Boron trihalide mediated haloallylation of aryl aldehydes and its application to the preparation of (E)-1,3-dienes

Article abstract of DOI:10.1055/s-0031-1289304

In the presence of boron trihalides, aryl aldehydes couple readily with allylmetals to afford haloallylated products. The reactions tolerate a variety of functional groups. Simple aqueous workup of haloallylation reactions, followed by treatment with 1,8-

Full text of DOI:10.1055/s-0031-1289304

PAPER
3815
Boron Trihalide Mediated Haloallylation of Aryl Aldehydes and Its
Application to the Preparation of (E)-1,3-Dienes
Boron
Trihalide
M
edia
i
ted
H
a
c
loallylation
h
of
A
ryl
A
ld
a
e
hydes el P. Quinn, Min-Liang Yao, Li Yong, George W. Kabalka*
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, TN 37996-1600, USA
Fax +1(865)9742997; E-mail: kabalka@utk.edu
Received 17 August 2011; revised 27 September 2011
ther (Z,E)-penta-1,4-dienes or (Z,Z)-penta-1,4-dienes.12
Interestingly, in these reactions boron trihalides are found
to simultaneously act as both Lewis acids and reactants.
Mechanistic investigation of these coupling reactions led
Abstract: In the presence of boron trihalides, aryl aldehydes couple
readily with allylmetals to afford haloallylated products. The reac-
tions tolerate a variety of functional groups. Simple aqueous work-
up of haloallylation reactions, followed by treatment with 1,8-
diazabicyclo[5.4.0]undec-7-ene, provides a straightforward route to to the discovery of a transition-metal-free, formal Suzuki
coupling of alkoxides with vinylboron dihalides13 and the
synthetically useful (E)-1,3-dienes. The mild reaction conditions,
readily available starting materials, and high stereoselectivity make
boron trichloride mediated coupling of alkoxides with al-
this two-step (E)-1,3-diene synthesis quite attractive.
lylsilane.14
Key words: boron trihalide, allylmetal, haloallylation, diene, ste-
We recently discovered that the reaction of aromatic alde-
reoselectivity
hydes with allyltrimethylsilane affords haloallylation
products rather than homoallylic alcohols in good to ex-
cellent yields when a slight excess of BX3 was used
Boron trihalides (BX3, X = F, Cl, Br, I) are strong Lewis
(Scheme 1).15 Through a series of control experiments, it
acids and are widely used as ether cleavage reagents.1 No-
was confirmed that chloroallylated product 2 was generat-
table features of boron trihalide ether cleavage reactions
ed from intermediate 1 through a C–O bond cleavage. In
include mild reaction conditions and high regio- and
fact, in a kinetic study of the reaction between a carbo-
chemoselectivities. In addition, there is a great deal of in-
cation and allylsilane, Mayr noted chloroallylation of the
terest in reactions of boron trihalides with N,O-based
aryl aldehyde in the presence of 2–4 equivalents of boron
chiral ligands because the chiral boron Lewis acids thus
trichloride.16
obtained induce enantioselective Diels–Alder reactions.2
As haloboration reagents, boron trichloride and boron tri-
Cl2BO
Cl
bromide are used to synthesize (Z)-2-haloalk-1-enylboron
halides,3 highly functionalized intermediates that play an
important role in the syntheses of vinyl halides, alka-
dienes, alkenynes, and polyenes.4 Boron trihalides are
used as halogenation reagents in conversions of alcohols
into the corresponding halides.5 Halogen exchange be-
tween alkyl halides and boron trihalides has also been re-
ported.6
CHO
BCl3
(1.1 equiv)
Z
Z
Z
allylsilane
hexanes
1
2
Scheme 1 Haloallylation of benzaldehyde derivatives
Considering the efficiency of this haloallylation reaction,
the ready availability of starting materials (when com-
pared to recent reports focused on the preparation of ha-
loallylated products based on N-allylhydrazones17 and 1-
arylbut-3-en-1-ols18) and the potential of converting ha-
loallylated products into synthetically useful 1,3-dienes,
we decided to investigate the haloallylation reaction in de-
tail. Reactions with allyltriethylgermane and allyltriphe-
nylstannane were also investigated. Herein we present the
details of a study focused on the haloallylation reaction to-
gether with its application in the synthesis of (E)-1,3-
dienes.
Boron trihalides readily form crystalline complexes with
carbonyl compounds.7 Boron trifluoride complexes are
quite stable and have been used as reaction accelerators8
while boron trichloride complexes tend to be unstable.
Boron trichloride complexes of aliphatic aldehydes, such
as propanal, have been found to undergo chlorination to
form bis(a-chloroethyl) ethers;9 while aromatic aldehydes
slowly form aryldichloromethanes.10
In recent years, our research group has discovered several
novel coupling reactions using BX3 reagents. These in-
clude the BX3-mediated coupling of aryl aldehydes and
styrene derivatives to regioselectively produce 1,3-diaryl-
1,3-dihalopropanes (syn/anti 50:50)11 and the BX3-medi-
ated coupling of aryl aldehydes and alkynes to afford ei-
As previously reported, in the presence of 1.1 equivalents
of a boron trihalide, most aryl aldehydes react smoothly
with allyltrimethylsilanes to afford the haloallylated prod-
ucts 2 in good to excellent yields with the exception of p-
anisaldehyde (due to a competing ether cleavage
reaction1). Generally speaking, reactions with aldehydes
bearing electron-donating groups take place smoothly at
SYNTHESIS 2011, No. 23, pp 3815–3820
x
x.
x
x
.
2
0
1
1
Advanced online publication: 20.10.2011
DOI: 10.1055/s-0031-1289304; Art ID: M81011SS
© Georg Thieme Verlag Stuttgart · New York

3816
M. P. Quinn et al.
PAPER
0 °C while reactions of aldehydes bearing electron-with-
drawing groups require elevated temperatures (Table 1).
Reactions with boron tribromide are faster than those us-
ing boron trichloride. Bromoallylated product 2n formed
exclusively when a mixture of boron tribromide and boron
trichloride (1.1 equivalents each) was added to 4-chlo-
robenzaldehyde, demonstrating a high chemoselectivity.
CHO
BCl3 (2.2 equiv)
0 °C to r.t., 1 h
SiMe3
+
hexanes
Me2N
3
81%
NMe2
Scheme 2 Direct formation of diene
Table 1 BX3-Mediated Haloallylation of Aryl Aldehydes Using Al-
Haloallylation using 2-bromoallyltrimethylsilane pro-
duced the desired chloroallylated product 4 along with the
unexpected 1,3-dichloro product 5 (Scheme 3).
lyltrimethylsilanea
CHO
X
R
BX3
R
Z
Z
+
CHO
Cl
Br
Cl
Cl
SiMe3
Br
hexanes
2
BCl3
Z
Z
+ Z
+
Entry
Z
R
X
Time
(min)
Product Yieldb
(%)
SiMe3
4a,b
5a,b
Total yield (4 + 5)
Ratio (4/5)
1
2
4-Cl
4-F
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
20
30
2a
2b
2c
2d
2e
2f
90
62
85
87
73
62
61
94
92
94
69
67
89
81
72
78
63
8 : 1
2 : 1
a Z = 2-Me
b Z = 4-Cl
92%
95%
H
Scheme 3 Chloroallylation using 2-bromoallyltrimethylsilane
3
H
H
30
A tentative reaction mechanism is presented (Scheme 4)
to explain the formation of product 5. Intermediate 6 is
generated by Lewis acid activation of the aryl aldehyde
with boron trichloride in the presence of 2-bromoallyltri-
methylsilane. Subsequent addition of chloride to interme-
diate 6 affords intermediate 7 (pathway a). Elimination of
the bromine during silyl electrofuge cleavage produces
the unintended dichloro compound 5. If the chloride at-
tacks the silyl group in intermediate 6 (pathway b), the re-
action will generate the desired chloroallylation product 4.
At present, it is difficult to rule out the possibility that 4
might be generated through intermediate 7. Notably, this
pathway would help explain the loss of stereochemistry in
Lewis acid mediated allylation reactions when stereode-
fined tri- or tetrasubstituted allylsilanes are employed.19
4
4-Br
2-Me
2-Br
3,5-Br2
4-F
H
30
5
H
20
6
H
180
120
60
7
H
2g
2h
2i
8
Me
Me
Me
Me
9
4-Cl
3-Br
2-Me
60
10
11
12
13
14
15
16
17
60
2j
60
2k
2lc
2m
2n
2o
2p
2q
2,3,4,5,6-F5 Me
180
120
10
4-CF3
4-Cl
4-Cl
4-Br
3-Cl
Me
H
Cl2B
Ar
ArCHO
+
pathway b
BCl3
O
Br
Cl
Br
Me
Me
Me
10
SiMe3
b
– Me3SiCl
Br
Ar
10
SiMe3
4
a
Cl
20
6
a Reaction carried out on a 1.5-mmol scale. For detailed reaction pro-
cedures, see the experimental section.
b Isolated yield based on aldehyde.
pathway a
– Me3SiCl
Cl2B
Ar
c Refluxing is required.
Cl
Cl
Cl
O
Br
Cl
SiMe3
– Me3SiBr
Ar
The haloallylation of 4-(dimethylamino)benzaldehyde
proved to be problematic when only 1.1 equivalents of bo-
ron trichloride were employed. Since coordination of di-
methylamine with boron trichloride would decrease the
Lewis acidity of boron trichloride, a separate reaction was
carried out using additional equivalents of boron trichlo-
ride (Scheme 2). Interestingly, (E)-1,3-diene 3 was isolat-
ed in 81% yield, as opposed to the expected haloallylated
product.
5
7
Scheme 4 Proposed pathway for formation of products 4 and 5
The boron trihalide mediated coupling reactions of aryl al-
dehydes with allyltriethylgermane and allyltriphenylstan-
nane were then examined (Tables 2 and 3). As shown in
the tables, the reactions proceed well for all aryl aldehydes
and generate the anticipated haloallylation products. For
aryl aldehydes bearing strong electron-withdrawing
Synthesis 2011, No. 23, 3815–3820 © Thieme Stuttgart · New York

PAPER
Boron Trihalide Mediated Haloallylation of Aryl Aldehydes
3817
groups (NO2, CN), elevated temperatures are required. In
most cases, reactions with allyltriethylgermane and allyl-
triphenylstannane produce higher yields than the corre-
sponding reactions utilizing allyltrimethylsilane. For
example, the reaction of 4-fluorobenzaldehyde with allyl-
trimethylsilane leads to a 62% yield of the desired product
2b whereas an 87% yield is obtained with allyltriethylger-
mane; the corresponding reaction using allyltriphenyl-
stannane produces a nearly quantitative yield.
Table 3 Haloallylation of Aryl Aldehydes Using Allyltriphenyl-
stannanea
CHO
X
BX3
SnPh3
Z
+
Z
hexanes
2
Entry
Z
X
Time (min) Product Yieldb (%)
1
2
3
4
5
6
7
8
4-F
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
60
60
2b
2d
2e
2f
99
81
96
68
93
65
79
74
Table 2 Haloallylation of Aryl Aldehydes Using Allyltriethylger-
manea
4-Br
2-Me
2-Br
3-Br
4-NO2
4-CN
4-Cl
CHO
X
60
BX3
GeEt3
60
Z
+
Z
hexanes
60
2s
2t
2
60c
120c
20
Entry
Z
X
Time (min) Product Yieldb (%)
2u
2n
1
2
4-Cl
4-F
H
Cl
Cl
Cl
Cl
60
60
2a
2b
2c
2e
2r
2s
2t
99
87
95
97
82
76
94
59
78
70
a Reaction was carried out on a 1.5-mmol scale. For detailed reaction
procedures, see the experimental section.
b Isolated yield based on aldehyde.
3
60
4
2-Me
60
c Refluxing is required.
5
1-naphthylc Cl
180
180
60d
60d
30
and Z-isomers. Therefore, the exploration of novel meth-
ods for the stereoselective synthesis of dienes, especially
those using readily available starting reagents, remains
important to the organic synthetic community.17a
6
3-Br
4-NO2
4-CN
4-Cl
H
Cl
Cl
Cl
Br
Br
7
8
2u
2n
2v
In view of the importance of 1,3-dienes in organic synthe-
ses, we decided to investigate the feasibility of converting
haloallylated products into 1,3-dienes. Initially, a variety
of inorganic bases were examined with only modest suc-
cess. Reactions resulted in either no reaction, degradation
of the haloallylated product to undesired byproducts, or
low yields of the expected diene with concomitant loss of
stereochemistry. Encouraged by the discovery that the bo-
ron trichloride mediated coupling of allyltrimethylsilane
and 4-(dimethylamino)benzaldehyde afforded a 1,3-diene
product directly (Scheme 2), we turned our attention to
the use of organic bases, such as triethylamine, N,N-diiso-
propylethylamine, piperidine, pyridine, and 1,8-diazabi-
cyclo[5.4.0]undec-7-ene (DBU). Among the bases
screened, DBU proved to be superior in terms of stereo-
chemical control and yield. As expected, the bromoally-
lated products undergo elimination more rapidly than
their chloroallylated counterparts.
9
10
30
a Reaction was carried out on a 1.5-mmol scale. For detailed reaction
procedures, see the experimental section.
b Isolated yield based on aldehyde.
c Substrate was 1-naphthaldehyde.
d Refluxing is required.
The 1,3-diene moiety is present in a wide range of bioac-
tive materials including terpenoids,20 fatty acid derived
lipids,21 pheromones,22 and polyketides.23 Diels–Alder re-
actions of 1,3-dienes are especially useful in the syntheses
of complex natural products due to the exceptional regio-
and stereochemical control.24 Recently it was also report-
ed that 1,3-dienes can undergo regioselective transition-
metal-catalyzed hydrocarbamoylation25 and hydro-
formylation26 to provide valuable b,g-unsaturated amides
and b,g-unsaturated aldehydes. The utility of dienes for
Ziegler–Natta polymerizations adds to their importance in
synthetic manipulations.27
Transition-metal-catalyzed sp2–sp2 coupling reactions of
stereodefined vinyl halides and vinylmetals have proven
to be powerful 1,3-diene preparations.28 In addition,
Wittig,29 Horner–Wadsworth–Emmons,30 Julia,31 and
Peterson32 reactions are employed to generate 1,3-dienes
although most of these reactions produce mixtures of E-
To enhance the efficiency of the syntheses, we examined
the feasibility of generating 1,3-dienes via treatment of
the crude bromoallylated compounds with DBU. In this
sequence, the crude bromoallylated product was subjected
to an aqueous wash using saturated aqueous sodium hy-
drogen carbonate prior to the addition of six equivalents
of DBU. The reaction produced the desired 1,3-dienes. It
is important to note that addition of dichloromethane to
the pre-washed crude bromoallylated was necessary due
to the poor solubility of DBU in hexanes. With reliable
Synthesis 2011, No. 23, 3815–3820 © Thieme Stuttgart · New York

3818
M. P. Quinn et al.
PAPER
to TMS and measured with respect to the residual protons in the
deuterated solvents.
conditions in hand, we then examined the scope of this
mild two-step procedure. The results are presented in
Table 4. Judging from the NMR data, the elimination re- The 1H and 13C NMR spectra of known compounds 2a,16 2c,16 2d,33
2f,34 2h,17a 2n,33 2t,18 2u,18 2v,34 4,29b 8a–c,17a 8d,e,36 8f,37 and 8g17a
action generates only the E-isomer, no Z-isomer was de-
are consistent with literature values.
tectable.
1-Chloro-4-(1-chlorobut-3-enyl)benzene (2a); Typical Proce-
dure
Table 4 Two-Step Procedure To Generate 1,3-Dienesa
CHO
Finely ground 4-chlorobenzaldehyde (210 mg, 1.5 mmol), allylmet-
al (2.25 mmol), and anhyd hexanes (16 mL) were placed in a dry ar-
gon-flushed flask equipped with a magnetic stirring bar. The soln
was cooled to 0 °C, and 1 M BCl3 in CH2Cl2 (1.65 mL, 1.65 mmol)
was added via syringe. [Note: for 4-(dimethylamino)benzaldehyde
reactions, BCl3 (3.30 mmol) was used.] After completion of the ad-
dition, the ice-bath was removed and the resulting soln allowed to
warm to r.t. The mixture was hydrolyzed with H2O and extracted
with hexanes (3 × 15 mL). The combined organic layers were dried
(anhyd MgSO4). After filtration and removal of solvent, the product
was isolated by flash column chromatography.
1. BBr3, 0 °C
hexanes
SiMe3
Z
+
Z
2. DBU, r.t.
CH2Cl2
8
Entry
Z
Product
Yieldb (%)
1
2
3
4
5
6
7
H
8a
8b
8c
8d
8e
8f
60
79
79
80
80
35
92
4-Cl
4-Br
3-Cl
3-Br
4-NO2
1-(1-Chlorobut-3-enyl)-4-fluorobenzene (2b)
1H NMR (250 MHz, CDCl3): d = 2.73–2.86 (m, 2 H), 4.83 (t, J = 7.3
Hz, 1 H), 5.08–5.15 (m, 2 H), 5.65–5.79 (m, 1 H), 7.00–7.08 (m, 2
H), 7.25–7.38 (m, 2 H).
13C NMR (63 MHz, CDCl3): 44.2, 61.3, 115.3, 115.6, 118.4, 128.7,
128.8, 133.6, 137.4, 160.5, 164.4.
c
1-naphthyld
8g
Anal. Calcd for C10H10ClF: C, 65.05; H, 5.46. Found: C, 65.48; H,
5.61.
a Reaction carried out on a 1.5-mmol scale. For detailed reaction pro-
cedures, see the experimental section.
b Isolated yield based on aldehyde.
1-(1-Chlorobut-3-enyl)-2-methylbenzene (2e)
c Refluxing required for bromoallylation step.
d Substrate was 1-naphthaldehyde.
1H NMR (250 MHz, CDCl3): d = 2.38 (s, 3 H), 2.81–2.91 (m, 2 H),
5.07–5.17 (m, 3 H), 5.74–5.80 (m, 1 H), 7.14–7.50 (m, 4 H).
13C NMR (63 MHz, CDCl3): d = 19.1, 43.0, 58.7, 118.1, 126.5,
128.1, 130.5, 134.2, 135.3, 139.1.
Encouraged by the successful syntheses of 1,3-dienes, we
investigated the preparation of a triene using a similar
Anal. Calcd for C11H13Cl: C, 73.12; H, 7.25. Found: C, 73.54; H,
strategy (Scheme 5). It was discovered that cinnamalde- 7.37.
hyde can undergo haloallylation, followed by elimination,
to generate stereodefined 1,3,5-triene 9.
1,3-Dibromo-2-(1-chlorobut-3-enyl)benzene (2g)
1H NMR (250 MHz, CDCl3): d = 2.73–2.81 (m, 2 H), 4.72–4.77 (m,
1 H), 5.09–5.16 (m, 2 H), 5.67–5.77 (m, 1 H), 7.45–7.61 (m, 3 H).
13C NMR (63 MHz, CDCl3): d = 43.9, 60.6, 119.1, 123.0, 129.0,
132.9, 133.9.
1. BBr3, 0 °C
CHO
hexanes
SiMe3
Ph
Ph
+
2. DBU, r.t.
CH2Cl2
Cl
Cl
HRMS: m/z [M]+ calcd for C10H9Br2Cl: 321.8760; found: 321.8757.
9
70%
1-Chloro-4-(1-chloro-3-methylbut-3-enyl)benzene (2i)
1H NMR (250 MHz, CDCl3): d = 1.69 (s, 3 H), 2.71–2.83 (m, 2 H),
4.73 (s, 1 H), 4.83 (s, 1 H), 4.97 (dd, J = 7.21, 7.19 Hz, 1 H), 7.23–
7.37 (m, 4 H).
13C NMR (63 MHz, CDCl3): d = 22.1, 47.9, 60.3, 114.4, 128.4,
128.7, 134.0, 140.0, 140.7.
Scheme 5 Two-step procedure for preparing a triene
In conclusion, aryl aldehydes couple readily with allyl-
metals to afford haloallylated products in good to excel-
lent yields in the presence of boron trihalide. The mild
reaction conditions, readily available starting materials,
and tolerance of many functional groups make this haloal-
lylation reaction quite attractive when compared to cur-
rently available synthetic strategies. A stereoselective
two-step synthesis of (E)-buta-1,3-dienes was also devel-
oped based on the boron trihalide mediated reactions of
aryl aldehydes followed by the base-induced b-elimina-
tion using DBU.
Anal. Calcd for C11H12Cl2: C, 61.42; H, 5.62. Found: C, 61.19; H,
5.25.
1-Bromo-3-(1-chloro-3-methylbut-3-enyl)benzene (2j)
1H NMR (250 MHz, CDCl3): d = 1.70 (s, 3 H), 2.74 (m, 2 H), 4.75
(s, 1 H), 4.84 (s, 1 H), 4.88–4.99 (m, 1 H), 7.19 (dd, J = 7.8, 7.3 Hz,
1 H), 7.30 (d, J = 7.3 Hz, 1 H), 7.41 (d, J = 7.8 Hz, 1 H), 7.54 (s, 1
H).
13C NMR (63 MHz, CDCl3): d = 22.1, 47.9, 60.2, 114.5, 122.5,
125.6, 130.1, 131.3, 140.6, 143.7.
All reagents were used as received. Column chromatography was
performed using silica gel (60 Å, 230–400 mesh). 1H and 13C NMR
spectra were recorded at 250.13 and 62.89 MHz, respectively.
Chemical shifts for 1H NMR and 13C NMR spectra were referenced
Anal. Calcd for C11H12BrCl: C, 50.90; H, 4.66. Found: C, 50.64; H,
4.64.
Synthesis 2011, No. 23, 3815–3820 © Thieme Stuttgart · New York

PAPER
Boron Trihalide Mediated Haloallylation of Aryl Aldehydes
3819
1-(1-Chloro-3-methylbut-3-enyl)-2-methylbenzene (2k)
1-Bromo-3-(1-chlorobut-3-enyl)benzene (2s)
1H NMR (250 MHz, CDCl3): d = 1.73 (s, 3 H), 2.39 (s, 3 H), 2.77–
2.85 (m, 2 H), 4.78 (s, 1 H), 4.85 (s, 1 H), 5.30 (dd, J = 6.43, 6.41
Hz, 1 H), 7.14–7.51 (m, 4 H).
1H NMR (250 MHz, CDCl3): d = 2.67–2.92 (m, 2 H), 4.77–4.84 (m,
1 H), 5.09 (s, 1 H), 5.13–5.15 (m, 1 H), 5.68–5.78 (m, 1 H), 7.18–
7.54 (m, 4 H).
13C NMR (63 MHz, CDCl3): d = 19.1, 22.2, 46.7, 57.3, 114.0, 126.5,
126.6, 128.0, 130.5, 135.0, 139.4, 141.2.
13C NMR (63 MHz, CDCl3): d = 44.0, 61.5, 118.7, 122.5, 125.7,
130.1, 131.4, 133.4, 143.3.
HRMS: m/z [M]+ calcd for C12H15Cl: 194.0862; found: 194.0874.
Anal. Calcd for C10H10BrCl: C, 48.51; H, 4.10. Found: C, 48.99; H,
4.03.
1-(1-Chloro-3-methylbut-3-enyl)-2,3,4,5,6-pentafluorobenzene
(2l)
1-(3-Bromo-1-chlorobut-3-enyl)-2-methylbenzene (5a) and
1-(1,3-Dichlorobut-3-enyl)-2-methylbenzene (6a)
Ratio of Br/Cl products ~ 8:1.
1H NMR (250 MHz, CDCl3): d = 1.73 (s, 3 H), 2.95 (d, J = 8.1 Hz,
2 H), 4.74 (s, 1 H), 4.81 (s, 1 H), 5.35 (t, J = 8.1 Hz, 1 H).
13C NMR (63 MHz, CDCl3): d = 21.8, 45.0, 48.5, 112.7, 114.8,
1H NMR (250 MHz, CDCl3): d = 2.32–2.52 (m, 3 H), 2.92–3.30 (m,
2 H), 5.20–5.32 (m, 0.25 H), 5.40–5.79 (m, 2.75 H), 7.09–7.61 (m,
4 H).
13C NMR (63 MHz, CDCl3): d = 19.1, 50.3, 56.3, 120.4, 126.5,
128.3, 129.0, 130.6, 135.4, 138.3.
120.8, 135.7, 140.2, 143.0, 147.0.
HRMS: m/z [M]+ calcd for C11H8ClF5: 270.0235; found: 270.0237.
1-(1-Chloro-3-methylbut-3-enyl)-4-(trifluoromethyl)benzene
(2m)
1H NMR (250 MHz, CDCl3): d = 1.58 (s, 3 H), 2.60–2.70 (m, 2 H),
4.62 (s, 1 H), 4.72 (s, 1 H), 4.90 (t, J = 7.5 Hz, 1 H), 7.35–7.50 (m,
4 H).
1-(3-Bromo-1-chlorobut-3-enyl)-4-chlorobenzene (5b) and
1-Chloro-4-(1,3-dichlorobut-3-enyl)benzene (6b)
Ratio of Br/Cl products ~ 2:1.
13C NMR (63 MHz, CDCl3): d = 22.1, 48.0, 60.1, 114.6, 125.5,
125.6, 126.1, 127.4, 130.2, 130.7, 140.5, 145.4.
1H NMR (250 MHz, CDCl3): d = 2.87–3.21 (m, 2 H). 5.07–5.35 (m,
1.80 H), 5.41–5.63 (m, 1.20 H), 7.26–7.42 (m, 4 H).
Anal. Calcd for C12H12ClF3: C, 57.96; H, 4.86. Found: C, 58.04; H,
4.91.
13C NMR (63 MHz, CDCl3): d = 49.4, 51.4, 58.6, 59.2, 116.2, 120.7,
128.4, 128.8, 134.3, 137.3, 138.6, 138.7.
1-(1-Bromo-3-methylbut-3-enyl)-4-chlorobenzene (2o)
1H NMR (250 MHz, CDCl3): d = 1.68 (s, 3 H), 2.86–2.97 (m, 2 H),
4.72 (s, 1 H), 4.82 (s, 1 H), 5.06 (t, J = 7.8 Hz, 1 H), 7.26–7.34 (m,
4 H).
13C NMR (63 MHz, CDCl3): d = 22.0, 47.9, 51.3, 114.3, 128.6,
128.7, 134.0, 140.3, 141.2.
1-(Buta-1,3-dienyl)-4-chlorobenzene (8b); Typical Procedure
Finely ground 4-chlorobenzaldehyde (210 mg, 1.5 mmol), allyltri-
methylsilane (257 mg, 2.25 mmol), and anhyd hexanes (16 mL)
were placed in a dry argon-flushed 50-mL round-bottomed flask
equipped with a magnetic stirring bar. The soln was cooled to 0 °C,
and 1.0 M BBr3 in CH2Cl2 (1.65 mL, 1.65 mmol) was added via sy-
ringe. After completion of the addition, the ice-bath was removed
and the resulting soln allowed to warm to r.t. until completion of the
reaction. The mixture was hydrolyzed with H2O and extracted with
CH2Cl2 (3 × 15 mL). The organic layer was washed with sat.
NaHCO3 soln (3 × 20 mL) and brine (1 × 20 mL). DBU (1.37 g, 9.0
mmol) was added neat and the mixture allowed to react until com-
pletion. The organic layer was then washed sequentially with aq 1.0
M HCl (3 × 15 mL) and brine (1 × 20 mL), and then dried (anhyd
MgSO4). After filtration and removal of solvent, the product was
isolated by column chromatography (hexanes).
Anal. Calcd for C11H12BrCl: C, 50.90; H, 4.66. Found: C, 50.67; H,
4.32.
1-Bromo-4-(1-bromo-3-methylbut-3-enyl)benzene (2p)
1H NMR (250 MHz, CDCl3): d = 1.70 (s, 3 H), 2.80–3.02 (m, 2 H),
4.74 (s, 1 H), 4.84 (s, 1 H), 5.03 (t, J = 7.7 Hz, 1 H), 7.23–7.39 (m,
4 H).
13C NMR (63 MHz, CDCl3): d = 22.0, 47.8, 51.1, 114.4, 125.5,
127.5, 128.5, 129.9, 134.3, 141.1, 143.7.
HRMS: m/z [M]+ calcd for C11H12Br2: C, 301.9306; found:
301.9312.
[(1Z,3E)-2-Chlorohexa-1,3,5-trien-1-yl]benzene (9)
1H NMR (250 MHz, CDCl3): d = 5.24 (d, J = 10.0 Hz, 1 H), 5.40 (d,
J = 16.7 Hz, 1 H), 6.48 (dt, J = 18.9, 11.8 Hz, 2 H), 6.67 (s, 1 H),
6.77 (dd, J = 14.3, 10.3 Hz, 1 H), 7.35 (dd, J = 14.7, 7.3 Hz, 3 H),
7.71 (d, J = 7.0 Hz, 2 H).
13C NMR (63 MHz, CDCl3): d = 119.7, 128.1, 128.2, 128.9, 129.6,
130.7, 131.9, 132.6, 134.9, 135.9.
1-(1-Bromo-3-methylbut-3-enyl)-3-chlorobenzene (2q)
1H NMR (250 MHz, CDCl3): d = 1.70 (s, 3 H), 2.80–3.02 (m, 2 H),
4.74 (s, 1 H), 4.84 (s, 1 H), 5.03, (t, J = 7.7 Hz, 1 H), 7.23–7.28 (m,
3 H), 7.39 (s, 1 H).
13C NMR (63 MHz, CDCl3): d = 22.0, 47.8, 51.1, 114.4, 125.5,
127.5, 128.5, 129.9, 134.3, 141.1, 143.7.
HRMS (ESI+): m/z [M + H]+ calcd for C12H12Cl: 191.063; found:
191.062.
Anal. Calcd for C11H12BrCl: C, 50.90; H, 4.66. Found: C, 51.07; H,
4.73.
Supporting Information for this article is available online at
1-(1-Chlorobut-3-enyl)naphthalene (2r)
http://www.thieme-connect.com/ejournals/toc/synthesis.
1H NMR (250 MHz, CDCl3): d = 3.03–3.07 (m, 2 H), 5.08–5.26 (m,
2 H), 5.64–5.76 (m, 1 H), 5.90 (m, 1 H), 7.45–7.62 (m, 3 H), 7.70
(d, J = 7.4 Hz, 1 H), 7.79–7.92 (m, 2 H), 8.14 (d, J = 8.1 Hz, 1 H).
Acknowledgment
13C NMR (63 MHz, CDCl3): d = 42.8, 58.6, 118.9, 122.8, 124.6,
125.2, 125.8, 126.5, 129.0, 129.1, 130.4, 133.8, 134.2, 136.3.
We wish to thank the U.S. Department of Energy and the Robert H.
Cole Foundation for partial support of this research.
Anal. Calcd for C14H13Cl: C, 77.59; H, 6.05. Found: C, 77.36; H,
5.99.
Synthesis 2011, No. 23, 3815–3820 © Thieme Stuttgart · New York

3820
M. P. Quinn et al.
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Synthesis 2011, No. 23, 3815–3820 © Thieme Stuttgart · New York