Readily available and recoverable chiral ionic phosphite ligands for the highly enantioselective hydrogenation of functionalized olefins

Article abstract of DOI:10.1016/j.tetasy.2011.04.011

A series of novel ionic phosphite ligands bearing carbohydrate groups were conveniently synthesized and successfully applied in the asymmetric hydrogenation of enamides, α-dehydroamino acid esters, and dimethyl itaconate. High efficiency and excellent reu

Full text of DOI:10.1016/j.tetasy.2011.04.011

Tetrahedron: Asymmetry 22 (2011) 769–774
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Readily available and recoverable chiral ionic phosphite ligands for the
highly enantioselective hydrogenation of functionalized olefins
Yingwei Zhao a, Hanmin Huang a,b, , Jianping Shao a, Chungu Xia a,
⇑
⇑
a State Key Laboratory of Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 March 2011
Accepted 11 April 2011
A series of novel ionic phosphite ligands bearing carbohydrate groups were conveniently synthesized and
successfully applied in the asymmetric hydrogenation of enamides,
a-dehydroamino acid esters, and
dimethyl itaconate. High efficiency and excellent reusability were obtained in an ionic liquid–toluene
biphasic system.
Ó 2011 Elsevier Ltd. All rights reserved.
Matched
monophosphite
1. Introduction
O
O
Ph
Ph
O
O
P
O
O
Ph
Ph
ClP
The reutilization of chiral catalysts and reaction media is very
important for developing sustainable chemistry.1,2 Among the
many strategies developed,3–8 catalytic reactions carried out in
ionic liquid or ionic liquid–organic solvent biphasic system is a
promising approach toward achieving this goal, which has received
considerable attentions both from academia and industry.9–12 To
achieve higher efficiency for this method, making the structure of
the catalysts similar to that of the ionic liquids is needed in order
to improve the immobilization of catalysts in ionic liquids, accord-
ing to the theory of similarity and intermiscibility. The direct ap-
proach to this problem is to incorporate an ionic tag to the parent
catalyst structure,13–20 which has been successfully applied in
asymmetric hydrogenations. Lee et al. introduced an imidazolium
moiety onto a 1,4-bisphosphine ligand and obtained good results
in recyclable asymmetric hydrogenations.21 Similar work was also
carried out by Reetz,22 Blaser,23 and others.24–27 However, only a
few good catalysts could be recycled more than ten times with no
or minimal loss of activity.23,28 Moreover, the synthetic procedure
for most of the reported ionic ligands was tedious and their catalytic
efficiencies were often inferior to those of non-ionic ones.25,29
Several years ago, one of us synthesized a series of monopho-
sphite ligands based on carbohydrates, which exhibited high effi-
ciency in asymmetric hydrogenations.30 The hydroxyl groups
contained in the backbone of these ligands inspired us to incorpo-
rate ionic tags on them and thus make them more convenient and
tunable. Moreover, since no major change was exerted on the
backbone, excellent performance in asymmetric hydrogenation
could be expected (Scheme 1).
O
O
O
O
O
O
O
O
HO
HO
N
R
N
-
N
R
N
BF4
-
BF4
Carbohydrate
Highly efficient
and reusable catalyst
Tunable
ionic tag
containing -OH
Scheme 1. Design of the ionic tagged chiral phosphite ligands.
2. Results and discussion
A facile synthetic route for chiral ionic monophosphites 1a–1e
is outlined in Scheme 2. Starting from the readily available -man-
D
nitol, chiral diol 3 was conveniently obtained according to the re-
ported method.31 Selective mono-O-alkylation of the chiral diol 3
was successfully controlled to give 4 in moderate yield. Quaterna-
rization of N-alkylimidazole with 4 afforded chiral alcohol 5, which
was then subjected to anion-exchange with NaBF4 to give com-
pound 6. The reaction of (R)-BINOL-derived chlorophosphite with
6 in the presence of pyridine led to ionic chiral phosphites 1a–1e
[our previous work has demonstrated that the (R)-BINOL matched
cooperatively to the corresponding
D-mannitol-derived back-
bone30]. Using a similar procedure, chiral biphosphite 1f was also
successfully obtained (see Section 4.4). The corresponding rhodium
complexes were obtained through the reaction of the chiral ionic
ligands with [Rh(COD)2]BF4 at room temperature. All of the com-
plexes and ligands were air-stable and fully characterized. They
are insoluble in hexane, ether, ethyl acetate, and toluene, but
soluble in CH2Cl2, THF, and other commonly used ionic liquids.
⇑
Corresponding authors. Tel.: +86 931 4968326; fax: +86 931 4968129.
E-mail addresses: hmhuang@licp.cas.cn (H. Huang), cgxia@licp.cas.cn (C. Xia).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.04.011

770
Y. Zhao et al. / Tetrahedron: Asymmetry 22 (2011) 769–774
R2
O
Ph
Ph
CH2OH
H
O
Ph
R1
HO
HO
H
O
O
N
N
O
O
HO
H
PhCHO
NaH, Br(CH2)nBr
HO
HO
O
n
OH
H2SO4
DMF, rt, 3 days
32%
DMF, rt, 24 h
34%-42%
ethyl acetate
reflux, 48 h
80%-91%
H
OH
Br
O
CH2OH
O
3
Ph
4a, n = 4
4d, n = 6
4e, n = 12
4
2
O
O
Ph
Ph
O
Ph
O
O
O
HO
P
Cl
O
O
HO
O
n
O
n
NaBF4
O
N
N
R2
MeCN, rt, 24 h
75%-91%
N
R2
O
Ph
pyridine, CH2Cl2, rt, 12 h
33%-55%
Br
N
R1
BF4
R1
5
6
O
O
Ph
Ph
O
O
Ph
Ph
O
O
O
O
P
O
O
n
O
P
O
O
O
Ph
O
N
N
O
O
O
N
BF4
BF4
R2
O
N
R1
O
O
P
O
O
1
Ph
O
5a, 6a and 1a, R1 = Me, R2 = H, n = 4
5b, 6b and 1b, R1 = Me, R2 = Me, n = 4
5c, 6c and 1c, R1 = n-Bu, R2 = H, n = 4
5d, 6d and 1d, R1 = Me, R2 = H, n = 6
5e, 6e and 1e, R1 = Me, R2 = H, n = 12
1f
Scheme 2. Synthesis of ionic monophosphites.
which were the same reaction conditions previously used for the
parent ligands;30 the results are summarized in Table 1. It was
found that all the ionic catalysts showed high activities (100% con-
versions were obtained in 1 h) and excellent enantioselectivities
(99% or >99% ee). These results indicated that the ionic tag moiety
has no significant effect on the conformations of native ligands or
transition states in Rh-catalyzed reactions. To explore the general
utilities of these ionic ligands, we employed one of the ionic li-
gands 1d in the asymmetric hydrogenation of a variety of ena-
mides under the same reaction conditions. Uniformly excellent
enantioselectivities (over 99% ee) were obtained in producing the
corresponding chiral amines from all of the substituted enamides
with different electronic properties 7b–7f (Table 1, entries 7–11).
The efficacy of these types of ligands for the hydrogenation of
enamides encouraged us to examine other functionalized olefins.
The catalyst precursor with these ionic ligands produced high ee
Table 1
a
Asymmetric hydrogenation of enamides in CH2Cl2
1 mol% [Rh(COD)L2]BF4
+
H2
Ar
NHAc
Ar
NHAc
CH2Cl2
7
8
Entry
Ar (substrate)
Ligand
Eeb (%)
1
2
3
4
5
6
7
8
Ph 7a
Ph 7a
Ph 7a
Ph 7a
Ph 7a
Ph 7a
4-BrC6H4 7b
4-FC6H4 7c
4-ClC6H4 7d
4-MeOC6H4 7e
2-Naphthyl 7f
1a
1b
1c
1d
1e
1f
1d
1d
1d
1d
1d
>99
>99
>99
>99
>99
99
>99
>99
>99
>99
>99
9
10
11
values for
With ligand 1d, excellent enantioselectivities (92–99% ee) were ob-
served for almost all -dehydroamino acid esters 9a–9f tested
a-dehydroamino acid ester 9a (Table 2, entries 1–6).
a
a
Enamide 0.25 mmol; [Rh(COD)L2]BF4 0.0025 mmol; H2 pressure: 10 atm; rt;
here, which bear different substituents in the phenyl ring, indicat-
ing their minimal electronic effects. Furthermore, dimethyl itaco-
nate (11) was also applicable for this catalyst system, with full
conversion and an ee value of up to 98% being obtained by employ-
ing the catalyst precursor containing ligand 1d (Scheme 3).
Encouraged by these preliminary results, we then turned our
attention to the role of the ionic moiety in the reusability of the
catalysts derived from these ionic ligands. The reactions were per-
formed in an ionic liquid [bmim][BF4]/toluene ([bmim]+ = 1-
reaction time: 1 h; CH2Cl2: 1 mL; 100% conversions obtained in all cases.
b
Ee values were determined by GC with CP-Chiralsil Dex CB column and the
absolute configuration was assigned as (S) by comparison of the specific rotation
with reported data.32
With these ligands in hand, we first examined their catalytic
performance on the asymmetric hydrogenation of N-acetylpheny-
lethenamine 7a with CH2Cl2 as the solvent under 10 atm of H2,

Y. Zhao et al. / Tetrahedron: Asymmetry 22 (2011) 769–774
771
Table 2
Asymmetric hydrogenation of
Table 3
a
a
-dehydroamino acid esters in CH2Cl2
Asymmetric hydrogenation of an enamide in [bmim][BF4]/toluene biphasic solvent
systema
R
R
1 mol% [Rh(COD)L2]BF4
1 mol% [Rh(COD)L2]BF4
+
H2
NHAc
H2
NHAc
+
CH2Cl2
[bmim][BF4]/toluene
AcHN
COOMe
AcHN
COOMe
7a
8a
9
10
Run
Conversionb (%)/eec (%)
Entry
R (substrate)
4-Cl 9a
4-Cl 9a
4-Cl 9a
4-Cl 9a
4-Cl 9a
4-Cl 9a
4-Me 9b
2-Cl 9c
Ligand
Eeb (%)
L = 1a
L = 1b
L = 1c
L = 1d
L = 1e
L
2 = 1f
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1d
1d
1d
1d
1d
97
97
94
97
94
96
98
92
99
96
96
1
2
3
4
5
6
7
100/>99
100/98
100/97
100/97
100/96
99/96
100/98
100/97
96/94
95/93
92/91
82/90
77/89
100/>99
100/>99
89/99
63/98
46/97
100/>99
100/99
100/99
100/98
100/98
99/97
100/95
100/93
100/91
100/92
98/87
100/98
100/97
84/95
67/90
57/88
46/83
39/81
37/95
94/85
90/83
94/93
28/94
97/97
9
10
11
4-MeO 9d
2-MeO 9e
3-MeO 9f
a
Enamide 0.25 mmol; [Rh(COD)L2]BF4 0.0025 mmol; [bmim][BF4]/toluene =
1 mL/1 mL; H2: 40 atm; rt; reaction time: 1 h;
b
Conversions were determined by GC using AT FFAP column.
Ee values were determined by GC with CP-Chiralsil Dex CB column.
a
c
a-Dehydroamino acid ester 0.25 mmol; [Rh(COD)L2]BF4 0.0025 mmol; H2
pressure: 10 atm; rt; reaction time: 1 h; CH2Cl2: 1 mL; 100% conversions obtained
in all cases.
b
Ee values were determined by chiral GC using CP-Chiralsil Dex CB column or by
To rationalize the deactivation of the catalyst during the recycle,
we checked catalyst leaching by ICP-AES analysis of the toluene
layers, which were separated from the first run. For these chiral li-
gands, nearly no leaching of the Rh catalysts (<0.1%) was observed,
indicating their good immobilization in the ionic liquid. These re-
sults together with the preliminary investigation on the ligand
structure/enantioselectivity/reusability relationship shown in
Table 3 indicate that a possible reason for the catalyst deactivation
may be due to some contamination with oxygen during the recy-
cling of the catalyst, which means that the ligands which have a
high affinity for the ionic liquid should be better protected against
reaction with oxygen.23
To further improve the reusability of these ionic tagged chiral
catalysts, the reactions were also carried out in two other com-
monly used ionic liquids using toluene as a co-solvent. The results
in Table 4 show that the observed reusability of the catalyst was
again sensitive to the structure of the cations contained in the li-
gands, which further confirmed that structure similarity between
the ionic tag of the chiral catalyst and the ionic liquid media used
in the reaction is crucial for the reutilization of the catalyst. The
best reusability was observed when using ionic liquid [bmim][PF6]
as the reaction media, in which the reusability of the Rh-catalyst
derived from ligand 1d was further enhanced compared to the
reaction performed in [bmim][BF4]: 95% conversion and 97% ee
were still obtained in the tenth run. Prolonging the reaction time
would further increase the reusability and prevent the decrease
of the conversions in the next two runs and only a slight loss of
enantioselectivity was observed.
HPLC using Chiralcel OJ-H column and the absolute configuration was assigned as
(S) by comparison of the specific rotation with reported data.33
H
2 (10 atm)
CO2Me
CO2Me
MeO2C
MeO2C
1 mol% [Rh(COD)(1d)2]BF4
11
CH2Cl2, rt, 1 h
12
98% ee
Scheme 3. Asymmetric hydrogenation of dimethyl itaconate in CH2Cl2.
methyl-3-butylimidazolium) biphasic system and after completion
of the hydrogenation, the toluene layer was separated automati-
cally from the ionic liquid layer. Simple extraction under an Ar
atmosphere afforded the products and the catalyst remaining in
the ionic liquid layer was then directly subjected to the next
catalytic reaction to examine the reusability.
The results are summarized in Table 3 and show that the ionic
tagged chiral monophosphites are efficient ligands for reutilization
in asymmetric hydrogenation. However, the reusability proved to
be significantly influenced by the structure of the ionic tag moiety.
A comparison of the results in Table 3 shows that the reusability
depends strongly on the structure of the cation contained in the
chiral ligands. In general, N-methylimidazolium cation tagged li-
gands 1a and 1d demonstrated better reusability than ligands 1b
and 1c with 1,2-dimethylimidazolium and N-butylimidazolium
as the cation, respectively. We speculated that the structures of
the ionic ligands containing N-methylimidazolium cations 1a and
1d are more similar to that of ionic liquid [bmim][BF4], which
showed a higher affinity of these ligands with the ionic liquid,
and thus displayed good reusability. On the other hand, the length
of the alkyl-chain (n), which links the cationic tag and the ligand
backbone, also affects the reusability of ionic catalysts. It seems
that longer alkyl-chains are better, for example, the results ob-
tained by 1d (n = 6) are better than those of 1a (n = 4). However,
increasing the length of alkyl-chain of the methylene group to 12
(ligand 1e) led to a significant catalytic efficiency decrease, which
suggests that if the long alkyl-chain is too long, it might weaken
the immobilization ability of the ionic ligand in ionic liquids. The
reusability of the ionic tagged biphosphite 1f is lower, and which
could only be recycled twice. With ligand 1d, the best reusability
was observed (it could be recycled seven times with only a slight
loss of enantioselectivity).
3. Conclusion
In conclusion, we have designed and synthesized a series of io-
nic monophosphite ligands based on
applied them in the Rh-catalyzed asymmetric hydrogenation of
enamides, -dehydroamino acid esters and dimethyl itaconate.
D-mannitol and successfully
a
These ionic tagged monophosphites have the advantages of being
readily available and can be easily recovered from the reaction
mixture, and can be recycled more than ten times in the biphasic
system without a significant loss of catalytic efficiency. The pro-
nounced effect of the ionic tags in these ligands on the reusability
of catalysts indicates that the structural similarity between the io-
nic tag of the chiral catalyst and the ionic liquid media is crucial for
improving the reusability.

772
Y. Zhao et al. / Tetrahedron: Asymmetry 22 (2011) 769–774
7.48–7.52 (m, 4H). 13C NMR (100 MHz, CDCl3): d 28.7, 29.5, 33.4,
33.4, 60.3, 67.5, 69.6, 71.2, 78.8, 101.2, 101.3, 126.2, 126.2, 128.2,
Table 4
Asymmetric hydrogenation of an enamide in ionic liquid/toluene biphasic solvent
systema
128.9, 129.0, 137.6, 137.7. HRMS: Calcd: for
C24H29BrO6Na
([M+Na]+) 515.1040 and 517.1021. Found: 515.1045 and 517.1032.
The synthetic procedures for 4d and 4e are similar to that of 4a.
1 mol% [Rh(COD)(1d)2]BF4
H2
NHAc
NHAc
+
ionic liquid/toluene
4.3. 1-(4-((4R,40R,5R,50R)-50-Hydroxy-2,20-diphenyl-4,40-bi(1,3-
dioxan)-5-yloxy)butyl)-3-methyl-1H-imidazol-3-ium bromide
8a
7a
5a
Run
Conversionb (%)/eec (%)
[bmmim][BF4]d
[bmim][BF4]
[bmim][PF6]
The chiral alcohol 4a (6 mmol), N-methylimidazole (12 mmol),
and ethyl acetate (20 mL) were heated at reflux with stirring for
48 h. Upon cooling, the precipitate was filtered off, washed with
ether (3 ꢂ 10 mL), and dried in vacuum to give 5a as white foam-
1
2
3
4
5
6
7
8
100/>99
100/99
100/99
100/98
100/98
99/97
97/97
96/94
ND
100/99
99/98
99/98
99/97
99/97
97/96
91/95
84/94
ND
100/>99
100/>99
100/>99
100/99
100/99
100/98
100/98
99/98
98/97
95/97
95/96
96/94
like solid. Yield: 86%, mp 73–76 °C. ½a D25
¼ ꢁ22:1 (c 1.00, CH2Cl2).
ꢀ
1H NMR (400 MHz, DMSO-d6): d 1.49–1.52 (m, 2H), 1.81–1.92
(m, 2H), 3.51–3.70 (m, 5H), 3.84 (s, 5H), 4.00–4.03 (m, 1H), 4.18–
4.26 (m, 3H), 4.39–4.43 (m, 1H), 5.43 (s, 1H), 5.55–5.57 (m, 2H),
7.36–7.44 (m, 10H), 7.72–7.80 (m, 2H), 9.17–9.24 (m, 1H). 13C
NMR (100 MHz, DMSO-d6): d 26.0, 26.2, 26.5, 35.7, 35.8, 47.9,
48.5, 58.7, 67.1, 68.7, 69.3, 70.8, 76.5, 78.3, 99.9, 100.1, 122.1,
122.2, 123.6, 125.9, 126.0, 127.9, 128.0, 128.6, 136.5, 136.6,
138.0, 138.9. ESI-MS: m/z (+) = 495.0; m/z (ꢁ) = 78.4, 80.4. HRMS:
Calcd: for C28H35N2O6 ([MꢁBr]+) 495.2490. Found: 495.2491.
The synthetic procedures of 5b, 5c, 5d and 5e are similar to that
of 5a.
9
10
11e
12f
ND
ND
ND
ND
ND
ND
a
Enamide 0.25 mmol; [Rh(COD)(1d)2]BF4 0.0025 mmol; IL/toluene = 1 mL/1 mL;
H2: 40 atm, rt; reaction time: 1 h.
b
Conversions were determined by GC with AT FFAP column.
c
Ee values were determined by GC with CP-Chiralsil Dex CB column.
[bmmim]+ = 1,2-dimethyl-3-butylimidazolium.
d
e
The reaction time was prolonged to 2 h.
The reaction time was prolonged to 4 h.
f
4.4. 3-(4-((4R,40R,5R,50R)-50-Hydroxy-2,20-diphenyl-4,40-bi(1,3-dio
xan)-5-yloxy)butyl)-1-(5-((4R,40R,5R,50R)-50-hydroxy-2,20-diphen
yl-4,40-bi(1,3-dioxan)-5-yloxy)pentyl)-1H-imidazol-3-ium bro
mide 5f38
4. Experimental
4.1. General
A solution of imidazole (0.34 g, 10.5 mmol) in dry THF was
added dropwise to an ice-cooled stirred solution of NaH (0.21 g
of 60% dispersion in mineral oil, 5.25 mmol) in dry THF. The mix-
ture was stirred for 1 h at room temperature and for 1 h at 55 °C
under an argon atmosphere. The formation of hydrogen gas could
be observed by the formation of bubbles in the solution. Next, a
solution of 4a (5.2 g, 10.5 mmol) in dry THF was added dropwise,
and the mixture was refluxed for 48 h under an argon atmosphere.
The solvent was removed under reduced pressure, and the result-
ing solid was washed with ethyl acetate (2 ꢂ 20 mL) and then dis-
solved in dichloromethane. The insoluble NaBr was filtered off and
the filtrate washed with water, dried over MgSO4, and concen-
trated under reduced pressure. A white foam-like solid was ob-
All solvents were dried and degassed by standard methods and
stored under nitrogen. The ionic liquids and dimethyl itaconate
were purchased from Alfa Aesar. Enamides,
a-dehydroamino es-
ters and [Rh(COD)2]BF4 were synthesized according to previous
articles.34–37 All other starting materials and solvents were com-
mercially available. 1H, 13C, and 31P NMR spectra were recorded
with a Bruker Avance III 400 MHz NMR spectrometer. HRMS were
recorded with a Bruker Daltonics APEX II mass spectrometer. GC
and HPLC analyses were carried out on an HP 6890 system and
an Agilent 1200 system, respectively. Optical rotations were deter-
mined on a PerkinElmer Model 341 LC polarimeter at 25 °C.
tained in 43% yield. Mp 117–119 °C.
½
a 2D5
ꢀ
¼ ꢁ30:6 (c 0.54,
CH2Cl2). 1H NMR (400 MHz, DMSO-d6): d 1.44–1.51 (m, 4H),
1.75–1.91 (m, 4H), 3.50–3.70 (m, 10H), 3.83 (s, 4H), 3.99–4.01
(m, 2H), 4.15–4.19 (m, 6H), 4.41 (q, J = 4.8 Hz, 2H), 5.46 (s, 2H),
5.53 (s, 2H), 5.55 (s, 2H), 7.36–7.44 (m, 20H), 7.78 (s, 2H), 9.22–
9.25 (m, 1H). 13C NMR (100 MHz, DMSO-d6): d 26.2, 26.4, 48.6,
58.7, 67.1, 68.7, 69.3, 70.8, 76.5, 78.3, 99.9, 100.1, 122.4, 125.9,
126.0, 128.0, 128.1, 128.6, 135.9, 137.9, 138.0. ESI-MS: m/z
(+) = 893.1; m/z (ꢁ) = 79.4, 80.4. HRMS: Calcd: for C51H61N2O12
([MꢁBr]+) 893.4219. Found: 893.4220.
4.2. 1,3:4,6-Di-O-benzylidene-2-O-(4-bromobutyl)-D-mannitol
4a
Chiral diol 3 (7.16 g, 20 mmol) was dissolved in 100 mL of dry
DMF. To this solution was slowly added sodium hydride (80% oil
suspension, 600 mg, 20 mmol) under ice-bath. The resulting mix-
ture was stirred at room temperature for 1 h, and then 1,4-dibro-
mobutane (20 mmol) was added dropwise under ice-bath. The
reaction mixture was stirred for 24 h at room temperature,
quenched by 200 mL of water, and extracted with ether. The com-
bined extracts were washed with water and brine, dried over
Na2SO4, and concentrated. The residue was purified by chromatog-
raphy on silica gel with ethyl acetate/petroleum ether (1:10) to
4.5. 1-(4-((4R,40R,5R,50R)-50-Hydroxy-2,20-diphenyl-4,40-bi(1,3-
dioxan)-5-yloxy)butyl)-3-methyl-1H-imidazol-3-ium tetraflu
oroborate 6a
give the product. Yield: 42%, mp 30–32 °C. ½a D25
¼ ꢁ29:5 (c 0.95,
ꢀ
CH2Cl2). 1H NMR (400 MHz, CDCl3): d 1.64–1.71 (m, 2H), 1.86–
1.94 (m, 2H), 3.36 (t, J = 6.8 Hz, 2H), 3.47–3.53 (m, 1H), 3.61–3.68
(m, 3H), 3.83–3.89 (m, 1H), 3.93 (d, J = 9.2 Hz, 1H), 4.02
(d, J = 9.2 Hz, 1H), 4.14–4.20 (m, 1H), 4.30 (q, J = 5.2 Hz, 1H), 4.42
(q, J = 5.2 Hz, 1H), 5.49 (s, 1H), 5.51 (s, 1H), 7.33–7.39 (m, 6H),
A mixture of 5a (3 mmol), NaBF4 (0.44 g, 4 mmol) and dry ace-
tonitrile (5 mL) was stirred at room temperature for 24 h. The
white precipitate (NaBr) was then filtered off and washed with
dichloromethane. The filtrate was concentrated in vacuum to give
5a as a white foam-like (which absorbs moisture easily) solid.

Y. Zhao et al. / Tetrahedron: Asymmetry 22 (2011) 769–774
773
Yield: 87%, ½a 2D5
ꢀ
¼ ꢁ25:8 (c 0.65, CH2Cl2). 1H NMR (400 MHz,
DMSO-d6): d 13.2, 18.7, 25.1, 26.2, 26.4, 31.2, 48.5, 48.6, 62.9,
63.1, 66.8, 67.0, 68.6, 68.8, 69.2, 76.2, 76.5, 100.0, 100.1, 121.5,
121.9, 122.0, 122.3, 122.4, 123.3, 123.4, 125.3, 125.5, 125.8,
125.9, 126.7, 126.9, 128.1, 128.2, 128.6, 128.7, 128.8, 130.3,
130.8, 130.9, 131.2, 131.7, 132.0, 135.8, 137.3, 137.6, 146.6,
146.9. 31P NMR (162 MHz, DMSO-d6): d 153.0. HRMS: Calcd: for
DMSO-d6): d 1.46–1.53 (m, 2H), 1.77–1.91 (m, 2H), 3.51–3.70 (m
5H), 3.82–3.85 (m, 5H), 3.99 (d, J = 9.2 Hz, 1H), 4.15–4.20 (m,
3H), 4.40 (q, J = 4.8 Hz, 1H), 5.42 (s, 1H), 5.53 (s, 1H), 5.55 (s, 1H),
7.35–7.44 (m, 10H), 7.67 (s, 1H), 7.74 (t, J = 2.0 Hz, 1H), 9.08 (s,
1H). 13C NMR (100 MHz, DMSO-d6): d 26.0, 26.2, 26.4, 35.7, 48.0,
48.6, 58.7, 67.1, 68.7, 69.3, 70.8, 76.6, 78.3, 99.9, 100.2, 122.2,
123.6, 125.9, 126.0, 127.9, 128.0, 128.6, 136.4, 137.9, 138.0. ESI-
MS: m/z (+) = 495.0; m/z (ꢁ) = 86.4. HRMS: Calcd: for C28H35N2O6
([MꢁBF4]+) 495.2490. Found: 495.2488.
C
51H52N2O8P ([MꢁBF4]+) 851.3456. Found: 851.3427.
Compound 1d was obtained as a white foam-like solid (47%)
from the reaction of 6d and (R)-BINOL-derived chlorophosphite.
Mp 129–131 °C.
½
a 2D5
ꢀ
¼ ꢁ216:0 (c 0.42, CH2Cl2). 1H NMR
The synthetic procedures for 6b, 6c, 6d, 6e and 6f are similar to
that of 6a.
(400 MHz, DMSO-d6): d 1.14–1.20 (m, 2H), 1.23–1.29 (m, 2H),
1.41–1.46 (m, 2H), 1.66–1.71 (m, 2H), 3.43–3.67 (m, 5H), 3.81 (s,
3H), 3.83–3.92 (m, 1H), 4.03–4.07 (m, 3H), 4.37–4.40 (m, 1H),
4.57–4.60 (m, 1H), 4.67–4.70 (m, 1H), 5.55 (s, 1H), 5.66 (s, 1H),
7.19–7.23 (m, 2H), 7.35–7.42 (m, 10H), 7.46–7.70 (m, 8H), 8.08–
8.18 (m, 4H), 9.03 (s, 1H). 13C NMR (100 MHz, DMSO-d6): d 24.8,
25.2, 29.1, 29.2, 35.7, 48.6, 62.8, 63.0, 66.5, 68.6, 68.8, 69.7, 76.1,
76.5, 100.0, 121.6, 121.9, 122.0, 122.2, 123.3, 123.5, 125.3, 125.5,
125.8, 125.9, 126.0, 126.7, 126.9, 128.1, 128.2, 128.6, 128.7,
128.8, 130.3, 130.8, 130.9, 131.2, 131.7, 132.0, 136.4, 137.4,
137.6, 146.6, 146.9. 31P NMR (162 MHz, DMSO-d6): d 152.8. HRMS:
Calcd: for C50H50N2O8P ([MꢁBF4]+) 837.3299. Found: 837.3291.
Compound 1e was obtained as a white foam-like solid (38%)
from the reaction of 6e and (R)-BINOL-derived chlorophosphite.
4.6. 1-(4-((4R,40S,5R,50R)-50-(Dinaphtho[2,1-d:10,20-f][1,3,2]diox
aphosphepin-4-yloxy)-2,20-diphenyl-4,40-bi(1,3-dioxan)-5-yloxy)
butyl)-3-methyl-1H-imidazol-3-ium tetrafluoroborate 1a
A solution of (R)-BINOL-derived chlorophosphite (1.5 mmol) in
CH2Cl2 (5 mL) was added dropwise to a vigorously stirred solution
of ionic chiral alcohol 6a (1 mmol) and pyridine (4 mmol) in CH2Cl2
(5 mL). The mixture was stirred at room temperature for an addi-
tional 12 h, and then concentrated. The residue was purified by
flash chromatography on silica gel with CH2Cl2/THF (1:1) to give
the ligand 1a as a white foam-like solid. Yield: 33%, mp 142–
Mp 103–105 °C.
½
a 2D5
ꢀ
¼ ꢁ194:4 (c 0.43, CH2Cl2). 1H NMR
143 °C.
½
a 2D5
ꢀ
¼ ꢁ224:4 (c 0.45, CH2Cl2). 1H NMR (400 MHz,
(400 MHz, DMSO-d6): d 1.15–1.21 (m, 16H), 1.40–1.45 (m, 2H),
1.73–1.76 (m, 2H), 3.40–3.68 (m, 4H), 3.78–3.91 (m, 5H), 4.06 (d,
J = 9.6 Hz, 1H), 4.12 (t, J = 7.2 Hz, 2H), 4.35–4.39 (m, 1H), 4.55–
4.59 (m, 1H), 4.63–4.70 (m, 1H), 5.50 (s, 1H), 5.65 (s, 1H), 7.18–
7.23 (m, 2H), 7.33–7.60 (m, 16H), 7.68 (s, 1H), 7.74 (s, 1H), 8.07–
8.17 (m, 4H), 9.07 (s, 1H). 13C NMR (100 MHz, DMSO-d6): d 25.4,
25.5, 28.3, 28.7, 28.8, 28.9, 29.2, 29.3, 35.7, 48.7, 62.8, 63.0, 66.5,
67.0, 68.6, 68.8, 69.7, 76.1, 76.6, 100.0, 121.6, 121.9, 122.0, 122.2,
123.4, 123.6, 125.3, 125.4, 125.8, 125.9, 126.0, 126.7, 126.8,
128.0, 128.1, 128.6, 128.7, 128.8, 130.2, 130.8, 131.2, 131.7,
132.0, 136.4, 137.4, 137.6, 146.6, 146.9. 31P NMR (162 MHz,
DMSO-d6): d 152.4. HRMS: Calcd: for C56H62N2O8P ([MꢁBF4]+)
921.4238. Found: 921.4204.
DMSO-d6): d 1.42–1.47 (m, 2H), 1.75–1.84 (m, 2H), 3.46–3.58 (m,
3H), 3.65–3.72 (m, 1H), 3.77 (s, 3H), 3.84–3.92 (m, 2H), 4.06–
4.11 (m, 3H), 4.39–4.24 (m, 1H), 4.58–4.61 (m, 1H), 4.66–4.72
(m, 1H), 5.56 (s, 1H), 5.67 (s, 1H), 7.21 (t, J = 7.2 Hz, 2H), 7.35–
7.40 (m, 10H), 7.47–7.68 (m, 7H), 7.69 (s, 1H), 8.07–8.17 (m, 4H),
9.00 (s, 1H). 13C NMR (100 MHz, DMSO-d6): d 26.2, 26.4, 35.6,
48.5, 62.9, 63.1, 66.8, 67.0, 68.5, 68.8, 69.2, 76.2, 76.5, 99.9,
100.0, 121.5, 121.9, 122.0, 122.1, 123.3, 123.5, 125.3, 125.5,
125.8, 125.9, 126.0, 126.7, 126.9, 128.1, 128.2, 128.6, 128.7,
128.8, 130.3, 130.8, 130.9, 131.2, 131.7, 132.0, 136.4, 137.3,
137.6, 146.6, 146.9, 147.0. 31P NMR (162 MHz, DMSO-d6): d
153.0. HRMS: Calcd: for C48H46N2O8P ([MꢁBF4]+) 809.2986. Found:
809.2991.
Compound 1f was obtained as a white foam-like solid (53%)
from the reaction of 6f and (R)-BINOL-derived chlorophosphite.
The synthetic procedures for 1b, 1c, 1d, 1e and 1f are similar to
that of 1a.
Compound 1b was obtained as a white foam-like solid (55%)
from the reaction of 6b and (R)-BINOL-derived chlorophosphite.
Mp 158–160 °C.
½
a 2D5
ꢀ
¼ ꢁ230:7 (c 0.44, CH2Cl2). 1H NMR
(400 MHz, DMSO-d6): d 1.37–1.40 (m, 4H), 1.66–1.73 (m, 4H),
3.43–3.55 (m, 6H), 3.65–3.67 (m, 2H), 3.80–3.89 (m, 4H), 4.01–
4.06 (m, 6H), 4.36–4.39 (m, 2H), 4.57–4.60 (m, 2H), 4.65–4.71
(m, 2H), 5.54 (s, 2H), 5.64 (s, 2H), 7.15–7.25 (m, 5H), 7.31–7.40
(m, 20H), 7.47–7.64 (m, 13H), 8.05–8.10 (m, 6H), 8.14 (s, 1H),
8.16 (s, 1H), 9.01 (s, 1H). 13C NMR (100 MHz, DMSO-d6): d 26.1,
26.3, 48.6, 62.9, 63.1, 66.8, 68.5, 68.8, 69.2, 76.1, 76.5, 100.0,
100.1, 115.4, 118.5, 121.5, 121.9, 122.0, 122.2, 122.3, 123.3,
123.4, 124.4, 125.3, 125.5, 125.8, 125.9, 126.0, 126.7, 126.9,
127.8, 128.1, 128.2, 128.6, 128.7, 128.8, 130.2, 130.8, 130.9,
131.2, 131.7, 132.0, 134.1, 135.8, 137.3, 137.6, 146.6, 146.9,
147.0, 153.0. 31P NMR (162 MHz, DMSO-d6): d 153.0. HRMS: Calcd:
for C91H83N2O16P2 ([MꢁBF4]+) 1521.5212. Found: 1521.5150.
Mp 148–149 °C.
½
a 2D5
ꢀ
¼ ꢁ225:0 (c 0.52, CH2Cl2). 1H NMR
(400 MHz, DMSO-d6): d 1.43–1.50 (m, 2H), 1.64–1.72 (m, 2H),
2.47 (s, 3H), 3.48–3.54 (m, 2H), 3.59–3.61 (m, 1H), 3.66 (s, 3H),
3.69–3.71 (m, 1H), 3.82–3.92 (m, 2H), 4.01–4.08 (m, 3H), 4.39–
4.42 (m, 1H), 4.58–4.62 (m, 1H), 4.68–4.74 (m, 1H), 5.56 (s, 1H),
5.67 (s, 1H), 7.19–7.23 (m, 2H), 7.35–7.40 (m, 10H), 7.47–7.59
(m, 8H), 8.07–8.17 (m, 4H). 13C NMR (100 MHz, DMSO-d6): d 9.0,
26.1, 26.2, 34.5, 47.2, 62.9, 63.1, 66.7, 67.0, 68.5, 68.8, 69.4, 76.2,
76.5, 99.9, 100.0, 120.7, 121.5, 121.9, 122.0, 122.2, 123.3, 123.4,
125.3, 125.5, 125.8, 125.9, 126.0, 126.7, 126.9, 128.1, 128.2,
128.6, 128.7, 128.8, 130.3, 130.8, 130.9, 131.2, 131.7, 132.0,
137.3, 137.6, 144.1, 146.6, 146.9, 147.0. 31P NMR (162 MHz,
DMSO-d6): d 153.0. HRMS: Calcd: for C49H48N2O8P ([MꢁBF4]+)
823.3143. Found: 823.3148.
4.7. Hydrogenation reaction in CH2Cl2
Compound 1c was obtained as a white foam-like solid (47%)
from the reaction of 6c and (R)-BINOL-derived chlorophosphite.
To a mixture of substrate (enamide,
a-dehydroamino ester or
Mp 116–118 °C.
½
a 2D5
ꢀ
¼ ꢁ213:3 (c 0.48, CH2Cl2). 1H NMR
dimethyl itaconate) (0.25 mmol) and Rh complex catalyst
(2.5 ꢂ 10ꢁ3 mmol) was added degassed CH2Cl2 (1 mL) and stirred
vigorously for 10 min. Hydrogenation was carried out in a stainless
autoclave at room temperature for 1 h. After releasing the H2, the
reaction mixture was passed through a short silica gel column to
remove the catalyst. The resulting solution was used directly for
GC or HPLC analysis.
(400 MHz, DMSO-d6): d 0.86 (t, J = 7.2 Hz, 3H), 1.16–1.25 (m, 2H),
1.42–1.47 (m, 2H), 1.65–1.76 (m, 2H), 3.46–3.72 (m, 5H), 3.82–
3.96 (m, 2H), 4.07–4.13 (m, 4H), 4.39–4.43 (m, 1H), 4.58–4.62
(m, 1H), 4.66–4.75 (m, 1H), 5.56 (s, 1H), 5.67 (s, 1H), 7.20–7.24
(m, 2H), 7.35–7.40 (m, 10H), 7.48–7.56 (m, 6H), 7.71 (s, 1H), 7.72
(s, 1H), 8.07–8.17 (m, 4H), 9.10 (s, 1H). 13C NMR (100 MHz,

774
Y. Zhao et al. / Tetrahedron: Asymmetry 22 (2011) 769–774
16. Bauerlein, P. S.; Fairlamb, I. J. S.; Jarvis, A. G.; Lee, A. F.; Muller, C.; Slattery, J. M.;
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4.8. Hydrogenation in the [bmim][BF4]/toluene system
To mixture of enamide or -dehydroamino acid ester
a
a
(0.25 mmol) and Rh complex catalyst (2.5 ꢂ 10ꢁ3 mmol) were
added ionic liquid [bmim][BF4] (1 mL) and toluene (1 mL). Hydroge-
nation was carried out in a stainless autoclave at room temperature.
After releasing the H2, the toluene layer was separated in a glovebox
and subjected to GC analysis without any purification. For catalyst
recycling, enamide (0.25 mmol), and toluene (1 mL) were added
again to the ionic liquid layer remaining in the reaction vessel.
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This work was supported by the Chinese Academy of Sciences,
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and the Research Foundation for the Returned Overseas Chinese
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