31 (d, J¼15.8 Hz, 2H), 4.69 (d, J¼
15.8 Hz, 2H), 6.84–7.35 (m, 30H); 13C NMR (CDCl3): d¼
10.0, 10.2, 34.8, 35.0, 46.2, 46.3, 55.6, 55.7, 55.8, 55.9, 127.0,
128.0, 128.1, 128.2, 128.3, 128.3, 128.4, 128.5, 128.8, 129.0,
133.1, 133.4, 133.6, 133.9, 137.0, 137.2, 137.4, 161.8; 31P NMR
(CDCl3): d¼4.02; HRMS: m/z calcd. for C45H44N2OP2:
691.3007; found: 691.3013.
(4S,5S)-1,3-Dibenzyl-4,5-bis[(1R,1’S)-diphenylphosphi-
noethyl]imidazolidin-2-one (1c): Yield: 47%; Rf ¼0.19 (ethyl
acetate:n-hexane¼1:5); [a]2D5: ꢀ44.7 (c 0.37, chloroform); 1H
NMR (CDCl3): d¼0.36 (dd, J¼6.9, 13.5 Hz, 3H), 0.61 (dd,
J¼6.9, 14.4 Hz, 3H), 2.35 (m, 1H), 2.71 (m, 1H), 3.31 (m,
1H), 3.90 (m, 1H), 3.95 (d, J¼15.1 Hz, 1H), 4.51 (dd, J¼5.0,
15.5 Hz, 1H), 5.05 (d, J¼15.0 Hz, 1H), 5.19 (d, J¼15.5 Hz,
1H), 7.15–7.39 (m, 30H); 13C NMR (CDCl3): d¼9.0, 9.2,
10.2, 10.4, 30.8, 31.0, 36.9, 37.1, 45.4, 46.9, 47.1, 52.8, 52.9,
57.7. 57.8, 57.9, 127.1, 127.6, 128.2, 128.2, 128.3, 128.3, 128.4,
128.5, 128.6, 128.6, 128.6, 128.7, 128.9, 128.9, 129.0, 129.1,
129.2, 133.2, 133.4, 133.5, 133.5, 133.7, 133.8, 134.5, 134.6,
134.8, 134.9, 135.3, 135.5, 135.8, 136.0, 136.0, 136.3, 136.8,
137.0, 137.3, 160.4; 31P NMR (CDCl3): d¼ ꢀ0.04, 8.85;
HRMS: m/z calcd. for C45H44N2OP2: 691.3007; found: 691.3019.
˜
X. Zhang, Org. Lett. 2002, 4, 4159; d) D. Pena, A. J. Min-
naard, J. G. de Vires, B. L. Feringa, J. Am. Chem. Soc.
2002, 124, 14552; e) J. You, H.-J. Drexler, S. Zhang, C.
Fischer, D. Heller, Angew. Chem. Int. Ed. 2003, 42,
913; f) J. W. Wu, X. Chen, R. Guo, C.-h. Yeung,
A. S. C. Chan, J. Org. Chem. 2003, 68, 2490; g) W.
Tang, W. Wang, Y. Chi, X. Zhang, Angew. Chem. Int.
Ed. 2003, 42, 3509; h) J. Holz, A. Monsees, H. Jia, J.
You, I. V. Komarov, C. Fischer, K. Drauz, A. Bçrner, J.
Org. Chem. 2003, 68, 1701.
General Procedure for Asymmetric Hydrogenation
In an inert atmosphere glove-box, a reaction flask was charged
with [Rh(cod)2]BF4 (2.3ꢁ10ꢀ3 mmol) and chiral ligand (2.7ꢁ
10ꢀ3 mmol) in 2 mL of solvent, and the mixture was stirred for
20 min at 208C. A substrate (0.23 mmol) was added to the re-
action mixture, and then hydrogenation was performed under
1 atm of H2 for 1 h. The reaction mixture was passed through a
[10] To date, BICP is the leading DIOP-type 1,4-bisphos-
phine ligand for the Rh(I)-catalyzed hydrogenation of
a-dehydroamino acids (96.8–99% ees), see: ref.[3a]
570
ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 563–570