Preparation of amino-substituted indenes and 1,4-dihydronaphthalenes using a one-pot multireaction approach: Total synthesis of oxybenzo[c]phenanthridine alkaloids

Article abstract of DOI:10.1021/jo5014492

Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction, catalyzed using the Hermann-Beller palladacycle was used to effect the key step during the synthesis of the natural products.

Full text of DOI:10.1021/jo5014492

Article
pubs.acs.org/joc
Preparation of Amino-Substituted Indenes and 1,4-
Dihydronaphthalenes Using a One-Pot Multireaction Approach: Total
Synthesis of Oxybenzo[c]phenanthridine Alkaloids
Ewen D. D. Calder, Fiona I. McGonagle, Alexander H. Harkiss, Grant A. McGonagle,
and Andrew Sutherland*
WestCHEM, School of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom
S
* Supporting Information
ABSTRACT: Allylic trichloroacetimidates bearing a 2-vinyl or
2-allylaryl group have been designed as substrates for a one-
pot, two-step multi-bond-forming process leading to the
general preparation of aminoindenes and amino-substituted
1,4-dihydronaphthalenes. The synthetic utility of the privileged
structures formed from this one-pot process was demonstrated
with the total synthesis of four oxybenzo[c]phenanthridine
alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction,
catalyzed using the Hermann−Beller palladacycle was used to effect the key step during the synthesis of the natural products.
As a result of these wide-ranging pharmacological activities,
methods for the synthesis of oxybenzo[c]phenanthridines have
received considerable attention.6−10 For example, Clark and
Jahangir reported the synthesis of oxynitidine (3) by forming
the benzo[c]phenanthridine skeleton through cycloaddition of
a lithiated toluamide with a benzaldimine.9b In an analogous
approach, Cho and co-workers showed that cycloaddition
between lithiated toluamides and benzonitriles could be used
for the general synthesis of this class of natural product.6c−e,7e,f
The research group of Harayama prepared a number of
oxybenzo[c]phenanthridines by initial formation of amide
intermediates via coupling of aminonaphthalenes with o-
halogenated benzoic acids.6h The key step, a challenging
intramolecular biaryl Heck coupling reaction, was then
optimized to complete the synthesis of the oxybenzo[c]-
phenanthridine skeleton.6a,b,7b−d,9c Cheng and co-workers
reported the preparation of a range of oxybenzo[c]-
phenanthridines using a nickel-catalyzed annulation and
regioselective cyclization of o-halobenzaldimines with a benzo-
[d][1,3]dioxol-5-yl substituted alkyne.6f Further development
of this process showed that a halide-free benzaldimine could be
subjected to a similar reaction through C−H activation
resulting in a highly efficient synthesis of oxychelerythrine
(1).7g
INTRODUCTION
■
Naturally occurring benzo[c]phenanthridines belong to an
extensive family of isoquinoline alkaloids, many of which have
important biological activities.1 In particular, the tetracyclic,
fully aromatic oxybenzo[c]phenanthridine alkaloids have
received much attention due to the discovery of wide-ranging
and significant medicinal properties. For example, oxycheler-
ythrine (1) isolated from the root bark of Zanthoxylum
integrifoliolum1b displays cytotoxic effects against P-388 and
HT-29 cell lines,2 while oxysanguinarine (2) from the tuberless
biennial herb Corydalis tashiroi possesses anti-platelet aggrega-
tion activity (Figure 1).3 The related oxybenzo[c]-
phenanthridines, oxynitidine (3)4 and oxyavicine (4),5 isolated
from various Zanthoxylum plant species inhibit DNA
replication in hepatitis B virus4c and exhibit analgesic and
anti-inflammatory activities.5 Oxyavicine (4) is also used for the
treatment of ophthalmic disorders.5
We recently reported the synthesis of amino-substituted
indanes and tetrahydronaphthalenes from alkyne-derived allylic
trichloroacetimidates using two consecutive one-pot multi-
reaction processes (Scheme 1a).11 The first of these involved an
Overman rearrangement and ring-closing enyne metathesis
(RCEYM) reaction to give cyclic exo-dienes. The amino-
Figure 1. Structures of oxychelerythrine (1), oxysanguinarine (2),
oxynitidine (3), and oxyavicine (4).
Received: June 30, 2014
© XXXX American Chemical Society
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Scheme 1. One-Pot Multireaction Processes for the Preparation of Amino-Substituted Indane and Naphthalene Ring Systems
substituted indanes and tetrahydronaphthalenes were then
formed following a one-pot Diels−Alder reaction and oxidation
step using alkynes and 1,4-quinones as dienophiles. While this
approach allowed the flexible synthesis of various ring sizes and
the late stage incorporation of aromatic ring substituents, we
found that only a limited number of electron-deficient alkynes
participated in the Diels−Alder reaction, restricting the variety
of compounds produced. To overcome this limitation, a new
strategy for the preparation of these types of ring systems was
devised (Scheme 1b). It was proposed that substituted 2-
bromobenzaldehydes could be used as starting materials for the
rapid preparation of allylic trichloroacetimidates bearing a 2-
vinyl- or 2-allylaryl group. A one-pot, two-step multireaction
process involving an Overman rearrangement and a ring-closing
metathesis (RCM) reaction would then allow a more direct
synthesis of these ring systems.12 In addition, the general
availability of 2-bromobenzaldehydes would result in the
preparation of a wider range of potential products, and the
formation of cyclic allylic amides from this particular one-pot
process (cf. Scheme 1a) would give an additional functional
handle for further transformations of these compounds. We
now report the general synthesis of aminoindenes and amino-
substituted 1,4-dihydronaphthalenes using a one-pot, two-step
multireaction process. As well as demonstrating the scope of
this process, we also describe its application for the total
synthesis of the oxybenzo[c]phenanthridine alkaloids oxy-
chelerythrine (1), oxysanguinarine (2), oxynitidine (3), and
oxyavicine (4).
Table 1. Synthesis of (E)-(2-Vinyl)cinnamyl Alcohols 8a−f
RESULTS AND DISCUSSION
■
Our studies began with the development of a short and efficient
synthesis of (E)-(2-vinyl)cinnamyl alcohols that would
ultimately generate amino-substituted indenes. Having identi-
fied 2-bromobenzaldehydes as suitable starting materials, we
initially investigated the incorporation of a vinyl group using a
Stille coupling with tri-n-butyl(vinyl)tin under standard
conditions.13 While this did give the coupled products in
good yields, the reactions were not always reproducible and
purification was complicated by the presence of the proto-
debrominated benzaldehydes and organotin residues. Instead, a
highly efficient, reproducible, and scalable synthesis of 2-
vinylbenzaldehydes 6a−f was achieved using a Suzuki−Miyaura
coupling with potassium vinyltrifluoroborate and catalyzed by
[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)
[PdCl2(dppf), 5 mol %] (Table 1).14 A Horner−Wadsworth−
Emmons (HWE) reaction of benzaldehydes 6a−f with triethyl
phosphonoacetate (TEPA) under mild Masamune−Roush
conditions gave (E)-α,β-unsaturated esters 7a−f as the sole
products in excellent yields (87−100%).15 Subsequent
reduction of esters 7a−f with DIBAL-H completed the three-
step synthesis of desired (E)-(2-vinyl)cinnamyl alcohols 8a−f
in high overall yields.
Optimization of the one-pot Overman rearrangement and
RCM reaction focused on the preparation of amino-substituted
indene 11a (Scheme 2). (2-Vinyl)cinnamyl alcohol 8a (R = H)
was converted to the corresponding allylic trichloroacetimidate
using trichloroacetonitrile and a catalytic amount of DBU, and
without purification this was subjected to a thermally mediated
Overman rearrangement at 160 °C.16 Grubbs first generation
catalyst was initially investigated for the RCM step.17 However,
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Scheme 2. Synthesis of Amino-Substituted Indenes 11a−f
Table 2. Synthesis of Allylic Alcohols 15a−h
for complete conversion, a high catalyst loading (25 mol %)
and long reaction time (96 h) were required, giving indene 11a
in 42% yield over the three steps. This stage of the one-pot
process was significantly improved using Grubbs second
generation catalyst.18 After 20 h, complete conversion was
achieved using a 5 mol % catalyst loading that gave indene 11a
in 82% overall yield from allylic alcohol 8a (Scheme 2).19 Using
these optimized conditions, the scope of the one-pot process
for the synthesis of a small library of amino-substituted indenes
was explored. Overall, the one-pot process was found to be
general for a range of allylic trichloroacetimidates 9b−f bearing
electron-rich or electron-deficient substituents, giving the
aminoindenes 11b−f in good yields from allylic alcohols 8b−f.
Attention then turned to the development of a short route
for the preparation of (E)-(2-allyl)cinnamyl alcohols that would
allow the preparation of dihydronaphthalene analogues. Some
optimization was required for incorporation of the allyl side-
chain. For this reason, the aldehyde moiety was initially
converted to the more stable (E)-α,β-unsaturated esters 12a−g
using a HWE reaction with TEPA (Table 2). Conditions for an
efficient allylation were then explored. The use of a Suzuki−
Miyaura reaction with allylboronic acid pinacol ester (13) and
Pd(PPh3)4 (10 mol %) as a catalyst at high temperature (>100
°C) gave the coupled products in high yields.20 However, these
were often contaminated with up to 30% of the proto-
debrominated (E)-α,β-unsaturated ester. This issue was
overcome with the use of PdCl2(dppf) (10 mol %) as a
catalyst and a lower reaction temperature (85 °C), which gave
allylated products 14a−g very cleanly and in essentially
quantitative yields.21 DIBAL-H reduction of esters 14a−g
then completed the three-step synthesis of (E)-(2-allyl)-
cinnamyl alcohols 15a−g. This series of allylic alcohols was
extended to include a heteroaromatic analogue. Allylic alcohol
a
Reaction performed at 100 °C.
15h bearing an allylfuran side-chain was prepared in four steps
from 3-bromofuran. Initially, 3-bromofuran was formylated at
the 2-position using Rieche conditions (MeOCHCl2/TiCl4),
which gave 3-bromo-2-furaldehyde (5h) in 96% yield.22
Application of the previously described three-step sequence
involving a HWE reaction, allylation, and DIBAL-H reduction
gave allylic alcohol 15h in 89% overall yield (Table 2).
With a series of (E)-(2-allyl)cinnamyl alcohols in hand,
conditions for the one-pot synthesis of amino-substituted 1,4-
dihydronaphthalenes were optimized. Overman rearrangement
of the allylic trichloroacetimidate derived from allylic alcohol
15a was found to proceed to full conversion after 18 h at 160
°C. Lower temperatures (120−140 °C) resulted in incomplete
conversion (∼80%) even after 24 h. A comparison of catalysts
for the RCM step showed again that a relatively high catalyst
loading of Grubbs first generation catalyst (15 mol %) was
required for complete conversion to the 1,4-dihydronaphtha-
lene, while under the same conditions, only 5 mol % of Grubbs
second generation catalyst was necessary. Using these
optimized conditions as a one-pot process gave 1,4-
dihydronaphthalene 16a in 89% yield from allylic alcohol 15a
(Scheme 3). The scope of this process for the general synthesis
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lowered to 2.5 mol %, while still maintaining consistently high
yields over the three steps (Scheme 3). For conversion of 16c
to the corresponding naphthalene 17, various oxidizing agents
were screened (Scheme 4).25 While the use of manganese
Scheme 3. Synthesis of Amino-Substituted 1,4-
Dihydronaphthalenes 16a−h
a,b
Scheme 4. Synthesis of Amides 22a−d
a
The RCM step was performed using 2.5 mol % of Grubbs second
generation catalyst.23 The RCM step required 10 mol % of Grubbs
b
second generation catalyst and was performed at 50 °C over 48 h.
of amino-substituted 1,4-dihydronaphthalenes 16b−g with
electron-rich or electron-deficient groups as well as various
substitution patterns was then explored and found to be
particularly robust for the high-yielding synthesis of this series
of compounds. In a similar fashion, conversion of the furan-
derived allylic alcohol 15h to the corresponding allylic
trichloroacetimidate and implementation of the one-pot two-
step process gave amino-substituted 1,4-dihydrobenzofuran
16h in 72% yield.
Indane and tetrahydronaphthalene ring systems with C-1
amino functionality are privileged structures found within a
range of pharmaceutically important agents used for the
treatment of diseases associated with neurology and cardiol-
ogy.24 However, in this study, we wanted to demonstrate the
synthetic utility of the compounds generated from the one-pot
multistep approach by application to the total synthesis of
natural products. In particular, 1,4-dihydronaphthalene 16c,
which was prepared in 75% overall yield from commercially
available 2-bromo-4,5-methylenedioxybenzaldehyde (5c), was
chosen as a key intermediate for the total synthesis of the
oxybenzo[c]phenanthridine alkaloids oxychelerythrine (1),
oxysanguinarine (2), oxynitidine (3), and oxyavicine (4). It
was proposed that aromatization of 16c followed by coupling of
the amino group with a suitably derived 2-bromobenzoic acid
and then an intramolecular biaryl Heck coupling reaction would
allow access to the oxybenzo[c]phenanthridine alkaloids in
relatively few steps.
dioxide did produce a quinone byproduct 18 (16%), the
reaction gave the best yield of naphthalene 17 (72%). Acid-
mediated hydrolysis of trichloroacetamide 17 was then followed
by coupling of the resulting amine 19 with various 2-
bromobenzoyl chlorides 20a−d under standard conditions.
Methylation with sodium hydride and iodomethane gave the
penultimate compounds 22a−d in excellent yields.
The last step for the synthesis of the oxybenzo[c]-
phenanthridine alkaloids required an intramolecular Heck
coupling reaction of aryl bromides 22a−d. Building on initial
work by Ames and Opalko,26 the research group of Harayama
has studied extensively this type of amide-tethered biaryl
coupling for the synthesis of oxychelerythrine (1), oxynitidine
(3), and other oxybenzo[c]phenanthridine alkaloids.6h They
found that Heck coupling of 22a using palladium(II) acetate
(20 mol %) in the presence of P(o-tol)3 and silver carbonate
gave oxychelerythrine (1) in 96% yield.7b−d While this is a
sterically demanding coupling, the transformation is assisted by
the presence of a substituent ortho to the amide (R3 = OMe),
which helps position the bromide for reaction. To produce
oxynitidine (3) using a similar coupling process is more
challenging as the Heck precursor for this reaction has no
directing group (R3 = H) to preorganize the substrate.
Therefore, in their synthesis of oxynitidine (3), Harayama
and co-workers found that a high-yielding reaction (89%) could
be achieved only by using a more reactive iodide analogue of
For this part of the program, multigram quantities of 1,4-
dihydronaphthalene 16c were produced by scale-up of the one-
pot two-step process. During these reactions, it was found that
the total loading of Grubbs second generation catalyst could be
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22c and high loading of palladium(II) acetate (100 mol %).9c
By repeating the Harayama conditions in the Heck reaction of
22a, we were able to isolate oxychelerythrine (1) in a similar
yield of 97%. However, attempted Heck coupling of aryl
bromides 22b, 22c, and 22d using the same reagents and
conditions with various catalyst loadings (30−100 mol %) gave
oxysanguinarine (2), oxynitidine (3), and oxyavicine (4)
respectively, in low yields (19−29%) with substantial amounts
of starting material recovered even after extended reaction
times (24 h). It was observed during repeated attempts of the
coupling reactions that palladium(0) precipitated at an early
stage from the reaction mixture. To develop a more general and
efficient intramolecular biaryl Heck reaction for the synthesis of
the oxybenzo[c]phenanthridine alkaloids using aryl bromide
precursors and at the high temperatures typically required, a
more stable palladium catalyst was required. The Hermann−
Beller palladacycle 23 is well-known for its reactivity at high
temperatures (Figure 2).27,28 This is due to the slow release of
catalyst in the presence of silver carbonate at 160 °C,
conversion was complete after 22 h. This allowed the isolation
of oxychelerythrine (1) in 95% yield. Using the same
conditions for aryl bromide 22b, the reaction was complete
after 3 h, giving oxysanguinarine (2) in 90% yield. The more
challenging Heck couplings of 22c and 22d required a higher
catalyst loading (20 mol %) for complete conversion and, after
22 h, oxynitidine (3) and oxyavicine (4) were isolated in 83%
and 78% yield, respectively. In all four cases, the use of the
Hermann−Beller palladacycle gave the natural products from
aryl bromide substrates in excellent yields and at substantially
lower catalyst loading compared to the combination of
palladium(II) acetate and P(o-tol)3.
CONCLUSIONS
■
In summary, short, flexible, and efficient synthetic routes for the
preparation of allylic alcohols bearing 2-vinylaryl and 2-allylaryl
side-chains have been developed. On conversion to the
corresponding allylic trichloroacetamides, these compounds
were found to be excellent substrates for a one-pot Overman
rearrangement and RCM reaction process, generating a diverse
library of aminoindenes and amino-substituted 1,4-dihydro-
naphthalenes in high overall yields. The synthetic utility of
these privileged structures was demonstrated by the use of 1,4-
dihydronaphthalene 16c for the synthesis of four oxybenzo[c]-
phenanthridine alkaloids. Optimization of the key step, an
intramolecular biaryl Heck coupling reaction using the
Hermann−Beller palladacycle, completed the total synthesis
of oxychelerythrine (1), oxysanguinarine (2), oxynitidine (3),
and oxyavicine (4) in 11 steps and in 46%, 42%, 38%, and 38%
overall yields, respectively. Work is currently underway to
investigate further synthetic applications of the aminoindenes
and amino-1,4-dihydronaphthalenes generated from this study
as well as extending the range of polycyclic classes of
compound that can be prepared using one-pot multireaction
processes.
Figure 2. Hermann−Beller palladacycle 23.
active Pd(0) during the reaction, which prevents deactivation
processes.29 Furthermore, palladacycle 23 has been utilized for
a number of challenging Heck reactions,30 including the
efficient intramolecular coupling of amine-tethered aryl
bromides with cyclic alkenes for the preparation of phenan-
thridine ring systems.30d
Palladacycle 23 was initially investigated for Heck coupling of
aryl bromide 22a (Scheme 5). Using 10 mol % loading of
Scheme 5. Synthesis of Oxybenzo[c]phenanthridine
Alkaloids 1−4
EXPERIMENTAL SECTION
■
a,b
All reagents and starting materials were obtained from commercial
sources and used as received. All dry solvents were purified using a
solvent purification system. All reactions were performed under an
atmosphere of argon unless otherwise mentioned. Brine refers to a
saturated solution of sodium chloride. Flash column chromatography
was performed using silica gel 60 (35−70 μm). Aluminum-backed
plates precoated with silica gel 60F254 were used for thin layer
chromatography and were visualized with a UV lamp or by staining
1
with potassium permanganate. H NMR spectra were recorded on a
NMR spectrometer at either 400 or 500 MHz, and data are reported as
follows: chemical shift in ppm relative to tetramethylsilane or the
solvent as the internal standard (CDCl3, δ 7.26 ppm or DMSO-d6, δ
2.50 ppm), multiplicity (s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet or overlap of nonequivalent resonances,
integration). 13C NMR spectra were recorded on a NMR spectrometer
at either 101 or 126 MHz, and data are reported as follows: chemical
shift in ppm relative to tetramethylsilane or the solvent as internal
standard (CDCl3, δ 77.2 ppm or DMSO-d6, δ 39.5 ppm), multiplicity
with respect to proton (deduced from DEPT experiments, C, CH,
CH2, or CH3). Infrared spectra were recorded on a FTIR
spectrometer; wavenumbers are indicated in cm−1. Mass spectra
were recorded using electron impact, chemical ionization, or
electrospray techniques. High resolution mass spectra were recorded
using a dual-focusing magnetic analyzer mass spectrometer. Melting
points are uncorrected.
2-Vinylbenzaldehyde (6a).31 Potassium vinyltrifluoroborate
(0.904 g, 6.75 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-
a
b
Reaction time was 3 h. Catalyst loading of 23 was 20 mol %.
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palladium(II) dichloride (0.276 g, 0.337 mmol) were added to a
degassed solution of 2-bromobenzaldehyde (5a) (0.624 g, 3.37 mmol)
and triethylamine (1.40 mL, 10.1 mmol) in propan-2-ol (34 mL). The
solution was then heated to 80 °C for 18 h. The reaction mixture was
cooled to room temperature, concentrated in vacuo, and purified by
filtration through a pad of silica (elution with 20% diethyl ether in
petroleum ether) to yield 2-vinylbenzaldehyde (6a) (0.374 g, 84%) as
a yellow oil. Spectroscopic data were in accordance with literature
values.31 1H NMR (400 MHz, CDCl3) δ 5.52 (dd, J 11.0, 1.2 Hz, 1H),
5.71 (dd, J 17.4, 1.2 Hz, 1H), 7.40−7.48 (m, 1-H), 7.49−7.60 (m,
3H), 7.81−7.86 (m, 1H), 10.30 (s, 1H); 13C NMR (101 MHz,
CDCl3) δ 119.6 (CH2), 127.6 (CH), 128.1 (CH), 131.4 (CH), 133.1
(C), 133.5 (CH), 133.9 (CH), 140.7 (C), 192.6 (CH); MS (EI) m/z
132 (M+, 60), 131 (20), 104 (53), 103 (52), 86 (92), 84 (100), 78
(42).
(0.269 g, 89%) as a yellow oil. Spectroscopic data were in accordance
with literature values.33 1H NMR (400 MHz, CDCl3) δ 3.87 (s, 3H),
5.45 (dd, J 10.9, 1.1 Hz, 1H), 5.61 (dd, J 17.3, 1.1 Hz, 1H), 7.13 (dd, J
8.6, 2.8 Hz, 1H), 7.34 (d, J 2.8 Hz, 1H), 7.42 (dd, J 17.3, 10.9 Hz, 1H),
7.51 (d, J 8.6 Hz, 1H), 10.32 (s, 1H); 13C NMR (101 MHz, CDCl3) δ
55.7 (CH3), 113.0 (CH), 118.3 (CH2), 121.3 (CH), 129.0 (CH),
132.4 (CH), 133.9 (C), 134.0 (C), 159.5 (C), 191.8 (CH); MS (EI)
m/z 162 (M+, 66), 134 (100), 119 (42), 91 (41), 84 (39), 49 (28).
Ethyl (2E)-3-(2′-Vinylphenyl)prop-2-enoate (7a).34 Lithium
bromide (0.583 g, 6.70 mmol) was added to a solution of triethyl
phosphonoacetate (1.13 mL, 5.69 mmol) and 1,8-diazabicyclo[5.4.0]-
undec-7-ene (0.848 mL, 5.69 mmol) in acetonitrile (25 mL) and
stirred at room temperature for 0.5 h. 2-Vinylbenzaldehyde (6a)
(0.221 g, 1.67 mmol) was added, and the solution was stirred at room
temperature for 18 h. The reaction was quenched by the addition of a
saturated solution of ammonium chloride (30 mL), concentrated to
half volume in vacuo, and extracted with diethyl ether (3 × 30 mL).
The combined organic layers were washed with water (100 mL) and
brine (100 mL), dried (MgSO4), filtered, and concentrated in vacuo.
Purification by filtration through a pad of silica (elution with 20%
diethyl ether in petroleum ether) gave ethyl (2E)-3-(2′-vinylphenyl)-
prop-2-enoate (7a) (0.331 g, 98%) as a yellow oil. Spectroscopic data
were in accordance with literature values.34 1H NMR (400 MHz,
CDCl3) δ 1.34 (t, J 7.2 Hz, 3H), 4.27 (q, J 7.2 Hz, 2H), 5.43 (dd, J
11.0, 1.2 Hz, 1H), 5.64 (dd, J 17.4, 1.2 Hz, 1H), 6.35 (d, J 15.9 Hz,
1H), 7.07 (dd, J 17.4, 11.0 Hz, 1H), 7.29 (td, J 7.5, 1.2 Hz, 1H), 7.36
(td, J 7.5, 1.2 Hz, 1H), 7.46−7.55 (m, 2H), 8.04 (d, J 15.9 Hz, 1H);
13C NMR (101 MHz, CDCl3) δ 14.5 (CH3), 60.7 (CH2), 118.2
(CH2), 120.5 (CH), 127.1 (CH), 127.2 (CH), 128.1 (CH), 130.1
(CH), 132.7 (C), 134.4 (CH), 138.1 (C), 142.5 (CH), 167.0 (C); MS
(EI) m/z 202 (M+, 10), 173 (4), 157 (10), 129 (100), 128 (58), 102
(5), 83 (12).
4-Methyl-2-vinylbenzaldehyde (6b).31 The reaction was carried
out according to the previously described procedure for 2-vinyl-
benzaldehyde (6a) using 2-bromo-4-methylbenzaldehyde (5b) (0.400
g, 2.01 mmol). This gave 4-methyl-2-vinylbenzaldehyde (6b) (0.264 g,
90%) as a yellow oil. Spectroscopic data were in accordance with
literature values.31 1H NMR (400 MHz, CDCl3) δ 2.43 (s, 3H), 5.49
(dd, J 11.0, 1.2 Hz, 1H), 5.69 (dd, J 17.4, 1.2 Hz, 1H), 7.24 (d, J 7.9
Hz, 1H), 7.37 (s, 1H), 7.53 (dd, J 17.4, 11.0 Hz, 1H), 7.73 (d, J 7.9 Hz,
1H), 10.23 (s, 1H); 13C NMR (101 MHz, CDCl3) δ 22.0 (CH3),
119.2 (CH2), 128.2 (CH), 128.9 (CH), 130.9 (C), 131.7 (CH), 133.7
(CH), 140.7 (C), 144.9 (C), 192.2 (CH); MS (EI) m/z 146 (M+,
100), 117 (71), 115 (37), 91 (25), 84 (11).
4,5-Methylenedioxy-2-vinylbenzaldehyde (6c).32 The reac-
tion was carried out according to the previously described procedure
for 2-vinylbenzaldehyde (6a) using 2-bromo-4,5-methylenedioxyben-
zaldehyde (5c) (0.400 g, 1.75 mmol). This gave 4,5-methylenedioxy-2-
vinylbenzaldehyde (6c) (0.296 g, 96%) as a yellow solid. Mp 50−53
°C (lit.32 52−54 °C); 1H NMR (500 MHz, CDCl3) δ 5.48 (dd, J 10.9,
0.8 Hz, 1H), 5.62 (dd, J 17.3, 0.8 Hz, 1H), 6.05 (s, 2H), 6.98 (s, 1H),
7.31 (s, 1H), 7.41 (dd, J 17.3, 10.9 Hz, 1H), 10.21 (s, 1H); 13C NMR
(126 MHz, CDCl3) δ 102.2 (CH2), 106.8 (CH), 108.1 (CH), 119.2
(CH2), 128.2 (C), 132.4 (CH), 138.5 (C), 148.1 (C), 152.7 (C),
189.6 (CH); MS (EI) m/z 176 (M+, 100), 147 (91), 84 (90), 49 (68).
5-Fluoro-2-vinylbenzaldehyde (6d).31 The reaction was carried
out according to the previously described procedure for 2-vinyl-
benzaldehyde (6a) using 2-bromo-5-fluorobenzaldehyde (5d) (0.500
g, 2.46 mmol) and potassium vinyltrifluoroborate (0.396 g, 2.96
mmol). This gave 5-fluoro-2-vinylbenzaldehyde (6d) (0.336 g, 91%)
as a yellow oil. Spectroscopic data were in accordance with literature
values.31 1H NMR (400 MHz, CDCl3) δ 5.50 (d, J 11.0 Hz, 1H), 5.62
(d, J 17.4 Hz, 1H), 7.18−7.26 (m, 1H), 7.38 (dd, J 17.4, 11.0 Hz, 1H),
7.44−7.54 (m, 2H), 10.24 (s, 1H); 13C NMR (101 MHz, CDCl3) δ
Ethyl (2E)-3-(4′-Methyl-2′-vinylphenyl)prop-2-enoate (7b).
The reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate (7a) using
4-methyl-2-vinylbenzaldehyde (6b) (0.258 g, 1.77 mmol). This gave
ethyl (2E)-3-(4′-methyl-2′-vinylphenyl)prop-2-enoate (7b) (0.385 g,
100%) as a yellow oil. IR (neat) 2980, 1710, 1631, 1313, 1266, 1176,
1
1158, 1037 cm−1; H NMR (400 MHz, CDCl3) δ 1.34 (t, J 7.1 Hz,
3H), 2.37 (s, 3H), 4.26 (q, J 7.1 Hz, 2H), 5.40 (dd, J 11.0, 1.3 Hz,
1H), 5.62 (dd, J 17.3, 1.3 Hz, 1H), 6.32 (d, J 15.9 Hz, 1H), 7.06 (dd, J
17.3, 11.0 Hz, 1H), 7.09−7.12 (m, 1H), 7.30 (s, 1H), 7.45 (d, J 8.0 Hz,
1H), 8.01 (d, J 15.9 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 14.5
(CH3), 21.5 (CH3), 60.6 (CH2), 117.9 (CH2), 119.4 (CH), 127.1
(CH), 127.7 (CH), 129.0 (CH), 129.9 (C), 134.5 (CH), 138.1 (C),
140.3 (C), 142.3 (CH), 167.2 (C); HRMS (ESI) calcd for
C14H16NaO2 (MNa+), 239.1043, found 239.1035.
Ethyl (2E)-3-(4′,5′-Methylenedioxy-2′-vinylphenyl)prop-2-
enoate (7c). The reaction was carried out according to the previously
described procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate
(7a) using 4,5-methylenedioxy-2-vinylbenzaldehyde (6c) (0.279 g,
1.59 mmol). This gave ethyl (2E)-3-(4′,5′-methylenedioxy-2′-
vinylphenyl)prop-2-enoate (7c) (0.367 g, 94%) as a white solid. Mp
82−84 °C; IR (neat) 2904, 1714, 1614, 1500, 1489, 1284, 1177 cm−1;
1H NMR (500 MHz, CDCl3) δ 1.33 (t, J 7.1 Hz, 3H), 4.26 (q, J 7.1
Hz, 2H), 5.35 (dd, J 10.9, 1.0 Hz, 1H), 5.53 (dd, J 17.2, 1.0 Hz, 1H),
5.98 (s, 2H), 6.21 (d, J 15.7 Hz, 1H), 6.95 (s, 1H), 7.00 (s, 1H), 7.03
(dd, J 17.2, 10.9 Hz, 1H), 7.98 (d, J 15.7 Hz, 1H); 13C NMR (126
MHz, CDCl3) δ 14.5 (CH3), 60.6 (CH2), 101.7 (CH2), 106.1 (CH),
106.6 (CH), 116.9 (CH2), 118.6 (CH), 126.9 (C), 133.8 (C), 133.9
(CH), 141.7 (CH), 148.1 (C), 149.8 (C), 167.1 (C); MS m/z 246
(M+, 76), 217 (30), 201 (30), 173 (100), 143 (38), 115 (96); HRMS
(EI) calcd for C14H14O4 (M+), 246.0892, found 246.0889.
2
2
116.1 (CH, d, JCF 22.1 Hz), 119.9 (CH2), 121.1 (CH, d, JCF 21.9
3
3
Hz), 129.7 (CH, d, JCF 7.3 Hz), 132.0 (CH), 134.4 (C, d, JCF 5.9
4
1
Hz), 137.0 (C, d, JCF 3.4 Hz), 162.3 (C, d, JCF 249.5 Hz), 190.6
(CH); MS (EI) m/z 150 (M+, 79), 122 (100), 121 (63), 101 (61), 96
(52), 75 (32).
1-Vinyl-2-naphthaldehyde (6e).31 The reaction was carried out
according to the previously described procedure for 2-vinylbenzalde-
hyde (6a) using 1-bromo-2-naphthaldehyde (5e) (0.400 g, 1.70
mmol). This gave 1-vinyl-2-naphthaldehyde (6e) (0.275 g, 89%) as a
yellow solid. Spectroscopic data were in accordance with literature
values.31 Mp 68−70 °C; H NMR (400 MHz, CDCl3) δ 5.49 (dd, J
1
17.5, 1.6 Hz, 1H), 6.01 (dd, J 11.3, 1.6 Hz, 1H), 7.38 (dd, J 17.5, 11.3
Hz, 1H), 7.58 (ddd, J 8.4, 6.9, 1.4 Hz, 1H), 7.63 (ddd, J 8.4, 6.9, 1.3
Hz, 1H), 7.83 (d, J 8.4 Hz, 1H), 7.87 (dd, J 8.4, 1.3 Hz, 1H), 8.00 (d, J
8.4 Hz, 1H), 8.18 (dd, J 8.4, 0.7 Hz, 1H), 10.46 (d, J 0.7 Hz, 1H); 13C
NMR (101 MHz, CDCl3) δ 123.1 (CH2), 126.0 (CH), 126.2 (CH),
127.1 (CH), 128.2 (CH), 128.6 (CH), 129.0 (CH), 130.8 (CH),
131.5 (C), 131.7 (C), 135.9 (C), 143.4 (C), 192.8 (CH); MS (EI) m/
z 182 (M+, 57), 153 (100), 152 (52), 127 (14), 84 (11), 76 (13).
5-Methoxy-2-vinylbenzaldehyde (6f).33 The reaction was
carried out according to the previously described procedure for 2-
vinylbenzaldehyde (6a) using 2-bromo-5-methoxybenzaldehyde (5f)
(0.400 g, 1.86 mmol). This gave 5-methoxy-2-vinylbenzaldehyde (6f)
Ethyl (2E)-3-(5′-Fluoro-2′-vinylphenyl)prop-2-enoate (7d).
The reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate (7a) using
5-fluoro-2-vinylbenzaldehyde (6d) (0.190 g, 1.27 mmol). This gave
ethyl (2E)-3-(5′-fluoro-2′-vinylphenyl)prop-2-enoate (7d) (0.247 g,
89%) as a yellow oil. IR (neat) 2982, 2932, 1712, 1636, 1486, 1316,
1
1237, 1176, 1034 cm−1; H NMR (400 MHz, CDCl3) δ 1.33 (t, J 7.1
F
dx.doi.org/10.1021/jo5014492 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Hz, 3H), 4.26 (q, J 7.1 Hz, 2H), 5.38 (dd, J 10.9, 0.7 Hz, 1H), 5.56
(dd, J 17.2, 0.7 Hz, 1H), 6.31 (d, J 15.9 Hz, 1H), 6.92−7.06 (m, 2H),
7.18 (dd, J 9.2, 2.7 Hz, 1H), 7.43 (dd, J 9.2, 5.7 Hz, 1H), 7.94 (dd, J
15.9, 1.3 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 14.4 (CH3), 60.8
1.4 Hz, 1H), 5.61 (dd, J 17.4, 1.4 Hz, 1H), 6.20 (dt, J 15.7, 5.7 Hz,
1H), 6.88 (d, J 15.7 Hz, 1H), 7.00 (dd, J 17.4, 11.0 Hz, 1H), 7.06 (d, J
7.9 Hz, 1H), 7.26 (s, 1H), 7.33 (d, J 7.9 Hz, 1H); 13C NMR (126
MHz, CDCl3) δ 21.3 (CH3), 64.2 (CH2), 116.3 (CH2), 126.7 (CH),
127.1 (CH), 128.9 (CH), 128.9 (CH), 130.3 (CH), 132.3 (C), 135.0
(CH), 136.2 (C), 137.6 (C); MS m/z 157 (MH+ − H2O, 98), 113
(31), 97 (38), 85 (85), 71 (100), 69 (90); HRMS (CI) calcd for
C12H13 (MH+ − H2O), 157.1017, found 157.1021.
(2E)-3-(4′,5′-Methylenedioxy-2′-vinylphenyl)prop-2-en-1-ol
(8c). The reaction was carried out according to the previously
described procedure for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a)
using ethyl (2E)-3-(4′,5′-methylenedioxy-2′-vinylphenyl)prop-2-
enoate (7c) (0.357 g, 1.45 mmol). This gave (2E)-3-(4′,5′-
methylenedioxy-2′-vinylphenyl)prop-2-en-1-ol (8c) (0.292 g, 99%)
as a white solid. Mp 73−76 °C; IR (neat) 3332, 2896, 1622, 1501,
1478, 1245, 1039 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.65 (s, 1H),
4.30 (dd, J 5.7, 1.5 Hz, 2H), 5.23 (dd, J 10.9, 1.0 Hz, 1H), 5.49 (dd, J
17.3, 1.0 Hz, 1H), 5.93 (s, 2H), 6.10 (dt, J 15.6, 5.7 Hz, 1H), 6.84 (dt,
J 15.6, 1.5 Hz, 1H), 6.89 (s, 1H), 6.93 (s, 1H), 6.94 (dd, J 17.3, 10.9
Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 62.9 (CH2), 100.2 (CH2),
105.0 (CH), 105.2 (CH), 113.9 (CH2), 127.6 (CH), 128.5 (C), 128.8
(CH), 129.7 (C), 133.4 (CH), 146.8 (C), 146.8 (C); MS m/z 204
(M+, 30), 173 (78), 115 (41), 82 (100); HRMS (EI) calcd for
C12H12O3 (M+), 204.0786, found 204.0790.
2
2
(CH2), 113.2 (CH, d, JCF 22.3 Hz), 117.1 (CH, d, JCF 21.6 Hz),
3
118.0 (CH2), 121.4 (CH), 128.9 (CH, d, JCF 8.1 Hz), 133.3 (CH),
134.3 (C, d, 4JCF 3.2 Hz), 134.4 (C, d, 3JCF 7.6 Hz), 141.1 (CH, d, 4JCF
1
2.3 Hz), 162.3 (C, d, JCF 247.3 Hz), 166.5 (C); HRMS (ESI) calcd
for C13H13FNaO2 (MNa+), 243.0792, found 243.0789.
Ethyl (2E)-3-(1′-Vinylnaphthalen-2′-yl)prop-2-enoate (7e).
The reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate (7a) using
1-vinyl-2-naphthaldehyde (6e) (0.271 g, 1.49 mmol). This gave ethyl
(2E)-3-(1′-vinylnaphthalen-2′-yl)prop-2-enoate (7e) (0.327 g, 87%)
as a yellow oil. IR (neat) 2978, 1711, 1627, 1293, 1256, 1175, 1038
cm−1; 1H NMR (500 MHz, CDCl3) δ 1.35 (t, J 7.1 Hz, 3H), 4.28 (q, J
7.1 Hz, 2H), 5.43 (dd, J 17.7, 1.8 Hz, 1H), 5.93 (dd, J 11.4, 1.8 Hz,
1H), 6.48 (d, J 16.0 Hz, 1H), 7.21 (dd, J 17.7, 11.4 Hz, 1H), 7.49−
7.55 (m, 2H), 7.71 (d, J 8.7 Hz, 1H), 7.77 (d, J 8.7 Hz, 1H), 7.80−7.85
(m, 1H), 8.10−8.14 (m, 1H), 8.24 (d, J 16.0 Hz, 1H); 13C NMR (126
MHz, CDCl3) δ 14.5 (CH3), 60.6 (CH2), 119.1 (CH2), 123.6 (CH),
124.4 (CH), 126.2 (CH), 126.8 (CH), 127.1 (CH), 128.0 (CH),
128.4 (CH), 129.6 (C), 131.9 (C), 132.7 (CH), 134.1 (C), 138.2 (C),
144.0 (CH), 167.3 (C); HRMS (ESI) calcd for C17H16NaO2 (MNa+),
275.1043, found 275.1037.
(2E)-3-(5′-Fluoro-2′-vinylphenyl)prop-2-en-1-ol (8d). The re-
action was carried out according to the previously described procedure
for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a) using ethyl (2E)-3-(5′-
fluoro-2′-vinylphenyl)prop-2-enoate (7d) (0.223 g, 1.01 mmol). This
gave (2E)-3-(5′-fluoro-2′-vinylphenyl)prop-2-en-1-ol (8d) (0.174 g,
97%) as a colorless oil. IR (neat) 3329, 2868, 1605, 1574, 1483, 1096,
Ethyl (2E)-3-(5′-Methoxy-2′-vinylphenyl)prop-2-enoate (7f).
The reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate (7a) using
5-methoxy-2-vinylbenzaldehyde (6f) (0.266 g, 1.64 mmol). This gave
ethyl (2E)-3-(5′-methoxy-2′-vinylphenyl)prop-2-enoate (7f) (0.376 g,
99%) as a yellow oil. IR (neat) 2980, 1709, 1634, 1603, 1493, 1314,
1236, 1167, 1035, 980 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.35 (t, J
7.1 Hz, 3H), 3.83 (s, 3H), 4.27 (q, J 7.1 Hz, 2H), 5.32 (dd, J 11.0, 1.1
Hz, 1H), 5.54 (dd, J 17.3, 1.1 Hz, 1H), 6.33 (d, J 15.8 Hz, 1H), 6.92
(dd, J 8.6, 2.7 Hz, 1H), 7.00 (dd, J 17.3, 11.0 Hz, 1H), 7.02 (d, J 2.7
Hz, 1H), 7.43 (d, J 8.6 Hz, 1H), 8.01 (d, J 15.8 Hz, 1H); 13C NMR
(126 MHz, CDCl3) δ 14.3 (CH3), 55.4 (CH3), 60.6 (CH2), 111.1
(CH), 116.2 (CH2), 116.5 (CH), 120.4 (CH), 128.2 (CH), 130.9 (C),
133.5 (CH), 133.6 (C), 142.3 (CH), 159.2 (C), 166.8 (C); MS m/z
232 (M+, 53), 203 (47), 187 (24), 159 (100), 144 (83), 115 (53);
HRMS (EI) calcd for C14H16O3 (M+), 232.1099, found 232.1099.
(2E)-3-(2′-Vinylphenyl)prop-2-en-1-ol (8a). Diisobutylalumi-
num hydride (3.33 mL, 3.33 mmol, 1 M solution in hexanes) was
added dropwise with stirring to a solution of ethyl (2E)-3-(2′-
vinylphenyl)prop-2-enoate (7a) (0.269 g, 1.33 mmol), in diethyl ether
(27 mL) at −78 °C. The solution was stirred at −78 °C for 3 h and
then warmed to room temperature over 15 h. The reaction was
quenched with 10% aqueous potassium sodium tartrate solution (30
mL), extracted with diethyl ether (2 × 20 mL), washed with water
(100 mL) and brine (100 mL), dried (MgSO4), filtered and
concentrated in vacuo. Purification by column chromatography
(elution with 50% diethyl ether in petroleum ether) yielded (2E)-3-
(2′-vinylphenyl)prop-2-en-1-ol (8a) (0.207 g, 97%) as a colorless oil.
1
964, 912 cm−1; H NMR (500 MHz, CDCl3) δ 1.54 (br s, 1H), 4.36
(dd, J 5.4, 1.5 Hz, 2H), 5.31 (dd, J 11.0, 0.9 Hz, 1H), 5.56 (dd, J 17.4,
0.9 Hz, 1H), 6.25 (dt, J 15.8, 5.4 Hz, 1H), 6.87 (dd, J 15.8, 1.5 Hz,
1H), 6.91−6.98 (m, 2H), 7.11 (dd, J 9.3, 2.7 Hz, 1H), 7.41 (dd, J 9.3,
5.9 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 63.7 (CH2), 112.9 (d,
2
2JCF 22.0 Hz, CH), 114.9 (d, JCF 21.6 Hz, CH), 116.4 (CH2), 127.6
4
3
(d, JCF 2.2 Hz, CH), 128.3 (d, JCF 8.3 Hz, CH), 132.2 (CH), 132.5
4
3
(d, JCF 3.1 Hz, C), 133.9 (CH), 137.0 (d, JCF 7.7 Hz, C), 162.6 (d,
1JCF 246.2 Hz, C); MS m/z 178 (M+, 4), 160 (11), 147 (100), 133
(13), 127 (10), 84 (5); HRMS (EI) calcd for C11H11FO (M+),
178.0794, found 178.0791.
(2E)-3-(1′-Vinylnaphthalen-2′-yl)prop-2-en-1-ol (8e). The re-
action was carried out according to the previously described procedure
for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a) using ethyl (2E)-3-(1′-
vinylnaphthalen-2′-yl)prop-2-enoate (7e) (0.325 g, 1.29 mmol). This
gave (2E)-3-(1′-vinylnaphthalen-2′-yl)prop-2-en-1-ol (8e) (0.248 g,
92%) as a yellow oil. IR (neat) 3327, 3056, 2859, 1508, 1418, 1094,
994, 970 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.49 (t, J 5.7 Hz, 1H),
4.38 (t, J 5.7 Hz, 2H), 5.43 (dd, J 17.8, 2.0 Hz, 1H), 5.84 (dd, J 11.4,
2.0 Hz, 1H), 6.41 (dt, J 15.9, 5.7 Hz, 1H), 7.07−7.15 (m, 2H), 7.43−
7.50 (m, 2H), 7.69 (d, J 8.7 Hz, 1H), 7.74 (d, J 8.7 Hz, 1H), 7.79−7.82
(m, 1H), 8.08−8.11 (m, 1H); 13C NMR (126 MHz, CDCl3) δ 64.3
(CH2), 122.9 (CH2), 123.8 (CH), 125.9 (CH), 125.9 (CH), 126.4
(CH), 127.6 (CH), 128.2 (CH), 129.6 (CH), 130.4 (CH), 131.5 (C),
132.0 (C), 133.1 (C), 133.5 (CH), 134.8 (C); MS m/z 210 (M+, 10),
179 (100), 165 (29), 152 (19), 139 (6), 115 (5), 67 (21); HRMS (EI)
calcd for C15H14O (M+), 210.1045, found 210.1049.
(2E)-3-(5′-Methoxy-2′-vinylphenyl)prop-2-en-1-ol (8f). The
reaction was carried out according to the previously described
procedure for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a) using ethyl
(2E)-3-(5′-methoxy-2′-vinylphenyl)prop-2-enoate (7f) (0.321 g, 1.38
mmol). This gave (2E)-3-(5′-methoxy-2′-vinylphenyl)prop-2-en-1-ol
(8f) (0.233 g, 89%) as a colorless oil. IR (neat) 3345, 2936, 1603,
1491, 1288, 1246, 1167, 1105, 1024 cm−1; 1H NMR (500 MHz,
CDCl3) δ 1.96 (br s, 1H), 3.81 (s, 3H), 4.33 (d, J 5.4 Hz, 2H), 5.22
(dd, J 11.0, 1.3 Hz, 1H), 5.52 (dd, J 17.4, 1.3 Hz, 1H), 6.22 (dt, J 15.7,
5.4 Hz, 1H), 6.81 (dd, J 8.6, 2.7 Hz, 1H), 6.89 (d, J 15.7 Hz, 1H),
6.91−6.98 (m, 2H), 7.40 (d, J 8.6 Hz, 1H); 13C NMR (126 MHz,
CDCl3) δ 55.5 (CH3), 63.9 (CH2), 111.4 (CH), 114.1 (CH), 114.7
(CH2), 127.7 (CH), 128.9 (CH), 129.3 (C), 131.4 (CH), 134.3 (CH),
1
IR (neat) 3329, 2922, 1624, 1476, 1414, 1099, 966 cm−1; H NMR
(500 MHz, CDCl3) δ 1.50 (br s, 1H), 4.35 (d, J 5.4 Hz, 2H), 5.34 (dd,
J 11.0, 1.2 Hz, 1H), 5.63 (dd, J 17.4, 1.2 Hz, 1H), 6.24 (dt, J 15.7, 5.4
Hz, 1H), 6.92 (d, J 15.7 Hz, 1H), 7.02 (dd, J 17.4, 11.0 Hz, 1H), 7.23−
7.27 (m, 2H), 7.41−7.47 (m, 2H); 13C NMR (126 MHz, CDCl3) δ
64.0 (CH2), 116.5 (CH2), 126.5 (CH), 126.7 (CH), 127.9 (CH),
128.0 (CH), 128.9 (CH), 131.2 (CH), 135.0 (CH), 135.1 (C), 136.3
(C); MS m/z 160 (M+, 5), 141 (13), 129 (100), 115 (21), 91 (9);
HRMS (EI) calcd for C11H12O (M+), 160.0888, found 160.0882.
(2E)-3-(4′-Methyl-2′-vinylphenyl)prop-2-en-1-ol (8b). The
reaction was carried out according to the previously described
procedure for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a) using ethyl
(2E)-3-(4′-methyl-2′-vinylphenyl)prop-2-enoate (7b) (0.286 g, 1.32
mmol). This gave (2E)-3-(4′-methyl-2′-vinylphenyl)prop-2-en-1-ol
(8b) (0.213 g, 92%) as a colorless oil. IR (neat) 3333, 2921, 1488,
1238, 1201, 1005, 910 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.42 (t, J
5.7 Hz, 1H), 2.35 (s, 3H), 4.33 (td, J 5.7, 1.0 Hz, 2H), 5.31 (dd, J 11.0,
G
dx.doi.org/10.1021/jo5014492 | J. Org. Chem. XXXX, XXX, XXX−XXX

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136.3 (C), 159.4 (C); MS m/z 190 (M+, 19), 172 (8), 159 (100), 144
(48), 115 (28), 83 (21); HRMS (EI) calcd for C12H14O2 (M+),
190.0994, found 190.0991.
a white solid. Mp 92−94 °C; IR (neat) 3321, 2916, 1695, 1506, 1477,
1270, 1234, 839, 821 cm−1; 1H NMR (500 MHz, CDCl3) δ 5.58−5.64
(m, 1H), 6.38 (dd, J 5.6, 2.0 Hz, 1H), 6.69 (br s, 1H), 6.87 (dd, J 5.6,
1.6 Hz, 1H), 7.03 (td, J 8.4, 2.4 Hz, 1H), 7.21 (dd, J 8.4, 2.4 Hz, 1H),
7.26 (dd, J 8.4, 4.9 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 58.4
1-(2′,2′,2′-Trichloromethylcarbonylamino)-1H-indene (11a).
(2E)-3-(2′-Vinylphenyl)prop-2-en-1-ol (8a) (0.051 g, 0.32 mmol) was
dissolved in dry dichloromethane (8 mL) and cooled to 0 °C with
stirring. Trichloroacetonitrile (0.048 mL, 0.48 mmol) was added to the
solution, followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (0.024 mL,
0.16 mmol), and the reaction mixture was warmed to room
temperature over 1.5 h. The reaction mixture was filtered through a
short pad of neutral alumina with diethyl ether (150 mL) and
concentrated in vacuo to yield the crude allylic trichloroacetimidate 9a
as a yellow oil, which was used without further purification. Allylic
trichloroacetimidate 9a was transferred to a dry Schlenk tube
containing a stirrer bar and potassium carbonate (15 mg, 3 mg/mL)
to which p-xylene (5 mL) was then added. The tube was purged with
argon, sealed, and heated to 160 °C for 18 h. The mixture was allowed
to cool to room temperature, Grubbs second generation catalyst
(0.011 g, 0.015 mmol) was added, and the solution was heated to 50
°C for 20 h. The reaction mixture was concentrated in vacuo and
purified by filtration through a short pad of silica (elution with 20%
diethyl ether in petroleum ether) to yield 1-(2′,2′,2′-trichloromethyl-
carbonylamino)-1H-indene (11a) (0.072 g, 82%) as a white solid. Mp
4
2
(CH, d, JCF 2.1 Hz), 92.4 (C), 112.0 (CH, d, JCF 24.1 Hz), 115.7
(CH, d, 2JCF 22.8 Hz), 122.7 (CH, d, 3JCF 8.6 Hz), 133.7 (CH, d, 5JCF
4
3
4.1 Hz), 134.2 (CH), 138.9 (C, d, JCF 2.6 Hz), 145.2 (C, d, JCF 8.3
1
Hz), 162.3 (C, d, JCF 246.5 Hz), 162.8 (C); HRMS (ESI) calcd for
C11H735Cl3FNNaO (MNa+), 315.9469, found 315.9461.
3-(2′,2′,2′-Trichloromethylcarbonylamino)-3H-benz[e]-
indene (11e). The reaction was carried out according to the
previously described procedure for 1-(2′,2′,2′-trichloromethylcarbo-
nylamino)-1H-indene (11a) using (2E)-3-(1′-vinylnaphth-2′-yl)prop-
2-en-1-ol (8e) (0.055 g, 0.26 mmol). This gave 3-(2′,2′,2′-
trichloromethylcarbonylamino)-3H-benz[e]indene (11e) (0.048 g,
56%) as a white solid. Mp 130−134 °C (decomposition); IR (neat)
1
3270, 3050, 1698, 1685, 1533, 1514, 1260, 841, 822 cm−1; H NMR
(500 MHz, CDCl3) δ 5.79−5.84 (m, 1H), 6.61 (dd, J 5.6, 1.8 Hz, 1H),
6.72 (br d, J 6.7 Hz, 1H), 7.47−7.59 (m, 3H), 7.63 (d, J 8.2 Hz, 1H),
7.79 (d, J 8.2 Hz, 1H), 7.91 (d, J 7.9 Hz, 1H), 8.06 (d, J 7.9 Hz, 1H);
13C NMR (126 MHz, CDCl3) δ 59.4 (CH), 92.5 (C), 121.3 (CH),
123.9 (CH), 126.3 (CH), 126.7 (CH), 127.2 (CH), 127.8 (C), 128.8
(CH), 132.1 (CH), 134.1 (C), 134.3 (CH), 139.7 (C), 140.4 (C),
163.0 (C); MS m/z 325 (M+, 58), 290 (54), 254 (91), 208 (46), 180
(91), 165 (100), 152 (83), 88 (40), 70 (70), 61 (57); HRMS (EI)
calcd for C15H1035Cl3NO (M+), 324.9828, found 324.9829.
1
73−75 °C; IR (neat) 3325, 2927, 1697, 1506, 1235, 819 cm−1; H
NMR (400 MHz, CDCl3) δ 5.62−5.68 (m, 1H), 6.42 (dd, J 5.6, 1.9
Hz, 1H), 6.66 (br d, J 5.2 Hz, 1H), 6.91 (ddd, J 5.6, 1.9, 0.8 Hz, 1H),
7.23−7.28 (m, 1H), 7.33−7.36 (m, 2H), 7.47−7.51 (m, 1H); 13C
NMR (126 MHz, CDCl3) δ 58.5 (CH), 92.5 (C), 122.0 (CH), 123.7
(CH), 126.7 (CH), 129.0 (CH), 134.0 (CH), 134.8 (CH), 142.9 (C),
143.2 (C), 162.8 (C); MS m/z 276 (MH+, 100), 242 (62), 208 (32),
172 (10), 85 (17), 69 (27); HRMS (CI) calcd for C11H935Cl3NO
(MH+), 275.9750, found 275.9753.
6-Methoxy-1-(2′,2′,2′-trichloromethylcarbonylamino)-1H-
indene (11f). The reaction was carried out according to the
previously described procedure for 1-(2′,2′,2′-trichloromethylcarbo-
nylamino)-1H-indene (11a) using (2E)-3-(5′-methoxy-2′-
vinylphenyl)prop-2-en-1-ol (8f) (0.049 g, 0.26 mmol). This gave 6-
methoxy-1-(2′,2′,2′-trichloromethylcarbonylamino)-1H-indene (11f)
(0.048 g, 61%) as a white solid. Mp 69−71 °C; IR (neat) 3314,
5-Methyl-1-(2′,2′,2′-trichloromethylcarbonylamino)-1H-in-
dene (11b). The reaction was carried out according to the previously
described procedure for 1-(2′,2′,2′-trichloromethylcarbonylamino)-
1H-indene (11a) using (2E)-3-(4′-methyl-2′-vinylphenyl)prop-2-en-1-
ol (8b) (0.063 g, 0.36 mmol). This gave 5-methyl-1-(2′,2′,2′-
trichloromethylcarbonylamino)-1H-indene (11b) (0.072 g, 68%) as
a white solid. Mp 88−92 °C; IR (neat) 3321, 2923, 1695, 1505, 1239,
1
2940, 1697, 1505, 1234, 1026, 818, 737 cm−1; H NMR (400 MHz,
CDCl3) δ 3.82 (s, 3H), 5.58−5.63 (m, 1H), 6.27 (dd, J 5.6, 2.1 Hz,
1H), 6.67 (br d, J 7.8 Hz, 1H), 6.80−6.88 (m, 2H), 7.07 (d, J 2.1 Hz,
1H), 7.23 (d, J 8.2 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 55.8
(CH3), 58.5 (CH), 92.5 (C), 110.7 (CH), 113.9 (CH), 122.4 (CH),
131.7 (CH), 134.5 (CH), 135.9 (C), 145.0 (C), 159.3 (C), 162.8 (C);
MS m/z 307 (M+, 59), 270 (82), 234 (48), 192 (15), 160 (60), 145
(64), 130 (40), 115 (42), 83 (100); HRMS (EI) calcd for
C12H1035Cl237ClNO2 (M+), 306.9749, found 306.9751.
1
837, 809 cm−1; H NMR (500 MHz, CDCl3) δ 2.39 (s, 3H), 5.58−
5.63 (m, 1H), 6.40 (dd, J 5.6, 2.0 Hz, 1H), 6.65 (br d, J 6.1 Hz, 1H),
6.86 (ddd, J 5.6, 1.8, 0.6 Hz, 1H), 7.07 (d, J 7.5 Hz, 1H), 7.16 (s, 1H),
7.37 (d, J 7.5 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 21.6 (CH3),
58.2 (CH), 92.5 (C), 122.8 (CH), 123.5 (CH), 127.3 (CH), 134.2
(CH), 134.8 (CH), 139.0 (C), 140.0 (C), 143.5 (C), 162.8 (C);
HRMS (ESI) calcd for C12H1035Cl3NNaO (MNa+), 311.9720, found
311.9707.
Ethyl (2E)-3-(2′-Bromophenyl)prop-2-enoate (12a).35 The
reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate (7a) using
2-bromobenzaldehyde (5a) (0.492 g, 2.66 mmol). This gave ethyl
(2E)-3-(2′-bromophenyl)prop-2-enoate (12a) (0.558 g, 82%) as a
colorless oil. Spectroscopic data were in accordance with literature
values.35 1H NMR (500 MHz, CDCl3) δ 1.35 (t, J 7.1 Hz, 3H), 4.28
(q, J 7.1 Hz, 2H), 6.39 (d, J 15.9 Hz, 1H), 7.22 (td, J 7.6, 1.6 Hz, 1H),
7.32 (t, J 7.6 Hz, 1H), 7.60 (dd, J 7.6, 1.6 Hz, 1H), 7.61 (dd, J 7.6, 1.6
Hz, 1H), 8.05 (d, J 15.9 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ
14.5 (CH3), 60.8 (CH2), 121.3 (CH), 125.4 (C), 127.8 (CH), 127.9
(CH), 131.3 (CH), 133.6 (CH), 134.7 (C), 143.1 (CH), 166.5 (C);
MS (EI) m/z 254 (M+, 25), 209 (45), 175 (86), 147 (100), 102 (62),
83 (31), 75 (21).
5,6-Methylenedioxy-1-(2′,2′,2′-trichloromethylcarbonylami-
no)-1H-indene (11c). The reaction was carried out according to the
previously described procedure for 1-(2′,2′,2′-trichloromethylcarbo-
nylamino)-1H-indene (11a) using (2E)-3-(4′,5′-methylenedioxy-2′-
vinylphenyl)prop-2-en-1-ol (8c) (0.057 mg, 0.28 mmol). This gave
5,6-methylenedioxy-1-(2′,2′,2′-trichloromethylcarbonylamino)-1H-in-
dene (11c) (0.050 g, 57%) as a white solid. Mp 106−108 °C; IR
(neat) 3325, 2901, 1696, 1502, 1472, 1337, 1276, 1039, 939, 838, 820
1
cm−1; H NMR (500 MHz, CDCl3) δ 5.47−5.52 (m, 1H), 5.95 (d, J
1.4 Hz, 1H), 5.96 (d, J 1.4 Hz, 1H), 6.30 (dd, J 5.6, 2.0 Hz, 1H), 6.71
(br d, J 8.4 Hz, 1H), 6.76 (dd, J 5.6, 1.3 Hz, 1H), 6.78 (s, 1H), 6.96 (s,
1H); 13C NMR (126 MHz, CDCl3) δ 58.1 (CH), 92.5 (C), 101.5
(CH2), 103.0 (CH), 105.4 (CH), 132.8 (CH), 134.4 (CH), 136.8 (C),
137.0 (C), 147.0 (C), 148.3 (C), 162.7 (C); MS m/z 321 (M+, 58),
284 (68), 248 (100), 218 (21), 202 (32), 174 (80), 159 (61), 116
(52), 103 (58), 89 (58); HRMS (EI) calcd for C12H835Cl237ClNO3
(M+), 320.9542, found 320.9539.
Ethyl (2E)-3-(2′-Bromo-4′-methylphenyl)prop-2-enoate
(12b). The reaction was carried out according to the previously
described procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate
(7a) using 2-bromo-4-methylbenzaldehyde (5b) (0.500 g, 2.51
mmol). This gave ethyl (2E)-3-(2′-bromo-4′-methylphenyl)prop-2-
enoate (12b) (0.648 g, 96%) as a white solid. Mp 37−41 °C; IR (neat)
1
2980, 1709, 1634, 1603, 1312, 1263, 1165, 1040, 978, 814 cm−1; H
NMR (400 MHz, CDCl3) δ 1.34 (t, J 7.1 Hz, 3H), 2.34 (s, 3H), 4.27
(q, J 7.1 Hz, 2H), 6.35 (d, J 15.9 Hz, 1H), 7.12 (d, J 7.9 Hz, 1H), 7.44
(s, 1H), 7.50 (d, J 7.9 Hz, 1H), 8.02 (d, J 15.9 Hz, 1H); 13C NMR
(101 MHz, CDCl3) δ 14.5 (CH3), 21.1 (CH3), 60.8 (CH2), 120.2
(CH), 125.4 (C), 127.5 (CH), 128.8 (CH), 131.7 (C), 134.0 (CH),
142.1 (C), 143.0 (CH), 166.7 (C); MS m/z 291 (MNa+, 100), 271
6-Fluoro-1-(2′,2′,2′-trichloromethylcarbonylamino)-1H-in-
dene (11d). The reaction was carried out according to the previously
described procedure for 1-(2′,2′,2′-trichloromethylcarbonylamino)-
1H-indene (11a) using (2E)-3-(5′-fluoro-2′-vinylphenyl)prop-2-en-1-
ol (8d) (0.048 g, 0.27 mmol). This gave 6-fluoro-1-(2′,2′,2′-
trichloromethylcarbonylamino)-1H-indene (11d) (0.052 g, 65%) as
H
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(6), 236 (22), 223 (64), 144 (19); HRMS (ESI) calcd for
C12H1379BrNaO2 (MNa+), 290.9991, found 290.9981.
(d, J 8.2 Hz, 1H), 7.87 (br s, 1H), 8.01 (d, J 16.0 Hz, 1H); 13C NMR
(126 MHz, CDCl3) δ 14.3 (CH3), 61.0 (CH2), 123.0 (C, q, 1JCF 272.7
Hz), 123.5 (CH), 124.7 (CH, q, 3JCF 3.6 Hz), 125.1 (C), 128.1 (CH),
130.4 (CH, q, JCF 3.9 Hz), 132.8 (C, q, JCF 33.4 Hz), 138.2 (C),
141.4 (CH), 165.9 (C); MS m/z 345 (MNa+, 100), 301 (65), 275
(40), 258 (26), 243 (19), 236 (49), 201 (28); HRMS (ESI) calcd for
C12H1079BrF3NaO2 (MNa+), 344.9708, found 344.9693.
Ethyl (2E)-3-(2′-Bromo-4′,5′-methylenedioxyphenyl)prop-2-
enoate (12c).36 The reaction was carried out according to the
previously described procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-
2-enoate (7a) using 2-bromo-4,5-methylenedioxybenzaldehyde (5c)
(0.600 g, 2.62 mmol). This gave ethyl (2E)-3-(2′-bromo-4′,5′-
methylenedioxyphenyl)prop-2-enoate (12c) (0.781 g, 100%) as a
white solid. Spectroscopic data were in accordance with literature
3
2
3-Bromofuran-2-carboxaldehyde (5h).38 Titanium tetrachlor-
ide (17.0 mL, 1.0 M in dichloromethane, 17.0 mmol) was added to
dichloromethane (70 mL) and cooled to −78 °C. Dichloromethyl
methyl ether (1.53 mL, 17.0 mmol) was added dropwise and stirred
for 0.1 h before 3-bromofuran (0.300 mL, 3.39 mmol) was added
dropwise with vigorous stirring. The reaction mixture was stirred at
−78 °C for 2 h, then warmed to 0 °C, quenched with water (20 mL),
and stirred as a slurry for a further 1 h. A saturated solution of sodium
hydrogen carbonate was added until gas evolution ceased. The
biphasic reaction mixture was filtered through a pad of Celite and then
extracted with dichloromethane (3 × 30 mL). The combined organic
layers were washed with water (50 mL) and then brine (50 mL), dried
(MgSO4), filtered, and concentrated in vacuo to yield 3-bromofuran-2-
carboxaldehyde (5h) (0.567 g, 96%) as a light brown oil.
Spectroscopic data were in accordance with literature values.38 1H
NMR (400 MHz, CDCl3) δ 6.66 (dd, J 1.8, 0.7 Hz, 1H), 7.63 (dd, J
1.8, 0.7 Hz, 1H), 9.71−9.73 (m, 1H); 13C NMR (126 MHz, CDCl3) δ
112.8 (C), 116.8 (CH), 148.1 (CH), 148.3 (C), 176.5 (CH); MS (EI)
m/z 175 (M+, 95), 173 (74), 149 (39), 111 (53), 97 (72), 85 (78), 71
(98), 57 (100).
values.36 Mp 101−105 °C; H NMR (400 MHz, CDCl3) δ 1.32 (t, J
1
7.1 Hz, 3H), 4.25 (q, J 7.1 Hz, 2H), 6.01 (s, 2H), 6.22 (d, J 15.9 Hz,
1H), 7.03 (s, 1H), 7.04 (s, 1H), 7.96 (d, J 15.9 Hz, 1H); 13C NMR
(101 MHz, CDCl3) δ 14.4 (CH3), 60.7 (CH2), 102.3 (CH2), 106.5
(CH), 113.2 (CH), 117.9 (C), 119.1 (CH), 127.8 (C), 142.8 (CH),
148.0 (C), 150.1 (C), 166.7 (C); MS (EI) m/z 298 (M+, 22), 219
(83), 191 (100), 174 (41), 133 (27), 84 (10).
Ethyl (2E)-3-(2′-Bromo-5′-fluorophenyl)prop-2-enoate
(12d).37 The reaction was carried out according to the previously
described procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate
(7a) using 2-bromo-5-fluorobenzaldehyde (5d) (0.300 g, 1.48 mmol).
This gave ethyl (2E)-3-(2′-bromo-5′-fluorophenyl)prop-2-enoate
(12d) (0.384 g, 95%) as a colorless oil. Spectroscopic data were in
accordance with literature values.37 1H NMR (400 MHz, CDCl3) δ
1.35 (t, J 7.1 Hz, 3H), 4.29 (q, J 7.1 Hz, 2H), 6.37 (d, J 15.9 Hz, 1H),
6.97 (ddd, J 8.8, 7.7, 3.0 Hz, 1H), 7.30 (dd, J 9.3, 3.0 Hz, 1H), 7.57
(dd, J 8.8, 5.3 Hz, 1H), 7.97 (dd, J 15.9, 1.5 Hz, 1H); 13C NMR (101
MHz, CDCl3) δ 14.4 (CH3), 61.0 (CH2), 114.6 (d, 2JCF 23.7 Hz, CH),
118.6 (d, 2JCF 22.7 Hz, CH), 119.6 (C), 122.4 (CH), 134.8 (d, 3JCF 7.9
Hz, CH), 136.4 (d, 3JCF 7.7 Hz, C), 142.1 (d, 4JCF 1.9 Hz, CH), 162.1
Ethyl (2E)-3-(3′-Bromofuran-2′-yl)prop-2-enoate (12h). The
reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate (7a) using
3-bromofuran-2-carboxaldehyde (5h) (0.550 g, 3.14 mmol). This gave
ethyl (2E)-3-(3′-bromofuran-2′-yl)prop-2-enoate (12h) (0.718 g,
93%) as an orange solid. Mp 44−46 °C; IR (neat) 2986, 1713,
1636, 1304, 1258, 1173, 1026, 964 cm−1; 1H NMR (500 MHz,
CDCl3) δ 1.32 (t, J 7.1 Hz, 3H), 4.25 (q, J 7.1 Hz, 2H), 6.39 (d, J 15.8
Hz, 1H), 6.53 (d, J 2.0 Hz, 1H), 7.42 (d, J 2.0 Hz, 1H), 7.48 (d, J 15.8
Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 14.4 (CH3), 60.8 (CH2),
105.5 (C), 116.0 (CH), 117.7 (CH), 128.1 (CH), 144.7 (CH), 148.2
(C), 166.8 (C); MS m/z 267 (MNa+, 100), 242 (8), 236 (36), 200
(4), 171 (4); HRMS (ESI) calcd for C9H979BrNaO3 (MNa+),
266.9627, found 266.9628.
1
(d, JCF 247.4 Hz, C), 166.2 (C); MS (EI) m/z 272 (M+, 14), 229
(23), 193 (36), 165 (100), 120 (47), 84 (20).
Ethyl (2E)-3-(1′-Bromonaphthalen-2′-yl)prop-2-enoate
(12e). The reaction was carried out according to the previously
described procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate
(7a) using 1-bromo-2-naphthaldehyde (5e) (0.500 g, 2.13 mmol).
This gave ethyl (2E)-3-(1′-bromonaphthalen-2′-yl)prop-2-enoate
(12e) (0.647 g, 100%) as a white solid. Mp 117−119 °C; IR (neat)
1
2976, 1707, 1632, 1308, 1283, 1180, 1157, 980 cm−1; H NMR (400
MHz, CDCl3) δ 1.37 (t, J 7.1 Hz, 3H), 4.32 (q, J 7.1 Hz, 2H), 6.50 (d,
J 15.9 Hz, 1H), 7.53−7.69 (m, 3H), 7.77−7.88 (m, 2H), 8.35−8.43
(m, 2H); 13C NMR (101 MHz, CDCl3) δ 14.5 (CH3), 60.9 (CH2),
121.8 (CH), 124.1 (CH), 126.9 (C), 127.9 (CH), 128.1 (CH), 128.2
(CH), 128.3 (CH), 128.4 (CH), 132.4 (C), 132.8 (C), 135.1 (C),
144.1 (CH), 166.7 (C); MS m/z 304 (M+, 31), 225 (100), 197 (43),
152 (15), 76 (4); HRMS (EI) calcd for C15H1379BrO2 (M+), 304.0099,
found 304.0101.
Ethyl (2E)-3-(2′-Allylphenyl)prop-2-enoate (14a).39 Cesium
fluoride (0.238 g, 1.57 mmol), [1,1′-bis(diphenylphosphino)-
ferrocene]palladium(II) dichloride (0.0320 g, 0.0392 mmol), and
allylboronic acid pinacol ester (13) (0.147 mL, 0.784 mmol) were
added to a degassed solution of ethyl (2E)-3-(2′-bromophenyl)prop-2-
enoate (12a) (0.100 g, 0.329 mmol) in 1,4-dioxane (5 mL). The
solution was heated to 85 °C for 18 h, cooled to room temperature,
and concentrated in vacuo. The reaction mixture was purified by
filtration through a pad of silica (elution with 20% diethyl ether in
petroleum ether) to yield ethyl (2E)-3-(2′-allylphenyl)prop-2-enoate
(14a) (0.0844 g, 100%) as a yellow oil. Spectroscopic data were in
accordance with literature values.39 1H NMR (500 MHz, CDCl3) δ
1.34 (t, J 7.1 Hz, 3H), 3.53 (br d, J 6.2 Hz, 2H), 4.27 (q, J 7.1 Hz, 2H),
5.00 (dq, J 17.1, 1.6 Hz, 1H), 5.09 (dq, J 10.1, 1.6 Hz, 1H), 5.96 (ddt, J
17.1, 10.1, 6.2 Hz, 1H), 6.36 (d, J 15.8 Hz, 1H), 7.20−7.27 (m, 2H),
7.32 (td, J 7.5, 1.3 Hz, 1H), 7.58 (dd, J 7.5, 1.3 Hz, 1H), 7.99 (d, J 15.8
Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 14.4 (CH3), 37.6 (CH2),
60.6 (CH2), 116.5 (CH2), 119.8 (CH), 126.7 (CH), 127.0 (CH),
130.2 (CH), 130.4 (CH), 133.6 (C), 136.7 (CH), 139.4 (C), 142.3
(CH), 167.1 (C); MS (EI) m/z 216 (M+, 68), 187 (24), 171 (30), 143
(100), 142 (99), 128 (94), 115 (97), 84 (42).
Ethyl (2E)-3-(2′-Bromo-5′-methoxyphenyl)prop-2-enoate
(12f). The reaction was carried out according to the previously
described procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-2-enoate
(7a) using 2-bromo-5-methoxybenzaldehyde (5f) (0.500 g, 2.33
mmol). This gave ethyl (2E)-3-(2′-bromo-5′-methoxyphenyl)prop-2-
enoate (12f) (0.619 g, 93%) as a yellow oil. IR (neat) 2987, 1710,
1
1637, 1465, 1288, 1177, 1017 cm−1; H NMR (500 MHz, CDCl3) δ
1.35 (t, J 7.1 Hz, 3H), 3.81 (s, 3H), 4.28 (q, J 7.1 Hz, 2H), 6.37 (d, J
15.9 Hz, 1H), 6.81 (dd, J 8.8, 3.0 Hz, 1H), 7.11 (d, J 3.0 Hz, 1H), 7.49
(d, J 8.8 Hz, 1H), 8.00 (d, J 15.9 Hz, 1H); 13C NMR (126 MHz,
CDCl3) δ 14.5 (CH3), 55.7 (CH3), 60.9 (CH2), 112.7 (CH), 116.1
(C), 117.8 (CH), 121.4 (CH), 134.1 (CH), 135.4 (C), 143.2 (CH),
159.2 (C), 166.5 (C); MS m/z 307 (MNa+, 100), 285 (6), 264 (32),
239 (43), 160 (100); HRMS (ESI) calcd for C12H1379BrNaO3
(MNa+), 306.9940, found 306.9936.
Ethyl (2E)-3-(2′-Bromo-4′-trifluoromethylphenyl)prop-2-
enoate (12g). The reaction was carried out according to the
previously described procedure for ethyl (2E)-3-(2′-vinylphenyl)prop-
2-enoate (7a) using 2-bromo-4-trifluoromethylbenzaldehyde (5g)
(0.500 g, 1.98 mmol). This gave ethyl (2E)-3-(2′-bromo-4′-
trifluoromethylphenyl)prop-2-enoate (12g) (0.562 g, 88%) as a yellow
oil. IR (neat) 2984, 1717, 1640, 1393, 1316, 1265, 1171, 1125, 1078
cm−1; 1H NMR (400 MHz, CDCl3) δ 1.35 (t, J 7.1 Hz, 3H), 4.30 (q, J
7.1 Hz, 2H), 6.45 (d, J 16.0 Hz, 1H), 7.58 (br d, J 8.2 Hz, 1H), 7.69
Ethyl (2E)-3-(2′-Allyl-4′-methylphenyl)prop-2-enoate (14b).
The reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-allylphenyl)prop-2-enoate (14a) using
ethyl (2E)-3-(2′-bromo-4′-methylphenyl)prop-2-enoate (12b) (0.050
g, 0.19 mmol). This gave ethyl (2E)-3-(2′-allyl-4′-methylphenyl)prop-
2-enoate (14b) (0.042 g, 99%) as a colorless oil. IR (neat) 2980, 1709,
1
1632, 1609, 1312, 1173, 1155 cm−1; H NMR (400 MHz, CDCl3) δ
1.33 (t, J 7.1 Hz, 3H), 2.34 (s, 3H), 3.50 (br d, J 6.2 Hz, 2H), 4.26 (q, J
I
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7.1 Hz, 2H), 5.00 (dq, J 17.0, 1.6 Hz, 1H), 5.08 (dq, J 10.1, 1.6 Hz,
1H), 5.95 (ddt, J 17.0, 10.1, 6.2 Hz, 1H), 6.33 (d, J 15.8 Hz, 1H), 7.03
(s, 1H), 7.06 (d, J 7.9 Hz, 1H), 7.49 (d, J 7.9 Hz, 1H), 7.96 (d, J 15.8
Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 14.5 (CH3), 21.5 (CH3),
37.6 (CH2), 60.5 (CH2), 116.4 (CH2), 118.6 (CH), 126.7 (CH),
127.8 (CH), 130.6 (C), 131.1 (CH), 136.8 (CH), 139.4 (C), 140.6
(C), 142.2 (CH), 167.3 (C); MS m/z 253 (MNa+, 100), 236 (8), 157
(36), 142 (28); HRMS (ESI) calcd for C15H18NaO2 (MNa+),
253.1199, found 253.1198.
Ethyl (2E)-3-(2′-Allyl-4′,5′-methylenedioxyphenyl)prop-2-
enoate (14c). The reaction was carried out according to the
previously described procedure for ethyl (2E)-3-(2′-allylphenyl)prop-
2-enoate (14a) using ethyl (2E)-3-(2′-bromo-4′,5′-
methylenedioxyphenyl)prop-2-enoate (12c) (0.270 g, 0.903 mmol).
This gave ethyl (2E)-3-(2′-allyl-4′,5′-methylenedioxyphenyl)prop-2-
enoate (14c) (0.235 g, 100%) as a white solid. Mp 63−67 °C; IR
(neat) 2982, 1694, 1499, 1476, 1256, 1036, 974 cm−1; 1H NMR (400
MHz, CDCl3) δ 1.32 (t, J 7.1 Hz, 3H), 3.45 (dt, J 6.2, 1.5 Hz, 1H),
4.24 (q, J 7.1 Hz, 2H), 4.99 (dq, J 17.0, 1.5 Hz, 1H), 5.07 (dq, J 10.1,
1.5 Hz, 1H), 5.91 (ddt, J 17.0, 10.1, 6.2 Hz, 1H), 5.97 (s, 2H), 6.21 (d,
J 15.7 Hz, 1H), 6.68 (s, 1H), 7.05 (s, 1H), 7.89 (d, J 15.7 Hz, 1H); 13C
NMR (101 MHz, CDCl3) δ 14.5 (CH3), 37.4 (CH2), 60.5 (CH2),
101.5 (CH2), 105.8 (CH), 110.3 (CH), 116.4 (CH2), 117.4 (CH),
126.8 (C), 134.9 (C), 136.7 (CH), 141.6 (CH), 146.9 (C), 149.6 (C),
167.3 (C); HRMS (ESI) calcd for C15H16NaO4 (MNa+), 283.0941,
found 283.0935.
(500 MHz, CDCl3) δ 1.34 (t, J 7.1 Hz, 3H), 3.46 (br d, J 6.2 Hz, 2H),
3.81 (s, 3H), 4.27 (q, J 7.1 Hz, 2H), 4.97 (dq, J 17.1, 1.6 Hz, 1H), 5.06
(dq, J 10.0, 1.6 Hz, 1H), 5.93 (ddt, J 17.1, 10.0, 6.2 Hz, 1H), 6.34 (d, J
15.8 Hz, 1H), 6.89 (dd, J 8.4, 2.7 Hz, 1H), 7.09 (d, J 2.7 Hz, 1H), 7.12
(d, J 8.4 Hz, 1H), 7.94 (d, J 15.8 Hz, 1H); 13C NMR (126 MHz,
CDCl3) δ 14.5 (CH3), 36.8 (CH2), 55.5 (CH3), 60.6 (CH2), 111.4
(CH), 116.1 (CH2), 116.4 (CH), 119.9 (CH), 131.5 (CH), 131.8 (C),
134.4 (C), 137.2 (CH), 142.3 (CH), 158.5 (C), 167.0 (C); HRMS
(ESI) calcd for C15H18NaO3 (MNa+), 269.1148, found 269.1141.
Ethyl (2E)-3-(2′-Allyl-4′-trifluoromethylphenyl)prop-2-
enoate (14g). The reaction was carried out according to the
previously described procedure for ethyl (2E)-3-(2′-allylphenyl)prop-
2-enoate (14a) using ethyl (2E)-3-(2′-bromo-4 ′-
trifluoromethylphenyl)prop-2-enoate (12g) (0.321 g, 1.00 mmol).
This gave ethyl (2E)-3-(2′-allyl-4′-trifluoromethylphenyl)prop-2-
enoate (14g) (0.282 g, 100%) as a yellow oil. IR (neat) 2984, 1715,
1638, 1333, 1314, 1279, 1163, 1123, 1078 cm−1; 1H NMR (500 MHz,
CDCl3) δ 1.34 (t, J 7.1 Hz, 3H), 3.56 (br d, J 6.2 Hz, 2H), 4.28 (q, J
7.1 Hz, 2H), 5.01 (dq, J 16.8, 1.5 Hz, 1H), 5.14 (dq, J 10.3, 1.5 Hz,
1H), 5.94 (ddt, J 16.8, 10.3, 6.2 Hz, 1H), 6.40 (d, J 15.9 Hz, 1H), 7.47
(s, 1H), 7.50 (d, J 8.2 Hz, 1H), 7.65 (d, J 8.2 Hz, 1H), 7.95 (d, J 15.9
Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 14.3 (CH3), 37.4 (CH2),
3
60.8 (CH2), 117.3 (CH2), 122.1 (CH), 123.7 (CH, q, JCF 3.7 Hz),
1
3
123.9 (C, q, JCF 272.3 Hz), 127.0 (CH, q, JCF 3.8 Hz), 127.1 (CH),
2
131.7 (C, q, JCF 32.5 Hz), 135.5 (CH), 137.1 (C), 139.8 (C), 140.7
(CH), 166.4 (C); MS m/z 307 (MNa+, 100), 301 (43), 236 (36), 209
(72); HRMS (ESI) calcd for C15H15F3NaO2 (MNa+), 307.0916, found
307.0907.
Ethyl (2E)-3-(2′-Allyl-5′-fluorophenyl)prop-2-enoate (14d).
The reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-allylphenyl)prop-2-enoate (14a) using
ethyl (2E)-3-(2′-bromo-5′-fluorophenyl)prop-2-enoate (12d) (0.254
g, 0.930 mmol). This gave ethyl (2E)-3-(2′-allyl-5′-fluorophenyl)prop-
2-enoate (14d) (0.214 g, 98%) as a yellow oil. IR (neat) 2982, 1711,
Ethyl (2E)-3-(3′-Allylfuran-2′-yl)prop-2-enoate (14h). The
reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-allylphenyl)prop-2-enoate (14a) using
ethyl (2E)-3-(3′-bromofuran-2′-yl)prop-2-enoate (12h) (0.230 g,
0.939 mmol). This gave ethyl (2E)-3-(3′-allylfuran-2′-yl)prop-2-
enoate (14h) (0.193 g, 100%) as a yellow oil. IR (neat) 2924, 1705,
1636, 1304, 1258, 1165, 1042, 972 cm−1; 1H NMR (500 MHz,
CDCl3) δ 1.32 (t, J 7.1 Hz, 3H), 3.29 (br d, J 6.3 Hz, 2H), 4.24 (q, J
7.1 Hz, 2H), 5.06−5.11 (m, 2H), 5.88 (ddt, J 16.2, 10.0, 6.3 Hz, 1H),
6.27 (d, J 15.6 Hz, 1H), 6.35 (d, J 1.6 Hz, 1H), 7.40 (d, J 1.6 Hz, 1H),
7.47 (d, J 15.6 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 14.5 (CH3),
29.4 (CH2), 60.5 (CH2), 113.9 (CH), 114.9 (CH), 116.5 (CH2),
128.0 (C), 129.1 (CH), 135.6 (CH), 144.3 (CH), 147.1 (C), 167.5
(C); HRMS (ESI) calcd for C12H14NaO3 (MNa+), 229.0835, found
229.0838.
1
1636, 1489, 1314, 1269, 1233, 1173, 1034, 976, 860 cm−1; H NMR
(400 MHz, CDCl3) δ 1.34 (t, J 7.1 Hz, 3H), 3.48 (br d, J 6.1 Hz, 2H),
4.27 (q, J 7.1 Hz, 2H), 4.96 (dq, J 17.1, 1.6 Hz, 1H), 5.09 (dq, J 10.1,
1.6 Hz, 1H), 5.93 (ddt, J 17.1, 10.1, 6.1 Hz, 1H), 6.33 (d, J 15.8 Hz,
1H), 7.02 (td, J 8.3, 2.7 Hz, 1H), 7.18 (dd, J 8.3, 5.8 Hz, 1H), 7.26 (dd,
J 9.8, 2.7 Hz, 1H), 7.90 (dd, J 15.8, 1.6 Hz, 1H); 13C NMR (101 MHz,
2
CDCl3) δ 14.5 (CH3), 36.9 (CH2), 60.8 (CH2), 113.1 (d, JCF 22.1
2
Hz, CH), 116.7 (CH2), 117.1 (d, JCF 21.2 Hz, CH), 120.9 (CH),
132.0 (d, 3JCF 7.9 Hz, CH), 135.1 (d, 4JCF 3.3 Hz, C), 135.3 (d, 3JCF 7.5
4
1
Hz, C), 136.5 (CH), 141.1 (d, JCF 2.2 Hz, CH), 161.7 (d, JCF 244.9
Hz, C), 166.8 (C); MS m/z 234 (M+, 32), 205 (12), 189 (15), 161
(95), 146 (100), 133 (54), 84 (16), 69 (20); HRMS (EI) calcd for
C14H15FO2 (M+), 234.1056, found 234.1053.
(2E)-3-(2′-Allylphenyl)prop-2-en-1-ol (15a).40 The reaction
was carried out according to the previously described procedure for
(2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a) using ethyl (2E)-3-(2′-
allylphenyl)prop-2-enoate (14a) (0.700 g, 3.24 mmol). This gave
(2E)-3-(2′-allylphenyl)prop-2-en-1-ol (15a) (0.456 g, 81%) as a
colorless oil. Spectroscopic data were in accordance with literature
values.40 1H NMR (400 MHz, CDCl3) δ 1.48 (t, J 5.4 Hz, 1H), 3.45
(dt, J 6.2, 1.7 Hz, 2H), 4.30−4.35 (m, 2H), 4.97 (dq, J 17.1, 1.7 Hz,
1H), 5.06 (dq, J 10.1, 1.7 Hz, 1H), 5.97 (ddt, J 17.1, 10.1, 6.2 Hz, 1H),
6.26 (dt, J 15.7, 5.7 Hz, 1H), 6.85 (dt, J 15.7, 1.5 Hz, 1H), 7.14−7.23
(m, 3H), 7.46−7.49 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 37.6
(CH2), 64.1 (CH2), 116.0 (CH2), 126.3 (CH), 126.8 (CH), 128.0
(CH), 128.9 (CH), 129.9 (CH), 130.4 (CH), 135.9 (C), 137.0 (CH),
137.3 (C); MS (EI) m/z 174 (M+, 8), 156 (31), 143 (62), 128 (100),
115 (70), 91 (23), 84 (12), 74 (5).
(2E)-3-(2′-Allyl-4′-methylphenyl)prop-2-en-1-ol (15b). The
reaction was carried out according to the previously described
procedure for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a) using ethyl
(2E)-3-(2′-allyl-4′-methylphenyl)prop-2-enoate (14b) (0.483 g, 2.10
mmol). This gave (2E)-3-(2′-allyl-4′-methylphenyl)prop-2-en-1-ol
(15b) (0.348 g, 88%) as a colorless oil. IR (neat) 3325, 2918, 1638,
1611, 1495, 1086, 995, 966 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.39
(t, J 5.9 Hz, 1H), 2.32 (s, 3H), 3.42 (dt, J 6.2, 1.6 Hz, 2H), 4.32 (td, J
5.9, 1.5 Hz, 2H), 4.98 (dq, J 17.0, 1.6 Hz, 1H), 5.06 (dq, J 10.1, 1.6 Hz,
1H), 5.95 (ddt, J 17.0, 10.1, 6.2 Hz, 1H), 6.22 (dt, J 15.7, 5.9 Hz, 1H),
6.81 (d, J 15.7 Hz, 1H), 6.97 (br s, 1H), 7.02 (d, J 7.9 Hz, 1H), 7.38
(d, J 7.9 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 21.3 (CH3), 37.6
Ethyl (2E)-3-(1′-Allylnaphthalen-2′-yl)prop-2-enoate (14e).
The reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-allylphenyl)prop-2-enoate (14a) using
ethyl (2E)-3-(1′-bromonaphthalen-2′-yl)prop-2-enoate (12e) (0.415
g, 1.36 mmol) at 100 °C. This gave ethyl (2E)-3-(1′-allylnaphthalen-
2′-yl)prop-2-enoate (14e) (0.355 g, 98%) as a yellow oil. IR (neat)
1
2978, 1707, 1626, 1256, 1173, 1153, 1036, 812 cm−1; H NMR (500
MHz, CDCl3) δ 1.36 (t, J 7.1 Hz, 3H), 4.01 (br d, J 5.6 Hz, 2H), 4.30
(q, J 7.1 Hz, 2H), 4.93 (dq, J 17.1, 1.7 Hz, 1H), 5.08 (dq, J 10.2, 1.7
Hz, 1H), 6.08 (ddt, J 17.1, 10.2, 5.6 Hz, 1H), 6.48 (d, J 15.8 Hz, 1H),
7.48−7.56 (m, 2H), 7.67 (d, J 8.7 Hz, 1H), 7.74 (d, J 8.7 Hz, 1H),
7.80−7.85 (m, 1H), 8.08 (d, J 8.1 Hz, 1H), 8.22 (d, J 15.8 Hz, 1H);
13C NMR (126 MHz, CDCl3) δ 14.5 (CH3), 32.3 (CH2), 60.7 (CH2),
116.6 (CH2), 120.5 (CH), 123.8 (CH), 125.1 (CH), 126.8 (CH),
126.8 (CH), 127.6 (CH), 128.8 (CH), 130.8 (C), 132.5 (C), 134.5
(C), 136.0 (CH), 136.1 (C), 142.7 (CH), 167.2 (C); MS m/z 289
(MNa+, 100), 236 (6), 193 (3), 178 (2); HMRS (ESI) calcd for
C18H18NaO2 (MNa+), 289.1199, found 289.1190.
Ethyl (2E)-3-(2′-Allyl-5′-methoxyphenyl)prop-2-enoate (14f).
The reaction was carried out according to the previously described
procedure for ethyl (2E)-3-(2′-allylphenyl)prop-2-enoate (14a) using
ethyl (2E)-3-(2′-bromo-5′-methoxyphenyl)prop-2-enoate (12f)
(0.619 g, 2.17 mmol). This gave ethyl (2E)-3-(2′-allyl-5′-
methoxyphenyl)prop-2-enoate (14f) (0.529 g, 99%) as a yellow oil.
1
IR (neat) 2980, 1709, 1634, 1495, 1233, 1165, 1036 cm−1; H NMR
J
dx.doi.org/10.1021/jo5014492 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(CH2), 64.2 (CH2), 115.9 (CH2), 126.2 (CH), 127.6 (CH), 128.9
(CH), 129.4 (CH), 130.6 (CH), 133.0 (C), 137.1 (CH), 137.2 (C),
137.8 (C); MS m/z 211 (MNa+, 24), 190 (22), 171 (29), 143 (100),
128 (46); HRMS (ESI) calcd for C13H16NaO (MNa+), 211.1093,
found 211.1096.
5.3 Hz, 1H), 6.78 (dd, J 8.4, 2.8 Hz, 1H), 6.81 (dt, J 15.7, 1.6 Hz, 1H),
7.02 (d, J 2.8 Hz, 1H), 7.07 (d, J 8.4 Hz, 1H); 13C NMR (126 MHz,
CDCl3) δ 36.8 (CH2), 55.4 (CH3), 64.0 (CH2), 111.4 (CH), 113.7
(CH), 115.7 (CH2), 128.9 (CH), 129.7 (C), 130.5 (CH), 131.0 (CH),
136.9 (C), 137.4 (CH), 158.4 (C); MS m/z 204 (M+, 74), 173 (100),
159 (74), 158 (73), 115 (53), 103 (18), 91 (23), 77 (13), 51 (10);
HRMS (EI) calcd for C13H16O2 (M+), 204.1150, found 204.1152.
(2E)-3-(2′-Allyl-4′-trifluoromethylphenyl)prop-2-en-1-ol
(15g). The reaction was carried out according to the previously
described procedure for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a)
using ethyl (2E)-3-(2′-allyl-4′-trifluoromethylphenyl)prop-2-enoate
(14g) (0.326 g, 1.23 mmol). This gave (2E)-3-(2′-allyl-4′-
trifluoromethylphenyl)prop-2-en-1-ol (15g) (0.256 g, 93%) as a
colorless oil. IR (neat) 3320, 2928, 1640, 1616, 1420, 1332, 1160,
1118, 1091 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.98 (br s, 1H), 3.48
(dt, J 6.2, 1.5 Hz, 2H), 4.36 (dd, J 5.4, 1.6 Hz, 2H), 4.98 (dq, J 16.7,
1.5 Hz, 1H), 5.11 (dq, J 10.1, 1.5 Hz, 1H), 5.94 (ddt, J 16.7, 10.1, 6.2
Hz, 1H), 6.32 (dt, J 15.8, 5.4 Hz, 1H), 6.86 (d, J 15.8 Hz, 1H), 7.41 (s,
1H), 7.44 (d, J 8.2 Hz, 1H), 7.54 (d, J 8.2 Hz, 1H); 13C NMR (126
MHz, CDCl3) δ 37.4 (CH2), 63.6 (CH2), 116.9 (CH2), 123.5 (CH, q,
(2E)-3-(2′-Allyl-4′,5′-methylenedioxyphenyl)prop-2-en-1-ol
(15c). The reaction was carried out according to the previously
described procedure for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a)
using ethyl (2E)-3-(2′-allyl-4′,5′-methylenedioxyphenyl)prop-2-enoate
(14c) (1.14 g, 4.37 mmol). This gave (2E)-3-(2′-allyl-4′,5′-
methylenedioxyphenyl)prop-2-en-1-ol (15c) (0.920 g, 97%) as a
white crystalline solid. Mp 45−49 °C; IR (neat) 3262, 2866, 1636,
1
1503, 1481, 1244, 1165, 1044, 1017, 995 cm−1; H NMR (400 MHz,
CDCl3) δ 3.30 (dt, J 6.1, 1.5 Hz, 2H), 3.68 (br s, 1H), 4.25 (br d, J 5.7
Hz, 2H), 4.95 (dq, J 17.0, 1.5 Hz, 1H), 5.02 (dq, J 10.1, 1.5 Hz, 1H),
5.85 (s, 2H), 5.88 (ddt, J 17.0, 10.1, 6.1 Hz, 1H), 6.08 (dt, J 15.6, 5.7
Hz, 1H), 6.60 (s, 1H), 6.71 (dt, J 15.6, 1.2 Hz, 1H), 6.94 (s, 1H); 13C
NMR (101 MHz, CDCl3) δ 37.4 (CH2), 64.1 (CH2), 101.1 (CH2),
106.0 (CH), 109.9 (CH), 116.0 (CH2), 128.6 (CH), 128.7 (CH),
129.2 (C), 131.4 (C), 137.0 (CH), 146.6 (C), 147.5 (C); MS m/z 218
(M+, 100), 200 (20), 173 (80), 160 (44), 149 (23), 115 (48), 103
(19), 83 (73), 77 (12); HRMS (EI) calcd for C13H14O3 (M+),
218.0943, found 218.0945.
1
3JCF 3.8 Hz), 124.3 (C, q, JCF 272.0 Hz), 126.6 (CH), 126.7 (CH, q,
2
3JCF 3.8 Hz), 127.2 (CH), 129.7 (C, q, JCF 32.3 Hz), 132.8 (CH),
135.9 (CH), 137.9 (C), 139.6 (C); MS m/z 225 (MH+ − H2O, 100),
197 (12), 125 (3), 81 (13), 69 (15); HRMS (CI) calcd for C13H12F3
(MH+ − H2O), 225.0891, found 225.0892.
(2E)-3-(2′-Allyl-5′-fluorophenyl)prop-2-en-1-ol (15d). The
reaction was carried out according to the previously described
procedure for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a) using ethyl
(2E)-3-(2′-allyl-5′-fluorophenyl)prop-2-enoate (14d) (0.190 g, 0.812
mmol). This gave (2E)-3-(2′-allyl-5′-fluorophenyl)prop-2-en-1-ol
(15d) (0.144 g, 92%) as a colorless oil. IR (neat) 3300, 2857, 1609,
(2E)-3-(3′-Allylfuran-2′-yl)prop-2-en-1-ol (15h). The reaction
was carried out according to the previously described procedure for
(2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a) using ethyl (2E)-3-(3′-
allylfuran-2′-yl)prop-2-enoate (14h) (0.235 g, 1.14 mmol). This gave
(2E)-3-(3′-allylfuran-2′-yl)prop-2-en-1-ol (15h) (0.180 g, 96%) as a
yellow oil. IR (neat) 3323, 2924, 1640, 1499, 1433, 1148, 1092, 1053,
1
1582, 1489, 1267, 1155, 964, 912, 870 cm−1; H NMR (400 MHz,
CDCl3) δ 1.61 (br s, 1H), 3.41 (br d, J 6.1 Hz, 2H), 4.34 (td, J 5.8, 1.6
Hz, 2H), 4.94 (dq, J 17.0, 1.6 Hz, 1H), 5.07 (dq, J 10.1, 1.6 Hz, 1H),
5.93 (ddt, J 17.0, 10.1, 6.1 Hz, 1H), 6.25 (dt, J 15.7, 5.8 Hz, 1H), 6.80
(dq, J 15.7, 1.6 Hz, 1H), 6.90 (td, J 8.3, 2.7, Hz, 1H), 7.10 (dd, J 8.3,
5.9 Hz, 1H), 7.16 (dd, J 10.2, 2.7 Hz, 1H); 13C NMR (101 MHz,
CDCl3) δ 36.8 (CH2), 63.7 (CH2), 112.6 (CH, d, 2JCF 21.9 Hz), 114.6
(CH, d, 2JCF 21.2 Hz), 116.2 (CH2), 127.7 (CH, d, 4JCF 2.2 Hz), 131.4
1
993, 959 cm−1; H NMR (500 MHz, CDCl3) δ 1.37−1.44 (m, 1H),
3.20 (br d, J 6.3 Hz, 2H), 4.31 (td, J 5.6, 1.2 Hz, 2H), 5.02−5.09 (m,
2H), 5.88 (ddt, J 16.7, 10.3, 6.3 Hz, 1H), 6.23−6.29 (m, 2H), 6.46 (dt,
J 15.7, 1.2 Hz, 1H), 7.29 (d, J 1.6 Hz, 1H); 13C NMR (126 MHz,
CDCl3) δ 29.2 (CH2), 63.7 (CH2), 113.1 (CH), 115.8 (CH2), 117.6
(CH), 120.6 (C), 126.3 (CH), 136.4 (CH), 141.6 (CH), 148.0 (C);
MS m/z 147 (MH+ − H2O, 16), 137 (100), 113 (6), 89 (22), 73 (12);
HRMS (CI) calcd for C10H11O (MH+ − H2O), 147.0810, found
147.0807.
3
4
(CH, d, JCF 8.7 Hz), 131.5 (CH), 132.9 (C, d, JCF 3.0 Hz), 136.8
(CH), 137.7 (C, d, 3JCF 7.5 Hz), 161.8 (C, d, 1JCF 243.7 Hz); MS m/z
175 (MH+ − H2O, 100), 147 (25), 113 (6), 85 (5), 73 (14); HRMS
(CI) calcd for C12H12F (MH+ − H2O), 175.0923, found 175.0919.
(2E)-3-(1′-Allylnaphthalen-2′-yl)prop-2-en-1-ol (15e). The
reaction was carried out according to the previously described
procedure for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a) using ethyl
(2E)-3-(1′-allylnaphthalen-2′-yl)prop-2-enoate (14e) (0.326 g, 1.23
mmol). This gave (2E)-3-(1′-allylnaphthalen-2′-yl)prop-2-en-1-ol
(15e) (0.256 g, 93%) as a yellow oil. IR (neat) 3320, 3055, 2859,
1-(2′,2′,2′-Trichloromethylcarbonylamino)-1,4-dihydro-
naphthalene (16a). The reaction was carried out according to the
previously described procedure for 1-(2′,2′,2′-trichloromethylcarbo-
nylamino)-1H-indene (11a) using (2E)-3-(2′-allylphenyl)prop-2-en-1-
ol (15a) (0.049 g, 0.28 mmol). The RCM step was performed at room
temperature. This gave 1-(2′,2′,2′-trichloromethylcarbonylamino)-1,4-
dihydronaphthalene (16a) (0.073 g, 89%) as a white solid. Mp 87−89
°C; IR (neat) 3271, 3032, 1682, 1520, 1250, 1018, 826, 741, 648 cm−1;
1H NMR (500 MHz, CDCl3) δ 3.39−3.54 (m, 2H), 5.71−5.77 (m,
1H), 5.93 (ddt, J 10.0, 3.6, 2.2 Hz, 1H), 6.20 (dtd, J 10.0, 3.6, 1.8 Hz,
1H), 6.83 (br d, J 5.7 Hz, 1H), 7.18−7.23 (m, 1H), 7.27−7.31 (m,
2H), 7.37−7.41 (m, 1H); 13C NMR (126 MHz, CDCl3) δ 29.5
(CH2), 48.0 (CH), 92.9 (C), 124.4 (CH), 127.3 (CH), 128.1 (CH),
128.4 (CH), 128.6 (CH), 128.7 (CH), 133.2 (C), 134.1 (C), 161.6
(C); HRMS (ESI) calcd for C12H1035Cl3NNaO (MNa+), 311.9720,
found 311.9719.
1
1636, 1510, 1449, 1373, 1090, 966, 739 cm−1; H NMR (400 MHz,
CDCl3) δ 1.58 (br s, 1H), 3.92 (dt, J 5.5, 1.8 Hz, 2H), 4.40 (d, J 5.7,
2H), 4.91 (dq, J 17.2, 1.8 Hz, 1H), 5.06 (dq, 10.2, 1.8 Hz, 1H), 6.08
(ddt, J 17.2, 10.2, 5.5 Hz, 1H), 6.39 (dt, J 15.7, 5.7 Hz, 1H), 7.07 (d, J
15.7 Hz, 1H), 7.45 (ddd, J 8.0, 7.0, 1.1 Hz, 1H), 7.50 (ddd, J 8.4, 7.0,
1.2 Hz, 1H), 7.63 (d, J 8.7 Hz, 1H), 7.72 (d, J 8.7 Hz, 1H), 7.81 (dd, J
8.0, 1.2 Hz, 1H), 8.03 (d, J 8.4 Hz, 1H); 13C NMR (101 MHz, CDCl3)
δ 32.3 (CH2), 64.2 (CH2), 116.1 (CH2), 124.5 (CH), 124.6 (CH),
125.6 (CH), 126.4 (CH), 127.2 (CH), 128.6 (CH), 129.4 (CH),
131.2 (CH), 132.5 (C), 132.6 (C), 133.0 (C), 133.5 (C), 136.2 (CH);
MS m/z 247 (MNa+, 100), 236 (49), 227 (40), 207 (29), 179 (100),
166 (17), 159 (11); HRMS (ESI) calcd for C16H16NaO (MNa+),
247.1093, found 247.1093.
(2E)-3-(2′-Allyl-5′-methoxyphenyl)prop-2-en-1-ol (15f). The
reaction was carried out according to the previously described
procedure for (2E)-3-(2′-vinylphenyl)prop-2-en-1-ol (8a) using ethyl
(2E)-3-(2′-allyl-5′-methoxyphenyl)prop-2-enoate (14f) (0.461 g, 1.87
mmol). This gave (2E)-3-(2′-allyl-5′-methoxyphenyl)prop-2-en-1-ol
(15f) (0.313 g, 82%) as a yellow oil. IR (neat) 3228, 2909, 1605, 1572,
1495, 1285, 1198, 1163, 1040, 964 cm−1; 1H NMR (500 MHz,
CDCl3) δ 1.46 (t, J 5.3 Hz, 1H), 3.39 (dt, J 6.2, 1.7 Hz, 2H), 3.81 (s,
3H), 4.33 (t, J 5.3 Hz, 2H), 4.95 (dq, J 16.9, 1.7 Hz, 1H), 5.04 (dq, J
10.2, 1.7 Hz, 1H), 5.94 (ddt, J 16.9, 10.2, 6.2 Hz, 1H), 6.25 (dt, J 15.7,
6-Methyl-1-(2′,2′,2′-trichloromethylcarbonylamino)-1,4-di-
hydronaphthalene (16b). The reaction was carried out according to
the previously described procedure for 1-(2′,2′,2′-trichloromethylcar-
bonylamino)-1H-indene (11a) using (2E)-3-(2′-allyl-4′-
methylphenyl)prop-2-en-1-ol (15b) (0.059 g, 0.31 mmol). The
RCM step was performed at room temperature. This gave 6-methyl-
1-(2′,2′,2′-trichloromethylcarbonylamino)-1,4-dihydronaphthalene
(16b) (0.078 g, 82%) as a white solid. Mp 118−122 °C; IR (neat)
1
3253, 3036, 1685, 1529, 1300, 1249, 1025, 823 cm−1; H NMR (500
MHz, CDCl3) δ 2.34 (s, 3H), 3.33−3.49 (m, 2H), 5.65−5.73 (m, 1H),
5.92 (ddt, J 10.1, 3.6, 2.2 Hz, 1H), 6.18 (dtd, J 10.1, 3.6, 1.8 Hz, 1H),
6.82 (br d, J 8.4 Hz, 1H), 7.02 (s, 1H), 7.09 (d, J 8.0 Hz, 1H), 7.28 (d,
J 8.0 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 21.2 (CH3), 29.4
(CH2), 47.9 (CH), 93.0 (C), 124.4 (CH), 128.2 (CH), 128.3 (CH),
K
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1
128.7 (CH), 129.0 (CH), 130.2 (C), 134.0 (C), 137.8 (C), 161.5 (C);
MS m/z 326 (MNa+, 100), 319 (14), 297 (6), 236 (10), 184 (14), 175
(14), 143 (36), 128 (7); HRMS (ESI) calcd for C13H1235Cl3NNaO
(MNa+), 325.9877, found 325.9864.
2935, 1704, 1613, 1501, 1261, 1241, 1033, 1021, 816 cm−1; H NMR
(500 MHz, CDCl3) δ 3.31−3.46 (m, 2H), 3.77 (s, 3H), 5.67−5.74 (m,
1H), 5.89 (ddt, J 10.1, 3.6, 2.3 Hz, 1H), 6.20 (dtd, J 10.1, 3.6, 1.8 Hz,
1H), 6.86 (dd, J 8.4, 3.0 Hz, 1H), 6.87−6.91 (m, 2H), 7.10 (d, J 8.4
Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 28.7 (CH2), 48.3 (CH3),
55.5 (CH), 92.9 (C), 111.8 (CH), 115.4 (CH), 123.9 (CH), 126.1
(C), 129.1 (CH), 129.6 (CH), 134.1 (C), 158.6 (C), 161.6 (C); MS
m/z 342 (MNa+, 100), 319 (83), 307 (7), 297 (6), 236 (10), 218 (6),
184 (11), 159 (22), 144 (4); HRMS (ESI) calcd for
C13H1235Cl3NNaO2 (MNa+), 341.9826, found 341.9811.
6,7-Methylenedioxy-1-(2′,2′,2′-trichloromethylcarbonylami-
no)-1,4-dihydronaphthalene (16c). The reaction was carried out
according to the previously described procedure for 1-(2′,2′,2′-
trichloromethylcarbonylamino)-1H-indene (11a) using (2E)-3-(2′-
allyl-4′,5′-methylenedioxy phenyl)prop-2-en-1-ol (15c) (1.96 g, 8.99
mmol). Grubbs second generation catalyst (0.114 g, 0.135 mmol) was
added, and the reaction mixture was stirred at room temperature for 3
h before a second portion of Grubbs second generation catalyst
(0.0763 g, 0.0899 mmol) was added and allowed to stir for a further 17
h. This gave 6,7-methylenedioxy-1-(2′,2′,2′-trichloromethylcarbonyla-
mino)-1,4-dihydronaphthalene (16c) (2.43 g, 81%) as a white solid.
Mp 114−116 °C; IR (neat) 3334, 2894, 1699, 1502, 1482, 1233, 1038,
819 cm−1; 1H NMR (500 MHz, CDCl3) δ 3.24−3.39 (m, 2H), 5.53−
5.60 (m, 1H), 5.85 (ddt, J 10.0, 3.9, 2.2 Hz, 1H), 5.88 (d, J 1.3 Hz,
1H), 5.89 (d, J 1.3 Hz, 1H), 6.13 (dtd, J 10.0, 3.5, 1.7 Hz, 1H), 6.55 (s,
1H), 6.75 (s, 1H), 6.87 (d, J 8.8 Hz, 1H); 13C NMR (126 MHz,
CDCl3) δ 29.6 (CH2), 48.2 (CH), 92.8 (C), 101.1 (CH2), 107.5
(CH), 107.7 (CH), 123.8 (CH), 125.9 (C), 127.6 (C), 128.5 (CH),
146.8 (C), 147.5 (C), 161.4 (C); MS m/z 356 (MNa+, 85), 346 (7),
242 (100), 236 (14), 184 (18), 173 (18), 142 (4); HRMS (ESI) calcd
for C13H1035Cl3NNaO3 (MNa+), 355.9618, found 355.9602.
1-(2′,2′,2′-Trichloromethylcarbonylamino)-6-trifluorometh-
yl-1,4-dihydronaphthalene (16g). The reaction was carried out
according to the previously described procedure for 1-(2′,2′,2′-
trichloromethylcarbonylamino)-1H-indene (11a) using (2E)-3-(2′-
allyl-4′-trifluoromethylphenyl)prop-2-en-1-ol (15g) (0.061 g, 0.25
mmol). Grubbs second generation catalyst (0.011 g, 0.013 mmol)
was added, and the reaction mixture was stirred at 50 °C for 24 h
before a second portion of Grubbs second generation catalyst (0.011 g,
0.013 mmol) was added and allowed to stir at 50 °C for a further 24 h.
This gave 1-(2′,2′,2′-trichloromethylcarbonylamino)-6-trifluorometh-
yl-1,4-dihydronaphthalene (16g) (0.065 g, 72%) as a colorless oil. IR
(neat) 3268, 2924, 1684, 1525, 1329, 1160, 1119, 822 cm−1; 1H NMR
(500 MHz, CDCl3) δ 3.43−3.59 (m, 2H), 5.74−5.80 (m, 1H), 5.94
(ddt, J 10.0, 3.5, 2.0 Hz, 1H), 6.24 (dtd, J 10.0, 3.5, 1.5 Hz, 1H), 6.86
(d, J 8.3 Hz, 1H), 7.47 (s, 1H), 7.51−7.53 (m, 2H); 13C NMR (126
MHz, CDCl3) δ 29.3 (CH2), 47.5 (CH), 92.6 (C), 123.9 (CH, q, 3JCF
7-Fluoro-1-(2′,2′,2′-trichloromethylcarbonylamino)-1,4-di-
hydronaphthalene (16d). The reaction was carried out according to
the previously described procedure for 1-(2′,2′,2′-trichloromethylcar-
bonylamino)-1H-indene (11a) using (2E)-3-(2′-allyl-5′-fluorophenyl)-
prop-2-en-1-ol (15d) (0.053 g, 0.28 mmol). The RCM step was
performed at room temperature. This gave 7-fluoro-1-(2′,2′,2′-
trichloromethylcarbonylamino)-1,4-dihydronaphthalene (16d) (0.076
g, 76%) as a white solid. Mp 123−127 °C; IR (neat) 3268, 3040, 1687,
1
3
3.6 Hz), 124.0 (C, q, JCF 272.3 Hz), 124.0 (CH), 125.6 (CH, q, JCF
2
3.8 Hz), 128.4 (CH), 128.9 (CH), 130.4 (C, q, JCF 32.5 Hz), 134.7
(C), 137.0 (C), 161.6 (C); MS m/z 380 (MNa+, 100), 301 (19), 236
(26), 199 (3), 136 (2); HRMS (ESI) calcd for C13H935Cl3F3NNaO
(MNa+), 379.9594, found 379.9581.
7-(2′,2′,2′-Trichloromethylcarbonylamino)-4,7-
dihydrobenzo[b]furan (16h). The reaction was carried out
according to the previously described procedure for 1-(2′,2′,2′-
trichloromethylcarbonylamino)-1H-indene (11a) using (2E)-3-(3′-
allylfuran-2′-yl)prop-2-en-1-ol (15h) (0.055 g, 0.33 mmol). The
RCM step was performed at room temperature. This gave 7-
(2′,2′,2′-trichloromethylcarbonylamino)-4,7-dihydrobenzo[b]furan
(16h) (0.052 g, 72%) as a white solid. Mp 102−104 °C; IR (neat)
1
1503, 1249, 1226, 1023, 815 cm−1; H NMR (500 MHz, CDCl3) δ
3.34−3.50 (m, 2H), 5.66−5.73 (m, 1H), 5.80 (ddt, J 10.1, 3.5, 1.9 Hz,
1H), 6.21 (dtd, J 10.1, 3.6, 1.9 Hz, 1H), 6.84 (br d, J 6.2 Hz, 1H), 6.99
(td, J 8.3, 2.6, Hz, 1H), 7.09 (dd, J 9.6, 2.6 Hz, 1H), 7.17 (dd, J 8.3, 5.7
Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 28.9 (CH2), 48.0 (CH, d,
4JCF 1.4 Hz), 92.8 (C), 114.5 (CH, d, 2JCF 21.6 Hz), 115.6 (CH, d, 2JCF
3275, 2886, 1686, 1517, 1244, 1036, 821 cm−1; H NMR (500 MHz,
1
4
21.6 Hz), 123.8 (CH), 128.8 (CH), 129.7 (C, d, JCF 3.1 Hz), 130.2
(CH, d, 3JCF 7.8 Hz), 135.1 (C, d, 3JCF 7.0 Hz), 161.7 (C), 161.8 (C, d,
1JCF 245.5 Hz); HRMS (ESI) calcd for C12H935Cl237ClFNNaO
CDCl3) δ 3.14−3.28 (m, 2H), 5.66−5.73 (m, 1H), 5.88 (ddt, J 9.9,
3.7, 2.1 Hz, 1H), 6.14 (dtd, J 9.9, 3.4, 1.7 Hz, 1H), 6.32 (d, J 1.9 Hz,
1H), 6.73 (br s, 1H), 7.41 (d, J 1.9 Hz, 1H); 13C NMR (126 MHz,
CDCl3) δ 25.1 (CH2), 44.8 (CH), 92.7 (C), 109.6 (CH), 118.4 (C),
123.7 (CH), 129.2 (CH), 143.0 (CH), 145.3 (C), 161.5 (C); MS m/z
302 (MNa+, 100), 236 (10), 218 (2), 184 (10); HRMS (ESI) calcd for
C10H835Cl3NNaO2 (MNa+), 301.9513, found 301.9512.
(MNa+), 331.9597, found 331.9588.
1-(2′,2′,2′-Trichloromethylcarbonylamino)-1,4-dihydrophe-
nanthrene (16e). The reaction was carried out according to the
previously described procedure for 1-(2′,2′,2′-trichloromethylcarbo-
nylamino)-1H-indene (11a) using (2E)-3-(1′-allylnaphthalen-2′-yl)-
prop-2-en-1-ol (15e) (0.059 g, 0.31 mmol). The RCM step was
performed at room temperature. This gave 1-(2′,2′,2′-trichlorome-
thylcarbonylamino)-1,4-dihydrophenanthrene (16e) (0.081 g, 84%) as
a white solid. Mp 150−152 °C (decomposition); IR (neat) 3250,
6,7-Methylenedioxy-1-(2′,2′,2′-trichloromethylcarbonyl-
amino)naphthalene (17). Manganese(IV) oxide (0.521 g, 5.99
mmol) was added to a solution of 6,7-methylenedioxy-1-(2′,2′,2′-
trichloromethylcarbonylamino)-1,4-dihydronaphthalene (16c) (0.200
g, 0.597 mmol) in chloroform (6 mL) and heated at 45 °C for 20 h.
The crude reaction mixture was filtered through a short pad of Celite
with chloroform (100 mL) and then concentrated in vacuo.
Purification by column chromatography (elution with 100% toluene)
y i e l d e d 6 , 7 - m e t h y l e n e d i o x y - 1 - ( 2 ′ , 2 ′ , 2 ′ -
trichloromethylcarbonylamino)naphthalene (17) (0.143 g, 72%) as a
white solid. Further elution gave 6,7-methylenedioxy-1,4-naphthoqui-
none (18) (0.019 g, 16%) as an orange solid. Data for 17: Mp 139−
140 °C; IR (neat) 3302, 2913, 1686, 1489, 1462, 1242, 1034, 849, 814
cm−1; 1H NMR (500 MHz, CDCl3) δ 6.05 (s, 2H), 7.05 (s, 1H), 7.13
(s, 1H), 7.32 (t, J 7.9 Hz, 1H), 7.55 (d, J 7.9 Hz, 1H), 7.60 (d, J 7.9
Hz, 1H), 8.46 (br s, 1H); 13C NMR (126 MHz, CDCl3) δ 93.1 (C),
97.6 (CH), 101.6 (CH2), 104.8 (CH), 121.4 (CH), 124.2 (CH), 125.3
(C), 127.0 (CH), 130.0 (C), 131.6 (C), 148.1 (C), 148.9 (C), 160.6
(C); MS m/z 354 (MNa+, 100), 301 (3), 236 (7), 227 (4), 159 (1);
HRMS (ESI) calcd for C13H835Cl3NNaO3 (MNa+), 353.9462, found
353.9452. Data for 18: Mp 196−200 °C; IR (neat) 2928, 1655, 1586,
1485, 1316, 1026, 976, 833 cm−1; 1H NMR (400 MHz, CDCl3) δ 6.14
(s, 2H), 6.88 (s, 2H), 7.45 (s, 2H); 13C NMR (101 MHz, CDCl3) δ
1
3042, 1678, 1510, 1308, 1248, 1020, 818 cm−1; H NMR (500 MHz,
CDCl3) δ 3.72−3.89 (m, 2H), 5.87−5.94 (m, 1H), 6.04 (ddt, J 10.0,
3.6, 2.5 Hz, 1H), 6.37 (dtd, J 10.0, 3.6, 1.6 Hz, 1H), 6.85 (d, J 8.3 Hz,
1H), 7.46 (d, J 8.5 Hz, 1H), 7.52−7.61 (m, 2H), 7.79 (d, J 8.5 Hz,
1H), 7.86 (dd, J 8.1, 0.9 Hz, 1H), 7.98 (d, J 8.5 Hz, 1H); 13C NMR
(126 MHz, CDCl3) 26.8 (CH2), 48.7 (CH), 92.9 (C), 123.4 (CH),
123.7 (CH), 126.0 (CH), 126.4 (CH), 126.8 (CH), 128.0 (CH),
128.4 (CH), 128.7 (CH), 129.7 (C), 130.1 (C), 131.3 (C), 133.0 (C),
161.6 (C); MS m/z 362 (MNa+, 56), 320 (61), 307 (10), 301 (7), 242
(7), 179 (100), 141 (3); HRMS (ESI) calcd for C16H1235Cl3NNaO
(MNa+), 361.9877, found 361.9866.
7-Methoxy-1-(2′,2′,2′-trichloromethylcarbonylamino)-1,4-
dihydronaphthalene (16f). The reaction was carried out according
to the previously described procedure for 1-(2′,2′,2′-trichloromethyl-
carbonylamino)-1H-indene (11a) using (2E)-3-(2′-allyl-5′-
methoxyphenyl)prop-2-en-1-ol (15f) (0.052 g, 0.26 mmol). The
RCM step was performed at room temperature. This gave 7-methoxy-
1-(2′,2′,2′-trichloromethylcarbonylamino)-1,4-dihydronaphthalene
(16f) (0.063 g, 76%) as a white solid. Mp 92−96 °C; IR (neat) 3293,
L
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102.6 (CH2), 105.9 (CH), 129.0 (C), 138.2 (CH), 152.3 (C), 184.0
(C); MS m/z 202 (M+, 100), 174 (37), 148 (22), 120 (29), 105 (20),
84 (41), 77 (19), 62 (24); HRMS (EI) calcd for C11H6O4 (M+),
202.0266, found 202.0264.
2-Bromo-4,5-dimethoxy-N-(6′,7′-methylenedioxynaphtha-
len-1-yl)benzamide (21c).42 The reaction was carried out according
to the previously described procedure for 6-bromo-2,3-dimethoxy-N-
(6′,7′-methylenedioxynaphthalen-1-yl)benzamide (21a) using 2-
bromo-4,5-dimethoxybenzoic acid (0.084 g, 0.32 mmol) and 6,7-
methylenedioxy-1-aminonaphthalene (19) (0.050 g, 0.27 mmol). This
gave 2-bromo-4,5-dimethoxy-N-(6′,7′-methylenedioxynaphthalen-1-
yl)benzamide (21c) (0.10 g, 88%) as a white solid. Mp 249−251
6,7-Methylenedioxy-1-aminonaphthalene (19).41 Hydro-
chloric acid (6 M, 15 mL) was added to a solution of 6,7-
methylenedioxy-1-(2′,2′,2′-trichloromethylcarbonylamino)-
naphthalene (17) (0.330 g, 0.991 mmol) in methanol (20 mL) and
heated with stirring to 90 °C for 60 h. The reaction mixture was
cooled to room temperature and washed with dichloromethane (2 ×
10 mL). The aqueous layer was basified to pH ≈ 10 with 12 M sodium
hydroxide solution and extracted with ethyl acetate (3 × 10 mL). The
combined ethyl acetate layers were dried (Na2SO4), filtered, and
concentrated in vacuo to yield 6,7-methylenedioxy-1-aminonaphtha-
lene (19) (0.182 g, 98%) as a white solid. Mp 151−152 °C (lit.41
°C (lit.42 250−252 °C); H NMR (500 MHz, DMSO-d6) δ 3.84 (s,
1
3H), 3.85 (s, 3H), 6.15 (s, 2H), 7.25 (s, 1H), 7.28 (s, 1H), 7.36 (t, J
7.7 Hz, 1H), 7.36 (s, 1H), 7.49 (s, 1H), 7.54 (d, J 7.7 Hz, 1H), 7.65 (d,
J 7.7 Hz, 1H), 10.22 (s, 1H); 13C NMR (126 MHz, DMSO-d6) δ 56.0
(CH3), 56.1 (CH3), 99.8 (CH), 101.3 (CH2), 103.8 (CH), 109.6 (C),
112.4 (CH), 115.7 (CH), 121.6 (CH), 123.9 (CH), 125.2 (CH),
125.6 (C), 131.1 (C), 131.1 (C), 132.8 (C), 147.3 (C), 147.6 (C),
148.0 (C), 150.1 (C), 166.4 (C); MS (ESI) m/z 452 (MNa+, 100),
413 (6), 381 (10), 353 (10), 301 (3), 236 (3).
2-Bromo-4,5-methylenedioxy-N-(6′,7′-methylenedioxy-
naphthalen-1-yl)benzamide (21d). The reaction was carried out
according to the previously described procedure for 6-bromo-2,3-
dimethoxy-N-(6′,7′-methylenedioxynaphthalen-1-yl)benzamide (21a)
using 2-bromo-4,5-methylenedioxybenzoic acid (0.031 g, 0.13 mmol)
and 6,7-methylenedioxy-1-aminonaphthalene (19) (0.020 g, 0.11
mmol). This gave 2-bromo-4,5-methylenedioxy-N-(6′,7′-methylene-
dioxynaphthalen-1-yl)benzamide (21d) (0.039 g, 89%) as a white
solid. Mp 236−238 °C; IR (neat) 3233, 2909, 1659, 1543, 1462, 1238,
1038, 934, 849 cm−1; 1H NMR (500 MHz, DMSO-d6) δ 6.15 (s, 2H),
6.16 (s, 2H), 7.31−7.38 (m, 4H), 7.48 (s, 1H), 7.52 (d, J 7.7 Hz, 1H),
7.65 (d, J 7.7 Hz, 1H), 10.24 (s, 1H); 13C NMR (126 MHz, DMSO-
d6) δ 99.7 (CH), 101.3 (CH2), 102.3 (CH2), 103.8 (CH), 108.9
(CH), 110.2 (C), 112.5 (CH), 121.6 (CH), 123.8 (CH), 125.2 (CH),
125.6 (C), 131.0 (2 × C), 132.6 (C), 146.9 (C), 147.3 (C), 147.6 (C),
148.8 (C), 166.2 (C); MS m/z 436 (MNa+, 100), 413 (8), 370 (4),
236 (7), 227 (8), 198 (3); HRMS (ESI) calcd for C19H1279BrNNaO5
(MNa+), 435.9791, found 435.9775.
1
151−153 °C); H NMR (500 MHz, CDCl3) δ 3.85 (s, 2H), 6.03 (s,
2H), 6.69 (dd, J 6.6, 1.9 Hz, 1H), 7.09 (s, 1H), 7.13 (s, 1H), 7.14−
7.18 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 97.9 (CH), 101.2
(CH2), 104.8 (CH), 109.7 (CH), 118.9 (CH), 120.3 (C), 125.0 (CH),
131.7 (C), 141.5 (C), 147.3 (C), 147.6 (C); MS (ESI) m/z 188
(MH+, 100), 158 (26), 146 (10), 130 (78).
6-Bromo-2,3-dimethoxy-N-(6′,7′-methylenedioxynaphtha-
len-1-yl)benzamide (21a).7c 6-Bromo-2,3-dimethoxybenzoic acid
(0.024 g, 0.10 mmol) was suspended in thionyl chloride (0.5 mL) and
heated with stirring to 65 °C for 1 h. The reaction mixture was cooled
and concentrated in vacuo to yield the acid chloride 20a, which was
used without further purification. In a second flask, N,N-
diisopropylethylamine (0.14 mL, 0.80 mmol) was added to a solution
of 6,7-methylenedioxy-1-aminonaphthalene (19) (0.015 g, 0.080
mmol) in dichloromethane (0.4 mL) and cooled to 0 °C. Acid
chloride 20a was dissolved in dichloromethane (0.4 mL) and added
dropwise to the cooled, stirring solution of amines. The reaction
mixture was stirred at 0 °C for 1 h and then allowed to return to room
temperature over 1 h. The reaction was quenched with 1 M
hydrochloric acid (1 mL) and extracted with dichloromethane (3 ×
10 mL). The combined organic layers were washed with a saturated
solution of sodium hydrogen carbonate (20 mL) and then brine (30
mL), dried (MgSO4), filtered, and concentrated in vacuo. The resulting
solid was washed with a minimal volume of ice cold chloroform to
yield 6-bromo-2,3-dimethoxy-N-(6′,7′-methylenedioxynaphthalen-1-
yl)benzamide (21a) (0.031 g, 89%) as a white solid. Mp 227−229
6-Bromo-2,3-dimethoxy-N-methyl-N-(6′,7′-methylenedioxy-
naphthalen-1-yl)benzamide (22a).7c Sodium hydride (60%
dispersion in mineral oil, 0.020 g, 0.51 mmol) was washed with
hexane (3 × 3 mL) under argon and dried under reduced pressure.
N,N′-Dimethylformamide (1 mL) was added to the sodium hydride
followed slowly by a solution of 6-bromo-2,3-dimethoxy-N-(6′,7′-
methylenedioxynaphthalen-1-yl)benzamide (21a) (0.087 g, 0.20
mmol) in N,N′-dimethylformamide (1 mL). The reaction mixture
was stirred at room temperature for 0.1 h, then methyl iodide (0.044
mL, 0.71 mmol) was added dropwise with vigorous stirring, and the
mixture was stirred for 18 h at room temperature. The reaction was
quenched by the slow addition of 1 M hydrochloric acid solution (3
mL), diluted with 5% lithium chloride solution (3 mL), and extracted
with diethyl ether (3 × 5 mL). The combined organic layers were
washed with brine (3 × 10 mL), dried (MgSO4), filtered, and
concentrated in vacuo. The crude product was washed with cold
hexane (5 × 1 mL), to yield 6-bromo-2,3-dimethoxy-N-methyl-N-
(6′,7′-methylenedioxynaphthalen-1-yl)benzamide (22a) (0.088 g,
98%) as a white solid. Mp 173−175 °C (lit.7c mp 178−179 °C);
the NMR spectra showed the presence of rotomers; for simplification,
°C (lit.7c 237.5−239 °C); H NMR (500 MHz, CDCl3) δ 3.92 (s,
1
3H), 3.98 (s, 3H), 6.05 (s, 2H), 6.88 (d, J 8.8 Hz, 1H), 7.15 (s, 1H),
7.34 (d, J 8.8 Hz, 1H), 7.38 (t, J 7.8 Hz, 1H), 7.47−7.52 (m, 2H), 7.61
(d, J 7.8 Hz, 1H), 7.69 (d, J 7.8 Hz, 1H); 13C NMR (126 MHz,
CDCl3) δ 56.3 (CH3), 62.5 (CH3), 99.0 (CH), 101.4 (CH2), 104.5
(CH), 110.0 (C), 114.6 (CH), 122.1 (CH), 124.4 (CH), 126.3 (C),
126.4 (CH), 128.6 (CH), 131.4 (C), 131.7 (C), 134.2 (C), 147.2 (C),
148.0 (C), 148.7 (C), 152.5 (C), 164.8 (C); MS (ESI) m/z 452
(MNa+, 100), 430 (1), 413 (3), 243 (1).
6-Bromo-2,3-methylenedioxy-N-(6′,7′-methylenedioxy-
naphthalen-1-yl)benzamide (21b). The reaction was carried out
according to the previously described procedure for 6-bromo-2,3-
dimethoxy-N-(6′,7′-methylenedioxynaphthalen-1-yl)benzamide (21a)
using 6-bromo-2,3-methylenedioxybenzoic acid (0.13 g, 0.51 mmol)
and 6,7-methylenedioxy-1-aminonaphthalene (19) (0.080 g, 0.43
mmol). This gave 6-bromo-2,3-methylenedioxy-N-(6′,7′-methylene-
dioxynaphthalen-1-yl)benzamide (21b) (0.16 g, 89%) as a white solid.
Mp 236−238 °C; IR (neat) 3237, 2905, 1655, 1543, 1493, 1451, 1238,
1038, 926, 849 cm−1; 1H NMR (500 MHz, DMSO-d6) δ 6.15 (s, 2H),
6.22 (s, 2H), 7.01 (d, J 8.3 Hz, 1H), 7.20 (d, J 8.3 Hz, 1H), 7.36 (t, J
7.6 Hz, 1H), 7.37 (s, 1H), 7.46 (s, 1H), 7.47 (d, J 7.6 Hz, 1H), 7.67 (d,
J 7.6 Hz, 1H), 10.52 (s, 1H); 13C NMR (126 MHz, DMSO-d6) δ 99.3
(CH), 101.4 (CH2), 102.6 (CH2), 103.9 (CH), 110.0 (C), 110.2
(CH), 121.3 (C), 121.5 (CH), 123.9 (CH), 125.2 (CH), 125.4 (CH),
125.4 (C), 131.1 (C), 132.1 (C), 145.7 (C), 147.2 (C), 147.4 (C),
147.7 (C), 162.2 (C); MS m/z 436 (MNa+, 98), 413 (13), 335 (13),
289 (3), 236 (8), 159 (6); HRMS (ESI) calcd for C19H1279BrNNaO5
(MNa+), 435.9791, found 435.9792.
1
only signals for the major rotomer are reported: H NMR (500 MHz,
CDCl3) δ 3.20 (s, 3H), 3.93 (s, 3H), 4.03 (s, 3H), 6.04 (d, J 1.5 Hz,
1H), 6.05 (d, J 1.5 Hz, 1H), 6.87 (d, J 9.0 Hz, 1H), 7.17 (s, 1H), 7.34
(d, J 9.0 Hz, 1H), 7.38−7.42 (m, 1H), 7.44−7.48 (m, 1H), 7.53 (s,
1H), 7.64−7.69 (m, 1H); 13C NMR (126 MHz, CDCl3) δ 39.6
(CH3), 56.2 (CH3), 61.9 (CH3), 99.7 (CH), 101.3 (CH2), 104.5
(CH), 109.4 (C), 114.0 (CH), 123.6 (CH), 124.7 (CH), 127.4 (CH),
128.2 (C), 128.5 (CH), 131.8 (C), 132.2 (C), 134.0 (C), 138.8 (C),
146.0 (C), 149.1 (C), 152.6 (C), 166.9 (C); MS (ESI) m/z 466
(MNa+, 100), 446 (1), 243 (1), 227 (1).
6-Bromo-2,3-methylenedioxy-N-methyl-N-(6′,7′-methylene-
dioxynaphthalen-1-yl)benzamide (22b). The reaction was carried
out according to the previously described procedure for 6-bromo-2,3-
dimethoxy-N-methyl-N-(6′,7′-methylenedioxynaphthalen-1-yl)-
benzamide (22a) using 6-bromo-2,3-methylenedioxy-N-(6′,7′-methyl-
M
dx.doi.org/10.1021/jo5014492 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
enedioxynaphthalen-1-yl)benzamide (21b) (0.140 g, 0.338 mmol).
This gave 6-bromo-2,3-methylenedioxy-N-methyl-N-(6′,7′-methylene-
dioxynaphthalen-1-yl)benzamide (22b) (0.138 g, 95%) as a white
solid. Mp 161−163 °C; IR (neat) 2901, 1651, 1462, 1447, 1373, 1246,
1038, 934 cm−1; the NMR spectra showed the presence of rotomers;
and then washing the resulting solid with hexane (3 × 1 mL) yielded
oxychelerythrine (1) (0.016 g, 95%) as a white solid. Mp 194−197 °C
(lit.6g 198−200 °C); 1H NMR (500 MHz, CDCl3) δ 3.89 (s, 3H), 3.98
(s, 3H), 4.08 (s, 3H), 6.09 (s, 2H), 7.15 (s, 1H), 7.38 (d, J 9.0 Hz,
1H), 7.52 (d, J 9.0 Hz, 1H), 7.53 (s, 1H), 7.98 (d, J 9.0 Hz, 2H); 13C
NMR (126 MHz, CDCl3) δ 40.9 (CH3), 56.8 (CH3), 61.9 (CH3),
101.6 (CH2), 102.6 (CH), 104.8 (CH), 117.3 (C), 117.9 (CH), 118.0
(CH), 118.6 (CH), 119.9 (C), 121.2 (C), 123.4 (CH), 129.1 (C),
131.8 (C), 135.8 (C), 147.2 (C), 147.6 (C), 150.3 (C), 152.9 (C),
162.8 (C); MS (ESI) m/z 386 (MNa+, 100), 371 (4), 227 (6).
Oxysanguinarine (2).6g The reaction was carried out according to
the previously described procedure for the synthesis of oxy-
chelerythrine (1) using 6-bromo-2,3-methylenedioxy-N-methyl-N-
(6′,7′-methylenedioxynaphthalen-1-yl)benzamide (22b) (0.020 g,
0.047 mmol). The reaction was complete after 3 h. Purification by
column chromatography (20−100% ethyl acetate in petroleum ether,
then 1% methanol in dichloromethane) and then washing the resulting
solid with hexane (3 × 1 mL) gave oxysanguinarine (2) (0.015 g, 90%)
as a white solid. Mp 356−358 °C (lit.6g 361−363 °C); 1H NMR (500
MHz, CDCl3) δ 3.91 (s, 3H), 6.10 (s, 2H), 6.27 (s, 2H), 7.16 (s, 1H),
7.24 (d, J 8.7 Hz, 1H), 7.53 (d, J 8.7 Hz, 1H), 7.57 (s, 1H), 7.76 (d, J
8.7 Hz, 1H), 7.98 (d, J 8.7 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ
41.0 (CH3), 101.7 (CH2), 102.7 (CH), 103.0 (CH2), 104.9 (CH),
111.1 (C), 113.3 (CH), 115.6 (CH), 117.4 (C), 118.9 (CH), 121.3
(C), 123.7 (CH), 129.0 (C), 132.0 (C), 135.7 (C), 147.3 (C), 147.7
(C), 147.8 (C), 147.9 (C), 162.8 (C); MS (ESI) m/z 370 (MNa+,
100), 354 (3), 342 (3), 236 (6), 227 (1).
1
for simplification, only signals for the major rotomer are reported: H
NMR (500 MHz, CDCl3) δ 3.52 (s, 3H), 5.13 (d, J 1.5 Hz, 1H), 5.79
(d, J 1.5 Hz, 1H), 6.04 (d, J 1.0 Hz, 1H), 6.08 (d, J 1.0 Hz, 1H), 6.36
(d, J 8.0 Hz, 1H), 6.82 (d, J 8.0 Hz, 1H), 7.07 (s, 1H), 7.13−7.17 (m,
1H), 7.34 (s, 1H), 7.51−7.55 (m, 1H), 7.66−7.71 (m, 1H); 13C NMR
(126 MHz, CDCl3) δ 37.3 (CH3), 100.6 (CH), 101.4 (CH2), 101.6
(CH2), 104.3 (CH), 109.4 (CH), 111.2 (C), 121.1 (C), 124.2 (2 ×
CH), 125.3 (CH), 125.8 (C), 127.9 (CH), 138.7 (C), 144.9 (C),
146.6 (C), 146.7 (C), 147.9 (C), 148.1 (C), 165.7 (C); MS m/z 450
(MNa+, 98), 430 (1), 413 (6), 236 (1), 227 (1); HRMS (ESI) calcd
for C20H1479BrNNaO5 (MNa+), 449.9948, found 449.9935.
2-Bromo-4,5-dimethoxy-N-methyl-N-(6′,7′-methylenedioxy-
naphthalen-1-yl)benzamide (22c).42 The reaction was carried out
according to the previously described procedure for 6-bromo-2,3-
dimethoxy-N-methyl-N-(6′,7′-methylenedioxynaphthalen-1-yl)-
benzamide (22a) using 2-bromo-4,5-dimethoxy-N-(6′,7′-methylene-
dioxynaphthalen-1-yl)benzamide (21c) (0.085 g, 0.20 mmol). This
gave 2-bromo-4,5-dimethoxy-N-methyl-N-(6′,7′-methylenedioxynaph-
thalen-1-yl)benzamide (22c) (0.083 g, 94%) as a white solid. Mp
182−184 °C (lit.42 186−187 °C); the NMR spectra showed the
presence of rotomers; for simplification, only signals for the major
1
rotomer are reported: H NMR (500 MHz, CDCl3) δ 3.32 (s, 3H),
Oxynitidine (3).6g The reaction was carried out according to the
previously described procedure for the synthesis of oxychelerythrine
(1) using 2-bromo-4,5-dimethoxy-N-methyl-N-(6′,7′-methylenediox-
ynaphthalen-1-yl)benzamide (22c) (0.019 g, 0.043 mmol) and trans-
bis(acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II) (23)
(0.0080 g, 0.0086 mmol). Purification was performed by washing
with hexane (5 × 2 mL) and then ice-cold diethyl ether (3 × 1 mL),
which yielded oxynitidine (3) (0.013 g, 83%) as a white solid. Mp
268−270 °C (lit.6g 270−272 °C); 1H NMR (500 MHz, CDCl3) δ 3.99
(s, 3H), 4.06 (s, 3H), 4.11 (s, 3H), 6.11 (s, 2H), 7.19 (s, 1H), 7.57 (d,
J 8.7 Hz, 1H), 7.60 (s, 1H), 7.65 (s, 1H), 7.93 (s, 1H), 8.00 (d, J 8.7
Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 41.4 (CH3), 56.3 (CH3),
56.4 (CH3), 101.7 (CH2), 102.8 (CH), 103.0 (CH), 104.9 (CH),
108.8 (CH), 116.9 (C), 118.5 (CH), 119.4 (C), 121.2 (C), 123.4
(CH), 129.1 (C), 132.0 (C), 136.1 (C), 147.2 (C), 147.7 (C), 149.9
(C), 153.7 (C), 164.4 (C); MS (EI) m/z 363 (M+, 100), 334 (17),
305 (15), 290 (8), 262 (9), 182 (10), 84 (11).
3.52 (s, 3H), 3.71 (s, 3H), 6.07 (s, 2H), 6.46 (s, 1H), 6.79 (s, 1H),
7.09 (s, 1H), 7.13 (dd, J 8.1, 7.5 Hz, 1H), 7.29 (dd, J 7.5, 1.1 Hz, 1H),
7.31 (s, 1H), 7.49 (br d, J 8.1 Hz, 1H); 13C NMR (126 MHz, CDCl3)
δ 37.2 (CH3), 55.6 (CH3), 56.1 (CH3), 99.2 (CH), 101.6 (CH2),
104.9 (CH), 110.6 (CH), 110.8 (C), 115.4 (CH), 124.4 (2 × CH),
127.5 (C), 127.7 (CH), 130.2 (C), 131.8 (C), 139.4 (C), 147.2 (C),
148.0 (C), 149.1 (C), 149.5 (C), 169.7 (C); MS (ESI) m/z 466
(MNa+, 100), 413 (1), 381 (4), 353 (4), 236 (2).
2-Bromo-4,5-methylenedioxy-N-methyl-N-(6′,7′-methylene-
dioxynaphthalen-1-yl)benzamide (22d). The reaction was carried
out according to the previously described procedure for 6-bromo-2,3-
dimethoxy-N-methyl-N-(6′,7′-methylenedioxynaphthalen-1-yl)-
benzamide (22a) using 2-bromo-4,5-methylenedioxy-N-(6′,7′-methyl-
enedioxynaphthalen-1-yl)benzamide (21d) (0.010 g, 0.024 mmol).
This gave 2-bromo-4,5-methylenedioxy-N-methyl-N-(6′,7′-methylene-
dioxynaphthalen-1-yl)benzamide (22d) (0.010 g, 98%) as a white
solid. Mp 193−196 °C; IR (neat) 2916, 1636, 1462, 1242, 1026, 934,
860 cm−1; the NMR spectra showed the presence of rotomers; for
Oxyavicine (4).6g The reaction was carried out according to the
previously described procedure for the synthesis of oxychelerythrine
(1) using 2-bromo-4,5-methylenedioxy-N-methyl-N-(6′,7′-methylene-
dioxynaphthalen-1-yl)benzamide (22d) (0.040 g, 0.093 mmol) and
trans-bis(acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II)
(23) (0.017 g, 0.019 mmol). Purification was performed by washing
with hexane (5 × 2 mL) and then ice-cold diethyl ether (3 × 1 mL),
which yielded oxyavicine (4) (0.025 g, 78%) as a white solid. Mp 265−
1
simplification, only signals for the major rotomer are reported: H
NMR (500 MHz, CDCl3) δ 3.48 (s, 3H), 5.74 (d, J 1.3 Hz, 1H), 5.78
(d, J 1.3 Hz, 1H), 6.08 (d, J 1.1 Hz, 1H), 6.11 (d, J 1.1 Hz, 1H), 6.42
(s, 1H), 6.80 (s, 1H), 7.09 (s, 1H), 7.15 (dd, J 8.1, 7.5 Hz, 1H), 7.24
(s, 1H), 7.34 (dd, J 7.5, 1.0 Hz, 1H), 7.51 (br d, J 8.1 Hz, 1H); 13C
NMR (126 MHz, CDCl3) δ 37.2 (CH3), 99.0 (CH), 101.5 (CH2),
101.7 (CH2), 104.6 (CH), 107.1 (CH), 111.5 (C), 112.9 (CH), 124.0
(CH), 124.2 (CH), 127.2 (C), 127.6 (CH), 131.5 (C), 131.7 (C),
139.0 (C), 146.3 (C), 148.1 (C), 148.3 (C), 149.1 (C), 169.3 (C); MS
m/z 450 (MNa+, 100), 413 (4), 301 (7), 257 (1), 236 (4), 199 (3);
HRMS (ESI) calcd for C20H1479BrNNaO5 (MNa+), 449.9948, found
449.9935.
268 °C (lit.6g 271−273 °C); H NMR (500 MHz, CDCl3) δ 3.97 (s,
1
3H), 6.10 (s, 2H), 6.13 (s, 2H), 7.17 (s, 1H), 7.54 (d, J 8.8 Hz, 1H),
7.60 (s, 1H), 7.62 (s, 1H), 7.89 (s, 1H), 7.92 (d, J 8.8 Hz, 1H); 13C
NMR (126 MHz, CDCl3) δ 41.4 (CH3), 100.8 (CH), 101.7 (CH2),
102.1 (CH2), 102.8 (CH), 104.9 (CH), 106.8 (CH), 117.0 (C), 118.7
(CH), 121.0 (C), 121.1 (C), 123.4 (CH), 131.2 (C), 132.1 (C), 136.0
(C), 147.2 (C), 147.7 (C), 148.3 (C), 152.6 (C), 164.2 (C); MS m/z
(ESI) 370 (MNa+, 49), 357 (57), 343 (100), 321 (6), 236 (6).
Oxychelerythrine (1).6g 6-Bromo-2,3-dimethoxy-N-methyl-N-
(6′,7′-methylenedioxynaphthalen-1-yl)benzamide (22a) (0.020 g,
0.045 mmol), trans-bis(acetato)bis[o-(di-o-tolylphosphino)benzyl]-
dipalladium(II) (23) (0.0042 g, 0.0045 mmol), and silver carbonate
(0.025 g, 0.090 mmol) were combined with a stirrer bar in a sealed
tube and placed under argon. Degassed N,N′-dimethylformamide (1.2
mL) was added, and the tube was sealed, heated to 160 °C for 22 h,
and then cooled to room temperature. The reaction mixture was
diluted with diethyl ether (4 mL) and filtered. The filtrate was then
further diluted with diethyl ether (10 mL), washed with 5% lithium
chloride solution (3 × 15 mL) and brine (15 mL), dried (MgSO4),
filtered, and concentrated in vacuo. Purification by column
chromatography (elution with 40% ethyl acetate in petroleum ether)
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: Andrew.Sutherland@glasgow.ac.uk.
■
N
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Article
Chem. 2011, 9, 2801. (d) Zaed, A. M.; Grafton, M. W.; Ahmad, S.;
Sutherland, A. J. Org. Chem. 2014, 79, 1511. (e) Calder, E. D. D.;
Grafton, M. W.; Sutherland, A. Synlett 2014, 25, 1068.
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the EPSRC (studentship to E.D.D.C.,
EP/P505534/1), the Scottish Funding Council (studentship to
F.I.M.), MSD, and the University of Glasgow is gratefully
acknowledged.
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