A method for synthesis of homoallylic bromide

Article abstract of DOI:10.1021/jo400580n

Cyclopropyl Grignard reagents react with carbonyl compounds in the presence of diethyl phosphite to give homoallylic bromides. The reaction is effectively carried out under mild conditions in a one-pot fashion with moderate to good yields.

Full text of DOI:10.1021/jo400580n

Article
pubs.acs.org/joc
A Method for Synthesis of Homoallylic Bromide
Wenke Qi, Peipei Wang, Liyuan Fan, and Songlin Zhang*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Dushu
Lake Campus, Soochow University, Suzhou 215123, People’s Republic of China
S
* Supporting Information
ABSTRACT: Cyclopropyl Grignard reagents react with carbonyl com-
pounds in the presence of diethyl phosphite to give homoallylic bromides.
The reaction is effectively carried out under mild conditions in a one-pot
fashion with moderate to good yields.
compound and the limitation of previous synthesis methods, we
believe it is necessary and meaningful to further investigate and
develop this method to afford homoallylic halides. Herein, we
report a convenient one-pot protocol for the synthesis of
homoallylic halides by the reaction of carbonyl compounds with
cyclopropyl Grignard reagents in the presence of diethyl
phosphite.
INTRODUCTION
■
Homoallylic halides have attracted a great deal of interest due to
their versatility as building blocks or starting substrates in organic
synthesis1 and in the pharmaceutical/agrochemical industries.2
However, the synthetic approaches of homoallylic halides are
very limited. Previously described methodologies involve
treatment of the appropriate cyclopropyl methanol with 48%
hydrobromic acid,3 PBr3,4 zinc bromide,,4c or a magnesium
halide.5 Shi et al. used the methylenecyclopropanes (MCPs) to
react with various metal chlorides or bromides to give the
corresponding homoallylic halides in good yields.6 However,
under the above conditions, the isolation of cyclopropylcarbinols
or methylenecyclopropanes is necessary, and a mixture of E and
Z alkenes is always obtained. In 2003, Wong et al. reported a one-
pot synthetic pathway for the preparation of homoallylic halides
by the in situ generated MgBrCl-promoted ring-opening of
cyclopropylcarbinyl acetates.7 But in this method, a mixture of
homoallylic bromide and chloride was obtained.
RESULTS AND DISCUSSION
■
Initially, ketone 1a and cyclopropylmagnesium bromide were
used as model substrates for the optimization of the reaction
conditions. As shown in Table 1, the additives were first
examined with THF as the solvent at room temperature. When
diethyl phosphite and diphenyl phosphite were employed as
additives, the desired product was obtained in good or moderate
yield (Table 1, entries 1 and 2). On the contrary, much less
product was isolated with diethyl chlorophosphite and
triphenylphosphine as additives (Table 1, entries 3 and 4).
Subsequently, we focused on the quantity of additive and
Grignard reagent (Table 1, entries 5−10). In the presence of 1.2
equiv of diethyl phosphite and 3 equiv of Grignard reagent, a
gratifying yield was obtained. In addition, the effect of
temperature was examined in a range from 0 to 60 °C (Table
1, entries 11−13). THF turned out to the best solvent for this
transformation (Table 1, entries 14−16) after solvent screening.
In order to investigate the generality of this reaction, different
carbonyl compounds were employed as substrates. Aryl ketones
react with cyclopropylmagnesium bromide under the conditions
listed in Table 2 to afford the corresponding homoallylic
bromides in 61−74% yield (Table 2, entries 1−5). Aryl
aldehydes (Table 2, entries 6−10, 13−17, 19) also can give
good to moderate yields in the reaction. When furaldehyde was
used as the substrate, a 68% yield was obtained (Table 2, entry
12). The reactions of cinnamaldehyde (Table 2, entry 11) and 2-
naphthaldehyde (Table 2, entry 18) proceeded smoothly to give
the desired products with 65% and 60% yields, respectively.
Additionally, benzaldehydes with electron-donating groups
(Table 2, entries 6, 8, 9, 13) afforded better yields than
benzaldehydes with electron-withdrawing groups (Table 2,
Recently, our group discovered an olefination reaction of
carbonyl compounds using Grignard reagents8 or organozinc
reagents9 (Scheme 1). A cyclopropylmagnesium bromide was
Scheme 1. Olefination of Carbonyl Compounds with
Grignard Reagents or Organozinc Reagents
employed; instead of the expected product methylenecyclopro-
pane, it was interesting to notice the formation of homoallylic
halide (Scheme 2). In view of the importance of this class of
Scheme 2. Reaction of Cyclopropylmagnesium Bromide with
Benzophenone in the Presence of Diethyl Phosphite
Received: March 19, 2013
© XXXX American Chemical Society
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a
To further investigate the role of diethyl phosphite and
Grignard reagents in the reaction, studies similar to our previous
work8 were carried out under the optimum reaction conditions
(Scheme 3). Cyclopropyl(phenyl)(p-tolyl)methanol (5a) was
employed to react with the diethyl phosphite, magnesium
bromide diethoxy(oxo)phosphite (6), or magnesium bromide
diethylphosphinite individually. The desired product was
obtained with moderate yield using 6 as an additive, which was
thus considered to be an important intermediate in the reaction.
Interestingly, when magnesium chloride diethoxy(oxo)-
phosphite (7) was used, the corresponding homoallylic chloride
was obtained in a good yield.
On the basis of our preliminary results, a plausible mechanism
for this transformation is proposed in Scheme 4. First, ketone 4
transforms into intermediate 5 through nucleophilic addition.
Then the oxygen atom of intermediate 5 coordinates with the
phosphorus atom of 6, which leads to the transition state 9.
Opening the strained cyclopropane ring with bromide and
elimination of phosphite gives homoallylic bromides 10 with 6
and MgO.
Table 1. Optimization of Reaction Conditions
additive
(equiv)
cyclopropylmagnesium
bromide (equiv)
T
yield
b
entry
1
(°C)
solvent
(%)
(EtO)2P(O)H
(1.0)
3
3
3
rt
rt
rt
THF
THF
THF
70
64
20
2
3
(PhO)2P(O)
H (1.0)
(EtO)2P(O)Cl
(1.0)
4
5
Ph3P (1.0)
3
3
rt
rt
THF
THF
0
(EtO)2P(O)H
(1.2)
73
6
(EtO)2P(O)H
(1.4)
3
rt
rt
rt
rt
rt
0
THF
THF
THF
THF
THF
THF
72
65
70
70
72
69
70
64
53
7
(EtO)2P(O)H
(0.8)
3
In summary, we have established an efficient one-pot synthetic
protocol for the preparation of homoallylic halides from carbonyl
compounds using cyclopropyl Grignard reagents in the presence
of diethyl phosphite. Efforts are in progress to elucidate the
mechanistic details of this reaction.
8
(EtO)2P(O)H
(1.2)
2
9
(EtO)2P(O)H
(1.2)
4
10
11
12
13
14
(EtO)2P(O)H
(1.2)
2.5
3
EXPERIMENTAL SECTION
(EtO)2P(O)H
(1.2)
■
General Information. THF was distilled from sodium
benzophenone under nitrogen. All reactions were conducted
under a nitrogen atmosphere. Metallic magnesium and all
solvents were purchased from a commercial source without
further purification before use. The flash column chromatog-
raphy was carried out on silica gel (300−400 mesh). 1H and 13C
NMR spectra (Supporting Information) were recorded on a 400
MHz spectrometer as solutions in CDCl3. Chemical shifts in 1H
NMR spectra are reported in parts per million (ppm, δ)
downfield from the internal standard Me4Si (TMS). Chemical
shifts in 13C NMR spectra are reported relative to the central line
of the chloroform signal (δ = 77.50 ppm). High-resolution mass
spectra were obtained with a GCT-TOF instrument.
(EtO)2P(O)H
(1.2)
3
40 THF
60 THF
(EtO)2P(O)H
(1.2)
3
(EtO)2P(O)H
(1.2)
3
rt
toluene/
THF
(1:1)
15
16
(EtO)2P(O)H
(1.2)
3
3
rt
rt
Et2O/THF
(1:1)
60
30
(EtO)2P(O)H
(1.2)
dioxane/
THF
(1:1)
a
Cyclopropylmagnesium bromide (1.5 mmol) in THF was added to a
solution of phenyl(p-tolyl)methanone (0.5 mmol) in THF (3 mL)
under a nitrogen atmosphere at room temperature. The mixture was
stirred for 3 h, and then diethyl phosphite (0.6 mmol) was added to
this mixture and stirred at room temperature for 5 h. Isolated yield
based on phenyl(p-tolyl)methanone after silica gel chromatography.
General Procedure for the Syntheses of Homoallylic
Bromides. Grignard reagent (1.5 mmol) in THF was added to a
solution of carbonyl compounds (0.5 mmol) in THF (3 mL)
under a nitrogen atmosphere at room temperature. The mixture
was stirred for 3 h, and then diethyl phosphite (0.6 mmol) was
added to this mixture and stirred at room temperature for 5 h
(the reaction was monitored by TLC). Then the mixture was
quenched with dilute hydrochloric acid. The resulting mixture
was extracted with diethyl ether (3 × 10 mL) and dried over
anhydrous Na2SO4. The solvent was removed by evaporation
under reduced pressure. Purification by column chromatography
on silica gel afforded the products (300−400 mesh, petroleum
ether and ethyl acetate as eluent).
1-((E)-4-Bromo-1-p-tolylbut-1-enyl)benzene (3a). Yel-
low oil. Yield: 109.5 mg, 73%. IR (KBr): 3053, 3017, 1653, 1510,
1491, 1451, 1261 cm−1. 1H NMR (CDCl3, 300 MHz): δ 7.27−
6.96 (m, 9H), 5.95 (t, J = 7.2 Hz, 1H), 3.33−3.28 (m, 2H), 2.62−
2.54 (m, 2H), 2.22 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
135.8, 133.6, 126.2, 126.1, 125.4, 124.8, 123.9, 123.8, 123.7,
122.0, 121.3, 29.5, 29.3, 17.6. HRMS (EI+): calcd for C17H1781Br
(M+) 302.0493, found 302.0487; calcd for C17H1779Br (M+)
300.0514, found 300.0511.
b
entries 7, 14, 15, 18). Geometries of alkene products were
determined by 1H NMR coupling constants and NOESY
analyses. Trisubstituted alkene products were obtained as a
mixture of E and Z isomers; however, (E)-alkenes were
preferable for disubstituted alkene bromides.
The scope of the Grignard reagents suitable for this reaction
was explored with 2-phenyl cyclopropylmagnesium bromide
(Table 3, entries 1−4), cyclobutylmagnesium bromide (Table 3,
entry 5), and cyclopentylmagnesium bromide (Table 3, entry 6).
When aryl aldehydes reacted with 2-phenyl cyclopropylmagne-
sium bromide, corresponding homoallylic bromides were
obtained with low to moderate yields (Table 3, entries 1−4).
As shown in Table 3, when cyclobutylmagnesium bromide or
cyclopentylmagnesium bromide was employed (Table 3, entries
5 and 6), only ordinary olefins were obtained in 40% and 15%
yields, respectively.
B
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a
Table 2. Reactions of Carbonyl Compounds with Cyclopropylmagnesium Bromide
a
Grignard reagent (1.5 mmol) in THF was added to a solution of carbonyl compounds (0.5 mmol) in THF (3 mL) under a nitrogen atmosphere at
room temperature. The mixture was stirred for 3 h, and then diethyl phosphite (0.6 mmol) was added to this mixture and stirred at room
b
temperature for 5 h. Isolated yield based on carbonyl compounds after silica gel chromatography.
4-Bromo-1,1-diphenylbut-1-ene (3b). Colorless oil.
Yield: 106.2 mg, 74%. IR (KBr): 3056, 3024, 1660, 1510,
1494, 1445, 1266 cm−1. 1H NMR (CDCl3, 300 MHz): δ 7.41−
7.16 (m, 10H), 6.09 (t, J = 7.3 Hz, 1H), 3.42 (t, J = 6.9 Hz, 2H),
2.68 (q, J = 7.0 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 145.9,
144.7, 142.6, 140.1, 130.2, 128.8, 128.6, 128.0, 127.8, 126.2, 33.4,
C
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Table 3. Reactions of Carbonyl Compounds with 2-Phenyl Cyclopropylmagnesium Bromide
a
Grignard reagent (1.5 mmol) in THF was added to a solution of carbonyl compounds (0.5 mmol) in THF (3 mL) under a nitrogen atmosphere at
room temperature. The mixture was stirred for 30 min, and then diethyl phosphite (0.6 mmol) was added to this mixture and stirred at room
b
temperature for 5 h. Isolated yield based on carbonyl compounds after silica gel chromatography.
Scheme 3. Reaction of Cyclopropyl(phenyl)(p-tolyl)methanol with Diethyl Phosphite, Magnesium Bromide
Diethoxy(oxo)phosphite, Magnesium Bromide Diethylphosphinite, or Magnesium Chloride Diethoxy(oxo)phosphite
Scheme 4. Probable Mechanism for Cyclopropyl Grignard Reagents Reacting with Carbonyl Compounds
33.2. HRMS (EI+): calcd for C16H1581Br (M+) 288.0337, found
288.0337; calcd for C16H1579Br (M+) 286.0357, found 286.0358.
4-Bromo-1,1-bis(4-methoxyphenyl)but-1-ene (3c).
Colorless oil. Yield: 117.6 mg, 68%. IR (KBr): 2923, 2831,
159.5, 159.2, 143.8, 135.7, 132.6, 131.3, 128.9, 124.2, 114.1,
113.9, 55.7, 33.5, 33.4. HRMS (EI+): calcd for C18H1981BrO2
(M+) 348.0548, found 348.0527; calcd for C18H1979BrO2 (M+)
346.0568, found 346.0568.
1
1604, 1510, 1462, 1244, 1175, 1109, 1035 cm−1. H NMR
4,4′-(4-Bromobut-1-ene-1,1-diyl)bis(chlorobenzene)
(CDCl3, 300 MHz): δ 7.16 (d, J = 8.8 Hz, 2H), 7.09 (d, J = 8.7
Hz, 2H), 6.91 (d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 5.94
(t, J = 7.2 Hz, 1H), 3.83 (s, 3H), 3.79 (s, 3H), 3.41 (t, J = 7.0 Hz,
2H), 2.68 (q, J = 7.1 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ
(3d). Colorless oil. Yield: 108.6 mg, 61%. IR (KBr): 3030, 2963,
1
1661, 1590, 1491, 1268, 1091 cm−1. H NMR (CDCl3, 400
MHz): δ 7.37 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.14
(d, J = 8.4 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 6.07 (t, J = 7.2 Hz,
D
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1H), 3.43 (t, J = 6.7 Hz, 2H), 2.67 (q, J = 6.8 Hz, 2H). 13C NMR
(75 MHz, CDCl3): δ 142.53, 140.59, 137.95, 133.92, 133.85,
131.50, 129.20, 128.99, 128.85, 127.30, 33.21, 32.87. HRMS
(EI+): calcd for C16H1335Cl279Br (M+) 353.9578, found
353.9579; calcd for C16H1335Cl37Cl79Br (M+) 355.9548, found
355.9548; calcd for C16H1335Cl2 81Br (M+) 355.9557, found
355.9557; calcd for C16H1337Cl279Br (M+) 357.9519, found
357.9503.
(E)-2-(4-Bromo-1-phenylbut-1-enyl)naphthalene (3e).
White solid. Yield: 115.9 mg, 69%. Compound purity: 98.21%. IR
(KBr): 3050, 3017, 1656, 1589, 1497, 1444, 1256 cm−1. 1H NMR
(CDCl3, 400 MHz): δ 7.90−7.74 (m, 3H), 7.62−7.26 (m, 9H),
6.27 (t, J = 7.3 Hz, 1H), 3.50 (t, J = 7.0 Hz, 2H), 2.78 (q, J = 7.0
Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 144.65, 144.61, 142.44,
139.98, 139.86, 137.50, 133.70, 133.12, 132.99, 130.25, 128.98,
128.87, 128.76, 128.66, 128.44, 128.37, 128.15, 127.95, 127.86,
127.83, 127.41, 127.03, 126.71, 126.58, 126.52, 126.34, 125.66,
33.47, 33.37, 33.22, 33.18. HRMS (EI+): calcd for C20H1781Br
(M+) 338.0493, found 338.0468; calcd for C20H1779Br (M+)
336.0514, found 336.0514.
(E)-(4-Bromobut-1-enyl)benzene (3f). Colorless oil.
Yield: 77.0 mg, 73%. IR (KBr): 3057, 3021, 2943, 1601, 1500,
1447, 1275, 961 cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.40 (d, J
= 7.4 Hz, 2H), 7.34 (t, J = 7.5 Hz, 2H), 7.26 (t, J = 7.2 Hz, 1H),
6.51 (d, J = 15.9 Hz, 1H), 6.21 (td, J = 6.9 Hz, J = 15.7 Hz, 1H),
3.50 (t, J = 7.1 Hz, 2H), 2.80 (q, J = 7.0 Hz, 2H). 13C NMR (75
MHz, CDCl3): δ 137.4, 133.1, 129.0, 127.9, 127.1, 126.6, 36.7,
32.8. HRMS (EI+): calcd for C10H1181Br (M+) 212.0024, found
212.0012; calcd for C10H1179Br (M+) 210.0044, found 210.0045.
(E)-1-(4-Bromobut-1-enyl)-4-methoxybenzene (3g).
Colorless oil. Yield: 85.6 mg, 71%. Compound purity: 98.77%.
IR (KBr): 3000, 2952, 1610, 1487, 1415, 1098, 964, 813 cm−1. 1H
NMR (CDCl3, 300 MHz): δ 7.29 (d, J = 8.6 Hz, 2H), 6.84 (d, J =
8.7 Hz, 2H), 6.42 (d, J = 15.8 Hz, 1H), 6.03 (td, J = 6.9 Hz, J =
15.7 Hz, 1H), 3.79 (s, 3H), 3.45 (t, J = 7.1 Hz, 2H), 2.74 (q, J =
7.0 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 159.5, 132.5, 130.3,
127.8, 124.8, 114.4, 55.7, 36.8, 33.0. HRMS (EI+): calcd for
C11H1381BrO (M+) 242.0129, found 242.0118; calcd for
C11H1379BrO (M+) 240.0150, found 240.0151.
(E)-1-(4-Bromobut-1-enyl)-4-chlorobenzene (3h). Col-
orless oil. Yield: 75.3 mg, 62%. Compound purity: 99.10%. IR
(KBr): 3041, 2975, 1634, 1502, 1417, 1093, 973, 820 cm−1. 1H
NMR (CDCl3, 400 MHz): δ 7.32−7.26 (m, 4H), 6.44 (d, J =
15.8 Hz, 1H), 6.17 (td, J = 6.9 Hz, J = 15.6 Hz, 1H), 3.48 (t, J =
6.9 Hz, 2H), 2.77 (q, J = 6.7 Hz, 2H). 13C NMR (75 MHz,
CDCl3): δ 135.9, 133.4, 131.9, 130.8, 129.1, 127.8, 36.6, 32.6.
HRMS (EI+): calcd for C10H1035Cl79Br (M+) 243.9654, found
243.9655; calcd for C10H1035Cl81Br (M+) 245.9634, found
245.9637; calcd for C10H1037Cl79Br (M+) 245.9625, found
245.9637.
NMR (CDCl3, 400 MHz): δ 7.45 (d, J = 7.6 Hz, 1H), 7.24 (t, J =
7.9 Hz, 1H), 6.94 (t, J = 7.5 Hz, 1H), 6.88 (t, J = 8.3 Hz, 1H), 6.84
(d, J = 16.0 Hz, 1H), 6.21 (td, J = 6.9 Hz, J = 14.3 Hz, 1H), 3.86
(s, 3H), 3.49 (t, J = 7.2 Hz, 2H), 2.81 (q, J = 7.1 Hz, 2H). 13
C
NMR (75 MHz, CDCl3): δ 156.9, 129.0, 127.8, 127.7, 127.1,
126.4, 121.1, 111.2, 55.9, 37.2, 33.0. HRMS (EI+): calcd for
C11H1381BrO (M+) 242.0129, found 242.0118; calcd for
C11H1379BrO (M+) 240.0150, found 240.0151.
((1E,3E)-6-Bromohexa-1,3-dienyl)benzene (3k). Color-
less oil. Yield: 76.7 mg, 65%. Compound purity: 98.35%. IR
1
(KBr): 3038, 2998, 1621, 1502, 1408, 955, 762, 691 cm−1. H
NMR (CDCl3, 400 MHz): δ 7.41 (d, J = 7.2 Hz, 2H), 7.33 (t, J =
7.6 Hz, 2H), 7.24 (t, J = 7.3 Hz, 1H), 6.78 (dd, J = 10.4 Hz, J =
15.7 Hz, 1H), 6.53 (d, J = 15.7 Hz, 1H), 6.31 (dd, J = 10.4 Hz, J =
15.1 Hz, 1H), 5.83−5.76 (m, 1H), 3.45 (t, J = 7.1 Hz, 2H), 2.73
(q, J = 7.0 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 137.7, 133.7,
132.3, 131.3, 129.1, 129.0, 127.9, 126.7, 36.5, 32.7. HRMS (EI+):
calcd for C12H1381Br (M+) 238.0180, found 238.0178; calcd for
C12H1379Br (M+) 236.0201, found 236.0201.
(E)-2-(4-Bromobut-1-enyl)furan (3l). Colorless oil. Yield:
67.6 mg, 68%. Compound purity: 99.01%. IR (KBr): 3076, 1645,
1511, 1418, 978 cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.34 (s,
1H), 6.37−6.36 (m, 1H), 6.31 (d, J = 15.8 Hz, 1H), 6.22−6.21
(m, 1H), 6.16−6.10 (m, 1H), 3.45 (t, J = 7.1 Hz, 2H), 2.75 (q, J =
7.1 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 152.9, 142.2, 125.8,
121.6, 111.7, 107.8, 36.5, 32.5. HRMS (EI+); calcd for
C8H981BrO (M+) 201.9816, found 201.9823; calcd for
C8H979BrO (M+) 199.9837, found 199.9838.
(E)-1-(4-Bromobut-1-enyl)-2-chloro-3,4-dimethoxy-
benzene (3m). Colorless oil. Yield: 99.9 mg, 74%. Compound
purity: 99.51%. IR (KBr): 3042, 2981, 1616, 1502, 1415, 961
cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.26 (d, J = 8.9 Hz, 1H),
6.82 (d, J = 8.6 Hz, 1H), 6.81 (d, J = 16.1 Hz, 1H), 6.08 (td, J = 7.0
Hz, J = 15.7 Hz, 1H), 3.89 (s, 3H), 3.87 (s, 3H), 3.50 (t, J = 7.0
Hz, 2H), 2.81 (q, J = 7.0 Hz, 2H). 13C NMR (100 MHz, CDCl3):
δ 153.3, 145.7, 129.2, 129.1, 128.3, 127.9, 122.0, 111.1, 61.0, 56.5,
36.7, 32.8. HRMS (EI+): calcd for C12H14O235Cl79Br (M+)
303.9866, found 303.9867; calcd for C12H14O235Cl81Br (M+)
305.9845, found 305.9845; calcd for C12H14O237Cl81Br (M+)
307.9816, found 307.9829.
1-((E)-4-Bromobut-1-enyl)-4-methylbenzene (3n). Col-
orless oil. Yield: 79.5 mg, 71%. Compound purity: 99.32%. IR
(KBr): 3055, 2980, 1671, 1592, 1455, 1384, 1283, 1038, 850
cm−1. 1H NMR (CDCl3, 300 MHz): δ 7.25 (d, J = 7.6 Hz, 2H),
7.11 (d, J = 7.3 Hz, 2H), 6.45 (d, J = 15.8 Hz, 1H), 6.12 (td, J = 6.7
Hz, J = 14.3 Hz, 1H), 3.45 (t, J = 6.9 Hz, 2H), 2.75 (d, J = 6.6 Hz,
2H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 137.5, 134.4,
132.8, 129.5, 126.3, 125.8, 36.6, 32.6, 21.4. HRMS (EI+): calcd
for C11H13Br (M+) 224.0201, found 224.0199.
4-((E)-4-Bromobut-1-enyl)-1,2-dichlorobenzene (3o).
Colorless oil. Yield: 55.7 mg, 40%. Compound purity: 99.03%.
IR (KBr): 3051, 2963, 2831, 1500, 1403, 1167, 970, 833 cm−1. 1H
NMR (CDCl3, 300 MHz): δ 7.44 (d, J = 1.6 Hz, 1H), 7.37 (d, J =
8.3 Hz, 1H), 7.20−7.16 (m, 1H), 6.39 (d, J = 15.9 Hz, 1H), 6.20
(td, J = 6.8 Hz, J = 15.8 Hz, 1H), 3.48 (t, J = 6.8 Hz, 2H), 2.82−
2.77 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 137.1, 132.6,
131.0, 130.4, 130.1, 128.8, 127.9, 125.4, 36.0, 31.9. HRMS (EI+):
calcd for C10H9Cl2Br (M+) 277.9265, found 277.9265.
1-((E)-4-Bromobut-1-enyl)-4-fluorobenzene (3p). Col-
orless oil. Yield: 56.0 mg, 49%. Compound purity: 98.97%. IR
(KBr): 3029, 2960, 1633, 1500, 1297, 1005, 810 cm−1. 1H NMR
(CDCl3, 300 MHz): δ 7.31 (d, J = 3.2 Hz, 2H), 6.99 (d, J = 4.5
Hz, 2H), 6.44 (d, J = 15.7 Hz, 1H), 6.09 (td, J = 6.5 Hz, J = 14.6
(E)-5-(4-Bromobut-1-enyl)benzo[d][1,3]dioxole (3i).
Colorless oil. Yield: 88.5 mg, 70%. Compound purity: 96.21%.
1
IR (KBr): 3032, 2947, 1611, 1507, 1441, 1231, 957 cm−1. H
NMR (CDCl3, 300 MHz): δ 6.91 (s, 1H), 6.76 (q, J = 8.0 Hz,
2H), 6.39 (d, J = 15.8 Hz, 1H), 6.05−5.98 (m, 1H), 5.94 (s, 2H),
3.45 (t, J = 7.1 Hz, 2H), 2.73 (q, J = 6.7 Hz, 2H). 13C NMR (75
MHz, CDCl3): δ 148.5, 147.5, 132.7, 132.0, 125.3, 121.2, 108.7,
106.0, 101.5, 36.7, 32.8. HRMS (EI+): calcd for C11H1181BrO2
(M+) 255.9922, found 255.9924; calcd for C11H1179BrO2 (M+)
253.9942, found 253.9942.
(E)-1-(4-Bromobut-1-enyl)-2-methoxybenzene (3j).
Colorless oil. Yield: 86.4 mg, 72%. Compound purity: 99.01%.
IR (KBr): 3012, 2980, 1613, 1500, 1423, 1108, 971, 733 cm−1. 1H
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Hz, 1H), 3.46 (dd, J = 4.1 Hz, J = 9.0 Hz, 2H), 2.77−2.73 (m,
2H). 13C NMR (100 MHz, CDCl3): δ 163.6, 161.2, 133.4, 133.4,
131.7, 127.9, 127.8, 126.6, 115.7, 115.6, 36.4, 32.5. HRMS (EI+):
calcd for C10H10FBr (M+) 227.9947, found 227.9950.
3.19−3.03 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 141.7,
135.7, 133.3, 132.2, 129.0, 128.9, 128.8, 127.7, 127.6, 127.2, 54.5,
43.5. HRMS (EI+): calcd for C16H14ClBr (M+) 319.9967, found
319.9958.
5-((E)-4-p-Tolylbut-1-enyl)benzo[d][1,3]dioxole (3x).
White solid. Yield: 44 mg, 40%. Compound purity: 98.94%. IR
(KBr): 3026, 2925, 1637, 1498, 1456, 840, 816 cm−1. 1H NMR
(CDCl3, 300 MHz): δ 7.29−7.16 (m, 10H), 2.93 (t, J = 7.9 Hz,
4H), 2.95−2.00 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 139.2,
138.7, 126.9, 126.3, 126.1, 124.3, 30.3, 15.4. HRMS (EI+): calcd
for C17H16 (M+) 220.1252, found 220.1250.
1-((E)-4-Bromobut-1-enyl)-4-(trifluoromethyl)benzene
(3q). Colorless oil. Yield: 62.3 mg, 45%. Compound purity:
98.74%. IR (KBr): 3062, 2871, 1659, 1491, 1375, 990, 810 cm−1.
1H NMR (CDCl3, 300 MHz): δ 7.57 (d, J = 5.9 Hz, 2H), 7.47 (d,
J = 5.8 Hz, 2H), 6.53 (dd, J = 4.3 Hz, J = 15.6 Hz), 6.31 (td, J = 6.1
Hz, J = 21.1 Hz, 1H), 3.54−3.49 (m, 2H), 2.83−2.80 (m, 2H).
13C NMR (100 MHz, CDCl3): δ 119.7, 118.7, 115.9, 114.9,
114.8, 113.3, 112.7, 110.9, 110.6, 110.5, 108.7, 21.4, 17.2. HRMS
(EI+): calcd for C11H10F3Br (M+) 277.9919, found 277.9918.
2-((E)-4-Bromobut-1-enyl)naphthalene (3r). Colorless
oil. Yield: 78.3 mg, 60%. Compound purity: 99.50%. IR (KBr):
1-((E)-4-(4-Chlorophenyl)but-3-enyl)-4-methylben-
zene (3y). White solid. Yield: 17.6 mg, 15%. Compound purity:
1
98.29%. H NMR (CDCl3, 400 MHz): δ 7.30−7.18 (m, 10H),
2.42−2.38 (m, 4H), 1.70−1.66 (m, 4H). HRMS (EI+): calcd for
C18H18 (M+) 234.1409, found 234.1411.
1
3064, 2959, 2925, 1609, 1509, 1457, 913, 743 cm−1. H NMR
Cyclopropyl(phenyl)(p-tolyl)methanol (5a). Cyclopro-
pylmagnesium bromide (4.5 mL, 4.5 mmol, 1 M in THF) was
added dropwise to a solution of phenyl(p-tolyl)methanone
(0.784 g, 4 mmol) in 40 mL of THF under a nitrogen atmosphere
at room temperature. Then the mixture was stirred at 40 °C for 2
h. The reaction was quenched with water, and the mixture was
extracted with diethyl ether (3 × 20 mL) and dried over
anhydrous Na2SO4. The solvent was removed by evaporation
under reduced pressure. Purification by column chromatography
on silica gel afforded the products (300−400 mesh, petroleum
ether and ethyl acetate as eluent). Colorless oil. Yield: 762 mg
yield: 80%. 1H NMR (CDCl3, 400 MHz): δ 7.35−7.00 (m, 9H),
2.2 (s, 3H), 1.82 (s, 1H), 1.51−1.48 (m, 1H), 0.507−0.42 (m,
2H), 0.395−0.366 (m, 2H). 13C NMR (100 MHz, CDCl3): δ
147.7, 144.6, 136.9, 128.9, 128.2, 127.2, 127.1, 77.7, 21.9.1, 21.4,
2.1, 2.0.
1-(4-Chloro-1-p-tolylbut-1-enyl)benzene (8). Isopropyl-
magnesium chloride (0.6 mL, 1.2 mmol, 2 M in THF) was added
to a solution of diethyl phosphite (1.2 mmol) in THF (6 mL)
under a nitrogen atmosphere at room temperature. The mixture
was stirred for 1 h, and then cyclopropyl(phenyl)(p-tolyl)-
methanol (5a) (0.238 g, 1.0 mmol) was added to the mixture.
After 5 h, the reaction was quenched with water, and the mixture
was extracted with diethyl ether (3 × 10 mL) and dried over
anhydrous Na2SO4. The solvent was removed by evaporation
under reduced pressure. Purification by column chromatography
on silica gel afforded the products (300−400 mesh, petroleum
ether and ethyl acetate as eluent). Colorless oil. Yield: 128 mg,
50%. 1H NMR (CDCl3, 400 MHz): δ 7.42−7.10 (m, 9H), 6.10
(t, J = 7.2 Hz), 3.60−3.57 (m, 2H), 2.65−2.57 (m, 2H), 2.41 (s,
1H), 2.35 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 144.3, 139.8,
139.3, 137.1, 136.9, 129.6, 129.0, 128.9, 128.3, 128.1, 127.3,
127.2, 124.6, 123.9, 44.4, 33.0, 32.9, 29.7, 21.1. HRMS (EI+):
calcd for C17H17Cl (M+) 256.1019, found 256.1022.
(CDCl3, 300 MHz): δ 8.10 (d, J = 6.6 Hz, 1H), 7.84−7.75 (m,
2H), 7.55−7.40 (m, 4H), 7.22 (d, J = 15.5 Hz, 1H), 7.20−6.14
(m, 1H), 3.56−3.51 (m, 2H), 2.89−2.86 (m, 2H). HRMS (EI+):
calcd for C14H13Br (M+) 260.0200, found 260.0201.
1-((E)-4-Bromobut-1-enyl)-2-chlorobenzene (3s). Col-
orless Oil. Yield: 52.2 mg, 40%. Compound purity: 99.26%. IR
(KBr): 3042, 2980, 1587, 1413, 1264, 1123, 990, 751 cm−1. 1H
NMR (CDCl3, 300 MHz): δ 7.52 (d, J = 5.9 Hz, 1H), 7.34 (d, J =
6.3 Hz, 1H), 7.21−7.17 (m, 2H), 6.88 (d, J = 15.5 Hz, 1H), 6.21−
6.14 (m, 1H), 3.50−3.48 (m, 2H), 2.83 (d, J = 5.9 Hz, 2H). 13C
NMR (100 MHz, CDCl3): δ 135.1, 132.8, 129.6, 129.6, 128.9,
128.5, 126.8, 126.7, 36.3, 32.1. HRMS (EI+): calcd for
C10H10ClBr (M+) 243.9654, found 243.9658.
5-((E)-4-Bromo-3-phenylbut-1-enyl)benzo[d][1,3]-
dioxole (3t). White solid. Yield: 62.9 mg, 38%. Compound
purity: 99.07%. IR (KBr): 3063, 3030, 2960, 1594, 1491, 1454,
1091, 1012 cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.41 (d, J = 7.2
Hz, 2H), 7.36−7.28 (m, 3H), 6.84 (s, 1H), 6.72 (s, 2H), 6.37 (d, J
= 15.8 Hz, 1H), 5.95−5.91 (m, 3H), 4.99 (t, J = 7.4 Hz, 1H),
3.14−3.02 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 146.0,
145.1, 139.6, 130.8, 129.5, 126.8, 126.5, 125.4, 122.5, 118.9,
106.3, 103.6, 99.1, 52.6, 41.3. HRMS (EI+): calcd for C17H15BrO2
(M+) 330.0255, found 330.0245.
1-((E)-1-Bromo-4-(4-methoxyphenyl)but-3-enyl)-
benzene (3u). Colorless oil. Yield: 44.3 mg, 28%. Compound
purity: 99.11%. IR (KBr): 3032, 1645, 1630, 1445, 912, 743
cm−1. 1H NMR (CDCl3, 400 MHz) δ 7.42 (d, J = 7.3 Hz, 2H),
7.37−7.23 (m, 5H), 6.82 (d, J = 8.4 Hz, 2H), 6.41 (d, J = 15.8 Hz,
1H), 6.01−5.93 (m, 1H), 5.00 (t, J = 7.4 Hz, 1H), 3.78 (s, 3H),
3.18−3.02 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 159.3,
141.9, 132.8, 130.0, 128.9, 128.6, 127.6, 127.6, 124.2, 114.1, 55.5,
54.9, 43.6. HRMS (EI+): calcd for C17H17BrO (M+) 316.0463,
found 316.0466.
1-((E)-1-Bromo-4-(4-bromophenyl)but-3-enyl)-
benzene (3v). White solid. Yield: 91 mg, 50%. Compound
purity: 96.30%. IR (KBr): 3033, 2988, 1595, 1490, 1440, 1029,
771, 701 cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.44−7.14 (m,
9H), 6.38 (d, J = 15.8 Hz, 1H), 6.14−6.07 (m, 1H), 4.99 (t, J =
7.4 Hz, 1H), 3.17−3.01 (m, 2H). 13C NMR (100 MHz, CDCl3):
δ 139.5, 134.0, 130.1, 129.7, 126.8, 126.6, 125.8, 125.4, 125.1,
119.2, 52.3, 41.3. HRMS (EI+): calcd for C16H14Br2 (M+)
363.9462, found 363.9450.
1-((E)-1-Bromo-4-(4-chlorophenyl)but-3-enyl)benzene
(3w). White solid. Yield: 61.0 mg, 38%. Compound purity:
98.41%. IR (KBr): 3064, 2959, 2925, 1609, 1509, 1457, 913, 743
cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.43−7.23 (m, 9H), 6.42
(d, J = 15.8 Hz, 1H), 6.14−6.06 (m, 1H), 5.00 (t, J = 7.4 Hz, 2H),
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: zhangsl@suda.edu.cn. Fax: +86-512-65880352.
Notes
The authors declare no competing financial interest.
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dx.doi.org/10.1021/jo400580n | J. Org. Chem. XXXX, XXX, XXX−XXX

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ACKNOWLEDGMENTS
■
We gratefully acknowledge A Project Funded by the Priority
Academic Program Development of Jiangsu Higher Education
Institutions and the National Natural Science Foundation of
China (21072143) for their financial support.
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