Carbohydrate-derived monophosphite ligands for Rh-catalyzed enantioselective hydrogenation of α- and β-dehydroamino acid esters

Article abstract of DOI:10.1016/j.tetasy.2004.05.037

A series of monophosphite ligands derived from D-fructose and D-glucose have been synthesized and employed in Rh-catalyzed asymmetric hydrogenation of α- and β-dehydroamino acid esters. A variety of chiral α- and β-amino acid esters have been obtained in

Full text of DOI:10.1016/j.tetasy.2004.05.037

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 2011–2019
Carbohydrate-derived monophosphite ligands for
Rh-catalyzed enantioselective hydrogenation of
a- and b-dehydroamino acid esters
Hanmin Huang, Xiongcai Liu, Song Chen, Huilin Chen and Zhuo Zheng*
Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian 116023, PR China
Received 26 April 2004; accepted 28May 2004
Available online
Abstract—A series of monophosphite ligands derived from D-fructose and D-glucose have been synthesized and employed in Rh-
catalyzed asymmetric hydrogenation of a- and b-dehydroamino acid esters. A variety of chiral a- and b-amino acid esters have been
obtained in excellent enantiomeric excess (up to 98.4% ee).
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
the ligand.7 These ligands exhibited excellent enantio-
selectivity in the Rh-catalyzed asymmetric hydrogena-
tion of dimethyl itaconate (up to 99.6%) and E/Z
mixtures of enamides (up to 98.5%).8 Further interest in
establishing the general utility of the design concept and
continuing our research interest to develop carbohy-
drate-derived chiral ligands9 for asymmetric catalysis led
us to examine the asymmetric hydrogenation of a- and
b-dehydroamino acid esters by using these ligands.
The enantioselective hydrogenation of prochiral olefins
constitutes a standard tool for the synthesis of optically
active amino acids.1 Although many efficient diphos-
phorus chiral ligands have been developed for this
asymmetric reaction, only a few efficient monophos-
phorus ligands are reported to date, which may be
ascribed to the free rotation of M–P bond in the com-
plexes of monodentate ligands. With leading efforts by
Pringle et al.,2 Reetz and Mehler3 and Feringa et al.,4
some easily prepared and efficient chiral monophos-
phorus ligands have been developed, and these have
exhibited high enantioselectivity in asymmetric hydro-
genation.5
2. Results and discussion
2.1. Synthesis of chiral monophosphite ligands
The ligands 1–4 were synthesized very efficiently from
commercial BINOL and the corresponding monosac-
charide alcohols, which were synthesized on a large scale
For many years, carbohydrates have been extensively
explored as backbones for chiral ligands due to their
easy modification and ready availability. Excellent
results have been obtained with carbohydrate-based
bidentate ligands in asymmetric hydrogenation.6 How-
ever, few good monodentate chiral ligands have been
reported based on carbohydrates.5a;b;8 Recently, we have
designed and synthesized a new class of chiral mono-
phosphorus ligands 1–4 from carbohydrates, which
contain additional groups in the appropriate spatial
configuration to effectively restrain the rotation of M–P
bond by secondary interactions between the metal and
from
D-fructose and D
-glucose.10 The RO–PCl2 inter-
mediates were prepared by the reaction of alcohols with
PCl3 in the absence of Et3N. These were then directly
reacted with BINOL in the presence of Et3N to afford
the desired product. Ligands 1–4 were easily purified
through a short silica gel plug and were stable in the
solid state (Fig. 1).
2.2. Asymmetric hydrogenation of acetamidoacrylic acid
esters
The active catalyst employed in our study was generated
in situ from cationic [Rh(COD)2]BF4 and the
* Corresponding author. Tel.: +86-411-84379276; fax: +86-411-8468-
4746; e-mail: zhengz@dicp.ac.cn
0957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.05.037

2012
H. Huang et al. / Tetrahedron: Asymmetry 15 (2004) 2011–2019
R
R
O
R
O
R
O
R
O
R
O
O
R
O
R
O
O
O
(1) PCl , THF
O
O
3
O
O
O
R
O
O
OH or
P
or
HO
O
P
O
(2) Et N,
3
O
O
R
O
R
O
O
R
O
O
R
O
O
R
R
R
3-4
1-2
10a-d
9a-d
R
O
R
R
O
R
R
O
O
O
O
O
R
O
O
O
O
O
O
3
O
3
P
O
O
O
3
P
O
O
P
R
O
O
R
O
R
O
R
O
R
R
1a: R= -CH3, (R)-BINOL
1b: R= -CH3, (S)-BINOL
1c: R= -(CH2)5-, (R)-BINOL
1d: R= -(CH2)5-, (S)-BINOL
2a: R= -CH3, (R)-BINOL
2b: R= -CH3, (S)-BINOL
2c: R= -(CH2)5-, (R)-BINOL
2d: R= -(CH2)5-, (S)-BINOL
3a: R= -CH3, (R)-BINOL
3b: R= -CH3, (S)-BINOL
3c: R= -(CH2)5-, (R)-BINOL
3d: R= -(CH2)5-, (S)-BINOL
R
O
O
Ph
R
O
O
O
O
O
O
3
O
3
O
O
O
O
O
O
O
O
P
O
P
O
3
P
R
O
O
O
R
O
O
Ph
4a: R= -CH3, (R)-BINOL
4b: R= -CH3, (S)-BINOL
1e
3e
4c: R= -(CH2)5-, (R)-BINOL
4d: R= -(CH2)5-, (S)-BINOL
Figure 1. Synthesis of monophosphite ligands 1–4.
Table 1. The effect of solvent and H2 pressure on the asymmetric
hydrogenation of methyl 2-acetamidoacrylatea
monophosphite (1:2.2). Methyl acetamidoacrylate 5a
was chosen as a model substrate and 3c was chosen as
a ligand to screen various reaction conditions. As
shown in Table 1, the enantioselectivity of the reaction
was sensitive to the solvent used, and CH2Cl2 is
the solvent of choice. In contrast, the hydrogen pressure
has only a small influence on these asymmetric cata-
lytic systems, lower hydrogen pressures gave higher
ee values. As a result of the high activity of these
catalysts, the reaction can be carried out at ambient
hydrogen pressure in quantitative conversion with
higher ee value.
[Rh(COD) ]BF + 3c
2
4
AcHN
COOCH
3
AcHN
COOCH
3
H
2
6a
5a
Entry
Solvent
P(H2) (atm)
Ee% (config.)b
1
2
3
4
5
6c
7
CH2Cl2
CH2Cl2
CH2Cl2
EtOAc
Toluene
CH3OH
THF
10
5
87.7 (S)
87.7 (S)
89.1 (S)
83.9 (S)
86.7 (S)
21.1 (S)
87.3 (S)
1.2
1.2
1.2
1.2
1.2
Optimal reaction conditions with the Rh-monophosph-
ite catalyst use CH2Cl2 as the solvent and an initial
hydrogen pressure of 1.2 atm. Under these conditions,
we next examined the catalytic properties of the other
ligands for the hydrogenation of 5a. The results are
summarized in Table 2 and show that the carbohydrate-
derived monophosphites are efficient ligands for this
asymmetric hydrogenation reaction. However, the
enantioselectivities proved to be dramatically influenced
by the structure of the ligands. Comparison of the re-
sults in the Table 2 shows that the enantiomeric excess
depends strongly on the absolute configuration of car-
bon atom at C-3 in carbohydrate backbone. In general,
a The reactions were carried out at room temperature for 12 h, sub-
strate/[Rh(COD)2]BF4/3c ¼ 1.0/0.01/0.022. 100% conversion in all
cases.
b Determined by GC with a Supelco Chiral Select 1000 capillary col-
umn and the absolute configuration was determined by comparing
the sign of specific rotation.
c 22% conversion.
ligands 1a–d with the opposite configuration on C-3.
Similarly, for the D-glucose-derived ligands 3–4, the
absolute configuration at C-3 in the carbohydrate
backbone also dramatically influenced the enantiomeric
excesses. These observations are in agreement with those
observed in the hydrogenation of dimethyl itaconate
D
-fructose-derived ligands 2a–d, with R configuration at
C-3, produced much higher enantioselectivities than

H. Huang et al. / Tetrahedron: Asymmetry 15 (2004) 2011–2019
2013
Table 2. Enantioselective hydrogenation of methyl 2-acetamidoacry-
latea
Table 3. Enantioselective hydrogenation of acetamidoacrylic acid
estersa
COOCH3
NHAc
COOCH3
NHAc
[Rh(COD)2]BF4 + 3c
[Rh(COD) ]BF + L*
*
2
4
AcHN
COOCH
3
AcHN
COOCH
3
H2
R
R
H
2
6a
5a
5
6
Entry
Ligand
Ee% (config.)b
Entry
Substrate
R
Ee% (config.)b
1
1a
1b
1c
1d
2a
2b
2c
2d
1e
3a
3b
3c
3d
4a
4b
4c
4d
3e
47.5 (R)
0
1
2
3
4
5
6
5a
5b
5c
5d
5e
5f
H
Ph
89.1 (S)
86.1 (S)
88.5 (S)
85.7 (S)
86.1 (S)
80.3 (S)
2
3
63.3 (R)
33.6 (S)
85.9 (S)
45.0 (R)
85.0 (S)
5.5 (R)
24.8( R)
87.9 (S)
79.9 (R)
89.1 (S)
75.3 (R)
26.5 (R)
5.5 (S)
p-CH3OC6H4
o-CH3OC6H4
p-ClC6H4
o-ClC6H4
4
5
6
7
a The reactions were carried out in CH2Cl2 at room temperature for
12 h, P(H2) ¼ 1.2 atm, substrate/[Rh(COD)2]BF4/3c ¼ 1.0/0.01/0.022.
100% conversion in all cases.
b Determined by GC with a Supelco Chiral Select 1000 and a CP-
Chrialsil-L-Val capillary column, the absolute configuration was
determined by comparing the sign of specific rotation.
8
9
10
11
12
13
14
15
16
17
18
2.3. Asymmetric hydrogenation of b-(acylamino)acrylates
38.1 (R)
4.4 (S)
39.0 (R)
Chiral b-amino acids have attracted great interest for
their utility as chiral building blocks in the synthesis of
b-peptides and b-lactams.12 One of the most promising
methodologies for their synthesis is the asymmetric
hydrogenation of the appropriate b-dehydroamino acid
precursors catalyzed by homogeneous Rh or Ru com-
plexes containing chiral phosphane ligands.13 However,
in striking contrast to the application of this method-
ology for the synthesis of a-amino acids, which was
developed over the last three decades to a standard
procedure in organic chemistry, there are few efficient
monophosphorus ligands employed in this reaction.5a;i;n
To broaden further the utility of our inexpensive
monophosphite ligands, we applied the monophosphite
1–4 in the Rh-catalyzed hydrogenation of b-(acyl-
amino)acrylates. The catalysts were also prepared in situ
by reacting the appropriate ligand with [Rh(COD)2]BF4
in the corresponding solvent at room temperature.
a The reactions were carried out in CH2Cl2 at room temperature for
12 h, P(H2) ¼ 1.2 atm, substrate/[Rh(COD)2]BF4/ligand ¼ 1.0/0.01/
0.022. 100% conversion in all cases.
b Determined by GC with a Supelco Chiral Select 1000 capillary col-
umn and the absolute configuration was determined by comparing
the sign of specific rotation.
and a-arylenamides.8 However, all carbohydrate back-
bones regardless of the R or S configuration at C-3 are
matched co-operatively to (R)-BINOL, which is quite
different to those observed in the hydrogenation of di-
methyl itaconate and a-arylenamides, in which the car-
bohydrate backbones with (R)-configuration at C-3 are
matched with (R)-BINOL while (S)-BINOL is matched
to the corresponding carbohydrate backbones with (S)-
configuration at C-3 in it.8 On the other hand, com-
parison of the results obtained by ligand 3b (entry 11,
Table 2, 79.9% ee) and 3e (entry 18, Table 2, 39.0% ee)
indicated that introducing an additional substitutent in
the 3,30-positions of the BINOL-framework has a dis-
To identify the most efficient ligands, the catalytic per-
formance of ligands 1–4 was thoroughly examined
under ‘standard’ conditions (a ligand-to-Rh ratio of 2.2,
an hydrogen pressure of 10 atm, i-PrOH as a solvent for
Z-isomer, CH2Cl2 as a solvent for E-isomer); the results
are given in Tables 4 and 5.
advantageous influence on the enantioselectivity. This is
11
€
consistent with Borner’s report.
To expand the utility of these monophosphite ligands,
we subsequently applied the efficient monophosphite 3c
in the Rh-catalyzed hydrogenation of other acetamido-
acrylic acid esters 5b–f, (Table 3). It was found that
good enantioselectivities were observed for the desired
products and the substitutents on the phenyl ring of the
methyl (Z)-2-acetamidocinnamate had little effect on the
enantioselectivity. Introducing an electron-withdrawing
group into the acetamidoacrylic acid esters resulted in
lower enantioselectivity (entries 5 and 6, Table 3) while
substrates with an electron-donating group showed
higher enantioselectivity (entry 2, Table 3, 88.5% ee).
The substitution at the ortho position of the phenyl ring
led to a lower ee value (entry 3 vs entry 4, entry 5 vs 6,
Table 3).
The screening of our ligands showed that the observed
enantioselectivities and activities were again strongly
sensitive to the configuration at C-3 and the protecting
groups of the carbohydrate skeletons. Fructose-derived
ligands 1a–d, with an S configuration at C-3, demon-
strated much higher activities and enantioselectivities
for both the E- and Z-b-(acylamino)acrylates than
ligands 2a–d with the opposite configuration at C-3. On
the other hand, the protecting groups on the carbohy-
drate moieties dramatically influenced the activities and
enantioselectivities of catalysts. In all cases, the sterically
more bulky cyclohexanone-protected ligands gave much
higher catalytic activity and enantioselectivity than the
corresponding acetone-protected ligands (1c–d vs 1a–b).

2014
H. Huang et al. / Tetrahedron: Asymmetry 15 (2004) 2011–2019
Table 4. Enantioselective hydrogenation of methyl 3-acetamido-2-
butenoatea
These observations are in contrast to those observed in
hydrogenations of other types of functionalized olefins.8
Similar observations were made with D-glucose-derived
ligands 3 and 4. In terms of reactivity and enantio-
selectivity, 1c, 3c and 3d are better chiral ligands, with
ligand 3c, the higher ee value 97.5% was obtained
with 40% conversion in the hydrogenation of E-methyl
3-acetamido-2-butenoate.
AcHN
AcHN
[Rh(COD) ]BF + L*
2
4
*
H
2
H C
3
CO CH
2 3
CO CH
H C
3
2
3
(E) or (Z)-7a
8a
Entry
Ligand
Substrate
Conv.%
Ee% (config.)b
1
1a
1b
1c
1d
2a
2b
2c
2d
1a
1b
1c
1d
2a
2b
2c
2d
E-7a
E-7a
E-7a
E-7a
E-7a
E-7a
E-7a
E-7a
Z-7a
Z-7a
Z-7a
Z-7a
Z-7a
Z-7a
Z-7a
Z-7a
<5
<5
40
10
<5
<5
<5
<5
25
73
100
6
N/A
N/A
2
The screening of solvents demonstrated that CH2Cl2 is
the best solvent for the E-isomer. The effect of hydrogen
pressure was also investigated with 3c as a ligand and E-
methyl 3-acetamido-2-butenoate as a modular substrate,
the results were collected in Table 6. The results show
that activity was notably enhanced when the hydrogen
pressure was raised from 10 to 30 atm (entries 1–3, Table
6), however, increasing the hydrogen pressure further
had a negative effect on activity (entry 4, Table 6). In
addition, on prolonging the reaction time from 12 to
48h, the conversion reminded the same (entry 3 vs entry
4, Table 6). The enantioselectivity was also slightly de-
creased when the H2 pressure increased (entries 1–3,
Table 6).
3
85.3 (R)
69.1 (S)
N/A
4
5
6
N/A
N/A
7
8
N/A
9
29.7 (S)
28.1 (S)
20.1 (R)
69.0 (R)
N/A
10
11
12
13
14
15
17
<5
53
13
12
7.1 (S)
6.7 (S)
29.3 (R)
a The reactions were carried out at room temperature for 12 h, the
solvent for E-substrate is CH2Cl2, for Z-substrate is i-PrOH,
P(H2) ¼ 10 atm, Substrate/[Rh(COD)2]BF4/ligand ¼ 0.5/0.01/0.022.
b Determined by GC with Chiral Select 1000 capillary column and the
absolute configuration was determined by comparing the sign of
specific rotation.
Table 6. Enantioselective hydrogenation of b-(acylamino)acrylatesa
AcHN
AcHN
[Rh(COD) ]BF + 3c
2
4
1
2
1
2
CO R
R
H
2
CO R
2
R
2
1
2
7a: R = CH , R = CH
7b: R = CH , R = C H
7c: R = C H , R = CH
7d: R = Ph, R = C H
3
3
1
2
8a-d
3
2
5
3
1
2
2
5
1
2
Table 5. Enantioselective hydrogenation of methyl 3-acetamido-2-
butenoatea
2
5
Entry Substrate
P(H2) (atm)
Conv.%
Ee% (config.)b
AcHN
AcHN
[Rh(COD) ]BF + L*
2
4
1
2
3
4c
5
6
7
8
E-7a
E-7a
E-7a
E-7a
E-7a
E-7b
E-7c
7d
10
20
30
30
40
30
30
30
40
52
97.5 (S)
95.0 (S)
95.3 (S)
S)
*
H
2
H C
3
CO CH
2 3
CO CH
H C
3
2
3
73
(E) or (Z)-7a
8a
7895.5 (
44
65
96.5 (S)
95.7 (S)
98.4 (S)
93.0 (S)
Entry
Ligand
Substrate
Conv.%
Ee% (config.)b
1
3a
3b
3c
3d
4a
4b
4c
4d
3e
3a
3b
3c
3d
4a
4b
4c
4d
3e
E-7a
E-7a
E-7a
E-7a
E-7a
E-7a
E-7a
E-7a
E-7a
Z-7a
Z-7a
Z-7a
Z-7a
Z-7a
Z-7a
Z-7a
Z-7a
Z-7a
<5
<5
40
52
7
N/A
N/A
92
80
2
3
97.5 (S)
88.4 (R)
87.1 (S)
N/A
a The reactions were carried out at room temperature for 12 h, the
solvent is CH2Cl2, substrate/[Rh(COD)2]BF4/3c ¼ 0.5/0.01/0.022.
b Determined by GC with Chiral Select 1000 capillary column and the
absolute configuration was determined by comparing the sign of
specific rotation.
4
5
6
<5
<5
10
<5
88
37
96
64
6
7
N/A
15.0 (R)
N/A
8
c The reaction time is 48h.
9
10
11
12
13
14
15
16
17
18
7.5 (S)
51.5 (R)
4.1 (S)
60.5 (R)
50.9 (S)
17.1 (S)
N/A
The hydrogenation of a series of E-b-alkyl-substituted
b-(acylamino)acrylates and b-aryl-substituted b-(acyl-
amino)acrylates was examined in CH2Cl2 under an
H2 pressure of 30 atm at room temperature
37
<5
30
19
with [Rh(COD)2]BF4/3c as
a
catalyst precursor
29.9 (S)
55.7 (R)
(entries 6–8, Table 6). For b-alkyl-substituted b-(acyl-
amino) acrylates, the ligand 3c exhibited excellent
enantioselectivities (95.0–98.4% ee) with moderate to
good conversion. Moreover, for the b-phenyl-substi-
tuted b-(acylamino)acrylates, high ee value (93% ee,
entry 8, Table 6) with good conversion also being
obtained.
a The reactions were carried out at room temperature for 12 h, the
solvent for E-substrate is CH2Cl2, for Z-substrate is i-PrOH,
P(H2) ¼ 10 atm, substrate/[Rh(COD)2]BF4/ligand ¼ 0.5/0.01/0.022.
b Determined by GC with Chiral Select 1000 capillary column and the
absolute configuration was determined by comparing the sign of
specific rotation.

H. Huang et al. / Tetrahedron: Asymmetry 15 (2004) 2011–2019
2015
3. Conclusions
4.2.1.
(1,10-binaphthyl)dioxophosphite)-
1,2:4,5-Di-O-isopropylidene-3-O-((R)-2,20-O,O-
-fructose 1a. The
D
In conclusion, we have carried out the asymmetric
hydrogenation of a- and b-dehydroamino acid esters
using Rh-complexes of the carbohydrate-derived
monophosphites 1–4 as catalysts. The pronounced effect
of the carbohydrate backbones of these ligands observed
in this asymmetric reaction further confirmed that the
additional groups orientated in a proper spatial config-
uration contained in monophosphites are beneficial for
improvement of enantioselectivity, which also provides
new insights into the design of efficient chiral mono-
phosphorus ligands. The design and synthesis of more
effective chiral monophosphorus ligands containing
additional groups and their applications in asymmetric
catalytic hydrogenation are currently in progress.
above procedure was followed using 9a and R-BINOL.
After workup, it gave 1a. Mp 121–122 °C;
12
1
½aŠ ¼ À430:5 (c 1.06, THF); H NMR (DMSO-d6): d
D
1.27 (s, 3H), 1.34 (s, 3H), 1.43 (s, 3H), 1.53 (s, 3H), 3.99
(m, 3H), 4.09 (t, J ¼ 6:4 Hz, 1H), 4.24 (d, J ¼ 9:2 Hz,
1H), 4.30 (t, J ¼ 4:8Hz, 1H), 4.43 (t, J ¼ 8:4 Hz, 1H),
7.21–7.24 (m, 2H), 7.34–7.36 (m, 2H), 7.47–7.57 (m,
4H), 8.05–8.10 (m, 3H), 8.17 (d, J ¼ 8:8Hz, 1H); 13C
NMR (DMSO-d6): d 26.15, 27.87, 59.96, 71.44, 73.35,
73.94, 74.11, 75.16, 103.74, 108.88, 111.62, 121.67,
122.00, 122.26, 123.56, 125.13, 125.37, 125.89, 126.01,
126.60, 126.78, 128.57, 128.71, 129.95, 130.75, 130.87,
131.20, 131.71, 132.02, 146.79, 147.36; 31P NMR
(DMSO-d6): d 159.37; HRMS (APCI) calcd for
C32H32O8P (Mþ+1): 575.1829, found: 575.1850.
4. Experimental
4.2.2.
(1,10-binaphthyl)dioxophosphite)-
1,2:4,5-Di-O-isopropylidene-3-O-((S)-2,20-O,O-
-fructose 1b. The
above procedure was followed using 9a and S-BINOL.
4.1. General methods
D
12
All reactions were carried out under an N2 atmosphere.
NMR spectra were measured on a Bruker DRX-400
NMR spectrometer. Optical rotations were measured
with a JASCO P-1020 automatic polarimeter. High
resolution mass spectra were recorded on Applied Bio-
systems Mariner System 5303. Enantiomeric excess (ee)
determination was carried out using GC with a Supelco
Chiral Select 1000 and a CP-chiralsil-L-Val capillary
column on an Agilent HP-4890 GC instrument with
FID as detector. All solvents were dried and degassed by
After workup, it gave 1b. Mp 107–108 °C; ½aŠ ¼ þ197:0
D
(c 1.20, THF); 1H NMR (DMSO-d6): d 0.90 (s, 3H), 1.33
(s, 3H), 1.39 (s, 3H), 1.51 (s, 3H), 3.84 (d, J ¼ 9:2 Hz,
1H), 3.95–3.99 (m, 3H), 4.27–4.37 (m, 3H), 7.21–7.23 (m,
2H), 7.33–7.35 (m, 2H), 7.51–7.54 (m, 3H), 7.61 (d,
J ¼ 8:8Hz, 1H), 8.04–8.17 (m, 4H); 13C NMR (DMSO-
d6): d 25.19, 26.37, 26.60, 27.92, 59.61, 70.54, 73.16,
73.31, 73.43, 75.51, 103.54, 108.92, 111.69, 121.70,
122.04, 123.50, 125.08, 125.31, 125.87, 126.02, 126.49,
126.72, 128.54, 128.69, 129.99, 130.76, 131.17, 131.64,
132.07, 146.96, 147.36; 31P NMR (DMSO-d6): d 158.48;
HRMS (APCI) calcd for C32H32O8P (Mþ+1): 575.1829,
found: 575.1841.
standard methods. 1,2:4,5-Di-O-isopropylidene-
tose 9a, 1,2:4,5-Di-O-cyclohexylidene- -fructose 9b,
1,2:4,5-Di-O-isopropylidene-b- -fructopyranose 9c,
1,2:4,5-Di-O-cyclo-hexylidene-b- -fructopyranose 9d,
1,2:5,6-Di-O-isopropylidene- -glucose 10a, 1,2:5,6-Di-
O-cyclohexylidene- -glucose 10b, 1,2:5,6-Di-O-isoprop-
ylidene-b- -glucofuranose 10c, 1,2:5,6-Di-O-cyclohexyl-
idene-b-
D-fruc-
D
D
D
D
D
4.2.3. 1,2:4,5-Di-O-cyclohexylidene-3-O-((R)-2,20-O,O-
(1,10-binaphthyl)dioxophosphite)-
D
D
-fructose
1c.
The
D
-glucofuranose 10d and (S)-3,30-diphenyl-2,20-
above procedure was followed using 9b and R-BINOL.
After workup, it gave 1c. Mp 135–136 °C;
dihydroxy-1,10-binaphthyl were prepared according to
the literature procedures.10;14 All other chemicals were
obtained commercially.
25
D
1
½aŠ ¼ À382:45 (c 1.08, THF); H NMR (DMSO-d6): d
1.24–1.75 (m, 20H), 3.97–4.04 (m, 3H), 4.10 (t,
J ¼ 6:4 Hz, 1H), 4.23 (d, J ¼ 9:2 Hz, 1H), 4.30 (d,
J ¼ 4:4 Hz, 1H), 4.42 (t, J ¼ 8:4 Hz, 1H), 7.21–7.24 (m,
2H), 7.33–7.38(m, 2H), 7.46–7.53 (m, 4H), 8.05–8.09 (m,
3H), 8.18 (d, J ¼ 8:8Hz, 1H); 13C NMR (DMSO-d6): d
23.32, 23.56, 23.68, 24.40, 24.54, 35.05, 35.16, 35.47,
37.32, 60.25, 71.06, 73.03, 74.25, 74.43, 74.80, 403.34,
109.45, 112.20, 121.49, 122.01, 122.32, 123.62, 125.14,
125.38, 125.89, 126.02, 126.62, 126.81, 128.59, 128.73,
129.76, 130.77, 130.95, 131.19, 131.73, 132.06, 146.83,
147.41; 31P NMR (DMSO-d6): 159.55; HRMS
(APCI) calcd for C38H40O8P (Mþ+1): 655.2455, found:
655.2508.
4.2. General procedures for the synthesis of monophos-
phite ligands 1–4
To a stirred solution of 9 or 10 (1.5 mmol) in THF (5 mL)
was slowly added PCl3 (132 lL, 1.5 mmol) as a solution
in THF (4 mL) and the resulting mixture was stirred for
1 h at room temperature. The reaction mixture was then
cooled to )10 °C and Et3N (1.07 mL, 4.5 mmol) was
slowly added. The reaction mixture was allowed to warm
to room temperature, maintained under these conditions
for 0.25 h, and then cooled to 0 °C, solid BINOL or bi-
phenol was added and the resulting mixture was allowed
to warm to room temperature and stirred overnight prior
to dilution with diethyl ether. The solid were removed by
filtration through a pad of Celite, the solvent was re-
moved in vacuo and the residue was purified by flash
chromatography (EtOAc/hexane: 1/20–1/10), furnished
the title ligands as white foam in 75–90% yield.
4.2.4. 1,2:4,5-Di-O-cyclohexylidene-3-O-((S)-2,20-O,O-
(1,10-binaphthyl)dioxophosphite)-
D-fructose 1d. The
above procedure was followed using 9b and S-BINOL.
25
D
After workup, it gave 1d. Mp 153–154 °C; ½aŠ ¼ þ147:9
1
(c 0.98, THF); H NMR (DMSO-d6): d 1.07–1.69 (m,
20H), 3.83–4.00 (m, 4H), 4.30–4.32 (m, 2H), 4.38 (m,

2016
H. Huang et al. / Tetrahedron: Asymmetry 15 (2004) 2011–2019
1H), 7.21–7.22 (m, 2H), 7.32–7.36 (m, 2H), 7.47–7.62 (m,
4H), 8.05–8.17 (m, 4H); 13C NMR (DMSO-d6): d 22.10,
22.54, 22.97, 23.38, 23.50, 24.28, 24.45, 34.29, 35.28,
36.05, 37.42, 59.78, 70.16, 73.14, 73.32, 73.47, 75.19,
103.19, 109.48, 112.17, 121.71, 121.96, 122.11, 123.52,
125.07, 125.32, 125.87, 126.01, 126.50, 126.73, 128.55,
128.70, 130.04, 130.77, 131.17, 131.67, 132.08, 146.99,
147.41; 31P NMR (DMSO-d6): d 158.47; HRMS
(APCI) calcd for C38H40O8P (Mþ+1): 655.2455, found:
655.2481.
(DMSO-d6): d 160.52; HRMS (APCI) calcd for
C32H32O8P (Mþ+1): 575.1829, found: 575.1797.
4.2.8. 1,2:4,5-Di-O-cyclohexylidene-3-O-((R)-2,20-O,O-
(1,10-binaphthyl)dioxophosphite)-b-
D-fructopyranose 2c.
The above procedure was followed using 9d and R-BI-
NOL. After workup, it gave 2c. Mp 134–135 °C;
25
D
1
½aŠ ¼ À325:4 (c 1.05, THF); H NMR (DMSO-d6): d
1.35–1.72 (m, 20H), 3.57 (d, J ¼ 13:2 Hz, 1H), 3.67 (d,
J ¼ 9:2 Hz, 1H), 3.84 (d, J ¼ 12:8Hz, 1H), 4.00 (t,
J ¼ 9:2 Hz, 1H), 4.41 (d, J ¼ 7:6 Hz, 1H), 4.72 (d,
J ¼ 8:0 Hz, 1H), 4.94 (d, J ¼ 10:4 Hz, 1H), 7.20–7.24
(m, 2H), 7.34–7.37 (m, 2H), 7.48–7.57 (m, 4H), 8.08 (m,
3H), 8.17–8.20 (d, J ¼ 8:8Hz, 1H); 13C NMR (DMSO-
d6): d 23.24, 23.36, 23.50, 24.56, 33.77, 35.21, 35.33,
35.52, 62.69, 70.06, 71.10, 71.29, 73.13, 73.53, 104.18,
109.29, 109.67, 121.37, 121.99, 122.08, 123.52, 125.23,
125.48, 125.84, 126.01, 126.68, 126.86, 128.66, 128.72,
129.98, 130.87, 131.05, 131.26, 131.79, 132.04, 146.54,
147.10; 31P NMR (DMSO-d6): d 153.43; HRMS (APCI)
calcd for C38H40O8P (Mþ+1): 655.2455, found:
655.2434.
4.2.5. 1,2:4,5-Di-O-isopropylidene-3-O-(2,20-O,O-(1,10-
biphenyl)dioxophosphite)-D-fructose 1e. The above pro-
cedure was followed using 9a and biphenol. After
25
D
workup, it gave 1e. Mp 117–118 °C; ½aŠ ¼ À123:6 (c
1
1.06, THF); H NMR (DMSO-d6): d 1.15 (s, 3H), 1.36
(s, 3H), 1.39 (s, 3H), 1.51 (s, 3H), 3.92 (d, J ¼ 8:8Hz,
1H), 3.99 (s, 2H), 4.07 (d, J ¼ 9:2 Hz, 1H), 4.19 (t,
J ¼ 6:4 Hz, 1H), 4.33–4.38(m, 2H), 7.23–7.26 (m, 2H),
7.33–7.36 (m, 2H), 7.41–7.46 (m, 2H), 7.55 (m, 2H), 13C
NMR (DMSO-d6): d 25.66, 26.32, 26.50, 27.92, 59.75,
70.95, 73.24, 73.40, 75.45, 103.67, 108.87, 111.75,
122.11, 125.48, 129.44, 129.86, 130.60, 148.59; 31P NMR
(DMSO-d6):
C24H28O8P (Mþ+1): 475.1516, found: 475.1502.
d 155.69; HRMS (APCI) calcd for
4.2.9. 1,2:4,5-Di-O-cyclohexylidene-3-O-((S)-2,20-O,O-
(1,10-binaphthyl)dioxophosphite)-b-
D-fructopyranose 2d.
The above procedure was followed using 9d and S-BI-
4.2.6.
(1,10-binaphthyl)dioxophosphite)-b-
1,2:4,5-Di-O-isopropylidene-3-O-((R)-2,20-O,O-
-fructopyranose 2a.
The above procedure was followed using 9c and R-BI-
NOL. After workup, it gave 2d. Mp 143–144 °C;
D
25
D
1
½aŠ ¼ þ151:8 (c 1.23, THF); H NMR (DMSO-d6): d
1.33–1.85 (m, 20H), 3.58 (d, J ¼ 13:2 Hz, 1H), 3.79–3.85
(m, 2H), 4.29–4.41 (m, 3H), 4.91 (d, J ¼ 8:4 Hz, 1H),
7.21–7.23 (m, 2H), 7.34–7.38(m, 2H), 7.51 (m, 2H), 7.58
(d, J ¼ 8:8Hz, 1H), 7.76 (d, J ¼ 8:8Hz, 1H), 8.06–8.10
(m, 2H), 8.14 (d, J ¼ 9:2 Hz, 1H), 8.17 (d, J ¼ 8:8Hz,
1H); 13C NMR (DMSO-d6): d 23.19, 23.34, 23.50, 24.56,
33.78, 34.56, 35.01, 35.48, 62.77, 70.58, 72.96, 73.18,
73.69, 104.72, 109.62, 109.72, 121.32, 121.49, 125.23,
125.42, 125.90, 126.01, 126.65, 126.78, 128.60, 128.67,
130.33, 130.80, 130.92, 131.21, 131.74, 132.02, 146.63;
31P NMR (DMSO-d6): d 154.91; HRMS (APCI) calcd
for C38H40O8P (Mþ+1): 655.2455, found: 655.2470.
NOL. After workup, it gave 2a. Mp 120–121 °C;
25
D
1
½aŠ ¼ À360:7 (c 1.20, THF); H NMR (DMSO-d6): d
1.27 (s, 3H), 1.33 (s, 3H), 1.40 (s, 3H), 1.46 (s, 3H), 3.57
(d, J ¼ 13:2 Hz, 1H), 3.67 (d, J ¼ 9:2 Hz, 1H), 3.82
(d, J ¼ 13:2 Hz, 1H), 4.04 (d, J ¼ 9:2 Hz, 1H), 4.40 (d,
J ¼ 7:6 Hz, 1H), 4.72 (d, J ¼ 8:0 Hz, 1H), 4.91 (d,
J ¼ 10:4 Hz, 1H), 7.20–7.22 (m, 2H), 7.34–7.38(m, 2H),
7.49–7.58 (m, 4H), 8.08–8.19 (m, 4H); 13C NMR
(DMSO-d6): d 24.60, 25.86, 26.06, 26.27, 62.59, 70.55,
71.09, 71.26, 73.40, 73.78, 104.70, 108.69, 109.02,
121.45, 121.98, 125.22, 125.47, 125.85, 126.01, 126.68,
126.85, 128.64, 128.72, 130.09, 130.86, 131.01, 131.26,
131.80, 132.03, 146.59, 147.08; 31P NMR (DMSO-d6): d
157.75; HRMS (APCI) calcd for C32H32O8P (Mþ+1):
575.1829, found: 575.1786.
4.2.10. 1,2:5,6-Di-O-isopropylidene-3-O-((R)-2,20-O,O-
(1,10-binaphthyl)dioxophosphite)-
above procedure was followed using 10a and R-BINOL.
D
-glucose
3a.
The
25
4.2.7.
(1,10-binaphthyl)dioxophosphite)-b-
1,2:4,5-Di-O-isopropylidene-3-O-((S)-2,20-O,O-
-fructopyranose 2b.
The above procedure was followed using 9c and S-BI-
After workup, it gave 3a. Mp 113–114 °C; ½aŠ ¼ À303:1
D
D
(c 1.14, THF); 1H NMR (DMSO-d6): d 1.28(s, 3H), 1.33
(s, 3H), 1.38(s, 3H), 1.42 (s, 3H), 3.74–3.77 (m, 1H),
3.96–4.02 (m, 2H), 4.15–4.18(m, 1H), 4.69 (d,
J ¼ 9:6 Hz, 1H), 4.81 (d, J ¼ 3:6 Hz, 1H), 5.80 (d,
J ¼ 3:2 Hz, 1H), 7.21–7.23 (m, 2H), 7.34–7.37 (m, 2H),
7.49–7.53 (m, 2H), 7.59 (d, J ¼ 8:4 Hz, 1H), 7.66 (d,
J ¼ 8:8 Hz, 1H), 8.08–8.21 (m, 4H); 13C NMR (DMSO-
d6): d 25.33, 26.09, 26.54, 26.66, 66.41, 71.72, 77.69,
77.82, 80.12, 83.68, 104.53, 108.62, 111.59, 121.55,
121.85, 125.25, 125.51, 125.98, 126.05, 126.69, 126.86,
128.68, 128.74, 130.40, 130.77, 131.06, 131.28, 131.64,
131.99, 146.52, 147.66; 31P NMR (DMSO-d6): d 147.75;
HRMS (APCI) calcd for C32H32O8P (Mþ+1): 575.1829,
found: 575.1802.
NOL. After workup, it gave 2b. Mp 147–148 °C;
25
D
1
½aŠ ¼ þ201:1 (c 0.89, THF); H NMR (DMSO-d6): d
1.23 (s, 3H), 1.32 (s, 3H), 1.48(s, 3H), 1.58(s, 3H), 3.58
(d, J ¼ 13:2 Hz, 1H), 3.82–3.85 (m, 2H), 4.32–4.36 (m,
2H), 4.42–4.44 (m, 1H), 4.92 (m, 1H), 7.23–7.25 (m, 2H),
7.34–7.36 (m, 2H), 7.50–7.52 (m, 2H), 7.59 (d,
J ¼ 8:8Hz, 1H), 7.77 (d, J ¼ 8:8Hz, 1H), 8.07–8.20 (m,
4H); 13C NMR (DMSO-d6): d 24.49, 25.44, 25.98, 26.06,
62.65, 70.90, 72.82, 73.03, 73.51, 73.87, 105.07, 108.86,
109.07, 121.46, 122.04, 123.43, 125.24, 125.40, 125.88,
126.00, 126.65, 126.80, 128.57, 128.69, 130.27, 130.81,
130.92, 131.20, 131.75, 132.04, 146.69, 147.75; 31P NMR

H. Huang et al. / Tetrahedron: Asymmetry 15 (2004) 2011–2019
2017
4.2.11. 1,2:5,6-Di-O-isopropylidene-3-O-((S)-2,20-O,O-
(1,10-binaphthyl)dioxophosphite)-
-glucose 3b. The
BINOL. After workup, it gave 4a. Mp 76–77 °C;
25
1
D
½aŠ ¼ À248:7 (c 0.98, THF); H NMR (DMSO-d6): d
D
above procedure was followed using 10a and S-BINOL.
After workup, it gave 3b. Mp 107–108 °C;
1.28(s, 3H), 1.30 (s, 3H), 1.33 (s, 3H), 1.44 (s, 3H), 3.74–
3.78(m, 1H), 3.9–84.08(m, 2H), 4.20–4.23 (m, 1H),
4.53–4.60 (m, 2H), 5.73 (d, J ¼ 3:6 Hz, 1H), 7.19–7.21
(m, 2H), 7.34–7.38(m, 2H), 7.49–7.51 (m, 3H), 7.60 (d,
J ¼ 8:8Hz, 1H), 8.07–8.19 (m, 4H); 13C NMR (DMSO-
d6): d 25.00, 26.15, 26.54, 26.63, 64.67, 73.88, 73.98,
74.71, 78.11, 78.44, 103.54, 108.89, 112.49, 121.62,
121.73, 121.88, 123.41, 125.21, 125.42, 125.90, 125.99,
126.67, 126.81, 128.61, 128.70, 130.12, 130.77, 130.95,
131.22, 131.77, 132.01, 146.70, 147.37; 31P NMR
25
1
½aŠ ¼ þ291:9 (c 1.11, THF); H NMR (DMSO-d6): d
D
1.20 (s, 3H), 1.38(s, 3H), 1.39 (s, 3H), 1.42 (s, 3H), 3.80–
3.83 (m, 1H), 3.96–4.00 (m, 1H), 4.08–4.10 (m, 1H),
4.22–4.25 (m, 1H), 4.59 (d, J ¼ 3:6 Hz, 1H), 4.79–4.82
(m, 1H), 5.82 (d, J ¼ 3:6 Hz, 1H), 7.20–7.22 (m, 2H),
7.35–7.36 (m, 2H), 7.49–7.52 (m, 2H), 7.57 (d,
J ¼ 8:8Hz, 1H), 7.66 (d, J ¼ 8:8 Hz, 1H), 8.08–8.21 (m,
4H); 13C NMR (DMSO-d6): d 25.20, 25.86, 26.43, 26.55,
66.21, 71.88, 77.16, 77.31, 80.18, 83.74, 104.54, 108.57,
111.40, 121.56, 121.64, 121.95, 123.35, 125.30, 125.49,
125.95, 126.75, 126.87, 128.66, 128.74, 130.30, 130.82,
131.03, 131.28, 131.74, 132.00, 146.65, 147.25; 31P NMR
(DMSO-d6): d 148.81; HRMS (APCI) calcd for
C32H32O8P (Mþ+1): 575.1829, found: 575.1786.
(DMSO-d6):
d
152.58; HRMS (APCI) calcd for
4.2.15. 1,2:5,6-Di-O-isopropylidene-3-O-((S)-2,20-O,O-
C32H32O8P (Mþ+1): 575.1829, found: 575.1795.
(1,10-binaphthyl)dioxophosphite)-b-
D-glucofuranose 4b.
The above procedure was followed using 10c and S-
BINOL. After workup, it gave 4b. Mp 111–112 °C;
25
1
4.2.12. 1,2:5,6-Di-O-cyclohexylidene-3-O-((R)-2,20-O,O-
½aŠ ¼ þ318:4 (c 1.15, THF); H NMR (DMSO-d6): d
D
(1,10-binaphthyl)dioxophosphite)-
procedure was followed using 10b and R-BINOL. After
D
-glucose 3c. The above
1.33 (s, 3H), 1.37 (s, 3H), 1.38(s, 3H), 1.46 (s, 3H), 3.73–
3.76 (m, 1H), 3.96–4.01 (m, 2H), 4.17 (t, J ¼ 5:6 Hz,
1H), 4.55–4.59 (m, 1H), 4.81 (t, J ¼ 4:2 Hz, 1H), 5.75 (d,
J ¼ 3:2 Hz, 1H), 7.20–7.24 (m, 2H), 7.33–7.36 (m, 2H),
7.48–7.58 (m, 4H), 8.06–8.19 (m, 4H); 13C NMR
(DMSO-d6): d 25.17, 26.28, 26.54, 26.60, 65.11, 74.14,
74.30, 74.82, 77.41, 78.54, 103.44, 109.01, 112.29,
121.58, 121.84, 122.35, 123.56, 125.13, 125.43, 125.87,
126.05, 126.54, 126.80, 128.59, 128.71, 129.89, 130.93,
131.24, 131.67, 132.02, 146.71, 147.51; 31P NMR
25
workup, it gave 3c. Mp 121–122 °C; ½aŠ ¼ À267:7 (c
D
1.13, THF); 1H NMR (DMSO-d6): d 1.33–1.59 (m,
20H), 3.74 (m, 1H), 3.97–4.12 (m, 3H), 4.79 (m, 2H),
5.85 (d, J ¼ 3:6 Hz, 1H), 7.22–7.24 (m, 2H), 7.35–7.37
(m, 2H), 7.50–7.54 (m, 3H), 7.65 (d, J ¼ 8:4 Hz, 1H),
8.08–8.15 (m, 3H), 8.18 (d, J ¼ 8:8Hz, 1H); 13C NMR
(DMSO-d6): d 22.39, 23.22, 23.58, 24.30, 24.65, 32.39,
33.47, 34.46, 35.17, 35.43, 35.91, 36.03, 66.34, 71.43,
77.77, 77.94, 80.40, 83.29, 104.31, 105.33, 109.10,
112.13, 121.38, 121.73, 121.86, 123.53, 125.22, 125.49,
125.91, 126.04, 126.67, 126.85, 128.67, 130.36, 130.79,
131.03, 131.25, 131.70, 132.02, 146.58, 147.47; 31P NMR
(DMSO-d6): d 151.85; HRMS (APCI) calcd for
C32H32O8P (Mþ+1): 575.1829, found: 575.1864.
(DMSO-d6):
d
149.34; HRMS (APCI) calcd for
4.2.16. 1,2:5,6-Di-O-cyclohexylidene-3-O-((R)-2,20-O,O-
C38H40O8P (Mþ+1): 655.2455, found: 655.2463.
(1,10-binaphthyl)dioxophosphite)-b-
D-glucofuranose 4c.
The above procedure was followed using 10d and R-
BINOL. After workup, it gave 4c. Mp 110–111 °C;
25
1
4.2.13. 1,2:5,6-Di-O-cyclohexylidene-3-O-((S)-2,20-O,O-
½aŠ ¼ À192:45 (c 1.00, THF); H NMR (DMSO-d6): d
D
(1,10-binaphthyl)dioxophosphite)-
D
-glucose
3d.
The
1.31–1.68(m, 20H), 3.70–3.74 (m, 1H), 3.97–4.00 (m,
1H), 4.07–4.10 (m, 1H), 4.14–4.17 (m, 1H), 4.52–4.54
(m, 1H), 4.60 (t, J ¼ 4:0 Hz, 1H), 5.75 (d, J ¼ 3:6 Hz,
1H), 7.20–7.22 (m, 2H), 7.34–7.37 (m, 2H), 7.49–7.56
(m, 4H), 8.07–8.13 (m, 3H), 8.18 (d, J ¼ 8:8Hz, 1H);
13C NMR (DMSO-d6): d 23.38, 24.32, 24.61, 34.20,
35.54, 35.83, 64.83, 74.71, 78.03, 78.25, 103.32, 109.42,
113.12, 121.52, 121.80, 122.00, 123.40, 125.15, 125.37,
125.89, 126.00, 126.61, 126.78, 128.61, 128.69, 130.07,
130.77, 130.92, 131.16, 131.77, 132.03, 146.90, 147.44;
31P NMR (DMSO-d6): d 148.71; HRMS (APCI) calcd
for C38H40O8P (Mþ+1): 655.2455, found: 655.2395.
above procedure was followed using 10b and S-BINOL.
After workup, it gave 3d. Mp 118–119 °C;
25
1
½aŠ ¼ þ262:7 (c 1.08, THF); H NMR (DMSO-d6): d
D
1.33–1.68 (m, 20H), 3.81–3.83 (m, 1H), 4.01–4.06 (m,
2H), 4.25–4.27 (m, 1H), 4.57 (m, 1H), 4.71 (d,
J ¼ 9:6 Hz, 1H), 5.87 (d, J ¼ 3:6 Hz, 1H), 7.20–7.22 (m,
2H), 7.33–7.36 (m, 2H), 7.50–7.52 (m, 2H), 7.57 (d,
J ¼ 8:8Hz, 1H), 7.65 (d, J ¼ 8:8Hz, 1H), 8.06–8.10 (m,
2H), 8.13 (d, J ¼ 8:8Hz, 1H), 8.18 (d, J ¼ 9:2 Hz, 1H);
13C NMR (DMSO-d6): d 23.19, 23.43, 23.51, 23.62,
24.31, 24.63, 34.34, 34.91, 35.74, 35.99, 66.18, 71.63,
77.49, 77.64, 80.33, 83.36, 104.28, 109.04, 111.81,
121.53, 121.92, 125.25, 125.44, 125.97, 126.70, 126.81,
128.60, 128.72, 130.38, 130.79, 131.00, 131.26, 131.77,
132.01, 146.69; 31P NMR (DMSO-d6): d 149.05; HRMS
(APCI) calcd for C38H40O8P (Mþ+1): 655.2455, found:
655.2507.
4.2.17. 1,2:5,6-Di-O-cyclohexylidene-3-O-((S)-2,20-O,O-
(1,10-binaphthyl)dioxophosphite)-b-
D-glucofuranose 4d.
The above procedure was followed using 10d and S-
BINOL. After workup, it gave 4d. Mp 131–132 °C;
25
D
1
½aŠ ¼ þ358:5 (c 1.00, THF); H NMR (DMSO-d6): d
1.37–1.65 (m, 20H), 3.70–3.74 (m, 1H), 3.92–3.95 (m,
1H), 3.98–4.02 (m, 1H), 4.15–4.18 (m, 1H), 4.60–4.66
(m, 1H), 4.82 (t, J ¼ 4:0 Hz, 1H), 5.77 (d, J ¼ 3:6 Hz,
1H), 7.20–7.25 (m, 2H), 7.33–7.39 (m, 2H), 7.48–7.57
4.2.14. 1,2:5,6-Di-O-isopropylidene-3-O-((R)-2,20-O,O-
(1,10-binaphthyl)dioxophosphite)-b-
The above procedure was followed using 10c and R-
D
-glucofuranose 4a.

2018
H. Huang et al. / Tetrahedron: Asymmetry 15 (2004) 2011–2019
2. Claver, C.; Fernandez, E.; Gillon, A.; Heslop, K.; Hyett,
D. J.; Martorell, A.; Orpen, A. G.; Pringle, P. G. Chem.
Commun. 2000, 961.
3. Reetz, M. T.; Mehler, G. Angew. Chem., Int. Ed. 2000, 39,
3889.
4. van den Berg, M.; Minnaard, A. J.; Schudde, E. P.; van
Esch, J.; de Vries, A. H. M.; de Vries, J. G.; Feringa, B. L.
J. Am. Chem. Soc. 2000, 122, 11539.
(m, 4H), 8.07–8.09 (m, 3H), 8.18 (d, J ¼ 8:8Hz, 1H);
13C NMR (DMSO-d6): d 23.46, 24.38, 24.71, 34.38,
35.63, 35.83, 65.25, 74.51, 74.70, 77.41, 78.18, 103.09,
109.55, 112.88, 121.33, 121.94, 122.46, 123.59, 125.15,
125.44, 125.83, 126.05, 126.57, 126.84, 128.60, 128.72,
129.75, 130.99, 131.21, 131.68, 132.05, 146.75, 147.48;
31P NMR (DMSO-d6): d 153.48; HRMS (APCI) calcd
for C38H40O8P (Mþ+1): 655.2455, found: 655.2416.
5. For other monophosphorus ligands, see: (a) Huang, H.;
Zheng, Z.; Luo, H.; Bai, C.; Hu, X.; Chen, H. J. Org.
Chem. 2004, 69, 2355; (b) Reetz, M. T.; Goossen, L. J.;
Meiswinkel, A.; Paetzold, J.; Jensen, J. F. Org. Lett. 2003,
5, 3099; (c) Hannen, P.; Militzer, H.-C.; Vogl, E. M.;
Rampf, F. A. Chem. Commun. 2003, 2210; (d) Reetz, M.
T.; Sell, T.; Meiswinkel, A.; Mehler, G. Angew. Chem., Int.
Ed. 2003, 42, 790; (e) Jia, X.; Li, X.; Xu, Li.; Shi, Q.; Yao,
X.; Chan, A. S. C. J. Org. Chem. 2003, 68, 4539; (f) Fu, Y.;
Xie, J.-H.; Hu, A.-G.; Zhou, H.; Wang, L.-X.; Zhou,
Q.-L. Chem. Commun. 2002, 480; (g) Hu, A.-G.; Fu, Y.;
Xie, J.-H.; Zhou, H.; Wang, L.-X.; Zhou, Q.-L. Angew.
Chem., Int. Ed. 2002, 41, 2348; (h) Reetz, M. T.; Mehler,
G.; Meiswinkel, A.; Sell, T. Tetrahedron Lett. 2002, 43,
7941; (i) Pena, D. M.; Minnaard, A. J.; de Vries, J. G.;
Feringa, B. L. J. Am. Chem. Soc. 2002, 124, 14552; (j)
Junge, K.; Oehme, G.; Monsees, A.; Riermeier, T.;
Dingerdissen, U.; Beller, M. Tetrahedron Lett. 2002, 43,
4977; (k) Zeng, Q.; Liu, H.; Cui, X.; Mi, A.; Jiang, Y.; Li,
X.; Choi, M. C. K.; Chan, A. S. C. Tetrahedron:
Asymmetry 2002, 13, 115; (l) Jia, X.; Guo, R.; Li, X.;
Yao, X.; Chan, A. S. C. Tetrahedron Lett. 2002, 43, 5541;
(m) van den Berg, M.; Haak, R. M.; Minnaard, A. J.; de
Vries, A. H. M.; de Vries, J. G.; Feringa, B. L. Adv. Synth.
Catal. 2002, 344, 1003; (n) Pena, D.; Minnaard, A. J.; de
Vries, A. H. M.; de Vries, J. G.; Feringa, B. L. Org. Lett.
2003, 5, 475.
4.2.18. 1,2:5,6-Di-O-isopropylidene-3-O-((S)-2,20-O,O-
(3,30-diphenyl-1,10-binaphthyl)dioxophosphite)-
D-glucose
4e. The above procedure was followed using 10a and
(S)-3,30-diphenyl-2,20-dihydroxy-1,10-binaphthyl. After
25
workup, it gave 4e. Mp 118–119 °C; ½aŠ ¼ þ350:0 (c
D
0.86, THF); 1H NMR (DMSO-d6): 1.12 (s, 3H), 1.15 (s,
3H), 1.17 (s, 3H), 1.28(s, 3H), 3.20–3.22 (m, 1H), 3.55–
3.57 (m, 2H), 3.70–3.72 (m, 1H), 3.93 (d, J ¼ 3:2 Hz,
1H), 4.24 (d, J ¼ 9:6 Hz, 1H), 5.57 (d, J ¼ 3:2 Hz, 1H),
7.21–7.24 (m, 2H), 7.38–7.57 (m, 10H), 7.70–7.75 (m,
4H), 8.14–8.30 (m, 4H); 13C NMR (DMSO-d6): d 25.31,
25.87, 26.29, 26.59, 65.67, 71.19, 77.02, 79.42, 82.88,
104.19, 108.21, 111.14, 123.13, 125.67, 125.99, 126.80,
126.95, 127.70, 127.91, 128.33, 128.81, 129.93, 129.61,
130.78, 131.17, 131.41, 131.73, 133.61, 133.73, 136.48,
137.08, 143.66, 144.84; 31P NMR (DMSO-d6): d 146.13;
HRMS (APCI) calcd for C44H40O8P (Mþ+1): 727.2455,
found: 727.2505.
4.3. General procedures for asymmetric hydrogenation
6. (a) Steiborn, D.; Junicke, H. Chem. Rev. 2000, 100, 4283;
(b) RajanBabu, T. V.; Casalnuovo, A. L.; Ayers, T. A. In
Advances in Catalytic Process; Doyle, M. P., Ed.;
JAI: Greenwhich, 1998; Vol. 2, p 1; (c) Yonehara, K.;
Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S. J. Org.
Chem. 1999, 64, 5593; (d) Yonehara, K.; Ohe, K.;
Uemura, S. J. Org. Chem. 1999, 64, 9381; (e) Hashizume,
T.; Yonehara, K.; Ohe, K.; Uemura, S. J. Org. Chem.
2000, 65, 5197.
In
a nitrogen-filled glovebox, to a solution of
[Rh(COD)2]BF4 (2.0 mg, 0.005 mmol) in anhydrous and
degassed CH2Cl2 (1 mL) was added ligand (0.011 mmol).
After stirring the mixture for 30 min, a substrate
(0.5 mmol) dissolved in CH2Cl2 (1 mL) was added. The
reaction mixture was transferred to a autoclave. The
autoclave was purged three times with hydrogen and
the pressure was set to the desired pressure, the hydro-
genation was performed at room temperature for 12 h.
After carefully releasing the hydrogen, the reaction
mixture was passed through a short silica-gel plug to
remove the catalyst. The resulting solution was directly
used for chiral GC to determine enantiomeric excesses.
7. For review of secondary interaction, see: (a) Sawamura,
€
M.; Ito, Y. Chem. Rev. 1992, 92, 857; (b) Borner, A. Eur.
J. Inorg. Chem. 2001, 327; (c) Komarov, I. V.; Borner, A.
€
Angew. Chem., Int. Ed. 2001, 40, 1197.
8. Huang, H.; Zheng, Z.; Luo, H.; Bai, C.; Hu, X.; Chen, H.
Org. Lett. 2003, 5, 4137.
9. For recent advances in this area, see: (a) Huang, H.; Chen,
H.; Hu, X.; Bai, C.; Zheng, Z. Tetrahedron: Asymmetry
2003, 14, 297; (b) Huang, H.; Zheng, Z.; Chen, H.; Bai, C.;
Wang, J. Tetrahedron: Asymmetry 2003, 14, 1285; (c) Ohe,
K.; Morioka, K.; Yonehara, K.; Uemura, S. Tetrahedron:
Asymmetry 2002, 13, 2155; (d) Dieguez, M.; Ruiz, A.;
Claver, C. J. Org. Chem. 2002, 67, 3796; (e) Dieguez, M.;
Ruiz, A.; Claver, C. Chem. Commun. 2001, 2702; (f) Park,
H.; RajanBabu, T. V.; Yan, Y.-Y.; Shin, S. J. Am. Chem.
Soc. 2001, 123, 10207; (g) Li, W.; Zhang, Z.; Xiao, D.;
Zhang, X. J. Org. Chem. 2000, 65, 3489; (h) Shin, S.;
RajanBabu, T. V. Org. Lett. 1999, 1, 1229.
Acknowledgements
Financial support from the National Science Founda-
tion of China (29933050) is gratefully acknowledged.
References and notes
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1. For recent reviews, see: (a) Ohkuma, T.; Noyori, R. In
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Wiley-VCH: Weinheim, 2000; p 1; (b) Brown, J. M. In
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€
€
H. J.; Lang, J.; Drauz, K.; Krimmer, H. P.; Borner, A. J.
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