A photochemical route to 2-substituted benzo[b]furans

Article abstract of DOI:10.1021/jo3010183

2-Substituted benzo[b]furans were synthesized by a one-step metal-free photochemical reaction between 2-chlorophenol derivatives and terminal alkynes by tandem formation of an aryl-C and a C-O bond via an aryl cation intermediate. The mild conditions and the application to chlorophenols rather of the more expensive bromo or iodo analogues makes this procedure environmentally convenient.

Full text of DOI:10.1021/jo3010183

Article
pubs.acs.org/joc
A Photochemical Route to 2‑Substituted Benzo[b]furans
Stefano Protti,* Maurizio Fagnoni, and Angelo Albini
PhotoGreen Lab, Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy
S
* Supporting Information
ABSTRACT: 2-Substituted benzo[b]furans were synthesized by a one-step
metal-free photochemical reaction between 2-chlorophenol derivatives and
terminal alkynes by tandem formation of an aryl-C and a C−O bond via an
aryl cation intermediate. The mild conditions and the application to
chlorophenols rather of the more expensive bromo or iodo analogues makes
this procedure environmentally convenient.
salt catalysts (e.g., FeCl3) has given poor results and then only
with aromatic alkynes after heating at 135 °C for 72 h.12
In polyhalophenols the reaction occurred selective at the
iodo atom with no competition by other halides.13
Bromophenols have been likewise used in the synthesis of
benzofurans,14,15 but the experimental procedure is less
straightforward than with the corresponding iodides, and in
some cases a preliminary protection of the hydroxy group as
acetate had to be adopted. As a matter of fact, iodophenols gave
benzofurans twice as efficiently14 and as fast16 as bromophe-
nols, while requiring a smaller amount of catalyst. Finally, we
are aware of two examples of the use of 2-chlorophenol for the
synthesis of benzofurans. In the first case the desired product is
obtained in a poor yield (under palladium/magnesium/
lanthanum mixed oxide catalysis),17 while in the second case,
various benzo[b]furans have been prepared having recourse to
a hydroxyterphenylphoshine−palladium catalyst, albeit the high
temperatures (110−120 °C) employed limited the procedure
exclusively to high-boiling alkynes such as dodecyne or phenyl-
acetylenes.18 On the other hand, we have developed a variety of
arylation reactions based on the photogeneration of phenyl
cations under mild conditions.19 These involve the heterolytic
cleavage in a polar solvent of an Ar−Cl or Ar−O bond upon
irradiation of electron-rich aryl chlorides20,21 or esters22 and the
addition of the thus formed triplet phenyl cation to π bond
nucleophiles. In particular, alkynylation has been successful
with the addition of a number of 4-substituted phenyl cations
onto terminal alkynes23 (Scheme 2, path a), one of the rare
examples of a metal-free Sonogashira reaction.19b
INTRODUCTION
■
The benzo[b]furan moiety is largely diffuse in nature, in
pharmaceutically active compounds,1 both natural and man
made, including antifungal, antimicrobial,1 antitumor agents, as
well as in drugs for the treatment of vascular diseases, such as
arrhythmia and hypertension.1c,d Furthermore, some benzofur-
an derivatives have found applications as light collectors in
photovoltaic cells.2 An important access to these heterocycles is
offered by metal-mediated heteroannulation of 2-halophenols
with alkynes, as first demonstrated by Castro and co-workers in
1966.3 This path has been strongly improved by the
introduction of the Sonogashira procedure. The interest for
this method is evidenced by the large number of reports in
recent years, generally starting from 2-iodophenols4−8 (Scheme
1 path a) in a one-pot procedure or with the separation of
crude 2-alkynylphenol9,1b (Scheme 1 path b).
Scheme 1. Metal-Catalyzed Synthesis of 2-Substituted
Benzo[b]furans from 2-Halophenols (FG = Functional
Group)
We reasoned that introducing an ortho phenolic group in the
starting aromatic may lead to a new synthesis of benzo[b]furans
if the vinyl cation intermediate would be trapped intra-
molecularly (Scheme 2, path b), thus offering a metal-free
annulation that would be environmentally advantageous,
particularly if a convenient solvent could be used. ortho-
Chloroanisole21a and ortho-chlorophenol21a,b have been used in
related arylations, although these are less photoreactive in
comparison to the corresponding para-derivatives. In fact, the
This valuable reaction occurs at a moderate temperature
(60−80 °C) and appears to be equally effective in water as in
an organic solvent,10 although the use of an expensive Pd
complex and, most often, of a Cu(I) salt as cocatalyst has a
negative environmental impact and increases the cost of the
reaction. Actually, both copper5,11 and palladium-free proce-
dures6 have been reported, but, particularly in the latter case,
these required a higher temperature or at any rate more drastic
conditions. Likewise, the use of less toxic and inexpensive iron
Received: May 17, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo3010183 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
but only a negligible amount (<5%) of 8 was formed.
Increasing the amount of acetone had a positive effect, with
the yield of 8 reaching 20% (entry 2) in a 1 to 1 v/v mixture
and 30% in neat acetone (no base added), although there the
photoreduction became predominant. The presence of solid
K2CO3 or of a protic solvent such as water led to a roughly
equimolar mixture of 8 and 1H (entries 4 and 5).
Scheme 2. Mechanism of Phenyl Cation Addition onto a
Triple Bond
In recent years,21,22,25 the use of aqueous acetonitrile has
emerged as a greener alternative to TFE for the photocleavage
of chlorophenols, as shown in the synthesis of γ-benzyl
lactones,21a substituted benzonitriles,25a γ-benzyl tetrahydrofur-
ans25b and allylphenols.25 We were delighted to find that a
MeCN/water 5/1 mixture was superior to all the other media
tested. In fact, photoreaction of 1a in this solvent (entries 6−8)
strongly reduced the reduction to phenol, although the amount
of benzofuran formed remained modest, and best results
obtained (1H, 16%; benzofuran 8, 49%) were those with 1.8 M
acetone (20% v/v) and of a large excess of the trap (7a, 1 M) .
Then, the effect of changing the leaving group in the starting
compound was explored. Irradiation of the catechol mesylate
1b gave 8 in only 31% yield, but competitive reduction was
almost suppressed. Under the same conditions, 2-fluorophenol
(1c) exhibited a low photoreactivity (only 38% consumption
after 24 h irradiation) and gave benzofuran in a reasonable yield
(38% yield based on the consumption of 1c accompanied by
some 1H).
reaction quantum yield of ortho-chlorophenol (1a) in protic
solvents such as MeOH and MeCN−H2O mixture 5/1 is 0.040
and 0.045, respectively, almost five times lower than that of 4-
chlorophenol in the same media (0.29 in MeOH and 0.26 in
MeCN/H2O). The fact that the reactivity was significant and
the prospective advantage of a metal-free benzofuran synthesis
made an exploratory study worthwhile.
The above data give some indication about the conditions
under which a benzofuran may be obtained. In particular, o-
chlorophenols appeared to be the best reagents. Thus the
exploration was extended to further substituted derivatives (2−
6) under the best conditions found (those of entry 8 in Table
1).
As shown in Table 2, the irradiation of 1a in the presence of
either 1-hexyne (7a) and trimethylsilylacetylene (7b) gave
respectively the 2-butyl- (8, 49% yield, a compound recently
investigated as antimicrobial1a) and the 2-trimethylsilyl
derivative (9, 37% yield), along with some phenol but no
significant amounts of the open-chain aryl alkynes. 5-Methyl-2-
chlorophenol (2) gave likewise the corresponding benzofurans
10, 11 in the presence of alkynes 7a and 7b, respectively. The
benzofuran yield bordered here 60%, but reduction remained
RESULTS
■
The first part of the study aimed to individuate the conditions
for a successful synthesis by using the reaction of phenol 1a in
the presence of 1-hexyne (7a) under different conditions.
As shown in Table 1, formation of the desired 2-butyl-
benzo[b]furan (8) was accompanied by some reduction to
phenol 1H. Compound 1a absorbs poorly at the wavelength
used (310 nm), and it was found expedient to carry out the
reaction under triplet sensitization (acetone, 0.9 M) and in the
presence of an equimolar amount of a base (Cs2CO3) to buffer
the acidity liberated.24 As for the solvent, our previous
alkynylation was carried out in CF3CH2OH (TFE), a rather
toxic and expensive solvent, that was unsuitable in the present
case since 1a was completely consumed after 24 h irradiation,
Table 1. Irradiation of o-Halophenols (1a, 1c) or Mesylate 1b in the Presence of 1-Hexyne (7a)
a
products (yield %)
entry
conditions
tirr (h)
consumption (%)
8
1H
1
2
1a, 7a 0.5 M, acetone 0.9 M, Cs2CO3 0.025 M, Solvent: CF3CH2OH
1a, 7a 0.5 M, Cs2CO3 0.025 M, Solvent: CF3CH2OH/acetone 1/1
24
24
24
24
24
35
24
24
24
24
100
100
80
<5
20
28
45
30
42
42
49
31
38
10
10
37
31
45
17
18
16
5
b
3
1a, 7a 0.5 M, Solvent: acetone
4
1a, 7a 0.5 M, K2CO3 (s), Solvent: acetone
100
90
b
5
1a, 7a 0.5 M, Solvent: acetone/H2O 9/1
b
6
1a, 7a 0.5 M, acetone 0.9 M, Solvent: MeCN/H2O 5/1
85
b
7
1a, 7a 0.5 M, acetone 1.8 M, Solvent: MeCN/H2O 5/1
100
100
100
38
b
8
1a, 7a 1.0 M, acetone 1.8 M, Solvent: MeCN/H2O 5/1
b
9
1b, 7a 1.0 M, acetone 1.8 M, Solvent: MeCN/H2O 5/1
b
10
1c, 7a 1.0 M, acetone 1.8 M, Solvent: MeCN/H2O 5/1
14
a
b
Yields were based on consumed phenol and determined by HPLC analysis. No base added.
B
dx.doi.org/10.1021/jo3010183 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Table 2. Photolysis of Chlorophenols 1−6 in the Presence of Alkynes 7a−d
a
Isolated yields in the case of benzofurans and compounds 9k and 13k, HPLC yields in the case of compounds 1−6H.
conspicuous (20%). Furthermore, in the reaction of 2 with 7a,
we obtained also a small amount (7%) of the aromatic ketone
10k.
(6a), where benzofuran 19 is obtained in only 21% yield, along
with a significant amount of ketone 19k.
Finally, it was tested whether the presence of a free OH
group in the ortho position was an absolute requirement for the
occurring of the reaction. Accordingly, the irradiation of 4-
chloro-3-methoxyphenol 6b in the presence of 7a (1 M) gave
compound 19, although in a moderate yield and at a slower rate
(80% consumption after 40 h). Obtaining a benzofuran directly
from ortho-haloanisoles has little precedent. Thus, the synthesis
of benzofurans from iodoanisoles under metal catalysis has
been found either to require two steps or to lead to mixtures.26
A further explorative study showed that no benzofurans were
formed when nonterminal alkynes such as 1-trimethylsilyl
propyne were used.
The yield of benzofurans (12, 13) further increased when
starting from 4-tert-butyl-2-chlorophenol (3) with both of the
alkynes considered. Furthermore, good yields (up to 85%) of
benzofurans, with no change in the paths followed, were
obtained when oxygen based substituents, such as a methoxy or
hydroxy group, were introduced. Thus, compound 14 was
smoothly accessed through the photochemical reaction
between chlorosesamol 4 and 1-hexyne (7a), while 4-
methoxy-2-chlorophenol (5) reacted efficiently with both
alkynes 7a and 7b, affording the corresponding benzofurans
(15, 16) in high yields. In this case, propargyl alcohols 7c,d
were added to the alkynes considered and gave indeed the
corresponding benzofurans (17, 18), though in less satisfactory
yields. The reaction was less satisfactory with 4-chlororesorcinol
Computational Studies. Experimental results were
supplemented by computational data. The geometry and
energy of both triplet and singlet 2-hydroxyphenyl cations
C
dx.doi.org/10.1021/jo3010183 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(1,320+, FG = H, see Scheme 3), as well as of β-(2-
hydroxyphenyl)-vinyl cations 1,322+ (FG = H) modeling the
3
322+
and 22+out−out) exhibited a comparable stability, the
out−in
last one being the most stable (ca. 7.5 kcal mol−1 below
322+in−in). Interestingly, optimization of a similar singlet adduct
led selectively to a protonated benzofuran structure (122+,
Figure 1e).
Scheme 3
DISCUSSION
■
The fact that benzofurans 8−19 are obtained as the only
arylated products from phenols 1−6 is remarkable and shows
the selective reactivity of the 2-hydroxy substituted phenyl
cation. This cation (320+, see Scheme 3) is formed in the triplet
state by irradiation of (substituted) 2-chlorophenol, as
previously proposed.21 The MeCN−H2O 5:1 mixture is
sufficiently polar and protic to favor the cleavage to 20+ and
3
was proved here again a useful substitute for 2,2,2-
3
trifluoroethanol (TFE). The deprotonation of 20+ in water
to yield the corresponding neutral carbene, 2-oxocyclohexa-3,5-
dienylidene carbene (21) is known to be facile (path a′).28
However, the presence of a sufficiently high concentration of a
π nucleophile prevents this alternative path and further limits
photoreduction (path b′), fueling trapping of the cation (path
c′), analogously to what observed with other phenyl cations29
and analogously leading to a triplet β-aryl vinyl cation (as
3
pointed out by computational data, addition of 20+ leads to
322+out−out as the preferred isomer),30 which finally intersystem
1
crosses (ISC) to the singlet cation 22+ (path d′). Notable in
the reaction are the C−O bonding step leading to ring closed
122+ and precluding the intermediacy of a vinylidene
phenonium ion,31 as general for phenyl cations not bearing
the OH group,23,30 and the lack of competitive paths from the
last intermediate. Thus, neither vinylic deprotonation (23, path
e′) nor water addition (path f′) appear to have any role, despite
the high water concentration (ca. 9 M in the solvent mixture).
None of the hydroxyketones 25 expected from enol ether 24
were detected in the reaction mixture even at low irradiation
times, and these may be intermediates in the way to
benzofurans, since such process is known to occur, as in
general “Paal-type” reactions, under acidic conditions.32 The
only exception was a minor product (hydroxyketones of
formulas 10k, 19k), formed in a low yields via hydride shift
from 322+ to form the more stable α-phenyl vinyl cation (326+,
path g′) followed by intersystem crossing and water addition
(path h′).33
putative intermediates in the described arylations, were
optimized by DFT calculations at UB3LYP/6-31G(d) level
(Supporting Information). Analogously to what was observed
for 2-methoxyphenyl cation,27 triplet 20+ resulted more stable
3
(3.6 kcal mol−1) than the corresponding singlet cation. Since
trapping by triple C−C bond took place only when the triplet
phenyl cation (320+) was involved, the cationic adducts were
first formed in the same spin state. Considering all the possible
orientations of both C(vinyl)−H and O−H bonds, four
isomeric structures were found for 322+, namely, 322+
in−in
These results further strengthen the knowledge about the
reactivity of phenyl cations. Addition to a π bond nucleophile is
always the preferred path for the selective triplet cation,
whereas any addition from the singlet is barrierless. Thus, one
takes full advantage from the selective trapping of the triplet
even with weak π bond nucleophiles such as alkynes, but then
at singlet multiplicity every nucleophile competes, with the
obvious preference for intramolecular processes (and thus path
d′ exclusively in the present case).
Finally, the formation of a benzofuran occurred in the case of
compound 6b, when a β-(2-methoxyphenyl)-vinyl cation is
involved. The occurrence of a similar intermediate has been
previously reported.34,35 Preparatively, a benzofuran is formed
directly from a 2-haloanisole, not requiring the intermediate
isolation of a 2-alkynyl-anisole, a rare instance.36
Figure 1. Calculated geometries of reaction intermediates: (a)
3
3
3
1
322+in−in; (b) 22+out−in; (c) 22+in−out; (d) 22+out−out; (e) 22+ (see
Scheme 3).
3
3
(Figure 1a), 22+
(Figure 1b), 22+
(Figure 1c) and
in−out
out−in
322+
(Figure 1d). Significant energy differences were
out−out
observed for the examined isomers and seemed to be due to
The present synthesis of 2-substituted benzo[b]furans from
2-chlorophenol derivatives and terminal alkynes is a further
addition to the synthetic versatility of phenyl cations, and give
the one-step synthesis of benzo heterocycles through the
steric effects, rather than electrostatic interactions. Thus, in
3
structure 22+
the planar geometry was distorted by the
in−in
steric hindrance of both H atoms, which lowered the stability of
this intermediate. The other three intermediates (322+
,
in−out
D
dx.doi.org/10.1021/jo3010183 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Synthesis of 2-Butyl Benzo[b]furan (8). From 156 μL (1.5
mmol) of 2-chlorophenol (1a), 3.40 mL (30 mmol) of 1-hexyne (7a),
and 6.0 mL of acetone (54 mmol) in 30 mL of MeCN−H2O 5:1,
irradiated for 24 h. Purification by column chromatography (eluant:
neat cyclohexane) afforded 110 mg of 2-butyl benzo[b]furan (8, oil,
42%). Compound 8 was likewise obtained in 31% yield (GC yield)
under the same conditions by irradiation of a solution of 1b and 7.
Similarly, 8 was also obtained by irradiation of a solution of 1c and 7
(38% GC yield based on the consumption of 1c). Spectroscopic data
of 8 are in accordance with the literature.42 Anal. Calcd for C12H14O:
C, 82.72; H, 8.10. Found: C, 82.7; H, 8.1.
Synthesis of 2-Trimethylsilyl Benzo[b]furan (9). 156 μL (1.5
mmol) of 1a, 4.0 mL (30 mmol) of ethynyl-trimethylsilane (7b), and
3.0 mL of acetone (27 mmol) in 30 mL of MeCN−H2O 5:1 were
irradiated for 34 h. Purification by column chromatography (eluant:
neat cyclohexane) afforded 106 mg of 2-trimethylsilyl benzo[b]furan
(9, oil, 30% yield). Spectroscopic data of 9 are in accordance with the
literature.43 Anal. Calcd for C11H14OSi: C, 69.42; H, 7.41. Found: C,
69.4; H, 7.4.
tandem formation of aryl−C and C−O bonds. This is a further
example of the ability of photochemical reactions via phenyl
cations to reproduce metal-catalyzed arylations, as well as of the
peculiar experimental simplicity of this method (compare the
often delicate requirement of the catalyzed method),36 as well
as the complementary nature (e.g., chlorides rather than iodides
as the starting compounds). Yields are variable, but the process
is quite general. In some cases, aromatic ketones (10k, 19k) are
formed and have to be separated by chromatography. In
general, however, benzofurans are the only aromatic products
formed, apart a variable amount of the low boiling phenol, and
thus essentially a silica gel filtration is sufficient for the isolation,
which adds synthetic interest to this protocol. Avoiding the use
(and the recovery) of metals, employing water as cosolvent and
using mild conditions are further appealing characteristics.
EXPERIMENTAL SECTION
■
Synthesis of 2-Butyl-6-methyl-benzo[b]furan (10). From 214
mg (1.5 mmol) of 5-methyl-2-chlorophenol (2), 3.40 mL (30 mmol)
of 7a, and 3.0 mL of acetone (27 mmol) in 30 mL of MeCN−H2O
5:1, irradiated for 30 h. Purification by column chromatography
(eluant: neat cyclohexane) gave 167 mg of 2-butyl-6-methylbenzo[b]-
furan (10, oil, 59% yield) and 22 mg of 1-(2-hydroxy-4-methylphenyl)-
NMR spectra were recorded on a 300 MHz spectrometer. The
attributions were made on the basis of H and 13C NMR, as well as
1
DEPT-135 experiments; chemical shifts are reported in ppm downfield
from TMS. The photochemical reactions were performed by using
nitrogen-purged solutions in quartz tubes and a multilamp reactor
fitted with 12 15 W phosphor coated lamps (maximum of emission
310 nm) for the irradiation. Quantum yields were measured at 254 nm
(4 Hg lamps, 15 W). The reaction course was followed by TLC
(cyclohexane−ethyl acetate), GC and HPLC analyses. Workup of the
photolytes involved concentration in vacuo and chromatographic
separation by using silica gel. Chlorophenols 1a,c, 2, 5, and 6a and
alkynes 7 are commercially available and freshly purified (by
distillation or crystallization) before use. Phenols 1b37 (Anal. Calcd
for C7H8O4S: C, 44.67; H, 4.28. Found: C, 44.7; H, 4.3), 338 (Anal.
Calcd for C10H13ClO: C, 65.04; H, 7.10. Found: C, 65.0; H, 7.1) and
1
hexan-1-one (10k, oil, 7% yield). 10: H NMR (CDCl3) δ 0.95−1.00
(t, 3H, J = 7 Hz), 1.40−1.50 (sext, 2H, J = 7 Hz), 1.70−1.80 (qui, 2H,
J = 7 Hz), 2.50 (s, 3H), 2.75−2.80 (t, 2H, J = 7 Hz), 6.30−6.55 (d, 1
H, J = 1 Hz), 7.00−7.10 (dd, 1H, J = 8 and 1 Hz), 7.55 (s, 1H), 7.30−
7.40 (d, 1H, J = 8 Hz); 13C NMR (CDCl3) δ 15.1 (CH3), 22.8 (CH3),
23.5 (CH2), 29.4 (CH2), 31.1 (CH2), 102.8 (CH), 112.3 (CH), 120.8
(CH), 124.9 (CH), 127.7, 134.5, 156.3, 160.4; IR (neat) ν/cm−1 2928,
1490, 1266, 1118, 955, 812. Anal. Calcd for C13H16O: C, 82.94; H,
8.57. Found: C, 83.0; H, 8.6. IR (neat) ν/cm−1 3392, 2958, 1627,
1489, 1145, 963. Spectroscopic data of 10k are in accordance with the
literature.44 Anal. Calcd for C13H18O2: C, 75.69; H, 8.80. Found: C,
75.8; H, 8.7.
4
39 (Anal. Calcd for C7H5ClO3: C, 48.72; H, 2.92. Found: C, 48.7; H,
2.9) have been synthesized by known procedures, and their
spectroscopic data are in accordance with the literature.41 Solvents
of HPLC purity grade have been employed in the photochemical
reactions.
Synthesis of 2-Trimethylsilyl-6-methyl-benzo[b]furan (11).
From 214 mg (1.5 mmol) of 2, 4.0 mL (30 mmol) of 7b, and 3.0 mL
of acetone (27 mmol) in 30 mL of MeCN−H2O 5:1 irradiated for 26
h (90% consumption of 2). Purification by column chromatography
(eluant: cyclohexane/ethyl acetate 99:1) afforded 155 mg of 2-
trimethylsilyl-6-methyl-benzo[b]furan (11, oil, 56% yield based on the
Synthesis of 4-Chloro-3-methoxyphenol (6b). A mixture of 4-
chlororesorcine (6a, 4 g, 27.7 mmol), iodomethane (1.9 mL, 29.5
mmol) and K2CO3 (7.4 g, 53.5 mmol) in acetone (100 mL) was
refluxed overnight. The solvent was then evaporated, and the residue
was dissolved in water, acidified with concentrated HCl and extracted
with Et2O (3 × 30 mL). The organic phases were collected, dried over
anhydrous Na2SO4 and Et2O eliminated in vacuo. The resulting
residue was purified by column chromatography (eluant: from neat
cyclohexane to cyclohexane/ethyl acetate 9:1) to afford 1.9 g of 6b
(white solid, 43% yield, mp 76−77 °C (lit. 78 °C)40 along with 1.5 g
(31% yield) of 1-chloro-2,4-dimethoxy-benzene. 6b: 1H NMR
(CDCl3) δ 3.85 (s, 3H), 5.35 (bs, 1H), 6.35−6.40 (dd, 1 H, J = 7
and 2 Hz), 6.45−6.50 (d, 1H J = 2 Hz), 7.20−7.25 (d, 1H, J = 7 Hz);
13C NMR (CDCl3) δ 56.0 (CH3), 100.5 (CH), 107.8 (CH), 113.9,
1
consumption of 2). 11: H NMR (CDCl3) δ 0.35 (s, 9H), 2.50 (s,
3H), 6.90−6.95 (d, 1H, J = 1 Hz), 7.00−7.10 (d, 1H, J = 8 and 1 Hz),
7.30 (s, 1H), 7.40−7.50 (d, 1H, J = 8 Hz); 13C NMR (CDCl3) δ −1.9
(CH3), 21.5 CH3), 111.4 (CH), 115.8 (CH), 120.2 (CH), 123.6
(CH), 125.4, 134.2, 158.5, 162.7; IR (neat) ν/cm−1 2927, 1475, 1253,
1131, 954. Anal. Calcd for C12H16OSi: C, 70.53; H, 7.89. Found: C,
70.6; H, 7.9.
Synthesis of 2-Butyl-5-tert-butyl-benzo[b]furan (12). From
277 mg of 4-tert-butyl-2-chlorophenol (3, 1.5 mmol), 3.40 mL of 7a
(30 mmol) and 6.0 mL (54 mmol) of acetone in MeCN−H2O 5:1,
irradiated for 32 h. Purification by column chromatography afforded
204 mg of 2-butyl-5-tert-butyl-benzo[b]furan (12, oil, 59% yield). 12:
1H NMR (CDCl3) δ 0.95−1.00 (t, 3H, J = 8 Hz), 1.40 (s, 9H), 1.40−
1.50 (m, 2H), 1.70−1.80 (qui, 2H, J = 8 Hz), 2.75−2.80 (t, 2H, J = 3
Hz), 6.35 (s, 1H), 7.35−7.45 (m, 2H), 7.05 (d, 1H, J = 2 Hz); 13C
NMR (CDCl3) δ 15.1 (CH3), 23.5 (CH2), 29.5 (CH2), 31.0 (CH2),
33.2 (CH3), 35.9, 103.2 (CH), 111.2 (CH), 117.7 (CH), 122.1 (CH),
129.5, 146.6, 154.1, 161.1. IR (neat) ν/cm−1 2958, 1600, 1478, 1271,
1124, 807. Anal. Calcd for C16H22O: C, 83.43; H, 9.63. Found: C,
83.4; H, 9.6.
Synthesis of 2-Trimethylsilyl-5-tert-butyl-benzo[b]furan
(13). From 277 mg of 3 (1.5 mmol), 4.00 mL of 7b (30 mmol)
and 6.0 mL (54 mmol) of acetone in MeCN−H2O 5:1, irradiated for
32 h. Purification by column chromatography afforded 240 mg of 2-
trimethylsilylbenzo[b]furan (13, oil, 65% yield). 13: 1H NMR
(CDCl3) δ 0.35 (s, 9H), 1.40 (s, 9H), 6.95 (d, 1H, J = 1 Hz),
7.30−7.35 (dd, 1H, J = 8 and 2 Hz), 7.45−7.50 (d, 1H, J = 8 Hz),
130.2 (CH), 155.2, 155.6; IR (neat) ν/cm−1 3450, 2930, 1591, 1490,
1299, 1199, 1067, 1025, 951. Anal. Calcd for C7H7ClO2: C, 53.02; H,
4.45. Found: C, 53.0; H, 4.5. Spectroscopic data of 6b are in
accordance with the literature.41
General Procedure for the Photochemical Synthesis of
Benzo[b]furans. A solution of the chlorophenol (1−6, 1.5 mmol,
0.05M), the alkyne (7a−d, 30 mmol) and acetone (54 mmol, 1.8M) in
MeCN−water 5:1 (30 mL) was argon purged in quartz tubes and
irradiated by means of 12 15-W phosphor-coated lamps (emission
centered at 310 nm) until complete consumption of the aromatic
substrate. The photolyzed solution was saturated with sodium chloride
and extracted with diethyl ether (3 × 20 mL). The organic phase was
then removed in vacuo, and the resulting residue was purified by
column chromatography (silica gel; cyclohexane/ethyl acetate as
eluant). The yield of photoreduced products 1−5H has been
quantified by means of GC analyses.
E
dx.doi.org/10.1021/jo3010183 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
7.55−7.60 (d, 1H, J = 2 Hz); 13C NMR (CDCl3) δ −1.9 (CH3), 31.8
(CH3), 34.5, 110.4 (CH), 116.1 (CH), 116.9 (CH), 122.2 (CH),
127.6, 145.3, 156.2, 163.6; IR (neat) ν/cm−1 2961, 1259, 1249, 1130,
1063, 843. Anal. Calcd for C15H22OSi: C, 73.11; H, 9.00. Found: C,
73.1; H, 9.0.
irradiated for 60 h. Purification by column chromatography (eluant:
cyclohexane/ethyl acetate 8:2) afforded 56 mg of 2-butyl-benzo[b]-
furan-6-ol (19, oil, 21% yield) along with a mixture of 19 (4 mg) and
of 1-(2,4-dihydroxyphenyl)hexan-1-one (19k, 37 mg, 12% yield). The
same reaction, when performed by using 4-chloro-3-methoxyphenol
(6b) in place of 6a, gave 19 in 41% yield. Spectroscopic data of 19 are
in accordance with the literature.47 Anal. Calcd for C12H14O2: C,
Synthesis of 2-Butyl-5,6-methylendioxy-benzo[b]furan (14).
From 259 mg (1.5 mmol) of 2-chloro-benzo-4,5-diox-1-ol (4), 3.40
mL of 7a (30 mmol) and 6.00 mL of acetone (54 mmol) in 30 mL of
MeCN−H2O 5:1 irradiated for 20 h. Purification by column
chromatography (eluant: neat cyclohexane) afforded 177 mg of 2-
1
75.76; H, 7.42. Found: C, 75.8; H 7.3. 19k: H NMR (CDCl3, from
the mixture) δ 0.95−1.00 (t, 3H, J = 7 Hz), 1.20−1.30 (m, 4H), 1.80−
1.90 (q, 2H, J = 7 Hz), 2.90−3.00 (t, 2H, J = 7 Hz), 5.80−5.90 (bs,
1H), 6.30−6.40 (m, 2H), 7.60−7.70 (d, 1H, J = 6.5 Hz), 12.40 (bs,
1H); 13C NMR (CDCl3, from the mixture) δ 13.4 (CH3), 22.0 (CH2),
24.1 (CH2), 31.0 (CH2), 37.5 (CH2), 100.9 (CH), 107.2 (CH), 113.4,
131.9 (CH), 162.0. 164.8, 204.9. IR (of the mixture) ν/cm−1 3307,
2957, 2872, 1633, 1455, 1245, 1145, 908.
Calculations. Geometries of all intermediates and adducts were
optimized in vacuo at the UB3LYP/6-31G(d) level, by using the
Gaussian03 package.48 Frequency calculations were performed at the
same level of theory, to check energy minima. Solvent effect was
calculated by CPCM-UB3LYP/6-31G(d) method (acetonitrile bulk)49
on the optimized geometries obtained in vacuo. Reported energies
were evaluated by adding ZPE energies obtained in vacuo, to CPCM
energies. Optimized geometries, listed in Cartesian format, and
minimum energies (in Hartree) are available as Supporting
Information.
1
butyl-5,6-methylendioxy-benzo[b]furan (14, oil, 54% yield). 14: H
NMR (CD3COCD3) δ 0.95−1.00 (t, 3H, J = 7 Hz), 1.20−1.45 (sext,
2H, J = 7 Hz), 1.65−1.80 (qui, 2H, J = 8 Hz), 2.70−2.85 (t, 2H, J = 8
Hz), 5.95 (s, 2H), 6.30 (s, 1H), 6.90 (s, 1H), 7.00 (s, 1H); 13C NMR
(CD3COCD3) δ 14.4 (CH3), 23.2 (CH2), 29.0 (CH2), 31.0 (CH2),
94.1 (CH), 100.1 (CH), 102.4 (CH2), 103.5 (CH), 123.4, 143.2,
145.5, 146.6, 160.2; IR (neat) ν/cm−1 2931, 1461, 1318, 1158, 945.
Anal. Calcd for C13H14O3: C, 71.54; H, 6.47. Found: C, 71.5; H, 6.4.
Synthesis of 2-Butyl-5-methoxy-benzo[b]furan (15). From
238 mg (1.5 mmol) of 2-chloro-4-methoxyphenol (5), 3.40 mL of 7a
(30 mmol) and 6.00 mL of acetone (54 mmol) in 30 mL of MeCN−
H2O 5:1 irradiated for 16 h. Purification by column chromatography
(eluant: cyclohexane/ethyl acetate 99:1) gave 260 mg of 2-butyl-5-
methoxy-benzo[b]furan (15, oil, 85% yield). 15: 1H NMR (CDCl3) δ
0.95−1.05 (t, 3H, J = 7 Hz), 1.40−1.50 (sext, 2H, J = 7 Hz), 1.70−
1.85 (qui, 2H, J = 7 Hz), 2.75−2.80 (t, 2H, J = 8 Hz), 3.85 (s, 3H),
6.55 (d, 1H, J = 1 Hz), 6.80−6.85 (dd, 1H, J = 9 and 3 Hz), 6.95−7.00
(d, 1H, J = 3 Hz), 7.25−7.30 (d, 1H, J = 9 Hz); 13C NMR (CDCl3) δ
13.7 (CH3), 22.2 (CH2), 28.1 (CH2), 29.7 (CH2), 55.8 (CH3), 101.8
(CH), 103.0 (CH), 110.9 (CH), 111.2 (CH), 129.4, 149.5, 155.6,
160.6; IR (neat) ν/cm−1 2939, 1465, 1248, 1145, 961. Anal. Calcd for
C13H16O2: C, 76.44; H, 7.90. Found: C, 76.4; H, 7.9.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C for compounds 1b, 3, 4, 6b, and 8−19 and
computational data for the involved intermediates. This
material is available free of charge via the Internet at http://
pubs.acs.org.
Synthesis of 5-Methoxy-2-trimethylsilyl-benzo[b]furan (16).
From 238 mg (1.5 mmol) of 5, 4.00 mL of 7b (30 mmol) and 6.0 mL
of acetone (54 mmol) in 30 mL of MeCN−H2O 5:1 irradiated for 16
h. Purification by column chromatography (eluant: cyclohexane/ethyl
acetate 99:1) afforded 205 mg of 5-methoxy-2-trimethylsilyl-benzo-
AUTHOR INFORMATION
Corresponding Author
*Tel: (+39)0382-987316. Fax: (+39)0382-987323. E-mail:
prottistefano@gmail.com.
■
1
[b]furan (16, oil, 62% yield). 16: H NMR (CDCl3) δ 0.40 (s, 9H),
3.85 (s, 3H), 6.85−6.95 (dd, 1H, J = 2 and 7 Hz), 6.90 (d, 1H, J = 1
Hz), 7.05−7.10 (d, 1H, J = 2 Hz), 7.40−7.45 (d, 1H, J = 7 Hz); 13C
NMR (CDCl3) δ −0.5 (CH3), 57.2 (CH3), 104.3 (CH), 112.9 (CH),
114.6 (CH), 117.4 (CH), 129.8, 154.5, 157.0, 165.9; IR (neat) ν/cm−1
2930, 1491, 1228, 1143, 955. Anal. Calcd for C12H16O2Si: C, 65.41; H,
7.32. Found: C, 65.4; H, 7.3.
Synthesis of 2-(Hydroxymethyl)-5-methoxy-benzo[b]furan
(17). From 238 mg (1.5 mmol) of 5, 1.75 mL (30 mmol) of propargyl
alcohol (7c), and 6.0 mL of acetone (54 mmol) in 30 mL of MeCN−
H2O 5:1 irradiated for 24 h. Purification by column chromatography
(eluant: cyclohexane/ethyl acetate 9:1) afforded 104 mg of 2-
(hydroxymethyl)-5-methoxy-benzo[b]furan (17, white solid, 39%
yield, mp = 64.5−65.0 °C). The spectroscopic data of compound 17
were in accordance with literature.45 Anal. Calcd for C10H10O3: C,
67.41; H, 5.66. Found: C, 67.4; H, 5.7.
Synthesis of 2-(1-Methyl-1-hydroxyethyl)-5-methoxybenzo-
[b]furan (18). From 238 mg (1.5 mmol) of 2-chloro-4-methox-
yphenol (5), 2.90 mL (30 mmol) of 3-methyl-1-butyn-3-ol (7d), and
6.0 mL of acetone (54 mmol) in 30 mL of MeCN−H2O 5:1 irradiated
for 24 h. Purification by column chromatography (eluant: cyclo-
hexane/ethyl acetate 9:1) afforded 136 mg of 2-(1-methyl-1-
hydroxyethyl)-5-methoxybenzo[b]furan46 (18, oil, 44% yield). 18:
1H NMR (CDCl3) δ 1.70 (s, 6H), 2.35 (bs, 1H), 3.80 (s, 3H), 6.55 (s,
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Dr. Valentina Dichiarante for her precious help. S.P.
acknowledges MIUR, Rome (FIRB-Futuro in Ricerca 2008
Project RBFR08J78Q) for financial support. We acknowledge
Dr. Daniele Dondi and Davide Ravelli (University of Pavia) for
fruitful discussion. This work was funded by the CINECA
Supercomputer Center, with computer time granted by ISCRA
COMPDHT (HP10CZEHG6) project.
REFERENCES
■
(1) (a) Khan, M. W.; Alam, M. J.; Rashid, M. A.; Chowdhury, R.
Bioorg. Med. Chem. 2005, 13, 4796−4805. (b) Jiang, X.; Liu, W.;
Zhang, W.; Jiang, F.; Gao, Z.; Zhuang, H.; Fu, L. Eur. J. Med. Chem.
2011, 46, 3526−3530. (c) Horton, D. A.; Bourne, G. T.; Smythe, M.
L. Chem. Rev. 2003, 103, 893−930 and references cited therein.
(d) Nattel, S.; Talajic, M.; Fermini, B.; Roy, D. J. Cardiovasc.
Electrophysiol. 1992, 3, 266−280.
(2) Jung, I.; Lee, J. K.; Song, K. H.; Song, K.; Kang, S. O.; Ko, J. J.
Org. Chem. 2007, 72, 3652−3658. Bogdal, D.; Matras, K.; Sanetra, J.;
Pokladko, M. Macromol. Symp. 2008, 268, 48−52.
1H), 6.85−6.90 (dd, 1H, J = 8 and 2 Hz), 7.00−7.05 (d, 1H, J = 2
Hz), 7.25−7.35 (d, 1H, J = 8 Hz). 13C NMR (CDCl3) δ 28.6 (CH3),
55.8 (CH3), 69.2, 100.4 (CH), 103.5 (CH), 111.5 (CH), 112.4 (CH),
128.7, 149.5, 155.8, 163.8; IR (neat) ν/cm−1 3450, 2967, 1490, 1287,
1167, 816. Anal. Calcd for C12H14O3: C, 69.88; H, 6.84. Found: C,
69.9; H, 6.8.
Synthesis of 2-Butyl-benzo[b]furan-6-ol (19). From 216 mg
(1.5 mmol) of 4-chloro-resorcin (6a), 1.70 mL (30 mmol) of 7a, and
6.00 mL of acetone (54 mmol) in 30 mL of MeCN−H2O 5:1
(3) Castro, C. E.; Gaughan, E. J.; Owsley, D. C. J. Org. Chem. 1966,
31, 4071−4078.
(4) Bernini, R.; Cacchi, S.; De Salve, I.; Fabrizi, G. Synthesis 2007,
873−882.
(5) Rollet, P.; Kleist, W.; Dufaud, V.; Djakovitch, L. J. Mol. Catal. A:
Chem. 2005, 241, 39−51.
F
dx.doi.org/10.1021/jo3010183 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(6) Li, J- H.; Li, J.-L.; Wang, D.-P.; Pi, S.-F.; Xie, Y.-X.; Zhang, M.-B.;
Hu, X.-C. J. Org. Chem. 2007, 72, 2053−2057.
cations (generated via solvolysis of iodonium salts) has been recently
resumed; see: Okuyama, T. Acc. Chem. Res. 2002, 35, 12−18.
(33) [1,2] H shift occurring in β-aryl vinyl cations to give the more
stable α-aryl vinyl cations has been reported in the literature; see, for
instance, Lee, C. C.; Ko, E. C. F. J. Org. Chem. 1975, 40, 2132−2133.
Gronheid, R.; Lodder, G.; Okuyama, T. J. Org. Chem. 2002, 67, 693−
702. Apeloig, Y.; Franke, W.; Rappoport, Z.; Schwarz, H.; Stahl, D. J.
Am. Chem. Soc. 1981, 103, 2770−2780.
(7) Bates, C. G.; Saejueng, P.; Murphy, J. M.; Venkataraman, D. Org.
Lett. 2002, 4, 4727−4729.
(8) Wang, L.; Li, P.; Zhang, Y. Chem. Commun. 2004, 514−515.
(9) Furstner, A.; Davies, P. W. J. Am. Chem. Soc. 2005, 127, 15024−
̈
15025. Liao, Y.; Smith, J.; Fathi, R.; Yang, Z. Org. Lett. 2005, 7, 2707−
2709.
(34) Suzuki, T.; Kitamura, T.; Sonoda, T.-a.; Kobayashi, S.;
Taniguchi, H. J. Org. Chem. 1981, 46, 5324−5328. Xu, M.; Zhang,
X.-H.; Zhong, P. Tetrahedron Lett. 2011, 52, 6800−6804.
(35) See, for instance, Maud Jacubert, M.; Hamze, A.; Provot, A.;
Peyrat, J.-F.; Brion, J.-D.; Alami, M. Tetrahedron Lett. 2009, 50, 3588−
3592. Kitamura, T.; Kobayashi, S.; Taniguchi, H. Chem. Lett. 1984,
547−548. Kitamura, T.; Kobayashi, S.; Taniguchi, H.; Hori, K. J. Am.
Chem. Soc. 1991, 113, 6240−6245.
(10) Pal, M.; Subramanian, V.; Yeleswarapu, K. R. Tetrahedron Lett.
2003, 44, 8221−8225. Genin, E.; Amengual, R.; Michelet, V.;
̂
Savignac, M.; Jutand, A.; Neuville, L.; Genet, J.-P. Adv. Synth. Catal.
2004, 346, 1733−1741.
(11) Gill, G. S.; Grobelny, D. W.; Chaplin, J. H.; Flynn, B. L. J. Org.
Chem. 2008, 73, 1131−1134.
(12) Carril, M.; Correa, A.; Bolm, C. Angew. Chem., Int. Ed. 2008, 47,
4862−4865.
(36) Doucet, H.; Hierso, J.-C. Angew. Chem., Int. Ed. 2007, 46, 834−
(13) Sanz, R.; Castroviejo, M. P.; Fernan
Chem. 2005, 70, 6548−6551.
́ ̌ ́
dez, Y.; Fananas, F. J. J. Org.
871 and references cited therein.
(37) Lin, K.-S.; Ding, Y.-S. Chirality 2004, 16, 475−481.
(38) Masilamani, D.; Rogic, M. M. J. Org. Chem. 1981, 46, 4486−
4489.
(14) Primault, G.; Legros, J.-Y.; Fiaud, J.-C. J. Organomet. Chem.
2003, 687, 353−364.
́ ́ ́
(15) Csekei, M.; Novak, Z.; Timari, G.; Kotschy, A. ARKIVOC 2004,
(39) Dichiarante, V.; Fagnoni, M.; Albini, A. Green Chem. 2009, 11,
942−946.
vii, 285−291. Harayama, T.; Nishita, Y. Chem. Pharm. Bull. 1996, 44,
1986−1988.
(40) Dodgson, W. Biochem. J. 1949, 45, 381−383.
(16) Dawood, K. M.; Solodenko, W.; Kirschning, A. ARKIVOC 2007,
v, 104−124.
(41) Bauta, W. E.; Lovett, D. P.; Cantrell, W. R., Jr.; Burke, B. D. J.
Org. Chem. 2003, 68, 5967−5973.
(17) Cwik, A.; Hell, Z.; Figueras, F. Tetrahedron Lett. 2006, 47,
3023−3026.
(42) Ackermann, L.; Kaspar, L. T. J. Org. Chem. 2007, 72, 6149−
6153.
(18) Wang, J. R.; Manabe, K. J. Org. Chem. 2010, 75, 5340−5342.
(19) (a) Fagnoni, M.; Albini, A. Acc. Chem. Res. 2005, 38, 713−721.
(b) Dichiarante, V.; Fagnoni, M. Synlett 2008, 787−800.
(20) Protti, S.; Fagnoni, M.; Mella, M.; Albini, A. J. Org. Chem. 2004,
69, 3465−3473.
(43) Crich, D.; Grant, D. J. Org. Chem. 2005, 70, 2384−2386.
(44) Sharghi, H.; Hosseini-Sarvari, M.; Eskandari, R. Synthesis 2006,
2047−2052.
(45) Gabriele, B.; Mancuso, R.; Salerno, G. J. Org. Chem. 2008, 73,
7336−7341.
(21) (a) Protti, S.; Fagnoni, M.; Albini, A. J. Am. Chem. Soc. 2006,
128, 10670−10671. (b) Protti, S.; Dondi, D.; Fagnoni, M.; Albini, A.
In Experiments in Green and Sustainable Chemistry; Roesky, H. W.,
Kennepohl, D. K., Eds.; Wiley-VCH: Weinheim, 2009; pp 260−265.
(22) De Carolis, M.; Protti, S.; Fagnoni, M; Albini, A. Angew. Chem.,
Int. Ed. 2005, 44, 1232−1236.
(46) De Bernardi, M; Vidari, G.; Vita Finzi, P; Fronza, G. Tetrahedron
1992, 48, 7331−7344.
(47) Misawa, N.; Shindo, K.; Takahashi, H.; Suenaga, H.; Iguchi, K.;
Okazaki, H.; Harayama, S.; Furukawa, K. Tetrahedron 2002, 58, 9605−
9612.
(48) Gaussian 03, Revision D.01; M. J. Frisch, M. J.; Trucks, G. W.;
Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;
Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam,
J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.;
Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P. J.; Dannenberg, J.; Zakrzewski, V. G.; Dapprich, S.;
Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-
Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P.
M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J.
A. Gaussian, Inc.: Wallingford, CT, 2004.
(23) Protti, S.; Fagnoni, M.; Albini, A. Angew. Chem., Int. Ed. 2005,
44, 5675−5678.
(24) Terpolilli, M.; Merli, D.; Protti, S.; Dichiarante, V.; Fagnoni, M.;
Albini, A. Photochem. Photobiol. Sci. 2011, 10, 123−127.
(25) (a) Dichiarante, V.; Fagnoni, M.; Albini, A. Chem. Commun.
2006, 3001−3003. (b) Protti, S.; Dondi, D.; Fagnoni, M.; Albini, A.
Eur. J. Org. Chem. 2008, 2240−2247. Protti, S.; Fagnoni, M.; Albini, A.
Org. Biomol. Chem. 2005, 3, 2868−2871.
(26) See, for instance ,Dyker, G. J. Org. Chem. 1993, 58, 6426−6428.
Colobert, F.; Castanet, A. S.; Abillard, O. Eur. J. Org. Chem. 2005,
3334−3341. Oppenheimer, J.; Johnson, W. L.; Tracey, M. R.; Hsung,
R. P.; Yao, P.-Y.; Liu, R.; Zhao, K. Org. Lett. 2007, 12, 2361−2364.
(27) Dichiarante, V.; Dondi, D.; Protti, S.; Fagnoni, M.; Albini, A. J.
Am. Chem. Soc. 2007, 129, 5605−5611; Correction: 2007, 129, 11662.
(28) Shi, Z.; Sigman, M. E.; Ghosh, M. M.; Dabestani, R. Environ. Sci.
Technol. 1997, 31, 3581−3587. Bonnichon, F.; Richard, C.; Grabner,
G. Chem. Commun. 2001, 73−74.
(29) Manet, I.; Monti, S.; Bortolus, P.; Fagnoni, M.; Albini, A.
Chem.Eur. J. 2005, 11, 4274−4282. Manet, I.; Monti, S; Fagnoni,
M.; Protti, S.; Albini, A. Chem.Eur. J. 2005, 11, 140−151.
(30) A related adduct cation has been previously observed by laser
flash photolysis experiments in the addition of the 4-methoxyphenyl
cation onto 1-hexyne; see: Manet, I.; Monti, S.; Grabner, G.; Protti, S.;
Dondi, D.; Dichiarante, V.; Fagnoni, M.; Albini, A. Chem.Eur. J.
2008, 14, 1029−1039.
(49) Barone, V.; Cossi, M. J. Phys. Chem. A 1998, 102, 1995−2001.
Cossi, M.; Rega, N.; Scalmani, G.; Barone, V. J. Comput. Chem. 2003,
24, 669−681.
(31) Stang, P. J.; Dueber, T. E. J. Am. Chem. Soc. 1973, 95, 2683−
2686. Stang, P. J.; Dueber, T. E. J. Am. Chem. Soc. 1973, 95, 2686−
2687.
(32) Macleod, C.; McKiernan, C. J.; Guthrie, E. J.; Farrugia, L. J.;
Hamprecht, D. W.; Macritchie, J.; Hartley, R. C. J. Org. Chem. 2003,
68, 387−401. The chemical behaviour of differently substituted vinyl
G
dx.doi.org/10.1021/jo3010183 | J. Org. Chem. XXXX, XXX, XXX−XXX