Fluorous chiral bis(oxazolines): Synthesis and application in asymmetric Henry reaction

Article abstract of DOI:10.1016/j.jfluchem.2013.09.014

A fluorous bis(oxazolines) was synthesized by a facile two-step process using malononitrile as the starting material. The compound was tested as a chiral ligand in copper-catalyzed Henry reactions of nitromethane with different aldehydes to afford the cor

Full text of DOI:10.1016/j.jfluchem.2013.09.014

Journal of Fluorine Chemistry 156 (2013) 183–186
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Fluorous chiral bis(oxazolines): Synthesis and application in
asymmetric Henry reaction
*
Tao Deng, Chun Cai
School of Chemical Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei Street, Nanjing, Jiangsu, People’s Republic of China
A R T I C L E I N F O
A B S T R A C T
Article history:
A fluorous bis(oxazolines) was synthesized by a facile two-step process using malononitrile as the
starting material. The compound was tested as a chiral ligand in copper-catalyzed Henry reactions of
Received 24 May 2013
Received in revised form 24 September 2013
Accepted 27 September 2013
Available online 8 October 2013
nitromethane with different aldehydes to afford the corresponding b-nitroalcohols in 61–75% yield with
enantioselectivities up to 99%. Furthermore, the fluorous ligand can be easily recovered and reused
without significant loss in its activity.
ß 2013 Elsevier B.V. All rights reserved.
Keywords:
Fluorous bis(oxazolines)
Malononitrile
Henry reaction
Asymmetric catalysis
1. Introduction
complexes have been successfully used as chiral ligands for the
enantioselective Henry reaction, either with concurrent or
There is increasing interest in developing catalytic asymmetric
C–Cformationprocesses[1,2]. The Henry reactionwhichcanbeused
independent activation of both reagents [14,15]. However, this
kind of ligands is always expensive and difficult to recycle during
the reactions. An alternative strategy is to design recyclable and
subsequently reusable versions of ligands by fluorous technology.
Curran’s group reported the first example of application of solid–
liquid separations based on fluorous silica gel in 1997 [16]. Then,
fluorous techniques have been applied to many chemical
transformations, replacing standard polymer-supported methods
in the production of recyclable and reusable reagents. Recently,
some fluorous chiral ligands have been designed for a variety of
reactions including Michael addition, Diels–Alder and Aldol
reactions.
to create a new chiral carboncenterat the
is a powerful and atom-economical carbon–carbon formation
reaction [3–5]. The resulting -nitro alcohols can be transformed
into various important building blocks of natural products and
pharmaceuticals, such as -amino alcohols, -hydroxy ketones,
b-positionof a nitro group
b
b
a
aldehydes, carboxylic acids, azides, and sulfides [6]. Consequently,
increasing attention has recently been focused on the development
of novel catalytic, asymmetric versions of the Henry reaction [7,8].
Since 1992, asymmetric catalytic Henry reactions have been
gained particular attention. For example, Shibasaki and co-workers
have reported that rare-earth-metal complex La3(O-t-Bu)9 can be
applied as a catalyst for the enantioselective reaction of aldehydes
with nitroalkanes [9]. Jørgensen and co-workers reported the
However, there are few reports describing the recoverability of
fluorous bis(oxazolines) for the asymmetric catalysis [17]. Along
this line, we tried to introduce
a fluorous tail C6F13- to
catalytic asymmetric Henry reaction of
a
-keto esters with
bis(oxazolines) and studied the activity of the designed fluorous
bis(oxazolines) (Fig. 1) which was synthesized by an easy method
from malononitrile (Scheme 1) as a ligand in the Cu(II)-catalyzed
asymmetric Henry reaction (Scheme 2). Compared to traditional
recyclable supported ligands, the fluorous ligands are soluble in
common reaction solvents, yet they can be easily separated and
recovered from the reaction mixture by fluorous solid-phase
extraction (F-SPE).
nitromethane in the presence of chiral ligands [10]. Trost et al.
have disclosed a catalytic enantioselective Henry reaction employ-
ing a bimetallic zinc complex [11]. Evans et al. successfully
developed the asymmetric Henry reaction of aldehydes using a
bis(oxazoline) complex [12].
As one of the most popular classes of chiral ligands, C2-
bis(oxazolines) has received a great deal of attention in coordina-
tion chemistry and asymmetric catalysis [13]. Bis-oxazoline-based
2. Results and discussion
We first carried out the reaction of 4-nitrobenzaldehyde and
nitromethane as a model to optimize the reaction conditions.
*
Corresponding author. Tel.: +86 25 84315514; fax: +86 25 84315030.
E-mail address: c.cai@njust.edu.cn (C. Cai).
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.09.014

184
T. Deng, C. Cai / Journal of Fluorine Chemistry 156 (2013) 183–186
Table 2
Effect of solvent on Henry reaction of 4-nitrobenzaldehyde with nitromethane.
Entry
Solvent
Yieldb (%)
eec (%)
Fig. 1. Fluorous bis(oxazolines).
1
2
3
4
5
Tetrahydrofuran
Ethanol
41
75
62
35
38
68
99
89
66
43
Methanol
Table 1
Acetonitrile
Dichloromethane
Effect of different copper sources on Henry reaction.
aReaction condition: 1 mmol of 4-nitrobenzaldehyde, 10 mmol of nitromethane,
0.1 mmol of Et3N, 0.05 mmol of ligand and 0.1 mmol Cu(OAc)2in 1 mL of solvent.
b
Determined by HPLC.
c
Determined by chiral HPLC using a Ultron ES-OVM column. Reported values are
the average of two runs.
O
OH
Cu salt, Ligand
EtOH, Et3N
CH3NO2
Yieldb (%)
eec (%)
NO2
Entry
Copper source
Base (mol%)
R1
H
R1
1
None
Et3N(10)
Et3N(10)
Et3N(10)
Et3N(10)
Et3N(10)
Et3N(10)
–
12
63
59
61
58
75
32
36
54
–
–
98
98
96
98
99
67
70
99
–
2
CuCl2
3
CuCl
5
6
4
4
CuSO4
5
Cu
Scheme 2. Cu-catalyzed Henry reaction.
6
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
7
8
Et3N(5)
9d
10
11
Et3N(15)
Pyridine(10)
DBU(10)
Other bases such as pyridine, DBU were also tested in the reaction.
However, no better results were obtained than Et3N (Table 1,
entries 10 and 11).
Different solvents were tested in the asymmetric Henry
reaction between 4-nitro-benzaldehyde and nitromethane. With
Cu(OAc)2 as a catalyst and Et3N as a base, the protonic solvents
were superior to the aprotonic ones (Table 2, entries 1–5). As
a result, ethanol was the best solvent for this reaction (Table 2,
entry 2).
6
–
aReaction condition: 1 mmol of 4-nitrobenzaldehyde, 10 mmol of nitromethane,
0.05 mmol of ligand and 0.1 mmol metal salt in 1 mL of EtOH.
b
Determined by HPLC.
c
Determined by chiral HPLC using a Ultron ES-OVM column. Reported values are
the average of two runs.
d
15 mol% of ligand was added.
With the optimized conditions in hand, the scope of the
substrate was extended. A variety of aldehydes were employed as
substrates to react with nitromethane, giving the corresponding
products with high yields and ee values, as shown in Table 3. The
data clearly showed that ligand 3 and the optimized reaction
conditions can be applied in a wide scope of substrates. The
aromatic aldehydes could undergo an asymmetric Henry reaction
smoothly with good yields and ee values. The steric hindrance had
little influence on this reaction (Table 3, entries 1–11). The
aldehydes with electron-withdrawing group gave higher yields
(entries 1–7 vs. entries 9–11).
Table 1 summarizes the results obtained with various copper salts
under the different reaction conditions. Cu(OAc)2 gave a high yield
and good enantioselectivity (Table 1, entry 6). It was found that the
amount of base had significant influence to the conversion and
enantioselectivity. The yield dropped from 75 to 32% in the absence
of Et3N with a low enantioselectivity (Table 1, entry 7). An increase
of the amount of Et3N to 15 mol% relative to the ligand (5 mol%)
gave the same enantioselectivity but low yield, while a decrease in
the amount of Et3N to 5 mol% resulted in an obvious reduction in
both conversion and enantioselectivity (Table 1, entries 8 and 9).
Scheme 1. Preparation of fluorous bis(oxazolines).

T. Deng, C. Cai / Journal of Fluorine Chemistry 156 (2013) 183–186
185
Table 3
Enantioselective Henry reaction of nitromethane with various aldehydes.
4.1. Synthesis of the fluorous malononitrile (2)
A 50 mL round-bottom flask with a magnetic stir bar was
charged with malononitrile 1 (660 mg, 10 mmol, 1 equiv), K2CO3
(138 mg, 1 mmol, 0.1 equiv), and 15 mL of DMSO.
1H,1H,2H,2H-Perfluoro-1-iodo-n-octane (5 mL, 20 mmol,
2
equiv) was added via syringe. The mixture was stirred at room
temperature for 24 h. The reaction was then partitioned between
dilute hydrochloric acid (75 mL) and EtOAc (3 Â 25 mL). The
combined organic layer was washed with brine (100 mL), and then
dried over Na2SO4, concentrated in vacuo to give a brown-red solid
which was used without further purification for the next reaction.
Yield: 73%.
Entry
Aldehyde (R1)
Time (h)
Product
Yieldb (%)
eec (%)
1
p-NO2–C6H4–
p-Br–C6H4–
p-Cl–C6H4–
o-NO2–C6H4–
p-F–C6H4–
24
24
24
24
24
48
24
24
48
36
36
6a
6b
6c
6d
6d
6f
75
69
67
73
70
70
62
61
64
n.r.
n.r.
99
94
90
94
93
90
96
72
96
–
2
3
4
5
6
1-Naphthyl
o-Br–C6H4–
C6H5–
7
6 g
6 h
6i
4.2. 1,1-Bis[(4S)-4-phenyl-1,3-oxazolin-2-yl]-(1H,1H,2H,2H)-
perfluorooctane(3)
8
9
p-CH3–C6H4–
p-OCH3–C6H4–
p-NMe2–C6H4–
10
11
–
A 50 mL two-necked round-bottomed flask fitted with a reflux
condenser was charged with the fluorous malononitrile (652 mg,
1 mmol), zinc acetate (46 mg, 0.2 mmol), and toluene (10 mL). The
–
–
aReaction condition: 1 mmol of aldehyde, 10 mmol of nitroalkane, 0.1 mmol of Et3N,
0.05 mmol of ligand and 0.1 mmol Cu(OAc)2 in 1 mL of EtOH.
b
Determined by HPLC.
solution was stirred for 5 min and a solution of L-2-phenylglycinol
c
Determined by chiral HPLC using a Ultron ES-OVM column.Reported values are
(411 mg, 3 mmol) in toluene was added. The system was heated at
reflux for 24 h. After cooling to room temperature, the reaction was
then partitioned between H2O (50 mL) and EtOAc (30 mL). The
organic layer was washed with brine (2 Â 50 mL) and NaHCO3
(2 Â 50 mL), dried over Na2SO4 and concentrated in vacuo. The
crude product was purified by column chromatography (petro-
leum ether/ethyl acetate, 4:1, 0.4% NEt3). Yield: 52%.
the average of two runs.
Table 4
Recycling and reuse of the fluorous ligand by F-SPE.
Run
Recovered ligand (%)a
Yield of product (%)b
eec (%)
4.3. General procedure for asymmetric Henry reaction
–
–
96
94
90
75
72
71
67
99
>98
>98
>98
First reuse
Second reuse
Third reuse
To the mixture of ligand (5 mol%) in EtOH (1 mL), aldehyde
(1 mmol), Cu(OAc)2 (10 mol%), Et3N (10 mol%) and nitromethane
(10 equiv) were added at room temperature. After 24 h, the solvent
was evaporated in vacuo. The residue was dissolved in H2O (30 mL)
and was extracted by EtOAc (3 Â 10 mL). The combined organic
layer was dried over Na2SO4, and concentrated in vacuo. The
product 6 was purified by column chromatography on silica-gel
column to give the desired nitroaldol adduct. Enatiomeric excesses
were determined by chiral HPLC analysis using an Ultron ES-OVM
column.
a
Recovered by F-SPE.
Determined by HPLC.
b
c
Determined by chiral HPLC using a Ultron ES-OVM column.
We also examined the recovery of this fluorous ligand. The
results are listed in Table 4. As can be seen, the fluorous ligand
could be reused for three times without a significant loss of both
yields of the products and their ee values.
4.4. General procedure for recovery of fluorous bis(oxazolines)
3. Conclusion
After the reaction was finished, the mixture was concentrated
and then loaded onto a FluoroFlash1 silica gel for F-SPE. The
residue was eluted by methanol: water (v/v = 80:20) at first for the
seperation of non-fluorous component, pure methanol was then
added onto the fluorous gel column continuously for obtaining the
elutant of fluorous bis(oxazolines). When the bulk of solvent was
removed and the residue was dried in vacuo at 50 8C for 8 h to give
the fluorous bis(oxazolines). The recovered ligand could be used
directly for the next run.
In conclusion, a novel fluorous chiral bis(oxazolines) has been
synthesized and used in enantioselective Henry reaction in the
presence of copper acetate. The reactions proceeded smoothly to
provide the corresponding products in high enantioselectivities for
a wide range of aryl substrates. The process was carried out in
ethanol, and the corresponding
b-nitroalcohols were obtained in
61–75% yield with enantioselectivities up to 99%. The fluorous
ligand can be easily recovered and reused at least three times
without significant loss in its activity.
4.5. 1,1-Bis[(4S)-4-phenyl-1,3-oxazolin-2-yl]-(1H,2H,2H)-
perfluorooctane(3)
4. Experimental
1H NMR (500 MHz, CDCl3)
2H), 4.85–4.81 (m, 2H), 4.38–4.35 (m, 2H), 3.28–3.25 (m, 2H), 2.76–
2.72 (m, 2H); 13C NMR (125 MHz, CDCl3)
: 161.5, 139.4, 128.0,
127.3, 125.2, 117.3–107.5, 75.1, 68.8, 41.3, 27.5, 26.5; 19F NMR
(500 MHz, CDCl3)
À123.42 (m, 2F), À123.20 to À122.85 (m, 2F), À122.23 to À121.85
(m, 2F), À115.40 to À114.87 (m, 2F), À81.32 to À80.60 (m, 3F); MS
(ESI) m/z 653 (MH+); Anal. Calc. forC27H21F13N2O2: C, 49.70; H, 3.24;
N, 4.29. Found: C, 49.83; H, 3.18; N, 4.35.
d: 7.40–7.20 (m, 10H), 5.39–5.35 (m,
All reagents, such as nitromethane, L-2-phenylglycinol, various
aldehydes, and copper acetate, malononitrile, were used as
received from commercial sources. All reactions were carried
out under indicated conditions. NMR spectra were recorded at
500 MHz and tetramethylsilane (TMS) was used as a reference.
Elemental analysis was performed on a Vario EL III recorder. Mass
spectra were obtained with an automated Fininigan TSQ Advan-
tage mass spectrometer. The enantiomeric excess of the Henry
products was determined by HPLC on Ultron ES-OVM column.
d
d
: À126.55 to À126.14 (m, 2F), À123.77 to

186
T. Deng, C. Cai / Journal of Fluorine Chemistry 156 (2013) 183–186
4.6. (S)-1-(4-Nitrophenyl)-2-nitroethanol (6a)
4.12. (S)-1-(2-Bromophenyl)-2-nitroethanol (6 g)
This compound was prepared according to Section 4.3 and
purified by column chromatography (Hexane–EtOAc 7:3) to give a
This compound was prepared according to Section 4.3 and
purified by column chromatography (Hexane–EtOAc 5:1) to give a
colorless oil (62% yield); 1H NMR (500 MHz, CDCl3)
d: 8.07 (d,
yellow oil (75% yield); 1H NMR (500 MHz, CDCl3)
d
: 8.24–8.26 (m,
2H), 7.73–7.56 (m, 2H), 5.61–5.63 (m, 1H), 4.60–4.62 (m, 2H), 3.49
(s, 1H). HPLC analysis: Ultron ES-OVM column, 30:70 alcohol/
KH2PO4 (0.02 mol/L), flow rate = 1.8 mL/min, UV = 254 nm, major
enantiomer t1 = 2.52 min, minor enantiomer t2 = 1.83 min;
99% ee.
J = 8.2 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.73–7.76 (m, 1H), 7.53–7.56
(m, 1H), 6.03–6.05 (m, 1H), 4.86–4.89 (m, 2H), 4.18 (s, 1H). HPLC
analysis: Ultron ES-OVM column, 30:70 alcohol/KH2PO4 (0.02 mol/
L), flow rate = 1.8 mL/min, UV = 210 nm, major enantiomer
t1 = 2.09 min, minor enantiomer t2 = 2.65 min; 96% ee.
4.7. (S)-1-(4-Bromophenyl)-2-nitroethanol (6b)
4.13. (S)-1-Phenyl-2-nitroethanol (6 h)
This compound was prepared according to Section 4.3 and
purified by column chromatography (Hexane–EtOAc 5:1) to give a
This compound was prepared according to Section 4.3 and
purified by column chromatography (Hexane–EtOAc 5:1) to give a
colorless oil (61% yield); 1H NMR (500 MHz, CDCl3)
d: 7.38–7.42
colorless oil (69% yield); 1H NMR (500 MHz, CDCl3)
d
: 7.54 (d,
J = 7.4 Hz, 2H), 7.29 (d, J = 7.7 Hz, 2H), 5.44 (d, J = 9.2 Hz, 1H), 4.62–
4.45 (m, 2H), 3.04 (s, 1H). HPLC analysis: Ultron ES-OVM column,
30:70 alcohol/KH2PO4 (0.02 mol/L), flow rate = 1.8 mL/min,
UV = 210 nm, major enantiomer t1 = 3.18 min, minor enantiomer
t2 = 1.85 min; 94% ee.
(m, 5H), 5.46 (d, J = 9.6 Hz, 1H), 4.68–4.47 (m, 2H), 3.14 (s, 1H).
HPLC analysis: Ultron ES-OVM column, 30:70 alcohol/KH2PO4
(0.02 mol/L), flow rate = 1.8 mL/min, UV = 210 nm, major enantio-
mer t1 = 2.62 min, minor enantiomer t2 = 1.95 min; 72% ee.
4.14. (S)-1-(4-Methylphenyl)-2-nitroethanol (6i)
4.8. (S)-1-(4-Chlorophenyl)-2-nitroethanol (6c)
This compound was prepared according to Section 4.3 and
purified by column chromatography (Hexane–EtOAc 8:1) to give a
This compound was prepared according to Section 4.3 and
purified by column chromatography (Hexane–EtOAc 5:1) to give a
colorless oil (64% yield); 1H NMR (500 MHz, CDCl3)
d: 7.70–6.86
colorless oil (67% yield); 1H NMR (500 MHz, CDCl3)
d: 7.67–7.68
(m, 4H), 5.44–5.46 (m, 1H), 4.50–4.65 (m, 2H), 2.87 (s, 1H), 2.38 (s,
3H).
HPLC analysis: Ultron ES-OVM column, 30:70 alcohol/KH2PO4
(0.02 mol/L), flow rate = 1.8 mL/min, UV = 230 nm, major enantio-
mer t1 = 2.01 min, minor enantiomer t2 = 1.80 min; 96% ee.
(m, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.41–7.42 (m, 1H), 7.30–7.23 (m,
1H), 5.81–5.83 (m, 1H), 4.42–4.72 (m, 2H), 3.11 (s, 1H). HPLC
analysis: Ultron ES-OVM column, 30:70 alcohol/KH2PO4 (0.02 mol/
L), flow rate = 1.8 mL/min, UV = 230 nm, major enantiomer
t1 = 2.17 min, minor enantiomer t2 = 2.44 min; 90% ee.
References
4.9. (S)-1-(2-Nitrophenyl)-2-nitroethanol (6d)
[1] E. Marqus-Lopez, P.Merino,T. Tejero, R.P.Herrera, Eur.J.Org. Chem.15(2009)2401–
2420.
This compound was prepared according to Section 4.3 and
purified by column chromatography (Hexane–EtOAc 5:1) to give a
[2] B. Zhang, L. Cai, H. Song, Z. Wang, Z. He, Adv. Synth. Catal. 352 (2010) 97–102.
[3] C. Baleizao, H. Garcia, Chem. Rev. 106 (2006) 3987–4043.
[4] J. Park, K. Lang, K.A. Abboud, S. Hong, J. Am. Chem. Soc. 130 (2008) 16484–16485.
[5] L.E. Blidi, Z. Assaf, F.C. Bres, H. Veschambre, V. Thery, J. Bolte, M. Lemaire,
ChemCatChem 1 (2009) 463–471.
[6] (a) For references on the Henry reaction in organic synthesis see: C. Palomo, M.
Oiarbide, A. Mielgo, Angew. Chem. Int. Ed. 43 (2004) 5442–5444;
(b) A. Zulauf, M. Mellah, E. Schulz, J. Org. Chem. 74 (2009) 2242–2245;
(c) C. Palomo, M. Oiarbide, A. Laso, Eur. J. Org. Chem. 16 (2007) 2561–2574;
(d) S.L. Liu, C. Wolf, Org. Lett. 10 (2008) 1831–1834;
(e) S. Selvakumar, D. Sivasankaran, V.K. Singh, Org. Biomol. Chem. 7 (2009) 3156–
3162;
(f) C.S. Gan, J. Pan, Chin. J. Org. Chem. 28 (2008) 1193–1198.
[7] M. Breuning, D. Hein, M. Steiner, V.H. Gessner, C. Strohmann, Chem. Eur. J. 15
(2009) 12764–12769.
[8] A. Noole, K. Lippur, A. Metsala, M. Lopp, T. Kanger, J. Org. Chem. 75 (2010) 1313–
1316.
[9] H. Sasai, T. Suzuki, S. Arai, T. Arai, M. Shibasaki, J. Am. Chem. Soc. 114 (1992) 4418–
4420.
[10] (a) C. Christensen, K. Juhl, K.A. Jøgensen, Chem. Commun. 21 (2001) 2222–2223;
(b) C. Christensen, K. Juhl, R.G. Hazell, K.A. Jørgensen, J. Org. Chem. 67 (2002)
4875–4881.
[11] (a) B.M. Trost, V.S.C. Yeh, Angew. Chem. Int. Ed. 41 (2002) 861–863;
(b) B.M. Trost, V.S.C. Yeh, H. Ito, N. Bremeyer, Org. Lett. 4 (2002) 2621–2623.
[12] D.A. Evans, D. Seidel, M. Rueping, H.W. Lam, J.T. Shaw, C.W. Downey, J. Am. Chem.
Soc. 125 (2003) 12692–12693.
yellow oil (73% yield); 1H NMR (500 MHz, CDCl3)
d: 8.07 (d,
J = 8.2 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.73–7.76 (m, 1H), 7.53–7.56
(m, 1H), 6.02–6.04 (m, 1H), 4.53–4.86 (m, 2H), 4.18 (s, 1H). HPLC
analysis: Ultron ES-OVM column, 30:70 alcohol/KH2PO4 (0.02 mol/
L), flow rate = 1.8 mL/min, UV = 254 nm, major enantiomer
t1 = 2.06 min, minor enantiomer t2 = 2.64 min; 94% ee.
4.10. (S)-1-(4-Fluorophenyl)-2-nitroethanol (6e)
This compound was prepared according to Section 4.3 and
purified by column chromatography (Hexane–EtOAc 7:3) to give a
colorless oil (70% yield); 1H NMR (500 MHz, CDCl3)
d
: 7.41–7.43
(m, 2H), 7.10–7.13 (m, 2H), 5.47–5.49 (m, 1H), 4.50–4.63 (m, 2H),
3.02 (s, 1H). HPLC analysis: Ultron ES-OVM column, 30:70 alcohol/
KH2PO4 (0.02 mol/L), flow rate = 1.8 mL/min, UV = 230 nm, major
enantiomer t1 = 2.04 min, minor enantiomer t2 = 1.82 min;
93% ee.
[13] H.A. McManus, P.J. Guiry, Chem. Rev. 104 (2004) 4151–4202.
[14] T. Risgaard, K.V. Gothelf, K.A. Jorgensen, Org. Biomol. Chem. 1 (2003) 153–156.
[15] K. Lang, J. Park, S. Hong, J. Org. Chem. 75 (2010) 6424–6435.
[16] D.P. Curran, S. Hadida, M. He, J. Org. Chem. 62 (1997) 6714–6715.
[17] (a) J. Bayardon, D. Sinou, J. Org. Chem. 69 (2004) 3121–3128;
(b) B. Simonelli, S. Orlandi, M. Benaglia, G. Pozzi, Eur. J. Org. Chem. 12 (2004)
2669–2673;
4.11. (S)-1-(Naphthalen-1-yl)-2-nitroethanol (6f)
This compound was prepared according to Section 4.3 and
purified by column chromatography (Hexane–EtOAc 5:1) to give a
yellow oil (70% yield). 1H NMR (500 MHz, CDCl3)
J = 8.4 Hz, 1H), 7.94 (d, J = 8.1 Hz, 2H), 7.89 (d, J = 8.2 Hz, 1H), 7.53–
7.63 (m, 3H), 6.30 (d, J = 8.6 Hz, 1H), 4.71 (m, 2H), 2.98 (s, 1H). HPLC
analysis: Ultron ES-OVM column, 30:70 alcohol/KH2PO4 (0.02 mol/
L), flow rate = 1.8 mL/min, UV = 230 nm, major enantiomer
t1 = 2.44 min, minor enantiomer t2 = 3.93 min; 90% ee.
d: 8.07 (d,
(c) J. Bayardon, D. Sinou, Tetrahedron Asymmetry 16 (2005) 2965–2972;
(d) J. Bayardon, O. Holczknecht, G. Pozzi, D. Sinou, Tetrahedron Asymmetry 17
(2006) 1568–1572;
(e) R. Kolodziuk, C. Goux-Henry, Denis Sinou, Tetrahedron Asymmetry 18 (2007)
2782–2786;
(f) R. Rasappan, T. Olbrich, O. Reiser, Adv. Synth. Catal. 351 (2009) 11961–11967.