Selective cross-coupling of organic halides with allylic acetates

Article abstract of DOI:10.1021/jo302086g

A general protocol for the coupling of haloarenes with a variety of allylic acetates is presented. Strengths of the method are a tolerance for electrophilic (ketone, aldehyde) and acidic (sulfonamide, trifluoroacetamide) substrates and the ability to couple with a variety of substituted allylic acetates. Secondary alkyl bromides can also be allylated under slightly modified conditions, demonstrating the generality of the approach. Finally, the coupling of a reactive vinyl halide could be achieved by the use of a very hindered ligand and more reactive, branched allylic acetates.

Full text of DOI:10.1021/jo302086g

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pubs.acs.org/joc
Selective Cross-Coupling of Organic Halides with Allylic Acetates
Lukiana L. Anka-Lufford,‡ Michael R. Prinsell,‡ and Daniel J. Weix*
Department of Chemistry, University of Rochester, Rochester, New York 14627-0216, United States
S
* Supporting Information
ABSTRACT: A general protocol for the coupling of haloarenes with a
variety of allylic acetates is presented. Strengths of the method are a
tolerance for electrophilic (ketone, aldehyde) and acidic (sulfonamide,
trifluoroacetamide) substrates and the ability to couple with a variety
of substituted allylic acetates. Secondary alkyl bromides can also be
allylated under slightly modified conditions, demonstrating the generality of the approach. Finally, the coupling of a reactive vinyl
halide could be achieved by the use of a very hindered ligand and more reactive, branched allylic acetates.
reagents are limited by the low commercial availability of
organometallic reagents and the reactivity of the organometallic
reagent itself.
1. INTRODUCTION
Allylarene derivatives are versatile synthetic intermediates to
which a variety of approaches have been developed: Friedel−
Crafts allylation, allylation of aryl nucleophiles by metal-
mediated allylic substitution chemistry,1 metal-mediated cross-
coupling of aryl halides with allyl nucleophiles,2 and Heck
reactions of olefins with aryl halides.3 We present here an
alternative disconnection, the cross-coupling of two electro-
philes, allylic acetates, and aryl halides (Figure 1). While the
Allylic acetate derivatives and aryl halides are more
convenient and affordable than organometallic reagents, but
few reports on the reductive coupling of substituted allylic
acetates with functionalized arenes exist. The reductive
coupling of aryl bromides and chlorides with an excess (2.0−
2.7 equiv) of allylic acetates has been reported to be catalyzed
by 13−40 mol % cobalt under both electrochemical6 and
chemical conditions (zinc or manganese reductant).7 The
principle side reactions observed were reduction of the aryl
halide and dimerization of the aryl halide to form biaryl.
Although aryl bromides and electron-poor aryl chlorides
worked well, no examples with aryl iodides were reported,
and it was noted that even more biaryl formation occurred with
these substrates. Selectivity for the cross product was the major
limitation.
Figure 1. Approaches to the synthesis of allylated arenes.
́ ́ ́
Durandetti, Nedelec, and Perichon had noted in 1996 that
bipyridine-ligated nickel catalysts could couple allylic acetates
with aryl halides, but slow addition of the allylic acetate was
required for high selectivity.8a Starting from a bipyridine
catalyst we had developed for the coupling of aryl halides with
alkyl halides,9 Gong recently reported that several additives
significantly improved yields for the coupling of three different
aryl bromides, but only with simple allyl acetate (CH2
CHCH2OAc).8b
Only four successful reactions with substituted allylic acetates
have been reported to date (Scheme 1). For the cobalt-
catalyzed reactions, yields and selectivities were modest and
relatively high catalyst loading was required. Similarly, two
nickel-catalyzed examples with crotyl acetate provided good
yield and regioselectivity but required the slow addition of the
allylic acetate to achieve high cross-selectivity. No examples of
substituted allylic acetates utilizing chemical reductants have
been reported.
coupling of simple allyl acetate with aryl halides has been
reported several times, few examples with substituted allylic
acetates have been reported. In our own studies, we have found
that the ligands previously used for such reactions, pyridine and
bipyridine ligands, were poorly selective. We report here a new
ligand that promotes selective coupling of aryl halides with
allylic acetates. These conditions, with a few modifications, can
also be used to couple allylic acetates with secondary alkyl
bromides and a vinyl bromide.
2. BACKGROUND
The reductive approach to allylated arenes (Figure 1) is
complementary to the other approaches, addressing some of
the limitations present in each. Friedel−Crafts is direct, but
precise control of the products is difficult and electron-rich
arenes are required. The Heck reaction is also direct, and
functional-group compatibility can be excellent, but selectivity
for allylarene over vinylarene is usually poor.3,4 In cases where
selectivity is achieved, it is for the styrene, not the allylated
arene.5 Methods that rely upon preformed organometallic
Received: October 4, 2012
Published: October 24, 2012
© 2012 American Chemical Society
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Scheme 1. All Previous Examples of Reductive Allylations
with Substituted Allylic Acetates
3. RESULTS
3.1. Reaction Optimization. Building on the observation
that 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine (L1) and
NiCl2(dme) formed a catalyst that was slow to dimerize
haloarenes, but was reactive with allylic acetates, we examined
its ability to mediate the coupling of cinnamyl acetate (2a) with
iodobenzene (Table 1). We found that it is highly selective for
a
Table 1. Ligand Effect on Cross-Selectivity
As evident in these prior studies, the major challenge
associated with the reductive coupling of two electrophiles is
the selective formation of cross-coupled product over
competitive dimerization reactions (Figure 2). The nickel-
b
c
entry
ligand
GC yield (%)
ratio 3a:B:C:D
1
2
3
4
5
L1
L2
90
62
100:1:2:15
100:37:5:5
100:11:0:20
100:17:1:4
100:0:0:86
d
pyridine (10 equiv)
45
L3
73
e
none
4
a
Reaction conditions: 1:1.5:2 cinnamyl acetate/Ph-I/Zn, 5 mol % of
NiCl2(dme) in 3:1 THF/NEP (NEP = N-ethylpyrrolidinone).
b
Reaction time was 15−24 h. Corrected GC yields; see the Supporting
c
Information for an example calculation. Ratios based upon GC area %
d
e
data. Reaction time was 96 h. Reaction was incomplete at 96 h; 31%
Figure 2. Selectivity challenge for reductive allylation.
of 1a and 51% of 2a remained.
cross-coupling over competing dimerization reactions (B and C
in Table 1, entry 1), although some hydrodehalogenation
competes (D). Our own studies on the coupling of aryl halides
with unactivated alkyl halides had previously found bipyridine
L3 to form a particularly selective catalyst,9 but biaryl formation
was a problem in reactions with allylic acetates (entry 2). Our
observed low selectivity mirrors previous reports with
pyridine6,7 as a cosolvent and ligand (entry 3) or a bipyridine8
(L3) as a ligand (entry 4). Finally, reactions conducted without
ligand (entry 5), without nickel, or without zinc produced little
or no cross-product, respectively (Table S6 in Supporting
Information).
Initial studies had found that dimethylacetamide (DMA) and
N-ethylpyrrolidinone (NEP) provided the best yields out of
various amide and urea solvents. In order to simplify product
isolation, we examined THF solvent mixtures and found that
NEP/THF provided the highest yields. In very cost-sensitive
situations, DMA/THF can be substituted for NEP/THF with
only a small decrease in yield (73% vs 90% in entry 1).
3.2. Aryl Halide Scope. In order to examine the
compatibility of these conditions with various functional
groups, the optimized conditions were applied to a series of
aryl iodides and aryl bromides (Table 2). Both electron-rich
and electron-poor aryl iodides formed product in high yield
(entries 3−11). Broad functional group tolerance is notable,
including an N-aryltrifluoroacetamide group (entry 6), which
bears a strongly acidic proton (similar to acetic acid, see also
entry 5) and is easily cleaved by nucleophiles. Although nickel
is known to catalyze both pinacol coupling14 and allylation15 of
ketones and aldehydes, products 3b and 3c were obtained in
catalyzed methods required slow addition of the allylic acetate
over the course of the electrolysis8a or 2 equiv of allyl acetate
for high yield.8b These conditions were proposed to favor
formation of arylnickel intermediates over allylnickel inter-
mediates.8a The cobalt-catalyzed methods,6,7 on the other hand,
were reported to suffer from large amounts of biaryl formation
or hydrodehalogenation, even with excess allyl acetate.
More selective, general conditions for the allylation of
substituted allylic acetates may require the development of new
catalysts and strategies for selective oxidative addition of either
the allylic acetate or the aryl halide. Few studies on the relative
rates at which nickel complexes react with different electro-
philes have been reported.8a In the course of studying
dimerization reactions, we had found that terpyridine-ligated
nickel complexes dimerized alkyl bromides and allylic acetates
but only slowly reacted with aryl halides.10 Because allylnickel-
(II) complexes are well-known to react with aryl halides to
form allylarenes,11 we hypothesized that a terpyridine-ligated
nickel complex could achieve better selectivity than bipyridine
catalysts. We report here our results with this same catalyst for
the coupling of substituted allylic acetates with a range of
organic halides.
During the course of these studies, Gosmini reported a Co-
catalyzed method for the allylation of alkyl halides,12 Gong
reported the use of our terpyridine−nickel system10 for the
allylation of alkyl halides,13 and Gong reported the coupling of
simple allyl acetate with three aryl bromides.8b None of these
manuscripts explored the coupling of substituted allylic acetates
with aryl halides or vinyl halides.
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a
Table 2. Allylation of a Variety of Aryl Halides
Table 3. Reaction of Iodoarenes with Various Allylic
a
Acetates
a
Reaction conditions as in Table 3. Reaction times were 15−18 h. See
b
Table S3 in the Supporting Information for full selectivity data. Yield
c
after purification. Product has a 86:14 [linear]/[branched] ratio.
d
e
Product has a 93:7 [linear]/[branched] ratio. Product is a mixture of
olefin isomers: 6.9:1:1 [2E,4E]/[2E,4Z]/[unidentified olefin isomer].
f
NMR yield of the E/Z mixture of linear products. Product has a 1.9:1
a
As in Table 1, but on a 1 mmol scale in 2 mL of THF/NEP. Reaction
[linear]/[branched] ratio. The linear product was a 1:1 mixture of E/Z
isomers. Product contains ∼3% of an unidentified side product.
b
g
times were 15−24 h. Yield after purification. For complete selectivity
data, see Tables S1 and S2 in the Supporting Information. A 1 mmol
c
scale reaction run on the benchtop (procedure B) gave an 82% GC
d
e
regardless of starting material, provide flexibility in synthesis
and suggest a common allylnickel intermediate (Table 2, entry
1, and Table 3, entries 2 and 3). Finally, cyclic and acyclic α-
substituted allylic acetates provide good yields of product
(entries 8 and 9). In the case of nonsymmetrical substrate 2j,
regioselectivity for α-substitution is high (entry 9). The
coupling of a γ,γ-disubstituted olefin, geranyl acetate (entry
7), provided a high yield of allylated products (80% total yield),
but the selectivity was poor (2:1 linear/branched, 1:1 E:Z for
linear).
3.4. Secondary Alkyl Bromides. We also investigated the
coupling of unactivated alkyl bromides with allylic acetates,
which builds upon our previous studies with (L1)Ni catalysts.10
We found that cross-selectivity was poor for reactions with
primary alkyl bromides due to rapid dimerization of the alkyl
bromide. Secondary alkyl bromides could be cross-coupled with
cinnamyl acetate derivatives with high selectivity and yield
(Table 4). Conditions are nearly the same as those used for aryl
halides except that THF/DMA mixtures performed best and
manganese provided the highest yields. During the course of
yield. Reaction was run on a 0.5 mmol scale. NMR yield of 3j.
Isolated product is contaminated with 9% of 3a from hydro-
f
deiodination. Yield is an average of two runs, one at 0.5 mmol scale
and one at 1 mmol scale.
high yield (entries 3 and 4). Because bromobenzene was
unreactive under these reaction conditions, we were able to
couple 1-bromo-4-iodobenzene with high chemoselectivity
(entry 14). Finally, meta- and ortho-substituted iodoarenes
also coupled in good yield (entries 16−18).
In contrast to electron-neutral bromoarenes, bromoarenes
containing an electron-withdrawing group couple in reasonable
yield (Table 2, entries 12−15).
3.3. Allylic Acetate Scope. A variety of different allylic
acetates were also examined (Table 3), with promising results.
Not only aryl-substituted cinnamyl acetate but also primary
alkyl- (entry 1), secondary alkyl- (entry 3), and vinyl-
substituted (entry 6) allylic acetates coupled in good yield,
with selectivity for the linear E-product. The high regiose-
lectivity and stereoselectivity obtained for the linear isomer,
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a
acetates in the literature, but the skipped diene products of such
reactions are valuable in synthesis.22 Preliminary investigations
on the coupling of cinnamyl acetate (2a) with 2-bromocyclo-
hexenone provided only small amounts of product 7a.
Monitoring reactions at low conversion revealed that
consumption of the vinyl bromide was much faster than
consumption of cinnamyl acetate. If our hypothesis that
selective formation of an allylnickel intermediate was required
for selective cross-coupling were correct, a more reactive allylic
alcohol donor would be required.
Table 4. Coupling of Allylic Acetates with Alkyl Bromides
Based upon this hypothesis, we examined reactions with
branched allylic acetate 2c because the less hindered olefin
should facilitate coordination and ionization (Table 5).
Table 5. Ligand Effect on Cross-Selectivity for Reactions
a
with 2-Bromocyclohex-2-enone
a
Reaction conditions: 1.5:1:2 allyl acetate/R-Br/Mn. Reaction times
were 15−18 h. See Table S4 in the Supporting Information for full
b
c
selectivity data. Yield after purification. Yield is an average of two
d
runs, one at 0.5 mmol scale and one at 1 mmol scale. Reagents were
weighed out on the benchtop in a vial that was then sparged with
argon gas through the septa cap.
b
GC area % (yield, %)
entry
ligand
2c
6
7a
8
9a
these experiments, the groups of Gosmini and Gong reported
Co-12 and Ni-catalyzed13 approaches to the same products.
Gong used very similar conditions but found that the addition
of large amounts of MgCl2 made the reaction more general. In
light of their results, we did not pursue our additive-free
conditions further.
1
2
3
4
L1
66
0
34
0
0
0
6
0
0
0
16
5
L2
78
L4
0
0
94 (78)
0
phen
66
34
0
a
Reactions run with a 1:1 ratio of reactants for 21 h. phen = 1,10-
phenanthroline. Results in table are GC area % data. The number in
b
3.5. Potential for RZnX, RMnX, or Radical Intermedi-
ates. We first considered the potential intermediacy of arylzinc
reagents, ArZnI, because we observed significant amounts of
hydrodehalogenation of the aryl halide in some cases (up to
29% GC area %, Table 1, D, and Tables S1−S5 in the
Supporting Information).16 Although direct insertion of
unactivated zinc into aryl iodides is reported to be slow,17
nickel can catalyze the process.17d Several observations lead us
to believe that ArZnI intermediates are unlikely: (1) reactions
without nickel only converted trace amounts of iodobenzene to
benzene (2% in 48 h, Table 2 in the Supporting Information);
(2) a reaction quenched at intermediate conversion with D2O
did not form increased amounts of C6H5D when compared to a
reaction quenched with H2O (GC/MS); (3) functional groups
reported to be reactive with ArZnI, such as aldehydes and acidic
protons, are well tolerated (Table 3, entries 4−6).18
We also considered aryl radical intermediates to explain the
observed hydrodehalogenation. An aryl radical could abstract a
hydrogen atom from the solvent to form Ar-H. If this was the
case, then a reaction conducted in a fully deuterated solvent
mixture could be expected to form Ar-D instead of Ar-H.19
Because deuterated NEP and DMA are not commercially
available, we conducted the experiment in a THF-d8/DMF-d7
mixture.20 We did not observe an increase in the amount of
C6H5D produced when compared to a reaction in protic
solvents (GC/MS). This argues against hydrogen atom
abstraction from solvent but does not completely rule out the
presence of radical intermediates.21
parentheses is yield after purification.
Reactions run with terpyridine L1 did not form the skipped
diene 7a and failed to consume starting materials (entry 1).
Bipyridine L2 provided better results, but significant allyl dimer
(9a) and vinyl dimer (8) were formed. Kishi has reported that
neocuproine (L4) nickel complexes are slow to dimerize aryl
halides,23 and we have also found that neocuproine was a
selective ligand for the reductive conjugate addition of aryl and
vinyl halides with enones, which we propose involves allylnickel
intermediates.24 Indeed, L4 formed a highly selective catalyst
for the cross-coupling of 2-bromocyclohexenone with the
branched allylic acetate 2c (entry 3). The results appear related
to sterics because the unsubstituted 1,10-phenanthroline
provided poor results (entry 4).
The less reactive alkyl-substituted allylic substrates 2k and 2l
provided low yields when the cross-coupling with the vinyl
bromide was attempted (Table 6, entries 1 and 2). Again, low
reactivity of the allyl derivative compared to vinyl bromide 6
appeared to be the problem. In order to further boost reactivity
of the allylic donor, we examined the methyl carbonates 2m
and 2n. These more reactive substrates coupled with higher
selectivities and resulted in better yields (entries 3 and 4).
Although preliminary, this approach compares favorably with
prior approaches to α-allylated enones (7). Those methods
relied upon tin and selenium chemistry,25 organocuprates,26,27
or a multistep sequence starting with the allylation of
cyclohexane dione.26,28 Product 7a has been used as a versatile
3.6. Extension to Vinyl Halide. We could find no
examples of the catalytic coupling of vinyl halides with allylic
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product and a nickel(II) salt is proposed to involve a radical-
chain-like process and has been studied extensively.30b−d
Separately, Gong has proposed the intermediate reduction of
allylnickel(II) intermediates into allylnickel(I) intermediates,31
but detailed mechanistic studies have not been conducted for
this alternative mechanism. At this time, we cannot differentiate
between the single-electron reduction mechanism and the
radical-chain mechanism.
Table 6. Effect of Leaving Group on Selectivity for Reactions
with 2-Bromocyclohex-2-enone
a
4.2. Scope of Reaction. Generally, reductive cross-
electrophile coupling reactions have displayed broad func-
tional-group tolerance.6−13 However, previous studies on
reductive allylation had not demonstrated compatibility with
enones, unprotected aldehydes, or highly acidic protons (Table
2).
Allylation of aryl halides with substituted allylic acetates had
been limited to only four examples (Scheme 1), but we have
found that reactions with (L1)Ni have broad scope, including
primary and secondary alkyl, cyclic, vinyl, and 1,3-disubstituted
allylic acetates (Table 3).
A wide variety of organic halides couple under similar
conditions using (L1)Ni as the catalyst. This includes, for the
first time, a vinyl bromide. Improvement of conditions for the
allylation of vinyl halides will be the subject of future studies.
4.3. Selectivity. Although the true order of reactivity for the
allylic acetate and haloarene with nickel has not yet been
unambiguously determined, our studies show that the inherent
reactivity of the substrate, ligand sterics, and ligand
coordination number can all be manipulated in a rational
manner to improve selectivity. For example, 1-phenyl-2-
propenyl acetate (2c) is a poor match for ligand L2 and vinyl
bromide 6, resulting in significantly more allyl dimerization.
With a more hindered ligand (L4), only a small amount of allyl
dimer is formed (Table 5).
Finally, looking over the comprehensive selectivity data in
the Supporting Information, it is clear that hydrodehalogena-
tion is the major side reaction for most examples and that this
side reaction appears to happen more with bromoarenes.
Development of catalysts and conditions that will suppress
hydrodehalogenation are needed to further improve the scope
and yields for arene allylation.
a
b
Reactions run with a 1:1 ratio of reactants for 19 h. Results in table
are GC area % data. Numbers in parentheses are yields after
purification.
precursor to the fused 6,3,5-tricyclic skeleton of mycorrhizin
A.28
4. DISCUSSION
4.1. Mechanism. Both arylmetal6b,8a and allylmetal8b
intermediates have been proposed for cobalt- and nickel-
catalyzed coupling of aryl halides with allylic acetates, but these
studies were conducted with monodentate or bidentate ligands.
Our previous studies with terpyridine nickel catalysts10
suggested an allylnickel intermediate (Figure 3) would be
formed preferentially in reactions catalyzed by terpyridine
nickel complexes.29
5. CONCLUSIONS
In conclusion, a new nickel-catalyzed coupling of aryl iodides,
electron-poor aryl bromides, and secondary alkyl bromides with
allylic acetates has been developed. This chemistry addresses
the regioselectivity and substrate availability limitations
observed for more well-developed approaches. The func-
tional-group compatibility, the scope of allylic acetate
substitution, and the potential for the allylation of vinyl halides
are promising. Finally, our results show that cross-selectivity
can be controlled by the choice of ligand, which provides a clear
path for future improvements.
Based upon studies by many groups, including Corey,
Semmelhack, Hegedus, and Kochi, preformed allylnickel(II)
reagents are known to react with aryl, alkyl, and vinyl halides,
consistent with the observed generality of our nickel-catalyzed
process.30 The conversion of the allylnickel intermediate into
6. EXPERIMENTAL SECTION
1
General. H and 13C NMR spectra were acquired on 500 or 400
MHz (proton) NMR instruments. NMR chemical shifts are reported
in ppm and referenced to the residual solvent peak as an internal
standard (for CDCl3 δ = 7.260 ppm, 1H; δ = 77.160 ppm, 13C).
Analysis of reaction mixtures was accomplished by quenching an
aliquot (10 μL) with 1 M NaHSO4(aq) (0.1 mL) and analysis of the
filtered (silica or Celite) ether extract (1 mL) by GC or GC/MS.
Dodecane was used as the internal standard. GC analyses (FID
detector) were performed on a DB-5 column (20 m × 0.18 mm × 0.18
Figure 3. Proposed mechanism.
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μm) with hydrogen as the carrier gas. Standard method: 1.8 mL/min
flow at 20.3 psi, 300 °C inj, 325 °C detector, oven program: 50 °C
(0.46 min), ramp at 65 °C/min to 300 °C, hold for 0.69 min. GC/MS
analyses (EI+, quadrupole mass analyzer) were performed on an
instrument equipped with an RTX-XLB column (30 m × 0.25 mm ×
0.28 μm) with helium carrier gas. Standard method: 1 mL/min flow at
7.8 psi, 225 °C inj, 250 °C interface/ion source, oven program: 50 °C
(3 min), ramp at 40 °C/min to 280 °C, hold for 3 min. Only the
parent ion and the base peak are reported. High-resolution mass
spectra (HRMS) were acquired on an instrument with electron-impact
(EI) ionization and a magnetic sector mass analyzer. Compounds were
either purified on an automated flash purification system on Redisep Rf
Gold normal-phase silica columns or by standard chromatography on
silica gel (EMD, silica gel 60, particle size 0.040−0.063 mm) using
standard flash techniques. Products were visualized by UV light,
KMnO4 stain, or GC.
Unless otherwise noted, all reagents and solvents were purchased
from commercial suppliers and were used as received. NiCl2(1,2-
dimethoxyethane) (NiCl2(dme)) was purchased from Strem or
synthesized.32 As we have reported elsewhere, the stoichiometry of
the NiCl2(dme) can be variable.10 The amount of NiCl2(dme) used
was corrected for the actual amount of dimethoxyethane present as
determined by elemental analysis. 4,4′,4″-Tri-tert-butyl-2,2′:6′,2″-
terpyridine33 (L1), 4,4′-di-tert-butyl-2,2′-bipyridine (L2), and bipyr-
idine (L3) were purchased or synthesized according to the literature
procedure. Zinc flakes (−325 mesh, purity 99.9%) and manganese
powder (−325 mesh, ≥99%) were stored under nitrogen. N-Ethyl-2-
pyrrolidone (NEP) was purified by stirring over CaH2 (48 h) followed
by distillation from CaH2. The purified NEP was stored under
nitrogen over 4 Å molecular sieves. Tetrahydrofuran (THF), N,N-
dimethylacetamide (DMA), dichloromethane (DCM), and pyridine
(py) were purified by passage through alumina and molecular sieves
and stored over 4 Å molecular sieves. 4-Iodotoluene, 4-bromobenzo-
trifluoride, and 3-iodotoluene were filtered through a short plug of
basic alumina (1 cm) in a glass pipet before use. 4-Iodobenzalde-
hyde,34 N-(4-iodophenyl)-4-methylbenzenesulfonamide,35 2,2,2-tri-
fluoro-N-(4-iodophenyl)acetamide,36 tert-butyl(4-iodophenoxy)-
dimethylsilane,37 4-iodo-N,N-dimethylaniline,38 cinnamyl acetate39
(2a), (E)-hex-2-en-1-yl acetate37 (2b), (Z)-3-phenylallyl acetate40
(2d), (E)-3-cyclohexylallyl acetate41 (2e), 2-methylallyl acetate42 (2f),
(2E,4E)-hexa-2,4-dien-1-yl acetate13a (2g), cyclohex-2-en-1-yl acetate43
(2i), (E)-4-phenylbut-3-en-2-yl acetate44 (2j), and (E)-3-(4-
methoxyphenyl)allyl acetate39,45 (2k), (E)-3-(4-trifluoromethyl)-
phenyl)allyl acetate46 (2l), and 2-Bromocyclohex-2-en-1-one47 (6)
were synthesized according to literature procedures.
1H), 5.33−5.24 (m, 2H), 2.12 (s, 3H). 13C NMR (101 MHz;
CDCl3): δ 170.0, 139.0, 136.4, 128.6, 128.3, 127.2, 117.0, 76.3, 21.4.
4-Ethylhex-1-en-3-yl Methyl Carbonate (2m). An oven-dried 250
mL, three-neck, round-bottom flask was equipped with a magnetic
stirbar, a nitrogen inlet, an addition funnel, and a rubber septum. 2-
Ethylbutyraldehyde (2.46 mL, 20 mmol, distilled over Na2SO4) and
dry Et2O (140 mL) were added to this vessel, and the mixture was
cooled to 0 °C. Vinylmagnesium bromide in THF (1.09 M, 22.02 mL,
24 mmol, 1.2 equiv) was added dropwise via the addition funnel. The
reaction was allowed to warm to rt and then stirred at rt for 1 h. The
white suspension was then poured onto ice-cold water (50 mL), the
organic layer separated and dried over Na2SO4, and supernatant
concentrated in vacuo in a 100 mL round-bottom flask to give the allyl
alcohol. The crude alcohol was then used without further purification
in the next step.
In the 100 mL vessel used above, a solution of the allyl alcohol
(assume 20 mmol from previous step), DCM (50 mL), and pyridine
(4.85 mL, 3 equiv) was cooled to 0 °C, under nitrogen with stirring.
Methyl chloroformate (3.09 mL, 2.0 equiv) was then added dropwise
by syringe, and the reaction mixture was allowed to warm to room
temperature overnight. The reaction mixture was treated with water
(25 mL), and the aqueous layer was separated and extracted with
additional Et2O (2 × 25 mL). The combined organic layers were
washed with saturated NaHCO3 (25 mL) and brine (25 mL) and
dried over Na2SO4, and the supernatant was concentrated in vacuo.
Purification by flash chromatography (2% EtOAc in hexanes) yielded
pure 4-ethylhex-1-en-3-yl methyl carbonate (1.50 g, 50%) as a clear oil.
1H NMR (400 MHz; CDCl3): δ 5.78 (ddd, J = 17.3, 10.5, 6.8 Hz, 1H),
5.30−5.21 (m, 2H), 5.10−5.07 (m, 1H), 3.76 (s, 3H), 1.50−1.36 (m,
4H), 1.25 (m, 1H), 0.89 (td, J = 7.4, 3.4 Hz, 6H). 13C NMR (101
MHz; CDCl3): δ 155.5, 134.6, 118.1, 81.0, 54.7, 44.9, 21.7 (d, J = 9.3
Hz), 11.5. Anal. Calcd for C10H18O3: C, 64.49; H, 9.74; N, 0.00.
Found: C, 64.69; H, 9.95; N, −0.065.
Methyl 5-Phenylpent-1-en-3-yl Carbonate (2n).49 An oven-dried,
250 mL, three-neck, round-bottom flask was equipped with a magnetic
stirbar, a nitrogen inlet, an addition funnel, and a rubber septum.
Hydrocinnamaldehyde (2.63 mL, 20 mmol, distilled over Na2SO4) and
dry Et2O (140 mL) were added to this vessel, and the mixture was
cooled to 0 °C. Vinylmagnesium bromide in THF (1.09 M, 22.02 mL,
24 mmol, 1.2 equiv) was added dropwise via the addition funnel. The
reaction was then stirred at room temperature for 1 h. The white
suspension was then poured onto ice-cold water (50 mL), the organic
layer separated and dried over Na2SO4, and the supernatant
concentrated in vacuo in a 100 mL round-bottom flask to give the
allyl alcohol. The crude alcohol was then used without further
purification in the next step.
Allylic Acetates and Carbonates. 1-Phenyl-2-propenyl Acetate
(2c).48 Benzaldehyde (2.31 mL, 22.73 mmol) was filtered though basic
alumina and added to a flame-dried 100-mL 1-neck round bottomed
flask. The flask was also charged with THF (25 mL) and a Teflon
coated magnetic stirbar and then cooled to 0 °C. A 1.09 M solution of
vinylmagnesium bromide in THF (25 mL, 25 mmol, 1.1 equiv) was
then added slowly via an addition funnel. After 4 h, no benzaldehyde
remained, and acetic anhydride (3.22 mL, 34.09 mmol, 1.5 equiv) was
added at 0 °C. After 2 h, an additional 1.0 equiv (2.15 mL) of acetic
anhydride was added, and the reaction was allowed to warm to room
temperature overnight. The reaction mixture was poured into a
separatory funnel and diluted with Et2O (50 mL), and the organic
layer was washed with 1 M HCl until the pH of the aqueous layer was
1. The organic layer was then washed with saturated NaHCO3 until
the pH of the aqueous layer was 7. The combined aqueous layers were
then back extracted with Et2O (2 × 50 mL). The combined organic
layers were then dried over MgSO4, and the supernatant was
concentrated in vacuo. The product was then isolated by flash
chromatography (5% EtOAc in hexanes, Rf = 0.24). Mixed fractions
were rechromatographed (2.5% EtOAc in hexanes). The combined
pure 1-phenyl-2-propenyl acetate (1.99 g, 88%) was isolated as a clear
In the 100 mL vessel used above, a solution of the allyl alcohol
(assume 20 mmol from previous step), DCM (50 mL), and pyridine
(4.85 mL, 3 equiv) was cooled to 0 °C under nitrogen with stirring.
Methyl chloroformate (3.09 mL, 2.0 equiv) was then added dropwise
by syringe, and the reaction mixture was allowed to warm to room
temperature overnight. The reaction mixture was treated with water
(25 mL), and the aqueous layer was separated and extracted with
additional Et2O (2 × 25 mL). The combined organic layers were
washed with saturated NaHCO3 (25 mL) and brine (25 mL) and
dried over Na2SO4, and the supernatant was concentrated in vacuo.
Purification of the residue by flash chromatography (2% EtOAc in
hexanes) yielded methyl 5-phenylpent-1-en-3-yl carbonate (2.60 g,
1
59%) as a clear oil. H NMR (400 MHz; CDCl3): δ 7.31−7.18 (m,
5H), 5.85 (ddd, J = 17.2, 10.5, 6.7 Hz, 1H), 5.36−5.24 (m, 2H), 5.10
(q, J = 6.6 Hz, 1H), 3.79 (s, 3H), 2.76−2.64 (m, 2H), 2.11−1.90 (m,
2H). 13C NMR (101 MHz; CDCl3): δ 155.3, 141.2, 135.8, 128.6,
128.5, 126.1, 117.9, 78.6, 54.8, 36.0, 31.4.
Procedure A: Allylic Acetates with Aryl Halides in a Nitrogen
Glovebox. A 1-dram vial containing a Teflon-coated magnetic stir was
sequentially charged with NiCl2(dme) (10.6 mg, 0.0483 mmol), L1
(20.0 mg, (0.0498 mmol), NEP (500 μL), THF (1500 μL), aryl halide
(1.50 mmol), allylic acetate (1.00 mmol), and zinc flakes (130 mg,
2.00 mmol). The vial was then capped with a screw cap fitted with a
PTFE-faced silicone septum. After removal from the glovebox, the vial
1
oil; analytical data matched those reported in the literature. H NMR
(400 MHz; CDCl3): δ 7.37 (d, J = 4.5 Hz, 4H), 7.32 (t, J = 4.3 Hz,
1H), 6.28 (dt, J = 5.9, 1.3 Hz, 1H), 6.02 (ddd, J = 17.1, 10.5, 5.9 Hz,
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was shaken for 15 s and then stirred (1300 rpm) at 40 °C until judged
complete (less than 1% allylic acetate remaining) by GC analysis (12−
15 h). In order to remove NEP, the reaction mixture was filtered
through a short plug of silica gel (1 in. wide, ∼3 in. high) in an 18 mL
disposable polyethylene fritted filter funnel, eluting with either hexanes
or diethyl ether, depending on the polarity of the expected product
(200 mL). The filtrate was concentrated in vacuo and the residue
purified by flash chromatography on a Teledyne-Isco combiflash Rf-
200.
Procedure B: Allylic Acetates with Aryl Halides on the Benchtop
under Argon (1 mmol Scale). Reactions set up as in procedure A
except that after the vial was sealed, the headspace was flushed with
argon gas for 1 min. The needles were then removed and the vial was
placed in a heating block at 40 °C in the usual manner.
flash chromatography (9% ethyl acetate in hexanes) afforded 155 mg
(70% yield) of the title compound as a pale yellow oil; analytical data
matched those reported in the literature. 1H NMR (400 MHz;
CDCl3): δ 10.05 (s, 1H), 7.89 (d, J = 8.1 Hz, 2H), 7.48−7.27 (m, 9H),
6.54 (d, J = 15.7 Hz, 1H), 6.39 (dt, J = 15.7, 6.9 Hz, 1H), 3.69 (d, J =
6.7 Hz, 2H). 13C NMR (101 MHz; CDCl3): δ 192.0, 147.6, 137.1,
134.8, 132.1, 130.1, 129.4, 128.6, 127.6, 127.5, 126.2, 39.5. GC−MS
(EI) m/z (rel intensity, ion): 222.05 (77.96, M+), 115 (100.00, M+ −
C7H5O). HRMS (EI): [M+] calcd for C16H14O 222.104, found
222.105.
(E)-N-(4-Cinnamylphenyl)-4-methylbenzenesulfonamide (3d)
(Table 2, Entry 5). Procedure A was followed with cinnamyl acetate
(2a) (166 μL, 1.00 mmol) and N-(4-iodophenyl)-4-methylbenzene-
sulfonamide (560 mg, 1.50 mmol). Purification by flash chromatog-
raphy (40% ethyl acetate in hexanes) afforded 265 mg (73% yield) of
Procedure C: Allylic Acetates with Aryl Halides on the Benchtop
under Argon (10 mmol Scale). On the benchtop, an oven-dried 50-
mL Schlenk flask containing a Teflon-coated magnetic stir bar was
charged with NiCl2(dme) (106 mg, 0.483 mmol) and 4,4′,4″-tri-tert-
butyl-2,2′:6′,2″-terpyridine (200 mg, (0.498 mmol). The flask was
then sealed with a rubber septa. NEP (500 μL), THF (1500 μL), aryl
halide (15.0 mmol), and allylic acetate (10.0 mmol) were then added
sequentially under a low flow of argon with an outlet needle (bubbler).
The flow of argon was then increased, the rubber septa removed, and
the zinc flake reductant was quickly tipped into the flask (1.30 g, 20
mmol). The septa was then replaced onto the flask, and the flask was
gently shaken for 15 s. The side arm valve was closed, the argon line
was removed, and the reaction mixture was then stirred at 40 °C until
judged complete by GC analysis. The workup and isolation was
performed as in procedure A except 400 mL of hexanes was used to
elute the crude product from the silica gel plug and one 120 g normal-
phase “gold” silica column (Teledyne-Isco) was used for chromatog-
raphy.
1
the title compound as a white solid. H NMR (400 MHz; CDCl3): δ
7.65−7.63 (m, 2H), 7.34−7.27 (m, 4H), 7.23−7.21 (m, 3H), 7.11 (d, J
= 8.4 Hz, 2H), 7.00−6.98 (m, 2H), 6.42−6.38 (m, 2H), 6.29 (dd, J =
14.6, 7.9 Hz, 1H), 3.47 (d, J = 6.5 Hz, 2H), 2.38 (s, 3H). 13C NMR
(101 MHz; CDCl3): δ 143.9, 137.7, 137.4, 136.3, 134.6, 131.4, 129.8,
129.7, 128.9, 128.7, 127.42, 127.37, 126.2, 122.4, 38.8, 21.7. Mp: 137−
o
138 C. IR (cm−1): 3240 (NH, strong), 3024, 2912, 2870 (CH,
weak), 1153 (SO, strong), 1508, 1469 (CC, medium). Product
1
contains 0.21 equiv of H2O by H NMR analysis (see the Supporting
Information for a copy of spectrum). Anal. Calcd for C22H21NO2S +
0.21H2O: C, 71.95; H, 5.88; N, 3.81. Found: C, 72.07; H, 5.88; N,
3.79.
(E)-N-(4-Cinnamylphenyl)-2,2,2-trifluoroacetamide (3e) (Table 2,
Entry 6). Procedure A was followed with cinnamyl acetate (2a) (166
μL, 1.00 mmol) and 2,2,2-trifluoro-N-(4-iodophenyl)acetamide (472
mg, 1.50 mmol). Purification by flash chromatography (4% ethyl
acetate in hexanes) afforded 195 mg (64% yield) of the title compound
(E)-Prop-1-ene-1,3-diyldibenzene (3a) (Table 2, Entry 1).50
Procedure A was followed with cinnamyl acetate (2a) (166 μL, 1.00
mmol) and iodobenzene (167 μL, 1.50 mmol). Purification by flash
chromatography (100% hexanes) afforded 171 mg (88% yield) of the
title compound as a colorless oil; analytical data matched those
1
as a white solid. H NMR (400 MHz; CDCl3): δ 7.84 (s, 1H), 7.54−
7.23 (m, 9H), 6.48 (d, J = 15.8 Hz, 1H), 6.35 (dt, J = 15.7, 6.8 Hz,
1H), 3.58 (d, J = 6.8 Hz, 2H). 13C NMR (101 MHz; CDCl3): δ 154.8,
154.5, 138.5, 137.3, 133.2, 131.5, 129.6, 128.6, 127.3, 126.1, 120.7,
116.9, 38.7. 19F NMR (376 MHz; CDCl3): δ 76.2. Mp: 143−145 o C.
IR (cm−1): 3302 (NH, medium), 3213, 3151, 2955 (CH, weak), 1701
(CO, strong), 1554, 1512 (CC, strong), 1145 (CF, strong). Anal.
Calcd for C17H14F3NO: C, 66.88; H, 4.62; N, 4.59. Found: C, 66.610;
H, 4.705; N, 4.517.
1
reported in the literature. H NMR (400 MHz; CDCl3): δ 7.42−7.25
(m, 10H), 6.51 (d, J = 15.8 Hz, 1H), 6.42 (dd, J = 14.6, 7.8 Hz, 1H),
3.61 (d, J = 6.7 Hz, 2H). 13C NMR (101 MHz; CDCl3): δ 140.2,
137.5, 131.1, 129.3, 128.7, 128.5, 127.1, 126.2, 126.1, 39.4. GC−MS
(EI) m/z (rel intensity, ion): 194.05 (100.00, M+). HRMS (EI): [M+]
calcd for C15H14 194.110, found 194.110.
(E)-tert-Butyl (4-Cinnamylphenoxy)dimethylsilane (3f) (Table 2,
Entry 7). Procedure A was followed with cinnamyl acetate (2a) (83
μL, 1.00 mmol) and tert-butyl(4-iodophenoxy)dimethylsilane (261
mg, 1.50 mmol). Purification by flash chromatography (1% ethyl
acetate in hexanes) afforded 135 mg (80% yield) of the title compound
as a colorless oil. 1H NMR (400 MHz; CDCl3): δ 7.40−7.23 (m, 9H),
6.46 (s, 1H), 6.40 (s, 1H), 4.76 (s, 2H), 3.57 (d, J = 6.6 Hz, 2H), 0.98
(s, 9H), 0.13 (s, 6H). 13C NMR (101 MHz; CDCl3): δ 139.7, 139.1,
137.9, 131.3, 129.8, 128.92, 128.88, 127.5, 126.7, 126.5, 65.2, 39.4,
26.4, 18.8, −4.8. GC−MS (EI) m/z (rel intensity, ion): 338.30 (0.83,
M+), 117.10 (100.00, M+ − C13H21OSi). HRMS (EI): [M+] calcd for
C22H30OSi 338.207, found 338.207.
(E)-3-(4-N,N-Dimethylaminophenyl)-1-phenylpropene (3g)
(Table 2, Entry 8).51 Procedure A was followed with cinnamyl acetate
(2a) (166 μL, 1.00 mmol) and 4-iodo-N,N-dimethylaniline (371 mg,
1.50 mmol). Purification by flash chromatography (3% ethyl acetate in
hexanes) afforded 130 mg (55% yield) of the title compound as a
yellow oil; analytical data matched those reported in the literature. 1H
NMR (400 MHz; CDCl3): δ 7.40−7.14 (m, 7H), 6.75 (d, J = 8.7 Hz,
2H), 6.45 (s, 1H), 6.41 (d, J = 6.3 Hz, 1H), 3.49 (d, J = 6.4 Hz, 2H),
2.95 (s, 6H). 13C NMR (101 MHz; CDCl3): δ 149.3, 137.7, 130.3,
130.2, 129.3, 128.5, 128.2, 126.9, 126.1, 113.1, 40.9, 38.4. GC−MS
(EI) m/z (rel intensity, ion): 238.15 (100.00, M+). HRMS (EI) [M+]
calcd for C17H19N 237.152, found 237.152.
(E)-Prop-1-ene-1,3-diyldibenzene (3a) (Table 2, Entry 2).50
Procedure C was followed for a large-scale reaction run outside the
glovebox with cinnamyl acetate (2a) (1.68 mL, 10 mmol) and
iodobenzene (1.67 mL, 1.50 mmol). Purification by flash chromatog-
raphy using (100% hexanes) afforded 157 mg (81% yield) of the title
compound as a colorless oil; analytical data matched those reported in
1
the literature. H NMR (400 MHz; CDCl3): δ 7.41−7.22 (m, 10 H),
6.50 (d, J = 15.8 Hz, 1H), 6.40 (dt, J = 15.1, 7.3 Hz, 1H), 3.59 (d, J =
6.6 Hz, 2H). 13C NMR (101 MHz; CDCl3): δ 140.6, 137.9, 131.5,
129.6, 129.1, 128.9, 127.5, 126.6, 126.5, 39.8. GC−MS (EI) m/z (rel
intensity, ion): 194.05 (100.00, M+). HRMS (EI): [M+] calcd for
C15H14 194.110, found 194.110.
(E)-1-[p-(3-Phenylallyl)phenyl]ethanone (3b) (Table 2, Entry 3).51
Procedure A was followed with cinnamyl acetate (2a) (166 μL, 1.00
mmol) and 4-iodoacetophenone (369 mg, 1.50 mmol). Purification by
flash chromatography (8% ethyl acetate in hexanes) afforded 168 mg
(71% yield) of the title compound as a pale yellow oil; analytical data
matched those reported in the literature. 1H NMR (400 MHz;
CDCl3): δ 7.97 (d, J = 8.2 Hz, 2H), 7.41−7.31(m, 9H), 6.53 (d, J =
15.8 Hz, 1H), 6.38 (t, J = 11.3 Hz, 1H), 3.66 (d, J = 6.8 Hz, 2H), 2.65
(s, 3H). 13C NMR (101 MHz; CDCl3): δ 198.2, 146.3, 137.6, 135.8,
132.3, 129.3, 129.1, 129.0, 128.3, 127.8, 126.6, 39.7, 27.0. GC−MS
(EI) m/z (rel intensity, ion): 236.15 (100.00, M+). HRMS (EI): [M+]
calcd for C17H16O 236.120, found 236.120.
(E)-1-Methyl-4-(3-phenyl-2-propen-1-yl)benzene (3h) (Table 2,
Entry 9).51 Procedure A was followed with cinnamyl acetate (2a) (166
μL, 1.00 mmol) and 4-iodotoluene (377 mg, 1.50 mmol). Purification
by flash chromatography (100% hexanes) afforded 179 mg (86%
yield) of the title compound as a colorless oil; analytical data matched
(E)-p-(3-Phenylallyl)benzaldehyde (3c) (Table 2, Entry 4).51
Procedure A was followed with cinnamyl acetate (2a) (166 μL, 1.0
mmol) and 4-iodobenzaldehyde (348 mg, 1.50 mmol). Purification by
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those reported in the literature. 1H NMR (400 MHz; CDCl3): δ 7.42−
7.17 (m, 9H), 6.51 (d, J = 15.7 Hz, 1H), 6.44−6.38 (m, 1H), 3.57 (d, J
= 6.6 Hz, 2H), 2.39 (s, 3H). 13C NMR (101 MHz; CDCl3) δ 137.6,
137.1, 135.7, 130.8, 129.5, 129.2, 128.6, 128.5, 127.1, 126.1, 39.0, 21.1.
GC−MS (EI) m/z (rel intensity, ion): 208.05 (100.00, M+). HRMS
(EI) [M+] calcd for C16H16: 208.125; found: 208.125.
bromobenzotrifluoride (105.0 μL, 0.75 mmol). Purification by flash
chromatography (100% hexanes) afforded 68.3 mg (52% yield) of the
title compound as a clear oil; analytical data matched those above.
GC−MS (EI) m/z (rel intensity, ion): 262.10 (100.00, M+). HRMS
(EI): [M+] calcd for C16H13F3 262.097, found 262.097.
(E)-3-(4-Cyanophenyl)-1-phenylpropene (3m) (Table 2, Entry
15).51 Procedure A was followed with cinnamyl acetate (2a) (166.7
μL, 1.00 mmol) and 4-bromobenzonitrile (273.0 mg, 1.50 mmol).
Purification by flash chromatography (2% ethyl acetate in hexanes)
afforded 168.3 mg (77% yield) of the title compound as a clear oil;
analytical data matched those reported in the literature. 1H NMR (400
MHz; CDCl3): δ 7.58−7.55 (m, 2H), 7.34−7.18 (m, 7H), 6.44 (d, J =
15.8 Hz, 1H), 6.26 (dt, J = 15.7, 6.9 Hz, 1H), 3.57 (d, J = 6.8 Hz, 2H).
13C NMR (101 MHz; CDCl3): δ 145.9, 137.0, 132.5, 132.4, 129.5,
(E)-1-methoxy-4-(3-phenyl-2-propen-1-yl)benzene (3i) (Table 2,
Entry 10).50 Procedure A was followed with cinnamyl acetate (2a)
(166 μL, 1 mmol) and 4-iodoanisole (351 mg, 1.5 mmol). Purification
by flash chromatography (4% hexanes) afforded 186 mg (83% yield)
of the title compound as a yellow oil; analytical data matched those
1
reported in the literature. H NMR (400 MHz; CDCl3): δ 7.39−7.17
(m, 7H), 6.90−6.86 (m, 2H), 6.48−6.33 (m, 2H), 3.81 (s, 3H), 3.51
(d, J = 6.5 Hz, 2H). 13C NMR (101 MHz; CDCl3): δ 158.2, 137.7,
132.3, 130.9, 129.8, 129.7, 128.6, 127.2, 126.2, 114.0, 55.4, 38.6. GC−
MS (EI) m/z (rel intensity, ion): 224.10 (100.00, M+). HRMS (EI):
[M+] calcd for C16H16O 224.120, found 224.121.
128.7, 127.6, 127.2, 126.3, 119.1, 110.2, 39.4. GC−MS (EI) m/z (rel
intensity, ion): 219.05 (100.00, M+). HRMS (EI): [M+] calcd for
C16H13N 219.105, found 219.106.
(E)-1-Bromo-4-cinnamylbenzene (3j) (Table 2, Entry 11).1g
Procedure A was followed with cinnamyl acetate (2a) (166 μL, 1.00
mmol) and 1-bromo-4-iodobenzene (424 mg, 1.50 mmol). Purifica-
tion by flash chromatography (3% ethyl acetate in hexanes) afforded
191 mg (64% yield) of the title compound as a pale yellow oil;
analytical data matched those reported in the literature. This product
was isolated as an inseparable mixture with 9% 3a due to competing
hydrodeiodination. Yield reported is the yield of 3j, calculated by
NMR analysis and comparison with isolated 3a. 1H NMR (400 MHz;
CDCl3): δ 7.47−7.15 (m, 9H), 6.48 (d, J = 15.8 Hz, 1H), 6.34 (dt, J =
15.7, 6.8 Hz, 1H), 3.59 (d, J = 6.7 Hz,), 3.53 (d, J = 6.7 Hz, 2H). 13C
NMR (101 MHz; CDCl3): δ 139.1, 137.2, 131.5, 130.4, 129.2, 128.6,
128.4, 127.3, 126.1, 120.0, 38.7. GC−MS (EI) m/z (rel intensity, ion):
273.00 (6.88, M+), 115.05 (100.00, M+ − C6H4Br). HRMS (EI) [M+]:
calcd for C15H13Br 272.020, found 272.020.
(E)-3-(3-Methylphenyl)-1-phenylpropene (3n) (Table 2, Entry
16).51 Procedure A was followed with cinnamyl acetate (2a) (166
μL, 1.00 mmol) and 3-iodotoluene (377 mg, 1.50 mmol). Purification
by flash chromatography (100% hexanes) afforded 162 mg (78%
yield) of the title compound as a colorless oil; analytical data matched
those reported in the literature. 1H NMR (400 MHz; CDCl3): δ 7.39−
7.17 (m, 7H), 6.90−6.86 (m, 2H), 6.48−6.33 (m, 2H), 3.81 (s, 3H),
3.51 (d, J = 6.5 Hz, 2H). 13C NMR (101 MHz; CDCl3): δ 140.1,
138.1, 137.5, 131.0, 129.44, 129.38, 128.5, 128.4, 127.1, 126.9, 126.1,
125.7, 39.3, 21.4. GC−MS (EI) m/z (rel intensity, ion): 208.10
(100.00, M+). HRMS (EI): [M+] calcd for C16H16 208.125, found
208.125.
2-[(2E)-3-Phenylprop-2-en-1-yl]benzonitrile (3o) (Table 2, Entry
17).52 Procedure A was followed with cinnamyl acetate (2a) (166 μL,
1.00 mmol) and 2-iodobenzonitrile (343 mg, 1.50 mmol). Purification
by flash chromatography (3% hexanes in ethyl acetate) afforded 188
mg (86% yield) of the title compound as a colorless oil; analytical data
matched those reported in the literature. 1H NMR (400 MHz;
CDCl3): δ 7.70 (dt, J = 7.7, 0.6 Hz, 1H), 7.59 (td, J = 7.7, 1.2 Hz, 1H),
7.46−7.26 (m, 7H), 6.58 (d, J = 15.8 Hz, 1H), 6.37 (dt, J = 15.7, 7.0
Hz, 1H), 3.83 (d, J = 6.9 Hz, 2H). 13C NMR (101 MHz; CDCl3): δ
144.4, 137.3, 133.3, 133.0, 130.1, 129.0, 127.9, 127.3, 126.9, 126.7,
126.0, 118.4, 112.9, 38.1. GC−MS (EI) m/z (rel intensity, ion):
218.10 (100.00, M+). HRMS (EI): [M+] calcd for C16H12N 218.097,
found 218.097.
(E)-p-(3-Phenylallyl)methyl Benzoate (3k) (Table 2, Entry 12).50
Procedure A was followed with cinnamyl acetate (2a) (166.7 μL, 1.00
mmol) and methyl 4-bromobenzoate (322.6 mg, 1.50 mmol).
Purification by flash chromatography (2% ethyl acetate in hexanes)
afforded 163.3 mg (65% yield) of the title compound as a clear oil;
analytical data matched those reported in the literature. 1H NMR (400
MHz; CDCl3): δ 8.02−7.99 (m, 2H), 7.42−7.29 (m, 6H), 7.25−7.21
(m, 1H), 6.48 (d, J = 15.7 Hz, 1H), 6.34 (dt, J = 15.8, 6.8 Hz, 1H),
3.92 (s, 3H), 3.61 (d, J = 6.8 Hz, 2H). 13C NMR (101 MHz; CDCl3):
δ 167.2, 145.7, 137.3, 131.9, 130.0, 128.8, 128.7, 128.3, 128.2, 127.4,
126.3, 52.1, 39.4. GC−MS (EI) m/z (rel intensity, ion): 252.10 (56.47,
M+), 193.05 (100.00, M+ − C2H3O2). HRMS (EI): [M+] calcd for
C17H16O2 252.115, found 252.116.
(E)-1-[p-(3-phenylallyl)phenyl]ethanone (3b) (Table 2, Entry
13).51 Procedure A was followed with cinnamyl acetate (2a) (166.7
μL, 1.00 mmol) and 4′-bromoacetophenone (298.6 mg, 1.50 mmol).
Purification by flash chromatography (5% ethyl acetate in hexanes)
afforded 114.3 mg (48% yield) of the title compound as a clear oil;
analytical data matched those reported in the literature. 1H NMR (400
MHz; CDCl3): δ 7.93 (d, J = 8.3 Hz, 2H), 7.39−7.21 (m, 7H), 6.48
(d, J = 15.8 Hz, 1H), 6.34 (dt, J = 15.8, 6.8 Hz, 1H), 3.61 (d, J = 6.7
Hz, 2H), 2.60 (s, 3H). 13C NMR (101 MHz; CDCl3): δ 197.9, 146.0,
137.2, 135.5, 132.0, 129.0, 128.8, 128.7, 128.0, 127.5, 126.3, 39.4, 26.7.
GC−MS (EI) m/z (rel intensity, ion): 236.10 (100.00, M+). HRMS
(EI): [M+] calcd for C17H16O 236.120, found 236.120.
(E)-1-Phenyl-3-[4-(trifluoromethyl)phenyl]propene (3l) (Table 2,
Entry 14).51 Run 1 (1.00 mmol): Procedure A was followed with
cinnamyl acetate (2a) (166.7 μL, 1.00 mmol) and 4-bromobenzotri-
fluoride (210.0 μL, 1.50 mmol). Purification by flash chromatography
(100% hexanes) afforded 130.8 mg (50% yield) of the title compound
as a clear oil; analytical data matched those reported in the literature.
1H NMR (400 MHz; CDCl3): δ 7.54 (d, J = 8.0 Hz, 2H), 7.35−7.18
(m, 7H), 6.45 (d, J = 15.8 Hz, 1H), 6.34−6.26 (m, 1H), 3.57 (d, J =
6.8 Hz, 2H). 13C NMR (101 MHz; CDCl3): δ 144.4, 137.3, 132.1,
129.1, 128.7, [lit.51 128.49 (q, J = 10.8 Hz) was unresolved], 128.0,
127.5, 126.3, 125.8, 125.5 (q, J = 3.7 Hz), 39.2. 19F NMR (376 MHz;
CDCl3): δ −62.7. Run 2 (0.50 mmol): Procedure A (but on half scale)
was followed with cinnamyl acetate (83.4 μL, 0.50 mmol) and 4-
(E)-1-Methoxy-2-(3-phenyl-2-propen-1-yl)benzene (3p) (Table 2,
Entry 18).50 Procedure A was followed with cinnamyl acetate (2a)
(166 μL, 1.00 mmol) and 2-iodoanisole (351 mg, 1.50 mmol).
Purification by flash chromatography (4% hexanes in ethyl acetate)
afforded 179 mg (80% yield) of the title compound as a yellow oil;
analytical data matched those reported in the literature. 1H NMR (400
MHz; CDCl3): δ 7.41−7.39 (m, 2H), 7.34−7.29 (m, 2H), 7.28−7.21
(m, 3H), 6.97−6.91 (m, 2H), 6.50−6.41 (m, 2H), 3.89 (s, 3H), 3.59
(d, J = 6.0 Hz, 2H). 13C NMR (101 MHz; CDCl3): δ 157.3, 137.8,
130.7, 129.9, 128.9, 128.7, 128.4, 127.4, 126.9, 126.1, 120.5, 110.4,
55.4, 33.4. GC−MS (EI) m/z (rel intensity, ion): 224.10 (100.00, M+).
HRMS (EI): [M+] calcd for C16H16O 224.120, found 224.120.
(E)-1-Phenylhex-2-ene (4a) (Table 3 Entry 1).53 Procedure A was
followed with (E)-hex-2-en-1-yl acetate (2b) (142 mg, 1 mmol) and
iodobenzene (167 μL, 1.5 mmol). Purification by flash chromatog-
raphy (100% hexanes) afforded 129 mg (81% yield) of the title
compound as a colorless oil. The isolated product had a 86:14
[linear]/[branched] ratio, as determined by analysis of the GC/MS
1
fragmentation patterns and comparison with literature NMR data. H
NMR (400 MHz; CDCl3) linear isomer:28,29 δ 7.33−7.21 (m, 5H),
5.64−5.50 (m, 2H), 3.37 (d, J = 6.1 Hz, 2H), 2.08−2.01 (m, 2H), 1.43
(tq, J = 7.4 Hz, 2H), 0.95−0.90 (t, 3H); branched isomer: δ 7.33−7.21
(m, 5H), δ 6.02−5.90 (m, 1H), δ 5.07−5.03 (m, 2H), δ 3.32−3.26 (m,
1H), δ 1.75−1.68 (m, 2H), δ 1.42−1.30 (m, 2H), 0.95−0.90 (t, 3H).
13C NMR (101 MHz; CDCl3) linear isomer: δ 141.3, 132.1, 129.0,
128.6, 128.53, 128.48, 126.0, 39.2, 34.8, 22.8, 13.9; Partial 13C NMR
for branched isomer, δ 127.7, 37.8, 20.8. GC−MS (EI) m/z (rel
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intensity, ion): 160.10 (54.39, M+), 117.05 (100.00, M+ C3H7). HRMS
(EI): [M+] calcd for C12H16 160.125, found 160.125.
2H), 1.86−1.84 (d, 3H). 13C NMR (101 MHz; CDCl3) linear 2E,4Z
isomer: δ 140.5, 132.4, 129.2, 128.6, 128.4, 126.6, 125.0, 39.3, 13.4;
linear 2E,4E and unidentified olefin isomer: δ 131.6, 131.4, 130.4,
130.1, 129.5, 128.5, 127.9, 127.4, 126.7, 126.1, 126.1, 126.0, 125.98,
125.95, 39.0, 33.9, 18.4, 18.1, 13.4 (no literature 13C NMR spectrum is
available for linear 2E,4E olefin isomer). GC−MS (EI) m/z (rel
intensity, ion): 158.10 (52.92, M+), 129.10 (100.00, M+ − C2H4).
HRMS (EI): [M+] calcd for C12H14 158.120, found 158.120.
(E)-Prop-1-ene-1, 3-diyldibenzene (3a) (Table 3, Entry 2).50
Procedure A was followed with 1-phenylallyl acetate (2c) (176 mg,
1.00 mmol) and iodobenzene (167 μL, 1.50 mmol). Purification by
flash chromatography (100% hexanes) afforded 101 mg (52% yield) of
the title compound as a colorless oil; analytical data matched those
1
reported in the literature. H NMR (400 MHz; CDCl3) δ 7.41−7.24
(m, 10H), 6.50 (d, J = 15.8 Hz, 1H), 6.40 (dt, J = 15.1, 7.3 Hz, 1H),
3.59 (d, J = 6.5 Hz, 2H). 13C NMR (101 MHz; CDCl3) δ140.6, 137.9,
131.5, 129.6, 129.1, 128.9, 127.5, 126.6, 126.5, 39.8. GC−MS (EI) m/z
(rel intensity, ion): 194.10 (100.00, M+). HRMS (EI) [M+]: calcd for
C15H14 194.120, found 194.120.
(3,7-Dimethylocta-2,6-dien-1-yl)benzene (4e) (Table 3, Entry
7).53a,56,57 Procedure A was followed with geranyl acetate (214 μL,
1.00 mmol) and iodobenzene (167 μL, 1.50 mmol). Purification by
flash chromatography (100% hexanes) afforded 171 mg (80% yield) of
a mixture of the three isomers as a colorless oil. Isolated product has a
1.9:1 [linear]/[branched] ratio. The linear and branched products
were identified by GC/MS fragmentation patterns and by comparison
with literature NMR values. By NMR, the yield of linear products is
52% and the yield of branched product is 28%. Linear (E and Z)
Isomers.53a,57 1H NMR (500 MHz; CDCl3): δ 7.36−7.21 (m, 10H),
5.40−5.36 (m, 2H), 5.19−5.07 (m, 2H), 3.40 (d, J = 7.2 Hz, 4H),
2.22−2.08 (m, 8H), 1.79 (s, 3H), 1.75 (s, 3H), 1.72 (s, 6H), 1.66 (s,
3H), 1.64 (s, 3H). 13C NMR (126 MHz; CDCl3): δ 142.0 (E), 141.9
(Z), 136.4 (E), 136.3 (Z), 131.9 (Z), 131.6 (E), 128.50 (E/Z), 128.47
(E/Z), 128.45 (E/Z), 125.83 (E/Z), 125.80 (E/Z), 124.4 (E), 124.3
(Z), 124.0 (Z), 123.2 (E), 39.9 (E), 34.33 (E/Z), 34.27 (E/Z), 32.1
(Z), 26.7 (E/Z), 25.9 (E), 25.8 (Z), 25.0 (Z), 23.6 (Z), 17.9 (E), 17.8
(Z), 16.3 (E). Branched isomer:56 1H NMR (500 MHz; CDCl3): δ
7.36−7.21 (m, 5H), 6.08 (dd, J = 17.5, 10.7 Hz, 1H), 5.19−5.07 (m,
2H), 1.91−1.82 (m, 4H), 1.69 (s, 3H), 1.55 (s, 3H), 1.42 (s, 3H). 13C
NMR (126 MHz; CDCl3): δ 147.6, 147.0, 131.5, 128.2, 126.7, 125.9,
124.8, 111.9, 44.4, 41.3, 25.9, 23.4, 17.7. GC−MS (EI) m/z (rel
intensity, ion): 214.15 (9.14, M+), 123.15 (100.00, M+ - C7H7). HRMS
(EI) [M+] calcd for C16H22: 214.172; found: 214.173.
(E)-Prop-1-ene-1,3-diyldibenzene (3a) (Table 3, Entry 3).50
Procedure A was followed with (Z)-3-phenylallyl acetate (2d) (176
mg, 1 mmol) and iodobenzene (167 μL, 1.5 mmol). Purification by
flash chromatography (100% hexanes) afforded 146 mg (75% yield) of
the title compound as a colorless oil; analytical data matched those
1
reported in the literature. H NMR (400 MHz; CDCl3): δ 7.41−7.22
(m, 10H), 6.50 (d, J = 15.8 Hz, 1H), 6.40 (dt, J = 15.7, 6.7 Hz, 1H),
3.60 (d, J = 6.6 Hz, 2H). 13C NMR (101 MHz; CDCl3): δ 140.6,
137.9, 131.5, 129.6, 129.1, 128.9, 127.5, 126.6, 126.5, 39.8. GC−MS
(EI) m/z (rel intensity, ion): 194.05 (100.00, M+). HRMS (EI): [M+]
calcd for C15H14 194.110, found 194.110.
(E)-1-Cyclohexyl-3-phenylpropene (4b) (Table 3, Entry 4).50
Procedure A was followed with 3-cyclohexylallyl acetate (2e) (182
mg, 1.00 mmol) and iodobenzene (167 μL, 1.50 mmol). Purification
by flash chromatography (100% hexanes) afforded 194 mg (97%
yield) of the title compound as a colorless oil. The isolated product has
a 93:7 [linear]/[branched] ratio, as determined by GC/MS
fragmentation patterns and by comparison with literature NMR
1
data. H NMR (400 MHz; CDCl3) linear isomer: δ 7.35−7.18 (m,
5H), 5.60−5.49 (m, 2H), 3.36 (d, J = 5.8 Hz, 2H), 2.01−1.96 (m,
1H), 1.78−1.66 (m, 5H), 1.34−1.09 (m, 5H); branched isomer: δ
7.35−7.18 (m, 5H), δ 6.06−5.98 (m, 1H), δ 5.06 (d, 1H), δ5.03 (d,
1H), 2.97 (t, 1H), 1.97−2.01 (m, 1H), 1.65−1.59 (m, 3H), 1.48−1.44
(m, 1H), 1.34−1.09 (m, 5H). 13C NMR (101 MHz; CDCl3) linear
isomer: δ 141.2, 138.1, 128.5, 128.3, 126.1, 125.8, 40.7, 39.1, 33.1,
26.2, 26.1; branched isomer: δ 141.2, 138.1, 128.5, 128.3, 126.1, 125.8,
40.7, 39.1, 33.1, 26.2, 26.1 (one peak was not visible). GC−MS (EI)
m/z (rel intensity, ion): 200.10 (14.90, M+), 109.10 (100.00, M+ −
C7H7). HRMS (EI): [M+] calcd for C15H20 200.157, found 200.157.
1-(4-(2-Methylallyl)phenyl)ethanone (4c) (Table 3, Entry 5).54
Procedure A was followed with 2-methylallyl acetate (2f) (114 mg,
1.00 mmol) and 4-iodoacetophenone (369 mg, 1.50 mmol).
Purification by flash chromatography (9% ethyl acetate in hexanes)
afforded 96 mg (55% yield) of the title compound as a pale yellow oil;
analytical data matched those reported previously. 1H NMR (400
MHz; CDCl3): δ 7.93−7.91 (m, 2H), 7.30 (t, J = 7.8 Hz, 2H), 4.88 (s,
1H), 4.77 (s, 1H), 3.40 (s, 2H), 2.61 (s, 3H), 1.70 (s, 3H). 13C NMR
(101 MHz; CDCl3): δ 197.8, 145.5, 144.1, 135.3, 129.1, 128.5, 112.7,
44.6, 26.6, 22.1. GC−MS (EI) m/z (rel intensity, ion): 174.10 (15.17,
M+), 115 (100.00, M+ − CH3). HRMS (EI): [M+] calcd for C12H14O
174.105, found 174.105.
1-phenyl-2-cyclohexene (4f) (Table 3, Entry 8).53a Procedure A
was followed with cyclohex-2-en-1-yl acetate (2i) (140 mg, 1.00
mmol) and iodobenzene (167 μL, 1.50 mmol). Purification by flash
chromatography (100% hexanes) afforded 126 mg (80% yield) of the
1
title compound as a colorless oil. H NMR (500 MHz; CDCl3): δ
7.35−7.22 (m, 5H), 5.95−5.91 (m, 1H), 5.78−5.74 (m, 1H), 3.45 (td,
J = 5.1, 2.5 Hz, 1H), 2.15−2.03 (m, 3H), 1.81−1.77 (m, 1H), 1.69−
1.55 (m, 2H). 13C NMR (101 MHz; CDCl3): δ 146.7, 130.2, 128.4,
128.3, 127.8, 126.0, 41.9, 32.7, 25.1, 21.2. GC−MS (EI) m/z (rel
intensity, ion): 158.10 (100.00, M+). HRMS (EI): [M+] calcd for
C12H14 158.120, found 158.110. NMR data matched those previously
reported.
(E)-But-1-ene-1,3-diyldibenzene (4g) (Table 3, Entry 9).53a
Procedure A was followed with but-1-ene-1,3-diyldibenzene (2j)
(190 mg, 1.00 mmol) and iodobenzene (167 μL, 1.50 mmol).
Purification by flash chromatography (100% hexanes) afforded 152 mg
1
(73% yield) of the title compound as a colorless oil. H NMR (400
MHz; CDCl3): δ 7.41−7.23 (m, 10H), 6.48−6.39 (m, 2H), 3.71−3.65
(m, 1H), 1.51 (d, J = 7.0 Hz, 3H). 13C NMR (101 MHz; CDCl3): δ
145.8, 137.7, 135.4, 128.7, 128.5, 127.4, 127.2, 126.4, 126.3, 42.7, 21.4
GC−MS (EI) m/z (rel intensity, ion): 208.10 (66.46, M+), 115
(100.00, M+ − C7H8). HRMS (EI): [M+] calcd for C16H16 208.125,
found 208.125. NMR data matched those previously reported.
Procedure D: Allylic Acetates with Alkyl Halides in a Nitrogen
Glovebox. A 1 dram vial was charged with NiCl2(dme) (10.6 mg,
0.0483 mmol), 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine (20.0 mg,
(0.0498 mmol), and DMA (500 μL), a Teflon-coated magnetic stirbar
was then added, and the reaction mixture was stirred for 5−10 min
before the sequential addition of allylic acetate (1.3 mmol), secondary
alkyl halide (1.0 mmol), THF (1500 μL), and manganese powder
(109.6 mg, 2.00 mmol). The vial was then capped with a screw cap
with a PTFE-faced silicone septum. The reaction was then treated as in
procedure A (vide supra).
(2E,4E)-Hexa-2,4-dien-1-ylbenzene (4d) (Table 3, Entry 6).55
Procedure A was followed with (2E, 4E)-hexa-2,4-dien-1-yl acetate
(2g) (140 mg, 1.00 mmol) and iodobenzene (167 μL, 1.50 mmol).
Purification by flash chromatography (100% hexanes) afforded 103 mg
(65% yield) of the title compound as a colorless oil. Product was a
mixture of olefin isomers: 6.9:1:1 [2E,4E]/[2E,4Z]/[unidentified
olefin isomer]. Olefin isomer ratio and identity were assigned based
upon GC/MS fragmentation patterns and by comparison to previously
reported NMR spectra (1H and 13C). We assigned one isomer as
2E,4E in analogy to the other products. 1H NMR (400 MHz; CDCl3)
linear 2E,4E isomer:56 δ 7.34−7.21 (m, 5H), 6.11−6.08 (m, 2H),
5.76−5.65 (m, 2H), 3.44 (d, J = 6.9 Hz, 2H), 1.78 (d, J = 6.2 Hz, 3H);
linear 2E,4Z isomer:57 δ 7.34−7.21 (m, 5H), 6.52−6.43 (dd, 1H),
6.11−6.08 (t, 1H), 5.76−5.65 (m, 1H), 5.51−5.46 (m, 1H), 3.50 (d, J
= 7.0 Hz,), 1.78 (dd, 3H); unidentified olefin isomer: δ 7.34−7.21 (m,
5H), 6.11−6.08 (m, 2H), 5.76−5.65 (m, 2H), 3.56 (d, J = 7.4 Hz,
Procedure E: Allylic Acetates with Alkyl Halides on the Benchtop
under Argon. As in procedure D, but set up on the bench, without
care to exclude air or moisture. Once the reaction was capped, the
reaction mixture was sparged with Ar gas for 1 min, followed by a
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purge of the vial head space for 1 min. The needles were then removed
and the vial placed in a heating block at 40 °C in the usual manner.
(E)-(4-Methylnon-1-en-1-yl)benzene (5a) (Table 4, Entry 1). Run 1
(1.00 mmol): General procedure D was followed with cinnamyl
acetate (2a) (216.7 μL, 1.30 mmol) and 2-bromoheptane (172.9 μL,
1.00 mmol, distilled purity was 90.7% so amount was scaled from
156.8 μL). Purification by flash chromatography (100% hexanes)
afforded 151.7 mg (70% yield) of the title compound as a clear oil. 1H
NMR (400 MHz; CDCl3): δ 7.38−7.18 (m, 5H), 6.39 (d, J = 15.8 Hz,
1H), 6.23 (dt, J = 15.4, 7.5 Hz, 1H), 2.27−2.02 (m, 2H), 1.62−1.56
(m, 1H), 1.37−1.28 (m, 7H), 1.20−1.14 (m, 1H), 0.95−0.90 (m, 6H).
13C NMR (101 MHz; CDCl3): δ 138.1, 131.0, 130.0, 128.6, 126.9,
126.1, 40.8, 36.8, 33.5, 32.3, 27.0, 22.9, 19.8, 14.3. GC−MS (EI) m/z
(rel intensity, ion): 216.15 (18.02, M+), 117.10 (100.00, M+ − C7H15).
HRMS (EI): [M+] calcd for C16H24 216.188, found 216.187. Run 2
(0.50 mmol): General procedure D was followed with cinnamyl
acetate (83.4 μL, 0.65 mmol) and 2-bromoheptane (86.2 μL, 0.50
mmol, Aldrich lot no. 12798PJ was 90.7% so amount was scaled from
78.4 μL). Purification by flash chromatography (100% hexanes)
Hz, 1H), 6.20 (dt, J = 15.8, 7.0 Hz, 1H), 2.24−2.14 (m, 2H), 2.07−
2.00 (m, 2H), 1.61−1.42 (m, 4H), 1.42−1.32 (m, 1H), 1.31−1.10 (m,
4H). 13C NMR (101 MHz; CDCl3): δ 138.1, 130.4, 130.3, 128.6,
126.9, 126.1, 42.2, 40.9, 40.4, 38.0, 36.9, 35.3, 30.2, 29.0. GC−MS (EI)
m/z (rel intensity, ion): 212.10 (12.51, M+), 95.10 (100.00, M+
−
C9H9). HRMS (EI): [M+] calcd for C16H20 212.157, found 212.157.
(E)-1-Methoxy-4-(4-methylnon-1-en-1-yl)benzene (5e) (Table 4,
Entry 6). General procedure D was followed with (E)-3-(4-
methoxyphenyl)allyl acetate (2k) (268.1 mg, 1.30 mmol) and 2-
bromoheptane (172.9 μL, 1.10 mmol because material was 90.7%
pure). Purification by flash chromatography (2% ethyl acetate in
hexanes) afforded 209.8 mg (85% yield) on run 1 and 178.2 mg (72%
1
yield) on run 2 of the title compound as a clear oil. H NMR (400
MHz; CDCl3): δ 7.31−7.27 (m, 2H), 6.87−6.83 (m, 2H), 6.32 (d, J =
15.7 Hz, 1H), 6.08 (dt, J = 15.7, 7.3 Hz, 1H), 3.81 (s, 3H), 2.24−1.99
(m, 2H), 1.61−1.53 (m, 1H), 1.39−1.27 (m, 7H), 1.20−1.13 (m, 1H),
0.93−0.89 (m, 6H). 13C NMR (101 MHz; CDCl3): δ 158.7, 131.0,
130.3, 127.8, 127.1, 114.0, 55.4, 40.7, 36.8, 33.5, 32.3, 27.0, 22.9, 19.8,
14.3. GC−MS (EI) m/z (rel intensity, ion): 246.20 (15.13, M+),
147.10 (100.00, M+ − C7H15). HRMS (EI): [M+] calcd for C17H26O
246.198, found 246.198.
1
afforded 95.6 mg (88% yield) of the title compound as a clear oil. H
NMR matched those reported in run 1.
(E)-(3-Cyclohexylprop-1-enyl)benzene (5b) (Table 4, Entry 2).58
General procedure D was followed with cinnamyl acetate (2a) (216.7
μL, 1.30 mmol) and bromocyclohexane (123.2 μL, 1.00 mmol).
Purification by flash chromatography (100% hexanes) afforded 180.6
mg (90% yield) on run 1 and 171.7 mg (86% yield) on run 2 of the
title compound as a clear oil; analytical data matched those reported in
(E)-(4-Methylnon-1-en-1-yl)-4-(trifluoromethyl)benzene (5f)
(Table 4, Entry 7). Run 1 (1.00 mmol): General procedure D was
followed with (E)-3-(4-trifluoromethyl)phenyl)allyl acetate (2l)
(317.5 mg, 1.30 mmol) and 2-bromoheptane (172.9 μL, 1.10 mmol
because material was 90.7% pure). Purification by flash chromatog-
raphy (100% hexanes) afforded 202.1 mg (71% yield) of the title
compound as a clear oil. 1H and 13C NMR spectra match those
reported for run 2. Run 2 (0.50 mmol): General procedure D was
followed with (E)-3-(4-trifluoromethyl)phenyl)allyl acetate (2l)
(175.2 mg, 0.65 mmol, 2l was 90.6% pure by GC so amount was
scaled from 158.5 mg) and 2-bromoheptane (86.5 μL, 0.50 mmol,
distilled purity was 90.7% so amount was scaled from 78.4 μL).
Purification by flash chromatography (100% hexanes) afforded 85.6
1
the literature. H NMR (400 MHz; CDCl3): δ 7.39−7.30 (m, 4H),
7.23−7.20 (m, 1H), 6.39 (d, J = 15.8 Hz, 1H), 6.25 (dt, J = 15.4, 7.5
Hz, 1H), 2.16−2.12 (m, 2H), 1.82−1.68 (m, 5H), 1.43 (ddtd, J = 14.5,
10.8, 7.2, 3.6 Hz, 1H), 1.32−1.14 (m, 3H), 1.04−0.94 (m, 2H). 13C
NMR (101 MHz; CDCl3): δ 138.1, 130.8, 129.9, 128.6, 126.9, 126.0,
41.2, 38.3, 33.4, 26.7, 26.5. GC−MS (EI) m/z (rel intensity, ion):
200.15 (23.74, M+), 104.10 (100.00, M+ − C7H13 + H). HRMS (EI):
[M+] calcd for C15H20 200.157, found 200.156.
1
mg (60% yield) of the title compound as a clear oil. H NMR (400
(E)-(3-Cyclohexylprop-1-enyl)benzene (5b) (Table 4, Entry 3).58
General procedure E was followed with cinnamyl acetate (2a) (216.7
μL, 1.30 mmol) and bromocyclohexane (123.2 μL, 1.00 mmol).
Purification by flash chromatography (100% hexanes) afforded 179.4
mg (90% yield) of the title compound as a clear oil; analytical data
matched those reported in the literature. 1H NMR (400 MHz;
CDCl3): δ 7.39−7.30 (m, 4H), 7.23−7.19 (m, 1H), 6.38 (d, J = 15.8
Hz, 1H), 6.25 (dt, J = 15.7, 7.2 Hz, 1H), 2.15−2.12 (m, 2H), 1.81−
1.67 (m, 5H), 1.43 (ddtd, J = 14.5, 10.9, 7.2, 3.6 Hz, 1H), 1.32−1.13
(m, 3H), 1.04−0.90 (m, 2H). 13C NMR (101 MHz; CDCl3): δ 138.1,
130.8, 129.9, 128.6, 126.9, 126.0, 41.2, 38.3, 33.4, 26.7, 26.5. GC−MS
(EI) m/z (rel intensity, ion): 200.15 (22.48, M+), 104.10 (100.00, M+
− C7H13 + H). HRMS (EI): [M+] calcd for C15H20 200.157, found
200.156.
MHz; CDCl3): δ 7.54 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 8.2 Hz, 2H),
6.42−6.28 (m, 2H), 2.28−2.03 (m, 2H), 1.64−1.54 (m, 1H), 1.37−
1.25 (m, 7H), 1.19−1.14 (m, 1H), 0.93−0.88 (m, 6H). 13C NMR
(101 MHz; CDCl3): δ 141.5, 132.9, 129.8, 126.2, 125.54, 125.51, 40.8,
36.8, 33.4, 32.3, 26.9, 22.9, 19.8, 14.3. We were unable to resolve one
of the expected carbon atoms. We presume the missing carbon to be
the CF3 quartet based upon literature data for similar compounds. 19
F
NMR (376 MHz; CDCl3): δ −62.8. GC−MS (EI) m/z (rel intensity,
ion): 284.20 (8.51, M+), 57.10 (100.00, M+ − C13H14F3). HRMS (EI):
[M+] calcd for C17H23F3 284.175, found 284.176.
Procedure F: Allylic Acetates and Carbonates with a Vinyl
Bromide in a Nitrogen Glovebox. A 1 dram vial was charged with
NiCl2(dme) (10.6 mg, 0.0483 mmol), 2,9-dimethyl-1,10-phenanthro-
line (10.4 mg, (0.0499 mmol), and DMA (500 μL) followed by a
Teflon coated magnetic stirbar. The reaction mixture was stirred for
5−10 min. In a separate 1 dram vial the branched allylic starting
material (1.0 mmol) and 2-bromocyclohex-2-en-1-one (1.0 mmol)
were massed. The catalyst solution was the added to the substrates,
followed by THF (1500 μL) and manganese powder (−325 mesh,
109.6 mg, 2.00 mmol), sequentially. The remainder of the procedure
followed proceure A (vide supra).
2-Cinnamylcyclohex-2-enone (7a) (Table 5, Entry 3). General
procedure F was followed with 1-phenyl-2-propenyl acetate (2c)
(176.2 mg, 1.00 mmol) and 2-bromocyclohex-2-en-1-one (6) (175.0
mg, 1.00 mmol). Purification by flash chromatography (5% ethyl
acetate in hexanes) afforded 165.3 mg (78% yield) of the title
compound as a pale yellow oil. 1H NMR (400 MHz; CDCl3): δ 7.36−
7.18 (m, 5H), 6.78 (t, J = 4.2 Hz, 1H), 6.41 (d, J = 15.8 Hz, 1H), 6.22
(dt, J = 15.8, 7.0 Hz, 1H), 3.12−3.09 (m, 2H), 2.48−2.44 (m, 2H),
2.36 (tdt, J = 6.0, 4.0, 1.9 Hz, 2H), 2.01 (dq, J = 12.9, 6.3 Hz, 2H). 13C
NMR (101 MHz; CDCl3): δ 199.1, 146.1, 138.4, 137.6, 131.7, 128.6,
127.7, 127.2, 126.2, 38.6, 32.9, 26.2, 23.2. GC−MS (EI) m/z (rel
intensity, ion): 212.00 (62.05, M+), 121.05 (100.00). HRMS (EI):
[M+] calcd for C15H16O 212.120, found 212.119.
(E)-(3-Cyclopentyl-1-propenyl)benzene (5c) (Table 4, Entry 4).59
General procedure D was followed with cinnamyl acetate (2a) (216.7
μL, 1.30 mmol) and bromocyclopentane (107.2 μL, 1.00 mmol).
Purification by flash chromatography (100% hexanes) afforded 129.1
mg (69% yield) on Run 1 and 123.7 mg (66% yield) on Run 2 of the
title compound as a clear oil; analytical data matched those reported in
1
the literature. H NMR (400 MHz; CDCl3): δ 7.37−7.29 (m, 4H),
7.20 (td, J = 7.2, 1.8 Hz, 1H), 6.39 (d, J = 15.8 Hz, 1H), 6.25 (dt, J =
15.8, 7.0 Hz, 1H), 2.26−2.22 (m, 2H), 1.97 (dquintet, J = 15.0, 7.5 Hz,
1H), 1.84−1.76 (m, 2H), 1.69−1.51 (m, 4H), 1.27−1.18 (m, 2H). 13C
NMR (101 MHz; CDCl3): δ 138.1, 130.7, 130.3, 128.6, 126.9, 126.1,
40.2, 39.6, 32.5, 25.3. GC−MS (EI) m/z (rel intensity, ion): 186.10
(25.68, M+), 117.10 (100.00, M+ − C5H9). HRMS (EI): [M+] calcd
for C14H18 186.141, found 186.141.
(E)-(1S,2R,4R)-2-Cinnamylbicyclo[2.2.1]heptane (5d) (Table 4,
Entry 5). General procedure D was followed with cinnamyl acetate
(2a) (216.7 μL, 1.30 mmol) and exo-2-bromonorborane (128.4 μL,
1.00 mmol). Purification by flash chromatography (100% hexanes)
afforded 179.0 mg (84% yield) on run 1 and 150.2 mg (71% yield) on
run 2 of the title compound as a clear oil. 1H NMR (400 MHz;
CDCl3): δ 7.38−7.29 (m, 4H), 7.23−7.18 (m, 1H), 6.38 (d, J = 15.8
9998
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The Journal of Organic Chemistry
Featured Article
(E)-2-(4-Ethylhex-2-en-1-yl)cyclohex-2-enone (7b) (Table 6, Entry
3). General procedure F was followed with 4-ethyl-hex-1-en-3-yl
methyl carbonate (2m) (186.3 mg, 1.00 mmol) and 2-bromocyclohex-
2-en-1-one (6) (175.0 mg, 1.00 mmol). Purification by flash
chromatography (5% ethyl acetate in hexanes) afforded 104.6 mg
(51% yield) of the title compound as a dark yellow oil. 1H NMR (400
MHz; CDCl3): δ 6.70 (t, J = 4.2 Hz, 1H), 5.32 (dt, J = 14.8, 7.2 Hz,
1H), 5.14 (dd, J = 15.2, 8.7 Hz, 1H), 2.89 (d, J = 6.8 Hz, 2H), 2.42 (t,
J = 6.8 Hz, 2H), 2.34 (tdt, J = 5.9, 4.0, 1.9 Hz, 2H), 2.03−1.94 (m,
2H), 1.73 (dtd, J = 13.3, 8.7, 4.7 Hz, 1H), 1.43−1.33 (m, 2H), 1.23−
1.14 (m, 2H), 0.82 (t, J = 7.4 Hz, 6H). 13C NMR (101 MHz; CDCl3):
δ 199.3, 145.2, 139.2, 137.1, 127.0, 46.4, 38.7, 32.3, 27.8, 26.2, 23.3,
11.9. GC−MS (EI) m/z (rel intensity, ion): 206.10 (3.97, M+), 135.05
(100.00, M+ − C5H11). HRMS (EI): [M+] calcd for C14H22O 206.167,
found 206.166.
(E)-2-(5-Phenylpent-2-en-1-yl)cyclohex-2-enone (7c) (Table 6,
Entry 4). General procedure F was followed with 5-phenyl-pent-1-
en-3-yl methyl carbonate (2n) (220.3 mg, 1.00 mmol) and 2-
bromocyclohex-2-en-1-one (6) (175.0 mg, 1.00 mmol). Purification by
flash chromatography (5% ethyl acetate in hexanes) afforded 104.6 mg
(51% yield) of the title compound as a pale yellow oil. 1H NMR (400
MHz; CDCl3): δ 7.29−7.16 (m, 5H), 6.52 (t, J = 4.2 Hz, 1H), 5.51−
5.35 (m, 2H), 2.86 (d, J = 6.3 Hz, 2H), 2.69 (t, J = 7.7 Hz, 2H), 2.42
(td, J = 6.8, 3.0 Hz, 2H), 2.37−2.28 (m, 4H), 1.96 (dt, J = 13.0, 6.4 Hz,
2H). 13C NMR (101 MHz; CDCl3): δ 199.3, 145.6, 142.1, 138.7,
131.7, 128.7, 128.3, 127.9, 125.8, 38.6, 36.0, 34.4, 32.2, 26.2, 23.2.
GC−MS (EI) m/z (rel intensity, ion): 240.10 (14.85, M+), 91.00
(100.00, M+ − C10H13O). HRMS (EI): [M+] calcd for C17H20O
240.151, found 240.151.
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ASSOCIATED CONTENT
* Supporting Information
■
S
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1996, 61, 1748−1755. (b) Wang, S.; Qian, Q.; Gong, H. Org. Lett.
Full selectivity data (Tables S1−S5), Table S6, details on
methods and starting materials, and copies of 1H and 13C NMR
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
2012, 14, 3352−3355.
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2010, 46, 5743−5745 and unpublished studies.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: daniel.weix@rochester.edu.
(11) Semmelhack, M. F. Org. React. 1972, 19, 115−198.
(12) Qian, X.; Auffrant, A.; Felouat, A.; Gosmini, C. Angew. Chem.,
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Author Contributions
(13) Dai, Y.; Wu, F.; Zang, Z.; You, H.; Gong, H. Chem.Eur. J.
‡These authors contributed equally.
2012, 18, 808−812.
(14) Shi, L.; Fan, C.-A.; Tu, Y.-Q.; Wang, M.; Zhang, F.-M.
Tetrahedron 2004, 60, 2851−2855.
Notes
The authors declare no competing financial interest.
(15) Durandetti, M.; Gosmini, C.; Per
1146−1153.
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ichon, J. Tetrahedron 2007, 63,
ACKNOWLEDGMENTS
■
(16) See Table 1 and Tables S1−S5 in the Supporting Information.
(17) (a) Majid, T. N.; Knochel, P. Tetrahedron Lett. 1990, 31, 4413−
4416. (b) Ikegami, R.; Koresawa, A.; Shibata, T.; Takagi, K. J. Org.
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Research reported in this publication was supported by the
National Institute of General Medical Science of the National
Institutes of Health under award no. R01 GM097243.
Analytical data were obtained from the CENTC Elemental
Analysis Facility at the University of Rochester, funded by NSF
CHE-0650456. Mass spectrometry data were obtained from the
Univeristy of Illinois, with instrumentation funded in part by
the NIH (RR 04648).
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