Concise methods for the synthesis of chiral polyoxazolines and their application in asymmetric hydrosilylation

Article abstract of DOI:10.3762/bjoc.6.29

Seven polyoxazoline ligands were synthesized in high yield in a one-pot reaction by heating polycarboxylic acids or their esters and chiral β-amino alcohols under reflux with concomitant removal of water or the alcohol produced in the reaction. The method is much simpler and more efficient in comparison to those methods reported in the literature.

Full text of DOI:10.3762/bjoc.6.29

Concise methods for the synthesis of chiral poly-
oxazolines and their application in asymmetric
hydrosilylation
Wei Jie Li*1, Zun Le Xu2 and Sheng Xiang Qiu1
Full Research Paper
Open Access
Address:
Beilstein Journal of Organic Chemistry 2010, 6, No. 29.
1Program for Natural Product Chemical Biology & Drug Discovery,
South China Botanical Garden, Chinese Academy of Sciences, 723
Xingke Road, Tianhe District, Guangzhou 510650, China and
2Department of Applied Chemistry, School of Chemistry and
Chemical Engineering, Sun Yat-Sen University, 135 Xingang West
Road, Haizhou District, Guangzhou 510275, China
doi:10.3762/bjoc.6.29
Received: 01 January 2010
Accepted: 16 March 2010
Published: 25 March 2010
Associate Editor: M. Rueping
Email:
Wei Jie Li* - weijieli1688@yahoo.com.cn
© 2010 Li et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
aromatic ketone; hydrosilylation; polyoxazoline; rhodium; synthesis
Abstract
Seven polyoxazoline ligands were synthesized in high yield in a one-pot reaction by heating polycarboxylic acids or their esters and
chiral β-amino alcohols under reflux with concomitant removal of water or the alcohol produced in the reaction. The method is
much simpler and more efficient in comparison to those methods reported in the literature.
The compounds were used as chiral ligands in the rhodium-catalyzed asymmetric hydrosilylation of aromatic ketones, and the
effects of the linkers and the substituents present on the oxazoline rings on the yield and enantioselectivity investigated. Compound
2 was identified as the best ligand of this family for the hydrosilylation of aromatic ketones.
Introduction
The design and development of effective chiral oxazoline [1-13]. Previously, polyoxazoline ligands were reported to have
ligands have played a significant role in the advancement of good catalytic activities and high enantioselectivities in various
asymmetric catalysis and have attracted a great deal of atten- asymmetric reactions [14-20]. For example, chiral 1,2,2-tris[2-
tion. Various chiral oxazoline ligands have been developed and (4-isopropyloxazolinyl)]propane was shown to lead to high
applied in many catalytic asymmetric reactions to prepare enan- enantioselectivities in the Cu(II)-catalyzed asymmetric Michael
tiomerically pure compounds; in particular, a range of mono- addition reaction between indole and alkylene malonates [19].
and bisoxazolines have been widely used as effective templates More recently, the complex from 2,2′,6,6′-tetrakis[(4S)-
for metal-catalyzed asymmetric reactions over the last 30 years phenyloxazolin-2-yl]-biphenyl and Pd(II) was reported to show
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Beilstein Journal of Organic Chemistry 2010, 6, No. 29.
Figure 1: Chemical structures of polyoxazolines.
Results and Discussion
excellent catalytic activities and enantioselectivities in the
Wacker-type cyclization of allylphenols with up to 99% ee [20]. Syntheses of polyoxazolines
Despite their great application potential, until now, only a few The conventional methods for the preparation of poly-
polyoxazoline ligands have been reported in the literature due to oxazolines from polycarboxylic acids or their esters have been
synthetic difficulties. In general, the syntheses of poly- often carried out via poly(β-hydroxylamide)s intermediates; the
oxazolines from polycarboxylic acids or polycarboxylates and latter were then cyclized in the presence of condensing agents
chiral amino alcohols are carried out via poly(β- such as thionyl chloride/NaOH, methanesulfonic chloride or
hydroxyamide)s as intermediates, followed by cyclization to PPh3 etc. to produce the desired compounds [19-21]. However,
afford the target compounds. The methods require activating these methods are associated with side reactions and low yields.
agents or cyclizing agents such as thionyl chloride, methane- To address these issues, we have successfully developed facile
sulfonic chloride or PPh3 etc. [19-21], which result in more side procedures for the syntheses of polyoxazolines starting from
reactions and low yields. Therefore, simpler and more efficient polycarboxylic acids or their esters, such as 3,4-dihydroxy-
synthetic strategies are required for the preparation of poly- furan-2,5-dicarboxylic acid (DFA) and its dimethyl ester
oxazoline ligands.
(DDFA), diglycolic acid and its dimethyl ester, triglycine and
its triethyl ester, 1,3,5-benzenetricarboxylic acid (BTA) and its
In the present study, we report the results of heating trimethyl ester (TBTA), ethylenediaminetetraacetic acid
polycarboxylic acids or their esters with chiral β-amino alco- (EDTA) and ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-
hols under reflux conditions with the simultaneous removal of tetraacetic acid (EGTA).
water or the alcohol produced in the reaction in a one-step
process for the preparation of novel chiral polyoxazoline As the data in Table 1 indicates, DFA, diglycolic acid or their
ligands (Figure 1). These processes are high yield reactions with dimethyl esters, respectively, react with (R)-2-amino-1-butanol
simple workup procedures. Furthermore, we have also investi- or L-phenylalaninol in toluene under reflux in 18–23 h with the
gated the reactivities and resulting enantioselectivities of the elimination of water or methanol in a one-pot reaction, to give
newly synthesized ligands in the asymmetric hydrosilylation the bisoxazolines 1–3 in good yields (entries 1–6). However,
catalyzed by [Rh(COD)Cl]2.
when triglycine or its triethyl ester, BTA or TBTA, was heated
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Beilstein Journal of Organic Chemistry 2010, 6, No. 29.
Table 1: The conditions and results of the reaction of polycarboxylic acids or their esters with chiral β-amino alcohols.
Entry
Reaction substrate
β-amino alcohol
Polyoxazoline
R1
R2
Reaction time (h)
Yielda (%)
1
2
DFA
(R)-2-amino-1-butanol
(R)-2-amino-1-butanol
L-phenylalaninol
1
1
2
2
3
3
4
4
5
5
6
7
H
Me
H
Et
Et
23
18
23
18
23
18
33
30
33
30
28
28
94b
93b
91b
90b
98b
96b
98c
96d
91c
93d
95e
93e
DDFA
3
DFA
Bn
4
DDFA
L-phenylalaninol
Me Bn
5
Diglycilic acid
Dimethyl diglycilate
Triglycine
Triethyl triglycinate
BTA
(R)-2-amino-1-butanol
(R)-2-amino-1-butanol
(R)-2-amino-1-butanol
(R)-2-amino-1-butanol
(R)-2-amino-1-butanol
(R)-2-amino-1-butanol
(R)-2-amino-1-butanol
(S)-2-amino-1-butanol
H
Me
H
Et
Et
Et
Et
Et
Et
Et
Et
6
7
8
Et
H
9
10
11
12
TBTA
Me
H
EDTA
EGTA
H
aReaction conditions: n[R(CO2R1)x]:n(β-amino alcohol) = 1:1.0x–1:1.1x (molar ratio).
bRefluxed.
cRefluxed for 24 h and then stirred for 9 h at 125 °C after toluene removal.
dRefluxed for 24 h and then stirred for 6 h at 125 °C after toluene removal.
eRefluxed for 20 h and then stirred for 8 h at 135 °C.
with (R)-2-amino-1-butanol in toluene, good yields of the subjects in modern synthetic chemistry. In this article, with the
desired products were not obtained, even after 24 h. To resolve new polyoxazoline ligands in hand, the Rh-catalyzed hydro-
this problem, the toluene was removed and the resulting mix- silylation of aromatic ketones was explored (Table 2 and
ture stirred for 6–9 h at 125 °C to complete the reaction. By Table 3).
employing this modified procedure, the trioxazolines 4 or 5
were obtained in excellent yields (entries 7–10). Similarly, The reduction of acetophenone was first examined, since this is
when a mixture of EDTA or EGTA and (R)- or (S)-2-amino-1- often used as the standard ketone in investigations of asym-
butanol in toluene was refluxed for 20 h, the tetraoxazolines 6 metric hydrosilylation. The reaction of acetophenone with
or 7 were obtained in poor yield. Again, after toluene was diphenylsilane in the presence of polyoxazolines 1–7 and
removed and the resulting mixtures stirred for 8 h at 135 °C, the [Rh(COD)Cl]2 was studied (Table 2, entries 1–15). First, the
desired tetraoxazolines were obtained in high yields (entries 11 effect of temperature on the catalytic reaction with bisoxazoline
and 12).
1 as a ligand was examined with THF as solvent (entries 1–3).
At −10 °C, the reaction proceeded very slowly and only a 51%
yield of 1-phenylethanol with low ee was obtained after 72 h
(entry 1). When the temperature was raised to −5 °C, the aceto-
phenone disappeared completely within 72 h to afford
1-phenylethanol in a yield of 86% with 89% ee (entry 2). As the
temperature was raised to room temperature, the reaction was
accelerated further, but the ee was slightly lower (entry 3).
Therefore, the reaction temperature was optimized to −5 °C. As
for solvent effect, the reaction displayed a preference for THF
as solvent. The reaction proceeded very fast in CH3OH, but the
ee was disappointingly low, only 55% (entry 4). However,
1-phenylethanol was obtained in high yield with high enantio-
selectivity in THF, exceeding that observed in either CCl4 or
CH3OH (entries 2, 4 and 5). Catalyst concentrations were
generally employed at 2 mol %, relative to acetophenone
Enantioselective Rh(I)-catalyzed hydrosilyla-
tion of aromatic ketones with various poly-
oxazoline ligands
Enantiomerically pure chiral alcohols are key intermediates in
the synthesis of numerous biologically active molecules [22].
For this reason, much effort has been made over the last 30
years to develop efficient techniques for asymmetric reduction
of prochiral ketones. In particular, asymmetric catalysis
provides organic chemists with a unique tool for their efficient
synthesis [23], although none of these are, as yet, optimal [24-
26]. In recent years, metal-catalyzed hydrosilylation of ketones
has been investigated using chiral ligands [27-33], while
enantioselective hydrogenation of prochiral ketones to optically
active secondary alcohols is among the most fundamental
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Beilstein Journal of Organic Chemistry 2010, 6, No. 29.
Table 2: Enantioselective Rh(I)-catalyzed hydrosilylation of acetophenone.
Entry
Ligand
Solvent
Time (h)
T (°C)
Ligand/PhCOMe Yielda (%)
(mol %)
eeb (%)
Abs. config.c
1
2
1
1
1
1
1
1
1
1
1
2
3
4
5
6
7
THF
THF
THF
CH3OH
CCl4
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
72
72
48
45
72
120
72
120
72
72
72
72
72
72
72
−10
−5
rt
2.0
2.0
2.0
2.0
2.0
2.0
1.0
0.5
4.0
2.0
2.0
2.0
2.0
2.0
2.0
51
86
95
81
78
87
81
76
86
84
64
74
70
78
74
68
89
80
55
70
90
81
73
90
97
32
37
20
55
48
R
R
R
R
R
R
R
R
R
S
R
R
R
R
S
3
4
−5
−5
−5
−5
−5
−5
−5
−5
−5
−5
−5
−5
5
6
7
8
9
10
11
12
13
14
15
aConditions: [Rh(COD)Cl]2 (0.01 mmol), PhCOMe (2.0 mmol), Ph2SiH2 (3.2 mmol) and solvent (5.0 mL).
bThe enantiomeric excess (ee) was determined by HPLC analysis using a Daicel Chiralcel OJ-H column.
cThe absolute configurations were determined by optical rotation.
(entry 2), although loadings as low as 0.5 mol % could be used, result indicated that the bulkiness of the substituents on the
a longer reaction time was required (entry 8). However, oxazoline rings affected the enantioselectivities. As shown in
whereas a higher catalyst loading of 4 mol % worked well, there Table 2, the absolute configurations of the resulting products
was no significant improvement in the ee (entry 9).
were in good agreement with those of the corresponding chiral
amino alcohols, because the enantioselectivities were deter-
Under the optimized conditions, the reactions with 2–7 as mined solely by the chirality of oxazoline rings derived from
ligands were carried out (Table 2, entries 10–15). The experi- the chiral amino alcohols.
mental results show that the ee with bisoxazoline 2 was higher
than those with the bisoxazoline 3 and the polyoxazolines 4–7, The reduction of various prochiral aryl-substituted ketones was
suggesting that the furan-containing bisoxazoline 2 held a good, examined in order to evaluate the influence of ligand 2 on
rigid C2-symmetric chirality-inducing unit, which led to good Rh(I)-catalyzed asymmetric hydrosilylation. Under the opti-
enantioselectivity. By contrast, the benzene-containing tri- mized conditions described above, the hydrosilylation of
oxazoline 5 led to low enantioselectivity probably because its various aryl-substituted ketones catalyzed by [Rh(COD)Cl]2 in
planar structure weakens the coordination of 5 to the presence of ligand 2 gave the corresponding secondary alco-
[Rh(COD)Cl]2. In addition, the experimental results also show hols with good enantioselectivities. The results of all the reac-
that flexible linkers of oxazoline rings result in low enantio- tions are shown in Table 3 in terms of the best ee values for
selectivities (entries 11, 12, 14, 15). Table 2 shows that bisoxa- each substrate. Reduction of acetophenone gave the correspond-
zoline 2 with benzyl group (entry 10) gave a higher ee than its ing alcohol in 84% yield and 97% ee (entry 1), while 2-acetyl-
counterpart, bisoxazoline 1 with an ethyl group (entry 2): this naphthalene led to 85% yield of product with 94% ee (entry 2).
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Beilstein Journal of Organic Chemistry 2010, 6, No. 29.
Table 3: Asymmetric hydrosilylation of aromatic ketones catalyzed by ligand 2 and [Rh(COD)Cl]2 under optimized conditions.
Entry
Ketone
Yielda (%)
eeb (%)
Abs. config.c
1
2
3
4
5
6
7
8
8a
8b
8c
8d
8e
8f
84
85
89
71
86
81
76
79
97
94
93
90
94
96
94
96
S
S
S
S
S
S
S
S
8g
8h
aConditions: ligand 2 (0.04 mmol), [Rh(COD)Cl]2 (0.01 mmol), ketone (2.0 mmol), Ph2SiH2 (3.2 mmol), THF (5.0 mL), −5 °C and 72 h.
bThe enantiomeric excess (ee) was determined by HPLC analysis with chiral stationary phases.
cThe absolute configurations were determined by optical rotation.
Experimental
It was found that ortho-substituted aromatic ketones resulted in
lower enantioselectivities (entries 3, 4); a similar trend was General
observed for the substrate with a bulkier alkyl group at the Melting points were determined by the capillary method and are
carbonyl unit (entry 5). para-Substituted aromatic ketones were uncorrected. 1H NMR spectra were measured on a Varian Unity
reduced to alcohols with high enantioselectivities, in most cases INOVI-500 NMR spectrometer or a Bruker Avance DPX300
(entries 6–8).
NMR spectrometer, using TMS as internal standard. Infrared
spectra were recorded on a Bruker Vector 22 FT-IR spectro-
meter. Mass spectra were taken on a LCQ DECA XP LC/MS
Conclusion
Facile methods for the synthesis of polyoxazolines (1–7) are system or a VG ZAB-HS mass spectrometer. Elemental
described, which are much simpler and more efficient in analyses were carried out on a Perkin-Elmer 240C elemental
comparison to those reported in the literature. With these chiral analyzer. Optical rotation values were measured on a
ligands as templates, the rhodium-catalyzed asymmetric hydro- Polartronic HNQW 5 polarimeter. Enantiomeric excess (ee) was
silylation of aromatic ketones was carried out. The effects of the determined by HPLC analysis with chiral Daicel Chiralcel OJ-H
linkers of oxazoline rings and the substituents on oxazoline (or OD-H, or OB-H) column on an Agilent HP-1100 HPLC
rings of the ligands on the reaction were investigated, and com- instrument.
pound 2 was identified as the best ligand of this family for the
hydrosilylation of aromatic ketones. A study of the potential of All solvents used for the synthesis were of analytical grade and
this type of ligand for other metal-catalyzed asymmetric reac- were dried and freshly distilled under a nitrogen atmosphere
tions is now in progress.
prior to use. (R)- or (S)-2-amino-1-butanol and L-phenyl-
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Beilstein Journal of Organic Chemistry 2010, 6, No. 29.
alaninol were purchased from Fluka Chemical Co. 3,4- (dd, J = 6.5, 11.0 Hz, 2H), 3.62 (dd, J = 4.0, 11.0 Hz, 2H),
Dihydroxyfuran-2,5-dicarboxylic acid and its dimethyl ester 7.23–7.34 (m, 10H) ppm. Among the protons described above,
were prepared as described in the literature [34]. Dimethyl two active hydrogens of OH were substituted by deuterium.
diglycolate, triethyl aminotriacetate and trimethyl-1,3,5- ESI-MS, m/z (%): 419 ([M+H]+, 100); Anal. Calcd for
benzenetricarboxylate were synthesized in our own laboratory. C24H22N2O5: C, 68.89; H, 5.30; N, 6.69. Found: C, 68.51; H,
Other reagents were all of analytical grade.
5.43; N, 6.86.
Syntheses of polyoxazoline ligands
3,4-Dihydroxy-2,5-bis(4-substituted-oxazolin-2-
yl)furan
(−)-Bis{[4-(R)-ethyloxazolin-2-yl]methyl} ether (3)
Method A: Diglycolic acid (1.34 g, 10.0 mmol), (R)-2-amino-1-
butanol (1.96 g, 22.0 mmol) and toluene (40 mL) were added to
Method A: 3,4-Dihydroxyfuran-2,5-dicarboxylic acid (0.75 g, a three-neck flask with a water segregator, a reflux condenser
4.0 mmol), the chiral amino alcohol (8.8 mmol) and toluene and a magnetic stirring bar. The mixture was refluxed with
(40 mL) were placed in a three-neck flask, fitted with a water continuous removal of water for 23 h. After cooling to room
segregator, a reflux condenser and a magnetic stirring bar. The temperature, the solvent was removed under reduced pressure
mixture was refluxed and with continuous water removal for and the residue was purified by silica gel column chromatog-
23 h. Then, toluene was removed under reduced pressure. After raphy with ethanol as eluant to give the pure title compound.
cooling to ambient temperature, the residue was purified by
silica gel column chromatography with ethanol as eluant to Method B: 1.62 g (10.0 mmol) of dimethyl diglycolate, 1.78 g
produce the desired compound.
(20.0 mmol) of (R)-2-amino-1-butanol and 40 mL of toluene
were added to a three-neck flask equipped with a water segreg-
Method B: 0.87 g (4.0 mmol) of dimethyl-3,4-dihydroxyfuran- ator, a reflux condenser and a magnetic stirring bar. The mix-
2,5-dicarboxylate, 8.0 mmol of the chiral amino alcohol and ture was refluxed for 18 h with continuous removal of meth-
40 mL of toluene were added to a three-neck flask equipped anol and water. After cooling to room temperature, the resulting
with a water segregator, a reflux condenser and a magnetic stir- mixture was concentrated and purified by silica gel column
ring bar. The mixture was heated under reflux for 18 h with chromatography with ethanol as eluant to afford the pure
continuous removal of methanol and water. Then, the solvent desired compound.
was removed under reduced pressure. After cooling to room
temperature, the residue was purified by column chromatog- This compound was obtained as a colorless oil in 98% yield by
raphy on silica gel with ethanol as eluant to yield the desired Method A, and in 96% yield following Method B. [α]D20 −27.0
compound.
(c 1.1, C2H5OH); IR (KBr): 2970, 2886, 2578, 1588, 1464,
1410, 1308, 1128, 1056 cm−1; 1H NMR (500 MHz, CD3OD): δ
1.02 (t, J = 7.5 Hz, 6H), 1.63–1.70 (m, 4H), 3.09–3.50 (m, 2H),
3.58 (dd, J = 6.5, 12.0 Hz, 2H), 3.74 (dd, J = 3.5, 12.0 Hz, 2H),
(−)-3,4-Dihydroxy-2,5-bis[4-(R)-ethyloxazolin-2-
yl]furan (1)
This compound was obtained as a sticky colorless liquid in 94% 3.94 (s, 4H) ppm; FAB-MS, m/z (%): 243 ([M+3]+, 5), 224
yield by Method A, and in 93% yield following Method B. ([M−16]+, 10); Anal. Calcd for C12H20N2O3: C, 59.98; H, 8.39;
[α]D20 −10.0 (c 0.5, C2H5OH); IR (KBr): 3276, 2968, 2941, N, 11.66. Found: C, 59.75; H, 8.51; N, 11.46.
2880, 1652, 1518, 1055 cm−1; 1H NMR (500 MHz, CD3OD): δ
1.03 (t, J = 7.5 Hz, 6H), 1.62–1.73 (m, 4H), 3.10–3.15 (m, 2H), (+)-N,N,N-Tris{[4-(R)-ethyloxazolin-2-
3.57 (dd, J = 7.0, 11.5 Hz, 2H), 3.77 (dd, J = 3.5, 11.5 Hz, 2H), yl]methyl}amine (4)
4.55 (s, 2H) ppm; ESI-MS, m/z (%): 317 ([M+Na]+, 100); Anal. Method A: Aminotriacetic acid (0.77 g, 4.03 mmol), (R)-2-
Calcd for C14H18N2O5: C, 57.13; H, 6.16; N, 9.52. Found: C, amino-1-butanol (1.19 g, 13.3 mmol) and toluene (40 mL) were
57.32; H, 6.38; N, 9.40.
added to a three-neck flask with a water segregator, a reflux
condenser and a magnetic stirring bar. The mixture was re-
fluxed for 24 h, then warmed to 125 °C and stirred for 9 h at the
same temperature. After cooling to room temperature, the
(+)-3,4-Dihydroxy-2,5-bis[4-(S)-benzyloxazolin-2-
yl]furan (2)
This compound was obtained as a white solid in 91% yield by resulting mixture was chromatographed on silica gel using
Method A, and in 90% yield following Method B. mp ethanol as eluant to yield the title compound.
162.0–163.5 °C; [α]D20 +18.0 (c 1.0, CH3OH); IR (KBr):
3344, 3034, 2935, 1605, 1496, 1454, 1378, 1322, 1057 cm−1; Method B: Triethyl aminotriacetate (1.10 g, 4.0 mmol), (R)-2-
1H NMR (500 MHz, CD3OD): δ 2.79 (dd, J = 7.0, 14.0 Hz, amino-1-butanol (1.07 g, 12.0 mmol) and toluene (40 mL) were
2H), 2.88 (dd, J = 7.0, 13.5 Hz, 2H), 3.26–3.31 (m, 2H), 3.46 added to a three-neck flask with a water segregator, a reflux
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Beilstein Journal of Organic Chemistry 2010, 6, No. 29.
condenser and a magnetic stirring bar. The mixture was re- fluxed for 20 h. Then toluene was removed and the residue
fluxed for 24 h, warmed to 125 °C and stirred for 6 h at the stirred for 8 h at 135 °C. After cooling to room temperature, the
same temperature. After cooling to room temperature, the resulting mixture was purified by silica gel column chromatog-
resulting mixture was chromatographed on silica gel using raphy using ethanol as eluant to obtain 1.93 g of the title com-
ethanol as eluant to obtain the title compound.
pound in 95% yield. Colorless oil; [α]D20 +198.0 (c 1.0,
C2H5OH); IR (KBr): 2966, 2875, 1590, 1062 cm−1; 1H NMR
This compound was obtained as a white solid in 98% yield by (500 MHz, CD3OD): δ 0.91–0.95 (m, 12H), 1.59–1.69 (m, 8H),
Method A, and in 96% yield following Method B. [α]D20 +6.0 2.77 (t, J = 7.5 Hz, 4H), 3.06–3.11 (m, 4H), 3.28 (s, 8H),
(c 1.0, CH3OH); mp 156.4–157.2 °C; IR (KBr): 3385, 2970, 3.51–3.58 (m, 8H) ppm; ESI-MS, m/z (%): 527 ([M+Na]+,
2946, 2886, 2567, 1634, 1404 cm−1; 1H NMR (500 MHz, 100); Anal. Calcd for C26H44N6O4: C, 61.88; H, 8.79; N, 16.65.
CD3OD): δ 1.02 (t, J = 7.5 Hz, 9H), 1.64–1.69 (m, 6H), Found: C, 62.10; H, 8.94; N, 16.86.
3.11–3.13 (m, 3H), 3.56 (dd, J = 6.5, 11.5 Hz, 3H), 3.72 (s, 6H),
3.76 (dd, J = 3.5, 11.5 Hz, 3H) ppm; ESI-MS, m/z (%): 351 (−)-N,N,N′,N′-Tetrakis{[4-(S)-ethyloxazolin-2-
([M+H]+, 100); Anal. Calcd for C18H30N4O3: C, 61.69; H, yl]methyl}ethylene glycol-bis(2-aminoethyl) ether (7)
8.63; N, 15.99. Found: C, 61.98; H, 8.80; N, 15.83.
Ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic
acid (1.53 g, 4.02 mmol), (S)-2-amino-1-butanol (1.58 g, 17.7
mmol) and toluene (40 mL) were added to a three-neck flask
(+)-1,3,5-Tris[4-(R)-ethyloxazolin-2-yl]benzene (5)
Method A: 1,3,5-Benzenetricarboxylic acid (0.84 g, 4.0 mmol), with a water segregator, a reflux condenser and a magnetic stir-
(R)-2-amino-1-butanol (1.18 g, 13.2 mmol) and toluene ring bar. The mixture was refluxed for 20 h. The toluene was
(40 mL) were added to a three-neck flask with a water segreg- removed and the residue stirred for 8 h at 135 °C. After cooling
ator, a reflux condenser and a magnetic stirring bar. The mix- to room temperature, the resulting mixture was purified by
ture was refluxed for 24 h, the toluene was removed and the silica gel column chromatography using ethanol as eluant to
residue was stirred for 9 h at 125 °C. After cooling to room tem- afford 2.21 g of the title compound in 93% yield. [α]D20 −21.6
perature, the resulting mixture was chromatographed on silica (c 1.0, C2H5OH); IR (KBr): 2968, 2938, 2880, 1580, 1066
gel using ethanol as eluant to give the title compound.
cm−1; 1H NMR (500 MHz, CD3OD): δ 1.00 (t, J = 7.5 Hz,
12H), 1.51–1.64 (m, 8H), 2.94–2.99 (m, 4H), 3.22 (t, J = 2.5
Method B: Trimethyl-1,3,5-benzenetricarboxylate (1.00 g, 4.0 Hz, 2H), 3.25 (t, J = 5.0 Hz, 2H), 3.29–3.31 (m, 2H), 3.49 (dd, J
mmol), (R)-2-amino-1-butanol (1.07 g, 12.0 mmol) and toluene = 6.5, 11.5 Hz, 4H), 3.54 (s, 2H), 3.58 (s, 4H), 3.60–3.64 (m,
(40 mL) were placed in a three-neck flask, fitted with a water 2H), 3.67 (s, 2H), 3.69 (dd, J = 3.5, 11.5 Hz, 4H), 3.76 (t, J =
segregator, a reflux condenser and a magnetic stirring bar. The 5.5 Hz, 2H), 3.79 (t, J = 5.0 Hz, 2H) ppm; ESI-MS, m/z (%):
mixture was refluxed for 24 h, toluene was removed and the 592 ([M−H]−, 100); Anal. Calcd for C30H52N6O6: C, 60.79; H,
residue stirred for 6 h at 125 °C. After cooling to room tempera- 8.84; N, 14.18. Found: C, 60.58; H, 8.98; N, 14.02.
ture, the resulting mixture was chromatographed on silica gel
General procedure for the rhodium-cata-
using ethanol as eluant to afford the title compound.
lyzed hydrosilylation of aromatic ketones
This compound was obtained as a sticky orange liquid in 91% A mixture of polyoxazoline (0.04 mmol), [Rh(COD)Cl]2 (0.01
yield by Method A, and in 93% yield following Method B. mmol) and aromatic ketone (2.0 mmol) in THF (5.0 mL) was
[α]D20 +1.5 (c 1.0, CH3OH); IR (KBr): 2971, 2941, 2886, stirred for 1 h at ambient temperature under a nitrogen atmos-
1611, 1558, 1464, 1429, 1358, 1064 cm−1; 1H NMR (500 MHz, phere. After diphenylsilane (3.2 mmol) was added to the mix-
CD3OD): δ 1.00 (t, J = 7.5 Hz, 9H), 1.61–1.69 (m, 6H), ture at −5 °C, the reaction mixture was stirred at this tempera-
3.08–3.12 (m, 3H), 3.56 (dd, J = 6.5, 11.5 Hz, 3H), 3.75 (dd, J ture until the aromatic ketone was consumed. The reaction mix-
= 4.0, 11.5 Hz, 3H), 8.70 (s, 3H) ppm; ESI-MS, m/z (%): 370 ture was quenched with methanol (1.0 mL), then acidified with
([M+H]+, 100); Anal. Calcd for C21H27N3O3: C, 68.27; H, dilute hydrochloric acid at 0 °C and the organic layer was separ-
7.37; N, 11.37. Found: C, 67.98; H, 7.63; N, 11.56.
ated. The aqueous layer was extracted with diethyl ether or
dichloromethane, and the organic layers were combined and
dried with anhydrous Na2SO4. After purification by column
chromatography on silica gel with CH2Cl2, the configuration of
(+)-N,N,N′,N′-Tetrakis{[4-(R)-ethyloxazolin-2-
yl]methyl}ethylenediamine (6)
Ethylenediaminetetraacetic acid (1.17 g, 4.0 mmol), (R)-2- the product was determined by optical rotation and its enantio-
amino-1-butanol (1.57 g, 17.6 mmol) and toluene (40 mL) were meric excess was determined by HPLC analysis with chiral
added to a three-neck flask with a water segregator, a reflux stationary phases.
condenser and a magnetic stirring bar. The mixture was re-
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Beilstein Journal of Organic Chemistry 2010, 6, No. 29.
16.Foltz, C.; Enders, M.; Bellemin-Laponnaz, S.; Wadepohl, H.;
Gade, L. H. Chem.–Eur. J. 2007, 13, 5994–6008.
doi:10.1002/chem.200700307
Supporting Information
Supporting information features spectroscopic data for the
hydrosilylation products of aromatic ketones (8a–8h) and
copies of 1H NMR and MS spectra for ligands (1–7).
17.Foltz, C.; Stecker, B.; Marconi, G.; Bellemin-Laponnaz, S.;
Wadepohl, H.; Gade, L. H. Chem.–Eur. J. 2007, 13, 9912–9923.
doi:10.1002/chem.200701085
18.Gade, L. H.; Bellemin-Laponnaz, S. Chem.–Eur. J. 2008, 14,
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Supporting Information File 1
19.Zhou, J.; Tang, Y. J. Am. Chem. Soc. 2002, 124, 9030–9031.
doi:10.1021/ja026936k
Concise methods for the synthesis of chiral polyoxazolines
and their application in asymmetric hydrosilylation.
[http://www.beilstein-journals.org/bjoc/content/
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Acknowledgements
The work was financially supported by the Guangdong Provin-
cial Research Foundation for Basic Research, China (Grant No.
04J004) and the National Research Foundation, South Africa
(Grant No. SFP 2007072300021).
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