Chiral diphosphites derived from (1R,2R)-trans-1,2-cyclohexanediol: A new class of ligands for asymmetric hydrogenations

Article abstract of DOI:10.1016/j.tetasy.2015.10.020

A series of novel chiral diphosphite ligands was easily prepared in a few steps from commercial (1R,2R)-trans-1,2-cyclohexanediol as the chiral source, and successfully employed in the Rh-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic ac

Full text of DOI:10.1016/j.tetasy.2015.10.020

Tetrahedron: Asymmetry 26 (2015) 1389–1393
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Chiral diphosphites derived from (1R,2R)-trans-1,2-cyclohexanediol:
a new class of ligands for asymmetric hydrogenations
Zeng-bo Pang a,b, Hai-feng Li a, Mi Tian a,b, Lai-lai Wang a,
⇑
a State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China
b University of Chinese Academy of Sciences, Beijing 100039, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 September 2015
Accepted 23 October 2015
A series of novel chiral diphosphite ligands was easily prepared in a few steps from commercial (1R,2R)-
trans-1,2-cyclohexanediol as the chiral source, and successfully employed in the Rh-catalyzed asymmet-
ric hydrogenation of
a
,b-unsaturated carboxylic acid derivatives and enamides with up to 99% ee for
-dehydroamino acid esters. The stereo-
dimethyl itaconate and enamides and with up to 94% ee for
a
chemically matched combination of (1R,2R)-trans-1,2-cyclohexanediol backbone and (S)-binaphthyl in
the ligand (1R,2R)-bis[(S)-1,10-binaphthyl-2,20-diyl]phosphitecyclohexanediol, was essential for inducing
high enantioselectivity. Moreover, the sense of enantiodiscrimination of the products was mainly deter-
mined by the configuration of the binaphthyl moieties.
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
O
O
O
O
In recent years, the industrial demand for optically active com-
pounds in the production of chiral drugs, agrochemicals, flavor, and
advanced materials has increased remarkably.1 Asymmetric hydro-
genation with transition-metal complex bearing chiral ligands is a
powerful approach to synthesize chiral substances from unsatu-
rated starting materials, and thus the design and development of
new catalysts, which provide high activity and enantioselectivity
for asymmetric hydrogenation reactions remain appealing
challenges.2 In this context, chiral P-donor ligands (phosphines,3
phosphites,4 phosphoroamidites5) have gathered much attention
in recent decades. Among the aforementioned ligands, phosphites,
which are attractive due to their high efficiency, facile synthesis,
and less sensitivity to air, have emerged as suitable ligands for
Rh-catalyzed enantioselective hydrogenations.6 Despite the
tremendous advance of this field, many research groups are still
focused on the search for new catalytic systems that can be easily
prepared and which can catalyze a wide range of substrates with
good activity and good enantioselectivity.5b
P
NH HN
P
Ar2PO
OPAr2
2
1a: R = 3,5-Me2C6H3
1b
: R = Ph
Figure 1. The representative examples of the application of trans-1,2-cyclohex-
anediol and (1R,2R)-diaminocyclohexane.
ligands 1a and 1b (Fig. 1), derived from (1S,2S)-trans-1,2-cyclohex-
anediol and the corresponding diarylchlorophosphines proved to
be effective for the hydrogenation of dimethyl itaconate with good
enantiomeric excesses (up to 79% ee) in 1999. Recently, Arena
et al.9 used (1R,2R)-diaminocyclohexane as the backbone, and pre-
pared enantiopure diphosphoramidite ligand 2 (Fig. 2), which was
successfully employed in Rh-catalyzed asymmetric hydrogena-
tions of dimethyl itaconate, methyl 2-acetamidoacrylate, and (Z)-
methyl-2-acetamido-3-phenylacrylate with up to 88% ee. To the
best of our knowledge, although a number of chiral, phosphorus-
donor ligands have been synthesized for transition-metal-
catalyzed asymmetric transformations, chiral phosphite ligands
derived from cyclohexanediol have been rarely studied, hence we
designed and synthesized novel diphosphite ligands 5a–5d by
changing the electron density at the phosphorus atom and the con-
figuration of the biaryl moieties of the ligands. These ligands were
successfully applied to Rh-catalyzed asymmetric hydrogenations
1,2-Cyclohexanediol is widely used in preparing polyester,
epoxy resin thinner, o-dihydroxybenzene, and so on. As an impor-
tant organic intermediate, 1,2-cyclohexanediol has enjoyed great
success over the years in the field of medicine, pesticide, spice,
and organic synthesis.7 For example, RajanBabu et al.8 found that
⇑
Corresponding author. Tel.: +86 931 4968161; fax: +86 931 4968129.
E-mail address: wll@licp.cas.cn (L.-l. Wang).
of
a,b-unsaturated carboxylic acid derivatives and enamides. It
http://dx.doi.org/10.1016/j.tetasy.2015.10.020
0957-4166/Ó 2015 Elsevier Ltd. All rights reserved.

1390
Z.-b. Pang et al. / Tetrahedron: Asymmetry 26 (2015) 1389–1393
COOMe
NHAc
COOMe
NHAc
COOMe
NHCOPh
6b
OMe
6c
6d
OMe
100%, 93% (R)
100%, 89% (R)
100%, 91% (R)
COOMe
NHAc
COOMe
NHAc
6f
COOMe
NHAc
Cl
6g
6e
MeO
Cl
100%, 94% (R)
100%, 90% (R)
100%, 89% (R)
100%, 91% (R)
COOMe
NHAc
COOMe
COOMe
NHAc
NHAc
6j
Cl
6i
F
Br
6h
100%, 91% (R)
100%, 91% (R)
COOMe
NHAc
6k
MeOOC
NHAc
Me
6l
100%, 93% (R)
100%, 92% (R)
Figure 2. Selected results for the asymmetric Rh-catalyzed hydrogenation of substrates 6b–6l using the [Rh(cod)2]BF4/5b catalytic system.
was found that the sense of enantiodiscrimination of the products
was mainly determined by the configuration of the binaphthyl
moieties.
the 31P NMR spectrum of 5d contains a singlet for the two equiva-
lent phosphorus atoms and moved to a high field (142.75 ppm).
This rule also applies to our previous literature data.11
2. Results and discussion
2.2. Asymmetric hydrogenation of
a
-dehydroamino acid esters
2.1. Synthesis of chiral phosphite ligands 5a–5d
The asymmetric hydrogenation of
a-dehydroamino acid deriva-
tives is considered to be one of the most important approaches for
the preparation of various chiral -amino acids, which are of great
As shown in Scheme 1, ligands 5a–5d were synthesized in one
step from commercially available (1R,2R)-trans-1,2-cyclohexane-
diol 3 (99% ee) and the corresponding diarylchlorophosphines 4,
which were derived from 2,20-dihydroxy-1,10-binaphthol (binaph-
thol), and 2,20-dihydroxy-5,50,6,60,7,70,8,80-octahydro-1,10-binaph-
thol (H8-binaphthol) by procedures reported previously10
a
synthetic importance in the preparation of chiral drugs and natural
products.12 In the first set of experiments, we evaluated the
diphosphite ligands 5a–5d in the Rh-catalyzed asymmetric hydro-
genation of (Z)-methyl 2-acetamido-3-phenylacrylate 6a, which
was used as a model substrate. The catalysts were prepared
in situ by adding the corresponding ligands to the catalyst precur-
sor [Rh(cod)2]BF4. The reaction proceeded smoothly at room tem-
perature using CH2Cl2 as the solvent under 10 atm of H2, and the
results are summarized in Table 1. It was found that the catalysts
showed high activities, and all catalysts completed the reactions
under the conditions specified. Ligand 5a give 22% ee (S) for methyl
2-acetamido-3-phenylpropanoate 7a (Table 1, entry 1), and ligand
5b, which bore (S)-binaphthyl in comparison with ligand 5a, gave
92% ee (R) (Table 1, entry 2). However, only 5% ee (S) was achieved
when using [Rh(cod)2]BF4/5c as the catalyst (Table 1, entry 3). In
contrast, the configuration of the H8-binaphthyl moiety was oppo-
site to that of 5c and gave 86% ee (R) (Table 1, entry 4) when 5d
was used as the ligand. It is noteworthy that ligand 5b was the
most efficient ligand in this reaction. The results indicated that
the matching combination of the stereogenic centers of the cyclo-
hexanediol backbone and the (S)-binaphthyl of ligand 5b was fun-
damental to obtain higher enantioselectivity. By comparing entries
1–4 of Table 1, it can be seen that the sense of enantioselectivity
was mainly determined by the configuration of the binaphthyl or
H8-binaphthyl moiety of ligands 5a–5d, and an (S)-binaphthyl
fragment gives an (R)-product and conversely an (S)-product for
an (R)-binaphthyl.
(Scheme 1). In the 31P NMR spectrum of 5a,
a singlet at
150.74 ppm was observed for the two equivalent phosphorus
atoms. However, the chemical shift of 5c moved to high field
(145.17 ppm) when the biaryl moieties changed to H8-binaphthol.
Similarly, in the 31P NMR spectrum of 5b, the two phosphorus
atoms appeared as a sharp singlet at 149.37 ppm. As expected,
O
P
OH
OH
O
O
*
O
O
O
THF, NEt3
DMAP
Cl
P
+
O
P
O
4
3
5a-5d
O
O
5a
5b
5c
5d
: δ 150.74 (s, 2P) ppm.
O
O
O
O
=
δ
δ
δ
:
:
:
149.37 (s, 2P) ppm.
145.17 (s, 2P) ppm.
142.75 (s, 2P) ppm.
ax
ax
: (R) 4b: (S)ax
4c
4a
: (R) 4d: (S)ax
Scheme 1. The synthesis of diphosphite ligands derived from (1R,2R)-trans-1,2-
cyclohexanediol.

Z.-b. Pang et al. / Tetrahedron: Asymmetry 26 (2015) 1389–1393
1391
Table 1
With the optimized reaction conditions in hand, the hydrogena-
tion of a variety of -dehydroamino acid esters were carried out
The effect of ligand structures and solvents on the enantioselectivity for the
a
hydrogenation of a
-dehydroamino acid estersa
using [Rh(cod)2]BF4/5b as the catalyst. As shown in Figure 2, it
can be seen that methyl 2-benzamido-3-phenylpropanoate was
obtained with 93% ee. The hydrogenation appeared to be insensi-
tive to the position of the substituent on the phenyl ring, and good
enantioselectivities (mostly over 90% ee) were observed for the
hydrogenation of substrates 6c–6h. Moreover, the enantioselectiv-
ity was also hardly affected by the presence of either electron-
donating or electron-withdrawing groups on the phenyl ring, for
example see substrates 6e, 6h–6k. Methyl 2-acetamidoacrylate 6l
was also examined and up to 92% ee was achieved.
COOMe
COOMe
[Rh(cod)2]BF4
*
H2, 25 oC, CH2Cl2
NHCOCH3
NHCOCH3
6a
7a
Entry
Ligands
Solvent
Conv.b (%)
eeb (%) (conf.)
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5b
5b
5b
5b
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
Et2O
Toluene
Hexane
100
100
100
100
41
6
80
n.d.
22 (S)
92 (R)
5 (S)
86 (R)
8 (R)
92 (R)
90 (R)
n.d.
2.3. Asymmetric hydrogenation of dimethyl itaconate
In order to further investigate the catalytic performance of this
catalytic system, we tested it in the Rh-catalyzed asymmetric
hydrogenation of dimethyl itaconate. The results are summarized
in Table 3. In general the results followed the same trend as
a
[Rh(cod)2]BF4 (0.0025 mmol), ligand/Rh = 1.1, substrate/Rh = 100, p(H2) 10 atm,
CH2Cl2 (3 mL), 25 °C, t = 6 h.
b
The data on the conversion and enantiomeric excess were measured by GC with a
Chirasil-
L
-Val column (25 m ꢀ 0.25 mm ꢀ 0.25 lm film thickness). The absolute
configuration of the products was determined by comparison with authentic samples.
Table 3
Rh-catalyzed asymmetric hydrogenation of dimethyl itaconatea
In addition, an obvious effect of the solvent on the reaction was
observed. Using THF as the solvent gave poor enantioselectivity
(Table 1, entry 5). Up to 92% ee (R) but only 6% conversion for 7a
was achieved when the reaction was carried out in Et2O, and the
poor solubility in Et2O of substrate 6a may give rise to this result
(Table 1, entry 6). Both good activity and enantioselectivity were
received when using toluene as the solvent (Table 1, entry 7). Hex-
ane was proven to be the worst solvent for this reaction (Table 1,
entry 8). In conclusion, CH2Cl2 was screened as the most appropri-
ate solvent in terms of both conversion and selectivity in our cases.
The effect of other reaction parameters, such as pressure of H2,
the ratio of L./Rh, reaction temperature, and catalyst loading, was
also investigated. No obvious change of enantioselectivity was seen
when increasing the pressure of H2 from 5 atm to 30 atm (Table 2,
entries 1 and 2 vs Table 1, entry 2). The addition of one fold excess
of ligand did not affect the outcome of the reaction (Table 2, entry
3). There was no change in the enantioselectivity when lowering
the reaction temperature to 5 °C (Table 2, entry 4). Up to 90% ee
was also achieved when the catalyst loading was decreased to
0.02 mol % (TON = 5000), which indicates that no decomposition
of catalyst took place (Table 2, entry 8).5b For practical terms,
this allowed us to perform the reaction at lower catalyst
concentration without loss in activity or enantioselectivity.
[Rh(cod)2]BF4, ligands
COOMe
COOMe
solvent, 25 oC, H2(10 atm)
MeOOC
MeOOC
9
8
Entry Ligands Sub./
Rh
p(H2) (atm) t (h) Conv.b (%) eeb (%) (conf.)
1
2
3
4
5
6
7
5a
5b
5c
5d
5b
5b
5b
100
100
100
100
100
5000
10,000
10
10
10
10
2.5
30
30
6
6
6
6
1
6
100
100
100
100
100
100
48 (R)
99 (S)
3 (R)
99 (S)
99 (S)
99 (S)
97 (S)
24 100
a
[Rh(cod)2]BF4 (0.0025 mmol), ligand/Rh = 1.1, substrate/Rh = 100, p(H2) 10 atm,
CH2Cl2 (3 mL), 25 °C, t = 6 h.
b
The data on the conversion and enantiomeric excess were measured by GC with a
gamma-DEX 225 column (30 m ꢀ 0.25 mm ꢀ 0.25
lm film thickness). The absolute
configurationoftheproductswas determinedbycomparisonwithauthenticsamples.
observed for the hydrogenation of 6a. Again, the highest enantios-
electivity (ee values up to 99%) was obtained when [Rh(cod)2]
BF4/5b was used (Table 3, entry 2). Ligand 5d also showed excel-
lent asymmetric induction ability as compared to ligand 5b
(Table 3, entry 4). In fact, this reaction can be completely reacted
within 1 h under 2.5 atm of H2. Moreover, up to 97% ee was still
attained although the value of TON reached 10,000 (Table 3, entry
7). It is worth mentioning that compared with substrates 6a–6k,
products with the opposite configuration were synthesized when
substrate 8 was used.
Table 2
Effect of other factors on the enantioselectivity for the hydrogenation of
a-
dehydroamino acid estersa
COOMe
COOMe
[Rh(cod)2]BF4, 5b
H2, CH2Cl2
*
NHCOCH3
NHCOCH3
6a
7a
2.4. Asymmetric hydrogenation of enamides
Entry Sub./Rh L./Rh p(H2) (atm) t (h) Conv.b (%) eeb (%) (conf.)
Enamides are important substrates for synthesis of optically
active secondary amines, which are useful building blocks for the
synthesis of fine chemicals.5b We subsequently applied ligands
5a–5d in the Rh-catalyzed asymmetric hydrogenation of several
enamides. Ligand 5b also proved to be effective for this reaction
using N-(1-phenylvinyl)acetamide 10a as the substrate (Table 4,
entries 1–4).
1
2
3
4c
5
6
7
8
100
100
100
100
100
50
1.1
1.1
2
1.1
1.1
1.1
1.1
1.1
5
30
10
10
10
10
30
30
6
6
6
6
2
6
100
100
100
100
100
100
92 (R)
91 (R)
90 (R)
92 (R)
91 (R)
91 (R)
91 (R)
90 (R)
1000
5000
12 100
24 100
No significant changes in catalytic performance were observed
when changing the hydrogen pressure and reaction temperature
(Table 4, entries 7–9). The Rh-catalyzed asymmetric hydrogena-
tion of other enamides was also assessed. Up to 99% ee for
a
[Rh(cod)2]BF4 (0.0025 mmol), CH2Cl2 (3 mL).
The data on conversion, the enantiomeric excess, and the absolute configura-
b
tion of the product were determined by the same condition as noted in Table 1.
c
Reaction carried out at 5 °C.

1392
Z.-b. Pang et al. / Tetrahedron: Asymmetry 26 (2015) 1389–1393
Table 4
85% H3PO4 as an external reference. Proton chemical shifts (d) and
coupling constants (J) are reported in ppm and Hz, respectively.
Spin multiplicities were given as s (singlet), d (doublet), t (triplet),
and m (multiplet). HRMS were recorded on a Bruker microTOF-QII
mass instrument. All the melting points were determined on an X-
4 melting point apparatus and are uncorrected. Optical rotations
were measured on a Perkin–Elmer 241 MC polarimeter at 20 °C.
All non-aqueous reactions and manipulations were performed
under an N2 atmosphere with standard Schlenk techniques. Reac-
tions were monitored by thin layer chromatography (TLC, silica
gel GF254 plates). Column chromatography separations were con-
ducted on silica gel (200–300 mesh). NEt3, THF, Et2O, hexane, and
toluene were distilled with Na and benzophenone as an indicator,
and CH2Cl2 was dried over CaH2 before use. H8-binaphthol was
prepared according to a literature procedure.13 All the other chem-
icals were obtained commercially and used without further
purification.
The Rh-catalyzed asymmetric hydrogenation of enamidesa
[Rh(cod)2]BF4, ligands
solvent, H2
NHAc
NHAc
R
R
11a:
10a:
R=H
R=H
11b: R=F
10b: R=F
10c: R=Cl
11c:
11d:
11e: R=Me
R=Cl
R=Br
10d:
10e: R=Me
R=Br
Entry Ligands Substrates Solvents p(H2)
Conv.b
(%)
eec (%)
(conf.)
(atm)
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5b
5b
5b
5b
5b
5b
5b
5b
5b
10a
10a
10a
10a
10a
10a
10a
10a
10a
10b
10c
10d
10e
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene 10
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
10
10
10
10
100
100
100
100
100
18
100
100
100
100
100
100
100
33 (S)
91 (R)
15 (S)
87 (R)
17 (R)
78 (R)
91 (R)
91 (R)
91 (R)
99 (R)
99 (R)
99 (R)
81 (R)
10
5
4.2. Synthesis of ligands 5a–5d
30
10
10
10
10
10
9d
10
11
12
13
4.2.1. (1R,2R)-Bis[(R)-1,10-binaphthyl-2,20-diyl]phosphitecyclo-
hexanediol 5a
To a 100 mL Schlenk flask equipped with a condenser were
added 2.0 g of (R)-binaphthol, 20 mL of toluene, and 12 mL of
PCl3. Under a nitrogen atmosphere, the mixture was refluxed for
20 h. After removal of the excess PCl3 and toluene, the residue
was dissolved in 20 mL of toluene, and then was transferred to
another Schlenk flask, and toluene was removed in vacuo to obtain
(R)-1,10-binaphthyl-2,20-diyl-chlorophosphite 4a as a white pow-
der, which was used directly in the following step without further
a
[Rh(cod)2]BF4 (0.0025 mmol), ligand/Rh = 1.1, substrate/Rh = 100, solvent
(3 mL), 25 °C, t = 6 h.
b,c
The data on the conversion were measured by GC with a AT FFAP column
(30 m ꢀ 0.25 mm ꢀ 0.25
l
m film thickness), and enantiomeric excess was mea-
m film
sured by GC with a CP-Chirasil-DEX CB column (25 m ꢀ 0.25 mm ꢀ 0.25
l
thickness). The absolute configuration of the products was determined by com-
parison with authentic samples.
d
Reaction carried out at 5 °C.
purification. To
a stirred solution of compound 3 (77.6 mg,
0.67 mmol), compound 4a (507.5 mg, 1.45 mmol), and 4-dimethy-
laminopyridine (DMAP) (17.7 mg, 0.15 mmol) in THF (10 mL) at
ꢁ15 °C, NEt3 (0.32 mL) was slowly added using a syringe over
2 min, after which the solution was stirred for 0.5 h at ꢁ15 °C.
The mixture was then stirred at room temperature for 1 h. Next,
THF was distilled off in vacuo, and toluene (20 mL) was added.
The solid was removed by filtration through a pad of silica gel,
and the solvent was removed under reduced pressure. The residue
was purified by flash chromatography (Rf = 0.48, n-hexane/
THF = 3:1), to furnish ligand 5a as a white foamy solid (223.2 mg,
N-[1-(4-fluorophenyl)ethyl]acetamide 11b, N-[1-(4-chlorophenyl)
ethyl]acetamide 11c and N-[1-(4-bromophenyl)ethyl]acetamide
11d were obtained (Table 4, entries 10–12). These results show
that the enantioselectivity is affected by the presence of electron-
withdrawing groups at the para positions of the aryl group.
3. Conclusion
In conclusion, we have described the application of novel
diphosphite ligands in the asymmetric hydrogenation reaction.
These ligands can be easily prepared in a few steps from commer-
cial (1R,2R)-trans-1,2-cyclohexanediol as a chiral source and the
NMR data were consistent with the expectation for these ligands.
Regarding both the good activity and the excellent enantioselectiv-
ity (up to 99% ee) obtained in the Rh-catalyzed asymmetric hydro-
44.77% yield). [
a]
20 = ꢁ499 (c 0.15, CH2Cl2); mp 132–133 °C; 1H
D
NMR (400 MHz, DMSO-d6) d 8.14 (d, J = 8.8 Hz, 2H, Ar), 8.06 (d,
J = 8.2 Hz, 4H, Ar), 7.99 (d, J = 8.8 Hz, 2H, Ar), 7.47–7.57 (m, 6H,
Ar), 7.44 (d, J = 8.8 Hz, 2H, Ar), 7.35 (dd, J = 15.6, 8.0 Hz, 4H, Ar),
7.25–7.29 (m, 2H, Ar), 7.22 (s, 2H, Ar), 4.17 (m, 2H, CH), 2.14 (t,
J = 12.0 Hz, 2H, CH2), 1.62 (s, 2H, CH2), 1.47 (d, J = 10.0 Hz, 2H,
CH2), 1.17–1.27 (m, 2H, CH2) ppm. 13C NMR (101 MHz, DMSO-d6)
d 147.94, 147.34, 132.46, 132.17, 131.58, 131.28, 131.09, 130.36,
129.08, 128.93, 127.13, 126.98, 126.39, 126.34, 125.72, 125.68,
124.02, 123.97, 122.45, 121.95, 77.56, 77.39, 32.75, 23.30 ppm.
31P NMR (162 MHz, DMSO-d6) d 150.74 ppm. HRMS (ESI+): calcd
for C46H34NaO6P2 [M+Na]+ 767.1723; found: 767.1725.
genations of
a,b-unsaturated carboxylic acid derivatives and
enamides, it can be demonstrated that the stereochemically
matched combination of (1R,2R)-trans-cyclohexanediol backbone
and (S)-binaphthyl in the ligand (1R,2R)-bis[(S)-1,10-binaphthyl-
2,20-diyl]phosphitecyclohexane-diol was essential for inducing
high enantioselectivity. The sense of enantiodiscrimination of
products was predominately determined by the configuration of
the biaryl moieties of ligands 5a–5d. The application of these
ligands to other transition metal-catalyzed asymmetric reactions
is ongoing in our laboratory.
4.2.2. (1R,2R)-Bis[(S)-1,10-binaphthyl-2,20-diyl]phosphitecyclo-
hexanediol 5b
(S)-1,10-Binaphthyl-2,20-diyl-chlorophosphite 4b was synthe-
sized by the same procedure as that of 4a, and was used directly
without further purification. Treatment of compound 3 (77.6 mg,
0.67 mmol), 4b (507.5 mg, 1.45 mmol), and DMAP (17.7 mg,
0.15 mmol) as described for the synthesis of ligand 5a afforded
ligand 5b, which was purified by flash chromatography (Rf = 0.53,
n-hexane/THF = 3:1) to produce a white solid (175.1 mg, 49.13%
4. Experimental section
4.1. General
NMR spectra were recorded on Bruker 300 MHz or Bruker
400 MHz spectrometers. 1H and 13C NMR spectra were reported
in parts per million with TMS (d = 0.00 ppm) as an internal stan-
dard. 31P NMR spectra were reported in parts per million with
yield). [
(400 MHz, DMSO-d6)
J = 8.2 Hz, 2H, Ar), 7.99 (t, J = 8.0 Hz, 4H, Ar), 7.57 (d, J = 8.8 Hz,
a]
D
20 = +180 (c 0.18, CH2Cl2); mp 138–139 °C; 1H NMR
d
8.14 (d, J = 8.8 Hz, 2H, Ar), 8.06 (d,

Z.-b. Pang et al. / Tetrahedron: Asymmetry 26 (2015) 1389–1393
1393
2H, Ar), 7.52–7.41 (m, 6H, Ar), 7.30 (t, J = 7.6 Hz, 4H, Ar), 7.22–7.18
(m, 4H, Ar), 4.28 (s, 2H, CH), 1.89 (d, J = 12.2 Hz, 2H, CH2), 1.59–
1.36 (m, 4H, CH2), 1.20 (s, 2H, CH2) ppm. 13C NMR (100 MHz,
the reaction mixture was passed through a short silica gel column
to remove the catalyst. After evaporation of the solvent under
reduced pressure, the residue was purified by flash chromatogra-
phy on silica gel. The data on conversion and enantiomeric excess
of the product were determined by GC with a gamma-DEX 225 col-
DMSO-d6)
d 148.06, 147.31, 132.45, 132.16, 131.56, 131.20,
131.08, 130.44, 129.04, 128.92, 127.08, 126.95, 126.40, 126.34,
125.67, 125.49, 123.87, 123.82, 122.10, 122.02, 77.12, 76.98,
31.95, 22.61 ppm. 31P NMR (161 MHz, DMSO-d6) d 149.37 ppm.
HRMS (ESI+): calcd for C46H34NaO6P2 [M+Na]+ 767.1723; found:
767.1732.
umn (30 m ꢀ 0.25 mm ꢀ 0.25
column (25 m ꢀ 0.25 mm ꢀ 0.25
rasil-DEX CB column (25 m ꢀ 0.25 mm ꢀ 0.25
m film thickness). The abso-
l
m film thickness) or Chirasil-
m film thickness) or CP-Chi-
m film thickness)
L-Val
l
l
or AT FFAP (30 m ꢀ 0.25 mm ꢀ 0.25
l
lute configuration was determined by comparison with authentic
4.2.3. (1R,2R)-Bis[(R)-1,10-H8-binaphthyl-2,20-diyl]phosphitecyclo-
hexanediol 5c
samples.
(R)-1,10-H8-Binaphthyl-2,20-diyl-chlorophosphite 4c was syn-
thesized by the same procedure as that of 4a, and was used directly
without further purification. Treatment of compound 3 (77.6 mg,
0.67 mmol), 4c (530.0 mg, 1.48 mmol), and DMAP (17.7 mg,
0.15 mmol) as described for the synthesis of ligand 5b afforded
ligand 5c, which was purified by flash chromatography (Rf = 0.77,
Acknowledgment
We are grateful for the financial support of this work by the
National Natural Science Foundation of China (Nos. 20773147,
21073211, and 21174155).
n-hexane/toluene = 1:1) to produce
a white solid (185.1 mg,
20 = ꢁ153 (c 0.11, CH2Cl2); mp 91–92 °C; 1H
References
46.34% yield). [
a
]
D
NMR (400 MHz, DMSO-d6) d 7.13 (d, J = 8.0 Hz, 2H, Ar), 7.06 (d,
J = 8.0 Hz, 2H, Ar), 6.98 (d, J = 8.0 Hz, 2H, Ar), 6.84 (d, J = 8.0 Hz,
2H, Ar), 4.04 (s, 2H, CH), 2.85–2.70 (m, 8H, CH2), 2.69–2.56 (m,
4H, CH2), 2.13 (ddd, J = 28.0, 16.8, 8.2 Hz, 6H, CH2), 1.81–1.67 (m,
12H, CH2), 1.63 (s, 2H, CH2), 1.57–1.30 (m, 8H, CH2) ppm. 13C
NMR (100 MHz, DMSO-d6) d 146.32, 145.82, 137.30, 135.01,
133.83, 129.87, 129.41, 127.76, 119.38, 119.07, 77.17, 76.97,
32.78, 28.86, 27.72, 27.59, 23.41, 22.50, 22.41, 22.39, 22.28 ppm.
31P NMR (161 MHz, DMSO-d6) d 145.17 ppm. HRMS (ESI+): calcd
for C46H50NaO6P2 [M+Na]+ 783.2975; found: 767.2947.
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4.2.4. (1R,2R)-Bis[(S)-1,10-H8-binaphthyl-2,20-diyl]phosphitecyclo-
hexanediol 5d
(S)-1,10-H8-Binaphthyl-2,20-diyl-chlorophosphite 4d was syn-
thesized by the same procedure as that of 4a, and was used directly
without further purification. Treatment of compound 3 (64.9 mg,
0.56 mmol), 4d (500.0 mg, 1.40 mmol), and DMAP (17.1 mg,
0.14 mmol) as described for the synthesis of ligand 5b afforded
ligand 5d, which was purified by flash chromatography (Rf = 0.45,
n-hexane/toluene = 2:1) to produce
a white solid (132.7 mg,
41.16% yield). [
a]
20 = +170 (c 0.10, CH2Cl2); mp 105–106 °C; 1H
D
NMR (400 MHz, DMSO-d6) d 7.13 (s, 2H, Ar), 7.06 (dd, J = 17.6,
8.2 Hz, 4H, Ar), 6.89 (d, J = 7.4 Hz, 2H, Ar), 4.16 (s, 2H, CH), 2.77
(s, 8H, CH2), 2.59 (s, 4H, CH2), 2.11 (d, J = 10.6 Hz, 6H, CH2), 1.72
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127.81, 119.43, 119.12, 77.22, 77.02, 32.83, 28.91, 27.77, 27.64,
23.46, 22.55, 22.46, 22.44, 22.33 ppm. 31P NMR (161 MHz,
DMSO-d6) d 142.75 ppm. HRMS (ESI+): calcd for C46H50NaO6P2 [M
+Na]+ 783.2975; found: 767.3002.
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After stirring a solution of [Rh(cod)2]BF4 (0.0025 mmol) and
ligand 5b (0.00275 mmol) in degassed CH2Cl2 (1 mL) at room tem-
perature for 1 h,
a solution of the corresponding substrate
(0.25 mmol) in degassed CH2Cl2 (2 mL) was added. The mixture
was transferred via syringe into a stainless autoclave that had been
previously purged with argon. The hydrogenation was carried out
in the autoclave at room temperature for 6 h. After releasing H2,