Rhodium-catalyzed asymmetric hydroformylation of vinylarenes with novel chiral P,N-ligands derived from 1,2:5,6-di-O-cyclohexylidene-d-mannitol

Article abstract of DOI:10.1016/j.tetasy.2005.08.040

Several new chiral P,N-ligands were prepared from 1,2:5,6-di-O- cyclohexylidene-d-mannitol, 1,1′-binaphthol, and phenyl isocyanate derivatives. Their Rh(I) complexes were applied as catalyst precursors in the asymmetric hydroformylation of vinylarenes. The steric and electronic properties of the phenylcarbamate substituents and the chiral binaphthyl moiety showed remarkable effects on the enantioselectivity and regioselectivity of the reaction. The matching combination of phenylcarbamate and the binaphthyl moiety of the ligand 1,2:5,6-di-O-cyclohexylidene-3-phenylcarbamate-4-[(S)-1,1′- binaphthyl-2,2′-diyl]phosphite-d-mannitol gave 50% ee and an 89/11 b/n ratio (branch-to-normal ratio). A synergic effect between the chiralities of mannitol and the binaphthol moieties was observed. Hydroformylation of the styrene gave the product in 75% ee when 1,2:5,6-di-O-cyclohexylidene-3,4-bis[(R) -1,1′-binaphthyl-2,2′-diyl]phosphite-d-mannitol was used as the chiral ligand.

Full text of DOI:10.1016/j.tetasy.2005.08.040

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 3198–3204
Rhodium-catalyzed asymmetric hydroformylation of
vinylarenes with novel chiral P,N-ligands derived from
1,2:5,6-di-O-cyclohexylidene-D-mannitol
Lai-Lai Wang,a,b Rong-Wei Guo,a Yue-Ming Lia and Albert S. C. Chana,*
aOpen Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and Synthesis and
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
bState Key Laboratory for Oxo Synthesis & Selective Oxidation, Lanzhou Institute of Chemical Physics,
Chinese Academy of Sciences, Lanzhou 730000, China
Received 21 July 2005; accepted 22 August 2005
Available online 28 September 2005
Abstract—Several new chiral P,N-ligands were prepared from 1,2:5,6-di-O-cyclohexylidene-D-mannitol, 1,10-binaphthol, and phenyl
isocyanate derivatives. Their Rh(I) complexes were applied as catalyst precursors in the asymmetric hydroformylation of vinyl-
arenes. The steric and electronic properties of the phenylcarbamate substituents and the chiral binaphthyl moiety showed remark-
able effects on the enantioselectivity and regioselectivity of the reaction. The matching combination of phenylcarbamate and the
binaphthyl moiety of the ligand 1,2:5,6-di-O-cyclohexylidene-3-phenylcarbamate-4-[(S)-1,10-binaphthyl-2,20-diyl]phosphite-D-man-
nitol gave 50% ee and an 89/11 b/n ratio (branch-to-normal ratio). A synergic effect between the chiralities of mannitol and the
binaphthol moieties was observed. Hydroformylation of the styrene gave the product in 75% ee when 1,2:5,6-di-O-cyclohexylid-
ene-3,4-bis[(R)-1,10-binaphthyl-2,20-diyl]phosphite-D-mannitol was used as the chiral ligand.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
catalyst applicable to the asymmetric hydroformylation
of a wide variety of substrates although the synthesis of
the ligand BINAPHOS was somewhat difficult. The cat-
alytic systems had some disadvantages such as high CO
pressure,5 and its regioselectivity was not completely sat-
isfactory.6 Therefore, the design and synthesis of new
chiral ligands for the asymmetric hydroformylation con-
tinues to be an active area of research.
Asymmetric hydroformylation is a useful method for the
preparation of optically active aldehydes, which are
important intermediates for synthesizing biologically
active compounds and new materials such as biodegrad-
able polymers and liquid crystals,1 The asymmetric
hydroformylation with rhodium and platinum/tin cata-
lytic systems bearing phosphine ligands have been
widely investigated in this type of reaction.1 However,
the enantioselectivity of the asymmetric hydroformyl-
ation of styrene for rhodium systems2 and the activity
and chemoselectivity for platinum/tin systems3 were
generally poor. Over the last decade, asymmetric hydro-
formylation using Rh-diphosphite4 and Rh-phosphine-
phosphite (BINAPHOS) catalyst systems5 gave better
activities and selectivities than the phosphine-based
ones. To date, the Rh-BINAPHOS system is the only
The use of carbohydrates as starting materials for the
synthesis of chiral ligands has several advantages: the
raw materials are highly enantiomerically pure and are
readily available, and the multifunctional property
makes it possible to design various structures through
a series of modifications. Chiral diphosphite ligands
starting from D-mannitol and L-diethyl tartrate have
been used in the asymmetric hydroformylation of styr-
ene, while the catalytic activity of the diphosphites
strongly depends on the bulkiness of the introduced sub-
stituents.7 Chiral diphosphite ligands derived from an
axially chiral biphenyl and D-galactopyranoside back-
bone have been used in the asymmetric hydroformyl-
ation of styrene, with up to 64% ee at 14% conversion
being obtained using hydridorhodium diphosphite
*
Corresponding author. Tel.: +852 2766 6693; fax: +852 2364 9932;
e-mail: bcachan@polyu.edu.hk
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.08.040

L.-L. Wang et al. / Tetrahedron: Asymmetry 16 (2005) 3198–3204
3199
R2
R3
R1
O
O
R1
R3
R1
O
O
O
O
O
C
O
P
CI
N
R2
O
OH
OH
O C
N
H
R2
O
O
NCO
O
H
O
R3
O
O
P
O
OH
O
O
1
O
O
2a-2c
3a-3f
2a: R1 = R3 = CH3, R2 = H;
2b: R1 = R3 = H, R2 = CH3;
2c: R1 = R2 = R3 = H.
3a: R1 = R3 = CH3, R2 = H; (S)-BINOL;
3b: R1 = R3 = CH3, R2 = H; (R)-BINOL;
3c: R1 = R3 = H, R2 = CH3; (S)-BINOL;
3d: R1 = R3 = H, R2 = CH3; (R)-BINOL;
3e: R1 = R2 = R3 = H; (S)-BINOL;
3f: R1 = R2 = R3 = H; (R)-BINOL.
O
O
O
O
O
O
P
O
P
CI
OH
OH
O
O
O
O
O
O
O
P
O
O
1
4a: (S)-BINOL
4b: (R)-BINOL
Scheme 1. The synthesis of chiral ligands.
dicarbonyl catalysts.8 A new series of phosphite–phos-
phoroamidite ligands based on a furanoside backbone
from glucose gave high regioselectivities and moderate
enantioselectivities (up to 65% ee) in the asymmetric
hydroformylation of styrene.9a Recently, new chelating
diphosphite ligands with the furanoside backbone from
glucose and axially chiral biphenyl or binaphthyl moie-
ties have been applied to the asymmetric hydroformyl-
ation of vinylarenes; up to 91% ee and 97/3 b/n ratio
were achieved under mild conditions.9b,c
mannitol 1. The reaction of 1 with phenyl isocyanate
derivatives produced the expected compounds 2a–c in
moderate yields. Reactions of compounds 2a–c with
1.1 equiv of the desired phosphorochloride synthesized
in situ10 afforded the corresponding chiral P,N-ligands
3a–f (Scheme 1). Chiral diphosphite ligands 4a and 4b
were synthesized from compound 1 and the desired
phosphorochloride synthesized in situ10 (Scheme 1).
All the ligands were stable on silica gel during the puri-
fication procedure under a nitrogen atmosphere. These
ligands were white solids and were stable to air at room
temperature.
Herein, we report the preparation and application of
several new chiral P,N-ligands derived from 1,2:5,6-di-
O-cyclohexylidene-D-mannitol, 1,10-binaphthol and
phenylisocyanate derivatives. The ligands have the axi-
ally chiral binaphthyl moiety and the phenylcarbamate
substituents at either the 3- or 4-position of D-mannitol
(Scheme 1). These Rh(acac)(CO)2–ligand complexes
were applied as catalyst precursors in the asymmetric
hydroformylation of vinylarenes. The effect of the steric
and electronic properties of phenylcarbamate substitu-
ents, and chiral binaphthyl moiety on the enantioselec-
tivity and regioselectivity of the reaction was studied.
A synergic effect between the stereogenic centers of D-
mannitol and the chiral binaphthol substituents was
observed.
2.2. Asymmetric hydroformylation of vinylarenes
The results of asymmetric hydroformylation of styrene11
are summarized in Table 1. It is interesting to note that
the chirality match between the mannitol backbone and
the binaphthyl functional group could significantly
influence the stereochemical outcome of the reaction.
The use of ligand 3a gave high regioselectivity (b/n =
93/7) but low enantioselectivity (34% ee) (Table 1,
entry 1). In contrast, the use of ligand 3b bearing the
same 3,5-dimethyl-phenylcarbamate substituent and
the axially chiral binaphthyl with a configuration oppo-
site to that of ligand 3a gave low regioselectivity (b/n =
87/13), the opposite sense of enantioselectivity with
6.7% ee (Table 1, entry 2). The use of ligand 3c gave high
regioselectivity (b/n = 91/9) and 19% ee (Table 1, entry
3). In contrast, the use of ligand 3d bearing the same 4-
methyl-phenylcarbamate substituent and the axially chi-
ral binaphthyl with a configuration opposite to that of
ligand 3c gave low regioselectivity (b/n = 83/17) and
racemic product (Table 1, entry 4). The use of ligands
2. Results and discussion
2.1. Synthesis of the chiral P,N-ligands
Chiral P,N-ligands 3a–f were synthesized stereospecifi-
cally in two steps from 1,2:5,6-di-O-cyclohexylidene-D-

3200
L.-L. Wang et al. / Tetrahedron: Asymmetry 16 (2005) 3198–3204
Table 1. Asymmetric hydroformylation of styrene catalyzed by Rh(acac)(CO)2/ligandsa
CHO
*
CHO
CO/H2
+
Rh(acac)(CO)2/ligands
5a
6a, (n)
7a, (b)
b/nb
Entry
L
Conv.b
%eec (conf.)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
25
32
27
30
22
28
0
93/7
87/13
91/9
83/17
89/11
84/16
0
34% (R)
6.7% (S)
19% (R)
Racemic
50% (S)
3.1% (S)
0
4a
4b
2.4
72/28
75% (S)
a Reaction conditions: styrene, 0.04 mL, 3.64 mg, 0.35 mmol; 0.5 mL of Toluene; S/C = 200, Rh(acac)(CO)2, 0.45 mg, 0.00175 mmol; L/Rh = 4; CO,
800 psi, H2, 800 psi; T, room temperature; t, 20 h.
b The data on the conversion and b/n ratio were determined by GC–MS analysis of styrene, 2-phenylpropanal, and 3-phenylpropanal.
c The ee was determined by GC analysis using a chiral capillary column (Chrompack Chirasil-Dex CB column, 50 m · 0.25 mm I.D.) of the
corresponding methyl-2-phenylpropionate derived by esterification and Jones oxidation of the product. The absolute configuration was determined
by methyl-2-phenylpropionate and the comparison of retention time with an authentic (R)-sample.
Table 2. The effect of solvents on asymmetric hydroformylation of
3e and 3f bearing the same phenylcarbamate substitu-
ents but opposite in the configuration of binaphthyl
styrene catalyzed by Rh(acac)(CO)2/ligand 3ea
Conv.b
b/nb
%eec (conf.)
moiety gave the same sense of enantioselectivity. How-
ever, ligand 3e gave higher regioselectivity (b/n = 89/11)
and better enantioselectivity (50% ee) (Table 1, entries
5 and 6). Comparison of these results clearly indicated
that the steric and electronic properties of the phenyl-
carbamate substituent and the axially chiral binaphthyl
moiety had a remarkable effect on the regioselectivity
and enantioselectivity of the reaction. No reaction oc-
curred when 4a was used as the ligand (Table 1, entry
7). These results were very similar to those previously
reported using 1,2:5,6-diisopropylidene-3,4-di(2,20-bis-
phenoxyphosphinoxy)-D-mannitol as the ligand.7 In
contrast, the use of ligand 4b, in which the chirality of
the binaphthyl moiety was opposite to that in ligand
4a, gave moderate enantioselectivity (75% ee) and regio-
selectivity (b/n, 72/28) even though the conversion was
low (Table 1, entry 8). These results clearly indicated
the existence of a synergic effect between the stereogenic
centers of mannitol and the chiral binaphthol
substituents.
Entry
L
1
2
3
4
5c
CH2Cl2
n-Hexane
Et2O
20
30
32
41
11
88/12
86/14
85/15
81/19
89/11
47% (S)
54% (S)
28% (S)
25% (S)
27% (S)
THF
Trimethylortho-
formate (C4H10O3)
Methanol
6
18
87/13d
34% (S)
a Reaction conditions: styrene, 0.04 mL, 3.64 mg, 0.35 mmol; 0.5 mL
of solvent; S/C = 200, Rh(acac)(CO)2, 0.45 mg, 0.00175 mmol; CO,
800 psi, H2, 800 psi; T, room temperature; t, 20 h.
b The data on the conv., b/n ratio, and ee were determined using the
same conditions as noted in Table 1.
c 0.5 mL of trimethylorthoformate (C4H10O3).
d The product: 2-phenylpropanal, 3-phenylpropanal, dimethyl acetal of
2-phenylpropanal, and dimethyl acetal of 3-phenylpropanal.
were obtained as the corresponding dimethyl acetals
(Table 2, entry 6), indicating that the reaction conditions
were fairly acidic in methanol.5
As shown in Table 1, only 3e and 4b gave notable results
in the asymmetric hydroformylation of styrene, and 3e
was used for the optimization of the reaction conditions
as it gave better conversion and regioselectivity although
the enantioselectivity was not high. A profound solvent
effect on the enantioselectivity of the reaction was
observed, although the solvent had little effect on the
regioselectivity of the reaction. The results are summa-
rized in Table 2. The use of dichloromethane or n-hex-
ane gave comparable results (Table 2, entries 1 and 2),
but ether solvents (ether and THF, Table 2, entries 3
and 4) seemed to be detrimental to the enantioselectiv-
ity. Contrary to the common notion that the use of tri-
Biologically active compounds bearing a trifluoromethyl
or pentafluorophenyl group may possess unique physio-
logical activities.13 Hydroformylation of fluorinated ole-
fins would be a convenient method to synthesize the
intermediates of such compounds. 3-Fluorostyrene 5b
and 4-fluorostyrene 5c were tested for asymmetric hyd-
roformylation with Rh(acac)(CO)2 in the presence of
ligands 3e and 4b, respectively. As shown in Table 3,
the reaction of substrate 5b in n-hexane gave 40% ee
when ligand 3e was used (Table 3, entry 1), while the
use of ligand 4b gave the product with 17% ee (Table
3, entry 2). The reaction of substrate 5c in n-hexane gave
the product in 27% ee when ligand 3e was used (Table 3,
entry 3), while the use of ligand 4b gave the product in
15% ee (Table 3, entry 4). It should be noted that the
reaction of substrates 5b and 5c showed significantly
methylorthoformate is effective in the reactions,3b,12
a
lower enantioselectivity (27% ee) was observed when
trimethylorthoformate as a solvent was used (Table 2,
entry 5). In methanol, most of the product aldehydes

L.-L. Wang et al. / Tetrahedron: Asymmetry 16 (2005) 3198–3204
3201
Table 3. Asymmetric hydroformylation of 3-fluorostyrene and 4-fluorostyrene catalyzed by Rh(acac)(CO)2/ligand 3e or 4b complexa
CHO
*
CHO
CO/H2
Rh(acac)(CO)2/ligands R2
+
R2
R2
R1
R1
R1
5b, R1 = F, R2 = H
5c, R1= H, R2 = F
6b, R1 = F, R2 = H
6c, R1 = H, R2 = F
7b, R1 = F, R2 = H
7c, R1 = H, R2 = F
Entry
Sub
L
Conv.b
b/nb
%eec (conf.)d
1
2
3
4
5b
5b
5c
5c
3e
4b
3e
4b
25
70
68
99
90/10
80/20
74/26
80/20
40% (S)
17% (R)
27% (S)
15% (R)
a Reaction conditions: substrate 5b or 5c, 0.35 mmol; 0.5 mL of solvent, n-C6H14; S/C = 200, Rh(acac)(CO)2, 0.45 mg, 0.00175 mmol; L/Rh = 4; CO,
800 psi, H2, 800 psi; T, room temperature; t, 20 h.
b The data on the conversion and b/n ratio were determined using the same conditions as noted in Table 1.
c The ee of the product of 5b was determined using the same conditions as noted in Table 1. The ee of the product of 5c was determined by HPLC
analysis of the corresponding methyl-2-(4-fluorophenyl)propionate derived by esterification and Jones oxidation of the product using a chiral
column (Chiralcel OJ 25 · 0.46 cm I.D.).
d The absolute configurations of compounds 7b and 7c were assigned from their chromatographic behavior.
different enantioselectivity in the presence of ligand 3e
(Table 3, entries 1 and 3). This possibly indicates that
the effect of the steric and electronic properties of sub-
strates 5b and 5c on the enantioselectivity was very
important when 3e was used as a chiral ligand.
available reagents were used as received without fur-
1
ther purification. H NMR, 13C NMR, and 31P NMR
were recorded on a Varian AS 500 at room temperature.
1H NMR spectra are reported in parts per million with
TMS as an internal standard (d = 0 ppm). 31P NMR
spectra are reported in parts per million with 85%
H3PO4 as an external reference.
3. Conclusion
4.2. 1,2:5,6-Di-O-cyclohexylidene-3-[(3,5-dimethyl)phen-
ylcarbamate]-D-mannitol 2a, 1,2:5,6-di-O-cyclohexylid-
ene-3-[(3-methyl)phenylcarbamate]-D-mannitol 2b, and
1,2:5,6-di-O-cyclohexylidene-3-phenyl-carbamate-D-
mannitol 2c
New chiral P,N-ligands were prepared from 1,2:5,6-
di-O-cyclohexylidene-D-mannitol, 1,10-binaphthol, and
phenyl isocyanate derivatives. The ligands had the
axially chiral binaphthyl moiety and the phenylcarb-
amate substituent at the 3- or 4-position of D-mannitol.
The Rh(acac)(CO)2–ligand complexes were applied as
catalyst precursors in the asymmetric hydroformylation
of vinylarenes. The steric and electronic properties of
the phenylcarbamate substituent and the axially chiral
binaphthyl moiety revealed a remarkable effect on
the b/n ratio and ee of the reaction. Ligand 3e gave
50% ee and regioselectivity 89/11 (b/n). A synergic
effect between the stereogenic centers C-3 and C-4 of
mannitol and the chiral binaphthol substituents was
also observed. Up to 75% ee using ligand 4b was
obtained.
1,2:5,6-Di-O-cyclohexylidene-D-mannitol 1 (1.0 g, 2.92
mmol) was dissolved in 20 mL of dichloromethane,
and mixed at room temperature with 4-N,N-dimethyl-
aminopyridine (DMAP, 0.025 g, 0.205 mmol) and 3,5-
dimethylphenyl isocyanate (0.43 g, 2.92 mmol). The
reaction mixture was stirred for 12 h at room tempera-
ture, and the dichloromethane was distilled off under
reduced pressure at room temperature. The residue was
purified by column chromatography (eluent: CH2Cl2/
EA = 10) to produce 2a as white powder (0.805 g,
1
58%). H NMR (CDCl3): d = 1.30–1.59 (m, 20H), 2.21
(s, 6H), 3.85 (m, 1H), 3.96 (m, 3H), 4.06 (m, 2H), 4.37
(dd, J = 6.5 and 12.0 Hz, 1H), 5.00 (d, J = 5.5 Hz, 1H),
6.65 (s, NH), 6.90–6.94 (m, 3H) ppm. 13C NMR
(125 MHz, CDCl3): d = 21.5, 23.9, 24.1, 24.2, 25.1,
25.2, 34.7, 34.8, 36.3, 36.7, 65.6, 66.2, 71.0, 73.4, 75.0,
75.3, 77.0, 77.2, 77.4, 77.5, 109.9, 110.6, 116.5, 125.6,
137.6, 139.0, 152.8 ppm.
4. Experimental
4.1. Reagents and materials
All experiments were carried out under a nitrogen atmo-
sphere. Phenyl isocyanate, 3-methylphenyl isocyanate,
and 3,5-dimethylphenyl isocyanate were purchased from
Acros and used without further purification. Styrene, 3-
fluorostyrene, and 4-fluorostyrene were purchased from
Aldrich, distilled, and degassed with dry nitrogen before
use. Toluene, ether, methanol, and THF were distilled
from sodium. Dichloromethane and n-hexane were dis-
tilled over calcium hydride. The other commercially
Treatment of compound 1 and 3-methylphenyl isocya-
nate as described for compound 2a yielded compound
1
2b as a white powder (0.62 g, 45%). H NMR (CDCl3):
d = 1.38–1.66 (m, 20H), 2.30 (s, 3H), 3.90–4.14 (m, 6H),
4.44 (dd, J = 6.0 and 12.0 Hz, 1H), 5.07 (d, J = 5.0 Hz,
1H), 6.84 (s, NH), 7.26–7.27 (m, 4H) ppm. 13C NMR
(125 MHz, CDCl3): d = 20.7, 23.7, 23.9, 24.0, 25.0,

3202
L.-L. Wang et al. / Tetrahedron: Asymmetry 16 (2005) 3198–3204
25.1, 30.9, 34.5, 34.6, 36.1, 36.5, 65.5, 66.0, 70.9, 75.1,
76.7, 77.0, 77.3, 77.5, 110.0, 110.7, 119.0, 129.9, 133.6,
135.2, 152.9 ppm.
4.4. 1,2:5,6-Di-O-cyclohexylidene-3-[(4-methylphenylcar-
bamate)]-4-[(S)-1,10-binaphthyl-2,20-diyl]phosphite-D-
mannitol 3c and 1,2:5,6-di-O-cyclohexylidene-3-[(4-meth-
ylphenylcarbamate)-4-[(R)-1,10-binaphthyl-2,20-diyl]phos-
phite-D-mannitol 3d
Treatment of compound 1 and phenyl isocyanate as
described for compound 2a yielded compound 2c as a
white powder (0.51 g, 39%). 1H NMR (CDCl3):
d = 1.53–1.66 (m, 20H), 2.8 (d, 1H), 3.93 (dd, 1H),
4.05 (m, 2H), 4.13 (m, 2H) ppm, 4.47 (dd, J = 6.5 and
12.5 Hz, 1H), 5.10 (d, J = 5.5 Hz, 1H), 6.81 (s, 1H),
7.26–7.27 (m, 5H). 13C NMR (125 MHz, CDCl3):
d = 19.7, 22.7, 23.8, 24.1, 25.0, 30.8, 34.4, 34.6, 35.8,
36.5, 65.4, 66.1, 71.9, 74.1, 75.7, 76.0, 76.3, 76.5, 109.0,
110.8, 118.0, 128.9, 133.6, 134.2, 150.9 ppm.
Treatment of the in situ formed10 (S)-1,10-binaphthyl-
2,20-diyl-chlorophosphine (0.87 mmol) and compound
2b afforded ligand 3c, which was purified by flash chromato-
graphy (CH2Cl2/Et2O, 9/1, Rf = 0.85) to produce a white
powder (0.25 g, 40%). 31P NMR (202 MHz, CDCl3), d =
1
154.5 ppm. H NMR (CDCl3): d = 1.32–1.74 (m, 20H),
2.23 (s, 3H), 3.86 (m, 1H), 3.95 (m, 1H), 4.13 (m, 3H),
4.40 (d, J = 6.0 Hz, 1H), 4.78 (d, J = 12.5 Hz, 1H), 5.08
(d, J = 7.0 Hz, 1H), 6.49 (s, NH), 6.91–7.91 (m, 16H, Ar–
H) ppm. 13C NMR (125 MHz, CDCl3): d = 21.5, 23.9,
24.3, 25.6, 33.0, 35.5, 35.8, 36.6, 64.7, 65.9, 71.9, 76.6,
76.9, 77.0, 77.9, 109.0, 110.8, 117.9, 121.0, 122.1, 122.2,
123.2, 124.6, 124.7, 125.0, 125.1, 125.3, 126.3, 126.5, 127.0,
127.2, 128.3, 128.6, 129.8, 130.1, 130.5, 131.2, 131.8,
132.9, 133.1, 133.6, 134.8, 147.6, 148.3, 148.6, 151.3 ppm.
4.3. 1,2:5,6-Di-O-cyclohexylidene-3-[(3,5-dimethyl)phen-
ylcarbamate]-4-[(S)-1,10-binaphthyl-2,20-diyl]phosphite-D-
mannitol 3a and 1,2:5,6-di-O-cyclohexylidene-3-[(3,5-di-
methyl)phenylcarbamate]-4-[(R)-1,10-binaphthyl-2,20-di-
yl]phosphite-D-mannitol 3b
(S)-1,10-Binaphthyl-2,20-diyl-chlorophosphine (0.87 mmol)
was synthesized in situ10 and dissolved in toluene
(10 mL). Compound 2a (0.381 g, 0.8 mmol) was azeo-
tropically dried with toluene (3 · 10 mL) and then
dissolved in triethylamine (4 mL) to which DMAP
(0.01 g, 0.083 mmol) had been added. A solution of
phosphorochloridite was transferred slowly to a solution
of compound 2a at 0 ꢁC. The reaction mixture was
stirred overnight at room temperature, and the formed
triethylamine salts were removed by filtration. Evapora-
tion of the solvent gave a white foam, which was purified
by flash chromatography (CH2Cl2/Et2O, 9/1, Rf = 0.86)
to produce 3a as white powder (0.42 g, 66%). 31P NMR
Treatment of the in situ formed10 (R)-1,10-binaphthyl-
2,20-diyl-chlorophosphine (0.87 mmol) and compound
2b afforded ligand 3d, which was purified by flash chro-
matography (CH2Cl2/Et2O, 9/1, Rf = 0.83) to produce
a white powder (0.27 g, 43%). 31P NMR (202 MHz,
1
CDCl3), d = 157.6 ppm. H NMR (CDCl3): d = 1.33–
1.84 (m, 20H), 2.20 (s, 3H), 3.73 (s, 1H), 3.94 (m, 2H),
4.07 (m, 1H), 4.18 (d, J = 8.0 Hz, 1H), 4.32 (s, 1H),
4.91 (d, J = 7.5 Hz, 1H), 5.01 (d, J = 6.5 Hz, 1H), 6.46
(s, NH), 6.99–7.88 (m, 16H, Ar–H) ppm. 13C NMR
(125 MHz, CDCl3): d = 21.0, 24.0, 24.3, 25.5, 33.9,
35.2, 35.9, 36.7, 64.0, 66.9, 72.9, 75.6, 77.0, 77.3, 77.5,
109.9, 110.5, 118.9, 122.0, 122.1, 122.2, 123.1, 124.6,
124.7, 125.0, 125.1, 125.3, 126.2, 126.5, 127.2, 127.3,
128.5, 128.6, 129.8, 130.2, 130.5, 131.4, 131.8, 132.9,
133.1, 133.7, 134.9, 147.6, 148.5, 148.6, 150.8 ppm.
1
(202 MHz, CDCl3), d = 153.7 ppm. H NMR (CDCl3):
d = 1.61–1.86 (m, 20H), 2.30 (s, 6H), 3.94–4.14 (m,
3H), 4.29 (s, 2H), 4.53 (d, J = 7.0 Hz, 1H), 4.92 (s,
1H), 5.22 (d, J = 7.5 Hz, 1H), 6.74 (s, NH), 7.01–8.02
(m, 15H, Ar–H) ppm. 13C NMR (125 MHz, CDCl3):
d = 21.6, 21.7, 24.0, 24.3, 25.5, 33.9, 35.3, 35.9, 36.8,
64.1, 66.9, 72.9, 74.3, 75.1, 75.6, 77.1, 77.3, 77.6, 110.0,
110.6, 116.6, 122.0, 122.3, 123.2, 124.7, 125.3, 125.6,
125.9, 126.3, 126.5, 127.3, 128.5, 128.6, 129.3, 130.2,
130.6, 131.4, 131.8, 132.9, 133.1, 137.3, 138.1, 139.1,
147.3, 147.6, 148.6, 152.3 ppm.
4.5. 1,2:5,6-Di-O-cyclohexylidene-3-phenylcarbamate-4-
[(S)-1,10-binaphthyl-2,20-diyl]phosphite-D-mannitol 3e and
1,2:5,6-di-O-cyclohexylidene-3-phenylcarbamate-4-[(R)-
1,10-binaphthyl-2,20-diyl]phosphite-D-mannitol 3f
Treatment of the in situ formed10 (S)-1,10-binaphthyl-
2,20-diyl-chlorophosphine (0.87 mmol) and compound
2c afforded ligand 3e, which was purified by flash chro-
matography (CH2Cl2/Et2O, 9/1, Rf = 0.87) to produce a
white powder (0.26 g, 43%). 31P NMR (202 MHz,
Treatment of the in situ formed10 (R)-1,10-binaphthyl-
2,20-diyl-chlorophosphine (0.87 mmol) and compound
2a afforded ligand 3b, which was purified by flash chro-
matography (CH2Cl2/Et2O, 9/1, Rf = 0.87) to produce a
white powder (0.30 g, 47%). 31P NMR (202 MHz,
1
CDCl3), d = 154.5 ppm. H NMR (CDCl3): d = 1.32–
1.74 (m, 20H), 2.23 (s, 3H), 3.86 (m, 1H), 3.95 (m,
1H), 4.13 (m, 3H), 4.40 (d, J = 6.5 Hz, 1H), 4.78 (d,
J = 7.0 Hz, 1H), 5.08 (d, J = 8.0 Hz, 1H), 6.49 (s,
NH), 6.91–7.91 (m, 16H, Ar–H) ppm. 13C NMR
(125 MHz, CDCl3): d = 24.1, 24.2, 24.7, 25.3, 25.6,
33.9, 35.2, 35.6, 36.7, 64.0, 66.3, 72.7, 75.0, 77.0, 77.3,
77.5, 109.0, 110.6, 113.3, 118.0, 118.4, 122.1, 122.8,
123.7, 124.0, 124.5, 124.6, 124.9, 125.6, 126.6, 127.0,
127.1, 127.7, 128.0, 128.9, 129.0, 129.3, 129.5, 130.0,
130.6, 131.6, 132.8, 133.1, 133.8, 152.6 ppm.
1
CDCl3), d = 156.6 ppm. H NMR (CDCl3): d = 1.32–
1.71 (m, 20H), 2.31 (s, 6H), 3.87 (s, 1H), 4.08 (d,
J = 22 Hz, 2H), 4.23 (s, 1H), 4.34 (d, J = 4.5 Hz, 1H),
4.46 (s, 1H), 5.06 (d, J = 7.0 Hz, 1H), 5.15 (d,
J = 6.5 Hz, 1H), 6.56 (s, NH), 6.75–8.01 (m, 15H, Ar–
H) ppm. 13C NMR (125 MHz, CDCl3): d = 21.0, 21.7,
24.0, 24.3, 26.5, 33.9, 35.3, 36.8, 64.1, 66.9, 73.9, 74.3,
75.1, 75.3, 75.9, 77.1, 77.3, 77.6, 110.0, 110.6, 116.6,
122.0, 122.8, 123.2, 124.7, 125.1, 125.3, 125.6, 125.9,
126.4, 126.5, 127.3, 128.5, 128.6, 129.3, 130.2, 130.6,
131.1, 131.8, 132.9, 133.1, 137.3, 138.1, 139.1, 147.2,
147.6, 148.9 ppm.
Treatment of the in situ formed10 (R)-1,10-binaphthyl-
2,20-diyl-chlorophosphine (0.87 mmol) and compound

L.-L. Wang et al. / Tetrahedron: Asymmetry 16 (2005) 3198–3204
3203
2c afforded ligand 3f, which was purified by flash chro-
matography (CH2Cl2/Et2O, 9/1, Rf = 0.84) to produce
a white powder (0.28 g, 46%). 31P NMR (202 MHz,
on the conversion and b/n ratio were determined by
GC–MS analysis of styrene, 2-phenylpropanal, and 3-
phenylpropanal on an HPG 1800c GCD system on a
Bexs column (30 m · 0.25 mm I.D.). The ee was deter-
mined by GC analysis of the corresponding methyl-2-
phenylpropionate derived by Jones oxidation and subse-
quent esterification of the product using an HP5890 gas
chromatograph equipped with Chrompack Chirasil-Dex
CB column (50 m · 0.25 mm I.D.). The absolute config-
uration of 7a was determined by methyl-2-phenylprop-
ionate and the comparison of retention time with an
(R)-sample. The absolute configurations of compounds
7b/7c were temporarily assigned from their chromato-
graphic behavior.
1
CDCl3), d = 156.1 ppm. H NMR (CDCl3): d = 1.17–
1.83 (m, 20H), 3.712 (s, 1H), 3.87 (s, 1H), 3.93 (s, 1H),
4.08 (s, 1H), 4.18 (d, J = 6.5 Hz, 1H), 4.31 (s, 1H),
4.90 (d, J = 7.5 Hz, 1H), 5.01 (d, J = 7.0 Hz, 1H), 6.51
(s, NH), 6.94–7.84 (m, 17H, Ar–H) ppm. 13C NMR
(125 MHz, CDCl3): d = 24.0, 24.2, 24.3, 25.5, 25.6,
34.0, 35.2, 35.9, 36.8, 64.1, 66.9, 72.9, 75.6, 77.1, 77.3,
77.6, 110.0, 110.6, 111.3, 118.1, 118.8, 122.0, 122.3,
123.2, 124.3, 124.5, 124.6, 124.7, 125.6, 126.6, 127.2,
127.3, 127.7, 128.5, 128.6, 129.1, 129.3, 129.7, 130.2,
130.6, 131.8, 132.9, 133.1, 133.7, 152.3 ppm.
4.6. 1,2:5,6-Di-O-cyclohexylidene-3,4-bis[(S)-1,10-bi-
naphthyl-2,20-diyl]phosphite-D-mannitol 4a and 1,2:5,6-
di-O-cyclohexylidene-3,4-bis[(R)-1,10-binaphthyl-2,20-
diyl]phosphite-D-mannitol 4b
Acknowledgments
We thank the University Grants Committee Area of
Excellence Scheme in Hong Kong (AoE P/10-01), and
The Hong Kong Polytechnic University ASD Fund
for financial support of this study.
Compound 1 (0.206 g, 0.6 mmol) and DMAP (0.015 g,
0.123 mmol) were put in a 50 mL round-bottomed flask.
Toluene (5 mL) and dry triethylamine (0.2 mL) were
added under dry nitrogen. The mixture was cooled to
0 ꢁC with an ice-bath, (S)-1,10-binaphthyl-2,20-diyl-chlo-
rophosphine (1.2 mmol) synthesized in situ10 in toluene
(5 mL) was added dropwise in the solution and stirred
for 30 min under 0 ꢁC, then left at room temperature
overnight. The solvent was removed in vacuo and the
residues were purified by flash chromatography (tolu-
ene, Rf = 0.33) to produce 4a as white powder (0.47 g,
81%). 31P NMR (202 MHz, CD2Cl2), d = 153.4 ppm.
1H NMR (CD2Cl2): d = 1.49–1.79 (m, 20H), 4.22–4.27
(m, 4H), 4.61–4.65 (m, 2H), 4.80–4.84 (m, 2H), 7.23–
8.06 (m, 12H) ppm. 13C NMR (125 MHz, CD2Cl2):
d = 24.1, 24.5, 25.5, 35.1, 37.0, 67.2, 73.9, 76.4, 110.9,
122.0, 122.3, 125.3, 125.5, 125.6, 126.6, 126.7, 127.1,
127.2, 128.5, 128.8, 129.3, 130.1, 130.8, 131.5, 132.0,
132.8, 133.1, 147.5, 148.3 ppm.
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Treatment of the in situ formed10 (R)-1,10-binaphthyl-
2,20-diyl]-chlorophosphine (1.2 mmol) and compound 1
afforded ligand 4b, which was purified by flash chroma-
tography (toluene, Rf = 0.34) to produce a white powder
(0.49 g, 84%). 31P NMR (202 MHz, CD2Cl2), d =
1
155.1 ppm. H NMR (CD2Cl2): d = 1.52–1.58 (m, 4H),
1.78–1.86 (m, 16H), 4.15–4.18 (m, 2H), 4.28–4.31 (m,
2H), 4.49–4.52 (m, 2H), 4.79–4.82 (m, 2H), 7.30–7.56
(m, 8H), 7.89–8.05 (m, 4H) ppm. 13C NMR (125 MHz,
CD2Cl2): d = 24.3, 24.4, 25.6, 34.7, 36.6, 66.5, 74.3,
76.9, 77.1, 110.5, 121.8, 121.9, 122.9, 124.6, 125.2,
125.4, 125.6, 126.4, 126.6, 127.1, 128.5, 128.7, 129.3,
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4.7. General procedure for the enantioselective
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magnetic stirrer at room temperature. After a prescribed
reaction time, the residue gas was released. The data
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L.-L. Wang et al. / Tetrahedron: Asymmetry 16 (2005) 3198–3204
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