A dehydrohalogenation methodology for synthesizing terminal olefins under mild conditions

Article abstract of DOI:10.1055/s-2006-950204

A new methodology for preparing terminal olefins in good yield by dehydrohalogenation of primary alkyl iodide with tetrabutylammonium fluoride in dimethyl sulfoxide at room temperature is presented. Optimization of the mild reaction conditions and assays on various alkyl iodides are described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950204

PAPER
3085
A Dehydrohalogenation Methodology for Synthesizing Terminal Olefins
under Mild Conditions
Synthesis of
Terminal
a
O
lefins und
r
er Mild
i
Condit
eions Bérubé, Fatima Kamal, Jenny Roy, Donald Poirier*
Medicinal Chemistry Division, CHUQ-CRCHUL and Université Laval, 2705 Laurier Boulevard, Sainte-Foy, Quebec, G1V 4G2, Canada
Fax +1(418)6542761; E-mail: donald.poirier@crchul.ulaval.ca
Received 8 December 2005; revised 23 May 2006
used for deprotecting silylated alcohol9 – can also convert
Abstract: A new methodology for preparing terminal olefins in
an alkyl halide into an alkyl fluoride by nucleophilic sub-
good yield by dehydrohalogenation of primary alkyl iodide with tet-
rabutylammonium fluoride in dimethyl sulfoxide at room tempera-
stitution.10 Interestingly, many investigators have ob-
served an alkene by-product under such experimental
conditions.10a,11 We thus decided to optimize the forma-
tion of this ‘by-product’, formed by dehydrohalogenation
of alkyl halides by the fluoride ion acting as a base. We
designed a series of experiments with the aim of improv-
ing the basicity of the fluoride ion over its nucleophilicity.
We undertook optimization of the following parameters:
nature of the fluoride or ammonium ion, type of solvent,
and nature of the dehydrohalogenating reagent. Herein,
we report an optimized new methodology for the synthe-
sis of terminal olefins by dehydrohalogenation at room
temperature of primary alkyl halides using TBAF as re-
agent.
ture is presented. Optimization of the mild reaction conditions and
assays on various alkyl iodides are described.
Key words: alkenes, alkyl halides, elimination, dehydrohalogena-
tion, tetrabutylammonium fluoride
Terminal olefins are widely used in C–C coupling reac-
tions such as Grubbs metathesis1 and as intermediates in
the preparation of typical functional groups such as ep-
oxides, diols or aldehydes. Olefins can be prepared by de-
hydrohalogenation under many different experimental
conditions.2 Few methods of dehydrohalogenation of pri-
mary alkyl halides have, however, been reported to pro-
duce terminal olefin as the major compound. Henningsen
et al.3 have developed a nickel-mediated elimination of
hydrogen halide from primary alkyl iodide or bromide.
The main disadvantage of this method is the production of
a mixture of internal olefins contaminating the major ter-
minal olefin product. With this methodology, terminal
olefins are generally obtained in good to excellent yields
(43–100%). Typical functional groups such as benzyl
ether, ketone, ester, hydroxy, olefin and phenyl support
the reaction conditions well, but aldehyde and cyanide
groups are not compatible. Soderquist et al.4 used a potas-
sium hydroxide/triisopropylsilanol (KOH/TIPSOH) sys-
tem as a phase-transfer catalyst for dehydrohalogenation
of primary alkyl halides. They quantitatively converted
primary alkyl halides to alkenes avoiding both ether and
alcohol by-products, but reported only a few examples of
application. Terminal olefins can also be obtained using a
strong base such as t-BuOK,5 or a hindered base such as
DBU,6 but both have drawbacks. Indeed t-BuOK as well
as KOH are not well tolerated by all functional groups and
by-products are produced, whereas DBU could be applied
only for the preparation of conjugated terminal olefins.7
Initially we examined the reaction of 11-halogenounde-
can-1-ols (compounds 1) with 1 M TBAF in THF at room
1
temperature. Analysis of the crude material by H NMR
revealed a low conversion with the chloride, while quan-
titative conversion was obtained with the iodide and the
bromide derivatives (Table 1, entries 1–3). A better dehy-
drohalogenation/substitution (E/SN) ratio was however
obtained with the iodide. Three sources of TBAF (1 M in
THF, hydrated or adsorbed on SiO2) were next investigat-
ed, but no major difference in the E/SN ratio (entries 1, 4,
5) was evident. 11-Iodoundecan-1-ol was also treated
with TBACl, TBABr and TBAI in THF. The results
showed that fluoride is a better base than the other halo-
gens, which yielded no olefin products (entries 6–8). Inor-
ganic fluoride salts such as LiF, KF and CsF, were found
ineffective as well (entries 9–11). Only the starting mate-
rial was detected after four hours of reaction. In summary,
the reaction of TBAF hydrate with a primary iodide in
THF gives the best E/SN ratio (43/57, entry 4).
We next examined the effect of solvent on the E/SN ratio.
11-Iodoundecan-1-ol (1a) was mixed with four equiva-
lents of TBAF hydrate in various solvents at room temper-
1
Our team was interested in developing a methodology for
the synthesis of terminal olefins under mild conditions,
for use in cross-metathesis reactions generating inhibitors
of 17b-hydroxysteroid dehydrogenase.8 We knew that tet-
rabutylammonium fluoride (TBAF) – a reagent widely
ature. The results obtained by H NMR analysis of the
crude material are shown in Table 2. Nonpolar solvents
such as hexanes and toluene (entries 1, 2) mostly gave the
fluoride compound with an E/SN ratio close to 15:85. A
similar E/SN ratio was observed with 1,4-dioxane, dimeth-
yl sulfide and triethylamine (entries 3–5). Furthermore, a
mixture of nucleophilicity and basicity of the fluoride ion
is observed with sulfolane, THF, acetonitrile, acetone, py-
ridine and N-methyl-2-pyrrolidinone. The average E/SN
SYNTHESIS 2006, No. 18, pp 3085–3091
x
x.
x
x
.
2
0
0
6
Advanced online publication: 21.08.2006
DOI: 10.1055/s-2006-950204; Art ID: M08306SS
© Georg Thieme Verlag Stuttgart · New York

3086
M. Bérubé et al.
PAPER
Table 1 Dehydrohalogenation (E) or Nucleophilic Substitution (SN)
of 11-Halogenoundecan-1-ols with Various Fluoride or Ammonium
Ions in THFa
Table 2 Dehydrohalogenation (E) or Nucleophilic Substitution (SN)
of 11-Iodoundecan-1-ol (1a) with TBAF Hydrate in Various Solventsa
OH
TBAF hydrate
F
OH
3a (SN)
I
OH
+
OH
9
9
9
Y
OH
reagent
X
OH
+
9
9
9
solvent, 4 h, r.t.
1a
2a (E)
THF, 4 h, r.t.
3 (SN)
1
2 (E)
Entry
1
Solvent
hexanes
toluene
1,4-dioxane
DMS
Conversion (%)b E/SN
b
Entry
X
I
Reagentsb
Conversion E/SN
(%)c
Y
c
100
>90
>90
82
16:84
2
18:82
15:85
23:77
18:82
37:63
40:60
43:57
35:65
46:54
36:64
nd
1
2
3
TBAF
1 M in THF
100
100
8
43:57
15:85
0:100
F
F
F
3
Br
Cl
TBAF
1 M in THF
4
5
Et3N
100
75
TBAF
1 M in THF
6
sulfolane
THF
4
5
I
I
I
I
I
I
I
I
TBAF hydrate
TBAF on SiO2
TBACl
TBABr
TBAI
100
85
100
100
nd
0
43:57
40:60
0:100
0:100
0:100
nd
F
F
7
>90
76
8
MeCN
acetone
pyridine
6
Cl
Br
I
9
82
7
10
11
12
13
14
15
16
17
100
8
N-methyl-2-pyrrolidinone >90
9
LiF
F
CH2Cl2
0
0
10
11
KF
0
nd
F
MeOH
nd
CsF
0
nd
F
ethylene glycol
DMF
0
nd
a Substrate is dissolved in THF (0.03 M) with the reagent (4 equiv)
and stirred for 4 h at r.t.
100
100
100
64:36
66:34
72:28
b TBAF: tetrabutylammonium fluoride; TBACl: tetrabutylammoni-
um chloride; TBABr: tetrabutylammonium bromide; TBAI: tetrabu-
tylammonium iodide.
dimethylacetamide
DMSO
c Determined by 1H NMR analysis of the crude material.
a 11-Iodoundecan-1-ol was dissolved in the solvent (0.03 M) with
TBAF hydrate (4 equiv) and stirred for 4 h at r.t.
b Determined by 1H NMR analysis of the crude material.
ratio with these solvents is around 40:60 (entries 6–11).
On the other hand, no reaction was observed with the ha-
logenated solvent dichloromethane or a polar protic sol-
vent such as MeOH and ethylene glycol (entries 12–14).
However, the reaction mostly produced the olefin when a
polar aprotic solvent was used (entries 15–17), giving
a good E/SN ratio, especially with dimethyl sulfoxide
(E/SN = 72:28). This study of the effect of the nature of the
solvent on the E/SN ratio with TBAF revealed that the flu-
oride ion has a better nucleophilic activity in nonpolar sol-
vents and that its basicity character is more important in
polar aprotic solvents, particularly in dimethyl sulfoxide
(entry 17).
it must be noted that the concentration of 1-iodododecane
in dimethyl sulfoxide has a significant impact on the E/SN
ratio. Formation of the fluoride compound (SN) is more
important at high concentrations, while the olefin product
(E) is more abundant at low concentrations. Thus, the E/
SN ratio varies from 53:47 at 0.3 M to 86:14 at 0.003 M
(entries 3–8). A concentration of 0.01 M of alkyl iodide in
dimethyl sulfoxide was chosen to continue our optimiza-
tion, because lower concentrations did not significantly
improve the ratio and would involve the use of a large vol-
ume of solvent. The quantity of TBAF hydrate needed to
complete the reaction was also evaluated. It was found
that four equivalents of TBAF hydrate in dimethyl sulfox-
ide (0.01 M) were needed to rapidly complete the reaction
– in less than one hour (data not shown). The optimal tem-
perature was also investigated, but no significant effect
was observed on the E/SN ratio (data not shown).
After selecting dimethyl sulfoxide as the best solvent for
the reaction of elimination, TMAF, TEAF and TBAF
were compared as dehydrohalogenating reagents of 1-io-
dododecane (1b) (Table 3). At a concentration of 0.03 M,
no major differences were observed between these three
reagents, and the E/SN ratio only ranged from 68:32 to
73:27 (entries 1, 2 and 4). TBAF hydrate was then select-
ed as the reagent because it is more readily available and
less expensive than the other ammonium salts. However,
Representative primary and secondary iodides and bro-
mides were next subjected to the optimized reaction con-
ditions (Table 4). In all cases, total conversion was
Synthesis 2006, No. 18, 3085–3091 © Thieme Stuttgart · New York

PAPER
Synthesis of Terminal Olefins under Mild Conditions
3087
Table 3 Dehydrohalogenation (E) or Nucleophilic Substitution (SN)
of 1-Iodododecane (1b) with Ammonium Fluoride Ions in Various
Concentrations of DMSOa
Table 4 Dehydrohalogenation (2, E) or Nucleophilic Substitution
(3, SN) of Various Substrates with TBAF in DMSOa
b
Entry Substrate
Conversion E/SN
Yield
(%)c
F
reagent
I
9
9
1
(%)b
2:3
+
9
DMSO, 4 h, r.t.
3b (SN)
1b
2b (E)
OH
a
100
83:17
76
71
74
I
10
Reagentsb
Concentration Conversion
E/SN
c
Entry
b
100
100
83:17
83:17
DMSO (M)
(%)c
100
100
100
100
100
100
100
100
I
10
c
OTHP
10
1
2
3
4
5
6
7
8
TMAF
TEAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
0.03
71:29
68:32
53:47
73:27
82:18
83:17
85:15
86:14
I
I
0.03
d
100
100
85:15
85:15
72
64
O
8
9
0.3
e
f
O
O
0.03
I
I
I
I
I
0.01
100
100
100
100
100
100
100
100
82:18
84:16
82:18
81:19
100:0e
100:0f
100:0
100:0
20
70
76
69d
75
64
77
76
0.007
0.005
0.003
OH
10
g
h
i
O
OMe
NH2
10
a Compound 1b was dissolved in DMSO with reagent hydrate (4
equiv) and stirred for 4 h at r.t.
O
b TMAF: tetramethylammonium fluoride; TEAF: tetraethylammoni-
um fluoride; TBAF: tetrabutylammonium fluoride.
c Determined by 1H NMR analysis of the crude material.
9
9
9
O
NBuMe
observed by NMR analysis of crude material. Aliphatic
alkyl iodides (entries a–i) with an alcohol, ether, epoxide,
ketone, carboxylic acid, ester, primary amide and tertiary
amide as functional groups gave excellent E/SN ratio of
81:19 to 85:15 and good isolated yields of 64–76%. How-
ever, an exception was observed for carboxylic acid 1f
with an isolated yield of 20%. Indeed, for carboxylic acids
(entry f) and phenols (data not shown), the fluoride ion
acting as a base produces a carboxylate or a phenolate an-
ion, which can displace the iodide to afford oligomers.
Secondary alkyl halides (entries j,k) and phenethyl halide
derivatives (entries l,m) gave, as expected, only the E
product with good isolated yields of 64–77%. The internal
olefin was, however, the major product obtained with the
secondary alkyl bromides and iodides tested (entries j,k).
j
I
k
l
Br
9
I
Br
m
Br
Br
a Substrate was dissolved in DMSO (0.01 M) with TBAF hydrate (5
equiv) and stirred for 4 h at r.t.
b Determined by 1H NMR analysis of the crude material.
c Determined after purification by SiO2 chromatography, but given
only for the major component, olefin 2, of the mixture obtained.
A mixture of olefin and alkyl fluoride generated by our
dehydrohalogenation methodology was also tested for the d Obtained as a pure compound after chromatography.
e Dodec-1-ene/dodec-2-ene (10:90).
Grubbs olefin metathesis. Using typical reaction condi-
f Dodec-1-ene/dodec-2-ene (17:83).
tions previously reported for steroid derivatives,8,12 the
metathesis with 16b-allyl-3-(tert-butyldimethylsilyl)-17-
(tetrahydro-2H-pyranyl)estradiol and 2g/3g afforded the
perimental conditions, we improved the basicity of the
fluoride ion over its nucleophilic character, allowing the
formation of the expected terminal olefin as the major
compound. This one-step easy dehydrohalogenation pro-
cedure is a reasonable alternative to other more drastic
conditions of olefin synthesis such as pyrolysis and Hof-
mann elimination. Furthermore, this optimized methodol-
ogy is a complementary approach to the procedures that
exist to prepare terminal olefins by dehydrohalogenation
of alkyl halides. Because typical functional groups can
desired cross-metathesis compound in 85% yield after pu-
rification by chromatography. This experiment clearly
demonstrated that the small quantity of alkyl fluoride 3g
present with the olefin 2g is not a problem for the Grubbs
reaction.
In conclusion, we have developed a methodology for eas-
ily and rapidly preparing terminal olefins by dehydrohalo-
genation of primary alkyl iodides with TBAF in dimethyl
sulfoxide, at room temperature. By optimization of the ex-
Synthesis 2006, No. 18, 3085–3091 © Thieme Stuttgart · New York

3088
M. Bérubé et al.
PAPER
evaporated to dryness to afford 688 mg of crude 2-(9-bro-
mononyl)oxirane. The crude oxirane (200 mg) was dissolved in ac-
etone (2 mL) and NaI (422 mg, 2.82 mmol) was added. The mixture
was refluxed for 16 h and the product was extracted as described for
compound 1a. Flash chromatography (hexanes–EtOAc, 98:2) af-
forded 1d (204 mg, 86%) as a colorless oil.
tolerate the reaction conditions (TBAF, DMSO, room
temperature) this new methodology could be useful for
preparing a variety of terminal olefins under mild condi-
tions.
Anhyd solvents were purchased from Aldrich and VWR in SureSeal
bottles, which were conserved under positive argon pressure. Usual
solvents were obtained from Fisher Scientific (Montreal, QC, Can-
ada) and VWR (Ville Mont-Royal, QC, Canada) and were used as
received. Reagents and starting material were obtained from Sigma-
Aldrich Canada Co. (Oakville, ON, Canada). TLC was performed
on 0.25 mm silica gel 60 F254 plates from Whatman (distributed by
Fisher Scientific) and compounds were visualized by exposure to
UV light (254 nm) and/or with a solution of ammonium molybdate/
H2SO4/H2O (with heating). Flash chromatography was performed
on Silicycle 60 (Québec, QC, Canada) 230–400-mesh silica gel. IR
spectra were obtained neat or from a thin film of the solubilized
compound on NaCl pellets (usually in CH2Cl2). They were recorded
on a PerkinElmer series 1600 FT-IR spectrometer (Norwalk, CT,
USA). 13C NMR spectra were recorded with a Bruker AC/F 300
spectrometer (Billerica, MA, USA) at 75 MHz and 1H NMR spectra
were recorded with a Bruker AVANCE 400 spectrometer at 400
MHz. The chemical shifts (d) are expressed in ppm and referenced
to CHCl3 (7.26 and 77.0 ppm) or acetone (2.07 and 206.0 ppm) for
1H and 13C respectively. Low-resolution mass spectra (LRMS) were
recorded with an LCQ Finnigan apparatus (San Jose, CA, USA)
equipped with an atmospheric pressure chemical ionization (APCI)
source on positive or negative mode.
IR (neat): 3044, 2926, 2853, 1716, 1456, 1428, 1362, 1258, 1221,
1190, 1167, 914, 832, 720 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.25–1.50 (m, 12 H, 6 × CH2),
1.51 (m, 2 H, CH2CO), 1.81 (m, 2 H, CH2CH2I), 2.45 (dd, J = 5.0,
2.8 Hz, 1 H, CH2O), 2.74 (dd, J = 5.0, 4.1 Hz, 1 H, CH2O), 2.90 (m,
1 H, CHO), 3.18 (t, J = 7.0 Hz, 2 H, CH2I).
13C NMR (75 MHz, CDCl3): d = 7.3, 25.9, 28.4, 29.3, 29.4 (2 ×),
30.4, 32.4, 33.5, 47.1, 52.4.
LRMS: m/z [M + H]+ calcd for C11H22IO: 297.1; found: 296.9.
12-Iodododecan-2-one (1e)
To a solution of 11-bromoundecanoic acid (1.01 g, 3.8 mmol) in
THF (25 mL) under argon was slowly added MeLi (4.69 mL, 7.5
mmol) at –78 °C and the reaction was kept at 0 °C for 1 h. An aq
solution of NH4Cl was then added and the product extracted with
Et2O. The organic phase was dried (MgSO4) and evaporated to dry-
ness (963 mg). A portion of the crude ketone (713 mg) was dis-
solved in acetone (13.5 mL) and NaI (1.6 g, 10.84 mmol) was
added. The mixture was refluxed for 24 h and the product was ex-
tracted as described for compound 1a. Flash chromatography (hex-
anes–EtOAc, 95:5) afforded 1e (598 mg, 69%) as a white solid.
IR (film): 2926, 2852, 1716, 1462, 1425, 1359, 1161 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.25 to 1.70 (m, 14 H, 7 × CH2),
1.82 (m, 2 H, CH2CH2I), 2.14 (s, 3 H, COCH3), 2.42 (t, J = 7.4 Hz,
2 H, CH2CO), 3.19 (t, J = 7.0 Hz, 2 H, CH2I).
13C NMR (75 MHz, CDCl3): d = 7.3, 23.8, 28.5, 29.1, 29.3 (3 ×),
29.8, 30.4, 33.5, 43.8, 209.3.
w-Halo-Substituted Substrates (Table 4)
11-Iodoundecan-1-ol (1a)13
11-Bromoundecan-1-ol (5.00 g, 19.9 mmol) was dissolved in ace-
tone (50 mL) and NaI (10.4 g, 69.6 mmol) was added. The mixture
was refluxed for 16 h. The product was then extracted with EtOAc
and the organic phase was washed with a sat. aq solution of
Na2S2O3, washed with brine, dried (MgSO4) and evaporated to dry-
ness. Flash chromatography (hexanes–EtOAc, 9:1 to 8:2) afforded
1a (5.63 g, 95%) as an off-white solid.
LRMS: m/z [M + H]+ calcd for C12H24IO: 311.1; found: 310.9.
12-Iodododecanoic Acid (1f)
12-Bromododecanoic acid (1.00 g, 3.58 mmol) was dissolved in ac-
etone (18 mL) and NaI (2.15 g, 14.3 mmol) was added. The mixture
was refluxed for 16 h. The mixture was cooled down to r.t. and the
crude product was extracted with Et2O. The organic phase was
washed with sat. aq solution of Na2S2O3. The product was next ex-
tracted with NaOH (10% in H2O). The aqueous phase was acidified
with HCl (10% in H2O) and the product was extracted with Et2O.
The last organic phase was washed with brine, dried (MgSO4) and
evaporated to dryness to afford 1f (788 mg, 68%) as a white solid.
1H NMR data are in agreement with those reported.16
IR (film): 3392, 2918, 2850, 1466, 1342, 1260, 1198, 1168, 1050,
1033, 908, 722, 604 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.28 (m, 14 H, 7 × CH2), 1.47 (br
s, 1 H, OH), 1.57 (m, 2 H, CH2CH2OH), 1.82 (m, 2 H, CH2CH2I),
3.19 (t, J = 7.0 Hz, 2 H, CH2I), 3.65 (t, J = 6.6 Hz, 2 H, CH2OH).
13C NMR (75 MHz, CDCl3): d = 7.3, 25.6, 28.4, 29.2 (2 ×), 29.3,
29.4, 30.3, 32.5, 33.4, 62.6.
LRMS: m/z [M – H2O + H]+ calcd for C11H22I: 281.1; found: 280.9.
13C NMR (75 MHz, CDCl3): d = 7.4, 24.6, 28.5, 29.0, 29.2, 29.3
(2 ×), 29.4, 30.5, 33.5, 34.0, 179.6.
12-Iodododecane (1b)
Commercially available.
Methyl 12-Iodododecanoate (1g)
2-[(11-Iodoundecyl)oxy]tetrahydro-2H-pyran (1c)
2-[(11-Bromoundecyl)oxy]tetrahydro-2H-pyran14 (400 mg, 1.19
mmol) was dissolved in acetone (3 mL) and NaI (626 mg, 4.2
mmol) was added. The mixture was refluxed for 16 h and the prod-
uct was extracted as described for compound 1a. Flash chromatog-
raphy (hexanes–EtOAc, 9:1) afforded 1c (320 mg, 70%) as a
colorless oil. 1H NMR data are in agreement with those reported.15
To a solution of 1f (350 mg, 1.07 mmol) in anhyd MeOH (10 mL)
at 0 °C under argon was added TMSCHN2 (2.0 M in hexanes) (3.2
mL, 6.43 mmol). After 15 min., the solvent was evaporated to dry-
ness. The crude product was purified by flash chromatography
(hexanes–EtOAc, 95:5) to afford 1g [232 mg, 64% (non-optimized
yield)] as a colorless oil.
IR (neat): 2925, 2853, 1740, 1461, 1437, 1361, 1249, 1196, 1167,
1120 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.25 to 1.40 (m, 14 H, 7 × CH2),
1.61 (m, 2 H, CH2CH2CO), 1.81 (m, 2 H, CH2CH2I), 2.30 (t, J = 7.5
Hz, 2 H, CH2CO), 3.19 (t, J = 7.0 Hz, 2 H, CH2I), 3.66 (s, 3 H,
OCH3).
2-(9-Iodononyl)oxirane (1d)
To a solution of 11-bromoundec-1-ene (420 mL, 2.14 mmol) in an-
hyd CH2Cl2 (40 mL) at 0 °C under argon was added MCPBA (554
mg, 3.2 mmol) and the mixture was stirred for 16 h at 0 °C. The sol-
vent was evaporated and the crude product was extracted with
EtOAc. The organic phase was washed with an aq solution of
Na2S2O3 (10%) and sat. aq solution of NaHCO3, dried (MgSO4) and
Synthesis 2006, No. 18, 3085–3091 © Thieme Stuttgart · New York

PAPER
Synthesis of Terminal Olefins under Mild Conditions
3089
13C NMR (75 MHz, CDCl3): d = 7.4, 24.9, 28.4, 29.1, 29.2, 29.3
(2 ×), 29.4, 30.4, 33.5, 34.0, 51.4, 174.3.
IR (neat): 3058, 2957, 1682, 1596, 1568, 1472, 1427, 1256, 1235,
1199, 1171, 1071, 997, 883, 846, 783, 689, 668, 630 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.15 (t, J = 7.7 Hz, 2 H,
CH2CH2I), 3.33 (t, J = 7.9 Hz, 2 H, CH2I), 7.13 (d, J = 7.6 Hz, 1 H,
4-CH), 7.20 (t, J = 7.7 Hz, 1 H, 5-CH), 7.35 (d, J = 1.6 Hz, 1 H, 2-
CH), 7.40 (dd, J = 7.9, 1.1 Hz, 1 H, 6-CH).
LRMS: m/z [M – H2O + H]+ calcd for C13H26IO2: 341.1; found:
340.9.
11-Iodoundecanamide (1h)
To a solution of 11-bromoundodecanoic acid (1.02 g, 3.9 mmol) in
anhyd CH2Cl2 (25 mL) were added oxalyl chloride (0.5 mL) and
DMF (1 mL). After 1 h at 0 °C, the solvent was evaporated and the
crude acid chloride was dissolved in anhyd benzene under argon
and reacted with 28% NH4OH (3 mL). After 15 min, H2O was add-
ed, the aqueous phase extracted with CH2Cl2 and the organic phase
dried (MgSO4) and evaporated under vacuum (952 mg). A portion
of the crude amide (707 mg) was dissolved in acetone (13.4 mL)
and NaI (1.6 g, 10.84 mmol) was added. The mixture was refluxed
for 24 h and the product was extracted as described for compound
1a. Flash chromatography (hexanes–acetone, 60:40) afforded 1h
(680 mg, 82%) as a white solid.
13C NMR (75 MHz, CDCl3): d = 4.9, 39.6, 122.6, 127.0, 129.9,
130.1, 131.3, 142.6.
1-Bromo-3-(2¢-bromoethyl)benzene (1m)
To a solution of 3-bromophenethyl alcohol (688 mg, 3.42 mmol) in
anhyd CH2Cl2 (43 mL) at 0 °C under argon was added Ph3P (1.79 g,
6.84 mmol) and CBr4 (2.27 g, 6.84 mmol). The mixture was stirred
at r.t. After 2 h, the mixture was quenched with a sat. aq solution of
NaHCO3. The product was extracted with CH2Cl2. The organic
phase was washed with brine, dried (MgSO4) and evaporated to dry-
ness. Purification by flash chromatography (hexanes–EtOAc, 99:1
to 95:5) provided 1m (528 mg, 58%) as a colorless oil.
IR (film): 3346, 3184, 2916, 2848, 1634, 1468, 1410, 1325, 1297,
1265, 1232, 1199, 1162, 1140 cm–1.
1H NMR (400 MHz, acetone-d6): d = 1.25–1.45 (m, 12 H, 6 × CH2),
1.59 (m, 2 H, CH2), 1.83 (m, 2 H, CH2CH2I), 2.16 (t, J = 7.5 Hz, 2
H, CH2CO), 3.30 (t, J = 7.0 Hz, 2 H, CH2I), 6.0 and 6.7 (2 br s, 2 H,
CONH2).
IR (neat): 3059, 2963, 2876, 1593, 1568, 1474, 1428, 1258, 1216,
1072, 997, 889, 849, 779, 697, 667, 651, 548 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.14 (t, J = 7.4 Hz, 2 H,
CH2CH2Br), 3.55 (t, J = 7.5 Hz, 2 H, CH2Br), 7.18 (m, 2 H, 4-CH
and 5-CH), 7.39 (m, 2 H, 2-CH and 6-CH).
13C NMR (75 MHz, CDCl3): d = 32.3, 38.7, 122.5, 127.3, 130.0,
130.1, 131.7, 141.0.
13C NMR (75 MHz, acetone-d6): d = 7.9, 26.2, ~30 (5 ×, under sol-
vent peaks), 31.1, 34.4, 36.1, 174.9.
LRMS: m/z [M + H]+ calcd for C11H23INO: 312.1; found: 312.0.
Dehydrohalogenation of w-Halo-Substituted Substrates; Un-
dec-10-en-1-ol (2a); Typical Procedure
11-Iodoundecanoic Acid Butylmethylamide (1i)
11-Iodoundecan-1-ol (200 mg, 0.67 mmol) was dissolved in DMSO
(70 mL). TBAF hydrate (876 mg, 3.35 mmol) was added and the
mixture was stirred for 4 h at r.t. The reaction was then quenched
with H2O and the product was extracted with EtOAc. The organic
phase was washed with H2O (to remove traces of DMSO), washed
with brine, dried (MgSO4) and evaporated to dryness. The crude
product was purified by silica gel chromatography with 10–30%
EtOAc in hexanes to afford a mixture of 2a19 (87 mg, 76%) and 11-
fluoroundecan-1-ol (3a); ratio 2a/3a = 83:17. In Table 4, yield of 2
N-Butyl-N-methyl-11-bromoundecanamide17 (400 mg, 1.196
mmol) was dissolved in acetone (3 mL) and NaI (627 mg, 4.2
mmol) was added. The mixture was refluxed for 16 h and the prod-
uct was extracted as described for compound 1a. Flash chromatog-
raphy (hexanes–EtOAc, 5:5) provided 1i (365 mg, 80%) as a yellow
viscous solid.
IR (film): 2926, 2853, 1648, 1458, 1296, 1260, 1210, 1079, 726
cm–1.
1
was calculated based on H NMR ratio. The peaks corresponding
1H NMR (400 MHz, CDCl3): d = 0.93 (m, 3 H, CH2CH3), 1.25–1.40
(m, 16 H, 8 × CH2), 1.50 (m, 2 H, CH2CH2N), 1.61 (m, 2 H,
CH2CH2CO), 1.80 (m, 2 H, CH2CH2I), 2.28 (m, 2 H, CH2CO), 2.90
and 2.96 (2 s, 3 H, NCH3), 3.17 (t, J = 7.0 Hz, 2 H, CH2I), 3.24 and
3.35 (2 t, J = 7.4 Hz, 2 H, CH2N).
13C NMR (75 MHz, CDCl3): d = 7.4, 13.8, 20.0, 25.1 (25.5), 28.5,
29.3 (5 ×), 29.4 (30.6), 30.4, 32.9 (33.3), 33.5 (35.3), 47.4 (49.8),
172.9.
specifically to the minor product 3 are written between brackets in
order to simplify the description of the 1H NMR spectra (Table 4).
1H NMR (400 MHz, CDCl3): d = 1.25–1.40 (m, 10 H, 5 × CH2),
1.46 (m, 2 H, CH2CH2CH=), 1.56 (m, 2 H, CH2CH2OH), [1.68 (m,
2 H, CH2CH2F)], 2.04 (m, 2 H, CH2CH=), 3.64 (t, J = 6.6 Hz, 2 H,
CH2OH), [4.44 (dt, J = 47.4, 6.2 Hz, 2 H, CH2F)], 4.96 (m, 2 H,
CH=CH2), 5.81 (m, 1 H, CH=CH2).
Dodec-1-ene (2b)19
Ratio 2b/3b = 83:17.
LRMS: m/z [M + H]+ calcd for C16H33INO: 382.2; found: 382.1.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 6.8 Hz, CH3), 1.20–
1.35 (m, 14 H, 7 × CH2), 1.37 (t, J = 6.9 Hz, 2 H, CH2CH2CH=),
[1.68 (m, 2 H, CH2CH2F)], 2.04 (m, 2 H, CH2CH=), [4.44 (dt,
J = 47.4, 6.2 Hz, 2 H, CH2F)], 4.97 (m, 2 H, CH=CH2), 5.82 (m,
1 H, CH=CH2).
2-Iodododecane (1j)
To a solution of 1k (400 mg, 1.60 mmol) in acetone (8 mL) was add-
ed NaI (962 mg, 6.42 mmol). The mixture was refluxed for 16 h and
the product was extracted as described for compound 1a. Flash
chromatography (hexanes–EtOAc, 95:5) afforded 1j (430 mg, 91%)
as a yellowish oil. 1H NMR data are in agreement with those report-
ed.18
11-(Tetrahydropyran-2¢-yloxy)undec-1-ene (2c)20
Ratio 2c/3c = 83:17.
2-Bromododecane (1k)
Commercially available.
1H NMR (400 MHz, CDCl3): d = 1.25–1.30 (m, 10 H, 5 × CH2),
1.35 (m, 2 H, CH2CH2CH=), 1.50–1.75 (m, 8 H, CH2CH2OTHP and
3 × CH2 of THP), 2.03 (m, 2 H, CH2CH=), 3.38 and 3.72 (2 m, 2 H,
CH2OTHP), 3.51 and 3.87 (2 m, 2 H, CH2O of THP), [4.43 (dt,
J = 47.4, 6.2 Hz, 2 H, CH2F)], 4.58 (m, 1 H, OCH of THP), 4.96 (m,
2 H, CH=CH2), 5.81 (m, 1 H, CH=CH2).
1-Bromo-3-(2¢-iodoethyl)benzene (1l)
To a solution of 1m (260 mg, 0.985 mmol) in acetone (5 mL) was
added NaI (738 mg, 4.92 mmol). The reaction mixture was refluxed
for 16 h and the product was extracted as described for compound
1a. Flash chromatography (hexanes–EtOAc, 95:5) afforded 1l (230
mg, 75%) as a yellowish oil.
Synthesis 2006, No. 18, 3085–3091 © Thieme Stuttgart · New York

3090
M. Bérubé et al.
PAPER
2-(Non-8-enyl)oxirane (2d)21
Ratio 2d/3d = 85:15.
1H NMR (400 MHz, CDCl3): d = 1.25–1.50 (m, 10 H, 5 × CH2),
1.52 (m, 2 H, CH2CHO), [1.68 (m, 2 H, CH2CH2F)], 2.04 (m, 2 H,
CH2CH=), 2.46 (dd, J = 5.0, 2.8 Hz, 1 H, CH2O), 2.75 (dd, J = 4.9,
4.2 Hz, 1 H, CH2O), 2.88 (m, 1 H, CHO), [4.44 (dt, J = 47.4, 6.2 Hz,
2 H, CH2F)], 4.96 (m, 2 H, CH=CH2), 5.81 (m, 1 H, CH=CH2).
3-Bromostyrene (2l and 2m)19
1H NMR (400 MHz, CDCl3): d = 5.30 (d, J = 10.9 Hz, 1 H,
CH2=CH), 5.76 (d, J = 17.5 Hz, 1 H, CH2=CH), 6.64 (dd,
J = 17.5, 10.9 Hz, 2 H, CH=CH2), 7.20 (t, J = 7.8 Hz, 1 H, 5-CH),
7.32 (d, J = 7.8 Hz, 1 H, 6-CH), 7.38 (dd, J = 7.8, 1.7 Hz, 1 H, 4-
CH), 7.56 (t, J = 1.7 Hz, 2-CH).
Acknowledgment
Dodec-11-en-2-one (2e)22
Ratio 2e/3e = 85:15.
We are grateful to the Canadian Institutes of Health Research
(CIHR) for funding (D.P.) and scholarships (M.B.). Careful reading
of the manuscript by Sylvie Méthot is also greatly appreciated.
Thanks also to Mohan S. Singh, René Maltais and Richard
Labrecque for discussions.
1H NMR (400 MHz, CDCl3): d = 1.20–1.50 (m, 10 H, 5 × CH2),
1.56 (m, 2 H, CH2CH2CH=), [1.70 (m, 2 H, CH2CH2F)], 2.03 (m, 2
H, CH2CH=), 2.13 (s, 3 H, COCH3), 2.42 (t, J = 7.4 Hz, 2 H,
CH2CO), [4.44 (dt, J = 47.3, 6.2 Hz, 2 H, CH2F)], 4.96 (m, 2 H,
CH=CH2), 5.81 (m, 1 H, CH=CH2).
References
Dodec-11-enoic Acid (2f)23
Ratio 2f/3f = 82:18.
(1) (a) Connon, S. J.; Blechert, S. Angew. Chem. Int. Ed. 2003,
42, 1900. (b) Grubbs, R. H.; Chang, S. Tetrahedron 1998,
54, 4413.
(2) Larock, R. C. Comprehensive Organic Transformations: A
Guide to Functional Group Preparations; 2nd ed., Wiley-
VCH: New York, 1999, 256–258.
(3) Henningsen, M. C.; Jeropoulos, S.; Smith, E. H. J. Org.
Chem. 1989, 54, 3015.
(4) Soderquist, J. A.; Vaquer, J.; Diaz, M. J.; Rane, A. M.
Tetrahedron Lett. 1996, 37, 2561.
(5) (a) Wood, N. F.; Chang, F. C. J. Org. Chem. 1965, 30, 2054.
(b) Veeravagu, P.; Arnold, R. T.; Eigenmann, E. W. J. Am.
Chem. Soc. 1964, 86, 3072. (c) Hostetler, E. D.; Fallis, S.;
McCarthy, T. J.; Welch, M. J.; Katzenellenbogen, J. A. J.
Org. Chem. 1998, 63, 1348.
1H NMR (400 MHz, CDCl3): d = 1.25–1.40 (m, 12 H, 6 × CH2),
1.63 (m, 2 H, CH2CH2CO), [1.66 (m, 2 H, CH2CH2F)], 2.03 (m, 2
H, CH2CH=), 2.34 (t, J = 7.5 Hz, 2 H, CH2CO), [4.44 (dt, J = 47.4,
6.2 Hz, 2 H, CH2F)], 4.96 (m, 2 H, CH=CH2), 5.80 (m, 1 H,
CH=CH2).
Methyl Dodec-11-enoate (2g)24
Ratio 2g/3g = 84:16.
1H NMR (400 MHz, CDCl3): d = 1.25–1.30 (m, 10 H, 5 × CH2),
1.36 (m, 2 H, CH2CH2CH=), 1.59 (m, 2 H, CH2CH2CO), [1.66 (m,
2 H, CH2CH2F)], 2.03 (m, 2 H, CH2CH=), 2.30 (t, J = 7.5 Hz, 2 H,
CH2CO), 3.66 (s, 3 H, CH3), [4.44 (dt, J = 47.4, 6.2 Hz, 2 H,
CH2F)], 4.96 (m, 2 H, CH=CH2), 5.81 (m, 1 H, CH=CH2).
(6) (a) Oediger, H.; Möller, F.; Eiter, K. Synthesis 1972, 591.
(b) Hareau, G. P. J.; Neya, S.; Funasaki, N.; Taniguchi, I.
Tetrahedron Lett. 2002, 43, 3109. (c) Bianco, A.;
Cavarischia, C.; Guiso, M. Eur. J. Org. Chem. 2004, 2894.
(7) No alkene was observed when a primary alkyl iodide (1-
iodododecane) was treated with DBU in benzene or DMSO
at r.t. or at 90 °C.
(8) Bérubé, M.; Poirier, D. Org. Lett. 2004, 6, 3127.
(9) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; 3rd ed., Wiley-Interscience: New York, 1999,
127–141.
Undec-10-enamide (2h)25
Ratio 2h/3h = 82:18.
1H NMR (400 MHz, acetone-d6): d = 1.25–1.50 (m, 10 H, 5 × CH2),
1.59 (m, 2 H, CH2CH2CH=), [1.65 (m, 2 H, CH2CH2F)], 2.03 (m, 2
H, CH2CH=), 2.17 (t, J = 7.4 Hz, 2 H, CH2CO), [4.44 (dt,
J = 47.6, 6.1 Hz, 2 H, CH2F)], 4.96 (m, 2 H, CH=CH2), 5.82 (m, 1
H, CH=CH2), 6.0 and 6.7 (2 br s, 2 H, CONH2).
Undec-10-enoic Acid Butylmethylamide (2i)
Compound 2i was obtained as a pure product after purification.
(10) (a) Cox, D. P.; Terpinski, J.; Lawrynowicz, W. J. Org.
Chem. 1984, 49, 3216. (b) Matsumoto, T.; Ohsaki, M.;
Matsuda, F.; Terashima, S. Tetrahedron Lett. 1987, 28,
4419.
(11) (a) Albanese, D.; Landini, D.; Penso, M. J. Org. Chem.
1998, 63, 9587. (b) Kvicala, J.; Mysik, P.; Paleta, O. Synlett
2001, 547. (c) Moughamir, K.; Atmani, A.; Mestdagh, H.;
Rolando, C.; Francesch, C. Tetrahedron Lett. 1998, 39,
7305. (d) Bosch, P.; Camps, F.; Chamorro, E.; Gasol, V.;
Guerrero, A. Tetrahedron Lett. 1987, 28, 4733.
(12) Bérubé, M.; Laplante, Y.; Poirier, D. Med. Chem. 2006, 2,
329.
(13) Percec, V.; Chu, P.; Kawasumi, M. Macromolecules 1994,
27, 4441.
(14) Reetz, M. T.; Rüggeberg, C. J.; Dröge, M. J.; Quax, W. J.
Tetrahedron 2002, 58, 8465.
(15) Wasserman, H. H.; Gambale, R. J.; Pulwer, M. J.
Tetrahedron 1981, 37, 4059.
(16) Schull, T. L.; Olano, L. R.; Knight, D. A. Tetrahedron 2000,
56, 7093.
IR (film): 2926, 2854, 1648, 1466, 1400, 1298, 1266, 1210, 1141,
1113, 1085, 997 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.94 (m, 3 H, CH2CH3), 1.25 to
1.40 (m, 12 H, 6 × CH2), 1.50 (m, 2 H, CH2CH2N), 1.62 (m, 2 H,
CH2CH2CO), 2.02 (m, 2 H, CH2CH=), 2.29 (t, J = 7.5 Hz, 2 H,
CH2CO), 2.91 and 2.96 (2 s, 3 H, NCH3), 3.25 and 3.36 (2 t, J = 7.2
Hz, 2 H, CH2N), 4.96 (m, 2 H, CH=CH2), 5.81 (m, 1 H, CH=CH2).
13C NMR (75 MHz, CDCl3): d = 13.9, 20.0, 25.1 (25.5), 28.9, 29.1,
29.4 (4 ×), 29.5 (30.6), 33.0 (33.6), 33.8 (35.3), 47.4 (49.8), 114.1,
139.2, 173.0.
LRMS: m/z [M + H]+ calcd for C16H32NO: 254.3; found: 254.2.
Dodec-2-ene26/Dodec-1-ene19 (2j: 90:10/ 2k: 83:17)
Peaks corresponding specifically to the minor product dodec-1-ene
are given between brackets.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 6.8 Hz, CH3), 1.20–
1.40 (m, 14 H, 7 × CH2), 1.64 (m, 3 H, CH3CH=), 1.95 (m, 2 H,
CH2CH=), [2.03 (m, 2 H, CH2CH=)], [4.97 (m, 2 H, CH=CH2)],
5.42 (m, 2 H, CH=CH), [5.82 (m, 1 H, CH=CH2)].
(17) Poirier, D.; Auger, S.; Mérand, Y.; Simard, J.; Labrie, F. J.
Med. Chem. 1994, 37, 1115.
Synthesis 2006, No. 18, 3085–3091 © Thieme Stuttgart · New York

PAPER
Synthesis of Terminal Olefins under Mild Conditions
3091
(18) Hamann-Gaudinet, B.; Namy, J. L.; Kagan, H. B. J.
Organomet. Chem. 1998, 567, 39.
(22) Sato, K.; Aoki, M.; Takagi, J.; Noyori, R. J. Am. Chem. Soc.
1997, 119, 12386.
(23) Godfrey, A. G.; Ganem, B. J. Am. Chem. Soc. 1990, 112,
3717.
(19) The Aldrich Library of 13C and 1H FT NMR Spectra; Aldrich
Chemical Co., Inc.: St. Louis MO, 1993.
(20) Cryle, M. J.; Matovic, N. J.; De Voss, J. J. Org. Lett. 2003,
5, 3341.
(24) Cardinale, G.; Laan, J. A. M.; Ward, J. P. Tetrahedron 1985,
41, 2899.
(21) Hwang, C. E.; Keum, G.; Sohn, K. I.; Lee, D. H.; Lee, E.
Tetrahedron Lett. 2005, 46, 6621.
(25) Dobashi, Y.; Hara, S. J. Org. Chem. 1987, 52, 2490.
(26) Baudin, J. B.; Julia, S. A. Tetrahedron Lett. 1989, 30, 1967.
Synthesis 2006, No. 18, 3085–3091 © Thieme Stuttgart · New York