Mandelic acid derived α-aziridinyl alcohols as highly efficient ligands for asymmetric additions of zinc organyls to aldehydes

Article abstract of DOI:10.1016/j.tetasy.2013.04.019

A straightforward synthesis of a series of new catalysts containing secondary hydroxyl and aziridine moieties as nucleophilic centers built on the chiral scaffold of (S)-(+)-mandelic acid is described. The new compounds have been tested for the enantioselective addition of diethylzinc and phenylethynylzinc to aryl and alkyl aldehydes, which yielded the corresponding chiral alcohols in high chemical yields (up to 95%) and with excellent ee's of ca. 90%. The strong influence of the stereogenic center located at the aziridine subunit on the stereochemical outcome is also reported on.

Full text of DOI:10.1016/j.tetasy.2013.04.019

Tetrahedron: Asymmetry 24 (2013) 689–693
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Tetrahedron: Asymmetry
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Mandelic acid derived
a-aziridinyl alcohols as highly efficient ligands
for asymmetric additions of zinc organyls to aldehydes
⇑
´
´
´
Michał Rachwalski , Szymon Jarzynski, Marcin Jasinski, Stanisław Lesniak
´
´
Department of Organic and Applied Chemistry, University of Łódz, Tamka 12, 91-403 Łódz, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 April 2013
Accepted 26 April 2013
A straightforward synthesis of a series of new catalysts containing secondary hydroxyl and aziridine moi-
eties as nucleophilic centers built on the chiral scaffold of (S)-(+)-mandelic acid is described. The new
compounds have been tested for the enantioselective addition of diethylzinc and phenylethynylzinc to
aryl and alkyl aldehydes, which yielded the corresponding chiral alcohols in high chemical yields (up
to 95%) and with excellent ee’s of ca. 90%. The strong influence of the stereogenic center located at the
aziridine subunit on the stereochemical outcome is also reported on.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Asymmetric catalysis represents one of the most important re-
search fields of modern organic chemistry.1 Typically in the search
for new enantiopure ligands, a chiral pool of carbohydrates, terp-
enes, amino acids, and hydroxy acids is of enormous synthetic va-
lue.2 Among the latter class of compounds, readily available
mandelic acid appears as a particularly attractive source of chiral-
ity.2 On the other hand, enantioselective carbon–carbon bond for-
mation using organozinc reagents (especially diethylzinc) is a
commonly used methodology for the preparation of non-racemic
compounds.3–6 More recently, we have described the synthesis of
a series of enantiomerically pure aziridine alcohols derived from
salicylic and 2-hydroxymethylbenzoic acid, and their excellent cat-
alytic properties for the asymmetric addition of diethylzinc and
phenylethynylzinc to various aliphatic and aromatic aldehydes.7
An easy access to both enantiomers of the products using isomeric
forms of the catalysts was presented. In a continuation of our cur-
rent interests in the field of asymmetric synthesis,8–15 and taking
into account the fact, that aziridines strongly coordinate to zinc
organyl species,16–18 we turned our attention to aziridine catalysts
with new substitution patterns. According to the literature reports,
some ligands derived from (S)- and (R)-mandelic acid functional-
ized with oxazoline moieties have been successfully used for
asymmetric phenyl transfer to aromatic aldehydes,2 affording the
corresponding products in high yields (up to 76%) and with prom-
ising ee’s (up to 35%). As a result, we decided to synthesize a series
of new compounds exploiting (S)-(+)-mandelic acid as a key build-
ing block, and to check their catalytic activity toward the addition
of diethylzinc and phenylethynylzinc to model aldehydes.
2.1. Synthesis of the ligands
The three step synthesis of our new ligands is depicted in
Schemes 1–3. First, the free OH group of commercially available
(S)-(+)-mandelic acid 1 was protected by treatment with freshly
distilled acetyl chloride. The resulting crude material was subse-
quently converted into the respective acid chloride by reaction
with excess oxalyl chloride to furnish (S)-O-acetylmandelic
derivative 2 in quantitative yield according to the literature
(Scheme 1).2
OAc
OH
1. AcCl, rt, 2h
2. (COCl)2/DCM, DMF, rt, 2h
Cl
OH
O
quant.
O
2
1
Scheme 1. Synthesis of (S)-O-acetylmandelic acid chloride 2.
Next, an ether solution of freshly prepared (S)-O-acetylmandelic
acid chloride 2 was treated with a series of aziridines 3a–d in the
presence of triethylamine at room temperature to afford the de-
sired amides of type 4 in excellent yields of >97% (Scheme 2). A
model achiral 2,2-dimethylaziridine 3a, and the three enantiome-
rically pure aziridine derivatives 3b–d, (S)-2-methylaziridine 3b,
(S)- and (R)-2-isopropylaziridines 3c and 3d, were synthesized
starting with the respective amino acids as reported previ-
ously.19,20 The specific rotations and absolute configurations of
the hitherto unknown acylaziridines 4a–d are shown in Table 1.
⇑
Corresponding author. Tel.: +48 42 6355756.
E-mail address: mrach14@wp.pl (M. Rachwalski).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.04.019

690
M. Rachwalski et al. / Tetrahedron: Asymmetry 24 (2013) 689–693
R2
R2
R1
OAc
OAc
R1
N
H
Cl
N
, Et3N
O
O
Et2O, rt
2
4a-d
aziridines
Pri
H
Me
Me
Me
Pri
3a
3b
H
2,2`-dimethylaziridine
N
H
H
N
H
N
H
N
H
(-)-(S)-2-methylaziridine
3c (-)-(S)-2-isopropylaziridine
3d (+)-(R)-2-isopropylaziridine
3a
3d
3b
3c
Scheme 2. Synthesis of amides 4a–d.
R2
R1
model transformations. As shown in Scheme 4, the reactions were
R2
R1
OAc
conducted under standard reaction conditions (in toluene or THF,
OH
respectively),9,10 and the results are summarized in Table 3.
1.(EtO)3SiH
Zn(OAc)2, THF
N
N
O
2. NaOH
OH
ligand, Et2Zn
5a-d
4a-d
PhCHO
Ph
toluene
Scheme 3. Reduction of amides 4a–d to form ligands 5a–d.
6a
Table 1
Synthesis of amides 4a–d
OH
Ph
ligand, Et2Zn
THF
Ph
PhCHO
Ph
+
a
Entry
Amide
Yield (%)
½
a D
ꢀ
Absolute configuration
1
2
3
4
4a
4b
4c
4d
98
97
98
98
+8.6
(S)
7a
+72.0
+23.8
+11.5
(S,R)
(S,R)
(S,S)
Scheme 4. Asymmetric addition of diethyl- and phenylethynylzinc to
benzaldehyde.
a
In chloroform (c 1).
Brief analysis of the results (Table 3) clearly shows that all new
aziridines 5a–d derived from (S)-mandelic acid are prone to cata-
lyze the selected model reactions and give the desired products
6a and 7a in high chemical yields (>92%) and with excellent enan-
tiomeric excesses of >92%. However, in the case of derivative 5a
bearing an achiral 2,20-dimethylaziridine group a significant de-
crease of conversion (62% and 59%, respectively) and stereoselec-
tivity (42% and 40%, respectively) was seen. The observed results
suggest that the presence of the stereogenic center at the aziridine
moiety is of crucial importance with respect to the stereochemical
outcome of the catalytic reactions. A series of experiments pro-
moted by diastereomeric ligands 5c and 5d led to products, which
exhibited comparable specific rotation values with opposite signs,
which in turn strongly supported this assumption. The absolute
configurations at the newly generated stereogenic centers of 6a
and 7a were attributed to the literature reports.22
The attempted conversion of amides 4 into the desired aziridine
alcohols of type 5 under the standard reaction conditions using
lithium aluminum hydride was unsuccessful. Usually, the reaction
provided complex mixtures containing trace amounts of the de-
sired material (<10%) only. Thus, acylaziridines 4a–d were reduced
to the corresponding aziridines 5a–d by the slightly modified pro-
cedure developed by Das et al.,21 utilizing excess triethoxysilane in
the presence of a stoichiometric amount of zinc acetate in refluxing
THF. As anticipated, subsequent basic work-up enabled the simul-
taneous deprotection of the hydroxyl group, and provided the de-
sired materials in high yields of 80% (Scheme 3, Table 1). The
1H NMR spectra of the new aziridine derivatives of type 5 also de-
serve some comment. Whereas in the case of compounds bearing
unsymmetrically substituted aziridine subunits compounds 5b–
5d only one set of signals could be observed, in the 1H NMR
spectrum of 2,2-dimethylaziridine derivative 5a, taken at room
temperature, two sets of signals attributed to the respective inver-
tomers were detected. This phenomenon is in full accordance with
our previous observations.9
2.3. Asymmetric additions of diethyl- and phenylethynylzinc to
selected aldehydes in the presence of ligand 5c
With new efficient ligands in hand, we next determined the
scope of the catalytic activity of selected ligand 5c. Thus, the title
transformations were performed with a series of aldehydes as
shown in Scheme 5. The results are summarized in Table 4.
The results shown in Tables 3 and 4 indicate that the selected
ligand 5c could be considered as a highly effective catalyst for
2.2. Screening of the ligands
In order to test the catalytic activity of novel ligands 5a–d in the
addition of zinc organyls to aldehydes, we selected the reactions of
diethylzinc and phenylethynylzinc with benzaldehyde as the

M. Rachwalski et al. / Tetrahedron: Asymmetry 24 (2013) 689–693
691
OH
the resulting oily residue was dissolved in dichloromethane
(70 mL). Next, DMF (0.7 mL) followed by a solution of oxalyl chlo-
ride (2.3 mL, 26.8 mmol, in 30 mL of dichloromethane) was added
slowly and the mixture was stirred at rt for 2 h. The resulting mix-
ture was concentrated on a rotary evaporator to afford spectro-
5c,
ligand
Et2Zn
RCHO
R
toluene
6a-e
scopically pure (S)-O-acetylmandelic acid chloride
2 as a
¼ þ186:0; 1H NMR (CDCl3):
OH
R
ligand 5c, Et2Zn
yellowish oil (5.1 g, quant.); ½a D
ꢀ
RCHO
Ph
+
Ph
d = 2.22 (s, 3H), 6.08 (s, 1H), 7.44–7.46 (m, 3H), 7.47–7.49 (m, 2H).
THF
7a-e
4.2.2. Synthesis of amides 4a–d—general procedure
In
a round-bottomed flask, the corresponding aziridine 3
Scheme 5. Additions of diethyl- and phenylethynylzinc to aldehydes in the
presence of ligand 5c.
(3.3 mmol), triethylamine (0.75 mL, 5.4 mmol) and diethyl ether
(10 mL) were placed, and the resulting mixture cooled to 0 °C using
an external ice bath was treated dropwise with a solution of (S)-O-
acetylmandelic acid chloride 2 (0.64 g, 3.0 mmol) in Et2O (3 mL).
After stirring for 30 min at room temperature the precipitate was
filtered off and the filtrate was concentrated on a rotary evaporator
to yield the corresponding amides 4a–d. Yields and specific rota-
tions are shown in Table 2.
the title reactions, leading to the target alcohols in excellent yields
and ee’s. Moreover, careful analysis of the absolute configurations
of the products listed in Table 4 suggests that the attack of the zinc
organyl species mediated by 5c always occurs from the same side,
irrespective to the substitution pattern of the electrophilic reaction
partner. For instance, the reaction of p-bromobenzaldehyde with
diethylzinc provided the (S)-configured product in 86% yield (89%
ee), whereas an analogous transformation using phenylethynylzinc
afforded the (R)-configured adduct in a high yield of 85% (90% ee)
(Table 4, entry 4). Comparable results with respect to yields and
ee’s were noticed in the case of other substituted benzaldehydes
and butyraldehyde.
Table 2
Reduction of amides 4a–d to form ligands 5a–d
a
Entry
Ligand
Yield (%)
½
a D
ꢀ
Absolute configuration
1
2
3
4
5a
5b
5c
5d
85
84
81
83
+16.8
+30.0
ꢁ47.7
+3.0
(S)
(S,R)
(S,R)
(S,S)
3. Conclusion
a
In chloroform (c 1).
The chiral bidentate ligands of type 5 derived from (S)-(+)-man-
delic acid containing two stereogenic centers were found to be
highly effective catalysts for the enantioselective addition of
diethyl- and phenylethynylzinc to various aldehydes. The stereo-
genic centers located at the amine moieties had a decisive influ-
ence on the stereochemistry of the products. Based on the
presented protocol, each enantiomer of the designed product
should be available by the use of the respective diastereomeric
ligands.
Amide 4a (colorless amorphous solid, mp. 92–93 °C); 1H NMR
(CDCl3): d = 1.29 (s, 3H), 1.36 (s, 3H), 2.18 (s, 4H), 2.29 (s, 1H),
5.95 (s, 1H), 7.36–7.40 (m, 3H), 7.49–7.51 (m, 2H); 13C NMR
(CDCl3): d = 20.8 (CH3), 22.7 (CH3), 23.0 (CH3), 37.4 (Cq), 42.3
(CH2), 76.7 (CH), 127.9 (Car), 128.7 (Car), 128.8 (Car), 128.9 (Car),
134.9 (Cq ar), 170.3 (C@O), 178.0 (C@O); MS (CI): m/z 248 (M+H).
Amide 4b (colorless oil); 1H NMR (CDCl3): d = 1.35 (d, J = 5.4 Hz,
3H), 1.95 (d, J = 3.6 Hz, 1H), 2.18 (s, 3H), 2.45 (d, J = 5.4 Hz, 1H),
2.79–2.83 (m, 1H), 5.91 (s, 1H), 7.36–7.41 (m, 3H), 7.50–7.56 (m,
2H); 13C NMR (CDCl3): d = 17.7 (CH3), 20.7 (CH3), 31.6 (CH), 34.0
(CH2), 76.8 (CH), 127.6 (Car), 127.9 (Car), 128.8 (Car), 129.1 (Car),
134.4 (Car), 170.6 (C@O), 180.8 (C@O); MS (CI): m/z 234 (M+H).
Amide 4c (colorless oil); 1H NMR (CDCl3): d = 0.98 (d, J = 7.2 Hz,
3H), 1.12 (d, J = 7.2 Hz, 3H), 1.59 (dh, J = 7.2 Hz, 7.5 Hz, 1H), 1.96 (d,
J = 3.6 Hz, 1H), 2.16 (s, 3H), 2.43 (d, J = 6.0 Hz, 1H), 2.67 (ddd,
J = 3.6 Hz, 6.0 Hz, 7.5 Hz, 1H), 5.91 (s, 1H), 7.36–7.43 (m, 3H),
7.52–7.57 (m, 2H); 13C NMR (CDCl3): d = 18.7 (CH3), 19.9 (CH3),
20.7 (CH3), 29.3 (CH), 30.7 (CH2), 44.8 (CH), 127.9 (Car), 128.8
(Car), 128.9 (Car), 129.2 (Car), 134.2 (Cq ar), 170.8 (C@O), 181.4
(C@O); MS (CI): m/z 262 (M+H).
4. Experimental
4.1. General
Unless otherwise specified, all reagents were purchased from
commercial suppliers and used without further purification. Tetra-
hydrofuran and toluene were distilled from sodium benzophenone
ketyl radical. 1H and 13C NMR spectra were recorded on a Bruker
instrument at 600 and 151 MHz, respectively, with CDCl3 as sol-
vent and relative to TMS as internal standard. Data are reported
as s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet,
b = broad. Optical rotations were measured on a Perkin–Elmer
241 MC polarimeter with a sodium lamp at room temperature (c
1). Melting points were determined on a MELTEMP apparatus
and are uncorrected. Column chromatography was carried out
using Merck 60 silica gel. TLC was performed on Merck 60 F254 sil-
ica gel plates. Visualization was accomplished with UV light
(254 nm). The enantiomeric excess (ee) values were determined
by chiral HPLC (Knauer, Chiralcel OD). Aziridines 3a–d were pre-
pared according to the literature procedure.19
Amide 4d (colorless oil); 1H NMR (CDCl3): d = 0.90 (d, J = 6.6 Hz,
3H), 0.98 (d, J = 6.6 Hz, 3H), 1.50 (dh, J = 6.6 Hz, 7.0 Hz, 1H), 2.10 (d,
J = 4.2 Hz, 1H), 2.16 (s, 3H), 2.24 (ddd, J = 3.6 Hz, 6.0 Hz, 7.5 Hz, 1H),
2.60 (d, J = 6.0 Hz, 1H), 5.96 (s, 1H), 7.37–7.41 (m, 3H), 7.49–7.52
(m, 2H); 13C NMR (CDCl3): d = 18.6 (CH3), 19.9 (CH3), 20.7 (CH3),
29.9 (CH), 30.3 (CH2), 43.5 (CH), 127.9 (2Car), 128.8 (Car), 129.1
(Car), 134.3 (Cq ar), 170.6 (C@O), 180.6 (C@O); MS (CI): m/z 262
(M+H).
4.2.3. Reduction of amides 4a–d to form chiral ligands 5a–d—
general procedure
In a round-bottomed flask zinc acetate (0.37 g, 1 mmol), trieth-
oxysilane (0.82 g, 5.0 mmol) and fresh distilled dry THF (3 mL)
were placed. The mixture was stirred for 30 min under argon fol-
lowed by the addition of the corresponding amide (1.0 mmol) in
4.2. Synthesis of the ligands 5a–d
4.2.1. Synthesis of (S)-O-acetylmandelic acid chloride 22
(S)-(+)-Mandelic acid (4.0 g, 26.3 mmol) was dissolved in acetyl
chloride (7.4 mL) and the mixture was stirred at room temperature
for 2 h. After the excess of acetyl chloride was removed in vacuo

692
M. Rachwalski et al. / Tetrahedron: Asymmetry 24 (2013) 689–693
Table 3
Screening of ligands 5a–d
Entry
Ligand
Product 6a
Product 7a
eeb (%)
a
a
Yield (%)
½
a D
ꢀ
eeb (%)
Abs. config.
Yield (%)
½
a D
ꢀ
Abs. config.c
1
2
3
4
5a
5b
5c
5d
62
92
97
96
ꢁ18.9
ꢁ41.4
ꢁ42.7
+41.8
42
92
95
93
(S)
(S)
(S)
(R)
59
93
95
93
ꢁ2.1
ꢁ4.8
ꢁ4.8
+4.6
40
93
94
90
(S)
(S)
(S)
(R)
a
b
c
In chloroform (c 1).
Determined using chiral HPLC.
According to the literature data.22
Table 4
Additions of diethyl- and phenylethynylzinc to aldehydes in the presence of ligand 5c
Entry
R
Products 6a–e
Products 7a–e
a
a
Yield (%)
½
a D
ꢀ
eeb (%)
Abs. config.c
Yield (%)
½
aꢀD
eeb (%)
Abs. config.c
1
2
3
4
5
Ph
97
90
93
86
88
ꢁ42.8
ꢁ46.0
+6.6
95
88
94
89
90
(S)
(S)
(S)
(S)
(S)
95
89
92
85
88
ꢁ4.8
ꢁ7.5
ꢁ3.1
+3.7
94
90
89
90
85
(S)
(R)
(S)
(R)
(R)
2-MeOC6H4
n-Pr
4-BrC6H4
2-MeC6H4
ꢁ7.8
ꢁ40.2
ꢁ10.6
a
b
c
In chloroform (c 1).
Determined using chiral HPLC.
According to the literature data.6,9,10,23
THF (2 mL). The mixture was heated at reflux on an oil bath and
after 6 h was cooled to room temperature and treated with 1 M
NaOH (3 mL). After 3 h of stirring, the mixture was extracted with
ethyl acetate (4ꢂ), and the combined organic phases were dried
over anhydrous Na2SO4 and concentrated in vacuo to afford the
crude products, which after column chromatography (hexane with
ethyl acetate in gradient) gave the final ligand structures 5a–d. The
chemical yields, specific rotation values and absolute configuration
of all ligands 5a–d are shown in Table 2.
Ligand 5a (as almost equimolar mixture of invertomers) (color-
less oil); 1H NMR (CDCl3): first invertomer d = 1.10 (s, 3H), 1.15 (s,
3H), 1.75 (s, 3H), 2.52 (dd, J = 9.0 Hz, 12.0 Hz, 1H), 2.77 (dd,
J = 3.6 Hz, 12.0 Hz, 1H), 3.64 (br s, 1H), 4.73 (dd, J = 3.6 Hz, 9.0 Hz,
1H), 7.25–7.28 (m, 2H), 7.32–7.39 (m, 3H); second invertomer
d = 1.16 (s, 3H), 1.19 (s, 3H), 1.21 (s, 3H), 1.77 (s, 1H), 2.31 (dd,
J = 3.6 Hz, 12.0 Hz, 1H), 2.78 (dd, J = 8.4 Hz, 12.0 Hz, 1H), 3.94 (br
s, 1H), 4.78 (dd, J = 3.6 Hz, 8.4 Hz, 1H), 7.25–7.28 (m, 2H), 7.32–
7.39 (m, 3H); 13C NMR (CDCl3): first invertomer d = 17.6 (CH3),
26.5 (CH3), 36.0 (Cq), 41.2 (CH2), 61.3 (CH2), 72.5 (CH), 125.9 (Car),
126.0 (Car), 127.4 (Car), 128.3 (Car), 142.4 (Cq ar) (as a superposition
for invertomers); second invertomer d = 17.3 (CH3), 26.7 (CH3),
35.4 (CH), 41.8 (CH2), 60.7 (CH2), 73.9 (CH), 125.6 (Car), 126.3
(Car), 127.8 (Car), 128.9 (Car), 142.4 (Cq ar) (as a superposition for
invertomers); MS (CI): m/z 192 (M+H); HRMS (CI): calcd for
73.0 (CH), 125.9 (2Car), 127.5 (Car), 128.3 (Car), 142.0 (Cq ar); MS
(CI): m/z 206 (M+H); HRMS (CI): calcd for C13H20NO: 206.1552;
found 206.1545.
Ligand 5d (colorless oil); 1H NMR (CDCl3): d = 0.95 (d, J = 6.6 Hz,
3H), 1.06 (d, J = 6.6 Hz, 3H), 1.25–1.30 (m, 2H), 1.60 (d, J = 3.0 Hz,
2H), 2.10 (dd, J = 3.0 Hz, 12.0 Hz, 1H), 2.81 (dd, J = 10.0 Hz,
12.0 Hz, 1H), 3.63 (br s, 1H), 4.79 (dd, J = 3.0 Hz, 10.0 Hz, 1H),
7.24–7.27 (m, 2H), 7.31–7.37 (m, 3H); 13C NMR (CDCl3): d = 19.6
(CH3), 20.4 (CH3), 31.3 (CH), 32.9 (CH2), 46.7 (CH), 68.8 (CH2),
73.1 (CH), 125.9 (Car), 127.4 (Car), 128.3 (2Car), 141.9 (Cq ar); MS
(CI): m/z 206 (M+H); HRMS (CI): calcd for C13H20NO: 206.1544;
found 206.1544.
4.3. Asymmetric addition of diethylzinc to aldehydes—general
procedure9
Chiral catalysts of type 5 (0.1 mmol) in dry toluene (5 mL) were
placed in a round-bottomed flask. The mixture was cooled to 0 °C
and a solution of diethylzinc (1.0 M soln in hexane, 3.0 mmol)
was added under argon. After stirring for 30 min, an aldehyde
(1.0 mmol) was added at 0 °C, and the mixture was stirred at room
temperature overnight. Next, 5% HCl aqueous solution was added,
and the layers were separated after which the aqueous phase was
extracted with diethyl ether (4 ꢂ 10 mL). The combined organic
layers were washed with brine (10 mL) and dried over anhydrous
MgSO4. The solvents were evaporated to afford the crude alcohols
6a–e, which were purified via column chromatography on silica gel
(hexane with ethyl acetate in gradient). The yields, specific rota-
tions, enantiomeric excess values, and the absolute configurations
of the products 6a–e are shown in Table 4. The spectroscopic data
are in full agreement with those reported in the literature.6,9,10,22
C
12H18NO: 192.1384; found 192.1388.
Ligand 5b (colorless oil); 1H NMR (CDCl3): d = 1.13 (d, J = 5.4 Hz,
3H), 1.27 (d, J = 6.6 Hz, 2H), 1.43–1.47 (m, 1H), 1.50 (d, J = 3.6 Hz,
1H), 2.28 (dd, J = 3.6 Hz, 12.0 Hz, 1H), 2.69 (dd, J = 9.0 Hz, 12.0 Hz,
1H), 4.82 (dd, J = 3.6 Hz, 9.0 Hz, 1H), 7.25–7.38 (m, 5H); 13C NMR
(CDCl3): d = 18.2 (CH3), 34.2 (CH2), 35.0 (CH), 68.4 (CH2), 72.9
(CH), 125.90 (2Car), 127.5 (Car), 128.3 (Car), 142.2 (Cq ar); MS (CI):
m/z 178 (M+H); HRMS (CI): calcd for C11H16NO: 178.1236; found
178.1232.
4.4. Asymmetric addition of phenylethynylzinc to aldehydes—
general procedure10
Ligand 5c (colorless oil); 1H NMR (CDCl3): d = 0.91 (d, J = 6.6 Hz,
3H), 1.01 (d, J = 6.6 Hz, 3H), 1.28–1.32 (m, 2H), 1.60 (d, J = 3.2 Hz,
2H), 2.10 (dd, J = 3.0 Hz, 12.0 Hz, 1H), 2.81 (dd, J = 10.0 Hz,
12.0 Hz, 1H), 3.39 (br s, 1H), 4.80 (dd, J = 3.6 Hz, 10.0 Hz, 1H),
7.25–7.28 (m, 2H), 7.32–7.37 (m, 3H); 13C NMR (CDCl3): d = 19.3
(CH3), 20.2 (CH3), 31.4 (CH), 32.6 (CH2), 46.1 (CH), 69.1 (CH2),
To a solution of ligand of type 5 (0.2 mmol) in THF (5 mL), was
added a solution of diethylzinc (1.4 mL, 1.4 mmol, 1.0 M in hexane)
at room temperature under argon. After the mixture was stirred at
ambient temperature for 30 min, phenylacetylene (154 lL,

M. Rachwalski et al. / Tetrahedron: Asymmetry 24 (2013) 689–693
693
4. Dabiri, M.; Salehi, P.; Kozehgary, G.; Heydari, A.; Esfandyari, M. Tetrahedron:
Asymmetry 2008, 19, 1970–1972.
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7. Rachwalski, M.; Jarzyn´ ski, S.; Les´niak, S. Tetrahedron: Asymmetry 2013. http://
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8. Rachwalski, M.; Kwiatkowska, M.; Drabowicz, J.; Kłos, M.; Wieczorek, W. M.;
1.4 mmol) was added, and stirring continued for another 30 min.
The solution was cooled to 0 °C (ice bath) and treated with the cor-
responding aldehyde (1.0 mmol). The resulting mixture was stirred
for 2 h at 0 °C and then overnight at room temperature. After com-
pletion of the reaction (TLC monitoring), it was quenched with 5%
aqueous HCl. The resulting mixture was extracted with diethyl
ether (4 ꢂ 10 mL) and the combined organic layers were washed
with brine. After the organics were dried over anhydrous MgSO4,
the solvents were removed in vacuo. The residue was purified by
column chromatography (silica gel, hexane with ethyl acetate in
gradient) to afford the corresponding products 7a–e. The yields,
specific rotations, enantiomeric excess values, and the absolute
configurations of the products 7a–e are shown in Table 4. The spec-
troscopic data are in full agreement with those reported in the
literature.6,9,10,22
´
´
Szyrej, M.; Sieron, L.; Kiełbasinski, P. Tetrahedron: Asymmetry 2008, 19, 2096–
2101.
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Asymmetry 2009, 20, 2311–2314.
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2687–2689.
11. Rachwalski, M.; Les´niak, S.; Kiełbasin´ ski, P. Tetrahedron: Asymmetry 2010, 21,
1890–1892.
12. Rachwalski, M.; Les´niak, S.; Sznajder, E.; Kiełbasin´ ski, P. Tetrahedron:
Asymmetry 2009, 20, 1547–1549.
´
´
13. Rachwalski, M.; Lesniak, S.; Kiełbasinski, P. Tetrahedron: Asymmetry 2011, 22,
1087–1089.
´
´
14. Rachwalski, M.; Lesniak, S.; Kiełbasinski, P. Tetrahedron: Asymmetry 2011, 22,
1325–1327.
Acknowledgments
15. Rachwalski, M.; Leenders, T.; Kiełbasin´ ski, P.; Les´niak, S.; Rutjes, F. P. J. T. Org.
Biomol. Chem., http://dx.doi.org/10.1039/C3OB40681D.
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Commun. 1981, 10, 515–519.
17. Bartnik, R.; Les´niak, S.; Laurent, A. Tetrahedron Lett. 1981, 4811–4812.
18. Bartnik, R.; Les´niak, S.; Laurent, A. J. Chem. Res. 1982, 287, 2701–2709.
19. Xu, J. Tetrahedron: Asymmetry 2002, 13, 1129–1134.
20. Cairns, T. L. J. Am. Chem. Soc. 1941, 63, 871–872.
Financial support by the National Science Centre (NCN), Grant
No. 2012/05/D/ST5/00505 for M.R., is gratefully acknowledged.
´
The scientific award of the Foundation of University of Łódz for
M.R. is also acknowledged.
21. Das, S.; Addis, D.; Zhou, S.; Junge, K.; Beller, M. J. Am. Chem. Soc. 2010, 132,
1770–1771.
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