Synthesis of novel chiral dopants based on optically active p-substituted mandelic acids

Article abstract of DOI:10.1016/S0957-4166(03)00576-7

Novel esters of optically active p-substituted mandelic acids (+)-1 and (+)-2 were prepared by a convergent synthetic strategy in high enantiomeric excess (99% ee). The esters (+)-1 and (+)-2 induce helical macrostructures in the mesophases of achiral liq

Full text of DOI:10.1016/S0957-4166(03)00576-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 2731–2737
Synthesis of novel chiral dopants based on optically active
p-substituted mandelic acids
a
a
a
b
a,
&
&
Andreja Lesac, Sanja Narancˇic´, Maja Sepelj, Duncan W. Bruce and Vitomir Sunjic´ *
aRu/er Bosˇkovic´ Institute, Bijenicˇka c. 54, HR-10000 Zagreb, Croatia
bSchool of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD, UK
Received 18 June 2003; accepted 16 July 2003
Abstract—Novel esters of optically active p-substituted mandelic acids (+)-1 and (+)-2 were prepared by a convergent synthetic
strategy in high enantiomeric excess (99% ee). The esters (+)-1 and (+)-2 induce helical macrostructures in the mesophases of
achiral liquid-crystal materials, although neither exhibits mesorphism on its own.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
to have a profound effect on the physical properties.12
In addition, there is restricted conformational mobility
of the stereogenic centre due to the steric constraint of
an adjacent phenyl ring on one side and intramolecular
hydrogen bonding between the oxygen atom of the
a-hydroxyl and the carboxyl group13 on the other.
Consequently, the eclipsed conformation of a-hydroxyl
and carboxyl group gives the molecule an overall bent
shape. The presence of a 4-hydroxy and a carboxylate
function offer possibilities for the elongation of the
aromatic core and/or the introduction of long hydrocar-
bon chains, leading to molecules in which the position
of the stereogenic centre may be varied. Since helical
macrostructures can be observed in the absence of
chirality in bent-core systems,8–10 it is of great interest to
study what effect chirality will have in conjunction with
the position of the stereogenic centre, on the mesogenic
properties of the system itself, as well as on the mesomor-
phism of the host while being used as a dopant.
Chirality is one of the most interesting and challenging
subjects in liquid crystals.1 Chiral phases can serve for
technical applications such as displays2 and pigments,3 as
well as for scientific objectives, for example determina-
tion of absolute configuration4 or detection of chirality.5
The induction of chirality in mesophases of non-chiral
mesogens can be achieved by adding a small quantity of
chiral dopant (up to 10%) to non-chiral liquid-crystalline
hosts,6 and molecular chirality is transferred to macro-
scopic chirality resulting in the formation of new phases
with helical ordering. The diversity of chiral dopants
reported to date has allowed certain empirical rules to be
postulated for efficient chirality transfer; for example
restricted conformational mobility in the chiral region of
a dopant and its mesogenic-like structure can be impor-
tant factors.7 Interestingly, however, spontaneous forma-
tion of helical macrostructures has been observed in
certain mesophases of bent-core mesogens,8–10 the chiral-
ity being a consequence of the polar order and the special
molecular packing of bent molecules within smectic
layers.11
Herein we describe the synthesis of two representative
esters of enantiomerically pure p-substituted (+)-man-
delic acid as potential chiral dopants. The first is repre-
sentative of group I, bearing a polar stereogenic centre
inside the rigid core at the centre of the molecule, while
the second is representative of group II, having a
stereogenic centre at the peripheral position of the rigid
core. Both groups are characterised by an overall bent
shape.
In the course of our project involving the synthesis of
novel chiral liquid crystals, we have sought enantiomer-
ically pure esters of p-substituted mandelic acid as
potential chiral dopants. The key building block, enan-
tiomerically pure p-hydroxymandelic acid, offers several
interesting features. Thus, it possesses a polar group at
the stereogenic carbon atom, a feature which is known
* Corresponding author. E-mail: sunjic@irb.hr
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00576-7

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A. Lesac et al. / Tetrahedron: Asymmetry 14 (2003) 2731–2737
2. Results and discussion
decylbenzene gave a mixture containing 20% of the o-
and 80% of the p-bromoisomer as confirmed by GC
analysis. Nevertheless, this mixture was used in the
Suzuki coupling21 with methoxyphenylboronic acid to
give 8 in 60% yield. The 1H NMR spectrum of the
coupled product revealed the presence of the p-isomer
only, coupling of the o-isomer presumably being hin-
dered sterically. Removal of the methyl group with
BBr3 in dichloromethane at −80°C22 gave phenol 9 in
91% yield. Esterification of 4-OTHP-protected benzoic
acid with phenol 9 using dicyclohexylcarbodiimide
(DCC) and dimethylaminopyridine (DMAP) in tetra-
hydrofuran,23 followed by removal of the protecting
group using catalytic pyridinium p-toluenesulphonate
(PPTS) in wet acetone,24 afforded 11 in 74% yield.
2.1. Synthesis and characterisation
The key precursors, racemic 4-decyloxymandelic acid 5
and 4-benzyloxymandelic acid 6, were prepared by the
addition of chlorocarbene to the corresponding p-sub-
stituted benzaldehyde in 40–70% yield (Scheme 1).
Dichlorocarbene was generated in situ from chloroform
under strongly basic conditions in the presence of ben-
zyltriethylammonium chloride (BTEAC) as a phase-
transfer catalyst. The isolation procedure published for
methoxymandelic acid14 was modified because of the
different solubilities of sodium decyloxy- and benzyl-
oxy-mandelate in water and organic solvents.
Scheme 1. Reagents and conditions: (i) CHCl3, NaOH (50%),
BTAC; (ii) (a) (R)-(+)-PEA, CHCl3, (b) HCl (2 M), Et2O.
We have recently reported a specific protocol for
efficient resolution of ( )-1-(9-anthryl)ethylamine with
(S)-(+)-mandelic acid in chloroform.15 Employing this
protocol, we completed the resolution of racemic man-
delic acids ( )-5 and ( )-6 with (R)-(+)-1-phenylethyl-
amine in chloroform by adding equimolar quantity of
the enantiomerically pure amine to hot, saturated solu-
tion of acids ( )-5 or ( )-6. Slow cooling to room
temperature led to the crystallisation of the
diastereomeric salt of (−)-mandelic acid. The enan-
tiomeric excesses of the (−)-enantiomers isolated from
the precipitated salt were routinely low, while those
from the (+)-enantiomers obtained from the soluble
diastereomeric salt were exceptionally high. Therefore
(+)-5 and (+)-6 were used in subsequent reactions.16
The enantiomeric excesses of the acids (+)-5 and (+)-6
were determined after esterification with diazomethane
by the Mosher ester method,17 using a chiral HPLC
column. The results revealed that resolution afforded
>99% ee of (+)-5 after a single crystallisation. All
attempts to separate methyl esters of (+)-6 and (−)-6
either on commercial or on our own, originally devel-
oped chiral HPLC columns failed.18,19 High enan-
tiomeric purity of (+)-6 (99% ee) was deduced from the
chiral HPLC analysis of the ester (+)-2 on a Chiralpak
AD column.
Scheme 2. Reagents and conditions: (i) Br2, CH2Cl2; (ii)
[Pd(PPh3)4], Na2CO3 (2 M); (iii) BBr3, CH2Cl2; (iv) (a) DCC,
DMAP, THF, (b) PPTS, wet acetone.
Finally, ester (+)-1, bearing a polar stereogenic centre
inside the rigid core, was obtained by esterification of
OTHP-mandelic acids (+)-5 with alcohol 11, followed
by deprotection using PPTS in wet acetone to give ester
(+)-1 (99% ee) in ca. 25% overall yield. The enan-
tiomeric purity of (+)-1 remained the same as deter-
mined for the starting decyloxymandelic acids (Scheme
3).
The convergent synthesis of mandelate (+)-1, represen-
tative of group I, required separate preparation of the
phenol derivative, 11, required for esterification of man-
delic acid (+)-5 (Scheme 2). Thus, bromination20 of
To incorporate the stereogenic centre at the peripheral
position relative to the rigid core in (+)-2, a long alkyl
chain was introduced on the carboxylic terminus of

A. Lesac et al. / Tetrahedron: Asymmetry 14 (2003) 2731–2737
2733
Scheme 3. Reagents and conditions: (i) (a) DHP, p-TsOH; then NaOH (1 M), (b) DCC, DMAP, THF; (ii) PPTS, wet acetone.
(+)-6 by DCC-promoted esterification of OTHP-pro-
tected chiral benzyloxymandelic acid with 1-
dodecanol23 (Scheme 4). Hydrogenolysis25 of the benzyl
group afforded 14 which, on acylation with 4-dodecyl-
oxybiphenyl carboxylic acid, followed by hydrolysis
under mild acidic conditions, gave (+)-2 (99% ee), in ca.
20% overall yield.
monotropic liquid crystal phase. Investigations of the
liquid-crystalline properties by polarising optical
microscopy of binary mixtures containing 4 mol% of
mandelic esters (+)-1 and (+)-2 with the mesomorphic
p-decyloxybenzoic acid as an achiral liquid crystalline
host, showed
a
helical macrostructure in the
mesophase. Thus, according to the textures, a N* (chi-
ral nematic) and a SmC* (chiral smectic C) mesophase
were observed instead of their achiral versions (Fig. 1).
2.2. Liquid crystal properties
Examination of the line periodicity of the fingerprint
texture of the chiral nematic phases (which is related to
the pitch26,27) indicated that chiral induction with (+)-2
possessing peripheral stereogenic centre, is stronger
Investigations by polarised optical microscopy showed
that both mandelates (+)-1 and (+)-2 melted directly
into isotropic liquid phases at 123 and 108°C, respec-
tively, and crystallised on cooling with no sign of a
Scheme 4. Reagents and conditions: (i) (a) DHP, p-TsOH; then NaOH (1 M), (b) C12H25OH, DCC, DMAP, THF; (ii) Pd/C
(10%), cyclohexene; (iii) (a) DCC, DMAP, THF, (b) PPTS, wet acetone.

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A. Lesac et al. / Tetrahedron: Asymmetry 14 (2003) 2731–2737
performed in chloroform affording, after a single crys-
tallisation, (+)-5 and (+)-6 with 99% ee. Esters (+)-1 and
(+)-2 were prepared by convergent syntheses without
lost of enantiomeric purity. Investigations of the liquid
crystal properties showed that while neither compound
was liquid-crystalline on its own, mixing these esters
with an achiral mesogenic material induced chiral
mesophases. As chirality transfer is affected also by the
nature of the host,30,31 binary mixtures containing opti-
cally active mandelic esters in different hosts are under
further investigation.
4. Experimental
All the solvents were either puriss p.a. quality or dis-
tilled over appropriate drying reagents. All the other
1
reagents were used as purchased from Aldrich. H (300
MHz) and 13C NMR (75.5 MHz) spectra: Varian XL-
Gemini 300 instrument with SiMe4 as internal standard,
in CDCl3 unless otherwise stated; l in ppm, J in Hz. IR
spectra: Bomem MB 102 spectrophotometer; absorption
bands in cm−1. Optical rotations: Automatic Polarimeter
AA-10 using NaD wavelength; c in g sample/100 ml
solvent. Mp: Electrothermal 9100 instrument. Bp: Bu¨chi
GKR-51 instrument for distillation under reduced pres-
sure. TLC: DC-Alufolien Kieselgel 60 F254, Merck
plates; substances detected with UV lamp (u=254 nm).
HPLC: Hewlett Packard 1050 instrument equipped
with UV detector; reverse phase column Nucleosil C-
187 mm (250×4.6 mm); flow 1 ml min−1, k (sample)
ꢀ0.5 g dm−3; mobile phases and gradient: from 70% to
pure MeOH in 20 min. Chiral HPLC analysis: Hewlett
Packard 1050 instrument equipped with UV detector
using Chiralcel ODH (hexane/i-PrOH, 19:1, 0.8 mL/
min) or Chiralpak AD (hexane–t-BuOH, 9:1, 1 mL/
min). GC: Hewlett Packard 5890 Series II equipped
with FI detector; column HP-17, initial temperature
70°C, final 250°C, heating rate 10°C min−1. Phase tem-
peratures and textures: Leitz Wetzlar polarizing micro-
scope equipped with Linkam TH600 hot stage and
PR600 temperature controller.
Figure 1. Textures of the chiral phases of binary mixture
containing 4 mol% of (+)-2 with the mesomorphic p-decyl-
oxybenzoic acid (a) chiral nematic phase obtained at 135°C
on cooling; (b) chiral smectic phase obtained at 112°C on
cooling.
than that with (+)-1 bearing stereogenic centre in the
rigid core. Molecular modelling28 revealed that, in both
esters (+)-1 and (+)-2 conformational mobility of the
chiral region of the molecule is reduced to the same
extent. However they differ in the position of the
stereogenic centre and in the degree of bending. Thus,
while the more pronounced bending observed for the
molecular structure of (+)-1 is expected to hinder rota-
tion around its molecular long axis and increase chiral-
ity transfer,29 preliminary results indicate that steric
shielding of the stereogenic centre is the prevailing
factor, causing higher chiral induction in the mixture
containing (+)-2 as dopant.
4.1. p-Substituted mandelic acid ( )-5,6—general
procedure
To a solution of aldehyde 3 or 4 prepared as reported32
(10 mmol), BTAC (0.5 mmol) in CHCl3 (4 mL), aq.
NaOH solution (4 mL, 50%) was added dropwise at
56°C. The mixture was heated at the same temperature
overnight. After being allowed to cool to rt, the mixture
was poured into H2O (100 mL) and extracted with
ether (3×10 mL). The aqueous layer was acidified with
H2SO4 (50%) to pH 1 and extracted with Et2O (5×20
mL). The combined organic extracts were dried over
Na2SO4, filtered and concentrated under vacuum to
give p-substituted mandelic acids ( )-5 and ( )-6 and in
42, and 72% yield, respectively.
3. Conclusion
In summary, two representative optically active, p-sub-
stituted mandelic acid derivatives were prepared as
chiral dopants. Efficient resolution of racemic acids
( )-5 and ( )-6 with (R)-(+)-1-phenylethylamine was
4.2. (+)-4-Decyloxymandelic acid, (+)-5
To the hot, saturated solution of ( )-5 (2.20 g, 7.15
mmol) in CHCl3 (25 mL), (R)-(+)-PEA (0.91 mL, 7.15

A. Lesac et al. / Tetrahedron: Asymmetry 14 (2003) 2731–2737
2735
mmol) was added in one shot. The solution was
allowed to cool to rt over 2 h. The precipitate was
separated by filtration and washed with cold CHCl3
(2×10 mL). Evaporation of the mother liquor gave the
diastereomeric salt of (+)-5, which was then suspended
in ether (20 mL) and HCl (2 M) was added until the
organic layer became clear. The organic layer was then
separated and the aqueous solution was extracted with
ether (2×15 mL). The combined organic extracts were
dried (Na2SO4), filtered and concentrated under vac-
uum to give (+)-5 (0.8 g, >99% ee, 72%) as a colourless
solid, mp 118–119°C; [h]2D5=+87 (c 1.0, EtOH). IR
(KBr): 3530, 2900, 1700, 1615, 1590, 1520, 1180 cm−1.
1H NMR (DMSO-d6): l=0.85 (t, J=6.5 Hz, 3H),
1.24–1.37 (m, 14H), 1.65–1.69 (m, 2H), 3.90 (t, J=6.3
Hz, 2H), 4.62 (s, 1H), 6.81 (d, J=8.4 Hz, 2H), 7.25 (d,
J=8.4 Hz, 2H). 13C NMR (DMSO-d6): l=16.69,
25.25, 28.59, 31.78, 31.89, 31.96, 32.15, 34.47, 70.68,
74.88, 117.32, 130.48, 131.90, 162.20, 180.26. Anal.
calcd for C18H28O4: C, 70.10; H, 9.15. Found: C, 70.19;
H, 9.23.
(t, J=7.4 Hz, 2H), 7.03 (d, J=8.2 Hz, 2H), 7.37 (d,
J=8.2 Hz, 2H).
4.5. 4%-Decyl-4-methoxybiphenyl, 8
To a vigorously stirred mixture of 7 (3.37 g, 11.34
mmol), [Pd(PPh3)4] (0.26 g, 2.22 mmol), aq Na2CO3 (2
M, 11.3 mL) in toluene (25 mL), was added (4-
methoxyphenyl)boronic acid (1.90 g, 12.50 mmol) dis-
solved in a minimum amount of EtOH (95%). The
reaction mixture was heated to 90–95°C overnight, after
which it was allowed to cool to room temperature and
was extracted with Et2O. The combined ether extracts
were washed with brine, dried (Na2SO4) filtered and
concentrated under reduced pressure. The crude
product was purified by crystallisation from EtOH to
give the pure product, 8 (2.20 g, 60%); mp 83–84°C. IR
(KBr): 2920, 2840, 1610, 1500, 810 cm−1. 1H NMR
(CDCl3): l=0.87 (t, J=5.7 Hz, 3H), 1.26–1.31 (m,
14H), 1.58–1.65 (m, 2H), 2.62 (t, J=7.7 Hz, 2H), 3.82
(s, 3H), 6.95 (d, J=8.24 Hz, 2H), 7.21 (d, J=7.9 Hz,
2H), 7.46 (d, J=7.7 Hz, 2H), 7.51 (d, J=8.24 Hz, 2H).
13C NMR (CDCl3): l=13.66, 22.21, 28.91, 29.06,
29.15, 31.08, 31.44, 35.09, 55.81, 113.60, 126.04, 127.45,
128.27, 133.23, 137.61, 140.95, 158.36. Anal. calcd for
C23H32O: C, 85.13; H, 9.94. Found: C, 85.25; H, 9.90.
4.3. (+)-4-Benzyloxymandelic acid, (+)-6
To the hot, saturated solution of ( )-6 (5.0 g, 19.4
mmol) in CHCl3 (500 mL), (R)-(+)-PEA (2.5 mL, 19.4
mmol) was added in one portion. The solution was
allowed to cool to rt over 3 h. The precipitate was
separated by filtration and washed with cold CHCl3
(2×15 mL). Evaporation of the mother liquor gave the
diastereomeric salt of (+)-6, which was then suspended
in ether (30 mL) and HCl (2 M) was added until the
organic layer became clear. The organic layer was then
separated and the aqueous solution was extracted with
ether (2×15 mL). The combined organic extracts were
dried (Na2SO4), filtered and concentrated under vac-
uum to give (+)-6 (1.8 g, 99% ee, 72%) as a colourless
solid, mp 153–154°C; [h]2D5=+103 (c 1.0, EtOH). IR
(KBr): 3425, 3357, 2915, 1708, 1250, 1179, 1056, 829
4.6. 4%-Decyl-4-hydroxybiphenyl, 9
A solution of BBr3 (6 mL, 6 mmol, 1 M in CH2Cl2) was
added carefully, through the condenser, to a stirred
solution of 8 (1.8 g, 5.5 mmol) in CH2Cl2 (12 mL) at
−80°C. The reaction mixture was allowed to attain
room temperature overnight with stirring. The mixture
was then hydrolysed by the careful addition of H2O (20
mL), thus precipitating a colourless solid, which was
dissolved by addition of Et2O (40 mL). The organic
layer was separated and the aqueous solution was
extracted with Et2O (2×15 mL). The combined ether
extracts were washed with brine, dried (Na2SO4) filtered
and concentrated under reduced pressure. The crude
product was purified by crystallisation from EtOH
affording compound 9 (1.54 g, 91%); mp 137–138°C IR
(KBr): 3500–3300, 2920, 2840, 1610, 1600, 1260, 810
1
cm−1. H NMR (DMSO-d6): l=4.92 (s, 1H), 5.06 (s,
2H), 5.73 (s, 1H), 6.94 (d, J=8.6 Hz, 2H), 7.27–7.59
(m, 7H), 12.51 (s, 1H). 13C NMR (DMSO-d6): l=
69.26, 71.97, 114.52, 127.74, 127.91, 127.99, 128.54,
132.64, 137.19, 157.96, 174.44. Anal. calcd for
C15H14O4: C, 69.76; H, 5.46. Found: C, 69.90; H, 5.35.
1
cm−1. H NMR (CDCl3): l=0.88 (t, J=5.7 Hz, 3H),
1.27–1.31 (m, 14H), 1.59–1.66 (m, 2H), 2.62 (t, J=7.6
Hz, 2H), 4.80 (s, 1H), 6.88 (d, J=8.5 Hz, 2H), 7.24 (d,
J=6.3 Hz, 2H), 7.43–7.48 (m, 4H). 13C NMR (CDCl3):
l=14.00, 22.57, 29.17, 29.29, 29.39, 31.43, 31.80, 35.47,
115.46, 126.42, 128.08, 128.66, 133.87, 137.96, 141.42,
154.68. Anal. calcd for C22H30O: C, 85.11; H, 9.74.
Found: C, 85.35; H, 9.69.
4.4. 1-Bromo-4-decylbenzene, 7
Bromine (1.5 mL, 29.2 mmol) was added dropwise to a
stirred and ice-cooled solution of decylbenzene (3.0 g,
13.7 mmol) and I2 (35 mg, 0.14 mmol) in CH2Cl2 (5
mL), with the rigorous exclusion of light. After stirring
for 1 day at rt, aq KOH (10 mL, 20%) was added. The
mixture was shaken until the colour disappears and was
then extracted with CH2Cl2 (3×20 mL). Combined
extracts were dried (Na2SO4), filtered and the solvent
was evaporated under vacuum. The crude product was
purified by distillation under reduced pressure affording
the compound 7 (3.37 g, 83%; bp 143–146°C at 0.2
mbar; 80% purity by GC) as a colourless oil which was
used in the next step. Around 20% of 1-bromo-2-decyl-
4.7. 4-(Tetrahydro-2H-pyran-2%-yloxy)benzoic acid, 10
A solution of p-hydroxybenzoic acid (2.0 g, 14.5
mmol), DHP (6.6 mL, 72.4 mmol) and catalytic
amount of p-TsOH in anhydrous THF (10 mL) was
stirred under Ar for 5 h at rt. Triethylamine (2 mL) was
added and the solvent was evaporated. The oily residue
was dissolved in acetone (20 mL) and NaOH (1 M, 20
mL) was added. After stirring overnight, acetone was
evaporated, H2O (10 mL) was added and the alkaline
1
benzene was identified. H NMR (CDCl3): l=0.91 (t,
J=6.3 Hz, 3H), 1.25 (m, 14H), 1.54–1.59 (m, 2H), 2.54

2736
A. Lesac et al. / Tetrahedron: Asymmetry 14 (2003) 2731–2737
solution was extracted with CH2Cl2 (3×15 mL). To the
remaining aqueous solution CH2Cl2 (20 mL) followed
by NaHSO4 (1 M, 10 mL) were added with vigorous
stirring. The organic layer was separated and the
aqueous layer extracted with CH2Cl2 (3×15 mL). The
combined extracts were dried (Na2SO4), filtered and
concentrated under vacuum affording compound 10
(2.79 g, 87%; 99% purity by HPLC). The product was
used in the subsequent reactions without further purifi-
diastereomers (58 mg, 65%) as a viscous oil, which was
used in the subsequent reactions without further purifi-
1
cation. H NMR (CDCl3): l=0.80–1.95 (m, 88H), 2.65
(t, J=7.6 Hz, 4H), 3.56–3.59 (m, 2H), 3.75–3.80 (m,
2H), 3.95–4.05 (m, 4H), 4.69–4.70 (m, 1H), 5.02 (m,
1H), 5.40 (s, 1H), 5.53 (s, 1H), 6.94–6.98 (m, 4H),
7.15–7.20 (m, 4H), 7.23–7.29 (m, 8H), 7.48–7.55 (m,
8H), 7.61–7.65 (m, 4H), 8.20–8.24 (m, 4H).
1
4.10. (+)-[(4%-Decylbiphenoxycarbonyl)phenil-4-yl]-2-(4-
decyloxyphenyl)-2-hydroxyacetate (+)-1
cation. H NMR (CDCl3): l=1.60–2.06 (m, 6H), 3.62–
3.66 (m, 1H), 3.83–3.91 (m, 1H), 5.55 (t, J=2.74 Hz,
1H), 7.11 (d, J=8.7 Hz, 2H), 8.07 (d, J=8.7 Hz, 2H).
13C NMR (CDCl3): l=18.36, 24.91, 29.96, 61.94,
95.91, 115.81, 132.09, 132.52, 161.42, 171.79.
A solution of 12 (58 mg, 0.07 mmol) and a catalytic
amount of PPTS in wet acetone (10 mL) was heated
under reflux for 2 h. After cooling, the solvent was
removed and the residue purified by column chro-
matography (silica gel; hexane–MTBE–CH2Cl2, 5:1:1)
followed by crystallisation from hexane affording (+)-1
(30 mg, >99% ee, 46%) as a colourless solid mp 123–
124°C; [h]2D5=+65 (c 0.67, CHCl3). IR (KBr): 3500–
4.8. (4%-Decylbiphenyl-4-yl)-4-hydroxybenzoate, 11
A solution of 9 (380 mg, 1.22 mmol), 10 (544 mg, 2.45
mmol), DCC (530 mg, 2.57 mmol) and a catalytic
amount of DMAP in anhydrous THF (20 mL) was
stirred under Ar for 48 h at rt. The reaction mixture
was filtered and the solvent removed under reduced
pressure. The remaining solid was dissolved in wet
acetone (10 mL) and a catalytic amount of PPTS was
added. The reaction mixture was heated under reflux
for 5 h. After cooling, the precipitate was collected by
filtration and washed with cold acetone (5 mL). Crys-
tallisation from EtOH gave the pure phenol 11 (390 mg,
74%), mp 200–201°C. IR (KBr): 3480–3300, 2954, 1726,
1
3350, 2962, 1731, 1289, 1250, 1083, 804 cm−1. H NMR
(CDCl3): l=0.88 (t, J=6.9 Hz, 6H), 1.26–1.84 (m,
32H), 2.64 (t, J=7.6 Hz, 2H), 3.97 (t, J=6.5 Hz, 2H),
5.41 (d, J=5.6 Hz, 1H), 6.96 (d, J=8.7 Hz, 2H), 7.17
(d, J=8.8 Hz, 2H), 7.15–7.32 (m, 4H), 7.44 (d, J=8.7
Hz, 2H), 7.50 (d, J=8.2 Hz, 2H), 7.62 (d, J=8.6 Hz,
2H), 8.23 (d, J=8.8 Hz, 2H). 13C NMR (CDCl3):
l=14.02, 22.58, 25.95, 29.14, 29.24, 29.29, 29.48, 31.39,
31.80, 35.51, 68.04, 72.78, 114.81, 121.33, 121.71,
126.86, 127.50, 127.94, 128.78, 129.26, 131.79, 137.53,
142.21, 149.85, 154.28, 171.88. Anal. calcd for
C47H60O6: C, 78.30; H, 8.39. Found: C, 78.40; H, 8.41.
1
1610, 1265, 1248, 960 cm−1. H NMR (CDCl3): l=0.91
(t, J=6.0 Hz, 3H), 1.11–1.36 (m, 14H), 1.68 (m, 2H),
2.67 (t, J=7.1 Hz, 2H), 5.8 (s, 1H), 6.91 (d, J=8.52 Hz,
2H), 7.26–7.28 (m, 4H), 7.51 (d, J=7.9 Hz, 2H), 7.63
(d, J=8.5 Hz, 2H), 8.13 (d, J=8.5 Hz, 2H). 13C NMR
(CDCl3): l=13.94, 22.57, 29.30, 29.44, 29.54, 31.31,
31.83, 35.55, 67.16, 115.39, 121.83, 122.34, 126.88,
127.88, 128.76, 132.53, 137.73, 138.91, 142.14, 150.26,
160.35, 164.84. Anal. calcd for C29H34O3: C, 80.89; H,
7.96. Found: C, 81.12; H, 8.06.
4.11. Dodecyl-2-(4-benzyloxyphenyl)-2-(tetrahydro-2H-
pyran-2-yloxy)acetate, 13
The title compound was obtained from (+)-6 (1.00 g,
3.87 mmol) and 1-dodecanol (0.66 g, 3.57 mmol)
according to the procedure described for the prepara-
tion of 12. the crude product was separated by flash
column chromatography (silica gel; hexane–MTBE–
CH2Cl2, 5:1:1). The mixture of diastereomers obtained
(1.23 g, 67%) was used in the next step without further
4.9. [(4%-Decylbiphenoxycarbonyl)phenyl-4-yl]-2-(4-decyl-
oxyphenyl)-2-(tetrahydro-2H-pyran-2-yloxy)acetate, 12
1
purification. H NMR (CDCl3): l=0.82–0.95 (m, 6H),
A solution of (+)-5 (80 mg, 1.26 mmol), DHP (0.5 mL,
5.7 mmol) and a catalytic amount of p-TsOH in anhy-
drous THF (6 mL) was stirred under Ar for 2 h at rt.
Triethylamine (0.3 mL) was added and the solvent was
evaporated. The oily residue was dissolved in acetone (6
mL) and NaOH (1 M, 2.2 mL) was added. After
stirring for 3 h, the acetone was evaporated, H2O (6
mL) was added and the alkaline solution was extracted
with CH2Cl2 (3×10 mL). To the remaining aqueous
solution CH2Cl2 (10 mL) followed by NaHSO4 (1 M, 5
mL) were added with vigorous stirring. The organic
layer was separated and the aqueous solution extracted
with CH2Cl2 (3×10 mL). The combined extracts were
dried over Na2SO4, filtered and the solvent evaporated
under vacuum. The oily residue so obtained was dis-
solved in anhydrous THF (10 mL) and DCC (0.5 g,
2.43 mmol), a catalytic amount of DMAP and phenol
11 (50 mg, 0.11 mmol) were added. The reaction mix-
ture was stirred overnight under argon at rt. Filtration
1.20–1.98 (m, 52H), 3.46–3.56 (m, 2H), 3.68–3.80 (m,
2H), 4.09–4.15 (m, 4H), 4.57–4.62 (m, 1H), 4.86–4.90
(m, 1H), 5.07 (s, 4H), 5.18 (s, 1H), 5.28 (s, 1H), 6.97 (d,
J=8.8 Hz, 4H), 7.34–7.43 (m, 14H).
4.12. Dodecyl-2-(4-hydroxyphenyl)-2-(tetrahydro-2H-
pyran-2-yloxy)acetate, 14
A suspension containing 13 (1.22 g, 2.38 mmol), Pd/C
(0.2 g, 10%) and cyclohexene (8 mL) in EtOH (15 mL)
was heated under reflux for 4 h. Filtration and removal
of the solvent gave the crude product which was
purified by flash column chromatography (silica gel;
hexane–MTBE–CH2Cl2, 5:1:1). The mixture of
diastereomers obtained (0.5 g, 50%) was used in the
next step without further purification. 1H NMR
(CDCl3): l=0.87–0.92 (m, 6H), 1.24–1.93 (m, 52H),
3.46–3.65 (m, 2H), 3.71–3.82 (m, 2H), 4.05–4.22 (m,
4H), 4.57–4.62 (m, 1H), 4.83–4.89 (m, 1H), 5.11 (s, 1H),
5.26 (s, 1H), 6.80–6.84 (m, 4H), 7.31–7.38 (m, 4H).
and removal of the solvent gave
a mixture of

A. Lesac et al. / Tetrahedron: Asymmetry 14 (2003) 2731–2737
2737
4.13. (+)-Dodecyl-2-(4%-dodecyloxybiphenyl-4-carboxy)-
phenyl-2-hydroxyacetate, (+)-2
9. Pelzl, G.; Diele, S.; Ja´kli, A.; Lischka, Ch.; Wirth, I.;
Weissflog, W. Liq. Cryst. 1999, 26, 135.
10. Ja´kli, A.; Lischka, Ch.; Weissflog, W.; Pelzl, G.; Saupe,
A. Liq. Cryst. 2000, 27, 1405.
11. Niori, T.; Sekine, F.; Watanabe, J.; Furukawa, T.; Take-
zoe, H. J. Mater. Chem. 1996, 6, 1231.
12. Goodby, J. W. J. Mater. Chem. 1991, 1, 307.
13. Kanters, J. A.; Kroon, J.; Peerman, A. F.; Schoone, J. C.
Tetrahedron 1967, 23, 4027.
The title compound was obtained from 4-dodecyloxy-
biphenyl carboxylic acid (91 mg, 0.24 mmol) and 14
(100 mg, 0.24 mmol) according to the procedure
described for the preparation of 11. The crude product
was purified by column chromatography (silica gel;
CH2Cl2) affording (+)-2 (92 mg, 99% ee, 55%) as white
solid, mp 108–109°C; [h]2D5=+31 (c 1.0, CH2Cl2). IR
(KBr): 2956, 2919, 1733, 1601, 1273, 1193, 828 cm−1. 1H
NMR (CDCl3): l=0.88 (t, J=6.4 Hz, 6H), 1.24–1.27
(m, 38H), 1.77–1.86 (m, 2H), 4.01 (t, J=6.5 Hz, 2H),
4.06–4.19 (m, 2H), 5.21 (s, 1H), 6.99 (d, J=8.6 Hz,
2H), 7.25 (m, 2H), 7.57–7.60 (m, 4H), 7.69 (d, J=8.3
Hz, 2H), 8.23 (d, J=8.3 Hz, 2H). 13C NMR (CDCl3):
l=14.01, 22.58, 25.54, 25.93, 28.29, 28.99, 29.13, 29.24,
29.53, 31.80, 66.43, 68.05, 72.20, 114.87, 121.72, 126.48,
127.22, 127.55, 128.26, 129.97, 130.60, 131.80, 135.80,
135.83, 145.95, 150.90, 159.50, 173.48. Anal. calcd for
C45H64O6: C, 77.10; H, 9.20. Found: C, 76.89; H, 9.08.
14. Merz, A. Synthesis 1974, 724.
&
15. Roje, M.; Hamersˇak, Z.; Sunjic´, V. Synth. Commun.
2002, 32, 3413.
16. The absolute configurations (S) of (+)-5 and (R) of (−)-5
are assumed by the analogy of the sign of [h]2D5 for
(S)-(+)-4-methoxymandelic acid.13
17. Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95,
512.
&
18. Vinkovic´, V.; Kontrec, D.; Sunjic´, V. Chirality 2000, 12,
63.
&
19. Vinkovic´, V.; Kontrec, D.; Lesac, A.; Sunjic´, V.; Aced, A.
Enantiomer 2000, 5, 333.
20. Rehahn, M.; Schlu¨ter, A.-D.; Feast, W. J. Synthesis 1988,
386.
Acknowledgements
21. Miller, R. B.; Dugar, S. Organometallics 1984, 3, 1261.
22. McOmie, J. F. W.; West, D. E. Org. Synth. 1969, 49, 50.
23. Shi, H.; Chen, S. H. Liq. Cryst. 1994, 17, 413.
24. Miyashita, N.; Yoshikoshi, A.; Grieco, P. A. J. Org.
Chem. 1977, 42, 3772.
The authors are thankful to the Ministry of Science and
Technology, Republic of Croatia and the Royal Society
for financial support.
25. Hanessian, S.; Liak, T. J.; Vanasse, B. Synthesis 1981,
396.
References
26. Spada, G. P.; Gottarelli, G.; Samori, B.; Bustamante, C.
J.; Wells, K. S. Liq. Cryst. 1988, 3, 101.
27. Korte, E. H. Appl. Spectrosc. 1978, 32, 568.
28. Molecular modeling was performed by molecular
mechanics using ChemOffice Ultra 7.0, CambridgeSoft
software, Nr. c 555937.
1. Chirality in Liquid Crystals; Kitzerow, H.-S.; Bahr, C.
Springer-Verlag: New York, Berlin, Heidelberg, 2001.
2. Van de Witte, P.; Neuteboom, E. E.; Brehmer, M.; Lub,
J. J. Appl. Phys. 1999, 85, 7517.
3. Maxein, G.; Mayer, S.; Zentel, R. Macromolecules 1999,
32, 5747.
29. Van der Meer, B. W.; Vertogen, G. Phys. Lett. 1976,
59A, 276.
4. Gottarelli, G.; Samori, B.; Stremmenos, C.; Torre, G.
30. Solladie, G.; Zimmermann, R. Angew. Chem., Int. Ed.
Engl. 1984, 23, 348.
Tetrahedron 1981, 37, 395.
5. Van Delden, R. A.; Feringa, B. L. Angew. Chem., Int. Ed.
2001, 40, 3198.
31. Superchi, S.; Donnoli, M. I.; Proni, G.; Spada, G. P.;
Rosini, C. J. Org. Chem. 1999, 64, 4762.
32. Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.;
Tatchell, A. R. Vogel’s Textbook of Practical Organic
Chemistry, 5th Ed.; John Wiley & Sons: New York, 1989;
p. 1078.
6. Gray, G. W.; Hird, M.; Lacey, D.; Toyne, K. J. J. Chem.
Soc., Perkin Trans. 2 1989, 2041.
7. Proni, G.; Spada, G. P. Enantiomer 1998, 6, 171.
8. Pelzl, G.; Diele, S.; Weissflog, W. Adv. Mater. 1999, 11,
707.