Buchwald protocol applied to the synthesis of N-heterotolan liquid crystals

Article abstract of DOI:10.1016/j.tet.2008.03.005

A homologous series of the new N-heterotolans 8a-d were synthesized using two cross-coupling reactions mediated by copper and palladium/copper. The final compounds present the phenyl-pyridyl framework connected by the acetylene group. The evaluation of th

Full text of DOI:10.1016/j.tet.2008.03.005

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 4619e4626
www.elsevier.com/locate/tet
Buchwald protocol applied to the synthesis
of N-heterotolan liquid crystals
Ursula B. Vasconcelos, Abel Schrader, Guilherme D. Vilela,
*
Antonio C.A. Borges, Aloir A. Merlo
Chemistry Institute, Federal University of Rio Grande do Sul, Bento Gonc¸alves Avenue, 9500, Campus do Vale, 91501 970 Porto Alegre, RS, Brazil
Received 27 April 2007; received in revised form 27 February 2008; accepted 3 March 2008
Available online 7 March 2008
Abstract
A homologous series of the new N-heterotolans 8aed were synthesized using two cross-coupling reactions mediated by copper and palla-
dium/copper. The final compounds present the phenyl-pyridyl framework connected by the acetylene group. The evaluation of thermal properties
for this series is described. All compounds exhibit the smectic A and X mesophase. For comparison were also synthesized compounds 10, 12,
and 14. Their LC properties are reported.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Liquid crystal; N-Heterotolan; Phenylpyridyl framework; Buchwald protocol; Sonogashira coupling
1. Introduction
recently received much effort since they exhibit interesting
electrical and optical properties.7
Liquid crystal displays (LCDs) have become essential as in-
formation displays in our technological society. Since highly bi-
refringent liquid crystal materials are required,1,2 many display
parameters such as response time, contrast ratio, brightness,
and viewing angle are important parameters to be considered.1b
High birefringence liquid crystals are useful materials for appli-
cation in reflective-type LCDs, spatial light modulators, com-
pensation film reflectors, and polarizers.
N-Heterotolan represents an interesting class of materials
considering that the nitrogen atom in pyridine alters the optical,
electrical, and thermal properties. Pyridine derivatives are
aimed to provide a satisfactory selection of the best components
of liquid crystals materials for TN and STN applications.8 They
also can be used as a template for high performance LC mate-
rials when substituted adequately by polar groups or alkyl/
alkoxy tails.
A number of calamitic nematic liquid crystals showing high
birefringence of relevance to LCDs such as cyanobiphenyls,3
phenylpyrimidines,4 phenylcyclohexanes,5 andcyanopyridines6
have been synthesized.
Tolan (diphenylacetylene) and its N-hetero version (pyri-
dylphenylacetylene) play a prominent role in the field of liquid
crystals science. From academic and technological research
point of view, the planning and construction of new molecular
materials containing such connectivity mentioned above have
Aromatic nucleophilic substitution using p-electron defi-
cient systems such as halopyridines is sometimes used for
the synthesis of pyridine derivatives. The major limitations of
this methodology are related to the substrate availability and
reactivity.9
The copper-mediated Ullmann-type condition10 is an alter-
native method to synthesize aromatic and heteroaromatic de-
rivatives. The nucleophilic aromatic substitution mediated
by copper between nucleophiles (e.g., substituted phenoxides
and amines) with aryl or heteroaryl halides allows the synthe-
sis of the corresponding aryl/heteroaryl ethers and amines.
However, the harsh reaction (125e220 ꢀC in neat phenol or
solvents such as pyridine, collidine, or DMF), which requires
* Corresponding author. Tel.: þ55 51 3308 7316; fax: þ55 51 3308 9304.
E-mail address: aloir@iq.ufrgs.br (A.A. Merlo).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.005

4620
U.B. Vasconcelos et al. / Tetrahedron 64 (2008) 4619e4626
OR
OH
stoichiometric (or greater) quantities of the copper complex,
and the fact that inactivated aryl halides usually react in low
yields have limited the utility of this reaction. These draw-
backs commonly result in low functional group tolerance
and low and/or irreproducible yields.
a
Br
Br
1
2
OR
b,c
Buchwald11 and Hartwig12 were pioneers in developing
interesting and practical protocols to construct aryl carbon
and aryleheteroatom bond mediated by metals, affording
many compounds that have important biological, pharmaceu-
tical, and materials properties.
For the synthesis of diaryl ethers, Buchwald et al. estab-
lished a general procedure using aryl bromides and iodides
with a variety of phenols catalyzed by copper complex, cesium
carbonate as a base, and 1,10-phenanthroline as a bidentate
nitrogenous ligand. The reaction conditions were compatible
with a wide range of functionalized substrates.13 Starting
from their initial reports concerning on the Ullmann diaryl
ether synthesis and the observation that the yields of N-aryla-
tion of imidazoles could be better when carried out in nonpolar
solvents,14 Buchwald’s group were able to demonstrated in
2002 that the copper-based protocols could be used to synthe-
size alkyl aryl ethers by Ullmann type reaction.15a
The authors reported a mild, practical, and efficient Cu-
catalyzed arylation of aryl halides with alcohols. The method
exhibit large substrate and reagent scope and it is extremely
selective. Both primary and secondary alcohols can be used,
which clearly distinguish this method from Pd-catalyzed reac-
tion, in which secondary alcohols give side products due to
ready PdH elimination.15b Allylic alcohols give the ethers
without allylic rearrangement, even for alcohols with a termi-
nal double bond, which are extremely liable to rearrange-
ments. For chiral alcohols, full retention of configuration is
observed.
As part of our ongoing studies dealing with the synthesis
of pyridine liquid crystals, we had previously reported that
2,5-disubstituted pyridine could easily be prepared16 using
the powerful protocol developed by Buchwald followed by
Sonogashira reaction. We now wish to present an extension
of application of this protocol to the other N-heterotolan
compounds.
R'
R = CnH2n+1
3 R'=CMe2OH a n-heptyl, b n-octyl
c n-nonyl, d n-decyl
4 R=H
Scheme 1. Alkynylation reaction by Sonogashira coupling. Conditions: (a)
RBr, KOH, DMF/C6H6 (65e75%); (b) mebynol, PPh3, PdCl2(PPh3)2, CuI,
Et3N (75e90%); (c) KOH, isopropanol (85e90%).
(mebynol) followed by de-protection with KOH and isopropa-
nol.18 The final compounds 4aed were obtained in 70e80%
yield from 2.
With compounds 4aed in hands, the synthesis of chiral key
intermediate 716a was achieved by using the Buchwald proto-
col. This method was particularly suitable for the conversion
of 5 to the chiral precursor 7 in acceptable yields according
to Scheme 2.
Br
Br
Buchwald
protocol
Br
O
N
N
5
7
Scheme 2. Arylation reaction under copper-mediated Buchwald protocol.
Buchwald conditions: CsCO3, CuI, 1,10-phenanthroline, toluene, (S)-6.
Thus, the arylation reaction using 2,5-dibromopyridine (5)
with (S)-(ꢁ)-2-methyl-1-butanol (6) in the presence of cesium
carbonate as a mild base, as well as 1,10-phenanthroline as
a bidentate nitrogenous ligand and catalytic amount of copper
iodide furnished the chiral intermediate 7 in 60% yield.
The synthesis of the N-heterotolan homologues 8aed was
achieved using a second Sonogashira coupling between 7
and 4aed, according to Scheme 3 (45e60%).
Br
OR
N
O
Sonogashira
coupling
H
R = CnH2n+1
4a-d
7
2. Results and discussion
RO
O
2.1. Synthesis
N
8a n-heptyl, b n-octyl
c n-nonyl, d n-decyl
R = CnH2n+1
The synthesis of the title compounds was carried out
according to the synthetic methods outlined in Schemes 1e3.
In order to establish the relationship between molecular struc-
ture and mesomorphic properties, we have introduced a pyri-
dine moiety to produce N-heterotolans using Buchwald
protocol15 and the alkynylation coupling through Sonogashira
reaction.17
The first step was the synthesis of the intermediates 4aed
according to Scheme 1. The alkylation of p-bromophenol
with n-alkylbromide gave the products 2aed in 65e75%
yields. Installation of the acetylene unit was accomplished by
Sonogashira alkynylation of 2aed with 2-methyl-3-butyn-2-ol
Scheme 3. Synthesis of 8aed using Sonogashira coupling. Sonogashira condi-
tions: PdCl2(PPh3)2, CuI, PPh3, Et3N (45e60%).
Attempting to compare the influence on liquid-crystalline
behavior of the carboxylate group and the relative position
of the nitrogen atom on the pyridine ring, we also synthesized
compounds 10 and 12. The liquid crystals properties were
compared with the series 8aed.
The synthesis of compound 10 was accomplished by alky-
nylation reaction between the chiral ester 9 and the selected

U.B. Vasconcelos et al. / Tetrahedron 64 (2008) 4619e4626
4621
alkyne 4d. The intermediate 9 was synthesized by exposure
of 4-bromobenzoic acid to SOCl2 solution and then a solution
of (S)-(ꢁ)-2-methyl-1-butanol (6) in triethylamine. The final
compound 10 was obtained in 75% yield (Scheme 4).
yield, which is a potential dopant with polar conformational
bias.20
OEt
OEt
O
RO
O
Br
O
O
N
N
OC10H21
Br
14 R=C10H21
13
O
Sonogashira
coupling
H
O
3. Liquid crystal properties
9
4d
Thermal analysis of all compounds synthesized was done by
differential scanning calorimetry (DSC) and the data are com-
piled in Table 1. The transition temperatures and enthalpy
values were collected from second heating scans. The texture
of the mesophase21 was identified by microscopic studies.
When the sample was cooled from its isotropic phase, the smec-
tic A phase appeared and exhibited focal-conic texture. The sta-
ble enantiotropic smectic A phase was found. For example, on
heating the sample 8a enters into the smectic A phase at 40.0 ꢀC
and finally melts to an isotropic liquid at 49.0 ꢀC. The range
of temperature for the mesophase is 9.0 ꢀC. The two peaks ob-
served at 40.0 ꢀC and 49.0 ꢀC were associated with K/SA and
SA/I transitions, respectively, during the microscopy studies.
The other members of this series exhibited smectic A phase
along with smectic X phase. Tolan 10 shows only SmA* phase.
The first change is associated with crystalecrystals transition.
On heating the sample 10, it enters into the crystal phase at
53 ꢀC followed by an SmA phase at 55 ꢀC and finally melts to
an isotropic liquid at 59 ꢀC. However, on cooling the sample did
not show the crystalecrystals transition. The texture that
emerges on cooling remains unchanged down to 50 ꢀC. Below
this temperature, the sample crystallizes.
O
O
H21C10
O
10
Scheme 4. Synthesis of 10.
Compound 12 was selected for the synthesis due to the
nitrogen atom in the pyridine ring. The chiral chloro-nicoti-
nate ester 11b was prepared by reaction of the acid 11a and
alcohol 6 in 89% yield mediated by DCC and DMAP. Com-
pound 12 was obtained through the PdeCu-mediated reaction
between 6-chloronicotinate ester 11b and the alkyne 4d with
65% yield.
Cl
O
OR1
N
H21C10O
O
N
O
11a R1 = Hydrogen
12
11b R1 = (S)-2-Methyl-1-butyl
The Buchwald protocol opens the possibility of accessing a
great variety of new products, which would be very difficult
to be made by a non-copper-mediated nucleophilic aromatic
substitution reaction. The protocol can be successfully applied
to the alkyl aryl ethers’ synthesis from secondary substrates
such as allylic and chiral sec-phenyl ethyl alcohol. To our
expectation the reaction conditions in the protocol could be
extended to more hindered substrates such as chiral ethyl
lactate19 to give 13, which is recognized as an attractive pre-
cursor for the synthesis of chiral liquid crystals. We explore
the O-arylation coupling to prepare compound 14 in a good
For compounds 12 and 14, the DSC and POM analyses re-
veal that samples are stable under heating. The melting point
temperatures and enthalpy values were collected from second
heating scans. However, the new compounds synthesized
didn’t show mesomorphic behavior. The absence of liquid-
crystalline properties makes them good candidates for dopants
for liquid crystals mixture studies. This study is in progress
and will be presented in due course.
Compounds 10 and 12 are similar in the chemical structure.
The difference between them is the nitrogen atom at 3-position
Table 1
Transition temperatures (ꢀC) for series 8aed, 10, 12, and 14 and enthalpy values (DH, kcal molꢁ1
)
Entry
Phase transition temperatures (ꢀC)
Heating
Enthalpy values
Melta
Cooling
Isob
8a
8b
8c
8d
10
12
14
K1 32 K2 40 SmA* 49 I
K 22 SmX 46 SmA* 55 I
K 25 SmX 39 SmA* 54 I
K 45 SmA* 56 I
K 35 SmA* 43 I
0.7
1.4
4.6
0.8
1.5
1.4
1.9
d
K1 1.5 K2 9.0 SmX 41 SmA* 49 I
K -2.2 SmX 34 SmA* 48 I
K 16 SmX 38 SmA* 52 I
K 30 SmA* 58 I
6.6
c
K1 53 K2 55 SmA* 59 I
K1 69 K2 72 I
K 25 I
c
K 52 I
K 18 I
d
d
6.3
Scan rate: 10 ꢀC minꢁ1 for all samples; K1 and K2¼crystal phase, SmA*¼Chiral smectic A phase.
a
Enthalpy values were determined from crystal phase to smectic A* phase for 8a and 8d and smectic X phase for 8b and 8c.
Enthalpy values were determined from isotropic phase to a liquid-crystalline SmA* phase at second heating stage.
Value not determined.
b
c

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U.B. Vasconcelos et al. / Tetrahedron 64 (2008) 4619e4626
on the nicotinate ester ring. However, by changing carbon to
nitrogen, the liquid crystals properties disappear for 12. The
non-liquid crystalline behavior of 12 may be associated with
the dipolar moment of the nitrogen atom on the nicotinate
ring, according to Refs. 16a and b.
(KOH) under argon immediately before use. The reactions were
monitored by analytical thin-layer chromatography (TLC) with
Merck aluminum plates with 0.2 mm of silica gel 60 F254 and
Shimadzu GC 17 A Series. Anhydrous sodium sulfate was used
to dry all organic extracts. Toluene was first heated at reflux
over sodium and then distilled under argon. All reactions in-
volving Sonogashira coupling were performed in one-neck
round-bottom flask equipped with septum stoppers and charged
with triethylamine (Et3N), aromatic iodide, and alkyne under
argon atmosphere for 20 min. Copper(I) iodide (CuI), triphenyl-
phosphine (PPh3), and bis-(triphenylphosphine)palladium(II)
chloride (PdCl2(PPh3)2) were then added.
4. Conclusions
In conclusion, we have synthesized new N-heterotolan
liquid crystals using two powerful methodologies. Using the
Buchwald protocol, we prepared a chiral intermediate 7 and
13 as a promising candidate for a variety of 2,5-disubstituted
pyridine liquid crystals. All final compounds were synthesized
through a double Sonogashira reaction. The series 8aed and
14 contains a nitrogen atom at 2-position on the aromatic
ring. For compounds 10 and 12, a carboxylate group was in-
serted between the benzene ring and the chiral tail. The final
compounds 8aed and 10 showed chiral smectic A* phase.
Compounds 12 and 14 did not show liquid-crystalline proper-
ties. These results suggest that the relative position of the ni-
trogen atom on pyridine ring and the nature of the polar
group linking the mesogenic core with alkyl chain are impor-
tant structural parameters to be considered in the design and
synthesis of potential technological molecular materials.
5.2. Representative procedure for homologues 2a
5.2.1. 1-Bromo-4-heptyloxybenzene (2a)
p-Bromophenol (5.5 g, 34.8 mmol) and potassium hydrox-
ide (2.2 g, 38.3 mmol) were added to benzene/DMF (1:1 v/v,
40 mL) solution and heated at 50 ꢀC for 20 min. Then, n-hep-
tylbromide (6.0 mL, 38.4 mmol) was added dropwise and the
mixture heated under reflux for 6 h. The solid formed was fil-
tered and the filtrate concentrated. The residue was dissolved
in diethyl ether (75 mL), washed with solution of 10% sodium
bicarbonate (2ꢂ75 mL) and water (75 mL), and dried over an-
hydrous sodium sulfate. The solvent was removed and a pale
yellow oil was distilled at reduced pressure yielding 95% of
5. Experimental
1
colorless oil. Bp 115 ꢀC at 1 mmHg. H NMR (CDCl3/TMS,
5.1. General
200 MHz) d (ppm): 0.9 (t, 3H, J¼6.4 Hz, CH3), 1.0 (m, 8H,
CH2), 1.2 (m, 2H, CH2), 3.9 (t, 2H, J¼6.6 Hz, OCH2), 6.7
(d, 2H, J¼9.0 Hz, Ar), 7.3 (d, 2H, J¼9.2 Hz, Ar).
1H and 13C NMR spectra in CDCl3 were obtained using
Varian-200 and 300 MHz spectrometers using TMS as the
internal standard. Optical rotations were recorded on a Perkine
Elmer 341 polarimeter at the sodium D line. The thermal tran-
sitions and the mesomorphic textures were determined using
an Olympus BX43 polarizing microscope in conjunction
with Mettler FP90 controller and HT84 heating stage and
PerkineElmer 141 differential scanning calorimeter. The
rate of heating or cooling was 10 ꢀC minꢁ1. ESI-MS data
were collected on a WatersÒ MicromassÒ Q-Tof microÔ mass
spectrometer with Z-spray electrospray source. Samples were
infused from a 100 mL gas-tight syringe at 5 mL minꢁ1, via a
syringe pump. Instrument settings were unexceptional: capil-
lary voltage 4500 V, cone voltage 50 V, source temperature
100 ꢀC, desolvation gas temperature 100 ꢀC. Nitrogen was
used as the desolvation gas. Elemental analyses were conducted
at the central analitica/IQ-UFRGS using a PerkineElmer 2400
CHN Analyser. Purification by column chromatography was
carried out on 70e230 mesh Merck silica gel 60. 4-Bromo-
benzoic acid, 6-chloro-nicotinic acid, 4-(N,N-dimethylamino)
pyridine, 2,5-di-bromopyridine, (S)-(ꢁ)-2-methyl-1-butanol
(w95%), 1,3-dicyclohexylcarbodiimide, triphenylphosphine,
palladium(II) chloride, 2-methyl-3-butyn-2-ol, and copper(I)
iodide were purchased from Aldrich, and used as-received un-
less otherwise specified. Chemicals were used without further
purification. Dichloromethane (CH2Cl2) was distilled over
calcium hydride (CaH2) under argon immediately before use.
Triethylamine (Et3N) was distilled over potassium hydroxide
5.2.2. Data for 1-bromo-4-octyloxybenzene (2b)
Bp 117 ꢀC at 1 mmHg. Yield: 90%. 1H NMR (CDCl3/TMS,
200 MHz) d (ppm): 0.9 (t, 3H, J¼6.4 Hz, CH3), 1.0 (m, 10H,
CH2), 1.3 (m, 2H, CH2), 3.9 (t, 2H, J¼6.6 Hz, OCH2), 6.8 (d,
2H, J¼9.0 Hz, Ar), 7.4 (d, 2H, J¼9.2 Hz, Ar).
5.2.3. Data for 1-bromo-4-nonyloxybenzene (2c)
Bp 115 ꢀC at 1 mmHg. Yield: 95%. 1H NMR (CDCl3/TMS,
200 MHz) d (ppm): 0.9 (t, 3H, J¼6.4 Hz, CH3), 1.0 (m, 12H,
CH2), 1.2 (m, 2H, CH2), 3.9 (t, 2H, J¼6.6 Hz, OCH2), 6.7 (d,
2H, J¼9.0 Hz, Ar), 7.3 (d, 2H, J¼9.2 Hz, Ar).
5.2.4. Data for 1-bromo-4-decyloxybenzene (2d)
Bp 143 ꢀC at 1 mmHg. Yield: 96%. 1H NMR (CDCl3/TMS,
200 MHz) d (ppm): 0.9 (t, 3H, J¼6.4 Hz, CH3), 1.0 (m, 14H,
CH2), 1.2 (m, 2H, CH2), 3.9 (t, 2H, J¼6.6 Hz, OCH2), 6.7 (d,
2H, J¼9.0 Hz, Ar), 7.3 (d, 2H, J¼9.2 Hz, Ar).
5.3. Representative procedure for homologues 3a
5.3.1. 4-(4-Heptyloxyphenyl)-2-methylbut-3-yn-2-ol (3a)
A test tube was charged with Et3N (2 mL), 2-methyl-3-bu-
tyn-2-ol (0.2 mL, 1.5 mmol), and 2a (0.3 g, 1.0 mmol) under ar-
gon. To the solution were added CuI (0.7 mg), PPh3 (4.3 mg),
and PdCl2(PPh3)2 (2.2 mg). The mixture was heated for 20 h
at 90 ꢀC. After cooling, the solid was filtered and washed with

U.B. Vasconcelos et al. / Tetrahedron 64 (2008) 4619e4626
4623
diethyl ether (20 mL). The filtered mixture was evaporated, and
the resulting dark yellow oil was dissolved in CH2Cl2 (30 mL)
and washed with water (3ꢂ20 mL), cold 5 N hydrochloric
acid (20 mL), and water (20 mL) again. The organic layer was
dried over anhydrous sodium sulfate. The solvent was evapo-
rated and the remaining solid was purified by chromatography.
d (ppm): 0.9 (t, 3H, J¼6.4 Hz, CH3), 1.3 (m, 8H, CH2), 1.8
(m, 2H, CH2), 3.0 (s, 1H, CH), 3.9 (t, 2H, J¼6.4 Hz, OCH2),
6.8 (d, 2H, J¼8.8 Hz, Ar), 7.4 (d, 2H, J¼8.8 Hz, Ar). 13C
NMR (CDCl3/TMS, 50 MHz) d (ppm): 159.5, 133.5, 114.4,
113.8, 83.7, 75.6, 68.0, 31.9, 29.3, 25.9, 22.6, 14.0.
1
A yellow oil was obtained with a yield of 75%. H NMR
5.4.2. Data for 1-ethynyl-4-octyloxybenzene (4b)
1
Yield: 77%. H NMR (CDCl3/TMS, 200 MHz) d (ppm):
(CDCl3/TMS, 200 MHz) d (ppm): 0.8 (t, 3H, J¼6.4 Hz, CH3),
1.2 (m, 8H, CH2), 1.5 (s, 6H, CH3), 1.6 (m, 2H, CH2), 2.1 (s,
1H, OH), 3.8 (t, 2H, J¼6.5 Hz, OCH2), 6.7 (d, 2H, J¼7.4 Hz,
Ar), 7.2 (d, 2H, J¼7.6 Hz, Ar). 13C NMR (CDCl3/TMS,
50 MHz) d (ppm): 159.0, 132.9, 114.5, 114.3, 92.3, 82.0,
68.0, 65.5, 31.8, 31.5, 29.3, 25.9, 22.6, 14.0.
0.9 (t, 3H, J¼6.4 Hz, CH3), 1.3 (m, 10H, CH2), 1.8 (m, 2H,
CH2), 3.0 (s, 1H, CH), 3.9 (t, 2H, J¼6.4 Hz, OCH2), 6.8 (d,
2H, J¼8.8 Hz, Ar), 7.4 (d, 2H, J¼8.8 Hz, Ar). 13C NMR
(CDCl3/TMS, 50 MHz) d (ppm): 159.5, 133.5, 114.4, 113.8,
83.7, 75.6, 68.0, 31.9, 29.5, 29.2, 25.9, 22.6, 14.0.
5.3.2. Data for 4-(4-octyloxyphenyl)-2-methylbut-3-yn-
2-ol (3b)
5.4.3. Data for 1-ethynyl-4-nonyloxybenzene (4c)
1
Yield: 71%. H NMR (CDCl3/TMS, 200 MHz) d (ppm):
1
Yield: 83%. H NMR (CDCl3/TMS, 200 MHz) d (ppm):
0.9 (t, 3H, J¼6.4 Hz, CH3), 1.3 (m, 12H, CH2), 1.8 (m, 2H,
CH2), 3.0 (s, 1H, CH), 3.9 (t, 2H, J¼6.4 Hz, OCH2), 6.8 (d,
2H, J¼8.8 Hz, Ar), 7.4 (d, 2H, J¼8.8 Hz, Ar). 13C NMR
(CDCl3/TMS, 50 MHz) d (ppm): 159.5, 133.5, 114.4, 113.8,
83.7, 75.6, 68.0, 31.9, 29.5, 29.3, 29.1, 25.9, 22.6, 14.0.
0.8 (t, 3H, J¼6.4 Hz, CH3), 1.2 (m, 10H, CH2), 1.5 (s, 6H,
CH3), 1.6 (m, 2H, CH2), 2.1 (s, 1H, OH), 3.8 (t, 2H,
J¼6.5 Hz, OCH2), 6.7 (d, 2H, J¼7.4 Hz, Ar), 7.2 (d, 2H,
J¼7.6 Hz, Ar). 13C NMR (CDCl3/TMS, 50 MHz) d (ppm):
159.0, 132.9, 114.5, 114.3, 92.3, 82.0, 68.0, 65.5, 31.8, 31.5,
29.5, 29.3, 25.9, 22.6, 14.0.
5.4.4. Data for 1-ethynyl-4-decyloxybenzene (4d)
1
Yield: 80%. H NMR (CDCl3/TMS, 200 MHz) d (ppm):
5.3.3. Data for 4-(4-nonyloxyphenyl)-2-methylbut-3-yn-
2-ol (3c)
0.9 (t, 3H, J¼6.4 Hz, CH3), 1.3 (m, 14H, CH2), 1.8 (m, 2H,
CH2), 3.0 (s, 1H, CH), 3.9 (t, 2H, J¼6.4 Hz, OCH2), 6.8 (d,
2H, J¼8.8 Hz, Ar), 7.4 (d, 2H, J¼8.8 Hz, Ar). 13C NMR
(CDCl3/TMS, 50 MHz) d (ppm): 159.5, 133.5, 114.4, 113.8,
83.7, 75.6, 68.0, 31.9, 29.5, 29.3, 29.2, 29.1, 25.9, 22.6, 14.0.
1
Yield: 78%. H NMR (CDCl3/TMS, 200 MHz) d (ppm):
0.8 (t, 3H, J¼6.4 Hz, CH3), 1.2 (m, 12H, CH2), 1.5 (s, 6H,
CH3), 1.6 (m, 2H, CH2), 2.1 (s, 1H, OH), 3.8 (t, 2H,
J¼6.5 Hz, OCH2), 6.7 (d, 2H, J¼7.4 Hz, Ar), 7.2 (d, 2H,
J¼7.6 Hz, Ar). 13C NMR (CDCl3/TMS, 50 MHz) d (ppm):
159.0, 132.9, 114.5, 114.3, 92.3, 82.0, 68.0, 65.5, 31.8, 31.5,
29.5, 29.3, 29.1, 25.9, 22.6, 14.0.
5.5. (S)-(þ)-5-Bromo-2-(methylbutyloxy)pyridine (7)
A one-neck round-bottom flask equipped with septum stoppers
was charged with CuI (0.3 g, 1.6 mmol), 1,10-phenanthroline
(0.6 g, 3.2 mmol), Cs2CO3 (10.4 g, 32.0 mmol), 2,5-dibromo-
pyridine (5) (3.8 g, 16.0 mmol), (S)-(ꢁ)-2-methyl-1-butanol
(6) (4 mL, 32.0 mmol), and dried toluene (8 mL). The tube was
sealed and the mixture was stirred at 110 ꢀC for 26 h. The reac-
tion mixture was cooled to room temperature and filtered
through a pad of silica gel, eluting with diethyl ether. The filtrate
was concentrated and the residue was purified by chromatogra-
phy. The colorless oil was obtained with a yield of 60%. [a]D20
þ12 (CH2Cl2). 1H NMR (CDCl3/TMS, 300 MHz) d (ppm): 0.9
(t, 3H, J¼7.5 Hz, CH3), 1.0 (d, 3H, J¼6.3 Hz, CH3), 1.2 (m, 1H,
CHHCH3), 1.4 (m, 1H, CHHCH3), 1.8 (m, 1H, CHCH3), 4.0
(dd, 1H, Jgem¼10.4 Hz, Jtrans¼6.8 Hz, OCH2), 4.1 (dd, 1H,
Jgem¼10.4 Hz, Jcis¼6.5 Hz, OCH2), 6.6 (d, 1H, J¼8.1 Hz, Ar),
7.6 (dd, 1H, J¼6.3 Hz, 2.6 Hz, Ar), 8.2 (d, 1H, J¼2.3 Hz, Ar).
13C NMR (CDCl3/TMS, APT, 75 MHz) d (ppm): 162.8, 147.3,
140.6, 112.4, 111.1, 70.9, 34.2, 26.0, 16.3, 11.1.
5.3.4. Data for 4-(4-decyloxyphenyl)-2-methylbut-3-yn-
2-ol (3d)
1
Yield: 87%. H NMR (CDCl3/TMS, 200 MHz) d (ppm):
0.8 (t, 3H, J¼6.4 Hz, CH3), 1.2 (m, 14H, CH2), 1.5 (s, 6H,
CH3), 1.6 (m, 2H, CH2), 2.1 (s, 1H, OH), 3.8 (t, 2H,
J¼6.5 Hz, OCH2), 6.7 (d, 2H, J¼7.4 Hz, Ar), 7.2 (d, 2H,
J¼7.6 Hz, Ar). 13C NMR (CDCl3/TMS, 50 MHz) d (ppm):
159.0, 132.9, 114.5, 114.3, 92.3, 82.0, 68.0, 65.5, 31.8, 31.5,
29.5, 29.3, 29.2, 29.1, 25.9, 22.6, 14.0.
5.4. Representative procedure for homologues 4a
5.4.1. 1-Ethynyl-4-heptyloxybenzene (4a)
Potassium hydroxide (0.3 g, 5.4 mmol) and isopropanol
(4 mL) were added to a round bottomed flask and heated
at 50 ꢀC for 10 min. Then, a solution of 4-(4-heptyloxy-
phenyl)-2-methylbut-3-yn-2-ol (0.5 g, 1.8 mmol) and isopropa-
nol (5 mL) was added at once. The mixture was heated under
reflux for 2 h. The solvent was evaporated, the residue was
dissolved in diethyl ether (30 mL), and washed with water
(3ꢂ20 mL). The organic layer was dried over anhydrous sodium
sulfate. The solvent was evaporated and a yellow oil was ob-
tained in 76% yield. 1H NMR (CDCl3/TMS, 200 MHz)
5.6. Representative procedure for homologues 8a
5.6.1. (S)-(þ)-5-(4-Heptyloxyphenylethynyl)-2-(2-methyl-
butyloxy)pyridine (8a)
A test tube was charged with Et3N (2 mL), 1-ethynyl-4-hep-
tyloxybenzene (4a) (0.3 g, 1.4 mmol), and 7 (0.2 g, 0.9 mmol)

4624
U.B. Vasconcelos et al. / Tetrahedron 64 (2008) 4619e4626
under argon. CuI (0.6 mg), PPh3 (4.0 mg), and PdCl2(PPh3)2
(2.1 mg) were added to the stirred solution. The mixture was
heated for 20 h at 90 ꢀC. After cooling, the solid was filtered
off and washed with diethyl ether (20 mL). The solution was
evaporated and the resulting dark yellow oil was dissolved in
CH2Cl2 (30 mL), and this phase was washed with water
(3ꢂ20 mL), cold 5 N hydrochloric acid (20 mL), and water
(20 mL). The organic phase was dried over anhydrous sodium
sulfate. The solvent was evaporated and the remaining solid
was purified by chromatography. The yellow oil was obtained
2H, J¼6.4 Hz, CH2O), 4.0 (m, 1H, OCHH), 4.1 (m, 1H,
OCHH), 6.6 (d, 1H, J¼8.8 Hz, Ar), 6.8 (d, 2H, J¼8.0 Hz,
Ar), 7.4 (d, 2H, J¼8.6 Hz, Ar), 7.5 (dd, 1H, J¼7.8 Hz,
2.2 Hz, Ar), 8.1 (d, 1H, J¼2.0 Hz, Ar). 13C NMR (CDCl3/
TMS, APT, 50 MHz) d (ppm): 163.2, 159.2, 149.7, 141.0,
132.9, 114.8, 114.5, 113.2, 110.7, 90.6, 84.8, 71.1, 68.1,
34.5, 31.9, 29.5, 29.4, 29.3, 29.2, 29.1, 26.2, 26.0, 22.7,
16.5, 14.2, 11.4. Anal. Calcd for C28H39NO2: C, 79.77;
H, 9.32; N, 3.32. Found: C, 79.71; H, 9.30; N, 3.70. HRMS
(ESI): m/z calcd for [M]þ 421.2980, found [Mþ1]þ: 422.3038.
with a yield of 54%. [a]2D0 þ3 (CH2Cl2). H NMR (CDCl3/
1
TMS, 200 MHz) d (ppm): 0.8e0.9 (m, 9H, CH3), 1.1e1.5 (m,
13H, CH, CH2), 3.9 (t, 2H, J¼6.4 Hz, CH2O), 4.0 (m, 1H,
OCH2), 4.1 (m, 1H, OCH2), 6.6 (d, 1H, J¼8.8 Hz, Ar), 6.8 (d,
2H, J¼8.0 Hz, Ar), 7.4 (d, 2H, J¼8.6 Hz, Ar), 7.5 (dd, 1H,
J¼7.8 Hz, 2.2 Hz, Ar), 8.1 (d, 1H, J¼2.0 Hz, Ar). 13C NMR
(CDCl3/TMS, APT, 50 MHz) d (ppm): 163.2, 159.2, 149.7,
141.0, 132.9, 114.8, 114.5, 113.2, 110.7, 90.6, 84.8, 71.1,
68.1, 34.5, 31.9, 29.4, 29.2, 26.2, 26.0, 22.7, 16.5, 14.2, 11.4.
Anal. Calcd for C25H33NO2: C, 79.11; H, 8.76; N, 3.69. Found:
C, 78.96; H, 8.42; N, 3.78. HRMS (ESI): m/z calcd for [M]þ
379.2511, found [Mþ1]þ: 380.2585.
5.7. (S)-(þ)-(2-Methyl)butyloxy-4-bromobenzoate (9)
4-Bromobenzoic acid (4.0 g, 20.0 mmol) and distilled
SOCl2 (7.3 mL, 92.5 mmol) were added to 20 mL of benzene
under argon atmosphere. The mixture was heated under re-
fluxed for 3 h. The reaction mixture was cooled and the sol-
vent and excess of SOCl2 were removed. The viscous oil
was dissolved in dried pyridine (10 mL, 71.0 mmol) under ar-
gon atmosphere. The mixture was cooled in an ice bath and a
solution of (S)-(ꢁ)-2-methyl-1-butanol (6) (2 mL, 20 mmol) in
dried CH2Cl2 (15 mL) was added dropwise. The mixture was
heated under reflux for 6 h and at room temperature for addi-
tional 12 h. The solid residue was filtered and the organic layer
was dissolved in diethyl ether (100 mL). The organic phase
was washed with a saturated solution of NaCl (20 mL),
NaHCO3 (2ꢂ20 mL), and NaCl (20 mL). The organic phase
was dried over anhydrous sodium sulfate and the solvent
was evaporated. The remaining solid was obtained with a yield
of 50%. 1H NMR (CDCl3/TMS, 200 MHz) d (ppm): 0.9 (t, 3H,
J¼7.4 Hz, CH3), 1.0 (d, 3H, J¼6.8 Hz, CH3), 1.2 (m, 1H,
CHHCH3), 1.5 (m, 1H, CHHCH3), 1.8 (m, 1H, CHCH3), 4.1
(dd, 1H, Jgem¼10.8 Hz, Jtrans¼6.6 Hz, OCH2), 4.2 (dd, 1H,
Jgem¼10.8 Hz, Jcis¼6.0 Hz, OCH2), 7.6 (d, 2H, J¼8.6 Hz,
Ar), 7.9 (d, 2H, J¼8.6 Hz, Ar). 13C NMR (CDCl3/TMS,
APT, 50 MHz) d (ppm): 165.8, 149.3, 132.2, 131.5, 127.8,
69.8, 34.2, 26.1, 16.5, 11.4.
5.6.2. Data for (S)-(þ)-5-(4-octyloxyphenylethynyl)-2-(2-
methylbutyloxy)pyridine (8b)
1
Yield: 60%. H NMR (CDCl3/TMS, 200 MHz) d (ppm):
0.8e0.9 (m, 9H, CH3), 1.2e1.6 (m, 15H, CH, CH2), 3.9 (t, 2H,
J¼6.4 Hz, CH2O), 4.0 (m, 2H, OCH2), 6.6 (d, 1H, J¼8.8 Hz,
Ar), 6.8 (d, 2H, J¼8.0 Hz, Ar), 7.4 (d, 2H, J¼8.6 Hz, Ar), 7.5
(dd, 1H, J¼7.8, 2.2 Hz, Ar), 8.1 (d, 1H, J¼1.9 Hz, Ar). 13C
NMR (CDCl3/TMS, APT, 50 MHz) d (ppm): 163.2, 159.2,
149.7, 141.0, 132.9, 114.8, 114.5, 113.2, 110.7, 90.6, 84.8,
71.1, 68.1, 34.5, 31.9, 29.5, 29.3, 29.2, 26.2, 26.0, 22.7,
16.5, 14.2, 11.4. Anal. Calcd for C26H35NO2: C, 79.35; H,
8.96; N, 3.56. Found: C, 79.30; H, 9.04; N, 3.34. HRMS
(ESI): m/z calcd for [M]þ 393.2667, found [Mþ1]þ: 394.2742.
5.6.3. Data for (S)-(þ)-5-(4-nonyloxyphenylethynyl)-2-(2-
methylbutyloxy)pyridine (8c)
1
Yield: 45%. H NMR (CDCl3/TMS, 200 MHz) d (ppm):
5.8. (S)-2-(2-Methyl)butyloxy-4-(4-decyloxyphenyl-
ethynyl)benzoate (10)
0.8 (d, 3H, J¼6.3 Hz, CH3), 0.9 (t, 6H, J¼6.6 Hz, CH3),
1.2e1.5 (m, 16H, CH2), 1.7 (m, 1H, CH), 3.9 (t, 2H,
J¼6.4 Hz, CH2O), 4.0 (dd, 1H, Jgem¼10.2 Hz, Jtrans¼6.6 Hz,
OCH2), 4.1 (dd, 1H, Jgem¼10.2 Hz, Jcis¼6.0 Hz, OCH2), 6.6
(d, 1H, J¼8.8 Hz, Ar), 6.8 (d, 2H, J¼8.0 Hz, Ar), 7.4 (d,
2H, J¼8.6 Hz, Ar), 7.5 (dd, 1H, J¼7.8, 2.2 Hz, Ar), 8.1 (d,
1H, J¼1.9 Hz, Ar). 13C NMR (CDCl3/TMS, APT, 50 MHz)
d (ppm): 163.2, 159.2, 149.7, 141.0, 132.9, 114.8, 114.5,
113.2, 110.7, 90.6, 84.8, 71.1, 68.1, 34.5, 31.9, 29.5, 29.4,
29.3, 29.2, 26.2, 26.0, 22.7, 16.5, 14.2, 11.4. Anal. Calcd for
C27H37NO2: C, 79.56; H, 9.15; N, 3.44. Found: C, 79.87; H,
9.27; N, 3.30. HRMS (ESI): m/z calcd for [M]þ 407.2824,
found [Mþ1]þ: 408.2906.
A test tube was charged with Et3N (6 mL), 4d (0.2 g,
0.75 mmol), and 9 (0.1 g, 0.5 mmol) under argon. CuI
(0.2 mg), PPh3 (1.3 mg), and PdCl2(PPh3)2 (0.7 mg) were
added to the stirred solution. The mixture was heated for
20 h at 90 ꢀC. After cooling, the solid was filtered off and
washed with diethyl ether (20 mL). The filtered mixture was
evaporated and the resulting dark yellow oil was dissolved
in diethyl ether (20 mL) and washed with water (3ꢂ20 mL),
cold 1 N hydrochloric acid (20 mL), and water (20 mL). The
organic phase was dried over anhydrous sodium sulfate and
the solvent was evaporated. The remaining solid was purified
by chromatography affording a yellow solid with a yield of
1
5.6.4. Data for (S)-(þ)-5-(4-decyloxyphenylethynyl)-2-(2-
75%. H NMR (CDCl3/TMS, 200 MHz) (ppm): 0.8e0.9 (m,
methylbutyloxy)pyridine (8d)
9H, CH3), 1.2e1.8 (m, 19H, CH2, CH), 3.9 (t, 2H,
J¼6.6 Hz, OCH2), 4.1 (m, 2H, COOCH2), 6.3 (d, 2H, Ar),
7.4 (d, 2H, Ar), 7.5 (d, 2H, Ar), 7.9 (d, 2H, Ar). 13C NMR
1
Yield: 57%. H NMR (CDCl3/TMS, 200 MHz) d (ppm):
0.8e0.9 (m, 9H, CH3), 1.2e1.7 (m, 19H, CH, CH2), 3.9 (t,

U.B. Vasconcelos et al. / Tetrahedron 64 (2008) 4619e4626
4625
(CDCl3/TMS, APT, 50 MHz) d (ppm): 166.1, 159.5, 133.2,
131.2, 129.4, 128.3, 114.5, 114.4, 92.6, 87.4, 69.6, 68.0,
34.3, 31.9, 29.5, 29.4, 29.3, 29.2, 26.2, 26.0, 22.7, 16.5,
14.2, 11.3. Anal. Calcd for C30H40O3: C, 80.32; H, 8.99.
Found: C, 79.87; H, 9.24. HRMS (ESI): m/z calcd for [M]þ
448.2977, found [Mþ1]þ: 449.3065.
(0.6 g, 3.2 mmol), Cs2CO3 (10.4 g, 32.0 mmol), 2,5-dibromo-
pyridine (5) (3.8 g, 16.0 mmol), (S)-(ꢁ)-ethyl lactate (3.6 mL,
32.0 mmol), and dried toluene (8 mL). The tube was sealed
and the mixture was stirred at 110 ꢀC for 26 h. The reaction
mixture was cooled to room temperature and filtered through
a pad of silica gel, eluting with diethyl ether. The filtrate was
concentrated and the residue was purified by chromatography.
1
5.9. (S)-2-(Methyl)butyloxy-6-chloronicotinate (11b)
The yellow oil was obtained with a yield of 30%. H NMR
(CDCl3/TMS, 200 MHz) d (ppm): 1.3 (t, 3H, J¼7.2 Hz, CH3),
1.6 (d, 3H, J¼7.0 Hz, CHCH3), 4.2 (q, 2H, J¼7.2 Hz,
OCH2CH3), 5.2 (q, 1H, J¼7.0 Hz, CHCH3), 6.8 (d, 1H,
J¼8.8 Hz, Ar), 7.7 (dd, 1H, J¼6.2, 2.6 Hz, Ar), 8.1 (d, 1H,
J¼2.4 Hz, Ar).
6-Chloronicotinic acid (11a) (3.0 g, 19.0 mmol) and (S)-
(ꢁ)-2-methyl-1-butanol (6) (2.0 mL, 19.0 mmol) were added
to dried CH2Cl2 (35 mL) and the mixture was stirred at
room temperature for 10 min. DCC (4.7 g, 22.8 mmol) and
DMAP (0.03 g, 0.22 mmol) were, then, added and the mixture
was stirred for 24 h at room temperature. The resulting solu-
tion was filtered over Celite and the solvent evaporated. The
remaining solid was recrystallized from ethanol. The white
5.12. (S)-(ꢁ)-Ethyl-2-{[5-(6-decyloxyphenyl)ethynyl]pyridin-
2-yl}oxypropionate (14)
1
solid was obtained with a yield of 40%. H NMR (CDCl3/
A test tube was charged with Et3N (7 mL), 4d (0.32 g,
1.23 mmol), and 13 (0.2 g, 0.8 mmol) under argon. CuI
(0.5 mg), PPh3 (3.2 mg), and PdCl2(PPh3)2 (1.8 mg) were
added to the stirred solution. The mixture was heated for
20 h at 90 ꢀC. After cooling, the solid was filtered off and
washed with diethyl ether (20 mL). The filtered mixture was
evaporated and the resulting dark yellow oil was dissolved
in diethyl ether (20 mL), and washed with water (3ꢂ20 mL),
cold 1 N hydrochloric acid (20 mL), and water (20 mL). The
organic phase was dried over anhydrous sodium sulfate and
the solvent evaporated. The remaining solid was purified by
chromatography and a yellow solid was obtained with 45%
TMS, 200 MHz) d (ppm): 0.8e1.0 (m, 6H, CH3), 1.3 (m, 1H,
CHHCH3), 1.5 (m, 1H, CHHCH3), 1.9 (m, 1H, CHCH3), 4.2
(dd, 1H, Jgem¼10.8 Hz, Jtrans¼6.6 Hz, OCH2), 4.3 (dd, 1H,
Jgem¼10.8 Hz, Jcis¼4.8 Hz, OCH2), 7.4 (d, 1H, J¼8.2 Hz,
Ar), 8.2 (dd, 1H, J¼6.0, 2.4 Hz, Ar), 9.0 (d, 1H, J¼1.6 Hz,
Ar). 13C NMR (CDCl3/TMS, APT, 50 MHz) d (ppm): 164.3,
155.4, 150.9, 139.4, 125.2, 124.1, 70.1, 34.1, 26.0, 16.4, 11.2.
5.10. (S)-2-(2-Methyl)butoxy-6-(4-decyloxyphenylethynyl)
nicotinate (12)
1
A test tube was charged with Et3N (7 mL), 4d (0.32 g,
1.23 mmol), and 11b (0.2 g, 0.8 mmol) under argon. CuI
(0.5 mg), PPh3 (3.2 mg), and PdCl2(PPh3)2 (1.8 mg) were
added to the stirred solution. The mixture was heated for
20 h at 90 ꢀC. After cooling, the solid was filtered off and
washed with diethyl ether (20 mL). The filtered mixture was
evaporated and the resulting dark yellow oil was dissolved
in diethyl ether (20 mL) and washed with water (3ꢂ20 mL),
cold 1 N hydrochloric acid (20 mL), and water (20 mL). The
organic phase was dried over anhydrous sodium sulfate and
the solvent was evaporated. The remaining solid was purified
by chromatography affording a yellow solid with a yield of
65%. 1H NMR (CDCl3/TMS, 200 MHz) d (ppm): 0.9e1.1 (m,
9H, CH3), 1.3e1.9 (m, 19H, CH, CH2), 4.0 (t, 2H, J¼6.6 Hz,
OCH2), 4.2 (m, 2H, COOCH2), 6.9 (d, 2H, J¼8.8 Hz, Ar), 7.6
(m, 3H, J¼8.6 Hz, Ar), 8.3 (dd, 1H, J¼6.0, 2.2 Hz, Ar), 9.2
(d, 1H, J¼1.4 Hz, Ar). 13C NMR (CDCl3/TMS, 50 MHz)
d (ppm): 164.9, 160.2, 150.9, 147.3, 137.0, 133.8, 128.2,
124.4, 114.8, 114.5, 113.3, 92.9, 87.4, 70.0, 68.1, 34.2, 31.8,
29.5, 29.4, 29.3, 29.1, 26.1, 26.0, 22.7, 16.5, 14.1, 11.3.
Anal. Calcd for C29H39NO3: C, 77.47; H, 8.74; N, 3.12.
Found: C, 77.14; H, 9.10; N, 3.17. HRMS (ESI): m/z calcd
for [M]þ 449.2929, found [Mþ1]þ: 450.3000.
yield. H NMR (CDCl3/TMS, 200 MHz) d (ppm): 0.9 (t, 3H,
J¼6.6 Hz, CH3), 1.3 (m, 17H, CH2 and CH3), 1.6 (d, 3H,
J¼7.0 Hz, CHCH3), 1.8 (m, 2H, CH2), 3.9 (t, 2H, J¼6.4 Hz,
OCH2), 4.2 (q, 2H, J¼7.2 Hz, OCH2), 5.3 (q, 1H, J¼6.8 Hz,
CHCH3), 6.7 (d, 1H, J¼8.4 Hz, Ar), 6.8 (d, 2H, J¼8.8 Hz, Ar),
7.4 (d, 2H, J¼8.6 Hz, Ar), 7.7 (dd, 1H, J¼6.4, 2.2 Hz, Ar), 8.2
(d, 1H, J¼2.2 Hz, Ar). 13C NMR (CDCl3/TMS, 50 MHz)
d (ppm): 172.2, 161.4, 159.2, 149.3, 141.2, 132.8, 114.7,
114.5, 114.1, 110.6, 90.9, 84.5, 70.1, 68.0, 61.0, 31.9, 29.5,
29.4, 29.3, 29.2, 26.0, 22.7, 17.6, 14.1. HRMS (ESI): m/z calcd
for [M]þ 451.2723, found [Mþ1]þ: 452.3101.
Acknowledgements
The authors acknowledge Edital Universal-2004-CNPq and
CAPES for financial support. Laboratory of Molecular Catal-
€
ysis-IQ-UFRGS and Prof. Jaırton. Dupont for ESI-MS facili-
ties. A.S. and G.D.V. are undergraduate students and thank
PIBIC-UFRGS and FAPERGS for their fellowship.
Supplementary data
The spectral and analytical data on isolated products, in-
cluding 1H, 13C NMR spectra, HRMS, DSC thermograms,
and mesophase photos are supplied. Supplementary data asso-
ciated with this article can be found in the online version, at
doi:10.1016/j.tet.2008.03.005.
5.11. (S)-Ethyl-2-(5-bromopyridin-2-yl)oxypropionate (13)
Aone-neckround-bottomflaskequippedwithseptum stopper
was charged with CuI (0.3 g, 1.6 mmol), 1,10-phenanthroline

4626
U.B. Vasconcelos et al. / Tetrahedron 64 (2008) 4619e4626
9. Paquette, L. A. Principles of Modern Heterocyclic Chemistry; The Benja-
min Cummings: Mexico, DF, 1987.
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