Asymmetric Henry reactions catalyzed by copper(II) complexes of chiral 1,2,4-triazine-oxazoline ligands: The impact of substitution in the oxazoline ring on ligand activity

Article abstract of DOI:10.1016/j.tetasy.2014.06.019

An enantiomerically pure 1,2,4-triazine-oxazoline ligand with an indanol-derived substituent in the oxazoline ring has been synthesized using Buchwald-Hartwig amination of 3-bromo-1,2,4-triazine. The catalytic efficiency of the ligand was estimated in the

Full text of DOI:10.1016/j.tetasy.2014.06.019

Tetrahedron: Asymmetry 25 (2014) 1122–1128
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric Henry reactions catalyzed by copper(II) complexes of
chiral 1,2,4-triazine-oxazoline ligands: the impact of substitution in
the oxazoline ring on ligand activity
⇑
´
Ewa Wolinska
Department of Chemistry, Siedlce University, 08-110 Siedlce, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 May 2014
Accepted 30 June 2014
An enantiomerically pure 1,2,4-triazine-oxazoline ligand with an indanol-derived substituent in the
oxazoline ring has been synthesized using Buchwald–Hartwig amination of 3-bromo-1,2,4-triazine.
The catalytic efficiency of the ligand was estimated in the asymmetric nitroaldol (Henry) reaction of
nitromethane with several aromatic and aliphatic aldehydes. The appropriate nitroaldol products were
formed in good yields (up to 91%) and with up to 92% ee. In order to investigate the influence of the con-
formational rigidity and the additional stereocenter in the oxazoline ring on the catalytic activity of the
ligand, a 1,2,4-triazine-oxazoline ligand with two phenyl substituents in the oxazoline ring was synthe-
sized and tested in the asymmetric nitroaldol reaction.
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
the Ni-catalyzed asymmetric synthesis of a precursor to the drug
Zoloft.5
Chiral oxazoline ligands can form complexes with various metal
ions; these complexes are excellent chiral catalysts in catalytic
asymmetric reactions. Since the first report in 1986 on the use of
chiral oxazoline based ligands, their applicability in asymmetric
metal-catalyzed transformations has been demonstrated in
numerous processes and has been reported in several comprehen-
sive reviews devoted to this class of ligands.1 A large number of
papers concerning chiral oxazoline ligands have been published
over the last year, thus proving the continued interest in these
ligands. For example, spiro phosphine–oxazoline ligands were suc-
cessfully applied in the asymmetric hydrogenation of cyclic
During our research, we recently developed chiral 1,2,4-tri-
azine-oxazoline ligands 1 (Fig. 1).6 These ligands differ in the type
of flexible substituent in the oxazoline ring and substitution in the
1,2,4-triazine.
The catalytic activity of the ligands was evaluated in the asym-
metric nitroaldol reaction of nitromethane with a variety of aro-
matic and aliphatic aldehydes. The best enantioselectivity was
achieved using ligand 1f. The corresponding nitroaldol products
were formed in yields of up to 95% and with enantioselectivities
a
-alkylidene carbonyl compounds.2 The high enantiocontrol of
R2
N
N
the oxazoline ligands arises from the fact that the stereogenic cen-
ter of the ligands is situated next to the coordinating nitrogen atom
of the oxazoline ring and therefore close to the metal active site
having a direct influence on the stereochemical outcome of the
process. Legault reported new iodoaryloxazoline catalysts bearing
stereogenic center alpha to the oxazoline oxygen and proved their
R3
N
N
H
N
O
∗
R1
1a - k
potential in catalyzing the enantioselective
a-tosyloxylation of
g: R2 = H, R3 = Ph, R1 = i-Pr (S)
a: R2 = R3 = Ph, R1 = t-Bu (S)
ketones.3 Tartrate-derived bisoxazoline ligands have been recently
found to be highly active in the asymmetric allylic alkylation reac-
tions of various allyl acetates.4 Bisoxazolines were also applied in
: R2 = R3 = Ph, R1 = Ph (S)
h
b
: R2 = H, R3 = t-Bu, R1 = t-Bu (S)
i: R2 = H, R3 = t-Bu, R1 = Ph (S)
c: R2 = R3 = Ph, R1 = i-Pr (S)
d
: R2 = H, R3 = t-Bu, R1 = i-Pr (S)
k: R2 = H, R3 = t-Bu, R1 = Bn (R)
: R2 = R3 = Ph, R1 = Bn (R)
j
e: R2 = H, R3 = Ph, R1 = t-Bu (S)
: R2 = H, R3 = Ph, R1 = Ph (S)
f
⇑
Tel.: +48 25 6431116; fax: +48 25 6442095.
E-mail address: ewol@uph.edu.pl
Figure 1. Previous work: 1,2,4-triazine-oxazoline ligands with
substituent in the oxazoline ring.
a flexible
http://dx.doi.org/10.1016/j.tetasy.2014.06.019
0957-4166/Ó 2014 Elsevier Ltd. All rights reserved.

´
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E. Wolinska / Tetrahedron: Asymmetry 25 (2014) 1122–1128
of 35–82%. The structure of ligand 1f is composed of a 1,2,4-tri-
azine with a phenyl ring at the 5-position and an oxazoline with
a Ph substituent. In line with our interest in developing chiral
ligands such as 1, we decided to study the influence of the substi-
tution in the oxazoline ring on the catalytic activity. Herein we
report the synthesis and catalytic activity of ligand 2 incorporating
the indane unit (Fig. 2). The indane ring prevents free rotation
about the CAPh bond, thus enforcing conformational rigidity.7
Oxazolines with an indane unit were found to be highly effective
chiral controllers for catalytic asymmetric Diels–Alder reactions8
and Friedel–Crafts alkylation.9 The structure of ligand 2 differs
from ligand 1f due to the additional stereocenter at the 5-position
of the oxazoline ring. For comparison studies ligand 3 with two
stereocenters in the oxazoline ring was synthesized (Fig. 2). In con-
trast to ligands 1a–c and 1e–j, ligands 2 and 3 possess an (R)-con-
figured stereocenter at the 4-position of the oxazoline ring. The
catalytic activity of ligands 2 and 3 in the asymmetric nitroaldol
reaction is discussed.
which shortened the reaction time to 24 h in comparison to exper-
iments carried out with a catalytic amount of ZnCl2.10 Subsequent
Buchwald–Hartwig amination of 3-bromo-5-phenyl-1,2,4-triazine
9 with oxazoline 711 using Pd2dba3 as the palladium source and
Xantphos as the ligand resulted in the formation of ligand 2 in
56% yield. An analogous reaction between triazine 9 and amino
derivative 8 provided ligand 3 in 51% yield.
2.2. Enantioselective Henry reactions
The asymmetric Henry reaction between 3-nitrobenzaldehyde
and nitromethane was selected as a model reaction in order to
evaluate the catalytic ability of ligand 2. Initially, the reaction
was investigated by using different metal salts and solvents at
room temperature and the results are shown in Table 1.
It was observed that the type of precatalyst used had a signifi-
cant effect on the yield and stereochemical outcome of the process.
The application of Cu(OAc)2ÁH2O in 2-propanol provided the best
results. The b-nitro alcohol was obtained in 71% yield and with
44% enantiomeric excess (Table 1, entry 1). Among the copper(I)
precatalysts, only copper(I) thiopheno-2-carboxylate (CuTC) and
copper(I) 3-methylsalicylate12 (CuSal) catalyzed the nitroaldol
reaction, but the yield of the product dropped dramatically to
61% and 36%, respectively. The reduction of the reaction yield
was probably caused by the bulkiness of the carboxylate ions.
The enantioselectivity of the reaction was unchanged when CuTC
was used as the metal source (Table 1, entry 2). The application
of CuSal afforded the product with a significantly higher enantiose-
lectivity of 61% (Table 1, entry 3). Catalysts CuCl, Cu(OTf)2, and
Zn(OTf)2 were inefficient in the asymmetric addition of nitrometh-
ane to 3-nitrobenzaldehyde (Table 1, entries 4–6). Next, the impact
of solvent was studied. 2-Propanol promoted the highest enanti-
oselectivity, although the yield was low due to the limited solubil-
ity in 2-propanol of the complexes generated (Table 1, entry 1).
When THF was used as the reaction medium, the product was
formed in a better yield of 82%, but with a much lower enantiose-
lectivity of 12% in comparison to that obtained in 2-propanol
(Table 1, entry 7). Similarly, the product was obtained in good yield
but with a decrease in enantioselectivity when the mixture of
2-propanol and THF (1:2) was applied as the solvent (Table 1, entry
8). The enantioselectivity increased to 38% if the ratio of 2-propa-
nol and THF was changed to 1:1 (Table 1, entry 9). Since the high-
N
N
N
N
Ph
N
N
H
Ph
N
N
H
N
O
N
O
Ph
Ph
2
3
Figure 2. Ligands 2 and 3.
2. Results and discussion
2.1. Synthesis of ligands
We envisaged that ligands 2 and 3 could be obtained by using
the synthetic strategy adopted for the synthesis of ligands 1.
Accordingly, the synthesis began with the preparation of oxazoline
derivatives 7 and 8 via the Zn-catalyzed condensation of 2-amino-
benzonitrile with the appropriate enantiopure aminoalcohols
(Scheme 1). A threefold excess of ZnCl2 was used in the reactions,
N
N
H2N
Ph
N
N
H
N
O
N
O
N
N
HO
N
H2N
5
Ph
Br
2
7
9
CN
ZnCl2
Pd2dba3, Xantphos
K2CO3
Chlorobenzene
dioxane
NH2
reflux
reflux
4
N
N
Ph
Ph
Ph
O
Ph
N
N
Ph
HO
NH2
H
N
N
O
6
NH2
Ph
Ph
3
8
Scheme 1. Synthesis of ligands 2 and 3.

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E. Wolinska / Tetrahedron: Asymmetry 25 (2014) 1122–1128
Table 1
Table 2
Optimization of reaction conditionsa
Scope of aldehydes in the catalytic enantioselective Henry reactiona
O
Cu(OAc)2·H2O (5 mol%)
OH
ligand 2 (5 mol%)
O
OH
precatalyst (5 mol%)
NO2
CH3NO2
+
H
ligand 2 (5 mol%)
NO2
R
H
2-propanol, rt
R
CH3NO2
+
solvent, rt
10a - r
11
12a - r
NO2
NO2
R
Aldehyde
Product
Yieldb
%
eec
%
10a
11
12a
1
2
3
4
5
6
7
8
3-NO2C6H4
Ph
2-NO2C6H4
4-NO2C6H4
2-ClC6H4
10a
10b
10c
10d
10e
10f
10g
10h
10h
10i
12a
12b
12c
12d
12e
12f
12g
12h
12h
12i
71
54
73
86
75
41
47
81
Traces
66
25
57
91
20
40
20
12
72
42
27
44 (R)
77 (R)
62 (R)
44 (R)
77 (R)
74 (R)
78 (R)
77 (R)
—
92 (R)
76 (R)
77 (R)
76 (R)
82 (R)
82 (R)
79 (R)
70 (R)
75 (R)
60 (R)
65 (R)
Solvent
Precatalyst
Yieldb
%
eec
%
1
2
3
4
5
6
7
8
9
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
THF
Cu(OAc)2ÁH2O
71
61
36
0
0
0
82
76
92
44 (R)
44 (R)
61 (R)
—
—
—
12 (R)
15 (R)
38 (R)
CuTCd
CuSale
3-ClC6H4
4-ClC6H4
CuCl
Cu(OTf)2
Zn(OTf)2
Cu(OAc)2ÁH2O
Cu(OAc)2ÁH2O
Cu(OAc)2ÁH2O
2-BrC6H4
2-BrC6H4
2-MeC6H4
3-MeC6H4
4-MeC6H4
2-MeOC6H4
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
9d
10
11
12
13
14d
15
16
17
18
19
20
i-PrOH/THF (1:2)
i-PrOH/THF (1:1)
10j
10k
10l
12j
12k
12l
a
All reactions were performed on a 0.5 mmol scale with 5 mol % of ligand and
5 mol % of precatalyst in 2 mL of solvent at room temperature for 98 h.
Yields of isolated products.
Enantiomeric excess was determined by HPLC using Chiracel OD-H column. The
absolute configuration was assigned by comparing their specific rotations or the
HPLC elution order with data from the literature.
10l
12l
b
10m
10n
10o
10p
10q
10r
12m
12n
12o
12p
12q
11r
c
3,4-(MeO)2C6H4
1-naphthyl
PhCH2CH2
d
Copper(I) thiopheno-2-carboxylate.
Copper(I) 3-methylsalicylate.
e
CH3(CH2)3
a
All reactions were performed on a 0.5 mmol scale with 5 mol % of ligand and
5 mol % of Cu(OAc)2ÁH2O in 2 mL of 2-propanol at room temperature for 98 h.
b
est enantioselectivity was generated in 2-propanol, it was chosen
for further studies.
Yields of isolated products.
c
Enantiomeric excess was determined by HPLC using Chiracel OD-H or AD-H
column. The absolute configuration was assigned by comparing their specific
rotations or the HPLC elution order with data from the literature.
Reaction was carried out in the presence of copper(I) thiopheno-2-carboxylate
(CuTC) instead of Cu(OAc)2ÁH2O.
The scope of the nitroaldol reaction was examined under the
optimized conditions described above. A variety of aldehydes were
subjected to reaction with 10 equiv of nitromethane in the pres-
ence of 5 mol % of ligand 2 and Cu(OAc)2ÁH2O in 2-propanol at
room temperature. The corresponding nitroaldol products were
obtained in 12–91% yield. In all cases, the (R)-enantiomer was
formed predominantly with enantiomeric excesses ranging from
44–92%.
d
of CuTC as a precatalyst in the addition of nitromethane to 2-
bromo- and 2-methoxybenzaldehyde was examined. Only trace
amounts of the product were formed in the reaction with 2-bromo-
benzaldehyde (Table 2, entry 9). The yield of reaction between
nitromethane and 2-methoxybenzaldehyde catalyzed by 2-CuTC
dropped dramatically to 20% (Table 2, entry 14).
Aldehydes substituted with electron-withdrawing groups
underwent the addition of nitromethane in higher yield than benz-
aldehyde and aldehydes possessing electron-donating groups
(Table 2, entries 1 and 3–8). The position of the substituent on
the aromatic ring strongly affected the chemical yield of the reac-
tion. When ortho-substituted aldehydes were subjected to the
addition of nitromethane, the reaction rate was significantly
higher, while substitution at the meta- or para-position resulted
in a decreased yield. This generalization was not valid in the case
of the three isomeric nitrobenzaldehydes, since 4-nitrobenzalde-
hyde was the most reactive among them (Table 2, entries 1, 3
and 4). The reactivity of methoxybenzaldehydes decreased in the
order ortho, meta, and para (Table 2, entries 13, 15, and 16).
Although, the lowest enentioselectivities were observed for nitro-
benzaldehydes, the electronic nature of the substituents had little
influence on the enantioselectivities. Inspection of Table 2 indi-
cates, that for aldehydes possessing electron-withdrawing as well
as electron-donating groups on the phenyl ring, high enantiomeric
excesses were observed. However, 2-methylbenzaldehyde pro-
duced the Henry adduct with the highest enantioselectivity of
92% (Table 2, entry 10). Very good enantioselectivities of 72–89%
were observed for methoxybenzaldehydes 10m, 10n, and 10l
(Table 2, entries 13–16). A relatively good yield (72%) and enantio-
meric excess (75%) were obtained for 1-naphthaldehyde (Table 2,
entry 18). The aliphatic aldehydes provided the respective nitroad-
duct in low yield and with moderate enantioselectivity (Table 1,
entries 19 and 20). Benzaldehyde substituted with two methoxy
groups gave the corresponding product in the lowest yield among
the aldehydes screened (Table 2, entry 17). In addition, the impact
In comparison to our previously described ligand 1f,6 ligand 2
possesses better asymmetric induction abilities. The enantiomeric
excesses observed using ligand 2 were significantly higher. Only
three isomeric nitrobenzaldehydes gave the products with enan-
tiomeric excesses similar to those obtained by using ligand 1f. It
is noteworthy that in the asymmetric addition of nitromethane
to 4-chlorobenzaldehyde catalyzed by 1f–Cu(OAc)2ÁH2O the
expected nitroaldol product was not formed. The application of
ligand 2 in the reaction resulted in the formation of product 12g
in 48% yield and with 78% ee (Table 2, entry 7). Similarly, only trace
amounts of product 12n were observed when 4-methoxybenzalde-
hyde was subjected to the addition of nitromethane in the pres-
ence of ligand 1f. When the reaction was conducted in the
presence of 2 product 12n was isolated in better yield (Table 2,
entry 16). Since ligand 2 has an opposite configuration of the ste-
reocenter at the 4-position of the oxazoline ring, the (R)-enantio-
mers of the b-nitro alcohols were predominantly formed in
comparison to those obtained by using 1f. Slightly lower chemical
yields were observed in reactions catalyzed by ligand 2 due to lim-
ited solubility of the complexes generated in 2-propanol. Improv-
ing the solubility by adding THF resulted in a decrease in the
enantioselectivity (Table 1). The higher rate of enantioselectivity
generated by ligand 2 could be due to two features: the conforma-
tional rigidity and/or presence of an additional stereocenter in the
oxazoline ring of ligand 2.

´
1125
E. Wolinska / Tetrahedron: Asymmetry 25 (2014) 1122–1128
Table 3
4. Experimental part
Application of ligand 3 in the catalytic enantioselective Henry reactiona
Cu(OAc)2·H2O (5 mol%)
ligand 3 (5 mol%)
4.1. General
OH
O
CH3NO2
NO2
+
1H and 13C NMR spectra were determined at 400 and 100 MHz,
respectively, with a Varian 400 MR spectrometer. Chemical shifts
(d) are reported in part per million from tetramethylsilane with
the solvent resonance as the internal standard. Coupling constants
are given as absolute values expressed in Hertz. Mass spectra were
obtained by using AMD 604 (AMD Intectra GmbH, Germany) and
GC/MS QP 5050 Shimadzu (30 m  0.25 mm ID-BPX 5 0.25 mm)
spectrometers. Infrared spectra were obtained by using a Magna
FTIR—760 Nicolet apparatus and Shimadzu FT IR Affinity-1 Spec-
trometer. Elemental analyses were recorded with a Elementar
Vario EL III CHNS analyzer and the results for indicated elements
were within 0.3% of the calculated values. Optical rotation values
were measured at room temperature with a Perkin–Elmer polarim-
eter. The ee values were determined by HPLC (Knauer) analysis by
using a chiral stationary phase column (Chiralcel OD-H or Chiralcel
AD-H), and elution with isopropanol–hexanes. Thin layer
chromatography (TLC) was carried out on aluminum sheets perco-
lated with silica gel 60 F254 (Merck). Column chromatography
separations were performed by using Merck Kieselgel 60 (0.040–
0.060 mm). Solvents were dried and distilled according to standard
procedures. 3-Bromo-5-phenyl-1,2,4-triazine13 9 and copper(I)
3-methylsalicylate12 were synthesized according to literature
procedures.
R
2-propanol, rt
R
H
12a, b, g - n, p
10a, b, g - n, p
11
R
Aldehyde
Product
Yieldb
%
eec
%
1
2
3
4
5
6
7
8
3-NO2C6H4
Ph
10a
10b
10g
10h
10i
10j
10k
10l
12a
12b
12g
12h
12i
12j
12k
12l
85
26
61
69
65
30
40
81
52
17
55
49 (R)
53 (R)
59 (R)
78 (R)
53 (R)
50 (R)
49 (R)
68 (R)
54 (R)
43 (R)
40 (R)
4-ClC6H4
2-BrC6H4
2-MeC6H4
3-MeC6H4
4-MeC6H4
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
1-Naphthyl
9
10
11
10m
10n
10p
12m
12n
12p
a
All reactions were performed on a 0.5 mmol scale with 5 mol % of ligand and
5 mol % of Cu(OAc)2ÁH2O in 2 mL of 2-propanol at room temperature for 98 h.
b
Yields of isolated products.
c
Enantiomeric excess was determined by HPLC using Chiracel OD-H column. The
absolute configuration was assigned by comparing their specific rotations or the
HPLC elution order with data from the literature.
To investigate the role of the additional stereocenter, the cata-
lytic activity of ligand 3 possessing two phenyl substituents in
the oxazoline ring was evaluated. Ligand 3 was used in the Henry
reaction between a few aromatic aldehydes and nitromethane. The
results are reported in Table 3. Comparing these results with those
summarized in Table 2, it is evident that ligand 3 possesses lower
enantiocontrolling abilities than ligand 2. In the presence of ligand
3, the same level of enantioselectivity was observed only for 2-bro-
mobenzaldehyde (Table 3, entry 4). The enantiomeric excesses of
the products in reactions with other aldehydes were significantly
lower than those obtained when using ligand 2. The enantioselec-
tivities obtained in reactions catalyzed by ligand 3 were similar to
those generated by ligand 1f.6 This proves that a second stereocen-
ter at the 5-position of the oxazoline ring of ligand 3 does not have
any influence on the stereochemical outcome of the nitroaldol
reaction. It can therefore be assumed that the impact of the addi-
tional stereocenter in ligand 2 on the enantioselectivity is insignif-
icant, and that the enantioselectivities obtained in reactions
catalyzed by this ligand are due to the conformational rigidity of
its structure.
4.2. Synthesis of 2-[(3aR,8aS)-8,8a-dihydro-3aH-indeno[1,2-d]-
oxazol-2-yl]aniline 7 and 2-[(4R,5S)-4,5-diphenyl-4,5-di-
hydrooxazol-2-yl]aniline 8
An oven dried two-necked flask was washed with argon and
charged with 2-aminobenzonitrile (118 mg, 1 mmol), (1R,2S)-1-
amino-2-indanol
5 or (1S,2R)-2-amino-1,2-diphenylethanol 6
(1.2 mmol), freshly flame dried ZnCl2 (405 mg, 3 mmol), and anhy-
drous chlorobenzene (6 mL). The mixture was stirred at reflux for
24 h. The solvent was then removed under reduced pressure and
the residue was stirred with 30% NaOH for 0.5 h. The product
was extracted with dichloromethane and purified by flash column
chromatography on silica gel (hexane/EtOAc, 5:1).
4.2.1. 2-[(3aR,8aS)-8,8a-Dihydro-3aH-indeno[1,2-d]oxazol-2-yl]-
aniline 7
All the physical and spectroscopic data of compound 7 are in
agreement with the published ones.14
4.2.2. 2-[(4R,5S)-4,5-Diphenyl-4,5-dihydrooxazol-2-yl]aniline 8
The product was obtained from (1S,2R)-2-amino-1,2-diphenyl-
ethanol 6 as a white solid, yield 57% (178 mg). Mp 91–92 °C.
3. Conclusion
[a
]
D
20 = À13.3 (c 1.00, CH2Cl2). 1H NMR (400 MHz, CDCl3) d: 7.91
In conclusion, we have reported on the synthesis of a new 1,2,4-
triazine-oxazoline ligand 2 with a restricted phenyl substituent at
the 4-position of the oxazoline ring and ligand 3 with two phenyl
substituents in the oxazoline. The synthesis was performed using
Buchwald–Hartwig amination as the key step. The catalytic effi-
ciency of both ligands was evaluated in the Cu-catalyzed asymmet-
ric nitroaldol reaction. The enantiocontrol of ligand 2 predominates
over the catalytic abilities of ligand 3. It was proven that the pres-
ence of a second stereocenter in the oxazoline ring of ligands 2 and
3 had no effect on the enantioselectivity of the nitroaldol reaction.
The enantioinduction generated by ligand 2 is governed by the
conformational rigidity of its structure. Studies aimed at elucidat-
ing upon the transition state for the catalysis are currently in
progress.
(dd, J = 1.2, 7.6 Hz, 1H), 7.29 (ddd, J = 1.6, 7.2, 8.4 Hz, 1H), 7.07–
7.02 (m, 6H), 6.97–6.95 (m, 4H), 6.78 (dd, J = 0.4, 8.0 Hz, 1H),
6.74 (dt, J = 1.2, 8.4 Hz, 1H), 6.24 (br s, 2H), 5.92 (d, J = 10.0 Hz,
1H), 4.80 (d, J = 10.0 Hz, 1H). 13C NMR (400 MHz, CDCl3) d: 165.4,
148.9, 137.9, 136.5, 132.6, 130.0, 127.7, 127.65, 127.6, 127.4,
127.0, 126.4, 116.3, 115.9, 108.4, 83.6, 74.3. HRMS (ESI, m/z): calcd
for C21H19N2O ([M+H]+), 315.1492, found 315.1487.
4.3. General procedure for the synthesis of ligands 2 and 3
An oven dried three-necked flask was washed with argon and
charged with Pd2dba3 (45.8 mg, 10 mol %), Xantphos (57.8 mg,
20 mol %), oxazoline derivative 7 or 8 (0.6 mmol), 3-bromo-5-phe-
nyl-1,2,4-triazine
9 (118 mg, 0.5 mmol), and K2CO3 (1.38 g,

´
E. Wolinska / Tetrahedron: Asymmetry 25 (2014) 1122–1128
1126
10 mmol). Next, the flask was evacuated and backfilled with argon.
Dioxane (10 mL) was added via the septum after which the mix-
ture was refluxed for 24 h. After cooling, the solid material was fil-
tered off and washed with CH2Cl2. The solvent was evaporated, and
the resulting crude products were purified by column chromatog-
raphy using hexanes/ethyl acetate (10:1 for 2 and 5:1 for 3) as the
eluent and recrystallized from ethanol.
CH2Cl2), 94% ee}. 1H NMR (400 MHz, CDCl3) d: 8.33 (s, 1H), 8.23
(d, J = 8.0 Hz, 1H), 7.77 (d, J = 7.6 Hz, 1H), 7.62 (t, J = 8.0 Hz, 1H),
5.62–5.59 (m, 1H), 4.66–4.56 (m, 2H), 3.12 (d, J = 4.0 Hz, 1H).
HPLC16 (Chiralcel OD-H, Hexane/i-PrOH = 90:10, flow rate:
1.0 mL/min, k = 215 nm), tmajor = 28.4, tminor = 33.0, 44% ee.
4.4.2. (R)-2-Nitro-1-phenylethanol 12b
Compound 12b was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
4.3.1. N-{2-[(3aR,8aS)-8,8a-Dihydro-3aH-indeno[1,2-d]oxazol-2-
yl]pheny}-5-phenyl-1,2,4-triazin-3-amine 2
tate 7:1) to give a colorless oil (45 mg, 54% yield). [
a]
20 = À42.5
D
The product was obtained from 3-bromo-5-phenyl-1,2,4-
triazine (9) and 2-[(3aR,8aS)-8,8a-dihydro-3aH-indeno[1,2-d]oxa-
zol-2-yl]aniline 7 as a yellow solid, yield 56% (113 mg). Mp
(c 1.00, CH2Cl2). {Lit.17
[a]
20 = À53.1 (c 1.01, CH2Cl2), 96% ee}. 1H
D
NMR (400 MHz, CDCl3) d: 7.42–7.36 (m, 5H), 5.47 (d, J = 8.8 Hz,
1H), 4.65–4.51 (m, 2H), 2.79 (br s, 1H). HPLC18 (Chiralcel OD-H,
Hexane/i-PrOH = 90:10, flow rate: 1.0 mL/min, k = 215 nm),
tmajor = 14.4, tminor = 17.8, 77% ee.
240–241 °C. [
a
]
D
20 = À408.4 (c 0.55, CH2Cl2). IR (KBr)
mmax: 3422,
3006, 2930, 1629, 1507 cmÀ1 1H NMR (400 MHz, CDCl3) d: 12.65
.
(s, 1H), 9.23 (s, 1H), 8.92 (dd, J = 0.5, 8.4 Hz, 1H), 8.21–8.19 (m,
2H), 7.91 (dd, J = 2.0, 8.0 Hz, 1H), 7.70–7.68 (m, 1H), 7.62–7.58
(m, 3H), 7.51 (ddd, J = 1.6, 7.2, 8.8 Hz, 1H), 7.29–7.27 (m, 3H),
7.03 (dt, J = 0.8, 8.0 Hz, 1H), 5.93 (d, J = 8.0 Hz, 1H), 5.47 (ddd,
J = 1.6, 6.8, 8.0 Hz, 1H), 3.55 (dd, J = 6.4, 17.6 Hz, 1H), 3.42 (d,
J = 18.0 Hz, 1H). 13C NMR (400 MHz, CDCl3) d: 163.9, 160.6, 155.4,
141.9, 140.6, 139.5, 139.0, 134.1, 132.3, 132.1, 129.5, 129.2,
128.6, 127.6, 127.5, 125.6, 125.3, 120.8, 119.0, 113.3, 81.9, 76.8,
39.6. HRMS (ESI, m/z): calcd for C25H20N5O ([M+H]+), 406.1662,
found 406.1657. Anal. calcd for C25H19N5OÁ1/3H2O (411.16): C,
72.98; H, 4.82; N, 17.02; found: C, 72.82; H, 5.00; N, 17.04.
4.4.3. (R)-2-Nitro-1-(2-nitrophenyl)ethanol 12c
Compound 12c was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
tate 5:1) to give a brown solid (77 mg, 73% yield). [
a]
20 = +147.5 (c
D
0.23, CH2Cl2). {Lit.19 20 = +225.3 (c 0.25, CH2Cl2), 96% ee}. 1H
[a]
D
NMR (400 MHz, CDCl3) d: 8.08 (dd, J = 1.2, 8.4 Hz, 1H), 7.95 (dd,
J = 1.2, 8.4 Hz, 1H), 7.77–7.73 (m, 1H), 7.58–7.53 (m, 1H), 6.07–
6.03 (m, 1H), 4.89 (dd, J = 2.4, 14.0 Hz, 1H), 4.57 (dd, J = 9.2,
14.0 Hz, 1H), 3.18 (d, J = 4.4 Hz, 1H). HPLC20 (Chiralcel OD-H, Hex-
ane/i-PrOH = 90:10,
flow
rate:
1.0 mL/min,
k = 215 nm),
tmajor = 16.1, tminor = 18.7, 62% ee.
4.3.2. N-{2-[(4R,5S)-4,5-Diphenyl-4,5-dihydrooxazol-2-yl]-phen-
yl}-5-phenyl-1,2,4-triazin-3-amine 3
4.4.4. (R)-2-Nitro-1-(4-nitrophenyl)ethanol 12d
The product was obtained from 3-bromo-5-phenyl-1,2,4-tri-
azine 9 and 2-[(4R,5S)-4,5-diphenyl-4,5-dihydrooxazol-2-yl]ani-
line 8 as a yellow solid, yield 51% (120 mg). Mp 173–174 °C.
Compound 12d was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
tate 5:1) to give a colorless solid (91 mg, 86% yield). [
a
]
20 = À21.1
D
[a
]
D
20 = À170.5 (c 0.77, CH2Cl2). IR (ZnSe)
m
max: 3217, 3103, 3062,
(c 0.30, CH2Cl2). {Lit.19
[a]
20 = À35.1 (c 0.24, CH2Cl2), 92% ee}. 1H
D
3032, 2924, 2908, 1637, 1555, 1498, 1448 cmÀ1
.
1H NMR
NMR (400 MHz, CDCl3) d: 8.27 (d, J = 8.8 Hz, 2H), 7.62 (d,
J = 8.6 Hz, 2H), 5.62–5.59 (m, 1H), 4.64–4.58 (m, 2H), 3.12 (d,
J = 4.0 Hz, 1H). HPLC20 (Chiralcel OD-H, Hexane/i-PrOH = 85:15,
flow rate: 1.0 mL/min, k = 215 nm), tmajor = 17.6, tminor = 22.5, 44%
ee.
(400 MHz, CDCl3) d: 12.73 (s, 1H), 9.24 (s, 1H), 9.09 (dd, J = 0.8,
8.4 Hz, 1H), 8.15–8.12 (m, 3H), 7.68–7.62 (m, 1H), 7.57–7.50 (m,
3H), 7.16–7.12 (m, 1H), 7.09–7.03 (m, 8H), 6.99–6.97 (m, 2H),
6.02 (d, J = 10 Hz, 1H), 5.97 (d, J = 10 Hz, 1H). 13C NMR (400 MHz,
CDCl3) d: 165.0, 160.5, 155.5, 141.0, 139.2, 137.4, 136.2, 133.8,
132.8, 132.1, 129.8, 129.2, 127.7, 127.7, 127.7, 127.6, 127.5,
126.9, 126.6, 121.1, 119.2, 112.8, 84.1, 74.3. HRMS (ESI, m/z): calcd
for C30H24N5O ([M+H]+), 470.1975, found 470.1962. Anal. calcd for
C30H23N5O (469.19): C, 76.74; H, 4.94; N, 14.92; found: C,76.77; H,
5.03; N, 14.93.
4.4.5. (R)-1-(2-Chlorophenyl)-2-nitroethanol 12e
Compound 12e was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
tate 7:1) to give a colorless oil (75 mg, 75% yield). [
a
]
20 = À46.6
D
(c 2.50, CH2Cl2). {Lit.21
[a
]
D
20 = À47.3 (c 2.85, CH2Cl2), 83% ee}. 1H
NMR (400 MHz, CDCl3) d: 7.67 (dd, J = 2.0, 7.6 Hz, 1H), 7.40–7.28
(m, 3H), 5.88–5.84 (m, 1H), 4.68 (dd, J = 2.4, 14.0 Hz, 1H), 4.46
(dd, J = 9.6, 14.0 Hz, 1H), 2.96 (dd, J = 0.4, 4.4 Hz, 1H). HPLC22
(Chiralcel OD-H, Hexane/i-PrOH = 98:2, flow rate: 1.0 mL/min,
k = 208 nm), tmajor = 27.8, tmajor = 30.6, 77% ee.
4.4. General procedure for the catalytic enantioselective Henry
reaction
A mixture of Cu(OAc)2ÁH2O (5 mg, 0.025 mmol, 5 mol %) and
ligand 2 or 3 (0.025 mmol, 5 mol %) in anhydrous 2-propanol
(2 mL) was stirred at room temperature for 4 h under an argon
atmosphere to give a red-brown solution. The aldehyde (0.5 mmol)
4.4.6. (R)-1-(3-Chlorophenyl)-2-nitroethanol 12f
Compound 12f was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
and the nitromethane (270 lL, 5 mmol) were added and the reac-
tion was conducted at room temperature for 4 days. The solvent
was then removed under reduced pressure and the product was
isolated by column chromatography. The ee values of the nitroal-
cohols 12a–r were determined by chiral HPLC analysis. The abso-
lute configurations of the products were assigned by comparing
their specific rotations or retention times in HPLC with literature
data.
tate 7:1) to give a colorless oil (41 mg, 41% yield). [
a
]
20 = À31.2 (c
D
0.50, CHCl3). {Lit.23
[a]
20 = À36.6 (c 0.55, CHCl3), 92% ee}. 1H NMR
D
(400 MHz, CDCl3) d: 7.44–7.43 (m, 1H), 7.35–7.34 (m, 2H), 7.30–
7.27 (m, 1H), 5.48–5.44 (m, 1H), 4.59 (dd, J = 9.2, 13.6 Hz, 1H),
4.52 (dd, J = 3.2, 13.6 Hz, 1H), 2.87 (d, J = 4.0 Hz, 1H). HPLC16 (Chi-
ralcel OD-H, Hexane/i-PrOH = 90:10, flow rate: 1.0 mL/min,
k = 215 nm), tminor = 12.2, tmajor = 15.8, 74 % ee.
4.4.1. (R)-2-Nitro-1-(3-nitrophenyl)ethanol 12a
4.4.7. (R)-1-(4-Chlorophenyl)-2-nitroethanol 12g
Compound 12a was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl
Compound 12g was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
acetate 2.5:1) to give
a
colorless solid (76 mg, 71% yield).
tate 7:1) to give a colorless oil 47 mg, 47% yield). [
a
]
D
20 = À36.9 (c
[a
]
D
20 = À21.0 (c 1.00, CH2Cl2). {Lit.15
[a
]
D
20 = À32.8 (c 1.00,
1.76, CH2Cl2). {Lit.17
[
a]
20 = À48.1 (c 1.01, CH2Cl2), 95% ee}. 1H
D

´
1127
E. Wolinska / Tetrahedron: Asymmetry 25 (2014) 1122–1128
NMR (400 MHz, CDCl3) d: 7.40–7.34 (m, 4H), 5.48–5.43 (m, 1H),
acetate 7:1) to give a yellow oil (40 mg, 40% yield). [
a
]
20 = À30.3
D
4.59 (dd, J = 9.6, 13.6 Hz, 1H), 4.49 (dd, J = 3.2, 13.6 Hz, 1H), 2.87
(d, J = 3.6, Hz, 1H). HPLC16 (Chiralcel OD-H, Hexane/i-PrOH = 90:10,
flow rate: 0.5 mL/min, k = 215 nm), tmajor = 28.5.1, tmajor = 37.0, 78%
ee.
(c 0.30, CH2Cl2). {Lit.17
[a]
20 = À38.8 (c 0.99, CH2Cl2), 94% ee}. 1H
D
NMR (400 MHz, CDCl3) d: 7.34–7.30 (m, 1H), 6.97–6.96
(m, 2H), 6.91–6.88 (m, 1H), 5.47–5.43 (m, 1H), 4.60 (dd,
J = 9.6, 13.6 Hz, 1H), 4.51 (dd, J = 3.2, 13.6 Hz, 1H), 3.83 (s, 3H),
2.76 (br s, 1H). HPLC16 (Chiralcel OD-H, Hexane/i-PrOH = 90:10,
flow rate: 1.0 mL/min, k = 215 nm), tmajor = 23.7, tminor = 30.8, 82%
ee.
4.4.8. (R)-1-(2-Bromophenyl)-2-nitroethanol 12h
Compound 12h was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
tate 8:1) to give a colorless oil (100 mg, 81% yield). [
a
]
20 = À38.6
D
4.4.14. (R)-1-(4-Methoxyphenyl)-2-nitroethanol 12n
Compound 12n was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
(c 1.00, CH2Cl2). {Lit.20
[a
]
D
20 = À35.2 (c 1.0, CH2Cl2), 89% ee}. 1H
NMR (400 MHz, CDCl3) d: 7.66 (dd, J = 1.6, 7.6 Hz, 1H), 7.57 (dd,
J = 1.2, 8.0 Hz, 1H), 7.41 (dt, J = 1.6, 7.6 Hz, 1H), 7.23 (dt, J = 1.6,
7.6 Hz, 2H), 5.81 (dd, J = 1.6, 9.6 Hz, 1H), 4.69 (dd, J = 2.0, 13.6 Hz,
1H), 4.44 (dd, J = 9.6, 13.6 Hz, 1H), 3.00 (brs, 1H). HPLC16 (Chiralcel
OD-H, Hexane/i-PrOH = 95:5, flow rate: 0.5 mL/min, k = 215 nm),
tmajor = 30.9, tminor = 34.4, 77% ee.
tate 7:1) to give a yellow oil (20 mg, 20% yield). [
a
]
20 = À38.0 (c
D
0.50, CH2Cl2). {Lit.17
[a
]
D
20 = À47.1 (c 1.0, CH2Cl2), 92% ee}. 1H
NMR (400 MHz, CDCl3) d: 7.32 (d, J = 8.8 Hz, 1H), 6.93 (d,
J = 8.8 Hz, 2H), 5.48–5.41 (m, 1H), 5.40–5.43 (m, 1H), 4.59 (dd,
J = 9.6, 13.2 Hz, 1H), 4.49 (dd, J = 2.4, 13.0 Hz, 1H), 3.82 (br s,
3H), 2.78 (d, J = 3.2 Hz, 1H). HPLC16 (Chiralcel OD-H,
Hexane/i-PrOH = 90:10, flow rate: 1.0 mL/min, k = 215 nm),
tmajor = 21.5, tminor = 28.1, 79% ee.
4.4.9. (R)-1-(2-Methylphenyl)-2-nitroethanol 12i
Compound 12i was obtained according to the general procedure
and purified by column chromatography (hexanes/ethyl acetate
10:1) to give a yellow oil (60 mg, 66% yield). [
a
]
20 = À45.1 (c
D
1.00, CH2Cl2). {Lit.24
[a
]
D
20 = À45.8 (c 1.0, CH2Cl2), 91% ee}. 1H
4.4.15. (R)-1-(3,4-Dimethoxyphenyl)-2-nitroethanol 12o
Compound 12o was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
NMR (400 MHz, CDCl3) d: 7.54–7.52 (m, 1H), 7.29–7.24 (m, 2H),
7.21–7.18 (m, 1H), 5.71–5.68 (m, 1H), 4.57 (dd, J = 9.6, 13.2 Hz,
1H), 4.45 (dd, J = 2.8, 13.6 Hz, 1H), 2.64 (d, J = 3.6 Hz, 1H), 2.40 (s,
3H). HPLC16 (Chiralcel OD-H, Hexane/i-PrOH = 90:10, flow rate:
1.0 mL/min, k = 215 nm), tmajor = 11.4, tminor = 18.0, 92% ee.
tate 2.5:1) to give a yellow oil (14 mg, 12% yield). [
a
]
20 = À22.3 (c
D
0.44, CH2Cl2). {Lit.20
[a
]
D
20 = À24.6 (c 1.0, CH2Cl2), 89% ee}. 1H NMR
(400 MHz, CDCl3) d: 6.93–6.84 (m, 3H), 5.41 (dd, J = 4.0, 12.0 Hz,
1H), 4.60 (dd, J = 12.0, 16.0 Hz, 1H), 4.50 (dd, J = 4.0, 12.0 Hz, 1H),
3.91 (s, 3H), 3.90 (s, 3H), 2.73 (br s, 1H). HPLC18 (Chiralcel OD-H,
Hexane/i-PrOH = 85:15, flow rate: 1.0 mL/min, k = 215 nm),
tmajor = 29.8, tminor = 40.7, 70% ee.
4.4.10. (R)-1-(3-Methylphenyl)-2-nitroethanol 12j
Compound 12j was obtained according to the general procedure
and purified by column chromatography (hexanes/ethyl acetate
8:1) to give a yellow oil (23 mg, 25% yield). [
a
]
20 = À21.2 (c
D
0.30, CH2Cl2). {Lit.25
[a
]
D
20 = À32.2 (c 0.3, CH2Cl2), 93% ee}. 1H
4.4.16. (R)-1-(1-Naphthyl)-2-nitroethanol 12p
Compound 12p was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
NMR (400 MHz, CDCl3) d: 7.29 (t, J = 7.6 Hz, 1H), 7.22–7.17 (m,
3H), 5.44–5.42(m, 1H), 4.61 (dd, J = 9.6, 13.6 Hz, 1H), 4.51 (dd,
J = 2.8, 13.6 Hz, 1H), 2.75 (d, J = 3.2, 1H), 2.38 (s, 3H). HPLC16 (Chi-
ralcel OD-H, Hexane/i-PrOH = 90:10, flow rate: 1.0 mL/min,
k = 215 nm), tmajor = 12.3, tminor = 14.4, 76% ee.
tate 10:1) to give a yellow oil (78 mg, 72% yield). [
a
]
20 = À22.8 (c
D
1.00, CH2Cl2). {Lit.17
[
a]
20 = À30.6 (c 1.1, CH2Cl2), 93% ee}. 1H NMR
D
(400 MHz, CDCl3) d: 8.05 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H),
7.87 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.62–7.51 (m, 3H),
6.61–6.58 (m, 1H), 4.75–4.64 (m, 2H), 2.82 (d, J = 3.6 Hz, 1H).
HPLC20 (Chiralcel OD-H, Hexane/i-PrOH = 90:10, flow rate:
1.0 mL/min, k = 215 nm), tmajor = 18.8, tmajor = 27.9, 75% ee.
4.4.11. (R)-1-(4-Methylphenyl)-2-nitroethanol 12k
Compound 12k was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
tate 5:1) to give a yellow oil (52 mg, 57% yield). [
a
]
20 = À34.4 (c
D
1.00, CH2Cl2). {Lit.18
[a
]
D
20 = À44.3 (c 1.0, CH2Cl2), 91% ee}. 1H
4.4.17. (R)-1-Nitro-4-phenylbutan-2-ol 12q
NMR (400 MHz, CDCl3) d: 7.28 (d, J = 8.0 Hz, 2H), 7.21 (d,
J = 8.0 Hz, 2H), 5.45– 5.41 (m, 1H), 4.62 (dd, J = 9.6, 13.2 Hz, 1H),
4.49 (dd, J = 3.2, 13.2 Hz, 1H), 2.76 (br s, 1H), 2.36 (s, 3H). HPLC16
(Chiralcel OD-H, Hexane/i-PrOH = 90:10, flow rate: 1.0 mL/min,
k = 215 nm), tmajor = 14.5, tminor = 18.9, 77% ee.
Compound 12q was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
tate 5:1) to give a colorless solid (41 mg, 42% yield). [
a]
20 = +9.2 (c
D
1.00, CH2Cl2). {Lit.24 20 = +12.03 (c 1.00, CH2Cl2), 92% ee}. 1H
[a]
D
NMR (400 MHz, CDCl3) d: 7.33–7.29 (m, 2H), 7.24–7.19 (m, 3H),
4.41–4.39 (m, 2H), 4.36–4.28 (m, 1H), 2.90–2.83 (m, 1H), 2.79–
2.71 (m, 1H), 2.57 (d, J = 4.8 Hz, 1H), 1.92–1.75 (m, 2H). HPLC24
(Chiralpak AD-H, Hexane/i-PrOH = 90:10, flow rate: 1.0 mL/min,
k = 215 nm), tmajor = 11.2, tminor = 14.2, 60% ee.
4.4.12. (R)-1-(2-Methoxyphenyl)-2-nitroethanol 12l
Compound 12l was obtained according to the general procedure
and purified by column chromatography (hexanes/ethyl acetate
10:1) to give a yellow oil (91 mg, 91% yield). [
a
]
20 = À38.4 (c
D
1.00, CH2Cl2). {Lit.17
[a
]
D
20 = À48.9 (c 0.99, CH2Cl2), 96% ee}. 1H
4.4.18. (B)-1-Nitrohexan-2-ol 12r
Compound 12r was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl ace-
NMR (400 MHz, CDCl3) d: 7.44 (dd, J = 1.2, 7.6 Hz, 1H), 7.33 (dt,
J = 1.6, 8.0 Hz, 1H), 7.02 (dt, J = 0.8, 7.6 Hz, 1H), 6.91 (d, J = 8.4 Hz,
1H), 5.65–5.62 (m, 1H), 4.65 (dd, J = 3.2, 13.2 Hz, 1H), 4.58 (dd,
J = 9.2, 13.2 Hz, 1H), 3.89 (s, 3H), 3.11 (d, J = 6.0 Hz, 1H). HPLC16
(Chiralcel OD-H, Hexane/i-PrOH = 90:10, flow rate: 1.0 mL/min,
k = 215 nm), tmajor = 11.6, tminor = 13.8, 76% ee.
tate 5:1) to give a yellow oil (20 mg, 27% yield). [
a
]
20 = À7.0 (c
D
0.40, CH2Cl2). {Lit.26
[a
]
D
20 = À9.2 (c 0.6, CH2Cl2), 94% ee}. 1H
NMR (400 MHz, CDCl3) d: 4.42 (dd, J = 2.4, 12.8 Hz, 1H), 4.40–
4.35 (m, 1H), 4.34–4.29 (m, 1H), 2.59 (br s, 1H), 1.59–1.42 (m,
3H), 1.41–1.32 (m, 3H), 0.92 (t, J = 7.2 Hz, 3H). HPLC27 (Chiralpak
AD-H, Hexane/i-PrOH = 98:2, flow rate: 0.8 mL/min, k = 215 nm),
tmajor = 31.3, tminor = 41.8, 65% ee.
4.4.13. (R)-1-(3-Methoxyphenyl)-2-nitroethanol 12m
Compound 12m was obtained according to the general proce-
dure and purified by column chromatography (hexanes/ethyl

´
1128
E. Wolinska / Tetrahedron: Asymmetry 25 (2014) 1122–1128
10. Fujisawa, T.; Ichiyanagi, T.; Shimizu, M. Tetrahedron Lett. 1995, 36, 5031–5034.
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Guiry, P. J. J. Org. Chem. 2002, 67, 8566–8573.
Acknowledgments
The authors are grateful to Prof. Andrzej Rykowski for helpful
discussions.
12. Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2001, 3, 91–93.
13. Rykowski, A.; van der Plas, H. C. J. Org. Chem. 1980, 45, 881–885.
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15. Qin, D.-D.; Lai, W.-H.; Hu, D.; Chen, Z.; Wu, A.-A.; Ruan, Y.-P.; Zhou, Z.-H.; Chen,
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