Structural and electronic effects of oxazolidine ligands derived from (1R,2S)-ephedrine in the asymmetric addition of diethylzinc to aldehydes

Article abstract of DOI:10.1016/j.tetasy.2010.02.029

The purpose of this research was to determine the activity of chiral oxazolidine ligands prepared from (1R,2S)-ephedrine for the enantioselective addition of diethylzinc to aldehydes. The configuration on the newly formed C2 stereogenic center was determined as (2S) by X-ray structural analysis. Oxazolidine ligands reveal medium enantioselectivity with the ee exceeding 57%, and the yields obtained being 68-99%. The results indicate that the absolute configuration of the addition product depends not only on the N3-methyl as an important stereocontrol element but also on both the electronic and steric effects of the substrates and oxazolidine ligands.

Full text of DOI:10.1016/j.tetasy.2010.02.029

Tetrahedron: Asymmetry 21 (2010) 571–577
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Structural and electronic effects of oxazolidine ligands derived from
(1R,2S)-ephedrine in the asymmetric addition of diethylzinc to aldehydes
b
a
b
Ewelina Błocka a, Magdalena Jaworska a, , Anna Kozakiewicz , Mirosław Wełniak , Andrzej Wojtczak
*
a
´
Department of Organic Chemistry, Nicolaus Copernicus University, Gagarina 7, 87-100 Torun, Poland
b Department of Crystallochemistry and Biocrystallography, Nicolaus Copernicus University, Gagarina 7, 87-100 Torun´, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
The purpose of this research was to determine the activity of chiral oxazolidine ligands prepared from
(1R,2S)-ephedrine for the enantioselective addition of diethylzinc to aldehydes. The configuration on
the newly formed C2 stereogenic center was determined as (2S) by X-ray structural analysis. Oxazolidine
ligands reveal medium enantioselectivity with the ee exceeding 57%, and the yields obtained being 68–
99%. The results indicate that the absolute configuration of the addition product depends not only on the
N3-methyl as an important stereocontrol element but also on both the electronic and steric effects of the
substrates and oxazolidine ligands.
Received 7 February 2010
Accepted 23 February 2010
Available online 13 April 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
in 45–77% yields (Scheme 1) as calculated after re-crystallization
of products. The stereochemistries of the investigated oxazolidines
One of the most important asymmetric transformations, the
carbon–carbon bond formation is explored extensively in modern
organic chemistry. There is a great variety of catalytic asymmetric
reactions for C–C bond formation including cyanosilylations of
aldehydes,1 nitroaldol reactions,2 alkynylations3, and additions of
diorganozinc reagents.4 The use of dialkylzinc reagents is a very
successful method to obtain chiral secondary alcohols often used
in the synthesis of many biologically active compounds, synthetic
drugs, and new materials with optical properties.5,6 Recently ami-
no alcohols,7 imines,8 salicylhydrazones9, and amides10 derived
from Ephedra alkaloids have been used as successful ligands in
diethylzinc addition to aldehydes. Many oxazolidines were used
as chiral auxiliaries.11,12 Hitchock et al.13 described some oxazoli-
dines derived from (1R,2S)-ephedrine and their catalytic activity
in the enantioselective addition of diethylzinc to aldehydes. There
are literature reports on the dependence of ee in the reaction of
diethylzinc on the steric hindrance caused by substituents near
to the postulated reaction center.14 Therefore, we decided to obtain
some new oxazolidines with different substituents in phenolic ring
to further investigate their effect on the ee’s in that reaction. Here-
in, we report the syntheses of seven different oxazolidines and
their use in the asymmetric synthesis of secondary alcohols.
were assigned based on the X-ray structures reported here and are
consistent with the literature reports.15
The structures of 1, 2, 3, 5, and 6 are reported here; the data col-
lection and refinement processes are summarized in Table 1. The
selected intramolecular geometrical parameters, as well as the
geometry of hydrogen bonds are presented in Tables 2 and 3,
respectively. The structure of 1 has already been published by
Bourne et al.16 We have re-determined the structure of 1 as a ref-
erence structure. Both these structures have the same space group
symmetry. However, there are slight differences in the crystal lat-
tice parameters, the largest one for the b angle reaching approxi-
mately 3%, with 100.32(2) reported in the literature16 and being
103.174(9) in the structure determined by us (Table 1). Compari-
son of these two structures revealed an almost identical molecular
geometry for oxazolidine.
The Flack method17 was used to determine the configuration of
the chiral center for oxazolidine 2 which was assigned as (2S,4S,5R)
and is consistent with the configuration of the substrate (1R,2S)-
ephedrine. The Flack parameters for other structures 1, 3, 5, and
6 were inconclusive (Table 1). However, we used the same sub-
strate for the synthesis of all the oxazolidines reported here, and
the configuration of the stereogenic centers was determined
unambiguously for compound 2 as stated above. Therefore, the
same configuration was assigned relative to the known chirality
of C4 and C5, corresponding to those of C2 and C1 in the substrate.
The resulting (2S)-configuration was detected in all of the oxazol-
idine structures reported here.
2. Results and discussion
(1R,2S)-Ephedrine in the reaction with salicylaldehydes or 2-hy-
droxy-1-naphthaldehyde formed the respective oxazolidines 1–7
The different configuration for 6 was determined by other
authors with the 1H NMR NOESY technique13 as (2R,4S,5R),
although the synthesis was performed under similar conditions
* Corresponding author. Tel.: +48 56 611 4521; fax: +48 56 654 2477.
E-mail address: magdajaworska@vp.pl (M. Jaworska).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.02.029

572
E. Błocka et al. / Tetrahedron: Asymmetry 21 (2010) 571–577
C
2 OH
NH
N
aldehyde,
R1
R2
ethanol
rt. 24h
O
OH
(1R,2S)-ephedrine
R4
R3
1
2
3
4
1
2
4
3
1
5
: R = -Bu, R =R =H, R =Me
t
: R =R =R =R =H;
2: R1=H, R2=H, R3=Br, R4=H; 6: R1=t-Bu, R2=R4=H, R3=t-Bu
1
2
3
4
1
2
3
4
3
7
: R =R =H, R =R = C6H4 (naphtalene),
: R =Me, R =R =R =H;
4: R1=i-Pr, R2=R3=R4=H
Scheme 1. Synthesis of oxazolidine ligands 1–7.
Table 1
Crystallographic data for oxazolidines 1, 2, 3, 5, and 6
1
2
3
5
6
Formula sum
Formula weight
Color
Crystal system
Space group
C17H19N1O2
269.33
Colorless
Monoclinic
P21
C17H18N1O2Br1
348.23
Colorless
Orthorhombic
P212121
C18H22N1O2
283.36
Colorless
Monoclinic
P21
C22H29N1O2
339.46
Colorless
Monoclinic
C2
C25H35N1O2
381.54
Colorless
Orthorhombic
P212121
Unit cell dimensions
0
9.6697(11)
7.7393(9)
7.9380(5)
9.2182(8)
7.4128(7)
12.6767(12)
13.496(3)
12.886(3)
24.554(5)
10.2959(15)
22.421(3)
31.247(4)
a (AÅ)
0
b (AÅ)
0
10.9340(7)
18.4872(11)
10.2593(11)
c (AÅ)
b (°)
V (AÅ3)
103.174(9)
747.57(15)
90.0
1604.58(17)
109.857(8)
814.73(13)
105.75(3)
4109.8(16)
90.0
7213.2(17)
0
Z
2
4
2
8
12
1.054
0.066
2496
Density, calculated (Mg/m3)
Absorption coefficient (mmꢀ1
F(0 0 0)
1.197
0.078
288
1.442
2.565
712
1.155
0.075
304
1.097
0.069
1472
)
Crystal size (mm)
h range for data collection (°)
Index ranges
0.65 ꢁ 0.26 ꢁ 0.16
2.16–31.26
ꢀ11 6 h 6 11
ꢀ14 6 k 6 15
ꢀ26 6 l 6 25
15898
4884 [R(int) = 0.0577]
0.6860/0.2848
—
0.52 ꢁ 0.27 ꢁ 0.16
2.35–31.21
ꢀ12 6 h 6 13
ꢀ10 6 k 6 9
ꢀ17 6 l 6 17
8114
3849 [R(int) = 0.0331]
0.9879/0.9621
—
0.84 ꢁ 0.77 ꢁ 0.48
2.23–25.00
ꢀ16 6 h 6 15
ꢀ15 6 k 6 15
ꢀ25 6 l 6 29
13900
6625 [R(int) = 0.0733]
0.9675/0.9444
0.0039(5)
0.38 ꢁ 0.29 ꢁ 0.20
2.24–25.00
ꢀ12 6 h 6 10
ꢀ26 6 k 6 26
ꢀ37 6 l 6 37
49204
12703 [R(int) = 0.1304]
0.9871/0.9757
—
3.29–31.11
ꢀ13 6 h 6 13
ꢀ10 6 k 6 9
ꢀ14 6 l 6 14
7411
3879 [R(int) = 0.0524]
0.9864/0.9645
—
Reflections collected
Independent reflections
Transmission max/min
Extinction
Data/restraints/parameters
3879/1/184
1.039
4884/0/193
0.927
3849/1/192
1.061
6625/1/466
1.074
12703/120/832
1.111
Goodness-of-fit on F2
Final R indices [I > 2
R indices (all data)
r
(I)]
R1 = 0.0475,
wR2 = 0.1195
R1 = 0.0657,
wR2 = 0.1311
0.120 and ꢀ0.155
R1 = 0.0443,
wR2 = 0.0891
R1 = 0.0978,
wR2 = 0.1070
0.204 and ꢀ0.490
R1 = 0.0565,
wR2 = 0.1435
R1 = 0.0966,
wR2 = 0.1652
0.133 and ꢀ0.144
R1 = 0.0678,
wR2 = 0.1766
R1 = 0.0781,
wR2 = 0.1865
0.210 and ꢀ0.205
R1 = 0.1034,
wR2 = 0.1606
R1 = 0.1865,
wR2 = 0.1978
0.134 and ꢀ0.172
Largest diff. peak and hole
(e Åꢀ3
Absolute structure parameter
)
1.0(12)
ꢀ0.026(9)
ꢀ2.7(17)
1.4(18)
1(2)
P
P
P
P
2
2 2 1=2
R1
=
||F0| ꢀ |Fc||/ ||F0|, wR2 ¼ ½ wðF20 ꢀ Fc2Þ = ðw j F0j Þ ꢂ
.
as in the research reported here. The only difference was the sol-
vent used for crystallization: in our work ethanol was used instead
of a mixture of ethyl ether and hexanes as used in the literature.13
It is difficult to rationalize the discrepancy in the assigned config-
uration at C2. The specific rotation measurement for 6 gave a value
similar to that reported in the literature,13 although that might be
inconclusive, since the specific rotation measurements were per-
formed in different solvents (methanol for 6 and chloroform in
the literature13). However, we observed the coupling between pro-
tons at the C2 and C5 positions in the NOE-difference experiment
performed for oxazolidine 6, which indicated the spatial arrange-
ment of both hydrogen atoms on being on the same side of the oxa-
zolidine ring. This is consistent with the configuration on C2 and
C5 as determined for 6 based on the structural data reported here-
in. Also, it is difficult to expect that we have obtained monocrystals
for only one of the synthesized diastereoisomers due to differences
in their solubility, since the NMR results reported here had re-
vealed the presence of only one product for 6.
The structure of 2 is analogous to the known structure of the
different diastereoisomer (2S,4R,5R) derived from pseudoephed-
rine.18 Despite the different conformations of the oxazolidine ring
and configuration at C4, the distances between the phenolic O and
oxazolidine N atoms are similar (2.665 Å in 2 and 2.672 Å in pseu-
doephedrine derivative), resulting in the presence of analogous
intramolecular interactions in both compounds.
The X-ray structural analysis of 1–6 revealed the similarity of
their molecular geometry. In particular the bond lengths and
angles within the oxazolidine ring are similar for most molecules
of the reported compounds (Table 2). Comparison with the struc-
ture of N3-isopropyl oxazolidine19 reveals that the C2–N3–C4

E. Błocka et al. / Tetrahedron: Asymmetry 21 (2010) 571–577
573
Table 2
Selected geometrical parameters for oxazolidines 1, 2, 3, 5 and 6
1
2
3
5–1
1.413(5)
1.431(5)
1.461(5)
1.471(5)
1.543(7)
5–2
1.419(5)
1.433(5)
1.457(5)
1.469(5)
1.554(6)
6–1
1.429(7)
1.437(7)
1.445(7)
1.485(7)
1.553(9)
6–2
1.417(7)
1.439(6)
1.443(7)
1.471(7)
1.553(8)
6–3
1.419(6)
1.427(6)
1.457(6)
1.456(6)
1.525(7)
O1–C2
O1–C5
C2–N3
N3–C4
C4–C5
1.419(2)
1.4368(19)
1.470(2)
1.469(2)
1.547(3)
1.405(4)
1.432(3)
1.469(4)
1.478(4)
1.541(4)
1.417(3)
1.431(3)
1.465(3)
1.472(3)
1.546(4)
C2–O1–C5
O1–C2–N3
C4–N3–C2
N3–C4–C5
108.38(13)
102.86(12)
103.85(12)
102.92(13)
104.78(13)
ꢀ35.47(15)
42.16(16)
ꢀ32.23(17)
11.21(16)
15.02(16)
74.87(19)
ꢀ42.8(2)
109.0(2)
107.67(17)
102.64(18)
105.95(17)
102.49(18)
105.58(17)
ꢀ37.9(2)
39.0(2)
109.2(3)
108.0(3)
108.3(5)
106.0(4)
109.4(4)
103.3(2)
103.3(2)
102.0(2)
105.1(2)
ꢀ32.9(3)
42.2(3)
103.1(3)
103.4(3)
102.0(3)
104.6(4)
ꢀ31.7(4)
42.6(4)
102.8(3)
103.9(3)
101.6(3)
105.1(3)
ꢀ35.5(4)
44.1(3)
102.7(5)
106.9(5)
100.9(5)
106.2(5)
ꢀ34.0(5)
39.8(5)
100.7(5)
105.1(5)
102.3(5)
103.5(5)
ꢀ46.3(6)
45.1(6)
ꢀ26.7(6)
ꢀ1.0(6)
29.2(6)
76.4(7)
ꢀ35.2(8)
7.020
44.3(2)
72.0(2)
77.7(2)
103.0(4)
104.1(4)
103.3(4)
104.5(4)
ꢀ30.7(5)
40.1(5)
O1–C5–C4
C5–O1–C2–N3
O1–C2–N3–C4
C2–N3–C4–C5
N3–C4–C5–O1
C2–O1–C5–C4
O1–C2–C14–C15
O1–C5–C8–C13
ꢀ34.4(3)
ꢀ24.9(2)
ꢀ36.4(4)
ꢀ34.7(3)
ꢀ29.3(6)
ꢀ34.0(5)
15.2(3)
2.2(2)
17.5(5)
13.5(4)
8.3(6)
15.5(6)
10.9(3)
78.6(4)
ꢀ41.8(4)
6.510
42.4(1)
76.3(1)
86.0(1)
22.2(2)
82.3(3)
ꢀ31.2(3)
6.735
52.8(1)
68.9(1)
72.9(1)
8.6(4)
82.4(4)
ꢀ33.2(6)
6.498
45.4(2)
71.7(1)
77.5(2)
13.4(4)
78.5(4)
ꢀ38.7(5)
6.664
45.1(2)
74.2(1)
79.3(2)
15.7(6)
81.4(6)
ꢀ29.3(8)
6.683
44.3(2)
70.7(2)
73.3(2)
9.5(6)
84.3(6)
ꢀ39.1(8)
6.416
51.1(2)
72.5(2)
80.8(2)
a
Phenyl Cgꢃ ꢃ ꢃCg
6.567
42.3(1)
78.8(1)
85.5(1)
b
Dihedral1
Dihedral2b
Dihedral3b
a
Intramolecular distance between centers of gravity of aromatic rings C8–C13 and C14–C19.
Dihedral 1: angle between best planes of rings C8–C13 and C14–C19, dihedral 2: angle between best planes of rings C8–C13 and O1–C5, dihedral 3: angle between best
b
planes of rings C14–C19 and O1–C5.
38% and 69/31%, respectively, with positions differing by approxi-
mately 30° rotation (Fig. 1).
Table 3
Hydrogen bonds in crystal structures of 1, 2, 3, 5, and 6
D–Hꢃ ꢃ ꢃA
d(D–H)
d(Hꢃ ꢃ ꢃA)
<DHA
d(Dꢃ ꢃ ꢃA)
1
O2–H2Oꢃ ꢃ ꢃN3
0.820
0.820
0.820
1.927
1.974
1.871
149.23
141.49
148.52
2.664
2.665
2.606
2
O2–H2Oꢃ ꢃ ꢃN3
3
O2–H2Oꢃ ꢃ ꢃN3
5
O2–H2Oꢃ ꢃ ꢃN3
O32–H32Oꢃ ꢃ ꢃN33
6
0.820
0.820
1.887
1.886
146.29
149.07
2.609
2.623
O2–H2Oꢃ ꢃ ꢃN3
O32–H32Oꢃ ꢃ ꢃN33
O62–H62Oꢃ ꢃ ꢃN33
0.820
0.820
0.820
1.849
1.954
1.848
148.38
146.53
151.65
2.583
2.675
2.599
Figure 1. Structure of molecule 1 of 2,4-di-tert-butyl-6-((2S,4S,5R)-3,4-dimethyl-5-
phenyl-oxazolidyn-2-yl)phenol 6. The thermal ellipsoids are displayed at a 30%
probability level. The hydrogen atoms of the hydroxyl group are displayed to
indicate the intramolecular H-bond existing in all molecules of the oxazolidines
investigated. For clarity all other hydrogen atoms are omitted.
angle for the N-methyl derivatives reported here (103.3(2)–
106.9(5)°) is significantly smaller than that of 106.12(19)° reported
for the N-isopropyl derivative, while the C5–O1–C2 in 1–6 rang-
ing from 106.0(4)° to 109.4(4)° is larger than the corresponding
105.83(18)° as reported in the literature.19 These differences
emphasize the steric effect of the N3-bound substituent on the
oxazolidines geometry, and are consistent with the results pub-
lished in the literature.13 This seems to be important for the Et2Zn
addition reaction, with the ee obtained for N3-methyl compound 1
being two times lower than that reported for the N3-isopropyl
analogue.19
In all structures reported here there is no systematic effect of
the substituents on the C14–C19 phenolic ring that would affect
the geometry of the molecule. However, the presence of the pheno-
lic oxygen in the ortho-position relative to one of the t-Bu groups in
6 results in restrictions on the rotational space available for that t-
Bu group. Consequently in 6, atoms of the t-Bu groups bound to
C16 and C46 revealed significantly smaller atomic displacement
parameters than those found for atoms of analogous groups bound
to C18 and C48. That effect is the most pronounced in molecules 1
and 2 of 6, where the rotational disorder is detected for the C18-
bound and C48-bound t-Bu with two discrete populations of 62/
In all the structures reported here there is an intramolecular H-
bond between the hydroxyl O and the oxazolidine N atom. The
geometry of these interactions is very close to each other in all
structures, with the Nꢃ ꢃ ꢃO distance ranging from O2ꢃ ꢃ ꢃN3 2.583 Å
to O32ꢃ ꢃ ꢃN33 2.675 Å, both in structure 6, and the O–Hꢃ ꢃ ꢃN angles
ranging from 141.5° in 2 to 151.6° in 6 (Table 3). These intramolec-
ular interactions seem to determine the molecular conformation
for all structures investigated. Also, no intermolecular H-bonds
were found in the structures investigated.
In structures 2, 3, 5, and 6 reported here, the conformation of
the central oxazolidine ring is similar (Fig. 2, Table 2). A detailed
analysis20 indicated that for 1, 2, both molecules of 5, as well as
molecules 1 and 3 of 6 the ring is twisted on C2–N3 or its equiva-
lent, while only in 3 and molecule 2 of 6 is the ring in an envelope
on C2 or its equivalent. Comparison of the oxazolidines ring con-
formation revealed that only molecule 2 of 6 has a conformation
similar to that reported for N3-isopropyl analogue.19 For all other

574
E. Błocka et al. / Tetrahedron: Asymmetry 21 (2010) 571–577
Initially oxazolidines 1–7 were used as chiral ligands in the
addition of Et2Zn to benzaldehyde (Scheme 2). For oxazolidines
1–4 only modest ee (13–17%) of 1-phenyl-1-propanol as a product
was observed. We were expecting to obtain results similar to those
previously published for oxazolidine 1 by Parrott II et al.13 Our re-
sults for 1 and 4 indicate that the presence of a methyl- and isopro-
pyl-group near the reaction center does not influence the reaction’s
enantioselectivity. This is consistent with the theory that enanti-
oselectivity and the absolute configuration of the reaction product
are not only related to the steric interactions of the alkyl groups
near the phenolic hydroxyl but also related to the N3-methyl group
being a stereocontrol element acting via an intramolecular chiral
relay.13 It has to be noted that only for ligand 2 was the yield of
the investigated addition low (24%). This can be related to the pres-
ence of the electron-withdrawing Br group in the structure, which
can significantly affect the reaction mechanism.
Figure 2. Superposition of oxazolidine molecules for structures 1, 2, 3, 5, and 6.
O
molecules of the reported structures 1–6, the oxazolidine rings
have a conformation characterized with the absolute values of tor-
sion angles being significantly smaller than those reported in the
literature.19
OH
*
20% mol ligand 1-7
H
Et2Zn, solvent
The molecular conformation may be analyzed in terms of the
dihedral angle between the aromatic rings or between these planes
and the best plane of the central oxazolidine ring. The dihedral an-
gle between the phenolic C14–C19 and the unsubstituted phenyl
ring is similar in all structures and varies from 42.4(1)° to
52.8(1)°. The rotation of the substituted phenolic ring around
C2–C14 is similar for all the structures, with the O1–C2–C14–C15
torsion angle ranging from 76.4(7)° to 84.3(6)° both values for 6,
the values are slightly larger than that of 74.87(19)° found for
the unsubstituted structure of 1 determined by us. The C8–C13
phenyl ring orientation described with the O1–C5–C8–C13 torsion
angle or its equivalents varies between ꢀ29.3(8)° for 6 and
ꢀ41.8(4)° for 2 while for 1 we found it to be ꢀ42.8(2)°. The rela-
tively small variability of these rotations and the observed similar-
ity in the conformation of the oxazolidine ring result in the similar
distances between the centroids of the aromatic rings ranging from
6.416 to 7.020 Å both observed for 6 (Table 2). Therefore, the struc-
tural data reported here indicate the similarity of the steric factors
contributing to the reactivity of the investigated compounds when
used in the reaction of diethylzinc addition. Furthermore, this sug-
gests the importance of other factors, such as electronic effects, for
explaining the observed differences in the activity of the investi-
gated oxazolidines in the above-mentioned reaction.
Scheme 2. Asymmetric addition of diethylzinc to benzaldehyde.
On the contrary, for more crowded ligands 5–7 with bulky tert-
butyl groups or with a naphthalene ring, much better ee’s (35–43%)
and good yields (68–92%) were observed in this reaction. These re-
sults can be related to steric hindrance caused by groups in the aro-
matic ring or by the ring itself.
Parrot et al.13 reported the use of oxazolidine 6 with an (R)-con-
figuration on carbon C2 in the reaction of diethylzinc addition to
benzaldehyde. In their research they obtained the product of (R)-
configuration with ee = 59%. In the research reported here we per-
formed the synthesis under similar conditions using ligand 6 with
(2S)-configuration, whichgave themajorproductwithan (S)-config-
uration and lower ee (39%). This phenomenon can be explained by
some differences between more crowded cis-geometry of C2–C5
and steric relationships between the alkyl groups in the phenol aro-
matic ring in ligand 6. It suggested to us that there are few intramo-
lecular stereocontrol elements in the mechanism of this reaction.
We were able to formulate the following hypothesis: obtaining
a good enantioselectivity for oxazolidine ligands in the addition of
diethylzinc to aldehydes requires not only the presence of an N3-
methyl group but also the presence of substituents in positions 3
and 5 of the phenolic ring. It should be noted that electronic effects
from the aromatic naphthalene ring are also important.
The oxazolidines obtained were employed as chiral ligands in
the enantioselective addition of diethylzinc to aldehydes. Ligands
1–7 were used in an amount of 20 mol % with 2 equiv of Et2Zn with
respect to 1 equiv of benzaldehyde at room temperature which
was maintained during the reaction time. The results of reactions
studied are summarized in Table 4.
To demonstrate the influence of electronic and steric effects of
the substrate in this asymmetric addition, a series of different aryl
aldehydes were evaluated for ligand 5 (because for this compound
the best ee’s for benzaldehyde as the substrate was obtained) and 7
(because the structure is different to the other oxazolidines tested).
The results for these two ligands are summarized in Table 5.
In the case of ligand 5 we did not notice significant differences
between ee’s of the addition products and the structure of sub-
strates (aryl aldehydes), but for ligand 7 the enantioselectivity of
the reactions is the most remarkable subject to an electronic effect.
In Table 5 (ligand 7), the substrates with electron-donating groups
in the para-, meta-, or ortho-positions (methoxy groups) of aryl
aldehydes (entries 9–11) afforded enantioselectivity at the same
rate as the unsubstituted benzaldehyde but those with electron-
withdrawing groups (entries 12–15) afforded enantioselectivity
at much lower (ortho groups) or much more higher (meta groups)
rate. To evaluate the effects of the substituents, the results in
Table 5 were analyzed by means of a Hammett plot (Figs. 3 and 4).
We did not observe any linear correlation between enantiose-
lectivity and the electronic constant for ligand 7. However, some
Table 4
Addition of diethylzinc to benzaldehyde catalyzed by oxazolidines 1–7
Entry
Ligand
Time (h)
Yielda (%)
eeb (%)
Config.c
1
2
3
4
5
6
7
1
2
3
4
24
24
24
24
24
24
24
75
24
94
99
85
92
68
17
17
13
16
43
39
35
(S)
(S)
(S)
(S)
(S)
(S)
(S)
5
6
7d
a
b
c
Isolated products.
Determined by HPLC using OD-H column.
Determined by measurement of the specific rotation and comparison with the
literature.21
d
Diethylzinc was added to a solution of chiral ligand at ꢀ70 °C.

E. Błocka et al. / Tetrahedron: Asymmetry 21 (2010) 571–577
575
Table 5
rate and enantioselectivity. It is known that the presence of elec-
tron-withdrawing groups (positive Hammett constants ) leads
to an increase in electrophilicity of the carbonyl carbon atom in
Addition of diethylzinc to substituted aldehydes catalyzed by oxazolidines 5 and 7
r
Entry Ligand Aldehyde
Time Yielda eeb Config.
c
(h)
(%)
(%)
aryl aldehydes, while the presence of electron-donating groups
(negative
r values) diminishes it. Thus, we expected that the sub-
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
5
5
5
5
5
5
5
5
7
7
7
7
7
7
7
o-Methoxybenzaldehyde
m-Methoxybenzaldehyde
p-Methoxybenzaldehyde
o-Chlorobenzaldehyde
o-Bromobenzaldehyde
m-Chlorobenzaldehyde
p-Chlorobenzaldehyde
Cyclohexanealdehyde
72
72
72
72
72
72
72
72
72
72
72
72
72
72
72
92
36
29
30
35
32
42
25
6
41
27
35
12
9
(S)
(S)
(S)
(S)
(S)
(S)
(S)
(S)
(S)
(R)
(R)
(R)
(S)
(S)
(S)
87
96
77
76
92
>99
78
74
86
60
73
41
77
56
strates with an electron-withdrawing substituent afforded a faster
reaction leading to higher enantioselectivity, which was true only
for m-chlorobenzaldehyde. In fact the lower ee values were ob-
tained in the case of ortho-substituted aryl aldehydes (Table 5, en-
tries 12–13). These results suggested that the enantioselectivity of
the diethylzinc addition to these ortho-substituted aldehydes with
7 as a chiral ligand was affected not only by electronic effects but
also by steric effect.
Surprisingly for ligand 7 in the addition of diethylzinc to
substituted benzaldehydes, we also observed a sudden change of
the product configuration from (S) to (R) when meta- or para-
methoxybenzaldehyde was used as a substrate. However, for
benzaldehyde with an ortho-methoxy group we did not observe
this phenomenon. These results were hard to explain, but we be-
lieve that it has to be related to some steric hindrance of the meth-
oxy groups which are playing a significant role in the reaction
mechanism.
o-Methoxybenzaldehyded
m-Methoxybenzaldehyded
p-Methoxybenzaldehyded
o-Chlorobenzaldehyded
o-Bromobenzaldehyded
m-Chlorobenzaldehyded
p-Chlorobenzaldehyded
57
32
a
b
c
Isolated products.
Determined by HPLC using OD-H column.
Determined by measurement of the specific rotation and comparison with the
literature.21
d
Diethylzinc was added to a solution of chiral ligand 7 at ꢀ70 °C.
For ligand 5 the reaction was also tested with an aliphatic alde-
hyde–cyclohexanoaldehyde (Table 5, entry 8) and provided the
corresponding secondary alcohol with a small ee = 6% in spite of
good chemical yield (78%).
60
50
40
30
20
10
0
Parrott II and Hitchcock13 proposed a possible mechanism for
asymmetric addition of Et2Zn to aldehydes catalyzed by chiral oxa-
zolidine ligands based on suspicions that the N3-methyl group is
an important stereocontrol element via an intramolecular chiral
relay. According to our observations we have to add that electronic
and steric effects of the substrates and oxazolidine ligands are also
significant.
m-C l
H
o-OMe
o-C l
o-Br
m-OMe
p-OMe
p-C l
3. Conclusions
(1R,2S)-Ephedrine was employed as a substrate for the prepara-
tion of a group of oxazolidine chiral ligands for conducting asym-
metric synthesis. All the oxazolidines were formed with a new
stereogenic center at C2 and was determined as (2S) by X-ray
structure. The formation of only the (2S)-epimer can be connected
with solvent effects and is probably related to its thermodynamic
stability. These ligands have been successfully used in the asym-
metric addition of diethylzinc to aldehydes affording moderate
enantioselectivities and very good chemical yields. It is observed
that some steric effects from the aromatic ring of the oxazolidine
are also very important for the mechanism proposed previously
by Parrott et al.13 Most importantly, the enantioselectivity of the
tested reaction can be dependent on the electronic and steric ef-
fects from the structure of substrate aryl aldehydes.
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
Hammett constant
Figure 3. Plot of the enantiomeric excess of the addition of Et2Zn to para-, meta-,
and ortho-substituted aryl aldehydes versus Hammett constant
r
for ligand 5.
60
50
m-C l
o-OMe
40
p-OMe
H
p-C l
30
m-OMe
4. Experimental
4.1. Instrumental
20
10
0
o-C l
o-Br
Melting points were determined with a Büchi apparatus in
open capillaries and are uncorrected. Optical rotation was mea-
sured with a PolAAr 3000 automatic polarimeter in a 10 cm cell
at 589 nm. Elemental analyses were performed with an Elemen-
tary Analysensysteme GmbH Vario MACRO CHN analyzer. The
1H and 13C NMR spectra were recorded with a Varian Gemini
200 multinuclear instrument and a Bruker AMX 300 MHz instru-
ment, respectively, in CDCl3 at ambient temperature. Chemical
shifts are reported in parts per million (d scale); coupling con-
stants (J values) are listed in hertz. Infrared spectra are reported
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
Hammett constant
Figure 4. Plot of the enantiomeric excess of the addition of Et2Zn to para-, meta-,
and ortho-substituted aryl aldehydes versus Hammett constant for ligand 7.
r
interactions suggested that the electronic property of a substituent
in the substrate may have a significant influence on the reaction

576
E. Błocka et al. / Tetrahedron: Asymmetry 21 (2010) 571–577
in reciprocal centimeters (cmꢀ1) and are measured as a HCB mull.
GC was performed on a Perkin–Elmer AutoSystem XL chromato-
graph using b-Dex 325 capillary column (30 m, 0.25 mm) or on
Shimadzu GC-14A using Zebron ZB-5 capillary column. HPLC
analyses were performed on a Shimadzu LC-10AT chromatograph
using Chiralcel OD-H column (250 ꢁ 4.6 mm). Crystals suitable
for the diffraction experiments were obtained by the vapor
diffusion method from an ethanol solution. The X-ray data for
all reported structures were collected at 293(2) K with an Oxford
4.3.2. 4-Bromo-2-((2S,4S,5R)-3,4-dimethyl-5-phenyl-
oxazolidyn-2-yl)phenol 2
4-Bromo-2-hydroxybenzaldehyde as a substrate. White solid
(77%). Purified by crystallization using ethanol at 4 °C (after 4 h).
Mp 182–185 °C,
½
a 2D0
ꢂ
¼ ꢀ79:2 (c 0.096, CH3OH). 1H NMR
(200 MHz, CDCl3): d 0.84 (d, J = 6.4 Hz, 3H, CH3), 2.38 (s, 3H,
CH3), 3.10 (qd, J = 2.2 Hz, J = 6.4 Hz, 1H, CH), 4.86 (s, 1H, CH), 5.26
(d, J = 8.6 Hz, 1H, CH), 6.83 (d, J = 8.6 Hz, 1H, CHAr), 7.34 (m, 7H,
CHAr), 11.51 (br s, 1H, OH). 13C NMR (50.3 MHz, CDCl3): d 15.67
(CH3), 35.87 (CH3), 63.53 (CH), 81.56 (CH), 98.22 (CH), 110.61
(CAr), 118.98 (CHAr), 121.01 (CAr), 126.93 (3 ꢁ CHAr), 127.99 (CHAr),
128.21 (CHAr), 133.53 (CHAr), 133.63 (CHAr), 137.92 (CAr), 157.45
(CAr). IR (HCB mull): 702.5, 716.0, 760.7, 1083.9, 1269.1, 1337.0,
1470.7, 1482.3, 2893.7, 2986.0. Anal. Calcd for C17H18BrNO2: C,
58.63; H, 5.21; Br, 22.95; N, 4.02; O, 9.19. Found: C, 58.61; H,
5.27; N, 4.22.
Sapphire CCD diffractometer using Mo Ka radiation k = 0.71073 Å
and
x
ꢀ 2h method. The numerical absorption correction was ap-
plied with CrysAlis171 package of programs, Oxford Diffraction,
2000.22 Structures were solved by direct methods and refined
with the full-matrix least-squares method on F2 with the use of
SHELX-97 program package.23 The hydrogen atoms have been lo-
cated from the difference electron density maps and constrained
during refinement. The absolute configuration for 2 was deter-
mined by the Flack method.17 The Flack parameter for 1, 3, 5,
and 6 was inconclusive, so the absolute configuration of C2 was
determined relative to the configuration of (1R,2S)-ephedrine
used as a substrate in the synthesis of the oxazolidines. The struc-
tural data have been deposited with Cambridge Crystallographic
Data Centre, the CCDC numbers 762318–762322 for 2, 3, 5, 6
and 1, respectively.
4.3.3. 2-((2S,4S,5R)-3,4-Dimethyl-5-phenyl-oxazolidyn-2-yl)-6-
methyl-phenol 3
2-Hydroxy-3-methylbenzaldehyde as a substrate. White solid
(50%). Purified by crystallization using ethanol at 4 °C (after 4 h).
Mp 125–127 °C,
½
a 2D0
ꢂ
¼ þ8:16 (c 0.56, CH3OH). 1H NMR
(300 MHz, CDCl3): d 0.83 (d, J = 6.6 Hz, 3H, CH3), 2.29 (s, 3H,
CH3), 2.39 (s, 3H, CH3), 3.09 (qd, J = 2.1 Hz, J = 6.6 Hz, 1H, CH),
4.91 (s, 1H, CH), 5.23 (d, J = 8.7 Hz, 1H, CH), 6.77 (t, J = 7.5 Hz, 1H,
CH), 7.06 (dd, J = 1.5 Hz, J = 7.7 Hz, 1H, CHAr), 7.17 (dd, J = 1.5 Hz,
J = 7.7 Hz, 1H, CHAr), 7.24–7.40 (m, 5H, CHAr), 11.54 (br s, 1H,
OH). 13C NMR (50.3 MHz, CDCl3): d 15.79 (CH3), 31.20 (CH3),
35.89 (CH3), 59.50 (CH), 81.40 (CH), 99.19 (CH), 118.19 (CAr),
118.56 (CHAr), 125.69 (CAr), 127.13 (2ꢁCHAr), 127.84 (CHAr),
128.13 (2 ꢁ CHAr), 128.64 (CHAr), 132.03 (CHAr), 138.23 (CAr),
156.35 (CAr). IR (HCB mull): 708.5, 753.7, 1262.9, 1382.3, 1454.7,
1471.9, 2917.0, 2969.4. Anal. Calcd for C18H21NO2: C, 76.29; H,
7.47; N, 4.94; O, 11.29. Found: C, 76.19; H, 7.27; N, 5.02.
4.2. Materials
TLC was performed on silica gel PolygramÒ Sil G/UV254 (0.2 mm).
Regular column chromatography was carried out using Silica Gel 60
(0.06–0.2 mm). All solvents were purchased from POCh Gliwice,
Poland. Toluene was distilled from sodium prior to use. Diethylzinc,
(ꢀ)-ephedrine, and aldehydes were purchased from Sigma–Aldrich
or Fluka. 3,5-Di-tert-butyl-2-hydroxybenzaldehyde, 3-tert-butyl-5-
methyl-2-hydroxybenzaldehyde, 2-hydroxy-3-methylbenzaldehyde,
and 2-hydroxy-3-isopropylbenzaldehyde were obtained according
to the literature procedures.24,25
4.3.4. 2-((2S,4S,5R)-3,4-Dimethyl-5-phenyl-oxazolidin-2-yl)-6-
isopropyl-phenol 4
2-Hydroxy-3-isopropylbenzaldehyde as a substrate. White solid
(73%). Purified by crystallization using ethanol at 4 °C (4 h). Mp
4.3. Preparation of oxazolidines
105–106 °C, ½a 2D0
ꢂ
¼ þ5:0 (c 2.09, CH3OH). 1H NMR (300 MHz,
CDCl3): d 0.84 (d, J = 6.3 Hz, 3H, CH3), 1.27 (d, J = 6.3 Hz, 3H, CH3-
iPr), 1.29 (d, J = 6.0 Hz, 3H, CH3-iPr), 1.57 (br s, 1H, OH), 2.38 (s,
3H, CH3), 3.08 (qd, J = 8.7 Hz, J = 6.6 Hz, 1H, CH), 3.39 (qt,
J = 6.9 Hz, 1H, CH), 4.92 (s, 1H, CH), 5.27 (d, J = 8.7 Hz, 1H, CH),
6.84 (t, J = 7.8 Hz, 1H, CHAr), 7.06 (dd, J = 1.8 Hz, J = 7.5 Hz, 1H,
CHAr), 7.23–7.41 (m, 6H, CHAr), 11.62 (br s, 1H, OH). 13C NMR
(50.3 MHz, CDCl3): d 15.65 (CH3), 22.54 (CH3), 26.52 (CH), 35.73
(CH3), 63.48 (CH), 81.36 (CH), 99.38 (CHAr), 118.30 (CAr), 118.69
(CHAr), 127.11 (2ꢁCHAr), 127.33 (CHAr), 127.76 (CHAr), 128.07
(2 ꢁ CHAr), 128.45 (CHAr), 135.98 (CAr), 138.33 (CAr), 155.48 (CAr).
IR (HCB mull): 713.5, 753.7, 827.8, 1249.8, 1270.1, 1454.2,
1467.6, 2858.3, 2968.3. Anal. Calcd for C20H25NO2: C, 77.14; H,
8.09; N, 4.50; O, 10.28. Found: C, 77.08; H, 7.94; N, 4.35.
A 50-ml round-bottomed flask equipped with a magnetic stir-
ring bar was filled with 3.05 mmol (0.5 g) of (1R,2S)-ephedrine,
2,77 mmol of appropriate aldehyde, and 30 ml of anhydrous etha-
nol. The reaction mixture was stirred for 24 h at room temperature
and then it was transferred to crystallizer. The precipitate was
drained, washed by ethanol (10 ml), and dried in the air. Yields
and physical properties are presented below.
4.3.1. ((2S,4S,5R)-3,4-Dimethyl-5-phenyl-oxazolidyn-2-yl)
phenol 1
2-Hydroxybenzaldehyde as a substrate. White solid (56%).
Purified by crystallization using ethanol at 4 °C (after 4 h). Mp
119–121 °C (lit.13 112–114 °C), ½a 2D0
¼ ꢀ32:6 (c 0.47, CH3OH)
ꢂ
(lit.13
½
a 2D0
ꢂ
¼ ꢀ32:3 (c 0.62, CHCl3)).1H NMR (300 MHz, CDCl3): d
4.3.5. 2-tert-Butyl-6-((2S,4S,5R)-3,4-dimethyl-5-phenyl-
oxazolidyn-2-yl)-4-methyl-phenol 5
0.83 (d, J = 6.6 Hz, 3H, CH3), 2.38 (s, 3H, CH3), 3.09 (qd,
J = 2.2 Hz, J = 6.5 Hz, 1H, CH), 4.92 (s, 1H, CH), 5.26 (d, J = 8.7 Hz,
1H, CH), 6.86 (td, J = 1.2 Hz, J = 7.5 Hz, 1H, CHAr), 6.90 (dd,
J = 0.9 Hz, J = 8.4 Hz, 1H, CHAr), 7.20–7.399 (m, 7H, CHAr), 11.38
(br s, 1H, OH). 13C NMR (75.5 MHz, CDCl3): d 15.71 (CH3), 35.86
(CH3), 63.59 (CH), 81.46 (CH), 99.08 (CH), 117.00 (CHAr), 119.08
(CHAr), 119.08 (CAr), 127.05 (2 ꢁ CHAr), 127.88 (CHAr), 128.16
(2 ꢁ CHAr), 130.92 (CHAr), 131.05 (CHAr), 138.26 (CAr), 158.23
(CAr). IR (HCB mull): 701.9, 715.6, 764.4, 1265.1, 1336.0, 1455.9,
1481.9, 2898.0, 2984.0. Anal. Calcd for C17H19NO2: C, 75.81; H,
7.11; N, 5.20; O, 11.88. Found: C, 75.51; H, 7.34; N, 5.43.
3-tert-Butyl-2-hydroxy-5-methylbenzaldehyde as a substrate.
White solid (58%). Purified by crystallization using ethanol at
4 °C (24 h). Mp 122–125 °C, ½a D20
ꢂ
¼ ꢀ7:2 (c 0.40, CH3OH). 1H NMR
(300 MHz, CDCl3): d 0.83 (d, J = 6.4 Hz, 3H, CH3), 1.46 (s, 9H,
3 ꢁ CH3, t-Bu), 2.27 (s, 3H, CH3), 2.36 (s, 3H, CH3), 3.07 (qd,
J = 2.0 Hz, J = 6.4 Hz, 1H, CH), 4.87 (s, 1H, CH), 5.24 (d, J = 8.8 Hz,
1H, CH), 6.87 (d, J = 2.2 Hz,1H, CHAr), 7.11 (d, J = 2.2 Hz, 1H, CHAr),
7.23–7.42 (m, 5H, CHAr), 11.54 (br s, 1H, OH). 13C NMR
(75.5 MHz, CDCl3): d 15.50 (CH3), 20.66 (CH3), 29.47 (3 ꢁ CH3),
35.57 (CH3), 63.64 (CH), 81.38 (CH), 99.90 (CH), 118.52 (CAr),

E. Błocka et al. / Tetrahedron: Asymmetry 21 (2010) 571–577
577
126.07 (CHAr), 125.90 (CHAr), 127.17 (2 ꢁ CHAr), 127.75 (CHAr),
128.02 (2 ꢁ CHAr), 128.83 (CHAr), 129.34 (CHAr), 136.90 (CAr),
138.57 (CAr), 154.96 (CAr). IR (HCB mull): 703.9, 749.8, 1255.3,
1343.1, 1455.6, 1487.9, 2890.8, 2964.0. Anal. Calcd for
C22H29NO2: C, 77.84; H, 8.61; N, 4.13; O, 9.43. Found: C, 77.72;
H, 8.48; N, 4.33.
turned to room temperature and aldehyde (1 mmol) was added.
The mixture was stirred for the appropriate time (Tables 1 and 2)
and the reaction was quenched with a saturated solution of ammo-
nium chloride (5 ml). The reaction mixture was extracted with
ethyl acetate (3 ꢁ 10 ml), dried over anhydrous MgSO4, and gravity
filtered. The solvent was stripped to obtain enantiomerically en-
riched 1-phenyl-1-propanol. When necessary, the crude product
was purified by the column chromatography using appropriate
eluents (hexane/ethyl acetate). The ee’s were determined with
HPLC using ODH-Chiralcel column or GC analysis using b-Dex cap-
illary column. Yield was determined via GC analysis using a ZB-5
capillary column or by isolation of the product (Tables 4 and 5).
4.3.6. 2,4-Di-tert-butyl-6-((2S,4S,5R)-3,4-dimethyl-5-phenyl-
oxazolidyn-2-yl)phenol 6
3,5-Di-tert-butyl-2-hydroxybenzaldehyde as a substrate. White
solid (49%). Purified by crystallization using ethanol at 4 °C (24 h).
Mp 138–141 °C,
½
a 2D0
ꢂ
¼ ꢀ27:85 (c 0.406, CH3OH). 1H NMR
(300 MHz, CDCl3): d 0.85 (d, J = 6.6 Hz, 3H, CH3), 1.29 (s, 9H,
3 ꢁ CH3, t-Bu), 1.47 (s, 9H, 3 ꢁ CH3, t-Bu), 2.38 (s, 3H, CH3), 3.07
(qd, J = 2.4 Hz, J = 6.9 Hz, 1H, CH), 4,91 (s, 1H, CH), 5.24 (d,
J = 8.7 Hz, 1H, CH), 7.04 (d, J = 2.4 Hz, 1H, CHAr), 7.19–7.43 (m,
6H, CHAr), 11.53 (br s, 1H, OH). 13C NMR (75.5 MHz, CDCl3): d
15.48 (CH3), 29.54 (3 ꢁ CH3), 31.61 (3 ꢁ CH3), 34.12 (C), 35.04
(CH3), 35.58 (C), 63.60 (CH), 81.37 (CH), 100.25 (CH), 117.87
(CAr), 125.19 (CHAr), 125.56 (CAr), 127.22 (2 ꢁ CHAr), 127.75 (CHAr),
128.01 (2 ꢁ CHAr), 136.15 (CAr), 138.58 (CAr), 140.25 (CAr), 154.78
(CAr). IR (HCB mull): 703.9, 721.0, 751.3, 1252.6, 1387.8, 1457.9,
1487.0, 2866.6, 2959.5. Anal. Calcd for C25H35NO2: C, 78.70; H,
9.25; N, 3.67; O, 8.39. Found: C, 78.67; H, 9.20; N, 3.51.
Acknowledgment
Research was partly supported by the Nicolaus Copernicus Uni-
versity grant UMK CH-526.
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4.3.7. 2-((2S,4S,5R)-3,4-Dimethyl-5-phenyl-oxazolidyn-2-ylo)
naphthalen-1-ol 7
2-Hydroxy-1-naphthaldehyde as a substrate. White solid (45%).
Purified by crystallization using ethanol at 4 °C (24 h). Mp 196–
199 °C, ½a 2D0
ꢂ
¼ ꢀ8:4 (c 0.16, CH3OH). 1H NMR (300 MHz, CDCl3): d
0.91 (d, J = 6.6 Hz, 3H, CH3), 2.47 (s, 3H, CH3), 3.21 (qd, J = 8.4 Hz,
J = 6.6 Hz, 1H, CH), 5.37 (d, J = 8.4 Hz, 1H, CH), 5.78 (s, 1H, CH),
7.15 (d, J = 8.7 Hz, 1H, CHAr), 7.23–7.39 (m, 6H, CHAr), 7.48 (ddd,
J = 7.2 Hz, J = 6.9 Hz, J = 1.5 Hz, 1H, CHAr), 7.78 (t, J = 8.1 Hz, 2H,
CHAr), 8.03 (d, J = 8.7 Hz, 1H, CHAr), 12.85 (br s, 1H, OH). 13C NMR
(50.3 MHz, CDCl3): d 15.62 (CH3), 36.76 (CH3), 63.83 (CH), 81.69
(CH), 95.01 (CH), 108.89 (CAr), 119.80 (CHAr), 121.15 (CHAr),
122.78 (CHAr), 126.96 (CHAr), 127.03 (2 ꢁ CHAr), 127.89 (CHAr),
128.18 (2 ꢁ CHAr), 128.45 (CAr), 128.67 (CHAr), 131.50 (CHAr),
133.94 (CAr), 138.22 (CAr), 157.18 (CAr). IR (HCB mull): 714.0,
751.2, 825.8, 1244.4, 1279.9, 1455.3, 1466.1, 2857.2, 2966.1. Anal.
Calcd for C21H21NO2: C, 78.97; H, 6.63; N, 4.39; O, 10.02. Found: C,
78.83; H, 6.56; N, 4.41.
9. Parrott, R. W., II; Dore, D. D.; Chandrashekar, S. P.; Bentley, J. T.; Morgan, B. S.;
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4.4. Typical procedure for the asymmetric addition of Et2Zn to
aldehydes
Diethylzinc (2 mmol, 2 ml, 1 M solution in hexanes) was added
to a solution of chiral oxazolidine (20 mol %) in dry toluene (5 ml)
at the appropriate temperature (room temperature or ꢀ70 °C) un-
der an atmosphere of N2. After 25 min the reaction mixture was
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