Synthesis and characterization of novel (E)-1-(hexa-3,5-dien-1-yl)-4-methoxybenzene via boronate complex

Article abstract of DOI:10.14233/ajchem.2014.17095

Novel (E)-1-(hexa-3,5-dien-1-yl)-4-methoxybenzene was synthesized through boronate complex. 3-(4-Methoxyphenyl)propyl diisopropylcarbamate was reacted with allylboronic acid pinacol ester in the presence of N,N,N,N-tetramethylethyllenediamine to give seco

Full text of DOI:10.14233/ajchem.2014.17095

Asian Journal of Chemistry; Vol. 26, No. 21 (2014), 7401-7403
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.17095
Synthesis and Characterization of Novel
(E)-1-(Hexa-3,5-dien-1-yl)-4-methoxybenzene via Boronate Complex
1,*
1
1
2
1
HABIB HUSSAIN , SYEDA RUBINA GILANI , ZULFIQAR ALI , HAJIRA REHMAN and IMDAD HUSSAIN
1Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan
2Department of Chemistry, University of Punjab, Lahore, Pakistan
*Corresponding author: Tel: +92 321 4618681, E-mail: hbubak@gmail.com
Received: 21 January 2014;
Accepted: 7 April 2014;
Published online: 30 September 2014;
AJC-16147
Novel (E)-1-(hexa-3,5-dien-1-yl)-4-methoxybenzene was synthesized through boronate complex. 3-(4-Methoxyphenyl)propyl
diisopropylcarbamate was reacted with allylboronic acid pinacol ester in the presence of N,N,N,N-tetramethylethyllenediamine to give
secondary boronic ester which was further reacted with (vinylsulfonyl)benzene by using Grubbs Hoveyda II. Resulting product (E)-2-(1-
(4-methoxyphenyl)-6-(phenylsulfonyl)hex-5-en-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane was then treated with 1-bromo-3,5-
bis(trifluoromethyl)benzene in the presence of n-BuLi to get nucleophilic boronate complex. (E)-1-(hexa-3,5-dien-1-yl)-4-methoxybenzene
was obtained in excellent yields by stirring boronate complex at 50 °C for 1 h and refluxing for 15 h.
Keywords: Lithiation borylation, Secondary boronic ester, 1-Bromo-3,5-bis(trifluoromethyl)benzene, Boronate complex.
In the recent paper, we reported the synthesis of novel
(E)-1-(hexa-3,5-dien-1-yl)-4-methoxybenzene (7). It was charac-
terized by IR, 1H, 13C and mass spectra. Lithiation-Borylation
was used to synthesize the secondary boronic ester and by using
olefin cross metathesis, it gave (E)-2-[1-(4-methoxyphenyl)-6-
(phenylsulfonyl)hex-5-en-3-yl]-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane when reacted with (vinylsulfonyl)benzene. (E)-
2-[1-(4-Methoxyphenyl)-6-(phenylsulfonyl)hex-5-en-3-yl]-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane was converted into ate-
complex which on heating produced the desired product.
INTRODUCTION
Olefin metathesis chemistry1 has led a number of oppor-
tunities in organic synthesis. Olefin metathesis2 involves the
redistribution of fragments of alkenes by regeneration of
carbon-carbon double bonds. There are numerous applications
of olefin metathesis and it is an important methodology to
produce reagents.
Addition of aryl lithium reagents to secondary boronic
esters results to a new class of chiral organometallic-type
reagents which have broad utility in asymmetric organic
synthesis. Larouche-Gauthier et al.3 formed intermediate
boronate complex by adding an aryl lithium reagent to a
secondary boronic ester. It behaved as a chiral nucleophile
and maximum enantioselectivity was found by using electron
withdrawing groups on aryllithium. Hussain et al.4 used
different aryl lithiums and studied stereoselectivity of boronate
complexes by tuning steric bulk. Hoffmann5 obtained chiral
Grignard reagents from sulfoxides Mg exchange reaction of
halosulfoxides. Brown et al.6 investigated iodination of the
ate-complexes from various B-alkoxyborinane derivatives and
1-alkynyl lithium. Vedejs et al.7 synthesized ate-complexes
which contained stereogenic boron by reacting trivalent
boranes with nucleophiles. They noticed that stability of ate-
complex depend upon the electronegativity of substituents
attached to boron. Ryschkewitsch and Garrett8 resolved chiral
boronate complexes by classical methods. Bernardi et al.9
determined the role of ate-complxes in aldol stereoselectivity.
EXPERIMENTAL
n-Butyl lithium (n-BuLi), sec-butyl lithium solution (s-
BuLi) (1.6 M), pinacol, N,N,N,N-tetramethylethylenediamine
(TMEDA), (vinylsulfonyl)benzene, Grubbs Hoveyda II and
1-bromo-3,5-bis(trifluoromethyl)benzene were taken from
Sigma Aldrich. All reagents were used without further purifi-
cation. To dry diethyl ether (Et2O) and tetrahydrofuran (THF)
4 A° molecular sieves were used. All experiments were done
in nitrogen atmosphere using schlenk lines.
Equipments: 1H and 13C spectral measurements were done
by using varian NMR (400 MHz) spectrometer (model DMX
400). For protons, chemical shifts were calculated correspon-
ding to tetramethylsilane (TMS) at δ = 0 ppm.
Synthesis and characterization of 2-[1-(4-methoxy-
phenyl)hex-5-en-3-yl]-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane (3): To a solution of 3-(4-methoxyphenyl)propyl

7402 Hussain et al.
Asian J. Chem.
diisopropylcarbamate (1 g, 3.41 mmol, 1 eq) (1) and N,N,N,N-
tetramethylethylenediamine (0.61 mL, 4.09 mmol, 1.2 eq) (2a)
in Et2O (17 mL) at -78 °C, sec-BuLi (1.6 M in 92:8 cyclohexane/
hexane, 2.9 mL, 3.75 mmol, 1.1 eq) was added dropwise and
stirred for 5 h at -78 °C. Then allyl boronic acid pinacol ester
(0.77 mL, 4.09 mmol, 1.2 eq) (2) was added dropwise to the
reaction mixture and further stirred at -78 °C for 1 h and warmed
to room temperature. At this stage, a solution of MgBr2·OEt2
in Et2O, made as follows, was added to the reaction mixture.
[At room temperature, 1,2-dibromoethane (0.60 mL, 6.88
mmol, 1 eq) was added into a suspension of magnesium (0.17
g, 6.88 mmol, 1 eq) in Et2O (8.6 mL). The reaction flask was
further stirred for 2 h after placing into a water bath in order to
control the moderate exotherm]. Biphasic mixture having two
layers thus obtained was added to the former reaction mixture
via syringe and then refluxed for 16 h. Reaction mixture was
then cooled to room temperature. Water was used to quench
the reaction. After adding diethyl ether, layers were extracted
and washed with 1 N hydrochloric acid, 1 N sodium hydroxide,
water and then brine. It was dried with MgSO4 and concen-
trated. Column chromatography (SiO2) was then used to purify
the crude product. Pure(R)-2-(1-(4-methoxyphenyl)hex-5-en-
3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3) (0.84 g,
77.60 %) was obtained as colorless oil. The reaction is given
in Fig. 1.
Synthesis and Characterization of (E)-2-[1-(4-methoxy-
phenyl)-6-(phenylsulfonyl)hex-5-en-3-yl]-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (5): Grubbs-Hoveyda II (4a) (3.9
mg, 0.0063 mmol, 0.05 eq) was added to a solution of 2-[1-
(4-methoxyphenyl)hex-5-en-3-yl]-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (3) (40 mg, 0.126 mmol, 1 eq) and (vinyl-
sulfonyl)benzene (4) (0.0635 g, 0.378 mmol, 3 eq) in CH2Cl2
(2 mL). After fitting a condenser to the flask, reaction mixture
was refluxed for 15 h under nitrogen. The reaction mixture
was reduced in volume to 0.5 mL and then purified directly
on a silica gel column eluting with 9:1 Pet. Ether/EtOAc to
get the desired product (E)-2-(1-(4-methoxyphenyl)-6-
(phenylsulfonyl)hex-5-en-3-yl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (5) as dark brown solid (0.0438 g, 77.25 %)10
m.p. 82 °C (Fig. 2).
O
B
O
O
S
Ph
+
O
(3)
O
(4)
O
O
O
B
O
Grubbs Hoveyda
2nd generation (4a)
40oC, 15h
S
Ph
O
O
N
+
B
O
O
O
(5)
(1)
O
(2)
Fig. 2. Synthesis of (E)-2-(1-(4-methoxyphenyl)-6-(phenylsulfonyl)hex-5-
en-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
O
O
B
1H NMR (400 MHz, CDCl3): δ ppm 7.88-7.84 (2H, m, 2
× ArH) 7.62-7.56 (1H, m, 1 × ArH) 7.54-7.48 (2H, m, 2 ×
ArH) 7.05-6.99 (2H, m, 2 ×ArH) 6.96 (1H, t, J = 6.97 Hz, CH2-
CH=CH) 6.84-6.77 (2H, m, 2 × ArH) 6.31 (1H, dt, J = 15.16,
1.47 Hz, CH2-CH=CH) 3.78 (3H, s, -CH3) 2.59-2.45 (2H, m,
CH2-CH2-CHB) 2.43-2.26 (2H, m, CH2-CHB-CH2) 1.77-1.66
(1H, m, CH2-CHB-CHH) 1.63-1.53 (1H, m, CH2-CHB-CHH)
1.27-1.21 (1H, m, CH2-CHB-CH2) 1.18 (12 H, s, 4 × CH3).
13C NMR (100 MHz, CDCl3): δ ppm 157.7 (1C, ArC-O)
146.9 (1C, ArC-S) 140.8 (1C, CH=CH-S) 134.2 (1C, CH=CH-
S) 133.1 (1C, ArC-CH2) 130.6 (1C, ArCH) 129.2 (2C, 2 ×
ArCH) 129.1 (2C, 2 × ArCH) 127.5 (2C, 2 × ArCH) 113.7
(2C, 2 × ArCH) 83.4 (2C, 2 × C(CH3)2) 55.2 (1C, OCH3) 34.1
(1C, CH2CHBCH2) 33.1 (1C, CH2CH2CHB) 32.8 (4C, 2 ×
(CH3)2C) 24.8 (1C, -CHBCH2CH) 24.7 (1C, CH2CH2CHB).
11B NMR (96.23 MHz, none): δ ppm 33.24, IR (film):
ν(cm-1) 2977, 2924 (sp3 C-H stretch), 1511, 1446 (sp2 C=C
stretch), 1244, 1176, 1141 (sp3C-O stretch), 822, 730, 687
(sp2 C-H oop bending).
s-BuLi
TMEDA
(2a)
Et2O
(3)
O
Fig. 1. Synthesis of 2-(1-(4-methoxyphenyl)hex-5-en-3-yl)-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane
1H NMR (400 MHz, CDCl3): δ ppm 7.09 (2H, d, J =
8.80 Hz, 2 × ArH) 6.81 (2H, d, J = 8.80 Hz, 2 × ArH) 5.86-
5.75 (1 H, m, CH=CH2) 5.04 (1H, d, J = 2.20 Hz, CH=CHH)
4.94 (1H, d, J = 10.27 Hz, CH=CHH) 3.78 (3H, s, OCH3)
2.63-2.48 (2H, m, ArCH2CH2CHBCH2) 2.27-2.11 (2H, m,
ArCH2 CH2CHBCH2) 1.78-1.58 (2H, m,ArCH2CH2CHBCH2)
1.25 (12 H, s, 4 × CH3) 1.08-1.18 (1 H, m,ArCH2CH2CHBCH2).
13C NMR (100 MHz, CDCl3): δ ppm 157.6 (1C, -OCH3),
138.4 (2C, 2 ×ArCH), 135 (2C, 2 ×ArCH), 129.2 (1C,ArC-O),
114.9 (1C, -CH2CH=CH2), 113.6 (1C, -CHb=CH2), 83 (2C, 2
× C(CH3)2), 55.2 (1C, ArCCH2), 35.3 (1C, -CH2CH2CHB),
34.5 (1C, -CH2CHB), 33.1 (1C, -CHBCH2CH), 24.9 (1C,
-CH2CH2CHB), 24.8 (4C, 2 × (CH3)2C).
Synthesis and characterization of (E)-1-(hexa-3,5-dien-
1-yl)-4-methoxybenzene (7): To a solution of 3,5-(CF3)2C6H3Br
(24.6 mg, 0.084 mmol, 1.2 eq) in THF (1.9 mL) at -78 °C
n-BuLi (1.6 M in hexanes, 0.053 mL, 0.084 mmol, 1.2 eq)
was dropwise added. Reaction mixture was then stirred for
11B NMR (96.23 MHz, none): δ ppm 33.24, IR (film):
ν(cm-1) 3026 (sp2C-H stretch), 2977, 2924, 2852 (sp3 C-H
stretch), 1511, 1456 (sp2 C=C stretch), 1243, 1175, 1142 (sp3
C-O stretch), 846, 822, 670 (sp2 C-H oop bending).

Vol. 26, No. 21 (2014)
Synthesis of Novel (E)-1-(Hexa-3,5-dien-1-yl)-4-methoxybenzene via Boronate Complex 7403
CF3
F3C
n-BuLi
O
O
B
O
O
O
S
(5a)
50oC/1hr
3,5-(CF3)2C6H3Br
THF, -78oC
O
S
B
Ph
Li
Ph
Refux for 15hr
(7)
O
O
O
(5)
O
(6)
O
Fig. 3. Synthesis of (E)-1-(hexa-3,5-dien-1-yl)-4-methoxybenzene (7)
TABLE-1
PHYSICAL STATES AND YIELDS
1 h at -78 °C and a solution of boronic ester (32 mg, 0.070
mmol, 1 eq) made in THF (1.5 mL) was dropwise added. The
mixture was stirred at -78 °C for 0.5 h and 0.5 h at room tempe-
rature to form boronate complex. Ate-complex was further
heated at 50 °C for 1 h and refluxed for 15 h (Fig. 3).
Reaction was quenched with water; EtOAc was added to
separate layers. Both layers were then combined, washed with
brine and dried using MgSO4. After concentrating, the crude
mixture was finally purified by column chromatography (SiO2,
2:1 Pet. ether/EtOAc) to get desired product as colorless oil
(19.87 mg, 62.10 %).
1H NMR (400 MHz, CDCl3): δ ppm 7.14-7.07 (2 H, m,
2 × ArH) 6.85-6.80 (2H, m, 2 × ArH) 6.30 (1H, dt, J = 17,
10.21 Hz, CH=CH-CH=CH2) 6.12-5.97 (1H, m, CH=CH-
CH=CH2) 5.78-5.69 (1H, m, CH=CH-CH=CH2) 5.21-5.06
(1 H, m, CH=CHH) 4.99-4.95 (1H, m, CH=CHH) 3.79 (3H,
s, -CH3) 2.70-2.60 (2H, m, CH2CH2CH) 2.52-2.33 (2H, m,
CH2CH2CH).
13C NMR (100 MHz, CDCl3): δ ppm 157.7 (1C, ArC-O)
137.0 (1C, CH=CH2) 133.7 (1C, CH=CH-CH=CH2) 132 (1C,
ArC-CH2) 129.5 (1C, CH=CH-CH=CH2) 129.1 (2C, 2 ×
ArCH) 114.9 (1C, CH=CH2) 113.6 (2C, 2 × ArCH) 55.1 (1C,
-CH3) 34.6 (1C, CH2CH2CH) 34.5 (1C, CH2CH2CH), IR (film):
ν(cm-1) 2955, 2921, 2852 (sp3 C-H stretch), 1737, 1461 (sp2
C=C stretch), 1277, 1184, 1137 (sp3 C-O stretch), 967, 805
(sp2 C-H oop bending). HRMS (ESI) Calcd. for C13H17O [M +
H]+ 189.1279, found 189.1287.
Physical
Melting Yield
(%)
Entry
1
Substances
States
points
O
O
Colorless
oil
B
—
77.60
O
O
O
Dark brown
solid
B
O
S
2
3
82 oC
—
77.25
62.10
Ph
O
O
Colorless
oil
O
Conclusion
Novel (E)-1-(hexa-3,5-dien-1-yl)-4-methoxybenzene has
been synthesized through a novel route and characterized by
spectral techniques like IR, 1H, 13C and MS. Boronate complex
was successfully converted into aromatic dienes. This novel
synthetic route resulted in excellent yields.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the financial support
by Higher Education Commission of Pakistan. Thanks are also
due to the Department of Chemistry, University of Engineering
and Technology, Lahore, Pakistan and Superior University
Lahore, Pakistan for guidance, research and laboratory facilities.
RESULTS AND DISCUSSION
REFERENCES
Starting material 2-[1-(4-methoxyphenyl)hex-5-en-3-yl]-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3) has been synthe-
sized as colorless oil in excellent yields (77.6 %) (Table-1,
entry 1) by using Lithiation-Borylation methodology; carba-
mate (1) was reacted with pinacol (2) by using TMEDA (2a)
at suitable conditions. Spectral studies proved the structure as
mentioned in literature11. By using application of olefin cross
metathesis, boronic ester (3) was then reacted with (vinylsul-
fonyl)benzene (4) to give (E)-2-(1-(4-methoxyphenyl)-6-
(phenylsulfonyl)hex-5-en-3-yl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (5) as dark brown solid. Yield was again exce-
llent (Table-1, entry 2) for this reaction.
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Boronate complex (6) which acted as nucleophile was
synthesized by reacting (E)-2-(1-(4-methoxyphenyl)-6-
(phenylsulfonyl)hex-5-en-3-yl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (5) with aryl lithium (5a). Boronate complex
(6) showed best nucleophilic character by using 3,5-
(CF3)2C6H3Br (5a) as aryl lithium11 and it was then stirred at 50
°C for 1 h and then refluxed for 15 h and desired product (E)-1-
(hexa-3,5-dien-1-yl)-4-methoxybenzene (7) was collected.
11. H. Hussain, S.R. Gilani, Z. Ali and I. Hussain, Asian J. Chem., (In press).