Enantioselective Addition of Diethylzinc to Aromatic Aldehydes Using Novel Thiophene-Based Chiral Ligands

Article abstract of DOI:10.1134/S1070428020050255

Abstract: Chiral norephedrine-derived β-amino alcohols with a thiophene moiety were synthesized from thiophene carbaldehydes (methyl- or ethyl-substituted) and chiral amino alcohols, such as both enantiomers of norephedrine and 2-aminopropanol. The synthesized ligands were applied to the catalytic asymmetric addition of diethylzinc to aldehydes to obtain optically active alcohols with a high conversion (92%) and excellent enantioselectivities (ee up to 99%). The highest enantioselectivity (ee 99%) was obtained with p-trifluorobenzaldehyde as the substrate containing the strongly electron-acceptor CF₃ group.

Full text of DOI:10.1134/S1070428020050255

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 5, pp. 901–909. © Pleiades Publishing, Ltd., 2020.
Enantioselective Addition of Diethylzinc to Aromatic
Aldehydes Using Novel Thiophene-Based Chiral Ligands
A. E. Aydina,*
a Department of Chemistry, Arts and Science Faculty, Hatay Mustafa Kemal University, Antakya, 31040 Turkey
*e-mail: aydin@mku.edu.tr
Received January 26, 2020; revised January 29, 2020; accepted January 31, 2020
Abstract—Chiral norephedrine-derived β-amino alcohols with a thiophene moiety were synthesized from thio-
phene carbaldehydes (methyl- or ethyl-substituted) and chiral amino alcohols, such as both enantiomers of nor-
ephedrine and 2-aminopropanol. The synthesized ligands were applied to the catalytic asymmetric addition of
diethylzinc to aldehydes to obtain optically active alcohols with a high conversion (92%) and excellent enantiose-
lectivities (ee up to 99%). The highest enantioselectivity (ee 99%) was obtained with p-trifluorobenzaldehyde as
the substrate containing the strongly electron-acceptor CF3 group.
Keywords: enantioselective synthesis, chiral amino alcohols, thiolated amino-alcohols, 1,2-addition
DOI: 10.1134/S1070428020050255
INTRODUCTION
excellent chemical yields and enantioselectivities
[41–45].
Enantioselective addition of organometallic reagents
to aldehydes is an important method for the synthesis
of optically active secondary alcohols, which are
building blocks for the preparation of natural products,
pharmaceuticals, agrochemicals, perfumes, and other
compounds. Derivatives of 1-phenylpropan-1-ol are
used in cancer therapy as stimulating drugs [1–6]. Since
the first report by Oguni and Omi [7, 8], several types of
ligands, including amino thiols [9–11], amino alcohols
[12–14], amino phenols [6, 15], amides [17, 18],
diamines [19–21], diols [22–24], and sulfonamides [25–
27], have been used to success as chiral ligands for the
enantioselective addition of dialkylzinc to aldehydes.
Among various organometallic compounds, diorga-
nylzinc acts as an ideal alkyl donor in enantioselective
alkylation reactions. In ordinary hydrocarbon and
ethereal solvents, dialkylzinc compounds do not react
with aldehydes in noncatalytic conditions [2, 4, 46–48].
Even though dialkylzinc reagents extremely slowly
react with carbonyl compounds, several ligands and
transition metal complexes proved to be effective
catalysts for these reactions. The high reactivity of
organozinc reagents in the presence of chiral ligands,
such as amino alcohols, can be explained as follows
[49–51]. Monomeric dialkylzinc compounds have a
linear geometry around the zinc atom, and, therefore,
the zinc–alkyl bond is nonpolar. However, the
complexation with a suitable ligand changes the linear
structure of R2Zn compounds to tetrahedral [2, 52] and
makes the Zn–C bond longer. Therefore, the energy of
the Zn–C bond decreases, and the nucleophilicity of the
alkyl group in dialkylzinc increases [53]. In this way,
the nucleophilicity of the alkyl group increases, and the
addition becomes possible [54]. The amino alcohol acts
as a Lewis base which activates the zinc reagent and
forms a Lewis acidic zinc species, which activates the
aldehyde. Upon treatment of an amino alcohol with an
alkylzinc reagent, donor atoms, such as nitrogen and
Chiral amino alcohols are often used as chiral ligands
in enantioselective reactions, because they are readily
available and provide efficient asymmetric induction.
The most successful results were obtained with steri-
cally constrained β-amino alcohols [28–32], such as
ephedrine or norephedrine, as well as proline [33–36].
Soai et al. [37–40] were the first to report the highly
enantioselective addition of diethylzinc to aldehydes
in the presence of enantiomerically pure norephedrine
derivatives, specifically N,N-dialkylnorephedrines. The
addition of diethylzinc to aromatic aldehydes catalyzed
by these chiral ligands gave 1-arylethan-1-ols in
901

902
AYDIN
Scheme 1.
H
N
H2N
HO
R2
R3
R2
R3
R1
O
1) Benzene, reflux
S
R1
+
S
2) LAH, Et2O
3) H3O+/H2O
H
HO
1a, 1b
2, 3
4–7
1, R1 = CH3 (a), CH2CH3 (b); 2, R2 = CH3, R3 = H; 3, R2 = CH3, R3 = C6H5; 4, R1 = CH3, R2 = CH3, R3 = H;
5, R1 = CH2CH3, R2 = CH3, R3 = H; 6, R1 = CH3, R2 = CH3, R3 = C6H5; 7, R1 = CH2CH3, R2 = CH3, R3 = C6H5.
Table 1. Preparation of thiophene-based chiral ligands 4–7
Entry
Thiopene carbaldehyde
Amino alcohol
(R)-2
Ligand
(R)-4
Yield, %
75
1a
1a
1b
1b
1a
1a
1b
1b
1
2
3
4
5
6
7
8
(S)-2
(S)-4
76
(R)-2
(R)-5
72
(S)-2
(S)-5
74
(1R,2S)-3
(1S,2R)-3
(1R,2S)-3
(1S,2R)-3
(1R,2S)-6
(1S,2R)-6
(1R,2S)-7
(1S,2R)-7
68
74
70
75
oxygen of the chiral ligands, coordinate to the zinc
atom to form chiral complexes which differentiate the
enantioface of the aldehyde [2].
RESULTS AND DISCUSSION
Chiral ligands 4 and 5 were easily synthesized from
both enantiomers of 2-aminopropanol according to our
previously reported procedure (Scheme 1) [55, 56].
The starting chiral amino alcohols are commercially
available reagents. The synthesis of compounds 4–7 can
be described as follows. (R)- and (S)-2-Aminopropanol
[(R)- and (S)-2] or (1R,2S)- or (1S,2R)-norephedrine
[(1R,2S)-3 or (1S,2R)-3], and 5-substituted thiophene-2-
carbaldehyde 1a or 1b were mixed in dry benzene and
refluxed for 4 h with a Dean–Stark trap to obtain the
corresponding Schiff base in a quantitative yield. The
resulting Schiff base was reduced in dry diethyl ether
with LiAlH4. All possible stereoisomers were isolated
after purification of the crude products by column
chromatography. The detailed results are presented in
Table 1.
We are interested in synthesizing and applying chiral
amino alcohol derivatives as ligands for metal complexes
in enantioselective catalysis, and we reported that using
chiral pyrrole substituted norephedrine-based amino
alcohols as ligands allows moderate enantioselectivities
and chemical yields in the additions of diethylzinc
to benzaldehyde and chalcone. We showed that the
absolute configuration of the norephedrine moiety plays
an important role in the configuration of the addition
products [55, 56].
In our previous studies, chiral norephedrine-based
β-aminoalcoholligandswithasubstitutedthiophenering
were synthesized from both norephedrine enantiomers
6a–6b, 7a–7b. The synthesized chiral ligands were
applied as catalysts in the Cu-catalyzed asymmetric
Henry reaction. Herein, we report the preparation of
substituted chiral 2-amino propanol and norephedrine-
based ligands bearing a substituted thiophene ring.
These ligands were used as catalysts in the asymmetric
addition of diethylzinc to aromatic aldehydes.
To assess the catalytic efficiency of amino alcohols
4–7, we chose as the model reaction the asymmetric
addition of Et2Zn to benzaldehyde in toluene at 0°C to
room temperature in the presence of 10 mol % of catalyst
at a 1 : 2 ratio of benzaldehyde and Et2Zn, leading to a
chiral 1-phenylpropan-1-ol. The results are summarized
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ENANTIOSELECTIVE ADDITION OF DIETHYLZINC TO AROMATIC ALDEHYDES
903
Table 2. Enantioselective addition of diethyzinc to benzaldehyde catalyzed by chiral ligands
O
OH
*
Ligand (5 mmol %)
Toluene, 0oC–rt
+ Et2Zn
H
8a
9a
Entry
Ligand
(R)-4
(S)-4
Yield of 9a, %a
ee, %b
Configurationc
1
2
3
4
5
6
7
8
75
76
78
78
82
83
80
79
66
67
69
70
78
79
81
83
R
S
(R)-5
(S)-5
R
S
(1R,2S)-6
(1S,2R)-6
(1R,2S)-7
(1S,2R)-7
S
R
S
R
a Yields of ligands after column chromatography.
b The ee values were determined by HPLC with a Chiralcel OD-H column.
c Absolute configurations were assigned by comparison of the HPLC retention times with published data [18].
in Table 2. As seen from Table 2, the product was
obtained in yields of 75–83% and ee 66–83%.
(1R,2S)-7 with an (R)-configuration of the OH-bearing
carbon gave the product with an (S)-configuration
(Table 2), while chiral ligands (1S,2R)-6 and (1S,2R)-7
with an (S)-configuration of the same stereogenic center
gave an (R)-product. The reactions with chiral ligands
(1R,2S)-6 and (1S,2R)-6 afford the secondary alcohol in
yields of 82% and 83% (ee 78 and 79%) for the major
(S)- and (R)-enantiomers, respectively (Table 2, entries
5 and 6).
Chiral ligands 4 and 5 were synthesized from (R)-
and (S)-2-aminopropan-1-ol that catalyzed the addition
of Et2Zn to benzaldehyde to form either (R)- or (S)-1-
phenylpropan-1-ol, respectively. In chiral ligands 4 and
5, the C–OH carbon atom is not a chiral center. With
ligands (R)-4 and (R)-5 as chiral catalysts, the corres-
ponding enantiomerically enriched (R)-1-phenylpropan-
1-ol was obtained in yields of 75 and 78% (ee 66 and
69%), respectively (Table 2, entries 1 and 3). The same
reaction with (S)-4 and (S)-5 gave an (S)-alcohol in
yields of 76% and 78% (ee 67 and 70%), respectively
(Table 2, entries 2 and 4). These observations are in
agreement with the observation of Soai et al. [57,
58], who reported that the enantioselectivity was
determined by the configuration of the homochiral
(S)-(+)-diphenyl(N-methylpyrrolidin-2-yl)methanol
(DPMPM), which has an asymmetric carbon bearing the
amino group: (S)-DPMPM gave (S)-1-phenylpropan-1-
ol, whereas (R)-DPMPM catalyzed the reaction to afford
the (R)-alcohol.
Chiral ligand (1S,2R)-7 gave the highest
enantioselectivity in the asymmetric addition of
diethyzinc to benzaldehyde (Table 2, entry 8), and,
therefore, it was selected for further optimization of the
reaction conditions, specifically solvent, temperature,
and amount of the ligand.
The results are summarized Table 3. The solvent was
found to have a remarkable effect on enantioselectivity
and conversion. In noncoordinating solvents, such as
toluene and hexane, higher enantioselectivities were
obtained compared to coordinating solvents, such as
THF and Et2O. Toluene gave the best results: yield
79% and ee 83% (Table 3, entry 1). In hexane, the
enantioselectivity was lower but the conversion was
higher increased (Table 3, entry 2). In THF and Et2O,
the enantioselectivity decreased dramatically (Table 3,
It is known that high enantioselectivities are obtained,
when the OH-bearing carbon atom of the chiral ligand
contains bulky substituents. Chiral ligands (1R,2S)-6 and
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904
AYDIN
Table 3. Asymmetric addition of diethyzinc to benzaldehyde in the presence of chiral ligand (1S,2R)-7
O
OH
Ligand
+ Et2Zn
H
Toluene, 0oC–rt
8a
(R)-9a
Entry
1
Ligand, mmol %
Solvent
Toluene
Hexane
THF
Yield, %a
79
ee, %b
83
5
2
5
75
78
3
5
70
62
4
5
Et2O
65
60
5
5
CH2Cl2
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
70
62
6c
7d
8e
9
5
70
52
5
80
57
5
72
95
10
15
2.5
84
79
10
11
85
70
80
75
a Yields of ligands after column chromatography.
b The ee values were determined by HPLC on a Chiralcel OD-H column.
c The reaction was performed at room temperature.
d The reaction was performed at –20°C.
e The reaction was performed with 2 mmol Ti(OiPr)4.
entries 3 and 4). The presence of dichloromethane
decreased the ee of the resulting alcohol (Table 3,
entry 5). Consequently, toluene was considered an
optimal solvent for the catalytic reaction.
showing that additives like titanium tetraisopropoxide
Ti(OiPr)4, which can act as Lewis acids, affect the
enantioselectivity and yield of similar reactions has
been reported [59–61]. The enantioselective addition
of diethylzinc to benzaldehyde in the presence of
Ti(OiPr)4 increases both yield and ee [62–64]. Using
catalytic amounts of chiral Lewis acids as catalysts
in such reactions provides an efficient way to
enantioselective creation of new carbon–carbon bonds.
In all cases, the complexation of Lewis acids with the
carbonyl group activates the system. In most cases,
chiral transition metal complexes, often prepared in situ,
are used as catalysts. Recent studies on the mechanism
of dialkylzinc addition to aldehydes in the presence
of Ti(OiPr)4 seem to indicate that the alkyl moiety is
transferred from zinc to titanium by transmetallation
and then transferred from the latter to the aldehyde [65].
Considering these published data, the enantioselective
reaction was performed with Ti(OiPr)4 as an additive in
the presence of chiral catalyst (1S,2R)-7. The resulting
The effect of the reaction temperature was also
investigated. Initially, the experiment was performed
by slowly adding Et2Zn to a solution of compound
(1S,2R)-7 at 0°C. After 1 h, benzaldehyde was added
at the same temperature, and then the reaction was kept
at room temperature. When the reaction was performed
at room temperature, the enantioselectivity decreased
to 52% (Table 3, entry 6). Conversely, decreasing the
reaction temperature to –20°C led to a lower ee of 57%
(Table 3, entry 7).
Ligands are essential for controlling the reactivity
and selectivity of metal-catalyzed reactions. Alkylzinc
reagents can be used in combination with titanium
alkoxides to promote the addition reaction of carbon
nucleophiles to carbonyl compounds. Evidence
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ENANTIOSELECTIVE ADDITION OF DIETHYLZINC TO AROMATIC ALDEHYDES
905
Table 4. Enantioselective addition of diethylzinc to various aromatic aldehydes catalyzed by (1S,2R)-6 and (1S,2R)-7a
OH
O
Ligand (5 mmol %)
Toluene, 0oC–rt
+ Et2Zn
Ar
Ar
8a–8p
H
(R)-9a–9p
Ligand (1S,2R)-6
Ligand (1S,2R)-7
Yield, %b
Entry
Aldehyde
Benzaldehyde (8a)
Product
Yield, %b
ee,%c
83
80
75
72
78
74
72
88
85
83
85
84
99
72
76
58
ee, %c
95
83
80
75
80
76
73
90
88
85
87
83
98
75
78
61
1
9a
9b
9c
9d
9e
9f
80
75
75
64
68
79
68
89
89
90
87
91
92
80
81
60
72
83
80
95
82
82
85
89
92
92
85
93
94
78
80
62
2
p-Methoxybenzaldehyde (8b)
m-Methoxybenzaldehyde (8c)
o-Methoxybenzaldehyde (8d)
p-Methylbenzaldehyde (8e)
m-Methylbenzaldehyde (8f)
o-Methylbenzaldehyde (8g)
p-Chlorobenzaldehyde (8h)
m-Chlorobenzaldehyde (8i)
o-Chlorobenzaldehyde (8j)
p-Bromobenzaldehyde (8k)
m-Bromobenzaldehyde (8l)
3
4
5
6
7
9g
9h
9i
8
9
10
11
12
13
14
15
16
9j
9k
9l
p-(Trifluoromethyl)benzaldehyde (8m)
Naphthalene-1-carbaldehyde (8n)
Naphthalene-2-carbaldehyde (8o)
Thiophene-2-carbaldehyde (8p)
9m
9n
9o
9p
a The reaction was performed with 2 mmol Ti(OiPr)4.
b Yields of ligands after column chromatography.
c The ee values were determined by HPLC on a Chiralcel OD-H column.
data showed that the use of Ti(OiPr)4 ensures high
enantioselectivity (ee 95%; Table 3, entry 8).
examined in toluene at 0°C in the presence (1S,2R)-6
or (1S,2R)-7 as chiral catalysts. The results are sum-
marized in Table 4. The additions to aromatic aldehydes
all gave the corresponding R-alcohols as the major
isomers with excellent enantiomeric excesses and high
yields. Table 4 shows that electron-acceptor substituents
increase the electrophilicity of the carbonyl carbon in
aryl aldehydes, whereas electron-donor groups decrease
it. These results suggest that substrates with electron-
acceptor substituents reacted faster, providing higher
yields of the products with higher enantiomeric excesses.
The loading of the chiral ligand was a crucial factor
affecting the catalytic activity in this reaction. When
the amount of ligand (1S,2R)-7 was increased to 10 and
15 mol %, the ee values decreased to 79 and 70%
(Table 3, entries 9 and 10), respectively. However, the
lowest loading of the chiral ligand (2.5 mol %) led
to a lower enantioselectivity (yield 80% and ee 74%;
Table 3, entry 11).
To demonstrate the influence of the electronic and
steric effects of the substrate on this asymmetric ad-
dition, a series of different aromatic aldehydes was then
Substrates with an electron-acceptor group in
aromatic aldehydes afforded than that of benzaldeyde,
but higher than those with electron-donating groups.
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906
AYDIN
A lower enantioselectivity was observed for ortho-
substituted aromatic aldehydes (Table 4, entries 4,
7, and 10) compared to their meta- and para-sub-
stituted analogs (Table 4, entries 3, 6, 9 and 2, 5, 8,
respectively). With both (1S,2R)-6 and (1S,2R)-7, lower
enantiomeric excesses were observed with aromatic
aldehydes bearing ortho-substituents, probably due to
the ortho-effect. With less crowded substrates, such as
m-methoxybenzaldehyde, a higher enantioselectivity
(ee 75%) was obtained (Table 4, entry 3). The highest
enantioselectivity was observed with p-(trifluorome-
thyl)benzaldehyde as the substrate with the strongly
electron-acceptor group–CF3 substituent (ee 99%). The
sterically less hindered naphthalene-2-carbaldehyde
gave a higher enantioselectivity than the sterically more
crowded naphthalene-1-carbaldehyde (Table 4, entries
14 and 15). In the case of thiophene-2-carbaldehyde,
the reaction provided the corresponding products with
moderate enantioselectivities: ee 58% with (1S,2R)-6
and 61% with (1S,2R)-7 (Table 4, entries 19 and 16).
chiral ligands 4–7 by the procedures in [55, 56].
1
(See Supplementary data for the H and 13C NMR of
compounds 4–7). New compounds are described below.
(R)-2-[(5-Methylthiophene-2-yl)methylamino]-
propanol [(R)-4] was prepared from (R)-2-amino
propanol (5 mmol) and 5-methylthiophene-2-car-
baldehyde (5 mmol). Yield 75%, Rf 0.30 (EtOAc–
hexane, 1 : 1); [α]D25 –0.80 (c 0.35, CHCl3). H NMR
1
spectrum (400 MHz, CDCl3), δ, ppm: 0.77 d (3H,
CHCH3, J 6.4 Hz), 2.40 s (3H, CH3), 2.89–2.99 m
(1H, CHCH3), 3.88 d (1H, NHCH2, J 14.4 Hz), 3.99 d
(1H, NHCH2, J 14.4 Hz), 3.92 m (1H, CH2OH), 6.49 d
(1H, C4H, thiophene ring, J 3.2 Hz), 6.62 d (1H, C3H,
thiophene ring, J 3.2 Hz). 13C NMR spectrum (100 MHz,
CDCl3), δ, ppm: 13.58 (CH3), 14.11 (CHCH3), 43.54
(CH2NH), 65.42 (CHCH3), 70.45 (CH2OH), 105.94 (C4,
thiophene ring), 108.08 (C3, thiophene ring), 137.6 (C5,
thiophene ring), 139.4 (C2, thiophene ring). Found, %:
C 58.30; H 8.14; N 7.58; S 17.32. C9H15NOS. Calcula-
ted, %: C 58.34; H 8.16; N, 7.56; O 8.63; S 17.31.
EXPERIMENTAL
(R)-2-[(5-Ethylthiophene-2-yl)methylamino]-
propanol [(R)-5] was prepared from (R)-2-amino-
propanol (5 mmol) and 5-ethylthiophene-2-car-
baldehyde (5 mmol). Yield 72%, brown oil, Rf 0.32
(EtOAc–hexane, 1 : 1); [α]D25 –0.74 (c 0.57, CHCl3). 1H
NMR (400 MHz, CDCl3), δ, ppm: 0.78 d (3H, CHCH3,
J 6.8 Hz), 1.25 t (2H, CH2CH3, J 7.2 Hz), 2.75 q (2H,
CH2CH3, J 7.2 Hz), 2.95–2.97 m (1H, CHCH3), 3.55–
3.62 m (2H, CH2OH), 3.88 d (1H, NHCH2, J 14.0 Hz),
3.96 d (1H, NHCH2, J 14.4 Hz), 6.55 br.s (1H, C4H,
thiophene ring), 6.65 d (1H, C3H, thiophene ring, J
3.2 Hz). 13C NMR spectrum (100 MHz, CDCl3), δ, ppm:
13.67 (CH2CH3), 17.81 (CHCH3), 26.67 (CH2CH3),
43.55 (NHCH2), 65.21 (CH3CH), 72.94 (CH2OH),
105.97 (C4, thiophene ring), 108.06 (C3, thiophene
ring), 136.75 (C5, thiophene ring), 139.56 (C2, thiophene
ring). Found, %: C 60.28; H 8.58; N 7.03; S 16.10.
C10H17NOS. Calculated, %: C 60.26; H 8.60; N 7.03;
S 16.09.
Reagents and solvents were purchased from Aldrich,
Merck, and Fluka. All solvents were dried before use by
standard procedures. The 1H and 13C NMR spectra were
recorded on a Bruker DPX-400 MHz spectrometer at
room temperature, internal reference TMS. Thin layer
chromatography was performed using Merck Kieselgel
60 F254 plates. Crude compounds were purified by
column chromatography on silica gel (60–200 mesh,
unless otherwise indicated). The IR spectra were run on
a 2000 Perkin–Elmer spectrometer. The optical rotations
were measured on an Autopol IV polarimeter. The
melting points were determined using an Electrothermal
melting point apparatus. The elemental analyses were
obtained on a LECO CHNS-932 series analyzer. The
enantiomeric excesses were determined by HPLC
analysis using Chiracel OD-H and OB and Chiralpak
AD-H chiral columns on Shimadzu LC-20AD or
Thermo Finnigan Surveyor HPLC instruments. The
absolute configurations of the major enantiomers were
determined by comparison of the retention times and the
signs of specific rotation of the synthesized compounds
with published data [55].
AdditionofEt2Zntoaldehydes(generalprocedure).
A solution of diethylzinc (2 mL of 1 M hexane solution,
2 mmol) was added dropwise to a solution of chiral
ligand 4–7 (0.05 mmol, 5 mol %) in dry toluene (2 mL)
under an argon atmosphere, and the mixture was stirred
at 0°C for 1 h. A solution of benzaldehyde (1 mmol)
in dry toluene (1 mL) was added with a syringe. After
stirringfor16h, thereactionwasquenchedwithsaturated
Synthesis of chiral ligands. Thiophene-2-car-
baldehydes 1a and 1b, synthesized by the Vilsmeier–
Haack method [66], were treated with both enantiomers
of 2-aminopropanol (2) and norephedrine (3) to obtain
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ENANTIOSELECTIVE ADDITION OF DIETHYLZINC TO AROMATIC ALDEHYDES
907
aqueous NH4Cl (5 mL). The mixture was extracted with
SUPPLEMENTARY MATERIALS
EtOAc (3 × 10 mL). The combined organic layers were
washed with brine, dried over anhydrous Na2SO4, and
evaporated under reduced pressure. The residue was
purified by silica gel flash column chromatography to
give the corresponding product. Secondary alcohols
9a–9p are known compounds; they were characterized
by comparing their 1H and 13C NMR spectra with those
reported in [49, 58, 60]. The enantiomeric excesses
were determined by HPLC on chiral columns. The
absolute configurations of the major enantiomers were
determined by comparison of the retention times and
the signs of specific rotation of known compounds with
published data [58, 59]. Compounds 9a–9p are known
compounds; they were characterized by comparing
Supplementary materials are available for this article at
https://doi.org/10.1134/S1070428020050255 and are acces-
sible for authorized users.
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1
13
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spectrum (100 MHz, CDCl3), δ, ppm: 10.53 (CH3),
32.29 (CH2), 76.43 (CH), 126.37 (CH), 127.89 (CH),
128.91 (CH), 145.01. Found, %: C 79.41; H 8.90.
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13
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In conclusion, thiophene-substituted chiral amino
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pure norephedrine were prepared and used as chiral
catalysts in the asymmetric addition of diethylzinc to
aldehydes. The use of these chiral amino alcohols has
several advantages, such as high reaction rates and
excellent yields, no side reactions, ease of preparation,
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The research was financially supported by the Scientific
Research Commission of the Hatay Mustafa Kemal University
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CONFLICT OF INTEREST
The authors declare no conflict of interest.
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