Bromination of olefins with HBr and DMSO

Article abstract of DOI:10.1021/acs.joc.5b00211

A simple and inexpensive methodology is reported for the conversion of alkenes to 1,2-dibromo alkanes via oxidative bromination using HBr paired with dimethyl sulfoxide, which serves as the oxidant as well as cosolvent. The substrate scope includes 21 olefins brominated in good to excellent yields. Three of six styrene derivatives yielded bromohydrins under the reaction conditions.

Full text of DOI:10.1021/acs.joc.5b00211

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Note
Bromination of Olefins with HBr and DMSO
Megha Karki, and Jakob Magolan
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 04 Mar 2015
Downloaded from http://pubs.acs.org on March 7, 2015
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Bromination of Olefins with HBr and DMSO
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Megha Karki and Jakob Magolan*
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Department of Chemistry, University of Idaho, Moscow, ID 83844, USA
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We dedicate this manuscript to the memory of the late Dr. Aaron D. Mills.
Abstract: A simple and inexpensive methodology is reported for the conversion of alkenes to
1,2ꢀdibromo alkanes via oxidative bromination using HBr paired with dimethylsulfoxide which
serves as the oxidant as well as coꢀsolvent. The substrate scope includes 21 olefins brominated
in good to excellent yields. Three of six styrene derivatives yielded bromohydrins under the
reaction conditions.
Keywords: Bromination, dimethylsulfoxide, HBr, alkene, 1,2ꢀdibromoalkane, bromohydrin
Vicinal dibromoalkanes (2) are useful synthetic precursors to cyclopropanes,1 alkynes,2 and
vinylbromides of value in crossꢀcoupling chemistry.2ꢀ3 Their various preparations from alkenes
(1) can be classified into three general approaches:1) treatment with molecular bromine in
halogenated solvent4 or alternative media,5 2) treatment with a bromine carrying agent such as a
tribromide salt6 or analogous reagent,7 and 3) treatment with bromide in the presence of a
stoichiometric oxidant such as Oxone,8 H2O2,9 O2,10 Selectfluor,11 and others12 (Scheme 1). The
third of these strategies, oxidative bromination, is analogous to the biological solution to
electrophilic halogenation which employs haloperoxidase (H2O2) or flavin dependent halogenase
(O2) enzymes to produce ‘X+’ from Xꢀ.13 In their 2008 comparative review of 24 methods,
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Eissen and Lenoir concluded that many modern bromination methods that circumvent the use of
molecular bromine suffer from significantly higher resource demands and waste production
compared to the traditional choice of Br2 in CHCl3.14 The authors emphasize the need for
continued development in this field and highlight oxidative bromination in general, and the use
of H2O2/HBr specifically,9c as the most favorable of current methods based on a number of
environmental, health, and safety factors.
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Scheme 1. General approaches to bromination of olefins.
Herein we present our discovery of a simple oxidative bromination of olefins using HBr and
dimethylsufoxide (DMSO). DMSO is a polar aprotic solvent widely used for synthetic
applications at all scales.15 In the presence of various activating reagents, DMSO is a mild
oxidant that has been employed primarily for the oxidation of alcohols.16 DMSOꢀbased
oxidations are metalꢀfree, mild, and inexpensive. For these reasons, we are interested in
expanding the use of this oxidant. In the present case we sought to test the potential applicability
of DMSO in the context of oxidative bromination. We began by treating allylbenzene (3) with
four bromide reagents in DMSO (Table 1).
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Table 1. Reaction discovery.a
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Entry
Brꢀ source
Bu4NBr
solvent
DMSO
DMSO
DMSO
DMSO
CHCl3
yieldb
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2
3
4
5
0
0
KBr
NaBr
0
HBr (48% aq.)
HBr (48% aq.)
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0
Reaction conditions: Substrate (0.5 mmol), solvent (0.5 mL), ‘Brꢀ source’ (2 equiv); reaction workup with
a
Et2O/H2O. b NMR yield with CH2Br2 as internal standard.
Although no reaction occurred with Bu4NBr, KBr, or NaBr in DMSO, we were pleased to
observe that HBr yielded some of the desired 2,3ꢀdibromopropylbenzene (4, entry 4). The
reaction did not proceed when DMSO was replaced with chloroform (entry 5) in which case
trace hydrobromination was observed but most of the substrate remained unreacted.
In previous literature the pairing of HBr and DMSO has been used for the alpha oxidation of
ketones,17 bromination of arenes,18 and benzylic oxidation.19 In most cases, it was believed that
HBr reacts with DMSO to yield bromodimethylsulfonium bromide (BDMS, 5), a wellꢀ
established electrophilic bromination reagent that is more commonly prepared from
dimethylsulfide and bromine.20 BDMS is an orange solid that precipitates from dichloromethane
solution upon addition of DMS and Br2.21 Most commonly this reagent has been used to
brominate various arenes and carbonyl derivatives.20 In 2008 Das and coꢀworkers reported
bromination of olefins with BDMS in acetonitrile.22 Earlier, similar reaction conditions were
employed by Chow and Bakker to form 1ꢀbromoꢀ2ꢀsulfonium bromides, such as 7, which
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precipitated in low yields upon treatment of olefins with BDMS in CH2Cl2 or CH3CN at 0° C
(Scheme 2a).23
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Scheme 2. Work of Chow and Bakker23 and our comparison of HBr with BDMS.
We compared directly the reactivity of HBr in DMSO to BDMS in DMSO using cyclohexene as
the substrate (Scheme 2b). In neither case was precipitation of sulfonium salts observed but
rather exclusive conversion to transꢀ1,2ꢀdibromocyclohexane in low yields after 12 hours at
room temperature. Upon addition of water to the BDMS/DMSO reaction (intended to mimic the
water present in our HBr/DMSO system) the rates of the two processes were similar with 18%
and 16% yields respectively after 12 hours at room temperature. These observations lend
support to the notion that the active brominating species in the HBr/DMSO process is BDMS.
We conducted a brief optimization of this reaction (Table 2).
The yield of (2,3ꢀ
dibromopropyl)benzene (4) from allylbenzene was improved to 57% and 96% by increasing the
amount of HBr to 5 and 10 equivalents respectively and extending reaction time to 24 hours
(entries 2 and 3). When the reaction temperature was warmed to 65 °C, a yield of 86% was
observed in just 12 hours with 5 equiv. of HBr (entry 4). A screen of coꢀsolvents identified the
two solvent mixture of DMSO and CHCl3 (1:1) as optimal giving nearly quantitative conversion,
and 80% isolated yield, of the desired product after 12 hours at 65 °C.
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Table 2. Reaction Optimization.a
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entry
Solvent
HBr
Temp.
(°C)
rt
Time
(h)
24
yieldb
(equiv.)
1
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5
DMSO
DMSO
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rt
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DMSO
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5
rt
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96
DMSO
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86
c
DMSO/CHCl3
5
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98 (80)d
a
b
c.
Reaction conditions: Substrate (0.5 mmol), solvent (0.5 mL). NMR yield with CH2Br2 as internal standard.
DMSO (0.5 mL) and CHCl3 (0.5 mL). d. Isolated yield.
The substrate scope of this bromination was evaluated with 10 terminal olefins and 8
polysubstituted olefins (Table 3).
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Table 3: Substrate Scope a
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a. Reaction Conditions: Alkene substrate (0.5 ꢀ 1.0 mmol), HBr (48% aq., 5 equiv.), DMSO (1 mL per mmol of
substrate), CHCl3 (1 mL per mmol of substrate); Reported yields are for isolated products after chromatography.
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Allyl alcohol was converted to 2,3ꢀdibromopropanꢀ1ꢀol (11) in 90% yield in 24 hours at room
temperature. 1ꢀoctene was brominated in 12 hours at 65 °C to yield the corresponding
dibromooctane 12 in 86% isolated yield. Allyl benzene and pꢀmethoxy allylbenezene were
readily brominated to give bromoalkanes 4 and 15 in 80% and 90% respectively. Reaction of
allyl benzoate gave dibromide 16 in 6 hours with 62% isolated yield. Longer reaction times
resulted in considerable hydrolysis of the ester. Nꢀallyl benzotriazoles gave compounds 18 and
19 in good yields. For cyclohexene, the reaction temperature was lowered to room temperature
to avoid loss of the volatile substrate. The reaction was completed in 12 hours giving transꢀ1,2ꢀ
dibromocyclohexane (8) in 72% isolated yield. Conversion of cyclooctene was also complete at
room temperature in 24 hours to give 20 in 99% yield. The temperature was also lowered for
two other substrates, acenaphthylene and cisꢀjasmone, to minimize the formation of unidentified
side products. In these cases the desired dibromoalkanes 21 and 22 were obtained in 67% and
50% after 32 and 24 hours respectively. A reaction time of 40 hours at 65 °C was required for
complete conversion of transꢀstilbene to the corresponding product (23) which was obtained in
87% yield. Carboxylic acids are well tolerated under these reaction conditions with compounds
24 and 25 obtained in good yields. Compound 25 was isolated as a single diastereomer in 74%
yield. Finally, 3ꢀmethylbutꢀ2ꢀenꢀ1ꢀol reacted rapidly giving the dibromoalcohol 26 in 66% yield.
We next applied this reaction to a series of styrene derivatives (Table 4). Styrene (30), pꢀ
bromostyrene (32), and mꢀmethoxystyrene (34) behaved as expected giving the corresponding
dibromides in good yields. However, in the case of αꢀmethylstyrene (36), we observed nearly
exclusive formation of the trans-bromohydrin 37 which was isolated in 93% yield. Similarly
1,2ꢀdihydronaphthalene (38) and indene (40) afforded trans-bromohydrins 39 and 41
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respectively in good isolated yields. In these two cases a small amount of dibromination was
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also observed via crude H NMR. A control experiment was conducted to determine the
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potential that bromohydrins 37, 39, and 41 are formed via initial bromination and subsequent
substitution of –Br with –OH. We subjected 1,2ꢀdibromoindane (prepared via standard Br2ꢀ
based bromination of indene) to our HBr/DMSO reaction conditions. We observed complete
conversion of 1,2ꢀdibromoindane to bromohydrin 41 in 12 hours. Thus it is possible that
substrates 36, 38, and 40 undergo initial dibromination before conversion to bromohydrins. The
isolated bomohydrins have a trans relationship between hydroxyl and bromide groups.
Therefore, if a substitution of –Br to –OH occurs, the observed stereochemistry indicates an SN1
process whereby a carbocation intermediate reacts with water at its less sterically hindered face.
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Table 4. Reaction of styrene derivatives
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Entry
Substrate
Product
Time
(h)
Temp
(° C)
Isolated
Yield
(%)
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93
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Scheme 3 offers a proposed mechanism for the conversion of DMSO to BDMS followed by
subsequent olefin bromination.
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Scheme 3. Proposed reaction mechanism.
This methodology was not suitable for the bromination of α,βꢀunsaturated carbonyl
derivatives. We also attempted to replace HBr with HCl for an analogous chlorination reaction
without success. We must report that our work directly contradicts Yusobov et al. who have
reported the oxidation of olefins to 1,2ꢀdiketones under identical conditions.24
In summary, we have described a unique process for dibromination of olefins with HBr and
DMSO. This methodology offers a simple, inexpensive, and mild alternative to the use of Br2 or
other more resourceꢀintensive strategies.
Experimental Section
General Considerations: Unless otherwise noted, commercially available reagents and solvents
were used without further purification. Infrared spectra were obtained on a Thermo Scientific
Nicolet 380 FTꢀIR spectrometer as thin films on ZnSe disks and peaks are reported in cmꢀ1. H
1
13
and C NMR experiments were performed on a Bruker AVANCE 500 MHz instrument and
1
samples were obtained in CDCl3 (referenced to 7.26 ppm for H and 77.0 ppm for 13C).
Coupling constants (J) are in Hz. The multiplicities of the signals are described using the
following abbreviations: s = singlet, d = doublet, t = triplet, m = multiplet, br = broad. MALDIꢀ
HRMS of compounds were recorded on a QꢀTOF mass spectrometer using 2,5ꢀdihydroxybenzoic
acid as a matrix and mixture of polyethylene glycol (PEG 600) and (PEG 1000) as internal
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calibration standards. Elemental analyses were obtained on a CE0440 elemental analyzer (EAI
Exeter Analytical). Reaction progress was monitored by thinꢀlayer chromatography (TLC, EMD
Chemicals Inc, Silica Gel 60 F254), visualized under UV light, and plates were developed using
pꢀanisaldehyde or potassium permanganate stains. Flash chromatography was performed using
silica gel (Sorbent Technologies, particle size 40ꢀ63 µm). Melting points were determined using
a MelꢀTemp II apparatus and are uncorrected.
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General Procedure for Dibromination Reaction: A solution of HBr (48% aq., 5 equiv.) in
DMSO (1 mL per mmol of substrate) is added to a reaction vial containing a magnetic stir bar
and the alkene substrate (0.5 ꢀ 1.0 mmol) in CHCl3 (1 mL per mmol of substrate). The reaction
vial is capped and stirred at the specified temperature (rt or 65 °C) until complete disappearance
of starting material is observed by TLC or 1H NMR (TLC plates visualized using pꢀanisaldehyde
or potassium permanganate stains). The reaction is transferred to a separatory funnel containing
water and extracted with ether (3 x 30 mL). The combined organic extracts are dried over
MgSO4, and solvent removed in vacuo. The residue is purified by flash column chromatography
on silica gel (gradient elution with EtOAc and hexanes). Note: Flash chromatography effectively
removes all trace DMSO that may remain after workup.
(2,3-Dibromopropyl) benzene (4): The standard procedure was used with allylbenzene (132.5
µL, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL). After 12 hours of stirring
at 65 oC, the reaction was worked up and purified as described above to yield compound 4 as oil
(0.223 g, 80% yield). Rf = 0.87 (Hexanes/EtOAc 70:30 v/v); 1H NMR (CDCl3, 500 MHz) δ 7.37
– 7.27 (m, 5H), 4.41 – 4.33 (m, 1H), 3.83 (dd, J = 10.5, 4.2 Hz, 1H), 3.64 (dd, J = 10.4, 8.9 Hz,
1H), 3.51 (dd, J = 14.5, 4.8 Hz, 1H), 3.14 (dd, J = 14.5, 7.8 Hz, 1H); 13C NMR (CDCl3, 125
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MHz) δ 136.9, 129.5, 128.5, 127.2, 52.4, 42.0, 36.0. H and 13C NMR spectral data is consistent
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with previously reported values.25
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trans-1,2-Dibromocyclohexane (8): The standard procedure was used with cyclohexene (101
µL, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL). After 12 hours of stirring
at room temperature, the reaction was worked up and purified as described above to yield
compound 8 as a colorless liquid product (175 mg, 72% yield). Rf = NA; 1H NMR (CDCl3, 500
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MHz) δ 4.45 (s, 2H), 2.57 – 2.31 (m, 2H), 1.96 – 1.74 (m, 4H), 1.57 – 1.46 (m, 2H); C NMR
(CDCl3, 125 MHz) δ 55.2, 32.1, 22.4. 1H and 13C NMR spectral data is consistent with
previously reported values.5d
2,3-Dibromopropan-1-ol (11): The standard procedure was used with allyl alcohol (68 µL, 1.0
mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL). The reaction was stirred for 24
hours at room temperature. After workup and purification above compound 11 was obtained as a
1
colorless liquid (196 mg, 90 % yield). Rf = 0.62 (Hexanes/EtOAc 70:30 v/v); H NMR (CDCl3,
500 MHz) δ 4.39 – 4.23 (m, 1H), 4.02 (d, J = 3.9 Hz, 2H), 3.88 – 3.74 (m, 2H), 1.94 (s, 1H); 13C
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13
NMR (CDCl3, 125 MHz) δ 64.2, 53.6, 31.5. H and C NMR spectral data is consistent with
previously reported values.26
1,2-Dibromooctane (12): The standard procedure was used with 1ꢀoctene (78.5 µL, 0.5 mmol),
o
HBr (48% aq., 0.28 mL, 2.5 mmol), and DMSO (0.5 mL). After 12 hours of stirring at 65 C,
the reaction was worked up and purified as described above to yield compound 12 as a colorless
1
liquid product (116.2 mg, 86% yield); Rf = 0.65 (Hexanes/EtOAc 70:30 v/v); H NMR (CDCl3,
500 MHz) δ 4.25 – 4.08 (m, 1H), 3.85 (dd, J = 10.2, 4.5 Hz, 1H), 3.63 (t, J = 9.9 Hz, 1H), 2.20 –
2.07 (m, 1H), 1.79 (dddd, J = 14.6, 10.0, 9.0, 4.6 Hz, 1H), 1.64 – 1.48 (m, 1H), 1.48 – 1.24 (m,
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6H), 0.94 – 0.86 (m, 3H); 13C NMR (CDCl3, 125 MHz) δ 53.2, 36.4, 36.1, 31.6, 28.5, 26.7, 22.5,
14.0. 1H and 13C NMR spectral data is consistent with previously reported values.5b
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1,2,4-Tribromobutane (13): The standard procedure was used with 4ꢀbromobutꢀ1ꢀene (102 µL,
1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL). After 24 hours of stirring at
65 °C, the reaction was worked up and purified as described above to yield compound 13 as clear
colorless oil (179 mg, 61 % yield); 1H NMR (CDCl3, 500 MHz) δ 4.38 (tdd, J = 9.8, 4.3, 2.8 Hz,
1H), 3.90 (dd, J = 10.5, 4.2 Hz, 1H), 3.72 – 3.51 (m, 3H), 2.68 (dddd, J = 15.5, 9.3, 6.4, 2.8 Hz,
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1H), 2.26 (dddd, J = 15.5, 10.0, 5.5, 4.3 Hz, 1H); C NMR (CDCl3, 125 MHz) δ 50.3, 39.2,
35.9, 30.4; IR (cmꢀ1): 2923.3, 1462.9, 736.8, 475.43; Elemental analysis: (C4H7Br3, 294.81)
Calcd: C, 16.3%; H, 2.39%. Found: C, 16.73%; H, 2.07%.
1,2,5-Tribromopentane (14): The standard procedure was used with 5ꢀbromopentꢀ1ꢀene (118.5
µL, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL). After 24 hours of stirring
at 65°C, the reaction was worked up and purified as described above to yield compound 14 as oil
(227 mg, 74 % yield); Rf = 0.66 (Hexanes/EtOAc 90:10 v/v); 1H NMR (CDCl3, 500 MHz) δ 4.18
(tdd, J = 9.8, 4.4, 3.0 Hz, 1H), 3.87 (dd, J = 10.3, 4.4 Hz, 1H), 3.63 (t, J = 10.1 Hz, 1H), 3.51 –
3.40 (m, 2H), 2.43 – 2.33 (m, 1H), 2.24 – 2.13 (m, 1H), 2.07 – 1.88 (m, 2H); 13C NMR (CDCl3,
125 MHz) δ 51.43, 35.82, 34.71, 32.27, 30.02; IR (cmꢀ1): 2959.7, 1257.0, 1141.0, 563.8;
Elemental analysis: (C5H9Br3, 308.84) Calcd: C, 19.45%; H, 2.94%. Found: C, 19.71%; H,
2.84%.
1-(2,3-Dibromopropyl)-4-methoxybenzene (15): The standard procedure was used with 1ꢀ
allylꢀ4ꢀmethoxybenzene (153.4 µL, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1
o
mL). After 12 hours of stirring at 65 C, the reaction was worked up and purified as described
above to yield compound 15 as colorless oil (276.6 mg, 90% yield); Rf = 0.65 (Hexanes/EtOAc
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90:10 v/v); 1H NMR (CDCl3, 500 MHz) δ 7.25 – 7.15 (m, 2H), 6.92 – 6.83 (m, 2H), 4.33 (dddd,
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J = 9.0, 7.4, 4.9, 4.2 Hz, 1H), 3.84 – 3.78 (m, 3H), 3.81 (s, 3H), 3.61 (dd, J = 10.5, 8.9 Hz, 1H),
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3.42 (dd, J = 14.6, 4.9 Hz, 1H), 3.10 (dd, J = 14.7, 7.5 Hz, 1H); C NMR (CDCl3, 125 MHz) δ
10
11
12
13
14
15
16
17
18
19
20
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22
23
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25
26
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158.8, 130.6, 128.8, 113.9, 55.2, 52.9, 41.1, 35.9; IR(cmꢀ1): 2929.8, 2833.6, 1610.4, 1509.9,
1463.1, 1430.4, 1242.7, 1176.3, 1031.6, 806.2, 594.5; Elemental analysis: (C10H12Br2O, 308.01)
Calcd: C, 38.99%; H, 3.93%. Found: C, 39.21%; H, 3.84%.
2,3-Dibromopropyl benzoate (16): The standard procedure was used with allyl benzoate (154
µL, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL). After 6 hours of stirring
at 65 °C, the reaction was worked up and purified as described above to yield compound 16 as
clear colorless oil (182 mg, 62% yield); Rf = 0.35 (Hexanes/EtOAc 90:10 v/v); 1H NMR (CDCl3,
500 MHz) δ 8.11 – 8.04 (m, 2H), 7.63 – 7.56 (m, 1H), 7.51 – 7.45 (m, 2H), 4.77 (dd, J = 12.2,
4.5 Hz, 1H), 4.72 (dd, J = 12.2, 5.3 Hz, 1H), 4.47 (ddt, J = 9.2, 5.3, 4.6 Hz, 1H), 3.88 (dd, J =
13
10.7, 4.8 Hz, 1H), 3.83 (dd, J = 10.7, 9.1 Hz, 1H); C NMR (CDCl3, 125 MHz) δ 165.8, 133.4,
129.8, 129.5, 128.5, 65.60, 47.0, 32.1; IR (cmꢀ1) 2950, 1720.6, 1602.1, 1451.92, 1377.2, 1267.7,
725.9, 707.04; APCIꢀHRMS Calcd for C10H11Br2O2 (M+H)+ : 320.9126. Found: 320.9115.
((2,3-Dibromopropoxy)methyl)benzene (17):
The standard procedure was used with
((allyloxy)methyl)benzene (77.6 µL, 0.5 mmol), HBr (48% aq., 0.28 mL, 2.5 mmol), and DMSO
(0.5 mL). After 5 hours of stirring at 65 °C, the reaction was worked up and purified as
described above to yield compound 17 as clear colorless oil (100 mg, 65% yield); Rf = 0.69
(Hexanes/EtOAc 90:10 v/v); 1H NMR (CDCl3, 500 MHz) δ 7.36 (d, J = 4.8 Hz, 5H), 4.66 – 4.58
13
(m, 2H), 4.27 (dd, J = 8.3, 4.9 Hz, 1H), 3.92 – 3.79 (m, 4H); C NMR (CDCl3, 125 MHz) δ
137.5, 128.5, 127.9, 127.7, 73.5, 71.1, 49.1, 33.1; IR (cmꢀ1) 3028.9, 2859.7, 1495.3, 1452.4,
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1360.0, 1072.6, 695.4, 573.9. H and 13C NMR spectral data is consistent with previously
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reported values.27
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2-(2,3-Dibromopropyl)-2H-benzotriazole (18): The standard procedure was used with 2ꢀallylꢀ
2Hꢀbenzotriazole (125 mg, 0.79 mmol), HBr (48% aq., 0.44 mL, 3.95 mmol), and DMSO (1
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60
o
mL). After 24 hours of stirring at 65 C, the reaction was worked up and purified as described
above to yield compound 18 as white solid (175 mg, 70% yield); mp = 81ꢀ83 ºC; Rf = 0.79
1
(Hexanes/EtOAc 70:30 v/v); H NMR (CDCl3, 500 MHz) δ 7.98 – 7.79 (m, 2H), 7.41 (dd, J =
6.6, 3.1 Hz, 2H), 5.34 (dd, J = 14.1, 5.4 Hz, 1H), 5.13 (dd, J = 14.1, 7.1 Hz, 1H), 4.87 (tt, J = 7.3,
5.4 Hz, 1H), 3.99 – 3.77 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ 144.6, 126.9, 118.2, 59.9, 47.0,
33.4; IR (cmꢀ1): 3041.2, 2922.59, 1561.2, 1425.4, 1345.9, 1168.2, 751.2; ESIꢀHRMS Calcd for
C9H9Br2N3 (M+H)+: 317.9243. Found: 317.9243.
1-(2,3-Dibromopropyl)-1H-benzotriazole (19): The standard procedure was used with 1ꢀallylꢀ
1Hꢀbenzotriazole (159 mg , 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL).
After 24 hours of stirring at 65 oC, the reaction was worked up and purified as described above to
yield compound 19 as white solid. (130 mg, 81% yield); Rf = 0.85 (Hexanes/EtOAc 90:10 v/v);
1H NMR (CDCl3, 500 MHz) δ 8.12 – 8.07 (m, 1H), 7.64 (dt, J = 8.4, 0.9 Hz, 1H), 7.57 – 7.51
(m, 1H), 7.41 (ddd, J = 8.4, 6.9, 1.0 Hz, 1H), 5.25 (dd, J = 14.9, 5.0 Hz, 1H), 5.05 (dd, J = 14.9,
13
6.9 Hz, 1H), 4.76 (dddd, J = 8.2, 6.9, 5.1, 4.5 Hz, 1H), 3.89 – 3.76 (m, 3H); C NMR (CDCl3,
125 MHz) δ 145.8, 133.6, 127.9, 124.2, 120.3, 109.4, 51.9, 47.8, 33.5, 29.7; IR (cmꢀ1): 2977.3,
1590.5, 1488.0, 1407.2, 1102.47, 728.77; ESIꢀHRMS Calcd for C9H9Br2N3 (M+H)+: 317.9241.
Found 317.9244.
1,2-Dibromocyclooctane (20): The standard procedure was used with cyclooctene (130 µL, 1.0
mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL). After 24 hours of stirring at room
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temperature, the reaction was worked up and purified as described above to yield compound 20
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as a colorless liquid product (268 mg, 99% yield); Rf = 0.81 (Hexanes/EtOAc 90:10 v/v); H
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NMR (CDCl3, 500 MHz) δ 4.64 – 4.51 (m, 1H), 2.41 (dddd, J = 15.8, 8.9, 3.6, 1.3 Hz, 1H), 2.09
(dddd, J = 15.7, 7.8, 5.0, 2.7 Hz, 1H), 1.90 – 1.79 (m, 1H), 1.72 – 1.54 (m, 2H), 1.53 – 1.42 (m,
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13
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1H); C NMR (CDCl3, 125 MHz) δ 61.5, 33.2, 25.9, 25.4. H and C NMR spectral data is
consistent with previously reported values.28
trans-1,2-Dibromoacenaphthene (21): The standard procedure was used with acenaphthylene
(100 mg, 0.66 mmol), HBr (48% aq., 0.37 mL, 5 mmol), and DMSO (0.5 mL). After 32 hours of
stirring at 35 oC, the reaction was worked up and purified as described above to yield compound
21 as light brown solid (138 mg, 67% yield); mp = 111ꢀ114 ºC; Rf = 0.83 (Hexanes/EtOAc 90:10
v/v); 1H NMR (CDCl3, 500 MHz) δ 7.82 (dd, J = 7.5, 1.4 Hz, 2H), 7.70 – 7.56 (m, 4H), 6.01 (s,
13
1
13
2H); C NMR (CDCl3, 125 MHz) δ 140.5, 134.8, 131.0, 128.8, 125.9, 122.5, 54.9; H and C
NMR spectral data is consistent with previously reported values.29
2-(2,3-Dibromobutyl)-3-methylcyclopent-2-enone (22): The standard procedure was used
with cisꢀjasmone (170 µL, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL).
After 24 hours of stirring at room temperature, the reaction was worked up and purified as
described above to yield compound 22 as clear oil (151 mg, 50% yield); Rf = 0.72
1
(Hexanes/EtOAc 70:30 v/v); H NMR (CDCl3, 500 MHz) δ 4.57 (td, J = 7.0, 2.3 Hz, 1H), 4.02
(ddd, J = 8.0, 5.5, 2.3 Hz, 1H), 2.88 (d, J = 7.0 Hz, 2H), 2.61 – 2.51 (m, 2H), 2.44 – 2.36 (m,
2H), 2.15 (s, 3H), 2.05 – 1.94 (m, 2H), 1.06 (t, J = 7.3 Hz, 3H); 13C NMR (CDCl3, 125 MHz) δ
209.2, 173.7, 136.5, 62.0, 56.9, 34.2, 32.0, 32.0, 30.6, 17.8, 12.4; IR (cmꢀ1): 2967.6, 2912.6,
1690.9, 1644.6, 1432.9, 1382.5, 545.91.512.9; Elemental analysis: (C11H16Br2O, 324.06) Calcd:
C, 40.77%; H, 4.98 %. Found: C, 40.95 %; H, 4.91 %.
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meso-1,2-Dibromo-1,2-diphenylethane (23): The standard procedure was used with transꢀ
stilbene (180 mg, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL). After 40
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8
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o
hours of stirring at 65 C, the reaction was worked up and purified as described above to yield
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compound 23 as white solid (295 mg, 87% yield); mp = 236ꢀ238 ºC; Rf = 0.78 (Hexanes/EtOAc
90:10 v/v); 1H NMR (CDCl3, 500 MHz) δ 7.55 – 7.49 (m, 4H), 7.45 – 7.34 (m, 6H), 5.48 (s, 2H);
13C NMR (CDCl3, 125 MHz) δ 140.0, 129.0, 128.8, 127.9, 56.1; Elemental analysis: (C14H12Br2,
1
13
340.06) Calcd: C, 49.45%; H, 3.56%. Found: C, 49.7%; H, 3.37%. H and C NMR spectral
data is consistent with previously reported values.11
3,4-Dibromocyclopentanecarboxylic acid (24): The standard procedure was used with
cyclopentꢀ3ꢀenecarboxylic acid (103 µL, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and
o
DMSO (1 mL). After 12 hours of stirring at 65 C, the reaction was worked up and purified as
described above to yield compound 24 as white powder (167 mg, 61% yield); mp = 111ꢀ113 ºC;
Rf = 0.51 (Hexanes/EtOAc 70:30 v/v); 1H NMR (CDCl3, 500 MHz) δ 4.63 (ddd, J = 4.8, 2.1, 1.2
Hz, 1H), 4.55 (dt, J = 6.2, 1.8 Hz, 1H), 3.45 – 3.33 (m, 1H), 3.11 – 2.97 (m, 2H), 2.68 – 2.57 (m,
1H), 2.49 (ddt, J = 15.0, 8.6, 1.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 179.0, 56.2, 54.3, 40.5,
37.2, 37.1; IR (cmꢀ1) 2920.93, 1686.83, 1315.21, 914.17, 535.45; Elemental Analysis:
(C6H8Br2O2, 271.94); Calcd: C, 26.50%; H, 2.97%; Found: C, 26.31%; H, 2.88%.
(1S,3R,4R)-3,4-dibromocyclohexanecarboxylic acid (25): The standard procedure was used
with cyclohexꢀ3ꢀenecarboxylic acid (117 µL, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and
DMSO (1 mL). After 12 hours of stirring at 65 °C, the reaction was worked up and purified as
described above to yield compound 25 as pale yellow solid (211.7 mg, 74% yield); mp = 80ꢀ82
ºC; Rf = 0.59 (Hexanes/EtOAc 70:30 v/v); δ 4.70 (dd, 1H), 4.60 (dd, J = 3.3 Hz, 1H), 3.01 – 2.92
(m, 1H), 2.67 – 2.59 (m, 1H), 2.57 – 2.47 (m, 1H), 2.28 – 2.20 (m, 1H), 2.08 – 1.93 (m, 4H). 13C
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NMR (CDCl3, 125 MHz) δ 180.2, 51.9, 51.8, 37.4, 30.7, 28.2, 23.0; IR (cmꢀ1) 2929.89, 2605.09,
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1
13
1701.33, 1451.40, 1283.43, 1026.09, 928.75, 889.46, 686.92, 541.99. H and C NMR spectral
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data is consistent with previously reported values.30
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2,3-Dibromo-3-methylbutan-1-ol (26): The standard procedure was used with 3ꢀmethylbutꢀ2ꢀ
enꢀ1ꢀol, (102 µL, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL). After 2
o
hours of stirring at 65 C, the reaction was worked up and purified as described above to yield
compound 26 as white crystals (162 mg, 66% yield); mp = 38ꢀ39 ºC; Rf = 0.59 (Hexanes/EtOAc
1
70:30 v/v); H NMR (CDCl3, 500 MHz) δ 4.42 (dd, J = 8.2, 2.9 Hz, 1 H), 4.33 (d, J = 12.6, 2.9
13
Hz, 1 H), 3.98 (dd, J = 8.2, 12.5 Hz, 1 H), 1.98 (s, 3 H), 1.84 (s, 3 H); C NMR (CDCl3, 125
MHz) δ 69.0, 66.1, 64.8, 35.5, 29.7; IR (cmꢀ1) 3243.76, 2972.09, 2953.23, 1376.92, 1093.64,
1067.70, 975.03, 548.19; Elemental analysis: (C5H10Br2O, 245.94) Calcd: C, 24.42%; H, 4.1%.
Found: C, 24.81%; H, 4.01%.
1,2-(Dibromoethyl)-benzene (31): The standard procedure was used with styrene (30, 57.5 µL,
0.5 mmol), HBr (48% aq., 0.28 mL, 2.5 mmol), and DMSO (0.5 mL). After 12 hours of stirring
o
at 65 C, the reaction was worked up and purified as described above to yield compound 30 as
1
white solid (80 mg, 61% yield); mp = 71ꢀ73 ºC; Rf = 0..79 (Hexanes/EtOAc 90:10 v/v); H
NMR (CDCl3, 500 MHz) δ 7.44 – 7.32 (m, 3H), 5.15 (dd, J = 10.6, 5.4 Hz, 1H), 4.11 – 3.99 (m,
13
13
1H); C NMR (CDCl3, 125 MHz) δ 138.7, 129.2, 128.9, 127.7, 50.9, 35.0. 1H and C NMR
spectral data is consistent with previously reported values.12f
1-Bromo-4-(1, 2-bromoethyl)benzene (33): The standard procedure was used with 4ꢀ
bromostyene (32, 131 µL, 1.0 mmol), HBr (48% aq., 0.56 mL, 5 mmol), and DMSO (1 mL).
After 24 hours of stirring at 65 oC, the reaction was worked up and purified as described above to
yield compound 33 as white solid (222 mg, 65% yield); mp = 56ꢀ58 ºC; Rf = 0.82
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(Hexanes/EtOAc 90:10 v/v); 1H NMR (CDCl3, 500 MHz) δ 7.54 – 7.50 (m, 2H), 7.30 – 7.26 (m,
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4
5
6
2H), 5.09 (dd, J = 11.0, 5.1 Hz, 1H), 4.06 (dd, J = 10.3, 5.1 Hz, 1H), 3.96 (dd, J = 11.0, 10.3 Hz,
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1H);13C NMR (CDCl3, 500 MHz) δ 137.7, 132.1, 129.3, 123.2, 49.6, 34.6. H and C NMR
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spectral data is consistent with previously reported values.31
1-(1,3-Dibromoethyl)-3-methoxybenzene (35): The standard procedure was used with 3ꢀ
methoxystyene (34, 69.4 µL, 0.5 mmol), HBr (48% aq., 0.28 mL, 2.5 mmol), and DMSO (0.5
o
mL). After 12 hours of stirring at 65 C, the reaction was worked up and purified as described
above to yield compound 35 as white solid (90 mg, 61% yield); mp = 64ꢀ66 ºC; Rf = 0.61
(Hexanes/EtOAc 90:10 v/v); 1H NMR (CDCl3, 500 MHz) δ 7.30 (t, J = 7.9 Hz, 1H), 6.99 (ddd, J
= 7.8, 1.6, 0.8 Hz, 1H), 6.94 (t, J = 2.1 Hz, 1H), 6.88 (ddd, J = 8.3, 2.6, 0.9 Hz, 1H), 5.11 (dd, J
13
= 10.5, 5.4 Hz, 1H), 4.11 – 3.93 (m, 2H), 3.83 (s, 3H); C NMR (CDCl3, 125 MHz) δ 159.8,
140.1, 129.9, 119.9, 114.6, 113.5, 55.3, 50.8, 35.0; IR (cmꢀ1): 2917.1, 2833.9, 1600.22, 1490.4,
1462.29, 1434.1, 1047.0, 698.3; Elemental analysis: (C9H10Br2O, 293.99) Calcd: C, 36.77%; H,
3.43%. Found: C, 36.44%; H, 3.45%.
1-Bromo-2-phenylpropan-2-ol (37): The standard procedure was used with αꢀ methylstyrene
(36, 65 µL, 0.5 mmol), HBr (48% aq., 0.28 mL, 2.5 mmol), and DMSO (0.5 mL). After 3 hours
o
of stirring at 65 C, the reaction was worked up and purified as described above to yield
1
compound 37 as colorless oil (100 mg, 93% yield); Rf = 0.76 (Hexanes/EtOAc 70:30 v/v); H
NMR (CDCl3, 500 MHz) δ 7.49 – 7.44 (m, 2H), 7.41 – 7.35 (m, 2H), 7.33 – 7.27 (m, 1H), 3.82 –
13
3.67 (m, 1H), 2.53 (s, 1H), 1.69 (s, 3H); C NMR (CDCl3, 125 MHz) δ 144.2, 128.4, 127.5,
124.9, 73.1, 46.3, 28.1; IR (cmꢀ1) 3437.57, 2975.72, 1492.64, 1445.88, 1373.48, 1064.98, 696.85.
1H and 13C NMR spectral data is consistent with previously reported values.32
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trans-2-Bromo-1,2,3,4-tetrahydronaphthalen-1-ol (39): The standard procedure was used
with 1,2ꢀdihydronaphthalene (38, 65.3 µL, 0.5 mmol), HBr (48% aq., 0.28 mL, 2.5 mmol), and
DMSO (0.5 mL). After 12 hours of stirring at 65 oC, the reaction was worked up and purified as
described above to yield compound 39 as white powder (82 mg, 72% yield); mp = 108ꢀ110 ºC;
Rf = 0.5 (Hexanes/EtOAc 90:10 v/v); 1H NMR (CDCl3, 500 MHz) δ 7.57 – 7.48 (m, 1H), 7.26 –
7.23 (m, 2H), 7.14 – 7.07 (m, 1H), 4.91 (d, J = 7.0 Hz, 1H), 4.37 (ddd, J = 10.0, 7.0, 3.2 Hz, 1H),
3.09 – 2.85 (m, 2H), 2.51 (td, J = 5.7, 3.1 Hz, 1H), 2.29 (dddd, J = 13.7, 9.7, 8.4, 6.0 Hz, 1H);
13C NMR (CDCl3, 125 MHz) δ 135.4, 135.0, 128.5, 128.03, 126.7, 74.2, 56.2, 29.8, 28.1. 1H and
13C NMR spectral data is consistent with previously reported values.33
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trans-2-Bromo-1-indanol (41): The standard procedure was used with indene (40, 57.8 µL, 0.5
mmol), HBr (48% aq., 0.28 mL, 2.5 mmol), and DMSO (0.5 mL). After 12 hours of heating at
o
65 C, the reaction was worked up and purified as described above to yield compound 41 as
white powder (69.3 mg, 65% yield); mp = 120ꢀ122 ºC; Rf = 0.68 (Hexanes/EtOAc 70:30 v/v); 1H
NMR (CDCl3, 500 MHz) δ 7.44 – 7.40 (m, 1H), 7.31 – 7.28 (m, 2H), 7.25 – 7.21 (m, 1H), 5.32
(d, J = 5.8 Hz, 1H), 4.29 (td, J = 7.3, 5.8 Hz, 1H), 3.59 (dd, J = 16.2, 7.3 Hz, 1H), 3.28 – 3.19
13
(m, 1H); C NMR (CDCl3, 125 MHz) δ 141.7, 139.7, 129.0, 127.6, 124.6, 124.1, 83.5, 54.5,
40.5; IR (cmꢀ1) 3211.77, 2908.20, 2849.39, 1477.19, 1461.02, 1438.36, 1343.48, 1289.79,
1
13
1183.46, 1063.85, 750.17, 729.86. H and C NMR spectral data is consistent with previously
reported values.8b
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Supporting Information: 1H and 13C NMR spectra are provided. This material is available free
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of charge via the Internet at http://pubs.acs.org/.
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Author Information
Corresponding Author
* Eꢀmail: jmagolan@uidaho.edu
Acknowledgements
We wish to acknowledge the support of the University of Idaho. We appreciate the work of Dr.
Alex Blumenfeld and Dr. Lee Deobald for NMR and HRMS analyses respectively. MK received
financial support from the Malcolm Renfrew Scholarship.
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References:
5
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8
(1) (a) Goudreau, N.; Brochu, C.; Cameron, D. R.; Duceppe, J.ꢀS.; Faucher, A.ꢀM.; Ferland, J.ꢀM.;
GrandꢀMaître, C.; Poirier, M.; Simoneau, B.; Tsantrizos, Y. S. J. Org. Chem. 2004, 69, 6185. (b)
Arrault, A.; Guillaumet, G.; Leger, J.ꢀM.; Jarry, C.; Merour, J.ꢀY. Synthesis 2002, 1879.
(2) Kutsumura, N.; Kubokawa, K.; Saito, T. Synthesis 2011, 2011, 2377.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3) Kutsumura, N.; Kiriseko, A.; Saito, T. Tetrahedron Lett. 2012, 53, 3274.
(4) Smith, M. B. In March's Advanced Organic Chemistry; 7th ed. Wiley, 2013, p 982.
(5) (a) Primerano, P.; Cordaro, M.; Scala, A. Tetrahedron Lett. 2013, 54, 4061. (b) Ryu, I.; Matsubara,
H.; Yasuda, S.; Nakamura, H.; Curran, D. P. J. Am. Chem. Soc. 2002, 124, 12946. (c) Chiappe, C.;
Capraro, D.; Conte, V.; Pieraccini, D. Org. Lett. 2001, 3, 1061. (d) Van Zee, N. J.; Dragojlovic, V. Org.
Lett. 2009, 11, 3190.
(6) (a) Cristiano, R.; Ma, K.; Pottanat, G.; Weiss, R. G. J. Org. Chem. 2009, 74, 9027. (b) Ma, K.; Li,
S.; Weiss, R. G. Org. Lett. 2008, 10, 4155. (c) Kaushik, M.; Polshettiwar, V. Indian J. Chem., Sect. B
2006, 45, 2542. (d) Kessat, A. Eur. Polym. J. 1996, 32, 193. (e) Bellucci, G.; Bianchini, R.;
Ambrosetti, R.; Ingrosso, G. J. Org. Chem. 1985, 50, 3313.
(7) (a) Zhu, M.; Lin, S.; Zhao, G.ꢀL.; Sun, J.; Córdova, A. Tetrahedron Lett. 2010, 51, 2708. (b) Levin,
Y.; Hamza, K.; Abu‐Reziq, R.; Blum, J. Eur. J. Org. Chem. 2006, 2006, 1396. (c) Shao, L.ꢀX.; Shi, M.
Synlett 2006, 2006, 1269. (d) Lakouraj, M. M.; Tajbakhsh, M.; Mokhtary, M. J. Chem. Res. 2005, 2005,
481. (e) Salazar, J.; Dorta, R. Synlett 2004, 2004, 1318. (f) Tanaka, K.; Shiraishi, R.; Toda, F. J. Chem.
Soc., Perkin Trans. 1 1999, 3069. (g) HernándezꢀTorres, G.; Tan, B.; Barbas III, C. F. Org. Lett. 2012,
14, 1858.
(8) (a) Wang, G.ꢀW.; Gao, J. Green Chem. 2012, 14, 1125. (b) Macharla, A. K.; Chozhiyath Nappunni,
R.; Nama, N. Tetrahedron Lett. 2012, 53, 1401. (c) Tozetti, S. D.; Almeida, L. S. d.; Esteves, P. M.;
Mattos, M. J. Braz. Chem. Soc. 2007, 18, 675. (d) De Almeida, L. S.; Esteves, P. M.; de Mattos, M. C.
Synlett 2006, 2006, 1515. (e) Kavala, V.; Naik, S.; Patel, B. K. J. Org. Chem. 2005, 70, 4267. (f) Kim,
K.ꢀM.; Park, I.ꢀH. Synthesis 2004, 2004, 2641. (g) Dieter, R. K.; Nice, L. E.; Velu, S. E. Tetrahedron
Lett. 1996, 37, 2377.
(9) (a) Yonehara, K.; Kamata, K.; Yamaguchi, K.; Mizuno, N. Chem. Commun. 2011, 47, 1692. (b)
Podgoršek, A.; Stavber, S.; Zupan, M.; Iskra, J. Green Chem. 2007, 9, 1212. (c) Barhate, N. B.; Gajare,
A. S.; Wakharkar, R. D.; Bedekar, A. V. Tetrahedron 1999, 55, 11127. (d) Podgoršek, A.; Zupan, M.;
Iskra, J. Angew. Chem., Int. Ed. 2009, 48, 8424.
(10) (a) ElꢀQisairi, A. K.; Qaseer, H. A.; Katsigras, G.; Lorenzi, P.; Trivedi, U.; Tracz, S.; Hartman, A.;
Miller, J. A.; Henry, P. M. Org. Lett. 2003, 5, 439. (b) Podgoršek, A.; Eissen, M.; Fleckenstein, J.;
Stavber, S.; Zupan, M.; Iskra, J. Green Chem. 2009, 11, 120.
(11) Ye, C.; Shreeve, J. n. M. J. Org. Chem. 2004, 69, 8561.
(12) (a) Yu, T.ꢀY.; Wang, Y.; Hu, X.ꢀQ.; Xu, P.ꢀF. Chem. Commun. 2014, 50, 7817. (b) Kikushima,
K.; Moriuchi, T.; Hirao, T. Tetrahedron Lett. 2010, 51, 340. (c) Khazaei, A.; Zolfigol, M. A.; Kolvari,
E.; Koukabi, N.; Soltani, H.; Komaki, F. Synthesis 2009, 2009, 3672. (d) Muathen, H. A. Synth.
Commun. 2004, 34, 3545. (e) Braddock, D. C.; Cansell, G.; Hermitage, S. A. Synlett 2004, 2004, 461
(f) Dewkar, G. K.; Narina, S. V.; Sudalai, A. Org. Lett. 2003, 5, 4501. (g) Nair, V.; Panicker, S. B.;
Augustine, A.; George, T. G.; Thomas, S.; Vairamani, M. Tetrahedron 2001, 57, 7417. (h) Sels, B.; De
Vos, D.; Buntinx, M.; Pierard, F.; KirschꢀDe Mesmaeker, A.; Jacobs, P. Nature 1999, 400, 855. (i)
Kabalka, G.; Yang, K.; Reddy, N.; Narayana, C. Synth. Commun. 1998, 28, 925.
.
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1
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5
6
(13) Vaillancourt, F. H.; Yeh, E.; Vosburg, D. A.; GarneauꢀTsodikova, S.; Walsh, C. T. Chem. Rev.
2006, 106, 3364.
(14) Eissen, M.; Lenoir, D. Chem.-Eur. J. 2008, 14, 9830.
7
8
9
(15) Roy, K.ꢀM. Ullmann's Encyclopedia of Industrial Chemistry 2000, 34, 705.
(16) (a) Epstein, W.; Sweat, F. Chem. Rev. 1967, 67, 247. (b) Tidwell, T. T. Org. React. 1990, 39, 297
(c) Tidwell, T. T. Synthesis 1990, 1990, 857.
.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
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35
36
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40
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44
45
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47
48
49
50
51
52
53
54
55
56
57
58
59
60
(17) (a) Cao, Z.; Shi, D.; Qu, Y.; Tao, C.; Liu, W.; Yao, G. Molecules 2013, 18, 15717. (b) Schipper,
E.; Cinnamon, M.; Rascher, L.; Chiang, Y.; Oroshnik, W. Tetrahedron Lett. 1968, 9, 6201. (c) Floyd,
M. B.; Du, M. T.; Fabio, P. F.; Jacob, L. A.; Johnson, B. D. J. Org. Chem. 1985, 50, 5022. (d) Bauer, D.
P.; Macomber, R. S. J. Org. Chem. 1975, 40, 1990.
(18) (a) Majetich, G.; Hicks, R.; Reister, S. J. Org. Chem. 1997, 62, 4321. (b) Liu, C.; Dai, R.; Yao,
G.; Deng, Y. J. Chem. Res. 2014, 38, 593. (c) Megyeri, G.; Keve, T. Synth. Commun. 1989, 19, 3415.
(19) Inagaki, M.; Matsumoto, S.; Tsuri, T. J. Org. Chem. 2003, 68, 1128.
(20) Choudhury, L. H.; Parvin, T.; Khan, A. T. Tetrahedron 2009, 65, 9513.
(21) Olah, G. A.; Vankar, Y. D.; Arvanaghi, M.; Surya Prakash, G. Synthesis 1979, 1979, 720.
(22) Das, B.; Srinivas, Y.; Sudhakar, C.; Ravikanth, B. J. Chem. Res. 2008, 2008, 188.
(23) Chow, Y. L.; Bakker, B. H. Synthesis 1982, 1982, 648.
(24) Yusubov, M. S.; Filimonov, V. D.; Vasilyeva, V. P.; Chi, K.ꢀW. Synthesis 1995, 1995, 1234.
(25) Rezekina, N.; Rakhmanov, E.; Lukovskaya, E.; Bobylyova, A.; Abramov, A.; Chertkov, V.;
Khoroshutin, A.; Anisimov, A. Chem. Heterocycl. Compd. 2006, 42, 216.
(26) Nikishin, G.; Sokova, L.; Kapustina, N. Russ. Chem. Bull. 2012, 61, 459.
(27) Zimmerman, S. C.; Cramer, K. D.; Galan, A. A. J. Org. Chem. 1989, 54, 1256.
(28) Wu, L.; Yin, Z. Eur. J. Inorg. Chem. 2013, 2013, 6156.
(29) Broadus, K. M.; Kass, S. R. J. Am. Chem. Soc. 2001, 123, 4189.
(30) Krajewski, K.; Ciunik, Z.; Siemion, I. Z. Tetrahedron Asymm. 2001, 12, 455.
(31) Das, B.; Srinivas, Y.; Sudhakar, C.; Damodar, K.; Narender, R. Synth. Commun. 2008, 39, 220.
(32) de Almeida, L. S.; Esteves, P. M.; de Mattos, M. Synlett 2007, 1687.
(33) Li, L.; Su, C.; Liu, X.; Tian, H.; Shi, Y. Org. Lett. 2014, 16, 3728.
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