Base-mediated cascade rearrangements of aryl-substituted diallyl ethers

Article abstract of DOI:10.1021/jo502403n

Two base-mediated cascade rearrangement reactions of diallyl ethers were developed leading to selective [2,3]-Wittig-oxy-Cope and isomerization-Claisen rearrangements. Both diaryl and arylsilyl-substituted 1,3-substituted propenyl substrates were examined, and each exhibits unique reactivity and different reaction pathways. Detailed mechanistic and computational analysis was conducted, which demonstrated that the role of the base and solvent was key to the reactivity and selectivity observed. Crossover experiments also suggest that these reactions proceed with a certain degree of dissociation, and the mechanistic pathway is highly complex with multiple competing routes.

Full text of DOI:10.1021/jo502403n

Article
pubs.acs.org/joc
Base-Mediated Cascade Rearrangements of Aryl-Substituted Diallyl
Ethers
Jolene P. Reid,†,‡ Catherine A. McAdam,† Adam J. S. Johnston,† Matthew N. Grayson,‡
Jonathan M. Goodman,‡ and Matthew J. Cook*,†
†School of Chemistry and Chemical Engineering, Queen’s University Belfast, Belfast BT9 5AG, Northern Ireland, United Kingdom
‡Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road,
Cambridge CB2 1EW, United Kingdom
S
* Supporting Information
ABSTRACT: Two base-mediated cascade rearrangement reactions of diallyl ethers were developed leading to selective [2,3]-
Wittig−oxy-Cope and isomerization−Claisen rearrangements. Both diaryl and arylsilyl-substituted 1,3-substituted propenyl
substrates were examined, and each exhibits unique reactivity and different reaction pathways. Detailed mechanistic and com-
putational analysis was conducted, which demonstrated that the role of the base and solvent was key to the reactivity and
selectivity observed. Crossover experiments also suggest that these reactions proceed with a certain degree of dissociation, and
the mechanistic pathway is highly complex with multiple competing routes.
numerous [3,3]−[3,3] cascades that have been reported,
there are only isolated examples of [2,3]−[3,3] cascades.16
Greeves first reported the combination of the [2,3]-Wittig
rearrangement and the anionic oxy-Cope in a tandem process
by treating an diallyl ether with KH and 18-crown-6.17 This led
to aldehyde products that could be isolated with good E/Z
control when large substituents were present and contiguous
stereogenic centers could be formed with good syn selectivity
(eq 1).18 Following this initial report, Hiersemann demon-
strated an LDA-mediated approach through the formation of an
extended enolate which produced α-ketoesters (eq 2).19 There
have also been reports of a sequential [2,3]-Wittig rearrange-
ment followed by an anionic oxy-Cope reaction which are
performed under separate reaction conditions;20 however, the
only reports of a true cascade sequence have come from the
Greeves and Heirsemann laboratories.17−19
An alternative rearrangement pathway for diallyl ethers is an
isomerization−Claisen reaction. There are two main strategies
to perform the isomerization of allyl ethers into vinyl ethers: a
transition-metal-catalyzed isomerization or a base-mediated
approach. Indeed, the transition-metal-catalyzed isomerization−
Claisen reaction is well developed with a range of catalysts
used. Isomerizations can be performed at elevated temperatures
using ruthenium, rhodium, palladium, and iridium catalysts,
which allow for a concomitant Claisen rearrangement.21 These
approaches generally lead to epimerization of the α-stereogenic
center in the presence of the Lewis acidic metal catalysts at
these elevated temperatures. Highly active cationic iridium(I)
INTRODUCTION
■
The development of new transformations that efficiently produce
molecular complexity in a step- and atom-efficient manner is an
important aspect of synthetic organic chemistry. One of the
most powerful strategies involves the use of cascade reactions
whereby multiple reactions can be performed in a domino
fashion, the result of which is many new bonds being formed
and broken in a single transformation which can lead to
impressive skeletal rearrangements and the formation of
multiple stereogenic centers.1 Historically significant examples
of cascade reactions include squalene oxide biosynthesis,2 the
Robinson tropinoine synthesis,3 and Johnson’s synthesis of
progesterone.4 In particular, pericyclic reactions are excellent
candidates for these types of transformations due to their
concerted nature and high levels of stereocontrol.5 Many of
these transformations also occur under similar reaction
conditions; therefore, the cascade sequence can proceed
without intervention, allowing for the formation of complex
molecules such as the endriandic acids in a single step.6
Sigmatropic rearrangements are a particularly attractive for
cascade processes7 with both the [2,3] and [3,3] variations
having found widespread use in synthesis.8 These rearrange-
ments generally occur with high levels of stereocontrol and
proceed through highly ordered cyclic transition states
where the most favorable geometry can often be predicted.9,10
Cascades that contain one or more sigmatropic rearrange-
ments are particularly appealing due to the significant skeletal
rearrangements possible. Notable examples include aza-
Claisen−Mannich,11 oxy-Cope−aldol,12 oxy-Cope−ene,13 and
oxy-Cope−ene−Claisen reactions.14,15 In contrast to the
Received: October 20, 2014
Published: December 16, 2014
© 2014 American Chemical Society
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our knowledge, no reports of base-mediated isomerization−
Claisen rearrangements have been disclosed to date.
We recently reported the treatment of γ-silyl allylic alcohols31
with sodium hydride and allyl bromide which results in an
isomerization−allylation reaction affording α-allylated ketones
(eq 4).32 During the course of studying this reaction, we
investigated the possibility of this reaction proceeding via diallyl
ether 1. Herein, we report our studies on the base mediated
cascade rearrangements of these diallyl ethers whereby
complete selectivity can be achieved for three different reaction
pathways using the same starting material simply by modulating
the base and conditions used (eq 5).
RESULTS AND DISCUSSION
■
We examined the reaction of γ-silylated allyl ether 1a with a
variety of bases (Table 1). n-Butyllithium resulted in a very
facile [2,3]-Wittig rearrangement to form 2a as had previously
reported by Takeda in similar systems.33 The use of sodium
bases such as sodium hydride and NaHMDS led to no reaction
or decomposition when 15-crown-5 was added. The use of
KHMDS provided a somewhat unexpected product with linear
ketone 3a being produced as a single product and in excellent
yield. When tert-butoxide bases were used other products were
formed, and with 3 equiv of potassium or sodium tert-butoxide,
an isomerization took place to form allyl vinyl ether 4a.
Interestingly, when the equivalents of base were reduced, a
second product began to appear with α-methyl ketone 5a being
produced as the major product. Ketone 5a could be isolated as
the only product by elevating the temperature of the reaction to
80 °C. If the reaction was performed at higher temperatures
selectivity is lost and a mixture of products is produced again,
where linear ketone 3a is the minor product.
complexes can be used to perform this isomerization at ambient
temperature.22 This can be coupled with a thermal Claisen,
following sequestration of the Lewis acidic catalyst with PPh3,
to provide isomerization−Claisen products with high stereo-
control.23 We have previous utilized this approach to form
highly substituted allylsilanes (eq 3).24
The proposed mechanisms that lead to 2−5 are shown in
Scheme 1. The first step is deprotonation at the benzylic
position to form an allylic anion 6 which is a common
intermediate for all pathways. This can then undergo one of
two pathways: the first is a [2,3]-Wittig rearrangement to form
a tertiary homoallylic alkoxide 7 which is perfectly orientated to
perform an anion-assisted oxy-Cope rearrangement to form
enolate 8, which following protodesilylation provides linear
ketone 3. The alternative reaction pathway is for the allylic
anion to be reprotonated as the allylsilane form 9 which
provides allyl vinyl ether 4.34 This then performs a Claisen
rearrangement to form ketone 10 followed by protodesilylation
to form the observed ketone 5. The protodesilylation process
appears to be mediated by the base and not from the workup
procedure. We have previously been able to isolate silane
product 10 following a similar workup procedure and appears
to be stable.32 Indeed, the stoichiometry of the base can dictate
the amount of protodesilylation observed (vide infra).
Next, we proceeded to study the scope of the base-mediated
rearrangements beginning with the [2,3]-Wittig-anionic oxy-
Cope pathway examined initially (Table 2). Using the op-
timized conditions (3 equiv of KHMDS, THF, 60 °C), it was
found to be very general for aromatic substrates with little
difference between electron-rich and -poor substitution patterns
1a−f, all of which are produced in good to excellent yields.
When alkyl-substituted groups 1g,h were used, no reaction was
observed with quantitive recovery of starting material. This can
be explained by the lower pKa of the allylic proton when the
anion-stabilizing aromatic groups are present.
Base-mediated isomerizations of allyl ethers proceed via an
allylic anion which is reprotonated as the thermodynamically
more stable enol ether product.25,26 Base-mediated methods
do generally provide the Z-enol ether product, making the two
pathways both distinct and complementary. The most com-
monly applied conditions to mediate this transformation are
t-BuOK in DMSO; however, the elevated temperatures required
can lead to side reactions and functional group incompatibility.27
Alternative bases include butyllithium,28 although unwanted
side reactions can occur,29 and an excess of LDA which allows
isomerization to occur at ambient temperature.30 To the best of
Next the scope of the isomerization−Claisen−protodesilyla-
tion pathway was examined (Table 3). Using the optimized
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Table 1. Optimization Studies
a,b
product ratios
a
entry
base
n-BuLi
equiv
temp (°C)
conv (%)
2a
3a
4a
5a
1
3
23
60
60
60
60
60
60
60
60
60
80
100
nr
100 (90)
2
NaH
3
3
NaH/15-C-5
NaHMDS
KHMDS
KHMDS
t-BuONa
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
3
dec
nr
4
3
5
3
100
65
100 (85)
6
1
100
7
3
37
100
8
3
100
52
100 (67)
57
9
1
43
61
10
11
12
0.5
0.5
0.5
80
39
100
100
100 (75)
c
100
26
74
a
b
c
1
Conversion and product distribution determined by H NMR. Values in parentheses indicate isolated yields of a single isomer. Performed in a
sealed tube.
Scheme 1. Possible Mechanistic Pathways
Table 2. [2,3]-Wittig−Oxy-Cope Substrate Scope
Table 3. Isomerization−Claisen Substrate Scope
conditions of 0.5 equiv of t-BuOK in THF at 80 °C, it was
discovered that electron-rich substrates promote this reaction
with high yields of the α-methyl ketones 5 being obtained.
When electron-deficient aromatic substrates are used, the reac-
tion is much less efficient with fluoro-substituted compounds
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Table 4. Diaryl Substrates Optimization Studies
a,b
product ratios
a
entry
base
n-BuLi
equiv
solvent
temp (°C)
conv (%)
12a
13a
14a
1
3
THF
23
80
100
100
75
100
2
KHMDS
3
THF
90
57
10
43
50
62
99
40
11
3
KHMDS
3
THF
60
4
KHMDS
1
THF
80
100
75
50
5
NaH
2
THF
80
38
6
t-BuONa
2
THF
80
64
1
7
t-BuOK
0.5
1
THF
80
25
60
8
t-BuOK
THF
80
52
89
9
t-BuOK
1.5
2
THF
80
80
100 (64)
100 (68)
100 (65)
100 (78)
100 (39)
100 (61)
100 (53)
100 (44)
100 (40)
10
11
12
13
14
15
16
17
18
19
20
t-BuOK
THF
80
85
t-BuOK
3
THF
80
84
t-BuOK/18-C-6
t-BuOK/18-C-6
t-BuOK/18-C-6
t-BuOK/18-C-6
t-BuOK/18-C-6
t-BuOK/18-C-6
t-BuOK
2
THF
80
80
100
47
2
DMF
DMSO
CPME
PhCl
2
80
72
2
80
58
2
80
60
2
dioxane
THF
80
52
0.5
1
60
46
100
7
t-BuOK
THF
60
100
76
93
1
t-BuOK
0.5
0.5
1
toluene
toluene
toluene
110
110
110
130
99
86
56
89
c
21
t-BuOK
96
14
44
11
22
t-BuOK
100
d
e
23
t-BuOK
0.5
toluene
100 (72)
a
b
c
1
Conversion and product distribution determined by H NMR. Values in parentheses indicate isolated yields of a single isomer. Reaction was
d
e
performed over 72 h. Reaction performed in a sealed tube. Combined isolated yield of a partially separable mixture of isomers.
5e,f providing low yields of the ketone product. In these cases, a
large amount of the [2,3]-Wittig−oxy-Cope−protodesilylation
product 3 was obtained as a byproduct. Once again, alkyl-
substituted compounds 1g,h provided no reaction with
quantitive recovery of starting materials. There is a clear
trend that electron-rich groups provide excellent yields, whereas
the electron-poor groups provide more moderate yields and
product selectivities. More electron density and less stabiliza-
tion on the intermediate allylic anion 9 would result in this
becoming more basic and hence faster to reprotonate via the
isomerization pathway. Contrary to this, stabilization of the
anion provides a long enough lived intermediate for the [2,3]-
Wittig rearrangement to occur and begin the alternative cascade
reaction.
As the silyl group is an anion-stabilizing group, in this case
through a vinyligous α-effect, we examined other anion-stabilizing
groups in the form of aromatic substituents. Again we began
screening basic conditions to examine the regiochemical out-
comes of the rearrangements. The use of n-butyllithium once
again provided the [2,3]-Wittig product 12 as a single isomer as
had been reported previously by Takeda.33 Using the optimized
[2,3]-Wittig−oxy-Cope conditions for the vinyl silanes 1 (3 equiv
of KHMDS, THF, 80 °C), we found that this did not translate
to this class of substrates in the same manner providing a mixture
of compounds with the [2,3]-Wittig−oxy-Cope 13a and isomer-
ization−Claisen 14a products formed in a 9:1 ratio. Lowering
the temperature of the reaction provided an almost 1:1 mixture
of compounds as did lowering the equivalents of base. Sodium
bases gave a preference for the isomerization−Claisen pathway
albeit in moderate conversions. Potassium tert-butoxide gave
poor conversions and selectivities with substoichiometric and
equimolar amounts of base; however, when an excess of base
was used, the [2,3]-Wittig−oxy-Cope product 13a is formed in
good conversions. Dissociating the anion through the use of
18-crown-6 provided complete conversion and 78% isolated
yield of 13a as a single regioisomer. A range of solvents were
examined; however, THF was optimal for this reaction.
We also wanted access to the regioisomeric isomerization−
Claisen product 14a. When 0.5 equiv of t-BuOK was used
(Table 4, entry 7), a 60:40 mixture of 13a:14a was obtained. By
simply lowering the temperature to 60 °C, complete selectivity
for 14a can be obtained; however, the reaction is very slow
(46% conversion after 3 days). Increasing the number of equiv-
alents of base reverses the selectivity; however, the use of
toluene as solvent at elevated temperature provides much higher
conversions with 14a being the major product (entry 20). Under
these conditions, the product selectivity is eroded over time,
possibly through the isomerization of 14a to 13a during the
reaction. Finally, the optimal combination of conversion and
selectivity was obtained by performing the reaction in a sealed
tube at 130 °C providing 100% conversion (72% isolated yield)
and 89:11 selectivity 14a:13a (entry 23).
With both sets of optimized conditions in hand, we began
examining the scope of the reaction. In the case of the [2,3]-
Wittig−oxy-Cope reaction, the scope was very general, with the
substituents on the aryl ring showing essentially no effect on
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Table 5. Diaryl [2,3]-Wittig−Oxy-Cope Substrate Scope
a
Isolated yields of a single regioisomer.
Table 6. Diaryl Isomerization−Claisen Substrate Scope
a
b
c
Isolated total yields of the isomeric mixture. Reaction performed in THF at 130 °C. Reaction performed in THF at 80 °C.
the reactivity. Good isolated yields were obtained with both
electron-rich and -poor groups, and all products 13a−n were
produced as a single regioisomer (Table 5). Pyridines 13g and
13h were tolerated with complete conversion being observed;
however, the yields are reduced in these cases due problems
encountered in their isolation.
We next turned our attention to the isomerization−Claisen
reaction using the conditions outlined above (Table 4, entry 23).
In general, this reaction was tolerant of most functionality
used providing good yields and >90:10 product ratios for the
isomerization−Claisen product 14 over the [2,3]-Wittig−
anionic-oxy-Cope rearrangement 13 (Table 6). Under these
standard conditions, substrates containing aromatic methyl
groups failed to react (11b, 11i, and 11m), providing quantative
recovery of starting diallyl ether. Reactivity could be achieved
through the modulation of the solvent from toluene to THF;
however, this affected the selectivity of the reaction. Substrate
11b was reluctant to rearrange solely via solvent modification
and also required elevated temperatures to achieve complete
conversion. As a consequence, no selectivity was observed with a
mixture of products being obtained in a 44:56 ratio of 14b:13b.
Methyl-substituted aromatics at the 1-position were better
tolerated with reactions proceeding at 80 °C in THF. When
p-methyl substituent 11i was used, good selectivity was observed;
however, this was eroded in m-xylyl substituent 11m possibly
due to increased steric effect of the group. Interestingly, when an
o-methyl group is present 11p, the reaction proceeds in toluene
under standard reaction conditions. This provided 14p with an
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excellent 95:5 regioselectivity; however, sterically encumbered
ortho-substitution led to less efficient reactions with lower
conversions and yields being obtained.
Mechanistic Studies. Because of the unusual and very
subtle reactivity observed, we began to examine the mechanism
of these reactions. We first examined the use of substituted allyl
ethers and prepared the crotyl analogue 15 as an 75:25 mixture
E/Z isomers (Scheme 2).35 When this was subjected to the
formed, and this was the styryl product 21 with no isomerization−
Claisen product 22 being observed. This product demonstrates
that the Claisen rearrangement is dissociative and the resulting
ion pair or diradical intermediates recombine to provide a single
regioisomer as the [1,3]-rearrangement product.
To further strengthen our mechanistic understanding of
these reactions a series of deuterium labeling experiments were
conducted. First, the vinylsilane was investigated, and deu-
terated analogue 23 was prepared and subjected to the reaction
conditions. Under the [2,3]-Wittig−oxy-Cope conditions, the
reaction proceeded with a 17% deuteration at the C-3 position
of 3a (eq 6). Alternatively, the isomerization−Claisen condi-
tions provided 70% deuteration at the C-1′ position of 5a (eq 7).
Scheme 2. Isomerization of Allyl Vinyl Ethers
[2,3]-Wittig−oxy-Cope conditions, a very smooth reaction
proceeded to provide the corresponding 3-substituted ketone
16 in good yields and enhanced E/Z selectivity. The methyl
group at the terminal position suggests the proposed
mechanistic pathway of a [2,3]-Wittig−oxy-Cope pathway is
in effect. The methyl group at the terminal position suggests
the proposed mechanistic pathway of a [2,3]-Wittig−oxy-Cope
pathway is in effect. The enhancement of the E/Z ratio is due
to a kinetic preference for the E-isomer in the [2.3]-Wittg
rearrangement (A versus B). The isomerization−Claisen
reaction also resulted in our expected product with the
branched methyl product 17 being obtained in good yield
and a 1:1 mixture of diastereoisomers. This is most likely due to
epimerization of the α-stereogenic center under the forcing
reaction conditions but could also be due to a dissociative ion-
pair or biradical Claisen pathway.
The small amount of deuteration at the C-3 position can be
explained by one of two mechanisms, both of which would be a
minor reaction pathway (Scheme 4). First, following the initial
deprotonation of at the benzylic position, the allylic anion is
then reprotonated by the conjugate acid α to the silyl group.
This can then undergo a second deprotonation to form an alter-
native allylic anion which then performs the rearrangement.
Alternatively, following the [2,3]-Wittig−oxy-Cope reaction, the
enolate product can perform a [1,4]-Brook rearrangement to
form a silyl enol ether and allylic anion which can be
reprotonated by the conjugate acid. Both of these pathways
are possible; however, no recovered starting material was
isolated with the deuterium isomerized from the original
position and no silyl enol ethers were ever detected despite our
efforts to isolate these sensitive intermediates. However, the
silicon−oxygen bond could be cleaved during the reaction
pathway prior to workup in a similar pathway to the proto-
desilylation observed.
We also discovered that the isomerization of the allyl vinyl
ethers36 to divinyl ethers can occur when an internal base is
utilized (Scheme 5). When an allyl vinyl ether containing an
alcohol 24 is treated with NaH and benzyl bromide under
standard benzylation conditions, both the isomerization of the
allyl ether and the benzylation occur. The amount of base used
also determines the degree of protodesilylation. When 1 equiv
of base is used, the major product is the allyl silane 25, whereas
when 1.5 equiv is used the protodesilyation predominates to
afford 26, which suggests the base is mediating the proto-
desilylation. In all cases there was complete benzylation of the
primary alcohol with no observed O-silylation.
We also examined the cinnamyl rearrangement to probe
whether these reactions were concerted in all cases (Scheme 3).
Scheme 3. Isomerization of Allyl Vinyl Ethers
To investigate this further, we removed the benzyl bromide
from the mixture and found a similar scenario with isomer-
ization occurring to form 27 and 28. The level of proto-
desilylation was once again determined by the stoichiometry of
base and no O-silylation was observed. A similar internal iso-
merization process has been reported by Maulide for the
conversion of alkynyl pyrrolidines to their corresponding
allenamine followed by subsequent cyclization reaction.37 In
When cinnamyl ether 18 was subjected to the 3-allylation
conditions, a 1.75:1 mixture of products was observed which
included the expected styryl product 19 and the terminal olefin
20, which was formed as a single diastereoisomer. This suggests
that in this case at least a significant degree of dissociation is
present due to the two regioisomeric products being formed. In
the case of the 2-allylated conditions, only one product was
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Scheme 4. Possible Deuterium Incorporation Mechanisms
Scheme 5. Isomerization of Allyl Vinyl Ethers
all cases, no O-silylation was ever detected, thus suggesting that
the protodesilylation is being performed by the excess base.
To probe any potential stereospecificity of the reaction we
prepared diallyl ether (S)-11a in 99% ee and subjected this
to both sets of reaction conditions (Scheme 6). When the
and led us to speculate where the additional proton content
originated from as there were no other obvious proton sources
in the reaction. These results, coupled with the issues that were
encountered when the methyl-substituted aromatic substrates
11b, 11i, and 11m were used, led us to believe that the addi-
tional protons were coming from the toluene solvent and that
deprotonation at the benzylic position was inhibiting the
reaction. To probe this, we performed the reaction with the
protio variant 11a in toluene-d8 and found that the product was
formed with no deuterium present (eq 10). A solvent KIE
study showed that there was a significant inverse solvent effect
which resulted in the rate of reaction in the deuterated solvent
being nearly 2.5 times that of the protio solvent.41 This suggests
that the solvent is involved in the reaction and that a competing
deprotonation reaction with the toluene solvent slows the
reaction rate. The deprotonation of toluene-d8 occurs at a much
slower rate; therefore, this side reaction is negligible, which
allows the base to shuttle the proton efficiently with no
incorporation of deuterium in the product. We also performed
the control experiment where the reaction was performed with
the deuterated substrate 29 and in toluene-d8 (eq 11). In this
case, almost complete deuteration is observed, and once again,
an inverse solvent kinetic isotope effect is observed albeit much
less pronounced.42
Scheme 6. Stereospecificity of Rearrangements
2-allylation pathway was tested, which we assumed to proceed
via an isomerization Claisen pathway, a racemic product was
obtained, thus suggesting the intermediacy of a planar achiral
intermediate. When the 3-allylation pathway was used, once
again completely racemic product was obtained, indicating an
achiral intermediate is also present in this pathway.
In the case of the deuterated diaryl substrate 29, the [2,3]-
Wittig−oxy-Cope rearrangement occurs with no visible sign
of deuterium in the resulting C-3 allylated ketone. A kinetic
isotope effect was also measured, and it was found to be 2.19,
which is a small primary effect suggesting proton transfer is rate
limiting (eq 8).38,39 When the isomerization−Claisen rear-
rangement occurs, the corresponding C-2 allylated ketone was
isolated with just 30% deuterium incorporation and a smaller
primary KIE (eq 9).40 The deuterium content of the product
14a is significantly different from when vinylsilane 1a is used
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Computational Methods. The B3LYP density func-
tional43,44 and split-valence polarized 6-31G** basis set45,46
were used for all geometry optimizations. All activation free
energies are quoted relative to infinitely separated reagents.
Quantum mechanical calculations were performed using
Gaussian03 (revision E.01).47 Single-point energies were
taken using the M06-2X density functional48 and the
6-31G** basis set using the Jaguar program (version 7.6).49
This energy was used to correct the gas-phase energy obtained
from the B3LYP calculations.50,51
A deuterium-trapping experiment was also performed
whereby the reactions were quenched with D2O (Scheme 7).
Free energies in solution were derived from gas-phase-
optimized structures (B3LYP/6-31G**) by means of a single-
point calculation using M06-2X/6-31G** with the polarizable
continuum model (PCM),52 as implemented in the Jaguar
program (version 7.6) using toluene (probe radius = 2.76 Å) or
THF (probe radius = 2.52 Å) as the solvent. These values were
used to correct the Gibbs free energy derived from the B3LYP
calculations.53,54
Scheme 7. Deuterium-Quenching Experiments
Anion-Assisted Oxy-Cope Rearrangement. Calculations
using PCM show that the products of radical dissociation in
the 3-allylation pathway which yield an intermediate alkoxide
and an allylic radical are disfavored relative to the undissociated
anion 31 (ca. 5 kcal·mol−1). If these radical intermediates
escape the solvent cage, they could recombine with the alter-
nate partner to form the observed crossover product. Inves-
tigation of the anion-assisted oxy-Cope rearrangement
identified two unique TSs corresponding to chair conforma-
tions for both possible diastereomers resulting from the [2.3]-
Wittig rearrangement (TS-1 and TS-2, Figure 1 and Table 7).
These TSs were strongly asymmetrical with the much longer
forming bond interatomic distances than those of breaking
bonds previously observed for rearrangements of this kind
(Table 8).55
However, TSs corresponding to the C−C bond cleavage
reaction were found to have lower activation energies than both
concerted TSs (TS-3 and TS-4). Houk et al. consider this
bond-cleavage reaction to be the rate-limiting step and that the
subsequent C−C bond-forming step is fast.56 Heterolytic
cleavage prior to C−C bond formation has been observed for
anionic amino-Cope reactions.55 While generally oxy-Cope re-
arrangements proceed via concerted mechanisms,56 the pathway
In the [2,3]-Wittig−oxy-Cope reaction 40% deuterium was
observed α to the ketone, thus confirming the presence of an
enolate product at the end of the reaction. In the isomer-
ization−Claisen reaction no deuterium was observed, thus
suggesting that following the rearrangement, the resulting
ketone 14a does not exist as an enolate.
We conducted crossover experiments with the allyl groups
whereby a mixture of allyl 11h and crotyl 15 ethers were subjected to
the reaction conditions (Scheme 8). When the mixture was subjected
to the [2,3]-Wittig−oxy-Cope reaction conditions, the products were
observed with 14% crossover. The majority of the products were the
expected products 16 and 12h; however, a relatively large proportion
of the products did show crossover, suggesting a dissociative pathway
in the reaction. When the isomerization−Claisen reaction conditions
were utilized, once again crossover was observed albeit in a lower
proportion. Again, this requires dissociation of the allyl vinyl ether for
this crossover to occur.
DFT Calculations. To further probe the pathways involved
in these rearrangements the reactions were investigated using
computational methods.
a
Scheme 8. Crossover Studies
a
1
Product distributions determined by H NMR and LCMS analysis of the crude reaction mixtures.
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Figure 1. Competing TSs for the 3-allylation pathway. Geometries B3LYP/6-31G**, single-point energies M06-2X/6-31G**. TS-1/2 are for the
concerted anion-assisted oxy-Cope rearrangement, TS-3/4 correspond to the dissociative C−C cleavage reaction.
experimental conditions. The calculated Boltzmann ratios
indicate that both bond-cleavage TSs are significantly populated
under the experimental reaction conditions.
Table 7. Reaction Barriers and Boltzmann Ratios for the
Competing TSs of the 3-Allylation Pathway
a
Boltzmann ratio
(gas phase 298 K)
Boltzmann ratio
(THF 353 K)
Claisen Rearrangement. Solvent-phase calculations sug-
gest that the dissociative pathway responsible for the observed
crossover in the Claisen rearrangement proceeds via radical
intermediates. The calculated free energy difference between
infinitely separated reactants corresponding to the radical and
ionic pathways suggests radical intermediates are favored (ca.
60 kcal mol−1). Comparing free energies of infinitely separated
reactants neglects the ionic stabilization between anion and
cation but does more accurately reflect the situation required
for crossover to occur with the ions having broken free of this
stabilization. The radical intermediates were calculated to be
disfavored relative to the undissociated diallyl ether suggesting
the preferred pathway proceeds via a concerted mechanism as is
generally observed for Claisen rearrangements of this kind.58
Investigation of the concerted pathway for diallyl ether
Claisen rearrangement identified four unique transition struc-
tures TSs) corresponding to chair and boat conformations
(Figure 2). Both geometries of the newly formed double bond
TS ΔΔG⧧ ΔΔGsol
⧧
TS-1
TS-2
TS-3
TS-4
4.1
3.6
0.4
0
3.8
4.1
0.7
0
9.6 × 10−4
4.6 × 10−3
2.4 × 10−3
2.7 × 10−3
0.5
1
0.4
1
a
Geometries B3LYP/6-31G**, single-point energies M06-2X/
6-31G**. All energies in kcal mol−1.
Table 8. 3-Allylation Interatomic Distances of Competing
TSs
interatomic distance (Å)
TS
C−C (breaking)
C−C (forming)
TS-1
TS-2
TS-3
TS-4
2.16
2.19
2.14
2.09
3.96
4.22
⧧
were considered. The values of ΔGsol suggest the most favorable
TS to be reaction of the E alkene in a chair conformation (Table 9,
TS-5). The corresponding Z alkene chair TS is destabilized by
2.7 kcal mol−1 (TS-6). Similarly higher energies were observed
for both boat TSs (TS-7 and TS-8). Solvent effects were shown
to have minimal impact on the relative free energies of the
competing TSs due to their concerted and apolar nature.54 The
calculated Boltzmann ratios indicate that the only significantly
populated TS under the experimental reaction conditions is TS-5.
Proposed Mechanism. Through the combination of
experimental observations and computational analysis we can
propose detailed mechanisms for both processes (Scheme 9).
First, the 3-allylated product was proposed to proceed via a
[2,3]-Wittig anionic oxy-Cope pathway to provide 13. This
proceeds through deprotonation at the benylic position to form
taken is substrate dependent and nonconcerted reactions
have also been reported.57 Experimental observation of the
rearranged product suggests the cleavage reaction must be
followed by a rapid recombination step of the two closely
associated intermediates.55 A small amount of these inter-
mediates that may escape the solvent cage and dissipate into
the solution could help account for the observed crossover.
Solvent effects were shown to have more of an impact on the
relative free energies of these competing TSs compared to
those of the Claisen rearrangement due to the net charge
associated with the TSs (Table 7). The crown ether present
in solution allows examination of the anion alone, without
associated cation, and therefore, the stabilization seen from the
solvent for the unassociated anion is representative of the
Figure 2. Competing TSs (TS-5−8) for diallyl ether Claisen rearrangement. Geometries B3LYP/6-31G**, single-point energies M06-2X/631G**.
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The 2-allylated product 14 can occur through an isomer-
ization−Claisen pathway as described previously; however, this
does not take into account all the mechanistic data. The strong
inverse solvent kinetic isotope effect observed indicates there is
a competitive deprotonation of the toluene solvent alongside
the diallyl ether. There are two possible scenarios which could
be occurring; the toluene anion is conducting the deprotona-
tion or the competitive reaction slows the rate of deprotona-
tion. Once the allylic anion 37 is formed, this will exist as a
closely associated ion pair due to the nonpolar solvent dis-
favoring solvent separation. A 1,3-metallotropic shift provides
allylic anion 37 which can be reprotonated by the conjugate
acid or toluene to provide our requisite allyl vinyl ether 38.
As the reaction is performed at elevated temperatures, 38
undergoes a spontaneous Claisen rearrangement to form our
2-allylated product 14.
The Claisen appears to proceed with some degree of dis-
sociation as judged by the crossover experiments. Although
Claisen rearrangements do generally proceed via a concerted
closed transition state,61 some can proceed through more
dissociative pathways. These can include dipolar ionizations to
form either a close contact or solvent-separated ion pair62 or
alternatively proceed through a homolytic pathway whereby a
diradical intermediate is formed.63 The DFT calculations sug-
gest that the concerted pathway is the lowest energy pathway;
however, a homolytic cleavage to provide diradical pair 39 is
the most likely cause of the crossover products. These radical
pairs can escape the solvent cage and recombine with the
alternate partner to provide the crossover product.
Table 9. Reaction Barriers and Boltzmann Ratios for the
Competing TSs of the 2-Allylation Pathway
a
Boltzmann ratio
(gas phase 298 K)
Boltzmann ratio
(toluene 403 K)
TS ΔΔG⧧ ΔΔGsol
⧧
TS-5
TS-6
TS-7
TS-8
0
0
1
1
3.1
4.9
8.4
2.7
4.6
7.6
5.3 × 10−4
2.5 × 10−4
8.1 × 10−8
6.2 × 10−3
3.1 × 10−3
1.3 × 10−5
a
Geometries B3LYP/6-31G**, single-point energies M06-2X/6-
31G**. All energies in kcal mol−1.
a highly dissociated “naked” anion 31 due to the presence of
the 18-crown-6. This dissociated anion then performs a [2,3]-
Wittig rearrangement to form 1,5-diene 32, which can further
undergo an anionic oxy-Cope to form enolate 35. However, the
presence of crossover product suggests that the classical
concerted mechanisms for these two pathways were not in
effect. An alternative dissociative pathway could be through
diradical pair as similar to the [1,2]-Wittig rearrangement. At
elevated temperatures, the [1,2]-Wittig rearrangement is
promoted where the intermediate anion can undergo a radical
dissociation to form an alkoxide and an allylic radical.59 These
can usually recombine to form the direct [2,3]-rearrangement
product 12; however, should these intermediates escape the
solvent cage, they could recombine with the alternate partner to
form the observed crossover product. Although much rarer than
the [1,2] variant, there have been several examples of the [1,4]-
Wittig rearrangement; however, its mechanism has not been fully
elucidated.60 Calculations suggest a second dissociative pathway
that involves the classical [2,3]-Wittig rearrangement followed by
a heterolytic dissociative Cope rearrangement. This pathway
which forms an enone 33 and an allylic anion 34 was found to
have the lowest transition state energy by 3.8 kcal·mol−1. These
intermediates can recombine in a 1,4-sense to form enolate 36,
which provides 3-allylated product 13 following workup. This
explains the presence of crossover product; however, this is a
minor pathway suggesting the recombination is fast which does
not allow the allylic anion to escape the solvent cage readily. The
small amount that does escape the solvent cage and dissipates
into the solution accounts for the crossover observed.
CONCLUSIONS
■
In conclusion, we have developed and investigated the
mechanism of new base-mediated rearrangements of diallyl
ethers. The reaction can proceed through a combination of
mechanisms which account for all the observations. Two classes
of compounds were examined aryl vinylsilanes and diaryl
substrates. Each of these classes react in their own unique
manner to provide similar products however the silanes always
proceed with protodesilylation. The rearrangement to the
3-allylated species appears to proceed via a [2,3]-Wittig anionic
Scheme 9. Proposed Mechanisms
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the KHMDS. After being quenched with a few drops of NH4Cl, the
reaction mixture was diluted with diethyl ether (25 mL), dried over
MgSO4, and concentrated in vacuo. The crude product was applied
directly onto a silica gel column and chromatographed to afford the
requisite ketone.
General Procedure E: Isomerization−Claisen Cascade (5a−f).
Potassium tert-butoxide (0.5 equiv) was added to a THF solution
(0.13 M) of the γ-silyl allylic alcohol in a clean, dry, argon-purged
5 mL round-bottomed flask at room temperature. A condenser was
attached and the reaction mixture heated to 60 °C and allowed to stir over-
night. After the mixture was quenched with distilled water (10 mL)
and extracted with EtOAc (2 × 25 mL), the combined organic phases
were washed with distilled water (25 mL) and brine (25 mL), dried
over MgSO4, and concentrated in vacuo. The crude product was
applied directly onto a silica gel column and chromatographed to
afford the requisite ketone.
General Procedure F: [2,3]-Wittig−Oxy-Cope Cascade(13a−n).
18-Crown-6 (2 equiv) followed by potassium tert-butoxide (2 equiv)
was added to a THF solution (0.13 M) of the diallyl ether (1 equiv) in
a dry, argon-purged 10 mL round-bottomed flask at room temper-
ature, after which the reaction mixture turned dark red. The flask was
fitted with a condenser, heated to 80 °C, and allowed to stir overnight.
After the mixtuer was quenched with distilled water (10 mL) and
extracted with EtOAc (2 × 25 mL), the combined organic phases were
washed with distilled water (25 mL) and brine (25 mL), dried over
MgSO4, and concentrated in vacuo. The crude product was applied
directly onto a silica gel column and chromatographed to afford the
requisite ketone.
oxy-Cope rearrangement; the oxy-cope rearrangement appears
to proceed via a heterolytic dissociative pathway due to the
presence of intermolecular rearrangements in crossover experi-
ments. The 2-allylated products proceed through an isomer-
ization−Claisen pathway however the reaction is slowed
through a competitive deprotonation of the solvent. It also
appears that a small proportion of the Claisen rearrangement
occurs through dissociative mechanism via a diradical pathway.
EXPERIMENTAL SECTION
■
All reactions were carried out under an atmosphere of argon in oven-
dried glassware otherwise mentioned elsewhere. All reaction were
monitored by thin-layer chromatography (TLC) using Merck TLC
silica gel 60 sheets, which were visualized with ultraviolet light and
then developed with iodine and basic potassium permanganate or
anisaldehyde solution. Flash chromatography was performed on
Sigma-Aldrich silica gel 60 as the stationary phase, and the solvents
employed were of analytical grade. Unless stated otherwise, all
commercially available reagents were used as received. When
necessary, commonly used organic solvents were dried prior to use
according to standard laboratory practices.64 NMR spectra were
recorded at 400 MHz (1H) and 100 MHz (13C) and were referenced
to CDCl3 δ 7.26 and 77.2 ppm, respectively. Infrared spectra
were recorded as a thin film on KBr discs. High-resolution mass
spectra were obtained on mass spectrometers using electrospray
ionization (ESI) or electron-impact ionization at 70 eV and TOF
analyzers.
General Procedure G: Isomerization−Claisen Cascade (14a−q).
Potassium tert-butoxide (0.5 equiv) was added to a toluene solution
(0.13 M) of the diallyl ether in a dry, argon-purged sealed tube at
room temperature. The reaction mixture was heated to 130 °C in a
sealed tube and allowed to stir for 16 h. After the mixture was
quenched with distilled water (10 mL) and extracted with EtOAc
(2 × 25 mL), the combined organic phases were washed with distilled
water (25 mL) and brine (25 mL), dried over MgSO4, and con-
centrated in vacuo. The crude product was applied directly onto a
silica gel column and chromatographed to afford the requisite ketone.
(E)-1-Phenyl-3-(4-fluorophenyl)prop-2-en-1-ol (S1).
General Procedure A: Formation of Propargylic alcohols. A
hexane solution of n-BuLi (2.5 M) (1.1 equiv) was added to a THF
(0.5 M) solution of phenylacetylene (1.1 equiv) at −78 °C. The
mixture was stirred for 1 h at that temperature before the aryl aldehyde
was added (1 equiv). The reaction mixture was warmed to room
temperature, stirred for 1 h, and quenched with a saturated aqueous
NH4Cl solution. The aqueous solution was extracted with EtOAc
(2 × 15 mL), and the combined organic layers were washed with brine
(20 mL). The organic layer was dried with Na2SO4 and concentrated
in vacuo. The crude product was applied directly onto a silica gel column
and chromatographed to afford the requisite propargylic alcohol.
General Procedure B: Formation of Allylic Alcohols.65 An
oven-dried round bottomed flask was purged with argon and cooled to
0 °C, and Red-Al (65% in PhMe) (2 equiv) was dissolved in diethyl
ether (0.5 M) followed by the dropwise addition of a solution of the
propargylic alcohol (1 equiv) in Et2O (0.5 M). The mixture was stirred
for 4 h, maintaining the temperature at 0 °C after which the reaction
was quenched with several drops of 1 M HCl solution (CAUTION:
Rapid evolution of hydrogen gas). The mixture was extracted with
Et2O (2 × 25 mL), washed with brine (25 mL), dried over anhydrous
MgSO4, and concentrated in vacuo. The crude product was applied
directly onto a silica gel column and chromatographed to afford the
requisite 1,3-diaryl propenol.
General Procedure C: Formation of Diallyl Ethers (1a−h and
11i−q).66 A solution of the diaryl allylic alcohol or vinylsilane
(1 equiv) in DMF (0.08 M) was prepared in an oven-dried, 50 mL
round-bottomed flask, purged with argon, and cooled to 0 °C. Allyl
bromide (2 equiv) followed by sodium hydride (60% suspension in
mineral oil; unwashed) (2 equiv) were added, after which the reaction
mixture turned pale yellow. The mixture was stirred at 0 °C under
argon for 1 h followed by quenching with saturated NH4Cl solution
(30 mL). The aqueous solution was extracted with diethyl ether (3 ×
60 mL) and the ether layer washed with distilled water (3 × 25 mL)
and brine (25 mL), dried over MgSO4, and concentrated in vacuo. The
crude product was applied directly onto a silica gel column and
chromatographed to afford the requisite allyl ether.
The title compound was prepared according to general procedure B
from 3-(4-fluorophenyl)-1-phenylprop-2-yn-1-ol67 (307 mg, 1.36
mmol) using Red-Al (65% in PhMe) (0.83 mL, 2.72 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (10% EtOAc in hexane) to afford S1 (250 mg, 81%)
as a colorless oil: Rf (9:1 hexane/EtOAc) = 0.13; IR νmax (thin film)/
1
cm−1 3415, 1656, 1640, 1505, 1266, 1227, 1158, 834, 741, 701; H
NMR (400 MHz, CDCl3) δ 7.45−7.28 (7H, m), 7.02−6.94 (2H, m),
6.63 (1H, d, J = 15.8 Hz), 6.28 (1H, dd, J = 15.6, 6.3 Hz), 5.34 (1H,
dd, J = 6.4, 2.4 Hz), 2.02 (1H, d, J = 2.4 Hz); 13C NMR (100 MHz,
CDCl3) δ 162.4 (d, JC−F = 245.4 Hz), 142.7, 132.7 (d, JC−F = 3.3 Hz),
131.3 (d, JC−F = 2.2 Hz), 129.4, 128.7, 128.1 (d, JC−F = 8.0 Hz), 127.9,
126.3, 115.5 (d, JC−F = 21.5 Hz), 75.1; HRMS (ES+) calcd for
+
C15H12OF [M + H] 227.0872, found 227.0864.
(E)-1-Phenyl-3-(4-trifluoromethoxyphenyl)prop-2-en-1-ol (S2).
The title compound was prepared according to general procedure B
from 1-phenyl-3-(4-trifluoromethoxyphenyl)prop-2-yn-1-ol32 (116 mg,
0.41 mmol) using Red-Al (65% in PhMe) (0.26 mL, 0.82 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (10% EtOAc in hexane) to afford S2 (95 mg, 79%) as
a colorless oil: Rf (9:1 hexane/EtOAc) = 0.23; IR νmax (thin film)/cm−1
3339, 1508, 1263, 1219, 1164, 966, 670; 1H NMR (400 MHz, CDCl3) δ
General Procedure D: [2,3]-Wittig−Oxy-Cope Cascade (3a−f).
KHMDS solution (0.5 M in toluene, 3 equiv) was added to a THF
solution (0.05 M) of the diallylic alcohol (1 equiv) in a dry, argon-
purged 10 mL round-bottomed flask at room temperature. The flask
was fitted with a condenser, heated to 60 °C, and allowed to stir over-
night. The reaction mixture slowly turned deep brown after addition of
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7.46−7.29 (7H, m), 7.22−7.11 (2H, m), 6.69 (1H, dd, J = 15.8, 1.3
Hz), 6.38 (1H, dd, J = 16.0, 6.2 Hz), 5.40 (1H, dd, J = 6.4, 2.3 Hz),
2.05 (1H, d, J = 3.3 Hz); 13C NMR (100 MHz, CDCl3) δ 145.6 (q,
JC−F = 245.8 Hz), 142.5, 135.3, 132.5, 128.9, 128.7, 128.0, 127.8, 126.3,
121.1, 74.9; HRMS (ES+) calcd for C16H13F 3O2Na [M +Na]+
317.0765, found 317.0761.
(10% EtOAc in hexane) to afford S6 (295 mg, 89%) as a colorless oil: Rf
(10% EtOAc in hexane) = 0.13; 1H NMR (400 MHz, CDCl3) δ 7.41−
7.38 (2H, m), 7.36−7.29 (3H, m), 7.28−7.24 (1H, m), 7.22−7.15
(2H, m), 7.02−6.59 (1H, m), 6.70 (1H, dd, J = 16.0, 1.0 Hz), 6.34
(1H, dd, J = 15.8, 6.8 Hz), 5.39 (1H, dd, J = 6.8, 3.8 Hz), 2.03 (1H, d,
J = 3.5 Hz); 13C NMR (100 MHz, CDCl3) δ 163.1 (d, J = 250.0 Hz),
145.4 (d, J = 7.0 Hz), 136.3, 131.2, 130.9, 130.1 (d, J = 8.0 Hz), 128.7,
128.0, 126.7, 121.9 (d, J = 3.0 Hz), 114.6 (d, J = 22.0 Hz), 113.2 (d,
J = 22.0 Hz), 74.6 (d, J = 1.0 Hz). Characterization in accordance with
literature data.66
(E)-1-Phenyl-3-(2-naphthyl)prop-2-en-1-ol (S3).
(E)-1-(o-Toyl)-3-phenylprop-2-en-1-ol (S7).
The title compound was prepared according to general procedure B
from 1-phenyl-3-(2-naphthyl)prop-2-yn-1-ol32 (381 mg, 1.48 mmol)
using Red-Al (65% in PhMe) (0.90 mL, 2.96 mmol). The crude prod-
uct was applied directly onto the top of a column and chromato-
graphed (10% EtOAc in hexane) to afford S3 (278 mg, 72%) as a
yellow oil: Rf (9:1 hexane/EtOAc) = 0.11; 1H NMR (400 MHz,
CDCl3) δ 8.18−8.14 (1H, m), 7.90−7.77 (2H, m), 7.62−7.31 (10H,
m), 6.46 (1H, dd, J = 15.3, 6.2 Hz), 5.53 (1H, d, J = 6.04 Hz), 2.15
(1H, s); 13C NMR (100 MHz, CDCl3) δ 142.8, 134.7, 134.3, 133.6,
131.2, 128.7, 128.5, 128.1, 127.9, 127.7, 126.4, 126.1, 125.8, 125.6,
124.0, 123.7, 75.3. Characterization in accordance with literature
data.32
The title compound was prepared according to general procedure B
from 3-phenyl-1-(o-tolyl)prop-2-yn-1-ol (683 mg, 3.07 mmol) using
Red-Al (65% in PhMe) (1.87 mL, 6.14 mmol). The crude product was
applied directly onto the top of a column and chromatographed (10%
EtOAc in hexane) to afford S7 (600 mg, 93%) as a colorless oil: Rf
(10% EtOAc in hexane) = 0.16; 1H NMR (400 MHz, CDCl3) δ 7.54-
7.52 (1H, m), 7.39−7.36 (2H, m), 7.32−7.15 (6H, m), 6.65 (1H, d,
J = 16.0 Hz), 6.36 (1H, dd, J = 16.0, 6.2 Hz), 5.58 (1H, d, J = 6.0 Hz),
2.39 (3H, s), 1.96 (1H, s, br); 13C NMR (100 MHz, CDCl3) δ 140.7,
136.6, 135.3, 130.8, 130.7, 130.6, 128.6, 127.8, 127.7, 126.6, 126.4,
125.9, 71.9, 19.2. Characterization in accordance with literature data.69
(E)-1-(3,5-Dimethylphenyl)-3-phenylprop-2-en-1-ol (S8).
(E)-1-Phenyl-3-(pyridin-3-yl)prop-2-en-1-ol (S4).
The title compound was prepared according to general procedure B
from 1-phenyl-3-(3-pyridyl)prop-2-yn-1-ol32 (304 mg, 1.50 mmol) using
Red-Al (65% in PhMe) (0.69 mL, 2.25 mmol). The crude crude product
was applied directly onto the top of a column and chromatographed
(10% EtOAc in hexane) to afford S4 (214 mg, 68%) as a colorless oil: Rf
(3:1 hexane/EtOAc) =0.09; IR νmax (thin film)/cm−1 3200, 2925, 1416,
1026, 968, 700; 1H NMR (400 MHz, CDCl3) δ 8.59 (1H, s), 8.46−8.44
(1H, m,) 7.71−7.68 (1H, m), 7.45- 7.21 (6H, m), 6.69 (1H, d, J = 16.0
Hz), 6.46 (1H, dd, J = 15.8, 6.0 Hz), 5.42 (1H, d, J = 6.0 Hz), 3.20 (1H,
s, br); 13C NMR (100 MHz, CDCl3) δ 148.7, 148.5, 142.5, 133.9, 133.0,
132.3, 128.8,128.1, 126.6, 126.4, 123.5, 74.9; HRMS (ES+) calcd for
C14H13NO [M + H]+ 212.1072, found 212.1060.
Magnesium turnings (100 mg, 3.96 mmol) and a single crystal of
iodine was added to an oven-dried round bottomed flask purged with
argon. A reflux condenser was fitted and Et2O (7.3 mL, 0.5 M) added.
This mixture was stirred for 10 min, after which time 1-bromo-3,5-
dimethylbenzene (0.50 mL, 3.63 mmol) was added dropwise. The
reaction mixture was heated to reflux for 20 min and then cooled to
room temperature, at which point the majority of Mg turnings had
disappeared. The freshly prepared Grignard solution was added
dropwise to a cooled (0 °C) solution of cinnamaldehyde (0.40 mL,
3.30 mmol) in THF (7.3 mL, 0.5 M). Once addition was complete, the
reaction mixture was warmed to room temperature and stirred
overnight. The reaction was quenched with saturated NH4Cl solution
(20 mL) and extracted with EtOAc (2 × 20 mL), and the combined
organic layers were washed with distilled water (20 mL) and brine
(20 mL), dried over anhydrous MgSO4, and concentrated. The crude
product was applied to a column and chromatographed (5% EtOAc in
hexane) to afford S8 (380 mg, 48%) as a yellow oil: Rf (10% EtOAc in
hexane) = 0.24; IR νmax (thin film)/cm−1; 3347, 2918, 1601.4, 1495,
(E)-3-(2-Fluoropyridin-5-yl)-1-phenylprop-2-en-1-ol (S5).
The title compound was prepared according to general procedure B
from 1-phenyl-3-(2-fluoro-pyrid-5-yl)prop-2-yn-1-ol32 (300 mg,
1.32 mmol) using Red-Al (65% in PhMe) (0.69 mL, 2.25 mmol).
The crude crude product was applied directly onto the top of a column
and chromatographed (10% EtOAc in hexane) to afford S5 (248 mg,
80%) as a colorless solid: Rf (3:1 hexane/EtOAc) = 0.31; νmax (thin
film)/cm−1; 3217, 3061, 3029, 1573, 1492, 1453, 1416, 1092, 1026,
1
965, 754; H NMR (400 MHz, CDCl3) δ 7.41−7.21 (5H, m), 7.04
(2H, s), 6.94 (1H, s), 6.69 (1H, d, J = 16.0 Hz), 6.38 (1H, dd, J = 16.0,
6.4 Hz), 5.33−5.31 (1H, m), 2.32 (6H, s), 1.96 (1H, d, J = 3.6 Hz);
13C NMR (100 MHz, CDCl3) δ 142.8, 138.3, 136.7, 131.7, 130.3,
129.5, 128.6, 127.7, 126.6, 124.11, 75.2, 21.3; HRMS (ES+) calcd for
C17H18ONa [M + Na]+ 261.1255, found 261.1264
1
969, 701; H NMR (400 MHz, CDCl3) δ 8.17−8.11 (1H, m), 7.83−
7.75 (1H, m), 7.44−7.28 (5H, m), 6.86 (1H, dd, J = 8.5, 2.8 Hz), 6.66
(1H, d, J = 15.8 Hz), 6.37 (1H, dd, J = 15.8, 6.04 Hz), 5.39 (1H, d,
J = 5.8 Hz), 2.49 (1H, s); 13C NMR (100 MHz, CDCl3) δ 162.9 (d,
1JC−F = 238.8 Hz), 146.0 (d, 3JC−F = 14.2 Hz), 142.3, 138.1 (d, 3JC−F
=
(E)-1-(Pyridin-3-yl)-3-phenylprop-2-en-1-ol (S9).
3
8.0 Hz), 133.7 (d, 4JC−F = 1.82 Hz), 130.4 (d, JC−F = 4.7 Hz), 128.7,
2
128.1, 126.3, 125.1, 109.4 (d, JC−F = 37.1 Hz), 74.7; HRMS (ES+)
calcd for C14H 13FNO [M + H]+ 230.0981, found 230.0993.
(E)-1-(3-Fluorophenyl)-3-phenylprop-2-en-1-ol (S6).
The title compound was prepared according to general procedure B
from 1-(3-pyridyl)-3-phenylprop-2-yn-1-ol32 (278 mg, 1.32 mmol)
using Red-Al (65% in PhMe) (0.6 mL, 1.98 mmol). The crude product
was applied directly onto the top of a column and chromatographed
(10% EtOAc in hexane) to afford S9 (200 mg, 72%) as a colorless oil: Rf
(10% EtOAc in hexane) = 0.06; IR νmax (thin film)/cm−1 1579, 1424,
The title compound was prepared according to general procedure B
from 1-(4-fluorophenyl)-3-phenylprop-2-yn-1-ol (329 mg, 1.45 mmol)68
using Red-Al (65% in PhMe) (0.88 mL, 2.90 mmol). The crude product
was applied directly onto the top of a column and chromatographed
1
1275, 1027, 967; H NMR (400 MHz, CDCl3) δ 8.67 (1H, s), 8.55−
8.53 (1H, m), 7.79−7.76 (1H, m), 7.40−7.24 (6H, m), 6.72 (1H, d,
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J = 16.0 Hz), 6.35 (1H, dd, J = 16.0, 6.8 Hz), 5.45 (1H, d, J = 6.4 Hz),
2.42 (1H, s, br); 13C NMR (100 MHz, CDCl3) δ 149.1, 148.2, 138.1,
136.1, 134.0, 131.6, 130.6, 128.7, 128.2, 126.7, 123.5, 73.1; HRMS
(ES+) calcd for C14H13NNaO [M + Na]+ 234.0895, found 234.0866.
(E)-(3-(allyloxy)-3-phenylprop-1-en-1-yl)dimethyl(phenyl)silane
(1a).
128.9, 128.7, 128.4, 127.7, 116.8, 113.8, 83.2, 69.1, 55.2, −2.6, −2.6;
HRMS (EI+) Calcd for C21H26O2SiNa [M + Na]+ 361.1600, found
361.1618.
(E)-(3-(Allyloxy)-3-(naphthalen-2-yl)prop-1-en-1-yl)dimethyl-
(phenyl)silane (1d).
The title compound was prepared according to general procedure C
from (E)-3-(dimethyl(phenyl)silyl)-1-(naphthalen-2-yl)prop-2-en-1-ol31b
(401 mg, 1.26 mmol), sodium hydride (60% suspension in mineral oil;
unwashed) (101 mg, 2.52 mmol), and allyl bromide (301 mg,
2.52 mmol) in DMF (16 mL) which following conversion to the allyl
ether and column chromatography (9:1 hexane/EtOAc) afforded 1d
as a colorless oil (453 mg, 99%): Rf (9:1 hexane/ethyl acetate) = 0.77;
IR νmax (thin film)/cm−1 3437, 3054, 2956, 1647, 1601, 1508, 1427,
1249, 1114, 1086, 990, 819, 732, 670, 478; 1H NMR (400 MHz,
CDCl3) δ 7.88−7.84 (3H, m), 7.85−7.80 (1H, m), 7.54−7.47 (5H,
m), 7.41−7.31 (3H, m), 6.31 (1H, dd, J = 18.8, 5.5 Hz), 6.14 (1H, dd,
J = 18.8, 1.3 Hz), 6.01−5.90 (1H, m), 5.33 (1H, ddd, J = 17.3, 1.9, 1.8
Hz), 5.22 (1H, ddd, J = 10.3, 1.2, 1.1 Hz), 5.04 (1H, d, J = 5.8 Hz),
4.02−3.99 (2H, m), 0.37 (3H, s), 0.36 (3H, s); 13C NMR (100 MHz,
CDCl3) δ 147.6, 138.6, 134.8, 134.4 133.8, 133.2, 133.0, 129.4, 128.9,
128.3, 128.0 127.9, 127.7, 126.2, 126.0, 125.9, 125.0, 117.0, 83.8, 69.4,
−2.6, −2.6; HRMS (EI+) Calcd for C24H30ONSi [M + NH4]+
376.2097, found 376.2098.
The title compound was prepared according to general procedure C
from (E)-3-(dimethyl(phenyl)silyl)-1-phenylprop-2-en-1-ol31a (200 mg,
0.746 mmol), sodium hydride (60% suspension in mineral oil;
unwashed) (36 mg, 1.49 mmol), and allyl bromide (181 mg,
1.49 mmol) in DMF (10 mL) which following conversion to the
allyl ether and column chromatography (9:1 hexane/EtOAc) afforded
1a as a colorless oil (161 mg, 70%): Rf (9:1 hexane−ethyl acetate) =
1
0.80; H NMR (400 MHz, CDCl3) δ 7.57−7.52 (2H, m), 7.42−7.30
(8H, m), 6.26 (1H, ddd, J = 18.8, 5.8, 1.7 Hz), 6.12 (1H, d, J = 18.8
Hz), 6.05−5.94 (1H, m), 5.33 (1H, ddd, J = 17.3, 3.0, 3.0 Hz), 5.23
(1H, ddd, J = 10.5, 2.8, 2.8 Hz), 4.89 (1H, d, J = 5.8 Hz), 4.03
(1H, m), 0.39 (3H, d, J = 1.5 Hz), 0.38 (3H, d, J = 1.5 Hz); 13C NMR
(100 MHz, CDCl3) δ 147.6, 140.8, 138.5, 134.8, 133.8, 129.2, 128.9,
128.4, 127.7, 127.6, 127.1, 116.9, 83.7, 69.3, −2.6, −2.7. Character-
ization in accordance with literature data.24
(E)-(3-(Allyloxy)-3-(p-tolyl)prop-1-en-1-yl)dimethyl(phenyl)silane
(1b).
(E)-(3-(Allyloxy)-3-(4-fluorophenyl)prop-1-en-1-yl)dimethyl-
(phenyl)silane (1e).
The title compound was prepared according to general procedure C
from (E)-3-(dimethyl(phenyl)silyl)-1-(p-tolyl)prop-2-en-1-ol31b (876 mg,
3.10 mmol), sodium hydride (60% suspension in mineral oil; unwashed)
(248 mg, 6.20 mmol), and allyl bromide (750 mg, 6.20 mmol) in
DMF (39 mL) which following conversion to the allyl ether and
column chromatography (19:1 hexane/EtOAc) afforded 1b as a
colorless oil (0.892 g, 89%): Rf (9:1 hexane/ethyl acetate) = 0.63; IR
νmax (thin film)/cm−1 3735, 3068, 3048, 2956, 2856, 1512, 1427, 1247,
The title compound was prepared according to general procedure C
from (E)-3-(dimethyl(phenyl)silyl)-1-(4-fluorophenyl)prop-2-en-1-ol31b
(300 mg, 1.12 mmol), sodium hydride (60% suspension in mineral oil;
unwashed) (90 mg, 2.24 mmol), and allyl bromide (273 mg,
2.25 mmol) in DMF (14 mL) which following conversion to the
allyl ether and column chromatography (3% EtOAc in hexane)
afforded 3e as a colorless oil (237 mg, 65%): Rf (9:1 hexane/ethyl
acetate) = 0.83; IR νmax (thin film)/cm−1 3433, 2957, 1604, 1508,
1223, 1114, 838, 670; 1H NMR (400 MHz, CDCl3) δ 7.52−7.49 (2H,
m), 7.38−7.29 (5H, m), 7.07−7.02 (2H, m), 6.18 (1H, dd, J = 18.8,
5.8 Hz), 6.05 (1H, dd, J = 18.6, 1.0 Hz), 5.94 (1H, ddd, J = 17.1, 11.0,
5.52 Hz), 5.28 (1H, ddd, J = 17.0, 1.5, 1.5 Hz), 5.20 (1H, ddd, J =
10.2, 1.2, 1.2 Hz), 4.83 (1H, d, J = 5.8 Hz), 3.98−3.93 (2H, m), 0.36
1
1114, 822, 730, 699; H NMR (400 MHz, CDCl3) δ 7.54−7.49 (2H,
m), 7.39−7.34 (3H, m), 7.26−7.16 (4H, m), 6.23 (1H, dd, J = 18.6,
5.52 Hz), 6.07 (1H, dd, J = 18.8, 1.3 Hz), 5.96 (1H, ddd, J = 17.3, 3.0,
3.0 Hz), 5.29 (1H, ddd, J = 17.3, 2.0, 1.8 Hz), 5.19 (1H, m), 4.83 (1H,
d, J = 5.8), 3.98 (2H, d, J = 5.5 Hz), 2.37 (3H, s), 0.36 (3H, s), 0.35
(3H, s); 13C NMR (100 MHz, CDCl3) δ 147.8, 138.6, 137.8, 137.3,
134.9, 133.8, 129.1, 128.9, 128.8, 127.7, 127.1, 116.8, 83.6, 69.3, 21.1,
−2.6; HRMS (ES+) calcd for C21H26ONaSi [M + Na]+ 345.1651,
found 345.1664.
(3H,s), 0.35 (3H, s); 13C NMR (100 MHz, CDCl3) δ 162.3 (d, JC−F
=
243.9 Hz), 147.4, 138.4, 136.6 (d JC−F = 3.3 Hz), 134.7, 133.8, 129.7,
129.0, 128.7 (d, JC−F = 8.02 Hz), 127.8, 117.0, 115.3 (d, JC−F = 21.1
Hz), 83.0, 69.4, −2.6, −2.6; HRMS (EI+) Calcd for C19H20OFSi
[M − CH3]+ 311.1267, found 311.1289.
(E)-(3-(Allyloxy)-3-(3-fluorophenyl)prop-1-en-1-yl)dimethyl-
(phenyl)silane (1f).
(E)-(3-(Allyloxy)-3-(4-methoxyphenyl)prop-1-en-1-yl)dimethyl-
(phenyl)silane (1c).
The title compound was prepared according to general procedure C
from (E)-3-(dimethyl(phenyl)silyl)-1-(4-methoxyphenyl)prop-2-en-1-ol31b
(399 mg, 1.34 mmol), sodium hydride (60% suspension in mineral oil;
unwashed) (112 mg, 2.81 mmol), and allyl bromide (343 mg, 2.25 mmol)
in DMF (17.5 mL) which following conversion to the allyl ether and
column chromatography (9:1 hexane/EtOAc) afforded 3b as a
colorless oil (389 mg, 86%): Rf (9:1 hexane/ethyl acetate) = 0.67 IR
νmax (thin film)/cm−1 3446, 1614, 1510, 1248, 823, 730, 699; 1H NMR
(400 MHz, CDCl3) δ 7.51−7.46 (2H, m), 7.35−7.30 (3H, m), 7.26−
7.22 (2H, m), 6.90−6.85 (2H, m), 6.20 (1H, dd, J = 18.6, 5.5 Hz),
6.02 (1H, d, J = 18.6 Hz), 5.97−5.86 (1H, m), 5.25 (1H, ddd, J = 17.4,
2.5, 2.4 Hz), 5.16 (1H, ddd, J = 10.7, 2.9, 2.9 Hz), 4.78 (1H, d, J = 5.5
Hz), 3.94 (2H, d, J = 5.5 Hz), 3.79 (3H, s), 0.33 (3H, s), 0.32 (3H, s);
13C NMR (100 MHz, CDCl3) δ 159.1, 147.9, 138.6, 134.9, 133.8,
The title compound was prepared according to general procedure C
from (E)-3-(dimethyl(phenyl)silyl)-1-(3-fluorophenyl)prop-2-en-1-ol31b
(1.0 g, 3.49 mmol), sodium hydride (60% suspension in mineral oil;
unwashed) (279 mg, 6.98 mmol), and allyl bromide (844 mg,
6.98 mmol) in DMF (44 mL) which following conversion to the allyl
ether and column chromatography (19:1 hexane/EtOAc) afforded 1f
as a colorless oil (892 mg, 89%): Rf (9:1 hexane/ethyl acetate) = 0.89;
IR νmax (thin film)/cm−1 3656, 3069, 2956, 2946, 2855, 1591, 1485,
1
1448, 1428, 1249, 1114, 991, 843, 699, 469; H NMR (400 MHz,
CDCl3) δ 7.51−7.44 (2H, m), 7.36−7.25 (4H, m), 7.11−7.04 (2H, m),
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6.99−6.92 (1H, m), 6.14 (1H, dd, J = 18.6, 5.2 Hz), 6.06 (1H, 18.6,
0.8 Hz), 5.93 (1H, m), 5.27 (1H, ddd, J = 17.3, 1.7, 1.7 Hz), 5.18 (1H,
ddd, J = 10.3, 1.5, 1.2 Hz), 5.01 (1H, d, J = 5.8 Hz), 4.04 (2H, m), 0.34
1-(p-Tolyl)hex-5-en-1-one (3b).
(3H, s), 0.33 (3H, s); 13C NMR (100 MHz, CDCl3) δ 163.0 (d, JC−F
=
244.3 Hz), 147.0, 143.6 (d, JC−F = 6.9 Hz), 138.3, 134.5, 133.9, 130.1,
129.9 (d, JC−F = 8.0), 129.0, 127.8, 122.6 (d, JC−F = 2.9 Hz), 117.1,
The title compound was prepared according to general procedure D
from 1b (57.3 mg, 0.178 mmol) and KHMDS (0.5 M in toluene)
(106 mg, 0.534 mmol) in THF (3.6 mL) which following conversion
to the ketone and column chromatography (1% EtOAc/hexane)
afforded 3b as a colorless oil (24.6 mg, 73%): Rf (9:1 hexane/ethyl
114.4 (d, JC−F = 21.2 Hz), 113.8 (d, JC−F = 21.9 Hz), 83.1 (d, JC−F
=
1.5 Hz), 69.4, −2.7; HRMS (ES+) calcd for C20H23OFNaSi
[M + Na]+ 349.1395, found 349.1389.
(E)-(3-(Allyloxy)-3-cyclohexylprop-1-en-1-yl)dimethyl(phenyl)-
silane (1g).
1
acetate) = 0.57; H NMR (400 MHz, CDCl3) δ 7.89−7.84 (2H, m),
7.29−7.24 (2H, m), 5.83 (1H, m), 5.05 (1H, ddd, J = 17.0, 3.5, 1.5
Hz), 5.00 (1H, ddd, J = 10.3, 2.0, 1.2 Hz), 2.96 (2H, t, J = 7.3 Hz),
2.41 (3H, s), 2.16 (2H, qt, J = 8.6, 1.3 Hz), 1.85 (2H, dt, J = 7.5, 7.3
Hz); 13C NMR (100 MHz, CDCl3) δ 199.8, 143.6, 138.1, 134.6, 129.2,
128.1, 115.2, 37.6, 33.2, 23.4, 21.6. Characterization in accordance with
literature data.69
The title compound was prepared according to general procedure C
from (E)-1-cyclohexyl-3-(dimethyl(phenyl)silyl)prop-2-en-1-ol31a
(399 mg, 1.46 mmol), sodium hydride (60% suspension in mineral
oil; unwashed) (117 mg, 2.94 mmol) and allyl bromide (350 mg,
2.89 mmol) in DMF (18 mL) which following conversion to the allyl
ether and column chromatography (9:1 hexane/EtOAc) afforded 1g as
a colorless oil (376 mg, 82%): Rf (9:1 hexane/ethyl acetate) = 0.80; 1H
NMR (400 MHz, CDCl3) δ 7.58−7.51 (2H, m), 7.40−7.35 (3H, m),
6.02−5.88 (3H, m), 5.26 (1H, ddd, J = 17.3, 2.0, 1.8 Hz), 5.16 (1H,
ddd, J = 10.2, 1.9, 1.8 Hz), 4.06 (1H ddd, J = 12.8, 5.1, 1.8 Hz), 3.81
(1H, ddd, J = 12.8, 6.1, 1.8 Hz), 3.47 (1H, t, J = 6.1 Hz), 1.82−1.69
(2H, m), 1.68−1.56 (3H, m), 1.52−1.45 (3h, m), 0.91−0.82 (3H, m),
0.38 (3H, s), 0.37 (3H, s); 13C NMR (100 MHz, CDCl3) δ 147.4,
138.8, 135.4, 133.8, 131.1, 129.0, 127.8, 116.4, 87.3, 69.6, 42.3, 29.0,
26.7, 26.2, −2.4, −2.5. Characterization in accordance with literature
data.24
1-(4-Methoxyphenyl)hex-5-en-1-one (3c).
The title compound was prepared according to general procedure D
from 1c (49.9 mg, 0.147 mmol) and KHMDS (0.5 M in toluene)
(82.0 mg, 0.441 mmol) in THF (3.0 mL) which following conversion
to the ketone and column chromatography (1% EtOAc/hexane)
afforded 3c as a colorless oil (26.9 mg, 90%): Rf (9:1 hexane/ethyl
1
acetate) = 0.42; H NMR (400 MHz, CDCl3) δ 7.95 (2H, m), 6.94
(2H, m), 5.83 (1H, m), 5.05 (1H, ddd, J = 17.1, 2.0, 1.5 Hz), 5.00
(1H, ddd, J = 10.3, 2.0, 1.3 Hz), 3.87 (3H, s), 2.93 (2H, t, J = 7.3 Hz),
2.16 (2H, br dd, J = 7.3, 1.2 Hz), 1.85 (2H, dt, J = 7.6, 7.2 Hz); 13C
NMR (100 MHz, CDCl3) δ 198.4, 163.3, 138.1, 130.3, 130.2, 115.7,
113.7, 55.4, 37.4, 33.2, 23.6. Characterization in accordance with
literature data.70
(E)-(3-(Allyloxy)-5-methylhex-1-en-1-yl)dimethyl(phenyl)silane
(1h).
1-(Naphthalen-2-yl)hex-5-en-1-one (3d).
The title compound was prepared according to general procedure C
from (E)-1-(dimethyl(phenyl)silyl)-5-methylhex-1-en-3-ol31a (319 mg,
1.10 mmol), sodium hydride (60% suspension in mineral oil; un-
washed) (110 mg, 2.75 mmol), and allyl bromide (336 mg, 2.72 mmol)
in DMF (14 mL) which following conversion to the allyl ether and
column chromatography (19:1 hexane/EtOAc) afforded 1h as a
The title compound was prepared according to general procedure D
from 1d (50.2 mg, 0.140 mmol) and KHMDS (0.5 M in toluene)
(83.8 mg, 0.420 mmol) in THF (2.8 mL) which following conversion
to the ketone and column chromatography (2% EtOAc/hexane)
afforded 3d as a colorless oil (17.2 mg, 55%): Rf (9:1 hexane/ethyl
1
colorless oil (299 mg, 81%): Rf (9:1 hexane/ethyl acetate) = 0.74; H
1
NMR (400 MHz, CDCl3) δ 7.56−7.51 (2H, m), 7.40−7.34 (3H, m),
5.99−5.88 (3H, m), 5.27 (1H, ddd, J = 17.1, 1.5 Hz), 5.18 (1H, ddd, J =
10.3, 1.5 Hz), 4.07 (1H, ddd, J = 12.8, 5.3, 1.5 Hz), 3.87−3.79 (2H, m),
1.84−1.73 (1H, m), 1.61−1.53 (1H, m), 1.36−1.27 (2H, m), 0.93 (6H,
dd, J = 6.7, 0.6 Hz), 0.38 (3H, s), 0.37 (3H, s); 13C NMR (100 MHz,
CDCl3) δ 148.9, 138.6, 135.2, 133.8, 129.7, 129.0, 127.8, 116.6, 80.8,
69.4, 44.5, 24.4, 23.0, 22.5, −2.5, −2.6 Characterization in accordance
with literature data.24
acetate) = 0.72; H NMR (400 MHz, CDCl3) δ8.48 (1H, m), 8.06−
8.02 (1H, m), 8.00−7.96 (1H, m), 7.92−7.86 (2H, m), 7.64−7.54
(2H, m), 5.87 (1H, m), 5.09 (1H, ddd, J = 17.0, 2.0, 1.5 Hz), 5.03
(1H, ddd, J = 10.3, 2.0, 1.2 Hz), 3.13 (2H, d, J = 7.3 Hz), 2.22 (2H,
m), 1.93 (2H, dt, J = 7.4, 7.2 Hz); 13C NMR (100 MHz, CDCl3) δ
200.2, 138.1, 135.5, 134.4, 132.5, 129.6, 129.5, 128.4, 128.3, 127.7,
126.7, 123.9, 115.3, 37.7, 33.2, 23.5. Characterization in accordance
with literature data.71
1-(4-Fluorophenyl)hex-5-en-1-one (3e).
1-Phenylhex-5-en-1-one (3a).
The title compound was prepared according to general procedure D
from 1a (144 mg, 0.371 mmol) and KHMDS (0.5 M in toluene)
(225 mg, 1.13 mmol) in THF (3.5 mL) which following conversion to
the ketone and column chromatography (4:1 hexane/DCM) afforded
3a as a colorless oil (55.5 mg, 85%): Rf (9:1 hexane/ethyl acetate) =
The title compound was prepared according to general procedure D
from 1e (54.5 mg, 0.167 mmol) and KHMDS (0.5 M in toluene)
(99.9 mg, 0.501 mmol) in THF (3.3 mL)which following conversion
to the ketone and column chromatography (4:1 hexane/DCM) afforded
3e as a colorless oil (15.6 mg, 49%): Rf (9:1 hexane/ethyl acetate) =
1
1
0.83; H NMR (400 MHz, CDCl3) δ8.00−7.94 (2H, m), 7.59−7.73
0.74; H NMR (400 MHz, CDCl3) δ8.02−7.96 (2H, m), 7.17−7.10
(1H, m), 7.50−7.44 (2H, m), 5.83 (1H, ddd, J = 17.1, 10.2, 6.1 Hz),
5.06 (1H, ddd, J = 17.0 2.0, 1.5 Hz), 5.01 (1H, dd, J = 10.3, 2.0 Hz),
2.99 (2H, t, J = 7.0 Hz), 2.17 (2H, dddd, J = 7.2, 6.8, 6.0, 0.5 Hz) 1.87
(2H, dt, J = 7.7, 7.2 Hz); 13C NMR (100 MHz, CDCl3) δ 200.2, 138.0,
137.1, 132.9, 128.5, 128.0, 115.3, 37.7, 33.2, 23.3. Characterization in
accordance with literature data.69
(2H, m), 5.83 (1H, m), 5.03 (2H, m), 2.96 (2H, t, J = 7.3 Hz), 2.16
(2H, br dd, J = 7.2, 1.2 Hz), 1.86 (2H, dt, J = 7.6, 7.1 Hz), 13C NMR
(100 MHz, CDCl3) δ 198.6, 165.6 (d, JC−F = 253 Hz), 138.0, 133.5 (d,
JC−F = 2.9 Hz), 130.6 (d, JC−F = 9.1 Hz), 115.6 (d, JC−F = 21.5 Hz),
115.4, 37.6, 33.1, 22.2. Characterization in accordance with literature
data.70
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1-(3-Fluorophenyl)hex-5-en-1-one (3f).
(1H, dtt, J = 14.1, 6.3, 1.2 Hz), 1.20 (3H, d, J = 6.9 Hz); 13C NMR
(100 MHz, CDCl3) δ 202.1, 163.4, 136.0, 130.5, 129.4, 116.5, 113.8,
55.4, 40.0, 37.8, 17.2. Characterization in accordance with literature
data.73
2-Methyl-1-(naphthalen-2-yl)pent-4-en-1-one (5d).
The title compound was prepared according to general procedure D
from 1f (51.6 mg, 0.159 mmol) and KHMDS (0.5 M in toluene)
(95 mg, 0.477 mmol) in THF (3.2 mL) which following conversion to
the ketone and column chromatography (2% EtOAc/hexane) afforded
3f as a colorless oil (23.8 mg, 78%): Rf (9:1 hexane/ethyl acetate) =
The title compound was prepared according to general procedure E
from 1d (49.1 mg, 0.137 mmol) and potassium tert-butoxide (7.7 mg,
0.069 mmol) in THF (1.0 mL) which following conversion to the
ketone and column chromatography (0.5% Et2O, 0.5% THF in
pentane) afforded 5d as a colorless oil (18.1 mg, 59%): Rf (5% Et2O in
pentane) = 0.62; IR νmax (thin film)/cm−1 3425, 1677, 1187, 1122,
1
0.83; H NMR (400 MHz, CDCl3) δ 7.76−7.73 (1H, m), 7.66−7.62
(1H, m), 7.48−7.41 (1H, m), 7.29−7.23 (1H, m), 5.83 (1H, m), 5.04
(2H, m), 2.97 (2H, t, J = 7.3 Hz), 2.17 (2H, dr dd, J = 7.3 Hz), 1.86
(2H, dt, J = 7.7, 7.1 Hz); 13C NMR (100 MHz, CDCl3) δ 199.9, 162.9
(d, JC−F = 246 Hz), 139.2 (d, JC−F = 6.2 Hz), 137.9, 130.2 (d, JC−F
=
1
7.6 Hz), 123.7 (d, JC−F = 2.9 Hz), 119.9 (d, JC−F = 21.1 Hz), 115.4,
114.7 (d, JC−F =22.2 Hz), 37.8, 33.0, 23.1. Characterization in
accordance with literature data.71
915, 760; H NMR (400 MHz, CDCl3) δ8.48 (1H, m), 8.07−7.87
(4H, m), 7.64−7.53 (2H, m), 5.84 (1H, m), 5.09 (1H, m), 5.04 (1H,
m), 3.73 (1H, td, J = 13.7, 6.8 Hz), 2.64 (1H, dtt, J = 14.3, 6.3, 1.5
Hz), 2.28 (1H, dtt, J = 14.3, 7.2, 1.3 Hz), 1.29 (3H, d, J = 6.8 Hz); 13C
NMR (100 MHz, CDCl3) δ 203.6, 135.8, 135.5, 133.8, 132.6, 129.7,
129.6, 128.5, 128.4, 127.7, 126.7, 124.2, 116.8, 40.5, 37.8, 17.2; HRMS
2-Methyl-1-phenylpent-4-en-1-one (5a).
+
(ES+) calcd for C16H17O [M + H] 225.1279, found 225.1273.
1-(4-Fluorophenyl)-2-methylpent-4-en-1-one (5e).
The title compound was prepared according to general procedure E
from 1a (54.4 mg, 0.176 mmol) and potassium tert-butoxide (9.9 mg,
0.088 mmol) in THF (1.5 mL) which following conversion to the
ketone and column chromatography (0.25% Et2O, 0.25% THF in
pentane) afforded 5a as a colorless oil (23.1 mg, 75%): Rf (1% Et2O in
hexane) = 0.40; IR νmax (thin film)/cm−1 3420, 2975, 2931, 1680,
1607, 1240, 1205, 1182, 974, 827, 748; 1H NMR (400 MHz, CDCl3) δ
7.99−7.94 (2H, m), 7.60−7.54 (1H, m), 7.51−7.45 (2H, m), 5.80
(1H, m), 5.09−5.00 (2H, m), 3.55 (1H, td, J = 13.8, 7.0 Hz), 2.57
(1H, dtt, J = 14.1, 6.5, 1.5 Hz), 2.21 (1H, dtt, J = 14.3, 7.3, 1.2 Hz),
1.22 (3H, d, J = 6.8 Hz); 13C NMR (100 MHz, CDCl3) δ201.6, 136.5,
135.8, 132.9, 128.6, 128.3, 116.7, 40.4, 37.6, 17.0; HRMS (EI+) Calcd
for C12H14O [M]+ 174.1045, found 174.1051. Characterization in
accordance with literature data.72
The title compound was prepared according to general procedure E
from 1e (55.1 mg, 0.163 mmol) and potassium tert-butoxide (9.1 mg,
0.082 mmol) in THF (1.6 mL) which following conversion to the
ketone and column chromatography (0.25% Et2O, 0.25% THF in
pentane) afforded an inseparable mixture of 5e (10.7 mg, 34%) and
regioisomeric product 3e (11.3 mg, 36%) as a colorless oil: Rf (1%
Et2O in hexane) = 0.39; IR νmax (thin film)/cm−1 3066, 2976, 2932,
1
1684, 1598, 1409, 1233, 1157, 978, 846, 759; H NMR (400 MHz,
CDCl3) δ 8.02−7.95 (2H, m), 7.17−7.10 (2H, m), 5.77 (1H, m), 5.04
(2H, m), 3.49 (1H, td, J = 13.6, 6.8 Hz), 2.55 (1H, ddd, J = 13.0, 6.5,
1.2 Hz), 2.20 (1H, ddd, J = 14.6, 7.5, 1.2 Hz), 1.20 (3H, d, J = 7.0 Hz);
13C NMR (100 MHz, CDCl3) δ 202.0, 165.6 (d, JC−F = 252 Hz),
135.6, 132.8 (d, JC−F = 3.3 Hz), 130.8 (d, JC−F = 9.12 Hz), 116.9, 115.7
(d, JC−F = 21.9 Hz), 40.4, 37.6, 17.0; HRMS (ES+) calcd for
C12H13FO [M + 2H]+ 194.1107, found 194.1132.
2-Methyl-1-(p-tolyl)pent-4-en-1-one (5b).
The title compound was prepared according to general procedure E
from 1b (62.0 mg, 0.192 mmol) and potassium tert-butoxide (10.8 mg,
0.096 mmol) in THF (1.5 mL) which following conversion to the
ketone and column chromatography (0.25% Et2O, 0.25% THF in
pentane) afforded 5b as a colorless oil (26.7 mg, 74%): Rf (5% Et2O in
pentane) = 0.54; 1H NMR (400 MHz, CDCl3) δ 7.89−7.85 (2H, m),
7.30−7.25 (2H, m), 5.79 (1H, m), 5.09−4.99 (2H, m), 3.52 (1H, td,
J = 13.6, 6.8 Hz), 2.56 (1H, ddd, J = 14.0, 6.5, 1.2), 2.42 (3H, s), 2.20
(1H, dtt, J = 14.3, 7.3, 1.2 Hz), 1.20 (3H, d, J = 6.8 Hz); 13C NMR
(100 MHz, CDCl3) δ 203.2, 143.6, 135.9, 133.9, 129.3, 128.4, 116.6,
40.4, 37.7, 21.6, 17.1. Characterization in accordance with literature
data.72
1-(3-Fluorophenyl)-2-methylpent-4-en-1-one (5f).
The title compound was prepared according to general procedure E
from 1f (52.1 mg, 0.160 mmol) and potassium tert-butoxide (9.0 mg,
0.080 mmol) in THF (1.2 mL) which following conversion to the
ketone and column chromatography (0.25% Et2O, 0.25% THF in
pentane) afforded 5f as a colorless oil (15.4 mg, 50%): Rf (1% Et2O in
pentane) = 0.65; IR νmax (thin film)/cm−1 3076, 2977, 2934, 1688,
1
1588, 1441, 1255, 991, 917, 750; H NMR (400 MHz, CDCl3) δ
1-(4-Methoxyphenyl)-2-methylpent-4-en-1-one (5c).
7.75−7.72 (1H, m), 7.65−7.61 (1H, m), 7.49−7.43 (1H, m), 7.30−
7.24 (1H, m), 5.78 (1H, m), 5.05 (2H, m), 3.48 (1H, td, J = 13.2, 6.5
Hz), 2.56 (1H, dtt, J = 11.5, 6.4, 1.2 Hz), 2.21 (1H, dtt, J = 14.3, 7.3,
1.2 Hz), 1.22 (3H, d, J = 6.8 Hz); 13C NMR (100 MHz, CDCl3) δ
202.3, 162.9 (d, JC−F = 246 Hz), 138.6 (d, JC−F F = 5.8 Hz), 135.5,
130.2 (d, JC−F = 7.3 Hz), 123.9 (d, JC−F = 2.9 Hz), 119.8 (d, JC−F
=
The title compound was prepared according to a modified general
procedure E where the reaction was carried out in an argon-purged
5 mL sealed tube at 100 °C from 1c (43.1 mg, 0.127 mmol) and
potassium tert-butoxide (7.0 mg, 0.062 mmol) in THF (1 mL).
Following conversion to the ketone, column chromatography (2%
THF in hexane) afforded 5c as a colorless oil (25.7 mg, 99%): Rf (1%
21.1 Hz), 117.0, 115.0 (d, JC−F = 21.9 Hz), 40.7, 37.5, 16.9; HRMS
+
(ES+) calcd for C12H13FNaO [M + Na] 215.0848, found 215.0861.
(E)-1-(Allyloxy)-1,3-diphenylprop-2-ene (11a).
1
Et2O in hexane) = 0.56; H NMR (400 MHz, CDCl3) δ 7.98−7.94
(2H, m), 6.97−6.93 (2H, m), 5.79 (1H, m), 5.05 (1H, ddd, J = 16.8,
3.2, 1.5 Hz), 5.01 (1H, ddd, J = 10.0, 1.8, 1.2 Hz), 3.88 (3H, s), 3.50
(1H, td, J = 13.9, 6.8 Hz), 2.55 (1H, dtt, J = 14.3, 5.0, 1.3 Hz), 2.20
Three drops of concd H2SO4 was added to a THF solution of (E)-1,3-
diphenylpropen-2-ol (837 mg, 3.99 mmol) and allyl alcohol (290 mg,
5.0 mmol). The solution was allowed to stir at room temperature for
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The Journal of Organic Chemistry
Article
1 h. The reaction was diluted with distilled water (20 mL), extracted
with Et2O (3 × 20 mL), dried over anhydrous MgSO4, and con-
centrated in vacuo. The crude product was loaded onto a column and
chromatographed (2% EtOAc in hexane) to afford 11a (847 mg, 85%)
10.4, 5.6 Hz), 5.31 (1H, ddd, J = 17.6, 1.6 Hz), 5.20 (1H, ddd, J =
10.4, 1.2 Hz), 4.97 (1H, d, J = 7.2 Hz), 4.04 (1H, ddd, J = 13.2, 5.6, 1.2
Hz), 4.00 (1H, ddd, J =13.2, 5.2, 1.6 Hz); 13C NMR (100 MHz,
CDCl3) δ 162.4 (d, JC−F = 246.0 Hz), 141.1, 134.8, 132.8 (d, JC−F
=
1
as a colorless oil: Rf (10% EtOAc in hexane) = 0.91; H NMR (400
3.0 Hz), 130.2 (m), 128.6, 128.1, 128.0 (d, JC−F = 40.0), 126.9, 117.0,
115.6, 115.3, 81.7, 69.3; HRMS (ES+) calcd for C18H18FO [M + H]+
269.1347, found 269.1342.
(E)-1-(Allyloxy)-1-phenyl-3-(4-trifluoromethoxyphenyl)prop-2-
ene (11e).
MHz, CDCl3) δ 7.43−7.34 (6H, m), 7.34−7.24 (3H, m), 7.24−7.18
(1H, m), 6.62 (1H, d, J = 16.1 Hz), 6.30 (1H, dd, J = 15.6, 6.5 Hz),
5.96 (1H, m), 5.31 (1H, m), 5.20 (1H, m), 4.98 (1H, d, J = 7.0 Hz),
4.03 (2H, m); 13C NMR (100 MHz, CDCl3) δ 141.2, 136.6, 134.9,
131.5, 130.3, 128.6, 127.8, 127.7, 127.1, 127.0, 126.6, 117.0, 81.8, 69.3.
Characterization in accordance with literature data.74
(E)-1-(Allyloxy)-1-phenyl-3-(4-methylphenyl)prop-2-ene (11b).
The title compound was prepared according to general procedure C
from (E)-1-phenyl-3-(4-(trifluoromethoxy)phenyl)prop-2-en-1-ol
(S2) (164 mg, 0.560 mmol) using allyl bromide (0.10 mL, 1.12 mmol)
and NaH (60% suspension in mineral oil; unwashed) (45.0 mg,
1.12 mmol). The crude product was applied directly onto the top of a
column and chromatographed (2% EtOAc in hexane) to afford 11e
(127 mg, 68%) as a yellow oil: Rf (10% EtOAc in hexane) = 0.28; IR
The title compound was prepared according to general procedure C
from (E)-1-phenyl-3-(p-tolyl)prop-2-en-1-ol66 (219 mg, 0.97 mmol)
using allyl bromide (0.17 mL, 1.94 mmol) and NaH (78.0 mg,
1.94 mmol). The crude product was applied directly onto the top of a
column and chromatographed (2% EtOAc in hexane) to afford 11b
(219 mg, 86%) as a colorless oil: Rf (10% EtOAc in hexane) = 0.53; IR
νmax (thin film)/cm−1 3025, 2923, 2854, 1512, 1495, 1449, 1260, 1071,
1
νmax (thin film)/cm−1 2926, 1508, 1260, 1220, 1166, 700; H NMR
(400 MHz, CDCl3) δ 7.41−7.27 (7H, m), 7.19−7.09 (2H, m), 6.60
(1H, d, J = 16.0 Hz), 6.29 (1H, d, J = 16.0, 6.8 Hz), 5.96 (1H, ddd, J =
17.2, 10.4, 5.6 Hz), 5.31 (1H, ddd, J = 17.2, 1.6 Hz), 5.21 (1H, ddd,
J = 10.4, 1.2), 4.98 (1H, d, J = 6.8 Hz), 4.07−3.98 (2H, m); 13C NMR
(100 MHz, CDCl3) δ 148.6 (q, JC−F = 245.1 Hz),, 140.9, 135.4, 134.7,
131.5, 129.7, 128.6, 127.9, 127.8, 127.0, 121.0 (q, JC−F = 1.0 Hz),
117.1, 81.5, 69.4; 357.1078 HRMS (ES) Calcd for C19H17F3Na O2
[M + Na]+ 357.1078, found 357.1102.
1
966, 922, 745; H NMR (400 MHz, CDCl3): δ 7.42−7.25 (7H, m),
7.10 (2H, d, J = 8.2 Hz), 6.58 (1H, d, J = 15.4 Hz), 6.24 (1H, dd,
J = 16.1, 7.2 Hz), 5.97 (1H, ddd, J = 17.2, 10.4, 5.6 Hz), 5.31 (1H,
ddd, J = 17.4, 1.6, 1.5 Hz), 5.20 (1H, ddd, J = 10.4, 1.4, 1.4 Hz), 4.97
(1H, d, J = 7.2 Hz), 4.06 (1H, ddd, J = 12.8, 5.5, 1.6 Hz), 4.01 (1H,
ddd, J = 13.2, 5.3, 1.5 Hz, 2.32 (3H, s); 13C NMR (100 MHz, CDCl3)
δ 141.3, 137.6, 134.9, 133.8, 131.5, 129.2,129.2, 128.5, 127.6, 126.9,
126.5, 116.9, 81.9, 69.2, 21.2; HRMS (ES+) calcd for C19H20NaO
[M + Na]+ 287.1412, found 287.1426.
(E)-1-(Allyloxy)-1-phenyl-3-(2-naphthyl)prop-2-ene (11f).
(E)-1-(Allyloxy)-1-phenyl-3-(4-methoxyphenyl)prop-2-ene (11c).
The title compound was prepared according to general procedure C
from (E)-3-(naphthalen-2-yl)-1-phenylprop-2-en-1-ol (S3) (263 mg,
1.01 mmol) using allyl bromide (0.18 mL, 2.02 mmol) and NaH (60%
suspension in mineral oil; unwashed) (81.0 mg, 2.02 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (1% EtOAc in hexane) to afford 11f (234 mg, 77%)
as a colorless oil: Rf (10% EtOAc in hexane) = 0.60; IR νmax (thin
film)/cm−1 2854, 1451, 1066, 969, 775, 771, 619; 1H NMR (400
MHz, CDCl3) δ 8.11−8.09 (1H, m), 7.85−7.75 (2H, m), 7.60−7.28
(10H, m,) 6.35 (1H, dd, J = 16.0, 6.8 Hz), 6.01 (1H, ddd, J = 17.2,
10.4, 5.6 Hz), 5.36 (1H, ddd, J = 17.2,1.6 Hz), 5.23 (1H, ddd, 1H, J =
10.4, 1.2 Hz), 5.12 (1H, d, J = 6.8 Hz), 4.14 (1H, ddd, J = 13.6, 5.6, 1.2
Hz), 4.09 (1H, ddd, J = 11.2, 5.6, 1.6 Hz); 13C NMR (100 MHz,
CDCl3) δ 141.2, 134.9, 134.4, 133.6, 133.5, 131.2, 128.6, 128.6, 128.5,
128.1,127.8, 127.0, 126.1, 125.8, 125.6, 124.0, 123.7, 117.0, 81.9, 69.4;
HRMS (ES+) calcd for C22H21O [M + H]+ 301.1592, found 301.1576.
(E)-1-(Allyloxy)-1-phenyl-3-(pyridin-3-yl)prop-2-ene (11g).
The title compound was prepared according to general procedure C
from (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-ol75 (142 mg, 0.6
mmol) using allyl bromide (0.10 mL, 1.20 mmol) and NaH (60%
suspension in mineral oil; unwashed) (48.0 mg, 1.20 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (1% EtOAc in hexane) to afford 11c (84 mg, 50%)
as a colorless oil: Rf (10% EtOAc in hexane) = 0.30; IR νmax (thin
1
film)/cm−1 2923, 1607, 1511, 1452, 1252, 750; H NMR (400 MHz,
CDCl3) δ 7.34−7.15 (7H, m), 6.75−6.73 (2H, m), 6.47 (1H, d, J =
15.8 Hz), 6.08 (1H, dd, J = 15.6, 7.2 Hz), 5.89 (1H, ddd, J = 17.2, 10.4,
5.6 Hz), 5.23 (1H, ddd, J = 17.2, 1.6 Hz), 5.11 (1H, ddd, J = 10.4, 1.6
Hz), 4.88 (1H, dd, J = 7.2 Hz), 3.98 (1H, ddd, J = 12.8, 5.2, 1.6 Hz),
3.92 (1H, ddd, J = 12.8, 5.6, 1.6 Hz), 3.70 (3H, s); 13C NMR (100
MHz, CDCl3) δ 158.3, 140.4, 130.9, 130.0, 128.3, 127.5, 127.1, 126.8,
126.6, 125.8, 115.8, 112.9, 80.9, 68.2, 54.2; HRMS (ES+) calcd for
C19H21O2 [M + H]+ 281.1542, found 281.1547.
(E)-1-(Allyloxy)-1-phenyl-3-(4-fluorophenyl)prop-2-ene (11d).
The title compound was prepared according to general procedure C
from (E)-1-phenyl-3-(pyridin-3-yl)prop-2-en-1-ol (S4) (113 mg,
0.53 mmol) using allyl bromide (0.09 mL, 1.06 mmol) and NaH
(60% suspension in mineral oil; unwashed) (43.0 mg, 1.06 mmol).
The crude product was applied directly onto the top of a column and
chromatographed (20% EtOAc in hexane) to afford 11g (94.2 mg,
90%) as a light yellow oil: Rf (50% Et2O in hexane) = 0.19; IR νmax
The title compound was prepared according to general procedure C
from (E)-3-(4-fluorophenyl)-1-phenylprop-2-en-1-ol (S1) (274 mg,
1.2 mmol) using allyl bromide (0.21 mL, 2.40 mmol) and NaH (60%
suspension in mineral oil; unwashed) (96.0 mg, 2.40 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (1% EtOAc in hexane) to afford 11d (221 mg, 69%)
as a light yellow oil: Rf (10% EtOAc in hexane) = 0.63; IR νmax
1
(thin film)/cm−1 3028, 1422, 1070, 967, 751, 700; H NMR (400
MHz, CDCl3) δ 8.59 (1H, s, br), 8.46 (1H, d, J = 3.8 Hz), 7.70−7.67
(1H, m), 7.41−7.24 (5H, m), 7.23−7.18 (1H, m), 6.62 (1H, d, J =
16.0 Hz), 6.39 (1H, dd, J = 16.0, 8.4 Hz), 5.97 (1H, ddt, J = 18.8, 12.0,
3.6 Hz), 5.31 (1H, dq, J = 17.4, 1.6 Hz) 5.21 (1H, dq, J = 10.4, 1.2
Hz), 5.01 (1H, d, J = 6.8 Hz), 4.03 (2H, dt, J = 5.6, 1.4 Hz); 13C NMR
1
(thin film)/cm−1 2924, 1508, 1275, 1227, 750; H NMR (400 MHz,
CDCl3) δ 7.41−7.27 (7H, m), 6.99−6.95 (2H, m), 6.59−6.55 (1H, d,
J = 15.6 Hz), 6.22 (1H, dd, J = 16.0, 6.8 Hz), 5.97 (1H, ddd, J = 17.2,
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(100 MHz, CDCl3) δ 148.8, 148.6, 140.6, 134.6, 132.9, 132.8, 132.3,
128.7, 128.0, 127.4, 127.0, 123.4, 117.2, 81.4, 69.4; HRMS (ES+) calcd
for C17H 18NO [M + H]+ 252.1388, found 252.1393.
The title compound was prepared according to general procedure C
from (E)-1-(4-fluorophenyl)-3-phenylprop-2-en-1-ol78(447 mg,
1.96 mmol) using allyl bromide (0.34 mL, 3.92 mmol) and NaH
(60% suspension in mineral oil; unwashed) (157 mg, 3.92 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (2% EtOAc in hexane) to afford 11k (447 mg, 85%)
as a light yellow oil: Rf (20% EtOAc in hexane) = 0.71; IR νmax (thin
film)/cm−1 3060, 3026, 2924, 2855, 1646, 1603, 1508, 1449, 1409,
(E)-1-(Allyloxy)-1-phenyl-3-(2-fluoropyridin-3-yl)prop-2-ene (11h).
1
1294, 1222, 1155, 1071, 1014, 968, 925, 833, 745; H NMR (400
The title compound was prepared according to general procedure C
from (E)-1-phenyl-3-(2-fluoropyridin-3-yl)prop-2-enol (S5) (163 mg,
0.71 mmol) using allyl bromide (0.13 mL, 1.42 mmol) and NaH (60%
suspension in mineral oil; unwashed) (57.0 mg, 1.42 mmol). The crude
product was applied directly onto the top of a column and chromato-
graphed (10% EtOAc in 60:40 petroleum ether) to afford 11h (139 mg,
73%) as a yellow oil: Rf (10% EtOAc in 60:40 petroleum ether) = 0.40; 1H
NMR (300 MHz, CDCl3) δ 8.17 (1H, d, J = 2.4 Hz), 7.81 (1H, td, J = 8.1,
2.6 Hz), 7.41−7.28 (6H, m), 6.88 (1H, dd, J = 8.7, 3.0 Hz), 6.60 (1H, d,
J = 16.1 Hz), 6.30 (1H, dd, J = 15.9, 6.3 Hz), 6.03−5.89 (1H, m), 5.35−
5.27 (1H, m), 5.25−5.19 (1H, m), 5.02−4.98 (1H, m), 4.03−3.99 (2H,
m): 13C NMR (100 MHz, CDCl3) δ = 146.2, 146.1, 139.3 (d, JC−F = 237
Hz), 138.0, 134.6, 132.6 (d, JC−F = 1.0 Hz), 128.7, 128.0, 127.0, 126.7,
125.9, 117.2, 109.4 (d, JC−F = 38.0 Hz), 81.3, 69.4; HRMS (ES+) calcd for
C17H17NFO [M + H]+ 270.1294, found 270.1298.
MHz, CDCl3) δ 7.39−7.21 (7H, m), 7.06−7.02 (2H, m), 6.60 (1H, d,
J = 16.0 Hz), 6.26 (1H, dd, J = 15.9, 6.8 Hz), 5.96 (1H, ddd, J = 17.2,
10.4, 5.6 Hz), 5.30 (1H, ddd, J = 17.2, 1.3 Hz) 5.20 (1H, ddd, 1H, J =
10.4, 1.3 Hz), 4.96 (1H, d, J = 7.0 Hz), 4.06 (1H, ddd, J = 12.8, 5.3, 1.3
Hz), 4.00 (1H, ddd, J = 12.8, 5.2, 1.6 Hz) 13C NMR (100 MHz,
CDCl3) δ 162.3 (d, JC−F = 244.0 Hz), 137.0 (d, JC−F = 3.0 Hz), 136.5,
134.7, 131.7, 130.0 (d, JC−F = 1.0 Hz), 128.6, 128.5, 127.8, 126.6,
117.0, 115.3 (d, JC−F = 21.0 Hz), 81.0, 69.2; HRMS (ES+) calcd for
C18H18FO [M + 2H]+ 270.1420, found 270.1447.
(E)-1-(Allyloxy)-1-(3-fluorophenyl)-3-phenylprop-2-ene (11l).
The title compound was prepared according to general procedure C
from (E)-1-(3-fluorophenyl)-3-phenylprop-2-en-1-ol (S6) (203 mg,
0.89 mmol) using allyl bromide (0.15 mL, 1.78 mmol) and NaH (60%
suspension in mineral oil; unwashed) (71.2 mg, 1.78 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (1% EtOAc in hexane) to afford 11l (226 mg, 95%)
as a colorless oil: Rf (10% EtOAc in hexane) = 0.62; IR νmax (thin
(E)-1-(Allyloxy)-1-(2-methoxyphenyl)-3-phenylprop-2-ene (11i).
The title compound was prepared according to general procedure C
from (E)-3-phenyl-1-(p-tolyl)prop-2-en-1-ol76 (239 mg, 1.07 mmol)
using allyl bromide (0.18 mL, 2.14 mmol) and NaH (60% suspension in
mineral oil; unwashed) (86.0 mg, 2.14 mmol). The crude product was
applied directly onto the top of a column and chromatographed (2%
EtOAc in hexane) to afford 11i (226 mg, 80%) as a colorless oil: Rf (10%
1
film)/cm−1 2924, 1591, 1486, 1070, 764, 692; H NMR (400 MHz,
CDCl3) δ 7.39−7.13 (8H, m), 6.99−6.94 (1H, m), 6.62 (1H, d, J =
16.2 Hz), 6.24 (1H, dd, J = 16.0, 7.2 Hz), 5.96 (1H, ddd, J = 17.2, 10.4,
5.6 Hz), 5.32 (1H, ddd, 1H, J = 17.2, 1.6 Hz) 5.21 (1H, ddd, 1H, J =
10.4, 1.2 Hz), 4.97 (1H, d, J = 7.4 Hz), 4.08 (1H, ddd, J = 13.2, 5.8, 1.2
Hz), 4.02 (1H, ddd, J = 12.8, 5.6, 1.6 Hz); 13C NMR (100 MHz,
CDCl3) δ 163.0 (d, JC−F = 244.0 Hz), 144.0 (d, JC−F = 7.0 Hz), 136.4,
134.6, 132.1, 130.0 (d, JC−F = 8.0 Hz), 129.6, 128.6, 127.9, 126.7, 122.4
1
EtOAc in hexane) = 0.68 ; H NMR (400 MHz, CDCl3) δ 7.31−7.28
(2H, m), 7.23−7.08 (7H, m), 6.53 (1H, d, J = 16.0 Hz), 6.22 (1H, dd, J =
16.0, 6.8 Hz), 5.89 (1H, ddd, J = 17.2, 10.4, 5.6 Hz), 5.23 (1H, ddd, 1H,
J = 17.0, 1.7, 1.6 Hz), 5.11 (1H, ddd, 1H, J = 10.4, 1.4, 1.2 Hz), 4.88 (1H,
d, J = 7.2 Hz), 3.97 (1H, ddd, J = 12.8, 5.6, 1.6 Hz), 3.92 (1H, ddd, J =
12.8, 5.6, 1.6 Hz), 2.27 (3H, s) 13C NMR (100 MHz, CDCl3) δ 137.1,
136.4, 135.7, 133.9, 130.1, 129.5, 128.2, 127.5, 126.6, 125.9, 125.6, 115.8,
80.6, 68.2, 20.1. Characterization in accordance with literature data.33
(E)-1-(Allyloxy)-1-(4-methoxyphenyl)-3-phenylprop-2-ene (11j).
(d, JC−F = 3.0 Hz), 117.2 114.5 (d, JC−F =22.0 Hz), 113.7 (d, JC−F
=
21.0 Hz), 81.1 (d, JC−F = 2.0 Hz), 69.4; Calcd for C18H18OF [M + H]+
269.1342, found 269.1342.
(E)-1-(Allyloxy)-1-(3,5-dimethylphenyl)-3-phenylprop-2-ene
(11m).
The title compound was prepared according to general procedure C
from (E)-1-(3,5-dimethylphenyl)-3-phenylprop-2-en-1-ol (S8) (149 mg,
0.430 mmol) using allyl bromide (0.075 mL, 0.860 mmol) and NaH (60%
suspension in mineral oil; unwashed) (35.0 mg, 0.860 mmol). The crude
product was applied directly onto the top of a column and chromato-
graphed (2% EtOAc in hexane) to afford 11m (122 mg, 70%) as a
colorless oil: Rf (10% EtOAc in hexane) = 0.84; IR νmax (thin film)/cm−1
2921, 1602, 1449, 1070, 966, 693; 1H NMR (400 MHz, CDCl3) δ 7.38−
7.36 (2H, m), 7.29−7.25 (2H, m), 7.22−7.18 (1H, m), 7.02−7.00 (2H,
m), 6.92−6.89 (1H, m), 6.61 (1H, d, J = 16.0 Hz), 6.29 (1H, dd, J = 16.0,
7.2 Hz), 5.97 (1H, ddd, J = 17.6, 10.6, 5.2 Hz), 5.30 (1H, ddd, J = 17.2, 1.2
Hz), 5.19 (1H, ddd, J = 10.8, 1.6, 1.6 Hz), 4.90 (1H, d, J = 6.8 Hz), 4.05
(1H, ddd, J = 13.2, 6.0, 1.2 Hz), 4.00 (1H, ddd, J = 13.2, 5.2, 1.6 Hz), 2.31
(6H,s) 13C NMR (100 MHz, CDCl3) δ 141.1, 138.1, 136.8, 135.0, 131.2,
130.5, 129.4, 128.6, 127.7, 126.7, 124.7, 116.9, 81.9, 69.3, 21.4; HRMS
(ES+) calcd for C40H44O2Na [2 M + Na]+ 579.3239, found 579.3209.
(E)-1-(Allyloxy)-1-(2-naphthyl)-3-phenylprop-2-ene (11n).
The title compound was prepared according to general procedure C
from (E)-1-(4-methoxyphenyl)-3-phenylprop-2-en-1-ol77 (463 mg,
1.93 mmol) using allyl bromide (0.33 mL, 3.86 mmol) and NaH
(60% suspension in mineral oil; unwashed) (155 mg, 3.86 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (2% EtOAc in hexane) to afford 11j (448 mg, 83%) as
a colorless oil: Rf (10% EtOAc in hexane) = 0.3; IR νmax (thin film)/cm−1
2835, 1610, 1511, 1248, 830, 693; 1H NMR (400 MHz, CDCl3) δ 7.38−
7.19 (7H, m), 6.90−6.88 (2H, m), 6.59 (1H, d, J = 16.0 Hz), 6.30 (1H,
dd, J = 16.0, 6.8 Hz), 5.96 (1H, ddd, J = 17.2, 10.4, 5.2) 5.30 (1H, ddd,
J = 17.2, 1.6), 5.19 (1H, ddd, J = 10.4, 1.2 Hz), 4.94 (1H, d, J = 6.8 Hz),
4.04 (1H, ddd, J = 12.8, 5.2, 1.6 Hz), 3.98 (1H, ddd, J = 13.2, 5.6, 1.6 Hz)
3.80 (3H, s); 13C NMR (100 MHz, CDCl3) δ 159.2, 136.7, 135.0, 133.3,
131.1, 130.5, 128.5, 128.2, 127.7, 126.6, 116.9, 114.0, 81.3, 69.2, 55.3;
HRMS calcd for C19H21O2 [M + H]+ 281.1542, found 281.1533.
(E)-1-(Allyloxy)-1-(4-fluorophenyl)-3-phenylprop-2-ene (11k).
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Article
The title compound was prepared according to general procedure C
from (E)-1-(naphthalen-2-yl)-3-phenylprop-2-en-1-ol79 (203 mg,
0.78 mmol) using allyl bromide (0.13 mL, 1.56 mmol) and NaH
(60% suspension in mineral oil; unwashed) (63.0 mg, 1.56 mmol).
The crude product was applied directly onto the top of a column and
chromatographed (1% EtOAc in hexane) to afford 11n (154 mg, 66%)
as a light yellow oil: Rf (20% EtOAc in hexane) = 0.91; IR νmax (thin
The crude product was applied directly onto the top of a column and
chromatographed (20% EtOAc in hexane) to afford 11q (174 mg,
84%) as a light yellow oil: Rf (50% Et2O in hexane) = 0.22 ; IR
1
νmax (thin film)/cm−1 2855, 1577, 1423, 1071, 750, 714; H NMR
(400 MHz, CDCl3) δ 8.65 (1H, s), 8.55−8.54(1H, m), 7.76−7.73
(1H, m), 7.40−7.23 (6H, m), 6.65 (1H, d, J = 16.0 Hz), 6.26 (1H, dd,
J = 16.4, 7.2 Hz), 5.97 (1H, ddt, J = 17.2, 10.0, 6.0 Hz), 5.32 (dq, 1H,
J = 17.6, 1.6 HZ), 5.23 (1H, dq, J = 10.4, 1.2 Hz), 5.03 (1H, d, J = 7.2
Hz), 4.11 (1H, ddt, J = 12.8, 5.6, 1.6 Hz) 4.03 (1H, ddt, J = 13.2, 5.6,
1.2 Hz); 13C NMR (100 MHz, CDCl3) δ 149.2, 148.7, 136.7, 136.2,
134.4, 134.4, 132.5, 129.2, 128.6, 128.1, 126.7, 123.5, 117.3, 79.5, 69.4;
HRMS (ES+) calcd for C17H18NO [M + H]+ 252.1388, found
252.1386.
1
film)/cm−1 2924, 1071, 819, 748, 692, 478; H NMR (400 MHz,
CDCl3) δ 7.85−7.83 (4H, m), 7.54−7.20 (8H, m), 6.66 (1H, d, J =
15.6 Hz), 6.38 (1H, dd, J = 16.0, 6.8 Hz), 6.00 (1H, ddd, J = 17.2, 10.4,
5.6 Hz), 5.33 (1H, ddd, 1H, J = 17.2, 2.1, 1.8 Hz), 5.22 (1H, ddd, 1H,
J = 10.1, 1.2, 1.2 Hz), 5.16 (1H, d, J = 6.8 Hz), 4.10 (1H, ddd, J = 12.4,
5.8, 1.2 Hz), 4.01 (1H, ddd, J = 13.2, 5.4, 1.2 Hz) 13C NMR (100
MHz, CDCl3) δ 138.6, 136.6, 134.8, 133.4, 133.1, 131.6, 130.2, 128.5,
128.4, 128.0, 127.7, 127.7, 126.6, 126.1, 125.9, 125.8, 125.0, 117.0,
81.8, 69.4; HRMS (ES+) calcd for C22H21O [M + H]+ 301.1592,
found 301.1576.
1,3-Diphenylhex-5-en-1-one (13a).
(E)-1-(Allyloxy)-1-(o-bromo)-3-phenylprop-2-ene (11o).
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1,3-diphenylprop-2-ene (11a) (170 mg, 0.68 mmol)
using 18-crown-6 (360 mg, 136 mmol) and potassium tert-butoxide
(153 mg, 1.36 mmol). The crude product was applied directly onto the
top of a column and chromatographed (1% Et2O in hexane) to afford
13a (132 mg, 78%) as a colorless oil: Rf (2% Et2O in hexane) = 0.25;
1H NMR (400 MHz, CDCl3) δ 7.90−7.88 (2H, m), 7.54−7.51 (1H,
m), 7.44−7.40 (2H, m), 7.30−7.15 (5H, m), 5.69 (1H, ddd, J = 17.2,
10.0, 7.2 Hz), 5.02−4.94 (2H, m), 3.51−3.44 (1H, m), 3.34−3.24
(2H, m), 2.52−2.40 (2H, m) 13C NMR (100 MHz, CDCl3) δ 198.9,
144.4, 137.3, 136.3, 132.9, 128.5, 128.4, 128.0, 127.6, 126.4, 116.8,
44.6, 40.8, 40.7. Characterization in accordance with literature data.81
1-Phenyl-3-(4-methylphenyl)hex-5-en-1-one (13b).
The title compound was prepared according to general procedure C
from (E)-1-(2-bromophenyl)-3-phenylprop-2-en-1-ol80 (238 mg, 0.82
mmol) using allyl bromide (0.14 mL, 1.64 mmol) and NaH (60%
suspension in mineral oil; unwashed) (66.0 mg, 1.64 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (1% EtOAc in hexane) to afford 11o (220 mg, 81%)
as a colorless oil: Rf (10% EtOAc in hexane) = 0.67; IR νmax (thin
1
film)/cm−1 2924, 1438, 1071, 965, 748, 693; H NMR (400 MHz,
CDCl3) δ 7.59 (1H, dd, J = 7.6, 1.6 Hz), 7.54 (1H, dd, J = 7.6, 0.8 Hz),
7.38−7.12 (m, 7H), 6.69 (d, 1H, J = 15.6 Hz), 6.22 (dd, 1H, J = 16.0,
6.8 Hz), 5.97 (1H, ddd, J = 17.2, 10.4, 5.6 Hz), 5.42 (1H, d, J = 6.8
Hz), 5.32 (1H, ddd, J = 17.2, 3.5, 1.5 Hz), 5.21 (1H, ddd, J = 10.4, 3.1,
1.2 Hz), 4.08−3.99 (2H, m) 13C NMR (100 MHz, CDCl3) δ 140.3,
136.6, 134.6, 132.8, 131.7, 129.1, 128.5, 128.5, 128.4, 127.9, 127.8,
126.7, 123.2, 117.2, 80.0, 69.6; HRMS (ES+) calcd for C18H18BrO
[M + H]+ 329.0541, found 329.0556.
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-phenyl-3-(4-methylphenyl)prop-2-ene (11b)
(58.5 mg, 0.22 mmol) using 18-crown-6 (116 mg, 0.44 mmol) and
potassium tert-butoxide (49.0 mg, 0.44 mmol). The crude product was
applied directly onto the top of a column and chromatographed (1%
Et2O in 60:40 petroleum ether) to afford 13b (45.0 mg, 77%) as a
colorless oil: Rf (4% Et2O in 60:40 petroleum ether) = 0.43; IR νmax
(E)-1-(Allyloxy)-1-(o-tolyl)-3-phenylprop-2-ene (11p).
1
(thin film)/cm−1 2921, 1686, 1515, 1448, 815, 690; H NMR (400
The title compound was prepared according to general procedure C
from (E)-3-phenyl-1-(o-tolyl)prop-2-en-1-ol (S7) (442 mg, 1.97 mmol)
using allyl bromide (0.34 mL, 3.94 mmol) and NaH (60% suspension
in mineral oil; unwashed) (158 mg, 3.94 mmol). The crude product
was applied directly onto the top of a column and chromatographed
(1% EtOAc in 60:40 petroleum ether) to afford 11p (466 mg, 90%) as
a light yellow oil: Rf (10% EtOAc in 60:40 petroleum ether) = 0.85; IR
MHz, CDCl3) δ 7.90−7.88 (2H, m), 7.55−7.50 (1H, m), 7.44−7.40
(2H, m), 7.13−7.07 (4H, m), 5.69 (ddd, 1H, J = 17.2, 12.8, 6.8 Hz),
5.02−4.94 (2H, m), 3.47−3.40 (1H, m), 3.32−3.21 (2H, m), 2.50−
2.38 (2H, m), 2.29 (3H, s) 13C NMR (100 MHz, CDCl3) δ 199.0,
141.3, 137.3, 136.4, 135.8, 132.9, 129.1, 128.5, 128.1, 127.4, 116.7,
44.7, 40.8, 40.4, 21.0; HRMS (ES+) calcd for C19H21O [M + H]+
265.1592, found 265.1594. Characterization in accordance with
literature data.82
1
νmax (thin film)/cm−1 2925, 1449, 1276, 1071, 967, 750; H NMR
(400 MHz, CDCl3) δ 7.51−7.49 (1H, m), 7.38−7.35 (2H, m), 7.30−
7.14 (6H, m) 6.56 (1H, d, J = 16.2 Hz), 6.27 (1H, dd, J = 16.0, 5.6
Hz), 5.97 (1H, ddd, J = 17.2, 10.6, 5.6 Hz), 5.30 (1H, ddd, 1H, J =
17.4, 3.3, 1.6 Hz), 5.20 (1H, ddd, 1H, J = 10.4, 3.0, 1.3 Hz), 5.16 (1H,
d, J = 7.0 Hz), 4.06−3.98 (2H, m), 2.36 (3H, s); 13C NMR (100 MHz,
CDCl3) δ 138.9, 136.7, 135.7, 134.9, 131.4, 130.5, 129.3, 128.5, 127.7,
127.5, 126.7, 126.6, 126.3, 117.0, 78.8, 69.3, 19.3; HRMS (ES+) calcd
for C19H21O [M + H]+ 265.1592, found 265.1561.
1-Phenyl-3-(4-methoxyphenyl)hex-5-en-1-one (13c).
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-phenyl-3-(4-methoxyphenyl)prop-2-ene 11c
(64.0 mg, 0.32 mmol) using 18-crown-6 (122 mg, 0.46 mmol) and
potassium tert-butoxide (52.0 mg, 0.46 mmol). The crude product was
applied directly onto the top of a column and chromatographed (4%
Et2O in hexane) to afford 13c (47.6 mg, 74%) as a light yellow oil: Rf
(8% Et2O in hexane) = 0.33: IR νmax (thin film)/cm−1 2920, 1248,
(E)-1-(Allyloxy)-1-(pyridin-3-yl)-3-phenylprop-2-ene (11q).
1
The title compound was prepared according to general procedure C
from (E)-3-phenyl-1-(pyridin-3-yl)prop-2-en-1-ol S9 (172 mg,
0.82 mmol) using allyl bromide (0.14 mL, 1.64 mmol) and NaH
(60% suspension in mineral oil; unwashed) (66.0 mg, 1.64 mmol).
1179, 1685, 1036, 1513; H NMR (400 MHz, CDCl3) δ 7.90−7.87
(2H, m), 7.54−7.51 (1H, m), 7.44−7.40 (2H, m), 7.16−7.13 (2H, m),
6.83−6.80 (2H, m), 5.69 (1H, ddd, J = 17.2, 10.0, 6.8 Hz), 5.02−4.95
(2H, m), 3.76 (3H, s), 3.46−3.39 (1H, m), 3.31−3.20 (2H, m),
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2.49−2.37 (2H, m) 13C NMR (100 MHz, CDCl3) δ 199.1, 158.0,
137.3, 136.4, 136.4, 132.9, 128.5, 128.5. 128.0, 116.7, 113.8, 55.2, 44.8,
40.9, 40.1; HRMS (ES+) calcd for C19H 21O2 [M + H]+ 281.1542,
found 281.1544. Characterization in accordance with literature data.82b
1-Phenyl-3-(4-fluorophenyl)hex-5-en-1-one (13d).
1-Phenyl-3-(pyridin-3-yl)hex-5-en-1-one (13g).
The title compound was prepared according to general procedure F from
(E)-1-(allyloxy)-1-phenyl-3-(pyridin-3-yl)prop-2-ene (11g) (52.3 mg,
0.21 mmol) using 18-crown-6 (111 mg, 0.42 mmol) and potassium tert-
butoxide (47.0 mg, 0.42 mmol). The crude product was applied directly
onto the top of a column and chromatographed (50% Et2O in hexane) to
afford 13g (21.1 mg, 40%) as a yellow oil: Rf (50% Et2O in hexane) =
0.18; IR νmax (thin film)/cm−1 2923, 1685, 1448, 1426, 715, 690; 1H NMR
(400 MHz, CDCl3) δ 8.58−8.53 (2H, m), 7.90−7.88 (2H, m), 7.58−7.42
(4H, m), 7.23−7.20 (1H, m), 5.68 (1H, ddt, J = 17.2, 10.0, 7.2 Hz), 5.04−
4.99 (2H, m), 3.55−3.48 (1H, m), 3.40−3.27 (2H, m), 2.55−2.41 (2H,
m);13C NMR (100 MHz, CDCl3) δ 198.2, 149.5, 147.9, 136.9, 135.4,
135.2, 133.2, 128.7, 128.0, 123.4, 117.6, 44.0, 40.1, 38.3; HRMS (ES+)
calcd for C17H17ONNa [M + Na]+ 274.1208, found 274.1200.
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-phenyl-3-(4-fluorophenyl)prop-2-ene (11d)
(67.0 mg, 0.25 mmol) using 18-crown-6 (132 mg, 0.50 mmol) and
potassium tert-butoxide (56.0 mg, 0.50 mmol). The crude product was
applied directly onto the top of a column and chromatographed (2%
Et2O in hexane) to afford 13d (50.3 mg, 75%) as a colorless oil: Rf
(4% Et2O in hexane) = 0.21; IR νmax (thin film)/cm−1 2921, 1684,
1448, 1001, 796, 778; 1H NMR (400 MHz, CDCl3) δ 7.89−7.87 (2H,
m), 7.56−7.52 (1H, m), 7.45−7.41 (2H, m), 7.20−7.17 (2H, m),
6.98−6.93 (2H, m), 5.67 (1H, ddd, J = 17.2, 10.0, 7.2 Hz), 5.02−4.96
(2H, m), 3.50−3.43 (1H, m), 3.32−3.21 (2H, m), 2.50−2.37 (2H, m)
13C NMR (100 MHz, CDCl3) δ 198.8, 161.4 (d, JC−F = 243.0 Hz),
140.0 (d, JC−F = 3.0 Hz), 137.2, 136.0, 133.0, 129.0 (d, JC−F = 8.0 Hz),
128.6, 128.0, 117.0, 115.2 (d, JC−F = 21.0 Hz), 44.6, 40.8, 40.1; HRMS
(ES+) calcd for C18H18FO [M + H]+ 269.1342, found 269.1331.
1-Phenyl-3-(4-trifluoromethyoxyphenyl)hex-5-en-1-one (13e).
1-Phenyl-3-(2-fluoropyridin-5-yl)hex-5-en-1-one (13h).
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-phenyl-3-(2-fluoropyridine-5-yl)prop-2-ene
(11h) (45.0 mg, 0.17 mmol) using 18-crown-6 (90.0 mg,
0.34 mmol) and potassium tert-butoxide (38.2 mg, 0.34 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (10% EtOAc in hexane) to afford 13h (11.0 mg,
25%) as a light yellow oil: Rf (10% Et2O in hexane) = 0.21; IR νmax
1
(thin film)/cm−1 2926, 1687, 1598, 1233, 1015, 700; H NMR (400
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-phenyl-3-(4-trifluoromethoxyphenyl)prop-2-
ene (11e) (40.0 mg, 0.13 mmol) using 18-crown-6 (69.0 mg,
0.26 mmol) and potassium tert-butoxide (29 mg, 0.26 mmol). The
crude product was applied directly onto the top of a column and
chromatographed (4% Et2O in hexane) to afford 13e (28.0 mg, 70%)
as a yellow oil: Rf (4% Et2O in hexane) = 0.16; IR νmax (thin film)/
cm−1 2926, 1687, 1598, 1233, 1015, 700; 1H NMR (400 MHz,
CDCl3) δ 7.90−7.87 (1H, m), 7.56−7.50 (1H, m), 7.45−7.41 (2H,
m), 7.36−7.10 (5H, m), 5.67 (1H, ddd, J = 17.2, 10.0, 6.8 Hz), 5.03−
4.97 (2H, m), 3.54−3.47 (1H, m), 3.34−3.22 (2H, m), 2.51−2.39
(2H, m) 13C NMR (100 MHz, CDCl3) δ 198.5, 147.9 (q, JC−F = 245.6
Hz) 143.1, 137.1, 135.8, 133.1, 128.9, 128.6, 128.0, 127.8, 120.9, 117.2,
MHz, CDCl3) δ 8.09 (1H, d, J = 2.0 Hz), 7.88 (2H, dd, J = 7.3, 1.3
Hz), 7.67 (1H, td, J = 8.0, 2.5 Hz), 7.58−7.53 (1H, m), 7.44 (2H, t, J =
7.8 Hz), 6.85 (1H, dd, J = 8.3, 2.8 Hz), 5.67 (1H, ddd, J = 16.3, 10.5,
7.3 Hz), 5.03 (1H, br d, J = 1.0 Hz), 5.01−4.99 (1H, m), 3.56−3.49
(1H, m), 3,36 (1H, dd, J = 17.0, 5.8 Hz), 3.27 (1H, dd, J = 17.3, 8.3
Hz), 2.54−2.39 (2H, m); 13C NMR (100 MHz, CDCl3) δ 198.1, 162.5
(d, JC−F = 237.6 Hz), 146.7 (d, JC−F = 14.7 Hz), 140.4 (d, JC−F = 7.7
Hz), 137.3 (d, JC−F = 4.1 Hz), 135.2, 133.3, 128.7, 128.0, 117.8, 109.4,
108.9, 44.3, 39.8, 37.2; HRMS (ES+) calcd for C17H16ONF [M + H]+
270.1294, found 270.1305.
1-(4-Methylphenyl)-3-phenylhex-5-en-1-one (13i).
44.4, 40.7, 40.1; HRMS (ES+) calcd for C19H17F O2Na [M + Na]+
3
357.1078, found 357.1077.
1-Phenyl-3-(2-naphthyl)-hex-5-en-1-one (13f).
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-(4-methylphenyl)-3-phenylprop-2-ene (11i)
(58.0 mg, 0.22 mmol) using 18-crown-6 (116 mg, 0.44 mmol) and
potassium tert-butoxide (49.0 mg, 0.44 mmol). The crude product was
applied directly onto the top of a column and chromatographed (2%
Et2O in hexane) to afford 13i (41.8 mg, 72%) as a colorless oil: Rf (4%
Et2O in hexane) = 0.16; IR νmax (thin film)/cm−12923, 1682, 1468,
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-phenyl-3-(2-naphthyl)prop-2-ene (11f) (59.7
mg, 0.195 mmol) using 18-crown-6 (103 mg, 0.39 mmol) and
potassium tert-butoxide (44.0 mg, 0.39 mmol). The crude product was
applied directly onto the top of a column and chromatographed (1%
Et2O in hexane) to afford 13f (44.0 mg, 74%) as a yellow oil: Rf (4%
Et2O in hexane) = 0.40; IR νmax (thin film)/cm−1 2921, 1684, 1597,
1448, 1001, 778; 1H NMR (400 MHz, CDCl3) δ 8.24−8.22 (1H, m),
7.93−7.91 (2H, m), 7.86−7.84 (1H, m), 7.73−7.70 (1H, m), 7.55−
7.41 (7H, m), 5.72 (1H, ddd, J = 17.2, 10.4, 6.8 Hz) 5.04−4.91 (2H,
m), 4.50−4.43 (1H, m), 3.48 (1H, dd, J = 16.8, 7.6 Hz), 3.38 (1H, dd,
J = 17.4, 5.6 Hz), 2.68−2.57 (2H, m) 13C NMR (100 MHz, CDCl3) δ
198.9, 140.4, 137.3, 136.2, 134.0, 133.0, 131.7, 129.0, 128.6, 128.1,
126.9, 126.1, 125.5, 125.3, 125.3, 123.5, 123.4, 116.9, 44.3,
40.0; HRMS (ES+) calcd for C22H 21O [M + H]+ 301.1592, found
301.1601.
1
1124, 821, 700; H NMR (400 MHz, CDCl3) δ 7.81−7.79 (2H, m),
7.34−7.15 (7H, m), 5.68 (1H, ddd, J = 16.8, 10.0, 6.8 Hz), 5.01−4.93
(2H, m), 3.50−3.43 (1H, m), 3.31−3.20 (2H, m), 2.51−2.41 (2H, m),
2.39 (3H, s); 13C NMR (100 MHz, CDCl3) δ 198.6, 144.5, 143.7,
136.3, 134.8, 129.2, 128.4, 128.2, 127.6, 126.4, 116.7, 44.5, 40.8, 40.7,
21.7; HRMS (ES+) calcd for C19H21O [M + H]+ 265.1592, found
265.1595.
1-(4-Methoxyphenyl)-3-phenylhex-5-en-1-one (13j).
1490
DOI: 10.1021/jo502403n
J. Org. Chem. 2015, 80, 1472−1498

The Journal of Organic Chemistry
Article
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-(4-methoxyphenyl)-3-phenylprop-2-ene (11j)
(76.4 mg, 0.27 mmol) using 18-crown-6 (143 mg, 0.54 mmol) and
potassium tert-butoxide (65.3 mg, 0.54 mmol). The crude product was
applied directly onto the top of a column and chromatographed (10%
Et2O in hexane) to afford 13j (54.2 mg, 71%) as a colorless oil:Rf
(10% Et2O in hexane) = 0.40; IR νmax (thin film)/cm−1 2924, 1586,
Et2O in hexane) = 0.40; IR νmax (thin film)/cm−1 2926, 1687, 1598,
1233, 1015, 700; H NMR (400 MHz, CDCl3) δ 7.49 (2H, s), 7.29−
7.15 (6H, m), 5.68 (1H, ddt, J = 17.2, 10.4, 7.2 Hz), 5.02−4.93 (2H,
m) 3.50−3.43 (1H, m), 3.30−3.20 (2H, m), 2.51−2.39 (2H, m), 2.33
(6H, s); 13C NMR (100 MHz, CDCl3) δ 199.3, 144.5, 138.2, 137.4,
136.4, 134.6, 128.4, 127.6, 126.4, 125.9, 116.7, 44.7, 40.8, 40.6, 21.3;
HRMS (ES+) calcd for C20H23O [M + H]+ 279.1749, found 279.1744.
1-(2-Naphthyl)-3-phenylhex-5-en-1-one (13n).
1
1
1255, 834, 750, 700; H NMR (400 MHz, CDCl3) δ 7.90−7.86 (2H,
m), 7.29−7.15 (5H, m), 6.91−6.88 (2H, m), 5.68 (1H, ddd, J = 17.2,
10.0, 6.8 Hz), 5.01−4.93 (2H, m), 3.85 (3H, s), 3.49−3.42 (1H, m),
3.28−3.18 (2H, m), 2.51−2.39 (2H, m) 13C NMR (100 MHz, CDCl3)
δ 197.5, 163.4, 144.5, 136.4, 130.4, 130.3, 128.4, 127.6, 126.3, 116.7,
113.7, 55.5, 44.3, 41.0, 40.7; HRMS (ES) calcd for C19H21O2
[M + H]+ 281.1542, found 281.1534.82a
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-(2-naphthyl)-3-phenylprop-2-ene 11n (63.4 mg,
0.21 mmol) using 18-crown-6 (111 mg, 0.42 mmol) and potassium tert-
butoxide (47.0 mg, 0.42 mmol). The crude product was applied directly
onto the top of a column and chromatographed (2% Et2O in hexane) to
afford 13n (44.0 mg, 69%) as a yellow oil: Rf (4% Et2O in hexane) =
1-(4-Fluorophenyl)-3-phenylhex-5-en-1-one (13k).
1
0.40; IR νmax (thin film)/cm−1 2922, 1682, 1607, 1180, 808, 700; H
NMR (400 MHz, CDCl3) δ 8.41−8.38 (1H, m), 7.98−7.92 (2H, m),
7.87−7.84 (2H, m), 7.60−7.52 (2H, m), 7.32−7.16 (5H, m), 5.72 (1H,
ddd, J = 17.2, 10.2, 7.0 Hz), 5.05−4.96 (2H, m), 3.57−3.50 (1H, m),
3.43−3.41 (2H, m), 2.57−2.45 (2H, m); 13C NMR (100 MHz, CDCl3)
δ 198.9, 144.4, 136.3, 135.5, 134.6, 132.5, 129.7, 129.6, 128.5, 128.4,
128.4, 127.8, 127.6, 126.8, 126.4, 123.9, 116.8, 44.7, 41.0, 40.7; HRMS
(ES) Calcd for C22H21O [M + H]+ 301.1592, found 301.1576.
2-Benzyl-1-phenylpent-4-en-1-one (14a).
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-(4-fluorophenyl)-3-phenylprop-2-ene (11k)
(52.6 mg, 0.20 mmol) using 18-crown-6 (106 mg, 0.40 mmol) and
potassium tert-butoxide (45.0 mg, 0.40 mmol). The crude product was
applied directly onto the top of a column and chromatographed (2%
Et2O in hexane) to afford 13k (49.1 mg, 74%) as a colorless oil: Rf (4%
1
Et2O in hexane) = 0.30; H NMR (400 MHz, CDCl3) δ 7.92−7.89
(2H, m), 7.29−7.15 (5H, m), 7.10−7.06 (2H, m), 5.69 (1H, ddd, J =
17.2, 10.4, 6.8 Hz), 5.03−4.95 (2H, m), 3.49−3.42 (1H, m), 3.26−
3.24 (2H, m), 2.48−2.44 (2H, m) 13C NMR (100 MHz, CDCl3) δ
197.3, 165.7 (d, JC−F = 223 Hz), 144.2, 136.2, 133.7 (d, JC−F = 4.0 Hz),
130.6 (d, JC−F = 9.0 Hz), 128.5, 127.6, 126.5, 116.9, 115.6 (d, JC−F = 22
Hz), 44.5, 40.9, 40.7; HRMS (ES) Calcd for C18H18OF [M + H]+
269.1342, found 269.1349.
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1,3-diphenylprop-2-ene (11a) (143 mg, 0.57 mmol)
using potassium tert-butoxide (33.0 mg, 0.29 mmol). The crude product
was applied directly onto the top of a column and chromatographed (2%
Et2O in hexane) to afford 14a (103 mg, 72%) as a colorless oil: Rf (4%
Et2O in hexane) = 0.42; 1H NMR (400 MHz, CDCl3) δ 7.85−7.83 (2H,
m), 7.52−7.49 (1H, m), 7.42−7.38 (2H, m), 7.24−7.12 (5H, m), 5.73
(ddd, 1H, J = 17.2, 10.0, 7.0), 5.04−4.97 (2H, m), 3.83−3.76 (1H, m),
3.10 (1H, dd, J = 13.6, 7.6 Hz), 2.81 (1H, dd, J = 14.0, 6.6 Hz), 2.57−2.50
(1H, m), 2.33−2.26 (1H, m); 13C NMR (100 MHz, CDCl3) δ 203.0,
139.7, 137.3, 135.3, 132.9, 129.1, 128.6, 128.4, 128.2, 126.3, 117.2, 48.1,
37.7, 36.3. Characterization in accordance with literature data.83
1-(3-Fluorophenyl)-3-phenylhex-5-en-1-one (13l).
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-(3-fluorophenyl)-3-phenylprop-2-ene (11l)
(59.0 mg, 0.22 mmol) using 18-crown-6 (116 mg, 0.44 mmol) and
potassium tert-butoxide (50.0 mg, 0.44 mmol). The crude product was
applied directly onto the top of a column and chromatographed (2%
Et2O in hexane) to afford 13l (41.0 mg, 70%) as a colorless oil: Rf (4%
Et2O in hexane) = 0.33; IR νmax (thin film)/cm−1 2925, 1690, 1589,
1443, 1249, 700; 1H NMR (400 MHz, CDCl3) δ 7.67−7.65 (1H, m),
7.57−7.54 (1H, m), 7.42−7.37 (1H, m), 7.30−7.15 (6H, m), 5.69
(1H, ddd, J = 17.2, 10.4, 6.8 Hz), 5.03−4.95 (2H, m), 3.50−3.42 (1H,
m), 3.31−3.21 (2H, m), 2.48−2.44 (2H, m) 13C NMR (100 MHz,
2-Allyl-1-phenyl-3-(p-toyl)prop-1-one (14b).
Potassium tert-butoxide (14.0 mg, 0.12 mmol) was added to a THF
solution (1.8 mL) of (E)-1-(allyloxy)-1-phenyl-3-(4-methylphenyl)-
prop-2-ene (11b) (60.0 mg, 0.23 mmol) in a dry, argon-purged sealed
tube flask at room temperature. The reaction heated to 130 °C and
allowed to stir for 16 h. After quenching with distilled water (10 mL)
and extraction (2 × 25 mL EtOAc), the organic layer was washed with
distilled water (25 mL) and brine (25 mL), dried over MgSO4, and
concentrated in vacuo. The crude mixture was applied directly onto
the top of a column and chromatographed (2% Et2O in hexane) to
afford 5i (41.0 mg, 68%) as a yellow oil: Rf (4% Et2O in hexane) =
CDCl3) δ 197.7 (d, J
= 2.0 Hz), 162.8 (d, JC−F = 247 Hz), 144.1,
C−F
139.3 (d, JC−F = 6.0 Hz), 136.2, 130.2 (d, JC−F = 7.0 Hz), 128.5, 127.5,
126.5, 123.7 (d, JC−F = 3.0 Hz), 119.9 (d, JC−F = 21.0 Hz), 116.9,
114.8 (d, JC−F = 22.0 Hz), 44.7, 40.8, 40.7; HRMS (ES) calcd for
C18H17FNaO [M + Na]+ 291.1161, found 291.1174.
1-(3,5-Dimethylphenyl)-3-phenylhex-5-en-1-one (13m).
1
0.24; IR νmax (thin film)/cm−1 2924, 1684, 1448, 1001, 915, 753; H
NMR (400 MHz, CDCl3) δ 7.83−7.77 (2H, m), 7.47−7.42 (1H, m),
7.36−7.32 (2H, m), 7.06−6.97 (4H, m), 5.70−5.56 (1H, m), 4.96−
4.87 (2H, m), 3.73−3.66 (1H, m), 2.99 (1H, dd, J = 14.0, 7.2 Hz),
2.68 (1H, dd, J = 14.0, 6.8 Hz), 2.48−2.41 (1H, m), 2.27−2.21 (1H,
m), 2.21 (3H, s); 13C NMR (100 MHz, CDCl3) δ 203.4, 141.3, 137.3,
136.5, 135.7, 135.4, 132.9, 129.1, 129.0, 128.6, 128.2, 48.1, 37.2, 36.2,
21.0; HRMS(ES+) calcd for C19H21O [M + H]+ 265.1592, found
265.1563.
The title compound was prepared according to general procedure F
from (E)-1-(allyloxy)-1-(3,3-dimethylphenyl)-3-phenylprop-2-ene (11m)
(86.0 mg, 0.32 mmol) using 18-crown-6 (169 mg, 0.64 mmol) and
potassium tert-butoxide (72.0 mg, 0.64 mmol). The crude product was
applied directly onto the top of a column and chromatographed (2%
Et2O in hexane) to afford 13m (59.2 mg, 69%) as a clear oil: Rf (4%
1491
DOI: 10.1021/jo502403n
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The Journal of Organic Chemistry
Article
2-Allyl-1-phenyl-3-(4-methoxyphenyl)prop-1-one (14c).
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1-phenyl-3-(2-fluoropyridine-5-yl)prop-2-ene
(11h) (68.0 mg, 0.25 mmol) using potassium tert-butoxide (14.0 mg,
0.125 mmol). The crude product was applied directly onto the top of a
column and chromatographed (5% EtOAc in hexane) to afford 14h
(26.0 mg, 38%) as a yellow oil: Rf (5% Et2O in hexane) = 0.22; IR νmax
1
(thin film)/cm−1; 2926, 1680, 1596, 1488, 1250, 831; H NMR (400
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1- phenyl-3-(4-methoxyphenyl)prop-2-ene
(11c) (48.0 mg, 0.17 mmol) using potassium tert-butoxide
(10.0 mg, 0.085 mmol). The crude product was applied directly
onto the top of a column and chromatographed (4% Et2O in hexane)
to afford 14c (41.8 mg, 87%) as a colorless oil: Rf (8% Et2O in hexane)
= 0.36; IR νmax (thin film)/cm−1 2921, 1681, 1513, 1247, 1036, 700;
1H NMR (400 MHz, CDCl3) δ 7.86−7.83 (2H, m), 7.53−7.50 (1H,
m), 7.43−7.39 (2H, m), 7.09−7.07 (2H, m), 6.78−6.76 (2H, m), 5.73
(1H, ddt, J = 17.2, 10.4, 7.2 Hz), 5.04−4.97 (2H, m), 3.74 (4H, m),
3.04 (1H, dd, J = 14.0, 7.6 Hz), 2.75 (1H, dd, J = 14.0, 6.4 Hz), 2.55−
2.48 (1H, m), 2.32−2.25 (1H, m); 13C NMR (100 MHz, CDCl3) δ
203.2, 158.1, 137.3, 135.4, 132.4, 131.7, 130.0, 128.6, 128.2, 117.1,
113.8, 55.2, 48.3, 36.8, 36.2; HRMS (ES+) calcd for C19H21O2 [M +
H]+ 281.1542, found 281.1545.84
MHz, CDCl3) δ 8.04−8.02 (1H, m), 7.84−7.82 (2H, m), 7.59−7.52
(2H, m), 7.45−7.41 (2H, m), 6.77 (1H, dd, J = 8.0, 2.8 Hz), 5.75 (1H,
ddd, J = 17.2, 10.8, 6.8 Hz), 5.09−5.05 (2H, m), 3.80−3.73 (1H, m),
3.11 (1H, dd, J = 14.0, 8.8 Hz), 2.84 (1H, dd, J = 14.0, 5.6 Hz), 2.57−
2.50 (1H, m), 2.34−2.27 (1H, m); 13C NMR (100 MHz, CDCl3) δ
202.0, 162.4 (d, JC−F = 236.0 Hz), 147.7 (d, JC−F = 14.0 Hz), 141.8 (d,
JC−F = 7.0 Hz), 136.8, 134.5, 133.3, 132.8 (d, JC−F = 5.0 Hz), 128.8,
128.2, 117.9, 109.1 (d, JC−F = 37.0 Hz), 47.7 (d, JC−F = 1.0 Hz), 36.7,
33.2 (d, JC−F = 2.0 Hz); HRMS calcd for C17H17NOF [M + H]+
270.1294, found 270.1298.
2-Benzyl-1-(4-methylphenyl)pent-4-en-1-one (14i).
2-Allyl-1-phenyl-3-(4-methoxyphenyl)prop-1-one (14d).
Potassium tert-butoxide (9.0 mg, 0.08 mmol) was added to a THF
solution (1.3 mL) of (E)-1-(allyloxy)-1-(4-methylphenyl)-3-phenyl-
prop-2-ene (11i) (42.8 mg, 0.16 mmol) in a dry, argon-purged 10 mL
round-bottom flask at room temperature. The reaction heated to
80 °C and allowed to stir for 16 h. The reaction was quenched with
distilled water (10 mL) and extracted with EtOAc (2 × 25 mL), and
the combined organic phases were washed with distilled water
(25 mL) and brine (25 mL), dried over MgSO4 and concentrated in
vacuo. The crude mixture was applied directly onto the top of a
column and chromatographed (2% Et2O in hexane) to afford 14i
(28.0 mg, 65%) as a yellow oil: Rf (4% Et2O in hexane) = 0.27; IR νmax
(thin film)/cm−1 3028, 2921, 1701, 1606, 1494, 1453, 1238, 1180, 917,
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1- phenyl-3-(4-fluorophenyl)prop-2-ene (11d)
(45.5 mg, 0.17 mmol) using potassium tert-butoxide (0.095 mg, 0.085
mmol). The crude product was applied directly onto the top of a
column and chromatographed (2% Et2O in hexane) to afford 14d
1
(43.0 mg, 96%) as a yellow oil: Rf (4% Et2O in hexane) = 0.22 H
NMR (400 MHz, CDCl3) δ 7.87 (2H, m), 7.23−7.19 (2H, m), 7.16−
7.12 (3H, m), 7.08−7.02 (2H, m), 5.72 (1H, ddd, J = 17.1, 10.0, 7.0
Hz), 5.05−4.97 (2H, m), 3.74 (1H, ddd, J = 13.8, 6.3, 6.0 Hz), 3.07
(1H, dd, J = 13.6, 7.8 Hz), 2.82(1H, dd, J = 13.6, 6.3 Hz), 2.52 (1H,
dddd, J = 13.1, 7.0, 6.0, 1.3 Hz), 2.30 (1H, dddd, J = 13.1, 7.0, 6.0, 1.3
Hz); 13C NMR (100 MHz, CDCl3) δ 201.5, 165.8 (d, JC−F = 254.9
Hz), 139.5, 135.1, 133.7 (d, JC−F = 2.9 Hz), 130.8 (d, JC−F = 10.0 Hz),
129.0, 128.4, 126.3, 117.2, 115.6 (d, JC−F =22.0 Hz), 48.0, 37.9, 36.4;
HRMS (ES+) calcd for C18H17OFNa [M + Na]+ 291.1161, found
291.1148
1
824, 752, 699; H NMR (400 MHz, CDCl3) δ 7.77−7.75 (2H, m),
7.27−7.12 (7H, m), 5.73 (1H, ddd, J = 17.2, 10.0, 7.2 Hz), 5.03−4.96
(2H, m), 3.80−3.73 (1H, m), 3.10 (1H, dd, J = 14.0, 8.0 Hz), 2.79
(1H, dd, J = 13.6, 6.4 Hz), 2.56−2.48 (1H, m), 2.37 (3H, s), 2.31−
2.25 (1H, m) 13C NMR (100 MHz, CDCl3) δ 202.5, 143.7, 139.8,
135.4, 134.8, 129.3, 129.1, 128.4, 128.4, 126.2, 117.1, 47.9, 37.7, 36.4,
21.6; HRMS calcd for C19H21O [M + H]+ 265.1592, found 265.1598.
2-Benzyl-1-(4-methoxyphenyl)pent-4-en-1-one (14j).
2-Allyl-1-phenyl-3-(2-naphthyl)prop-1-one (14f).
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1-(4-methoxyphenyl)-3-phenylprop-2-ene 11j
(70.0 mg, 0.25 mmol) using potassium tert-butoxide (14.0 mg, 0.125
mmol). The crude product was applied directly onto the top of a
column and chromatographed (10% Et2O in hexane) to afford 14j
(49.8 mg, 71%) as a colorless oil: Rf (10% Et2O in hexane) = 0.42; IR
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1- phenyl-3-(2-naphthyl)prop-2-ene (11f)
(58.0 mg, 0.19 mmol) using potassium tert-butoxide (11.0 mg, 0.095
mmol). The crude product was applied directly onto the top of a
column and chromatographed (1% Et2O in hexane) to afford 14f
(45.8 mg, 79%) as a yellow oil: Rf (4% Et2O in hexane) = 0.39; IR νmax
1
νmax (thin film)/cm−1 2922, 1671, 1599, 1243, 1170, 750; H NMR
1
(thin film)/cm−1 2922, 1678, 1607, 1454, 1181, 916; H NMR (400
(400 MHz, CDCl3) δ 7.85−7.83 (2H, m), 7.25−7.12 (5H, m), 6.89−
6.86 (2H, m), 5.72 (dtt, 1H, J = 17.2, 10.4, 6.8 Hz), 5.04−4.96 (2H,
m), 3.84 (3H, s), 3.77−3.70 (1H, m), 3.09 (1H, dd, J = 13.6, 7.6 Hz),
2.80 (1H, dd, J = 13.6, 6.4 Hz), 2.56−2.49 (1H, m), 2.32−2,25 (1H,
m) 13C NMR (100 MHz, CDCl3) δ 201.4, 163.4, 139.9, 135.5, 130.5,
130.3, 129.1, 128.4, 126.2, 117.0, 113.7, 55.4, 47.6, 37.9, 36.5; HRMS
(ES+) calcd for C19H21O2 [M + H]+ 281.1542, found 281.1541.
2-Benzyl-1-(4-fluorophenyl)pent-4-en-1-one (14k).
MHz, CDCl3) δ 8.06−8.04 (1H, m), 7.84−7.82 (1H, m), 7.71−7.64
(2H, m), 7.56−7.41 (4H, m), 7.32−7.27 (4H, m), 5.79 (1H ddd, J =
16.8, 10.2, 7.2 Hz), 5.09−5.01 (2H, m), 4.02−3.95 (1H, m), 3.50 (1H,
dd, J = 13.6, 8.0 Hz), 3.35 (1H, dd, J = 14.0, 6.2), 2.66−2.59 (1H, m),
2.41−2.34 (1H, m); 13C NMR (100 MHz, CDCl3) δ 203.4, 137.3,
135.6, 135.2, 134.0, 132.9, 131.9, 129.0, 128.5, 128.1, 127.5, 127.1,
126.0, 125.5, 125.4, 123.5, 117.5, 46.8, 37.0, 34.7; HRMS calcd for
C22H21O [M + H]+ 301.1592, found 301.1594.
2-Allyl-1-phenyl-3-(2-fluoropyridin-3-yl)prop-1-one (14h).
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1-(4-fluorophenyl)-3-phenylprop-2-ene (11k)
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DOI: 10.1021/jo502403n
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(56.0 mg, 0.21 mmol) using potassium tert-butoxide (12.0 mg,
0.105 mmol). The crude product was applied directly onto the top of a
column and chromatographed (2% Et2O in hexane) to afford 14k
(40.0 mg, 71%) as a yellow oil: Rf (4% Et2O in hexane) = 0.31; IR νmax
column and chromatographed (2% Et2O in hexane) to afford 14n
(39.1 mg, 80%) as a colorless oil: Rf (4% Et2O in hexane) = 0.40; IR
1
νmax (thin film)/cm−1 2925, 1375, 1675, 1276, 1186, 917; H NMR
(400 MHz, CDCl3) δ 8.22 (1H, s), 7.88−7.75 (4H, m), 7.52−7.42
(2H, m), 7.21−7.03 (5H, m), 5.70 (1H, ddd, J = 17.2, 10.4, 6.8 Hz),
4.99−4.90 (2H, m), 3.91−3.84 (1H, m), 3.09 (1H, dd, J = 13.6, 8.0
Hz), 2.80 (1H, dd, J = 13.6, 6.8 Hz), 2.56−2.49 (1H, m), 2.32−2.26
(1H, m) 13C NMR (100 MHz, CDCl3) δ 203.0, 139.8, 135.5, 135.3,
134.6, 132.5, 129.8,129.6, 129.1, 128.5, 128.4, 128.4, 127.7, 126.7,
126.3, 124.1, 117.2, 48.2, 37.2, 36.6; HRMS (ES+) calcd for C22H
20ONa [M + Na]+ 323.1407, found 323.1436.
1
(thin film)/cm−1 1681, 1598, 1506, 1234, 1156, 700; H NMR (400
MHz, CDCl3) δ 7.86−7.82 (2H, m), 7.25−7.03 (7H, m), 5.72 (1H,
ddt, J = 17.2, 10.0, 7.2 Hz), 5.04−4.98 (2H, m), 3.77−3.7 (1H, m),
3.07 (1H, dd, J = 14.0, 6.4 Hz), 2.82 (1H, dd, J = 13.6, 6.4 Hz), 2.56−
2.49 (1H, m), 2.33−2.27 (1H, m); 13C NMR (100 MHz, CDCl3) δ
201.5, 165.6 (d, JC−F = 254 Hz), 139.5, 135.2, 133.8 (d, JC−F = 3.0 Hz),
130.8 (d, JC−F = 10.0 Hz), 129.0, 128.4, 126.3, 117.2, 115.6 (d,
JC−F =22.0 Hz), 48.1, 37.9, 36.5; HRMS calcd for C18H18OF [M + H]+
269.1342, found 269.1354.
2-Benzyl-1-(2-bromophenyl)pent-4-en-1-one (14o).
2-Benzyl-1-(3-fluorophenyl)pent-4-en-1-one (14l).
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1-(2-bromophenyl)-3-phenylprop-2-ene (11o)
(58.2 mg, 0.18 mmol) using potassium tert-butoxide (10.0 mg,
0.090 mmol). The crude product was applied directly onto the top of a
column and chromatographed (1% Et2O in hexane) to afford 14o
(19.6 mg, 34%) as a colorless oil: Rf (4% Et2O in hexane) = 0.39; IR
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1-(3-fluorophenyl)-3-phenylprop-2-ene 11l
(47.3 mg, 0.176 mmol) using potassium tert-butoxide (10.0 mg,
0.09 mmol). The crude product was applied directly onto the top of
a column and chromatographed (2% Et2O in hexane) to afford 14l
(34.2 mg, 72%) as a yellow oil: Rf (4% Et2O in hexane) = 0.33 ; IR
1
νmax (thin film)/cm−1 2924, 1679, 1583, 1257, 974, 757; H NMR
(400 MHz, CDCl3) δ 7.58−7.56 (1H, m), 7.28−7.16 (7H, m), 7.09−
7.07 (1H, m), 5.76 (1H, ddd, J = 17.2, 10.0, 7.2 Hz), 5.09−5.03 (2H,
m), 3.66−3.60 (1H, m), 3.14 (1H, dd, J = 13.6, 7.6 Hz), 2.80 (1H, dd,
J = 13.6, 6.8 Hz), 2.52−2.43 (1H, m), 2.30−2.23 (1H, m) 13C NMR
(100 MHz, CDCl3) δ 205.9, 141.6, 139.5, 134.9, 133.7, 131.5, 129.2,
128.9, 128.4, 127.2, 126.3, 119.3, 117.7, 52.5, 36.6, 35.4; HRMS (ES+)
calcd for C36H34O2Br2Na [2 M + Na]+ 679.0823, found 679.0836.
2-Benzyl-1-(2-methylphenyl)pent-4-en-1-one (14p).
1
νmax (thin film)/cm−1 2926, 1683, 1587, 1490, 1443, 1257, 757; H
NMR (400 MHz, CDCl3) δ 7.60−7.58 (1H, m), 7.51−7.48 (1H, m),
7.40−7.34 (1H, m), 7.25−7.14 (6H, m), 5.72 (1H, ddd,, J = 17.2, 10.0,
6.8 Hz), 5.05−4.99 (2H, m), 3.76−3.69 (1H, m), 3.08 (1H, dd, J =
13.6, 8.0 Hz), 2.82 (1H, dd, J = 13.6, 6.4 Hz), 2.56−2.49 (1H, m),
2.34−2.27 (1H, m) 13C NMR (100 MHz, CDCl3) δ 201.9 (d, JC−F
=
2.0 Hz), 162.8 (d, JC−F =246 Hz), 139.5 (d, JC−F = 6.0 Hz), 139.4,
135.0, 130.2 (d, JC−F = 8 Hz), 129.0, 128.5, 126.4, 123.9 (d, JC−F = 4.0
Hz), 119.9 (d, JC−F = 21.0 Hz), 117.4, 115.0 (d, JC−F = 22.0 Hz), 48.4,
37.8, 36.3; HRMS (ES+) calcd for C18H 18OF [M + H]+ 269.1342,
found 269.1348.
2-Benzyl-1-(3,5-methylphenyl)pent-4-en-1-one (14m).
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1-(2-methylphenyl)-3-phenylprop-2-ene (11p)
(56.1 mg, 0.21 mmol) using potassium tert-butoxide (12.0 mg, 0.105
mmol). The crude product was applied directly onto the top of a
column and chromatographed (0.5% EtOAc in hexane) to afford 14p
(31.0 mg, 55%) as a colorless oil: Rf (4% Et2O in hexane) = 0.31; IR
Potassium tert-butoxide (9.0 mg, 0.08 mmol) was added to a THF
solution (1.3 mL) of (E)-1-(allyloxy)-1-(3,5-dimethylphenyl)-3-
phenylprop-2-ene 11m (42.9 mg, 0.16 mmol) in a dry, argon-purged
10 mL round-bottom flask at room temperature. The reaction heated
to 80 °C and allowed to stir for 16 h. After quenching with distilled
water (10 mL) and extraction (2 × 25 mL EtOAc), the organic layer
was washed with distilled water (25 mL) and brine (25 mL), dried
over MgSO4 and concentrated in vacuo. The crude mixture was
applied directly onto the top of a column and chromatographed (2%
Et2O in hexane) to afford 14m (31.0 mg, 72%) as a colorless oil: Rf
(4% Et2O in hexane) = 0.45; IR νmax (thin film)/cm−1; 2921, 1679,
1
νmax (thin film)/cm−1 2926, 1684, 1455, 1232, 918, 749; H NMR
(400 MHz, CDCl3) δ 7.32−7.14 (9H, m), 5.73 (1H, ddd, J = 16.8,
10.0, 7.2 Hz), 5.06−4.99 (2H, m), 3.66- 3.59 (1H, m), 3.09 (1H, dd,
J = 13.6, 8.0 Hz), 2.77 (1H, dd, J = 13.6, 6.4 Hz), 2.52−2.45 (1H, m),
2.37 (3H, s), 2.29−2.23 (1H, m) 13C NMR (100 MHz, CDCl3) δ
206.9, 139.0, 138.8, 138.1, 135.3, 131.7, 131.0, 129.1, 128.4, 127.9,
126.3, 125.5, 117.3, 51.4, 37.4, 36.3, 20.8; HRMS calcd for C19H21O
[M + H]+ 265.1592, found 265.1599.
2-Benzyl-1-(pyridin-3-yl)pent-4-en-1-one (14q).
1
1604, 1293, 915, 700; H NMR (400 MHz, CDCl3) δ 7.43 (2H, s),
7.29−7.14 (6H, m), 5.72 (1H, ddd, J = 17.2, 10.0, 6.8 Hz), 5.04−4.94
(2H, m), 3.79−3.72 (1H, m), 3.08 (1H, dd, J = 13.6, 7.6), 2.79 (1H,
dd,J = 13.6, 6.4 Hz), 2.55−2.48 (1H, m), 2.35−2.24 (1H, m), 2.32
(6H, s) 13C NMR (100 MHz, CDCl3) δ 203.3, 139.9, 138.2, 135.4,
134.6, 129.1, 128.4, 126.2, 126.0, 117.1, 48.1, 37.7, 36.3, 21.2; HRMS
(ES+) calcd for C20H23O [M + H]+ 279.1749, found 279.1752.
2-Benzyl-1-(2-naphthyl)pent-4-en-1-one (14n).
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1-(pyridin-3-yl)-3-phenylprop-2-ene (11q)
(40.0 mg, 0.16 mmol) using potassium tert-butoxide (9.0 mg, 0.080
mmol). The crude product was applied directly onto the top of a
column and chromatographed (50% Et2O in hexane) to afford 14q
(31.0 mg, 77%) as a colorless oil: Rf (50% Et2O in hexane) = 0.19; IR
1
νmax (thin film)/cm−1 2924, 1684, 1584, 1417, 1244, 701; H NMR
(400 MHz, CDCl3) δ 9.01−8.97 (1H, m), 8.73−8.68 (1H, m), 8.06−
8.03 (1H, m), 7.36−7.12 (6H, m), 5.71 (1H, ddd, J = 17.2, 10.0, 6.8
Hz), 5.00−4.97 (2H, m), 3.80−3.73 (1H, m), 3.08 (1H, dd, J = 13.6,
8.4 Hz), 2.86 (1H, dd, J = 13.6, 6.0 Hz), 2.59−2.52 (1H, m), 2.37−
2.31 (1H, m); 13C NMR (100 MHz, CDCl3) δ 202.2, 153.2, 149.6,
139.1, 135.5, 134.8, 128.9, 128.5, 127.5, 126.5, 123.5, 117.6, 48.8, 37.9,
The title compound was prepared according to general procedure G
from (E)-1-(allyloxy)-1-(2-naphthyl)-3-phenylprop-2-ene (11n)
(48.9 mg, 0.16 mmol) using potassium tert-butoxide (9.0 mg, 0.080
mmol). The crude product was applied directly onto the top of a
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36.4; HRMS (ES+) calcd for C17H18NO [M + H]+ 252.1388, found
252.1389.
(E)-1-(2-Butenyloxy)-1,3-diphenylprop-2-ene (15).
53.6 μL, 0.57 mmol) was added via syringe. The solution was stirred
at this temperature for 30 min, followed by the addition of brine
(10 mL). The solution was extracted with Et2O (2 × 20 mL), dried,
and concentrated to give a yellow oil.
This was then transferred to a separate flask containing diphenyl-2-
propen-1-ol (0.571 mml, 120 mg) using DMF (2 mL). The resultant
clear solution was cooled to 0 °C, and NaH (60% suspension in
mineral oil; unwashed) (45.6 mg, 1.14 mmol) was added as a single
portion.
The title compound was prepared according to general procedure D
from (E)-1,3-diphenylpropen-2-ol (266 mg, 1.26 mmol) using crotyl
bromide (0.26 mL, 2.52 mmol) and NaH (60% suspension in mineral
oil; unwashed) (101 mg, 2.52 mmol). The crude product was applied
directly onto the top of a column and chromatographed (1% EtOAc in
hexane) to afford 15 (290 mg, 87%) as a yellow oil: Rf (10% EtOAc in
hexane) = 0.61;IR νmax (thin film)/cm−1 2854, 1395, 1276, 1067, 764,
After being stirred at the same temperature for 1.5 h, the reaction
was quenched with NH4Cl (10 mL), extracted with ether (3 × 10 mL),
dried over MgSO4, and concentrated in vacuo. The crude product was
applied directly onto the top of a column and chromatographed (2.5%
EtOAc in hexane) to afford 18 (157 mg, 83%) as a colorless oil: Rf (10%
1
700; H NMR (400 MHz, CDCl3) δ 7.39−7.19 (10H, m), 6.60 (1H,
1
d, J =16.0 Hz), 6.30 (1H, dd, J = 16.0, 7.2 Hz), 5.77−5.60 (2H, m),
4.97 (1H, d, J = 6.8 Hz), 4.00−3.91 (2H, m), 1.72 (d, 3H, J= 6.0 Hz)
13C NMR (100 MHz, CDCl3) δ 141.3, 136.7, 131.3, 130.5, 129.5,
128.5, 127.6, 127.0, 126.6, 81.6, 69.1, 17.9 HRMS (ES+) calcd for
C19H20NaO [M + Na]+ 287.1412, found 287.1389. Characterization in
accordance with literature data.23a
EtOAc in hexane) = 0.59; H NMR (400 MHz, CDCl3) δ 7.46−7.37
(6H, m), 7.37−7.28 (5H, m), 7.28−7.19 (4H, m), 6.65 (1H, d, J = 16.0
Hz), 6.63 (1H, dt, J = 16.0, 2.4 Hz), 6.34 (1H, dd, J = 16.9, 0.8 Hz),
6.32 (1H, d, J = 16.0 Hz), 5.05 (1H, d, J = 7.0 Hz), 4.21 (2H, ddd, J =
6.0, 3.6, 1.3 Hz). Characterization in accordance with literature data.85
(E)-1,3,6-Triphenylhex-5-en-1-one (19) and 1,3,4-Triphenylhex-5-
en-1-one (20).
1,3-Diphenylhept-5-en-1-one (16).
The title compounds were prepared according to general procedure F
from (E)-1-(3-phenylallyloxy)-1,3-diphenylprop-2-ene (18) (50.9 mg,
0.15 mmol) using 18-crown-6 (80.4 mg, 0.305 mmol) and potassium
tert-butoxide (34.1 mg, 0.305 mmol). The crude product was applied
directly onto the top of a column and chromatographed (0.5% Et2O in
hexane) to afford 21 and 22 (30.0 mg, 59%) as an inseparable mixture
in the form of a clear oil.
The title compound was prepared according to general procedure F
from (E)-1-(2-butenyloxy)-1,3-diphenylprop-2-ene (15) (86.0 mg,
0.32 mmol) using 18-crown-6 (169 mg, 0.64 mmol) and potassium
tert-butoxide (72.0 mg, 0.64 mmol). The crude product was applied
directly onto the top of a column and chromatographed (2% Et2O in
hexane) to afford 16 (59.2 mg, 69%) as a colorless oil: Rf (2% Et2O in
hexane) = 0.35; νmax (thin film)/cm−1; 3407, 3170, 2936, 1690, 1571,
1561, 1506, 1463, 1336, 1301, 962, 750; 1H NMR (400 MHz, CDCl3)
δ = 7.91−7.88 (2H, m), 7.55−7.50 (1H, m), 7.44−7.40 (2H, m),
7.29−7.14 (5H, m), 5.50−5.27 (2H, m), 3.47−3.36 (1H, m), 3.32−
3.20 (2H, m), 2.54−2.35 (2H, m), 1.57−1.52 (3H, m) 13C NMR (100
MHz, CDCl3) δ = 199.2, 144.8, 137.9, 132.9, 128. 7, 128.5, 128.4,
128.0, 127.9, 127.6, 127.4, 44.5, 41.2, 39.7, 17.9; HRMS (ES+) calcd
for C19H22O [M + 2H]+ 266.1671, found 266.1701.
19 and 20: Rf (19:1 hexane/Et2O) = 0.34.
19 and 20: νmax (thin film)/cm−1; 3531 (br), 2977, 2861, 1679,
1662, 1645, 1412, 1238, 1054, 1032, 1012, 896, 766.
19: 1H NMR (400 MHz, CDCl3) δ 7.77−7.64 (2H, m), 7.48−7.31
(2H, m), 7.33−7.27 (3H, m), 7.19−7.04 (6H, m), 7.03−6.99 (2H, m)
6.33 (1H, dt, J = 15.8, 6.0 Hz), 6.14 (1H, dt, J = 15.8, 9.2 Hz), 5.21
(1H, d, J = 5.8 Hz), 4.22 (1H, dd, J = 6.0, 1.3 Hz), 3.75 (1H, t, J = 9.5
Hz), 3.11 (2H, d, J = 9.8 Hz).
20: 1H NMR (400 MHz, CDCl3) δ 7.77−7.64 (2H, m), 7.48−7.31
(2H, m), 7.33−7.27 (3H, m), 7.19−7.04 (6H, m), 7.03−6.99 (2H, m)
5.89 (1H, ddd, J = 18.3, 17.0, 7.0 Hz), 4.91 (1H, dt, J = 16.8, 1.0 Hz),
4.87 (1H, dt, J = 16.8, 1.0 Hz), 4.14−4.06 (1H, m), 2.93 (1H, dd, J =
13.0, 11.4 Hz), 2.66 (1H, dd, J = 13.0, 3.3 Hz).
2-Benzyl-3-methyl-1-phenylpent-4-en-1-one (17).
19: 13C NMR (100 MHz, CDCl3) δ 204.0, 132.6, 132.5, 128.5,
128.3, 128.2, 128.0, 127.7, 127.0, 126.9, 126.6, 126.1, 126.0, 116.4,
60.8, 55.0, 53.7, 37.9.
The title compound was prepared according to general procedure G
from 15 (100.0 mg, 0.38 mmol) using potassium tert-butoxide (21.1
mg, 0.19 mmol). The crude product was applied directly onto the top
of a column and chromatographed (2% Et2O in hexane) to afford 17
(67.3 mg, 67%) as a clear oil and as an inseparable mix of isomers: Rf
(2% Et2O in hexane) = 0.41; νmax (thin film)/cm−1 3434, 3120, 3074,
20: 13C NMR (100 MHz, CDCl3) δ 203.1, 142.0, 139.9, 138.6,
132.2, 129.0, 128.9, 128.4, 128.3, 127.9, 127.9, 127.6, 126.5, 126.1,
117.3, 70.8, 54.1, 53.8, 37.3.
19 and 20: HRMS (ES+) calcd for C24H22ONa [M + Na]+
349.1568, found 349.1572.
1
1684, 1571, 1549, 1506, 1463, 1336, 1207, 974, 750; H NMR (400
(E)-2-Benzyl-1,5-diphenylpent-4-en-1-one (21).
MHz, CDCl3) δ 7.77−7.64 (2H, m), 7.48−7.31 (2H, m), 7.19−7.04
(6H, m), 5.87 (0.5H, ddd, J = 17.4, 10.1, 7.0), 5.77 (0.5H, ddd, J =
17.4, 10.1, 7.0), 5.12−5.00 (2H, m), 3.76 (0.5H, ddd, J = 10.2, 6.3, 3.6
Hz), 3.62 (0.5H, ddd, J = 10.2, 6.3, 3.6 Hz), 3.21−2.93 (1H, m), 2.83
(1H, dd, J = 13.4, 8.0 Hz), 2.69−2.59 (1H, m), 1.02 (3H, dd, J = 9.3,
6.9 Hz); 13C NMR (100 MHz, CDCl3) δ 144.8, 137.3, 132.9, 128.8,
128.5(0.5 C), 128.4(0.5 C), 128.0, 127.9, 127.4, 126.3(0.5 C),,
126.2(0.5 C),, 125.8, 44.7 (0.5 C), 44.5(0.5 C), 41.3, 39.7, 33.5, 17.9;
HRMS (ES+) calcd for C19H 20ONa [M + Na]+ 287.1412, found
287.1404.
The title compound was prepared according to general procedure G
from (E)-1-(3-phenylallyloxy)-1,3-diphenylprop-2-ene (18) (50.8 mg,
0.152 mmol) using potassium tert-butoxide (8.5 mg, 0.076 mmol).
The crude product was applied directly onto the top of a column and
chromatographed (0.5% Et2O in hexane) to afford 19 (67.3 mg, 64%)
as a colorless solid: Rf (29:1 hexane/Et2O) = 0.17; IR νmax (thin film)/
cm−1 3536 (br), 2906, 2771, 1679, 1650, 1492, 1423, 1257, 1054,
1032, 1012, 897, 766; 1H NMR (400 MHz, CDCl3) δ 7.89 (1H, d, J =
7.3 Hz), 7.57−7.48 (2H, m), 7.47−7.43 (3H, m), 7.41 (2H, t, J = 7.8
Hz), 7.30−7.23 (6H, m), 7.16−7.12 (1H, m). 6.35 (1H, d, J = 15.8
Hz), 6.13−6.04 (1H, m), 3.56 (1H, dd, J = 14.3, 5.0 Hz), 3.39 (1H, dd,
J = 14.3, 5.0 Hz), 3.33 (1H, dd, J = 7.0, 5.3 Hz), 2.61 (2H, t, J = 8.3 Hz);
(E)-1-(3-Phenylallyloxy)-1,3-diphenylprop-2-ene (18).
Cinnamyl alcohol (0.146 mL, 1.14 mmol) was added to an oven-dried
round-bottom flask and placed under argon. Dry diethyl ether (3 mL)
was added, the reaction was cooled to 0 °C, and PBr3 (154 mg,
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13C NMR (100 MHz, CDCl3) δ 133.0, 132.1, 129.1, 128.5, 128.5,
128.0, 127.9, 127.6, 126.0, 125.2, 125.1, 72.4, 62.0, 49.2, 44.3,
36.5,31.9; HRMS (ES+) calcd for C24H22ONa [M + Na]+ 349.1568,
found 349.1579.
(E)-Ethyl 3-((E)-3-(Dimethyl(phenyl)silyl)-1-phenylallyl)oxy)-
acrylate (S10).
by alcohol 22 (49.8 mg, 0.156 mmol). The resultant solution was
cooled to 0 °C. NaH (60% in mineral oil; unwashed) (6.22 mg,
0.156 mmol) was added in one portion, swiftly followed by dropwise
addition of benzyl bromide (18.6 μL, 0.156 mmol). The reaction was
stirred at this temperature for 1 h before being warmed to room
temperature. The reaction was stirred overnight. When the reaction
was found to be complete by TLC, it was quenched with saturated
NH4Cl solution (5 mL). The resultant solution was extracted with
Et2O (3 × 10 mL) and the combined organic layers were washed with
brine (2 × 10 mL), dried over MgSO4, and concentrated in vacuo.
Column chromatograpy (pure hexane) afforded 25 (26.5 mg, 46%) as
a colorless oil: Rf (9:1 hexane/EtOAc) = 0.67; νmax (thin film)/cm−1
Following a modified form of the procedure reported by Wulff,36 to an
oven-dried round-bottom flask equipped with a magnetic stirrer bar
and purged with argon was added dry methylene chloride (4 mL),
followed by (E)-3-(dimethyl(phenyl)silyl)-1-phenylprop-2-en-1-ol23a
(300 mg, 1.125 mmol) (1 equiv) and ethyl propiolate (0.114 mL,
1.125 mmol) (1 equiv). The resultant solution was cooled to 0 °C. In
a separate oven-dried round-bottom flask, a solution of trimethyl
phosphine (1 M in a solution of THF) (0.22 mL, 0.225 mmol) (0.2
equiv) in dry methylene chloride (4 mL) was prepared and cooled to
0 °C. This solution was then slowly transferred, via cannula, to the flask
containing the alcohol and alkyne solution. The reaction was allowed
to warm to room temperature over the course of 1 h, heated to 40 °C,
and stirred at this temperature for 48 h. When the reaction was found
to be complete by TLC, the methylene chloride was removed under
reduced pressure, and the crude mixture was applied directly to a
column containing base washed silica. Column chromatograpy (9:1
EtOAc/hexane) afforded S10 as a yellow oil (412 mg, 90%): Rf (9:1
1
2924, 2854, 1654, 1456, 1275, 972, 749, 698; H NMR (400 MHz,
CDCl3) δ 7.57−7.51 (2H, m), 7.48−7.42 (2H, m), 7.39−7.29 (13H,
m), 6.46 (1H, d, J = 12.3 Hz), 5.70 (1H, q, J = 7.0 Hz), 5.17 (1H, dt,
J = 12.6, 5.3 Hz), 4.40 (2H, s), 3.90 (2H, d, J = 7.53 Hz), 1.79 (2H, d,
J = 7.5 Hz), 0.32 (6H, s); 13C NMR (100 MHz, CDCl3) δ 140.0,
137.5, 134.4, 132.9, 132.1, 128.4, 127.6, 127.5, 127.0, 127.0, 126.9,
126.8, 126.7, 124.3, 110.1, 102.6, 71.3, 70.2, 66.1, 10.4, −4.0, −4.1;
HRMS (ES+) calcd for C27H 31O2Si [M + H+]+ 415.2093, found
415.2115.
(1-((E)-3-(Benzyloxy)prop-1-en-1-yl)oxy)prop-1-en-1-yl)benzene (26).
To a dried 5 mL round-bottom flask equipped with a magnetic stirrer
bar and purged with argon was added dry DMF (0.75 mL) followed by
alcohol 22 (148 mg, 0.462 mmol). The resultant solution was cooled
to 0 °C. NaH (60% in mineral oil; unwashed) (27.7 mg, 0.693 mmol)
was added in one portion, swiftly followed by dropwise addition of
benzyl bromide (0.185 mL, 1.39 mmol). The reaction was stirred at
this temperature for 1 h before warming to room temperature. The
reaction was stirred overnight. When the reaction was found to be
complete by TLC, it was quenched with saturated NH4Cl solution
(5 mL). The resultant solution was extracted with Et2O (3 × 10 mL),
and the combined organic layers were washed with brine (2 × 10 mL),
dried over MgSO4, and concentrated in vacuo. Column chromatogr-
apy (pure hexane) afforded the desired product (81 mg, 64%) as a
colorless oil: Rf (9:1 hexane/EtOAc) = 0.55; νmax (thin film)/
cm−1;2856, 1654, 1495, 1453, 1275, 1261, 1155, 1066, 929, 763, 749,
1
hexane/ethyl acetate) = 0.26; H NMR (400 MHz, CDCl3) δ 7.58
(1H, d, J = 12.6 Hz), 7.50−7.46 (2H, m), 7.40−7.28 (8H, m), 6.20
(1H, dd, J = 18.6, 5.0 Hz), 6.10 (1H, dd, J = 18.6, 1.0 Hz), 5.37 (1H, d,
J = 5.0 Hz), 5.31 (1H, d, J = 12.6 Hz), 4.13 (2H, dq, J = 7.3, 0.7 Hz),
1.26 (3H, t, J = 7.0), 0.37 (3H,s), 0.36 (3H, s) 13C NMR (100 MHz,
CDCl3) δ 167.7, 160.9, 144.5, 138.3, 137.7, 133.9, 131.4, 129.2, 128.8,
128.5, 128.4, 127.9, 126.9, 98.9, 86.2, 59.7, 14.4, −2.8; HRMS (EI+)
calcd for C22H26O3NaSi [M + Na]+ 398.1549, found 398.1539.
(E)-2-((E)-3-(Dimethyl(phenyl)silyl)-1-phenylallyl)oxy)ethanol (24).
1
697; H NMR (400 MHz, CDCl3) δ 7.47−7.41 (2H, m), 7.36−7.24
To a dried 10 mL round-bottom flask equipped with a magnetic stirrer
bar and purged with argon was added ether (not dried) (2 mL),
followed by S11(161 mg, 0.44 mmol) (1 equiv). The resultant
solution was cooled to −78 °C. DIBAL (1.5 M solution in toluene)
(0.78 mL, 0.968 mmol) (2.2 equiv) was added dropwise, and the
solution stirred at −78% °C for 1 h. The temperature was then
brought up to −40 °C and the reaction stirred for a further 2 h. When
the reaction was found to be complete by TLC, it was quenched with
NH4Cl and allowed to warm to room temperature. This was then
transferred to a conical flask and stirred rigorously in NaOH to
dissolve aluminum salts. The resultant solution was extracted with
Et2O, and the combined organic layers were washed with brine.
Column chromatograpy in base washed silica (25% EtOAc/hexane)
afforded 24 as a colorless oil (98 mg, 69%): Rf (9:1 hexane/ethyl
(8H, m), 6.46 (1H, d, J = 12.3 Hz), 5.69 (1H, q, J = 7.0 Hz), 5.17 (1H,
dt, J = 12.6, 5.3 Hz), 4.40 (2H, s), 3.90 (2H, d, J = 7.53 Hz), 1.78 (3H,
d, J = 7.5 Hz); 13C NMR (100 MHz, CDCl3) δ 151.1, 148.3, 128.4,
128.3, 127.9, 127.8, 127.5, 127.4, 125.3, 111.0, 103.5, 85.6 71.2, 66.6,
11.5; HRMS (ES+) calcd for C19H21O2 [M + H+]+ 281.1542, found
281.1531.
Dimethyl(phenyl)((Z)-3-phenyl-3-((E)-prop-1-en-1-yloxy)allyl)silane
and (1-((E)-Prop-1-en-1-yloxy)prop-1-en-1-yl)benzene (27 + 28).
To a dried 5 mL round-bottom flask equipped with a magnetic stirrer
bar and purged with argon was added dry DMF (0.25 mL), followed
by alcohol 22. The resultant solution was cooled to 0 °C. NaH of the
quantity stated (60% in mineral oil; unwashed) was added in one
portion. The reaction was stirred at this temperature for 1 h before
warming to room temperature. The reaction was stirred overnight.
When the reaction was found to be complete by TLC, it was quenched
with saturated NH4Cl solution (5 mL). The resultant solution was
extracted with Et2O (3 × 10 mL), and the combined organic layers
were washed with brine (2 × 10 mL), dried over MgSO4 and con-
centrated in vacuo. Column chromatograpy (pure hexane) provided
27 and 28 as an inseparable mixture.
1
acetate) = 0.09; H NMR (400 MHz, CDCl3) δ 7.55−7.44 (2H, m),
7.41−7.28 (8H, m), 6.54 (1H, dt, J = 12.3, 0.8 Hz), 6.20 (1H, dd,
J = 18.8, 5.3 Hz), 6.08 (1H, dd, J = 18.8, 1.3 Hz), 2.20 (1H, s), 5.18
(1H, dt, J = 12.6, 7.5 Hz), 3.99 (2H, dd, J= 6.5, 5.3 Hz), 0.34 (3H, s),
0.33 (3H, s) 13C NMR (100 MHz, CDCl3) δ 148.6, 145.8, 139.4,
138.1, 133.8, 130.2, 129.7, 129.1, 128.7, 128.1, 126.8, 105.8, 84.3, 60.7,
−2.7, −2.7; HRMS (ES+) calcd for C20H 25O2Si [M + H]+ 325.1624,
found 325.1611.
((Z)-3-((E)-3-(Benzyloxy)prop-1-en-1-yl)oxy)-3-phenylallyl)-
dimethyl(phenyl)silane (25).
27 and 28: νmax (thin film)/cm−1; 2941, 2906, 2856, 2743, 1632,
1493, 1450, 1274, 1137, 1013, 971, 930, 860.
27: 1H NMR (400 MHz, CDCl3) δ 7.59−7.51 (2H, m), 7.48−7.40
(2H, m), 7.36−7.27 (3H, m), 7.25−7.21 (2H, m), 6.32 (1H, d,
J = 12.4 Hz), 5.07 (1H, dt, J = 12.4, 7.5 Hz), 4.57 (2H, t, J = 6.6 Hz),
3.91 (2H, d, J = 7.5 Hz), 0.94−0.85 (2H, m), 0.24 (6H, s).
To a dried 5 mL round-bottom flask equipped with a magnetic stirrer
bar and purged with argon was added dry DMF (0.25 mL), followed
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DOI: 10.1021/jo502403n
J. Org. Chem. 2015, 80, 1472−1498

The Journal of Organic Chemistry
Article
28: 1H NMR (400 MHz, CDCl3) δ 7.48−7.40 (2H, m), 7.36−7.27
(3H, m), 6.49 (1H, d, J = 12,4 Hz), 5.72 (1H, q, J = 7.0 Hz), 5.25 (1H,
dt, J = 11.9, 7.5 Hz), 4.02 (2H, d, J = 7.3 Hz), 1.78 (3H, d, J = 7.0 Hz).
27: 13C NMR (100 MHz, CDCl3) δ 147.6, 139.1, 132.7,
132.2, 128.4, 127.6, 127.5, 127.0, 126.9, 124.3, 110.1, 102.6, 70.2,
66.1, −3.9, −4.0.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Eli Lilly (Dr. Magnus Walter and Dr. Maria
Whatton) for a CASE award to C.A.M. and Queen’s University
Belfast for funding. We also thank Girton College, Cambridge
(Research Fellowship to M.N.G.). and Unilever for support.
28: 13C NMR (100 MHz, CDCl3) δ 150.2, 137.5, 134.4, 128.1,
127.4, 126.8, 125.6, 101.3, 83.8, 71.3
27: HRMS (ES+) calcd for C20H 25O2Si [M + H]+ 325.1624, found
325.1652.
28: HRMS (ES+) calcd for C12H14NaO2 [M + Na]+ 213.0891,
found 213.0889.
REFERENCES
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122.4, 88.7, 86.7. Characterization in accordance with literature data.86
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The title compound was prepared according to general procedure B
from S11 (277 mg, 1.32 mmol) using Red-Al (65% in PhMe) (0.80 mL,
2.64 mmol). The crude product was applied directly onto the top of a
column and chromatographed (20% EtOAc in hexane) to afford S1
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νmax (thin film)/cm−1 3348, 1494, 1448, 965, 746, 695; 1H NMR (400
MHz, CDCl3) δ 7.44−7.17 (10H, m), 6.68 (1H, d, J = 16.0 Hz), 6.37
(1H, d, J = 16.0 Hz), 2.11 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
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The title compound was prepared according to general procedure C
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(1H, m), 5.21- 5.19 (1H, m), 4.09−3.99 (1H, m); 13C NMR (100 MHz,
CDCl3) δ 141.1, 136.6, 134.9, 131.5, 130.2, 128.5, 127.7 (d, J = 3.0 HZ),
126.9, 126.6, 117.0, 69.2. Characterization in accordance with literature
data.66
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H and13C NMR spectra, additional experimental information,
and tables containing the full computational analysis. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: m.cook@qub.ac.uk.
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