Gold-catalyzed intermolecular hydrophenoxylation of unactivated Internal alkynes

Article abstract of DOI:10.1021/jo1000143

Chemical Reaction Reprentation A general and simple strategy for the synthesis of functionally diverse arylvinyl ethers is reported through gold-catalyzed intermolecular addition of electronically and sterically substituted phenols with unactivated alkynes. Addition of phenols to unsymmetrical alkynes provides the corresponding mixture of regioisomers with appreciable selectivity. Multiple hydrophenoxylations of polyphenols with diphenylacetylene are demonstrated successfully.

Full text of DOI:10.1021/jo1000143

pubs.acs.org/joc
Gold-Catalyzed Intermolecular Hydrophenoxylation of Unactivated
Internal Alkynes
Malleswara Rao Kuram, M. Bhanuchandra, and Akhila K. Sahoo*
School of Chemistry, University of Hyderabad, Hyderabad 500046, India
akssc@uohyd.ernet.in
Received January 5, 2010
A general and simple strategy for the synthesis of functionally diverse arylvinyl ethers is reported
through gold-catalyzed intermolecular addition of electronically and sterically substituted phenols
with unactivated alkynes. Addition of phenols to unsymmetrical alkynes provides the corresponding
mixture of regioisomers with appreciable selectivity. Multiple hydrophenoxylations of polyphenols
with diphenylacetylene are demonstrated successfully.
Introduction
organic chemistry.1 Addition of an alcoholic O-H bond
across alkynes through either inter- or intramolecular fash-
ion provides general access to enol ethers or cyclic ethers with
100% atom efficiency.2 Generally, the precursors for the
intramolecular reactions are obtained through specialized
protocols involving multiple synthetic steps, whereas simple
starting materials are adequate for the intermolecular re-
actions.3 Although entropically unfavorable due to the
decrease of disorder in the system, the intermolecular mode
of reaction is often advantageous over its intramolecular
variant. While transition-metal-catalyzed intramolecular
hydroalkoxylations to alkynes are relatively well-known,4
the intermolecular version is little explored.5 The challenge
lies in effecting the nucleophilic attack of the hard alko-
xides obtained from the corresponding alcohols, on soft
electron-rich alkynes. A solution would be to use soft and
alkynophilic cationic gold complexes that are known to
Development of new methods for the direct formation of
the O-C(sp2) bond is of fundamental interest in synthetic
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DOI: 10.1021/jo1000143
r
Published on Web 03/05/2010
J. Org. Chem. 2010, 75, 2247–2258 2247
2010 American Chemical Society

Kuram et al.
JOCArticle
accomplish complicated transformations with ease.6 For
example, gold catalysts promote cyclization through the
reaction of phenolic/alcoholic-OH group with tethered
alkynes and provide complex oxygen-functionalized hetero-
cycles efficiently.7 A recent report for the synthesis of iso-
flavanone involves gold(I)-catalyzed annulation of salicylal-
dehydes and aryl acetylenes without direct formation of the
O-C bond.8 Intermolecular hydration and hydroalkoxy-
lations of terminal and internal alkynes using water and
1°- or 2°-alcohols have been achieved with gold catalysis;9
however, 3°-alcohol and phenols were found to be unreac-
tive.9k The interesting disclosure of the Yamamoto group
describes the success in effecting phenol addition to specific
diyne precursors; the reaction proceeds either involving the
η2-coordinated Pd(0) complex or via the active σ-cumulenyl
palladium intermediate.10 A regioselective addition of acti-
vated 4-chlorophenol to the specific case of ruthenocene-
bearing alkyne was demonstrated by Sato and co-workers.11
The transannular addition of 4-chlorophenol to 1,10-dialky-
nylferrocene was reported recently.12 The reactivity of inter-
nal unactivated alkynes with oxygen-bearing nucleophiles is
poor compared to that of terminal alkynes.9g,j Considering
the above shortcomings, we envisioned that the simple
intermolecular addition of phenols to unactivated alkynes
is a challenging problem (eq 1).13 It would provide a novel
synthetic strategy for creating a range of arylvinyl ether
skeletons exclusively with Z-olefin stereochemistry in one
step. Furthermore, this new transformation would find wide
application in the synthesis of benzofuran, benzoxathiin, and
flavonoid frameworks of medicinally useful targets.14 Herein
we report an operationally simple strategy for the synthesis
of functionally diverse vinyl(1,2-disubstituted)aryl ethers
involving gold-catalyzed addition of phenols to aryl- and
alkyl-substituted alkynes (eq 1).
Results and Discussion
Our research plan is to find a simple synthetic protocol for
the preparation of benzofurans through metal-catalyzed
intermolecular annulation of phenols and alkynes involving
C-H bond functionalization. To start with, reaction of a
simple and activated nucleophilic substrate 3-nitrophenol
(1a) with diphenylacetylene (2a) under different catalytic
conditions was explored (Table 1). During the optimization
process, a negligible amount of byproduct showing a mole-
cular ion peak at 318 was noticed in the GC-MS analysis.
Formation of a small amount of the byproduct was observed
when a combination of gold(III) chloride (AuCl3), 4a/4b,
and Ag2CO3 in nitromethane was employed at 100 °C
(Table 1, entries 1 and 2). To our surprise, the byproduct
was found to be the hydrophenoxylation product 3aa exclu-
sively with Z-olefin stereochemistry (entry 2; see the Sup-
porting Information for X-ray structure of 3aa).15 Other
silver salts, such as AgOTf, AgOAc, AgBF4, and AgNO3,
were found to be ineffective. Not even a trace of 3aa was
detected in the absence of ligands or by the use of other
phosphines such as PPh3 and PCy3 (entries 3-5). Explora-
tions of various combinations of ligands with gold catalysts
such as AuCl, PPh3AuCl, PPh3AuOTf, PPh3AuSbF6, and
AuBr3 also led to poor yields of 3aa. AuCl3 turned out to be
superior in comparison among other gold catalysts screened.
With a selective base and catalyst in hand, solvents and other
Buchwald ligands were then surveyed. 1,2-Dichloroethane,
THF, and 1,4-dioxane provided lower amounts of 3aa, as
detected in GC, whereas CH2Cl2 appeared to be effective.
Among other Buchwald ligands screened (entries 6-9), 4b
(JohnPhos) with Ag2CO3 in CH2Cl2 was found to be the best,
and the yield of 3aa was 98% by GC (entry 7). In general, the
sterically encumbered ligand 4d is more active than 4b in the
cross-coupling reactions; however, the reverse trend of
ligand activity (4b > 4d) was observed in the current study.16
Optimizations using mixture of various gold catalysts, bases,
and solvents with 4b resulted in poor yield of the product
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Yamamoto, Y. Chem. Rev. 2008, 108, 3395. (b) Li, Z.; Brouwer, C.; He, C.
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Fitzgernald, P.M. D.; Sharma, N.; Dahllund, J.; Thorsell, A.-G.; DiNinno,
F.; Rohrer, S. P.; Schaeffer, J. M.; Hammond, M. L. J. Med. Chem. 2004, 47,
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Nishiyama, T.; Tsukagawa, M.; Konishi, E.; Takahashi, K.; Kawada, T.;
Nakagawa, K.; Kitahara, M. Bioorg. Med. Chem. Lett. 2003, 4267. (e)
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16, 1859.
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Obshchei Khim. 1958, 28, 1253.
(15) The structure of products 3aa and 8a having Z-olefinic stereochem-
istry was confirmed by X-ray crystallography. See Supporting Information.
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2248 J. Org. Chem. Vol. 75, No. 7, 2010

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JOCArticle
TABLE 1. Optimization of Reaction Conditionsa
entry
1
gold
AuCl3
ligand
base
solvent
time (h)
product (3)
yield (%)d
1b
2b
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
4a
4b
Nil
PPh3
PCy3
4a
4b
4c
4d
4b
4b
4b
4b
4b
4b
4b
4b
4b
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
AgOTf
AgOAc
AgSbF6
K2CO3
K2CO3
Ag2CO3
K2CO3
K3PO4
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
36
36
48
48
48
36
24
36
36
48
48
36
36
48
36
48
36
24
36
48
48
48
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3ba
3ba
3ba
3ba
3ba
4
16
0
0
0
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
Ph3PAuCl
AuCl
AuBr3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
3b
4b
5b
6b
11
98
39
52
trace
trace
13
28
trace
35
<5
15
7
7b
8b
9b
10b
11b
12b
13b
14b
15b
16b
17b
18c
19c
20c
21c
22c
CH2Cl2
CH2Cl2
THF
THF
THF
4b
4b
4b
4b
<1
84
95
51
K2CO3
Cs2CO3
aReactions were carried out using 1 (0.5 mmol), 2a (0.25 mmol), and base (0.5 mmol) in solvent (0.3 mL) at 100 °C. bAuCl3 and ligand (3 mol % each)
were used for 24 h. cAuCl3 and ligand (5 mol % each) were used for 48 h. dGC yields based on alkynes using dodecane as standard.
(entries 10-17). Under the optimized condition shown in
entry 7, addition of unactivated 4-methoxyphenol (1b) with
2a produced 3ba in only 7% yield (entry 18). Further screen-
ing of bases and solvents (entries 19-22) revealed that
K2CO3 in THF improved the yield of 3ba to 95% (entry
21). The effective addition of respective phenols to alkynes
solely depends on the nature of bases and solvents used. Such
divergence in the behavior of bases is interesting; however,
the origin of this effect is unclear. It appears that relatively
strong bases, such as K2CO3, are required in the case of
electron-rich phenols having higher pKa, and a milder base,
such as Ag2CO3, is sufficient for activated phenols with lower
pKa.17,18
base in THF at 100 °C] is employed for nonactivated
phenols. The effect of substitution on the phenols in the
hydrophenoxylations with diphenylacetylene was surveyed
at first (Table 2). Electron-donating substituent at the 4-posi-
tion on phenols reacted effectively with 2a in good yields
(3ba, 3ca, and 3da). The Z-selectivity of 3ba is established
based on the NOESY studies; intramolecular NOEs between
vinyl-H (δ=6.62 ppm) and the ortho-hydrogens (δ=7.60,
7.68 ppm) of the phenyl groups of 3ba are clearly seen,
whereas the NOEs between vinyl-H and ortho-hydrogens
(δ=6.78 ppm) of the 4-methoxyphenyl moiety of 3ba are
not observed.19 However, addition of 3-methoxyphenol to
2a afforded the corresponding product 3ka in 51% yield;
incomplete conversion of 2a was noticed even with
To investigate the generality of the addition of various
phenols with symmetrical and unsymmetrical alkynes, con-
dition A [AuCl3 (3 mol %), ligand 4b (3 mol %), Ag2CO3
base in CH2Cl2 at 100 °C] is used for activated phenols and
condition B [AuCl3 (5 mol %), ligand 4b (5 mol %), K2CO3
(19) NOESY studies confirmed the Z-olefin stereochemistry of com-
pounds 3ba, 3fa, 3ma, 3oa, 3ab, 3cc, 3hd, 6b, 6b0, and 8b. See Supporting
Information.
(17) For absolute pKa values for substituted phenols, see: Liptak, M. D.;
Gross, K. C.; Seybold, P. G.; Feldgus, S.; Shields, G. C. J. Am. Chem. Soc.
2002, 124, 6421.
(18) (a) Kumar, N. N. B.; Reddy, M. N.; Swamy, K. C. K. J. Org. Chem.
2009, 74, 5395. (b) Shi, Y.-L.; Shi, M. Org. Biomol. Chem. 2007, 5, 1499. (c)
Dai, L.-Z.; Shi, Y.-L.; Zhao, G.-L.; Shi, M. Chem.;Eur. J. 2007, 13, 3701.
(d) Shi, M.; Dai, L.-Z.; Shi, Y.-L.; Zhao, G.-L. Adv. Synth. Catal. 2006, 348,
967. (e) Zhao, G.-L.; Shi, Y.-L.; Shi, M. Org. Lett. 2005, 7, 4527. (f) Shi,
Y.-L.; Shi, M. Org. Lett. 2005, 7, 3057.
J. Org. Chem. Vol. 75, No. 7, 2010 2249

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JOCArticle
TABLE 2. Hydrophenoxylation of 1 with Diphenylacetylenea,b
aReactions were performed employing 1 (2.0 mmol) and 2 (1.0 mmol) at 100 °C. Condition A: Ag2CO3 (2.0 mmol), AuCl3, and 4b (3 mol % each) in
CH2Cl2 (1.0 mL) were used. Condition B: K2CO3 (2.0 mmol), AuCl3, and 4b (5 mol % each) in THF (1.0 mL) were used. bIsolated yields based on
alkynes; average of two runs.
prolonged reaction time, justifying the moderate yield
encountered in this reaction. Activated phenols bearing F,
Cl, or CF3 groups at the 4- and/or 3-positions gave the
desired hydrophenoxylation products in good to excellent
yields (3ea, 3fa, and 3ga); the required product 3la was
prepared in 72% yield from 3-fluorophenol (1l) and 2a.
The presence of common functional groups such as nitro,
cyano, and formyl on phenols was well-tolerated, and the
respective products were obtained in excellent yields (3ha,
3ia, 3aa, and 3ma). However, meta-directing groups on the
phenol (3-formylphenol, 1m) impart moderate reactivity,
and the synthesis of 3ma resulted in 50% isolated yield.
NOESY studies confirmed the Z-olefin stereochemistry
of 3fa and 3ma.19 Poor yield, sluggish reaction profile, and
incomplete conversion of 2a was observed in the addition of
electronically neutral phenol (1j) to 2a even with the exten-
ded reaction time. Our experimental results reveal that the
para-directing group on phenol leads to better yield, while
meta- and unsubstituted phenols are less effective in the
hydrophenoxylations of alkynes. Presumably, the electronic
effect of the functional group in the para-position decides the
rate and stability of the phenolate and therefore influences
the attack on alkynes.
sterically demanding substrates such as 2-methyl- and
2-nitrophenols proceeded in low to moderate yields (3na
and 3pa). Similarly, hydrophenoxylation of 2-phenylphenol
(1q) with 2a gave 3qa in 68% yield. Unfortunately, the
reaction failed completely when the sterically encumbered
substrate 2,6-dimethylphenol was run with 2a. Hydrophe-
noxylations of phenols with terminal alkyne were then
explored; a reaction of 4-nitrophenol (1h) with phenylacety-
lene under the optimized catalytic condition A was perfor-
med, and the corresponding Markovnikov’s addition pro-
duct was obtained in poor yield.20
Next, we turned our attention to evaluate the effect of
substitution on symmetrical alkynes (Table 3). At first, we
tested the addition of phenols to the alkyl-substituted alkynes.
Excellent yields of the desired hydrophenoxylation products
were attained in the reaction of 3-hexyne (2b) or 4-octyne (2c)
with electron-rich phenols having a methoxy or methyl
group at the 4- and/or 3-position (3bb, 3cc, and 3kc). Phenols
bearing an electron-withdrawing group at the para-position
underwent hydrophenoxylation with 2c efficiently, providing
yields over 95% (3sc and 3ec). Product 3ab was obtained from
the addition of 3-nitrophenol (1a) and 2b, albeit in moderate
yield, a consequence of the meta-substitution on phenols.
Similarly, addition of sterically demanding 2-phenylphenol
(1q) with 2c afforded 3qc in 67% yield. Once again, the
Z-selectivity of 3ab and 3cc was established based on the
NOESY studies.19
The effect of ortho-substitution on phenols was next
examined to assess the steric effect in the hydrophenoxyla-
tion reaction, and the results are summarized in Table 2. The
presence of a compact electron-poor o-substituent, such as a
F group, did not affect the reaction efficiency, and the
product 3oa was obtained in 90% yield under the optimized
condition B. However, bulky the ortho-moiety on phenols
inhibits the effective addition to 2a. Reaction of 2a with
These results suggest that the addition of phenols to alkyl-
substituted alkynes is more effective than to aryl-substituted
(20) For the details of spectral data, see Supporting Information.
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TABLE 3. Hydrophenoxylation of 1 with Symmetrical Alkynesa,b
aReactions were performed employing 1 (2.0 mmol) and 2 (1.0 mmol) at 100 °C. Condition A: Ag2CO3 (2.0 mmol), AuCl3, and 4b (3 mol % each) in
CH2Cl2 (1.0 mL) were used. Condition B: K2CO3 (2.0 mmol), AuCl3, and 4b (5 mol % each) in THF (1.0 mL) were used. bIsolated yields based on
alkynes; average of two runs. c2d (0.5 mmol) was used.
alkynes. We also believe that the efficiency of the reaction
depends primarily on the facile attack of the phenol nucleophile
on the activated electrophilic Au-alkyne-π intermediate. More-
over, carbophilic gold preferably activates the electron-
rich alkynes over the electron-deficient alkynes.21,22b The
inductively donating alkyl group would enhance the electron
density on alkynes, thereby promoting activation by cationic
gold. However, the electron density migration is reversed by a
neutral or electron-deficient aryl group, diminishing the effec-
tive activation by cationic gold. Therefore, we conclude that
electron-rich alkynes would show better reactivity in this
transformation.22b
To further expand the scope of the reaction, we have
explored the utility of electron-rich and -deficient aryl-
substituted internal alkynes. Addition of 4-nitrophenol (1h)
to the electron-rich 4-methoxyphenyl-substituted alkyne
(2d) was performed, and 3hd was isolated in 83% yield
(Table 3).19 However, moderate yield of 3ie was produced
when electron-deficient 4-chlorophenyl-substituted alkyne
(2e) reacted with 4-cyanophenol (1i) under the optimized
condition A. Unfortunately, the attempt to obtain the expected
product from the addition of 4-methoxyphenol (1b) to the
electronically and sterically demanding substrate bis(trime-
thylsilyl)acetylene (2f) turned out to be futile (Table 3, 3bf).
Addition of nucleophile to unactivated unsymmetrical
alkynes is very important; first, it would provide two new
molecular entities corresponding to the regioisomeric pro-
ducts, and second, better regioselectivity through preferen-
tial attack of oxygen nucleophile to alkynes would be
realized. Our experience with hydrophenoxylation of sym-
metrical alkynes revealed that the gold catalyst activates
electron-rich-substituted alkynes efficiently. Therefore, we
decided to evaluate the reactivity of unsymmetrical alkynes
toward the addition of phenols. Table 4 summarizes the
scope of the hydrophenoxylation of substituted phenols with
unsymmetrical alkynes.
Reaction of 4-nitrophenol (1h) with electron-rich unsym-
metrical alkyne 5a afforded the corresponding mixture of
products in 94% yield with moderate regioselectivity
(Table 4, entry 1). Excellent yields of the desired regioiso-
meric products were isolated in the hydrophenoxylation of
1h with phenyl alkyl acetylenes (5b and 5c) (Table 4, entries 2
and 3); this observation clearly demonstrates the effective
reactivity of unsymmetrical alkyl-substituted alkynes in the
addition to phenols. Pure products 6b and 6b0 (Table 4, entry
(21) A competitive experiment was performed reacting 4-nitrophenol (1h,
30 mg, 0.2 mmol) with 1,2-bis(4-methoxyphenyl)ethyne (2d, 50 mg, 0.2
mmol) and 1,2-bis(3-(trifluoromethyl)phenyl)ethyne (2g, 65 mg, 0.2 mmol)
in the presence of AuCl3 (1.9 mg, 3 mol%), ligand 4b (1.8 mg, 3 mol %), and
Ag2CO3 (115 mg, 0.4 mmol) at 100 °C for 72 h. The respective vinyl-H
integration in the crude 1H NMR spectrum showed the formation of the
corresponding products 3hd and 3hg in a 2:1 ratio. This signifies that the
reaction of 4-nitrophenol with electron-rich alkyne 2d is preferred over the
electron-deficient alkyne 2g. See Supporting Information.
€
(22) (a) Furstner, A.; Davis, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410.
(b) Reetz, M. T.; Sommer, K. Eur. J. Org. Chem. 2003, 3485.
J. Org. Chem. Vol. 75, No. 7, 2010 2251

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TABLE 4. Hydrophenoxylation of 1 with Unsymmetrical Alkynes (5)
aReactions were carried out using condition A. bReactions were performed employing condition B. cIsolated yields of the mixture of regioisomers.
dRatios of regioisomers were determined by HPLC analysis. eRegioisomers are purified.
2) could be successfully isolated by column chromatography.
The Z-olefin stereochemistry of 6b and 6b0 is again estab-
lished based on the NOESY studies.19 When the reaction was
run for meta-substituted 3-methoxyphenol (1k) and elec-
tron-rich unsymmetrical alkyne 5a, the product was ob-
tained in modest yield with better regioselectivity (91:9;
Table 4, entry 4). This again demonstrates the reduction in
reactivity with meta-substituted phenols. The regioselectivity
observed in these reactions warrants further investigations of
the mode of addition of phenols to unsymmetrical alkynes. It
is likely that electronic effects of unsymmetrical alkynes and
phenols contribute to the moderate regioselectivity. Gold
and other catalytic systems used in the hydration and
hydroalkoxylations of unsymmetrical alkynes have led to
moderate regioselectivity in the product,9a,11,22 and our
current observations are consistent with this. However,
electron-deficient alkyne 5d reacted sluggishly with 1r, and
an inseparable mixture of regioisomers 6e and 6e0 was
produced in poor yield (Table 4, entry 5); a substantial
amount of precursor 5d was recovered even after continuing
the reaction for 4 days. This indicates poor reactivity of
phenolic-OH to electron-poor alkynes under the optimized
gold-catalyzed reaction condition.
arylvinyl ether moieties in the molecule, multiple hydrophe-
noxylation of polyphenols with symmetrical alkynes was
envisaged. Previous experimental results prompted us to
use the optimized condition B in evaluating the addition of
a series of electron-rich polyphenols with diphenylacetylene,
and the results are shown in Table 5. At first, the reaction of
hydroquinone (7a) with 2a was performed, and the corre-
sponding di-O-vinylated product was isolated in 55% yield
along with trace amount of monoadduct (Table 5, entry 1).
The reaction could not be completed even after 4 days; we
infer that the addition of the potential intermediate, benzene-
1,4-bis(olate),23 to the electrophilic Au-alkyne-π complex is
inefficient, thereby limiting the yield of the product. X-ray
crystallographic analysis unambiguously elucidated the
structure of 8a having Z-olefin stereochemistry (see the
Supporting Information).15
Resorcinol (7b) underwent efficient addition with 2a under
the optimized condition to furnish the desired di-O-vinylated
product in 94% yield (Table 5, entry 2). NOESY studies
confirm the Z-selectivity of 8b.19 Further, we were interested
in examining the possibility of hydrophenoxylations of steri-
cally encumbered catechol (7c) with 2a. The bond formation
(23) (a) Gao, C.; Gao, L.; Ding, M. U. S. Patent 0272957, 2005. (b) Forsyth,
T. P.; Williams, D. B. G.; Montalban, A. G.; Stern, C. L.; Barrett, A. G. M.;
Hoffman, B. M. J. Org. Chem. 1998, 63, 331.
In order to enlarge the molecular diversity based on
extended conjugation through the incorporation of more
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TABLE 5. Hydrophenoxylation of Polyphenols (7) with 2aa
SCHEME 1. Proposed Catalytic Cycle
bulkiness enhances the reactivity of the gold complex and
triggers the subsequent nucleophilic addition of phenols.24
The phenolate attack from the opposite side of 9 to yield
O-vinyl-Au species 10.18,25 Protodemetalation furnishes
arylvinyl ethers with Z-olefins 3 and regenerates the active
gold catalyst, as depicted in cycle A. An alternate pathway
B would involve coordination of phenols to gold com-
plex 99k,25b followed by base-induced deprotonation and
C-O bond formation leading to the O-vinyl-Au species 12
with Z-configuration. Protodemetalation would generate
(E)-arylvinyl ethers 13. Even though the transformation of
11 to 12 should be possible with any mild base, our observa-
tion for the hydrophenoxylation reaction is that it requires
specific choices of base and solvent. Further, exclusive
formation of Z-olefins is observed in the reaction. On the
basis of this evidence, route B appears unlikely.
Experimental results reveal that the gold(III) chloride and
ligand 4b mixture allows the intermolecular addition of
phenols to alkynes at 100 °C without losing its activity for
at least 4-6 days. In order to understand the plausible
reactive species involved in the catalytic system, NMR
experiment is performed by reacting 4-methoxyphenol (1b),
diphenylacetylene (2a), K2CO3, AuCl3, and 4b in THF-d8
solvent at room temperature. In the 31P NMR, three new
signals at δ=106.8, 59.6, and 55.0 ppm appear and the signal
at δ=17.4 ppm corresponding to the ligand 4b is absent. At
about 30 min, the signal at δ=106.8 ppm disappears. The
peaks at δ = 55.0 and 59.6 ppm can be assigned to the
phosphineoxide (14) and phosphine-Au(I) complex (15),
respectively (Figure 1).24a,26,27 However, efforts to isolate the
species with a signal at δ=106.8 ppm failed; therefore, the
structure of this species cannot be established. The sample of
aReactions were performed using 7 (1.0 mmol) and THF (2.0 mL) in
condition B. bIsolated yields based on 7. cReaction was carried out
employing 2a and K2CO3 (4.0 mmol each), AuCl3 and 4b (10 mol %
each), and continued for 96 h. dReaction was continued for 168 h;
monoadduct (8c0) was also obtained. eReaction was performed using 2a
and K2CO3 (6.0 mmol each), AuCl3 and 4b (15 mol % each), and
continued for 168 h; di- (8d0) and mono-O-vinylated phloroglucinols
(8d00) were obtained.
between 7c and 2a would be difficult, in view of the close
proximity of the -OH groups in the catechol. It is worth
noting that di-O-vinylated catechol (8c) was isolated in only
7% yield after continuing the reaction for 7 days (Table 5,
entry 3). Moderate yield of the corresponding mono-O-
vinylated catechol (8c0) was also produced along with un-
reacted 7c. Finally, we have explored the challenging hydro-
phenoxylation of phloroglucinol (7d) with 2a. Tri-O-vinyl-
ated phloroglucinol (8d) was obtained, although in poor
yield, when the reaction between 7d and 2a was executed
under the optimized condition for 7 days; the corresponding
di- and mono-O-vinylated phloroglucinols were also pro-
duced in 9 and 32%, respectively. To the best of our know-
ledge, these new molecular entities are prepared for the first
time via simultaneous addition of phenols to the alkynes
catalyzed by gold.
(24) (a) Nieto-Oberhuber, C.; Lopez, S.; Echavarren, A. M. J. Am. Chem.
Soc. 2005, 127, 6178. (b) Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.; Qian, H;
Widenhoefer, R. A. J. Am. Chem. Soc. 2006, 128, 9066.
(25) (a) For gold-catalyzed carboxylate addition to alkynes, see: Harkat,
H.; Weibel, J.-M.; Pale, P. Tetrahedron Lett. 2006, 47, 6273. (b) For gold-
catalyzed intermolecular hydroamination of alkynes, see: Mizushima, E.;
Hayashi, T.; Tanaka, M. Org. Lett. 2003, 5, 3349.
(26) (a) Baillie, C.; Xiao, J. Tetrahedron 2004, 60, 4159. (b) Wolfe, J. P.;
Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121,
9550.
(27) It is likely that a part of phosphine is involved for the conversion of
Au(III) to Au(I) species in the redox process with simultaneous formation of
phosphine oxide using a trace amount of adventitious water present in the
system.
Even though the detailed mechanism of this reaction is not
yet established, it is likely to proceed through the following
catalytic cycle, as shown in Scheme 1. The soft and carbo-
philic JohnPhos ligated Au complex activates the alkyne to
provide gold-alkyne-π complex 9.16,22 This ligand is found to
be very crucial for the present reaction, suggesting that its
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General Procedure for the Reaction of Unactivated Phenols to
Alkynes (GP-2, Condition B): In an oven-dried Schlenk flask,
phenol (2.0 mmol), alkyne (1.0 mmol), and K2CO3 (2.0 mmol)
were taken. The flask was evacuated and backfilled with argon
three times. A solution of AuCl3 (0.05 mmol) and 4b (JohnPhos,
0.05 mmol) in THF (1.0 mL) was freshly prepared in a separate
Schlenk flask and introduced to the parent mixture under an
argon atmosphere. The resulting reaction mixture was heated at
100 °C. Progress of the reaction was monitored by GC analysis
while noticing complete consumption of alkynes employed.
Reaction was continued for the time shown in the respective
tables and allowed to cool to room temperature. The reaction
mixture was diluted with dichloromethane (5 mL) and filtered
over a small pad of Celite. Solvent was evaporated under
reduced pressure, and the crude reaction mixture was purified
using silica gel column chromatography.
(Z)-(1-(4-Methoxyphenoxy)ethene-1,2-diyl)dibenzene (3ba):
251 mg, 83% yield; colorless solid; mp 102-104 °C; Rf=0.56
(49:1 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.71-7.66
(m, 2H), 7.63-7.58 (m, 2H), 7.38-7.28 (m, 5H), 7.27-7.21 (m,
1H), 7.01-6.93 (m, 2H), 6.82-6.75 (m, 2H), 6.62 (s, 1H), 3.74 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 154.6, 150.2, 150.1, 136.1,
134.9, 128.9, 128.5, 128.3, 127.3, 126.2, 117.1, 116.5, 114.7, 55.5;
IR (KBr) νmax 3074, 2928, 1630, 1502, 1444, 1205, 1103, 1037,
759 cm-1; MS (EI) m/z (%) 303 (Mþ þ 1, 100), 211 (73), 197 (3).
Anal. calcd for C21H18O2: C, 83.42; H, 6.00. Found: C, 83.56; H,
5.95.
(Z)-(1-(4-Methylphenoxy)ethene-1,2-diyl)dibenzene (3ca): 198
mg, 69% yield; colorless solid; mp 90-92 °C; Rf=0.43 (hexane);
1H NMR (400 MHz, CDCl3) δ 7.67 (d, J=8.0 Hz, 2H), 7.61 (d,
J=7.6 Hz, 2H), 7.39-7.19 (m, 6H), 7.04 (d, J=8.0 Hz, 2H), 6.95
(d, J=8.4 Hz, 2H), 6.66 (s, 1H), 2.26 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 154.1, 149.9, 136.1, 134.8, 131.2, 130.1, 128.9,
128.5, 128.4, 128.3, 127.3, 126.1, 116.6, 116.1, 20.5; IR (KBr)
νmax 3030, 2916, 2860, 1608, 1506, 1448, 1219, 1168, 806, 688,
569 cm-1; MS (EI) m/z (%) 287 (Mþ þ 1, 100), 211 (54), 179 (3).
Anal. calcd for C21H18O: C, 88.08; H, 6.34. Found: C, 88.16; H,
6.28.
(Z)-(1-(4-sec-Butylphenoxy)ethene-1,2-diyl)dibenzene (3da):
233 mg, 71% yield; colorless solid; mp 78-79 °C; Rf = 0.75
(hexane); 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J=6.4 Hz, 2H),
7.62 (d, J=6.4 Hz, 2H), 7.37-7.26 (m, 5H), 7.23 (t, J=6.0 Hz,
1H), 7.03 (d, J=6.8 Hz, 2H), 6.95 (d, J=6.8 Hz, 2H), 6.65 (s,
1H), 2.63-2.45 (m, 1H), 1.61-1.47 (m, 2H), 1.19 (d, J=5.6 Hz,
3H), 0.81 (t, J=6.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
154.4, 150.0, 141.2, 136.3, 134.9, 129.0, 128.5, 128.3, 128.1,
127.3, 126.2, 116.6, 116.0, 40.8, 31.3, 21.7, 12.2; IR (KBr) νmax
3028, 2957, 2918, 1604, 1504, 1221, 1020, 821, 767 cm-1; MS
(EI) m/z (%) 329 (Mþ þ 1, 100), 211 (86), 197 (7). Anal. calcd for
C24H24O: C, 87.76; H, 7.37. Found: C, 87.58; H, 7.41.
FIGURE 1. 31P NMR chemical shifts of the mixture of JohnPhos
and AuCl3.
AuCl3 and 4b in THF-d8 at room temperature shows iden-
tical results in the 31P NMR spectrum to that observed in the
previous reaction. Similarly, the 31P NMR spectrum of the
sample of AuCl3 and 4b in CDCl3 at room temperature
shows three peaks at δ=106.2, 59.9, and 18.0 ppm; the signal
at δ=18.0 ppm corresponds to 4b in CDCl3, and the peaks at
δ=106.2 and 59.9 ppm resemble those from the previous
reaction. We believe that 15 may be responsible for the
hydrophenoxylations to alkynes at the elevated temperature.
The formation of 15 can also be expected in the reactions of
AuCl and Ph3PAuCl with 4b (entries 10 and 11, Table 1).
However, the 31P NMR spectrum of a mixture of AuCl and
4b in CDCl3 shows two signals at δ=60.0 and 17.9 ppm in a
1:4 ratio corresponding to 15 and 4b, respectively, and the
sample of Ph3PAuCl and 4b in CDCl3 shows no formation of
15; the latter shows signals at δ = 18.2 (for 4b) and 29.0
ppm.28 These observations account for the trace formation
of 3aa in these reactions (entries 10 and 11 in Table 1).
Conclusion
In summary, we have demonstrated an efficient and atom-
economical gold-catalyzed intermolecular hydrophenoxyla-
tion of alkynes. The present methodology provides a new
one-step protocol for the synthesis of a wide array of vinyl-
(1,2-disubstituted)aryl ethers. We believe that the current
strategy would trigger synthetic explorations of oxygen-
containing heterocycles of pharmaceutical interest.7 Efforts
are underway to optimize milder reaction conditions, un-
ravel mechanistic details, and investigate novel synthetic
applications.
Experimental Section
General Procedure for the Reaction of Unactivated Phenols to
Alkynes (GP-1, Condition A): In an oven-dried pressure tube,
phenol (2.0 mmol), alkyne (1.0 mmol), and Ag2CO3 (2.0 mmol)
were taken. The tube was evacuated and backfilled with argon
three times. In a separate Schlenk flask, a heterogeneous solu-
tion of AuCl3 (0.03 mmol) and ligand [4b (JohnPhos), 2-(di-tert-
butylphosphino)biphenyl, 0.03 mmol] in DCM (1.0 mL) was
freshly prepared and introduced to the parent reaction mixture
under an argon atmosphere. The resulting reaction mixture was
heated at 100 °C. Progress of the reaction was monitored by GC
analysis while noticing complete consumption of alkynes
employed. Reaction was continued for the time shown in the
respective tables and brought to room temperature. The reac-
tion mixture was diluted with dichloromethane (5 mL) and
filtered over a small pad of Celite. Solvent was evaporated under
reduced pressure, and the crude reaction mixture was purified
using silica gel column chromatography.
(Z)-(1-(4-Fluorophenoxy)ethene-1,2-diyl)dibenzene (3ea): 262
mg, 90% yield; colorless solid; mp 62-65 °C; Rf=0.71 (hexane);
1H NMR (400 MHz, CDCl3) δ 7.71-7.64 (m, 2H), 7.62-7.58
(m, 2H), 7.39-7.31 (m, 5H), 7.30-7.22 (m, 1H), 7.03-6.89 (m,
4H), 6.68 (s, 1H); 13C NMR (101 MHz, CDCl3) δ 159.1, 156.7,
152.2, 149.8, 135.7, 134.6, 128.9, 128.6, 128.59, 128.54, 127.5,
126.1, 117.3, 117.2, 116.8, 116.2, 116.0; 19F NMR (376 MHz,
CDCl3) δ -122.2; IR (KBr) νmax 3043, 1633, 1502, 1446, 1195,
1093, 516 cm-1; MS (EI) m/z (%) 291 (Mþ þ 1, 100), 211 (79),
197 (3), 179 (5). Anal. calcd for C20H15FO: C, 82.74; H, 5.21.
Found: C, 82.57; H, 5.26.
(Z)-(1-(4-Chlorophenoxy)ethene-1,2-diyl)dibenzene (3fa): 270
mg, 88% yield; colorless solid; mp 88-90 °C; Rf=0.75 (hexane);
1H NMR (400 MHz, CDCl3) δ 7.61 (d, J=7.2 Hz, 2H), 7.57 (d,
J=8.4 Hz, 2H), 7.39-7.28 (m, 5H), 7.27-7.14 (m, 3H), 6.95 (d,
J=8.8 Hz, 2H), 6.67 (s, 1H); 13C NMR (101 MHz, CDCl3) δ
154.9, 149.4, 135.6, 134.5, 129.7, 128.9, 128.7, 128.6, 127.6,
127.0, 126.0, 117.5, 116.9; IR (KBr) νmax 3072, 3020, 1591,
(28) Duan, H.; Sengupta, S.; Petersen, J. L.; Akhmedov, N. G.; Shi, X.
J. Am. Chem. Soc. 2009, 131, 12100.
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1485, 1446, 1221, 1093, 815 cm-1; MS (EI) m/z (%) 305 (Mþ - 1,
44), 283 (82), 255 (84), 127 (100). Anal. calcd for C20H15ClO: C,
78.30; H, 4.93. Found: C, 78.41; H, 4.88.
Anal. calcd for C20H15FO: C, 82.74; H, 5.21. Found: C, 82.65;
H, 5.26.
(Z)-(1-(3-Nitrophenoxy)ethene-1,2-diyl)dibenzene (3aa): 270
mg, 85% yield; pale yellow solid; mp 112-114 °C; Rf =0.53
(49:1 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.66-7.58
(m, 4H), 7.51 (d, J=8.8 Hz, 2H), 7.41-7.30 (m, 5H), 7.29-7.22
(m, 1H), 7.12 (d, J=8.8 Hz, 2H), 6.75 (s, 1H); 13C NMR (101
MHz, CDCl3) δ 156.9, 149.3, 148.7, 134.8, 134.0, 130.3, 129.0,
128.9, 128.8, 128.6, 127.8, 125.8, 122.3, 117.4, 117.1, 111.3; IR
(KBr) νmax 3080, 2932, 1645, 1521, 1446, 1350, 1269, 1022, 767
cm-1; MS (EI) m/z (%) 318 (Mþ þ 1, 68), 302 (2), 288 (18), 211
(100), 197 (4). Anal. calcd for C20H15NO3: C, 75.70; H, 4.76; N,
4.41. Found: C, 75.68; H, 4.81; N, 4.46.
(Z)-(1-(4-(Trifluoromethyl)phenoxy)ethene-1,2-diyl)dibenzene
(3ga): 279 mg, 82% yield; colorless solid; mp 58-60 °C; Rf=0.78
1
(hexane); H NMR (400 MHz, CDCl3) δ 7.66-7.57 (m, 4H),
7.51 (d, J=8.4 Hz, 2H), 7.41-7.31 (m, 5H), 7.29-7.22 (m, 1H),
7.12 (d, J = 8.4 Hz, 2H), 6.76 (s, 1H); 13C NMR (101 MHz,
CDCl3) δ 158.9, 148.9, 135.2, 134.2, 129.0, 128.8, 128.7, 128.6,
127.7, 127.2, 127.1, 125.8, 117.2, 116.2; 19F NMR (376 MHz,
CDCl3) δ -61.7; IR (KBr) νmax 3061, 1612, 1512, 1325, 1232,
1066, 839, 692 cm-1; MS (EI) m/z (%)=341 (Mþ þ 1, 100), 211
(82), 197 (2), 179 (8). Anal. calcd for C21H15F3O: C, 74.11; H,
4.44. Found: C, 74.23; H, 4.48.
(Z)-3-(1,2-Diphenylvinyloxy)benzaldehyde (3ma): 151 mg,
50% yield; yellow solid; mp 78-81 °C; Rf=0.43 (49:1 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 9.90 (s, 1H), 7.69-7.59
(Z)-(1-(4-Nitrophenoxy)ethene-1,2-diyl)dibenzene (3ha): 273
mg, 86% yield; pale yellow thick liquid; Rf=0.43 (49:1 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J=8.8 Hz, 2H),
7.60-7.53 (br d, J=7.6 Hz, 4H), 7.40-7.29 (m, 5H), 7.28-7.20
(m, 1H), 7.11 (d, J=8.8 Hz, 2H), 6.78 (s, 1H); 13C NMR (101
MHz, CDCl3) δ 161.5, 148.5, 142.6, 134.8, 133.8, 129.0, 128.9,
128.7, 128.0, 126.1, 125.7, 117.4, 116.3; IR (neat) νmax 3059,
2924, 1647, 1518, 1489, 1340, 750 cm-1; MS (EI) m/z (%) 318
(Mþ þ 1, 98), 302 (7), 288 (30), 211 (100), 197 (8), 178 (8). Anal.
calcd for C20H15NO3: C, 75.70; H, 4.76; N, 4.41. Found: C,
75.62; H, 4.81; N, 4.48.
(m, 4H), 7.55-7.46 (m, 2H), 7.45-7.20 (m, 8H), 6.75 (s, 1H); 13
C
NMR (101 MHz, CDCl3) δ 191.7, 157.0, 149.1, 138.0, 135.3,
134.3, 130.3, 129.0, 128.7, 128.6, 128.5, 127.6, 125.9, 124.0,
122.4, 117.1, 116.2; IR (KBr) νmax 3059, 2924, 2845, 1697,
1591, 1446, 1244, 761, 692 cm-1; MS (EI) m/z (%) 301 (Mþ þ
1, 77), 211 (100), 179 (4). Anal. calcd for C21H16O2: C, 83.98; H,
5.37. Found: C, 84.12; H, 5.33.
(Z)-(1-(o-Tolyloxy)ethene-1,2-diyl)dibenzene (3na): 129 mg,
45% yield; colorless solid; mp 72-73 °C; Rf =0.37 (hexane):
1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz, 2H),
7.65-7.58 (m, 2H), 7.42-7.31 (m, 5H), 7.31-7.22 (m, 2H),
6.99 (td, J=8.0, 4.0 Hz, 1H), 6.92 (td, J=8.0, 4.0 Hz, 1H), 6.79
(d, J=8.0 Hz, 1H), 6.73 (s, 1H), 2.59 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 154.3, 150.0, 136.1, 135.0, 131.1, 128.9, 128.6,
128.5, 128.4, 127.4, 126.9, 126.6, 125.9, 121.8, 116.7, 114.3, 16.6;
IR (KBr) νmax 3057, 2924, 1639, 1489, 1448, 1180, 1116, 1076,
754, 692 cm-1; MS (EI) m/z (%) 287 (Mþ þ 1, 100), 211 (73), 197
(4), 179 (8), 165 (3). Anal. calcd for C21H18O: C, 88.08; H, 6.34.
Found: C, 88.21; H, 6.29.
(Z)-4-(1,2-Diphenylvinyloxy)benzonitrile (3ia): 259 mg, 87%
yield; colorless solid; mp 88-89 °C, Rf = 0.37 (49:1 hexane/
1
EtOAc); H NMR (400 MHz, CDCl3) δ 7.71-7.65 (m, 2H),
7.64-7.58 (m, 2H), 7.38-7.27 (m, 5H), 7.26-7.18 (m, 3H), 6.95
(dt, J=8.8, 2.0 Hz, 2H), 6.74 (s, 1H); 13C NMR (101 MHz,
CDCl3) δ 159.8, 148.5, 134.9, 134.3, 133.9, 129.0, 128.9, 128.88,
128.7, 127.9, 125.7, 118.8, 117.3, 116.9, 105.6; IR (KBr) νmax
3045, 2226, 1601, 1502, 1331, 918, 777 cm-1; MS (EI) m/z (%)
298 (Mþ þ 1, 88), 211 (100), 197 (2), 179 (5), 165 (2). Anal. calcd
for C21H15NO: C, 84.82; H, 5.08; N, 4.71. Found: C, 84.75; H,
5.12; N, 4.76.
(Z)-(1-(2-Fluorophenoxy)ethene-1,2-diyl)dibenzene (3oa): 262
mg, 90% yield; colorless thick liquid; Rf = 0.68 (hexane); H
1
(Z)-(1-Phenoxyethene-1,2-diyl)dibenzene (3ja): 96 mg, 35%
yield; colorless solid; mp 58-61 °C; Rf=0.27 (hexane); 1H NMR
(400 MHz, CDCl3) δ 7.66 (dt, J=7.6, 1.6 Hz, 2H), 7.62 (dt, J=
8.4, 1.6 Hz, 2H), 7.38-7.19 (m, 8H), 7.08-7.01 (m, 2H),
6.99-6.93 (m, 1H), 6.68 (s, 1H); 13C NMR (101 MHz, CDCl3)
δ 156.3, 149.6, 136.0, 134.7, 129.6, 128.9, 128.6, 128.5, 128.4,
127.4, 126.1, 122.0, 116.7, 116.3; IR (KBr) νmax 3055, 3022,
1591, 1487, 1222, 1167, 1020, 763 cm-1; MS (EI) m/z (%) 273
(Mþ þ 1, 100), 211 (33), 179 (4). Anal. calcd for C20H16O: C,
88.20; H, 5.92. Found: C, 88.31; H, 5.86.
NMR (400 MHz, CDCl3) δ 7.71 (dt, J=7.2, 1.6 Hz, 2H), 7.63
(dt, J=7.2, 1.6 Hz, 2H), 7.40-7.27 (m, 5H), 7.25-7.22 (m, 1H),
7.19-7.11 (m, 1H), 6.95-6.83 (m, 3H), 6.69 (s, 1H); 13C NMR
(101 MHz, CDCl3) δ 153.6, 151.7, 149.7, 144.0, 143.9, 135.5,
134.5, 128.9, 128.7, 127.62, 127.59, 125.9, 124.4, 124.3, 122.7,
122.6, 117.4, 116.8, 116.7, 116.5; 19F NMR (376 MHz, CDCl3)
δ -134.4; IR (neat) νmax 3059, 3026, 1645, 1610, 1500, 1448,
1199, 1018, 750, 692 cm-1; MS (EI) m/z (%) 291 (Mþ þ 1, 100),
211 (94), 197 (3), 180 (5). Anal. calcd for C20H15FO: C, 82.74; H,
5.21. Found: C, 82.65; H, 5.28.
(Z)-(1-(2-Nitrophenoxy)ethene-1,2-diyl)dibenzene (3pa): 70
mg, 22% yield; pale yellow thick liquid; Rf=0.28 (hexane); 1H
NMR (400 MHz, CDCl3) δ 7.93 (dd, J=8.4, 1.6 Hz, 1H), 7.65
(br d, J=8.4 Hz, 4H), 7.39-7.20 (m, 7H), 7.05-6.96 (m, 2H),
6.78 (s, 1H); 13C NMR (101 MHz, CDCl3) δ 149.5, 148.3, 139.6,
134.8, 134.2, 133.8, 129.1, 129.0, 128.9, 128.7, 127.9, 125.8,
121.8, 117.6, 117.1; IR (neat) νmax 3059, 2930, 1732, 1602,
1352, 1089, 920 cm-1; MS (EI) m/z (%) 318 (Mþ þ 1, 47), 286
(13), 225 (9), 211 (100), 197 (54), 186 (7). Anal. calcd for
C20H15NO3: C, 75.70; H, 4.76; N, 4.41. Found: C, 75.62; H,
4.81; N, 4.51.
(Z)-(2-(1,2-Diphenylvinyloxy)biphenyl (3qa): 237 mg, 68%
yield; colorless solid; mp 84-86 °C; Rf = 0.50 (hexane); 1H
NMR (400 MHz, CDCl3) δ 7.74 (dt, J=7.2, 1.2 Hz, 2H), 7.63
(dt, J=7.2, 1.2 Hz, 2H), 7.54-7.44 (m, 3H), 7.43-7.38 (m, 3H),
7.33-7.18 (m, 6H), 7.10 (ddd, J=9.6, 7.6, 1.6 Hz, 1H), 7.03
(ddd, J=9.6, 7.6, 1.6 Hz, 1H), 6.92 (dd, J=8.0, 1.2 Hz, 1H), 6.64
(s, 1H); 13C NMR (126 MHz, CDCl3) δ 153.0, 150.1, 138.2,
135.9, 134.9, 131.4, 131.0, 129.7, 128.9, 128.5, 128.48, 128.4,
128.3, 128.1, 127.3, 127.2, 126.0, 122.3, 116.5, 115.5; IR (KBr)
νmax 3032, 2922, 1628, 1475, 1446, 1332, 1253, 1022, 746, 690
(Z)-(1-(3-Methoxyphenoxy)ethene-1,2-diyl)dibenzene (3ka):
155 mg, 51% yield; colorless solid; mp 98-100 °C; Rf =0.62
(49:1 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.69-7.58
(m, 4H), 7.38-7.27 (m, 5H), 7.26-7.20 (m, 1H), 7.13 (t, J=8.4
Hz, 1H), 6.67 (s, 1H), 6.66-6.60 (m, 2H), 6.56-6.50 (m, 1H),
3.75 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 160.9, 157.5, 149.5,
136.0, 134.7, 130.0, 128.9, 128.6, 128.5, 128.4, 127.4, 125.9,
116.8, 108.7, 107.5, 102.7, 55.2; IR (KBr) νmax 2959, 1591,
1491, 1446, 1259, 1020, 758 cm-1; MS (EI) m/z (%) 303 (Mþ
1, 100), 211 (26), 179 (5). Anal. calcd for C21H18O2: C, 83.42; H,
6.00. Found: C, 83.35; H, 5.97.
þ
(Z)-(1-(3-Fluorophenoxy)ethene-1,2-diyl)dibenzene (3la): 209
mg, 72% yield; colorless solid; mp 80-82 °C; Rf=0.75 (hexane);
1H NMR (400 MHz, CDCl3) δ 7.68-7.57 (m, 4H), 7.41-7.28
(m, 5H), 7.28-7.21 (m, 1H), 7.21-7.13 (m, 1H), 6.83 (br d, J=
8.2 Hz, 1H), 6.81-6.73 (m, 1H), 6.71 (s, 1H), 6.70-6.62 (m, 1H);
13C NMR (101 MHz, CDCl3) δ 164.6, 162.7, 157.8, 157.7, 149.3,
135.6, 134.4, 130.5, 130.4, 129.0, 128.7, 128.61, 128.59, 127.6,
125.9, 117.0, 112.03, 112.01, 109.1, 108.9, 104.2, 104.1; 19F
NMR (376 MHz, CDCl3) δ -111.2; IR (KBr) νmax 3080,
1608, 1485, 1446, 1338, 1263, 1126, 1020, 835, 688 cm-1; MS
(EI) m/z (%) 291 (Mþ þ 1, 100), 211 (65), 197 (2), 179 (8).
J. Org. Chem. Vol. 75, No. 7, 2010 2255

Kuram et al.
JOCArticle
cm-1; MS (EI) m/z (%) 349 (Mþ þ 1, 100), 271 (65), 257 (21), 211
(44). Anal. calcd for C26H20O: C, 89.62; H, 5.79. Found: C,
89.55; H, 5.83.
þ 1, 75), 161 (6), 143 (100), 129 (18). Anal. calcd for C14H19FO:
C, 75.64; H, 8.61. Found: C, 75.59; H, 8.67.
(Z)-2-(Oct-4-en-4-yloxy)biphenyl (3qc): 187 mg, 67% yield;
colorless thick liquid; Rf=0.57 (hexane); 1H NMR (400 MHz,
CDCl3) δ 7.61 (d, J=7.6 Hz, 2H), 7.47-7.31 (m, 4H), 7.26 (t,
J=7.2 Hz, 1H), 7.06 (t, J=7.2 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H),
5.01 (t, J=7.2 Hz, 1H), 2.09 (t, J=7.2 Hz, 2H), 2.02 (q, J=7.2
Hz, 2H), 1.44-1.32 (m, 4H), 0.89 (t, J=7.2 Hz, 3H), 0.84 (t,
J=7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 153.5, 150.7,
138.4, 131.0, 129.5, 128.3, 127.9, 126.8, 121.4, 115.6, 114.7,
34.3, 29.7, 27.3, 22.7, 20.1, 13.9, 13.5; IR (neat) νmax 3061,
(Z)-1-(Hex-3-en-3-yloxy)-4-methoxybenzene (3bb): 194 mg,
94% yield; colorless liquid; Rf=0.43 (hexane); H NMR (400
MHz, CDCl3) δ 6.94-6.81(m, 4H), 4.99 (br t, J=7.2 Hz, 1H),
3.79 (s, 3H), 2.19-2.05 (m, 4H), 1.07 (t, J=7.6 Hz, 3H), 0.99 (t,
J=7.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 154.2, 152.1,
150.5, 116.8, 115.9, 114.5, 55.5, 25.2, 18.4, 14.2, 11.5; IR (neat)
1
ν
max 3043, 2966, 2935, 2878, 2835, 1684, 1504, 1462, 1296, 1211,
1101, 1039, 829 cm-1; MS (EI) m/z (%) 207 (Mþ þ 1, 100), 194
(2), 165 (2), 115 (14). Anal. calcd for C13H18O2: C, 75.69; H,
8.80. Found: C, 75.88; H, 8.75.
2959, 2934, 2872, 1682, 1583, 1477, 1217, 1118, 750, 698 cm-1
;
MS (EI) m/z (%) 281 (Mþ þ 1, 100), 161 (5), 143 (46), 129 (11).
Anal. calcd for C20H24O: C, 85.67; H, 8.63. Found: C, 85.74;
H, 8.59.
(Z)-1-(Hex-3-en-3-yloxy)-3-nitrobenzene (3ab): 122 mg, 55%
yield; pale yellow liquid; Rf=0.32 (hexane); 1H NMR (400 MHz,
CDCl3) δ 7.82 (d, J=8.0 Hz, 1H), 7.72 (s, 1H), 7.43 (t, J=8.0 Hz,
1H), 7.24 (br d, J=1.2 Hz, 1H), 5.12 (t, J=6.8 Hz, 1H), 2.16 (q,
J=7.2 Hz, 2H), 1.98 (q, J=7.2 Hz, 2H), 1.06 (t, J=7.6 Hz, 3H),
0.94 (t, J=7.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 157.6,
150.9, 149.3, 130.1, 122.1, 118.0, 116.2, 110.2, 25.4, 18.6, 13.9,
11.4; IR (neat) νmax 3082, 2970, 2937, 2879, 1685, 1614, 1531,
1350, 1277, 1232, 1024, 796 cm-1; MS (EI) m/z (%) 222 (Mþ þ 1,
100), 206 (53), 192 (54), 156 (53), 115(54). Anal. calcd for
C12H15NO3: C, 65.14; H, 6.83; N, 6.33. Found: C, 65.10; H,
6.88; N, 6.45.
(Z)-4,40-(1-(4-Nitrophenoxy)ethene-1,2-diyl)bismethoxyben-
zene (3hd): 157 mg, 83% yield; thick yellow liquid; Rf =0.43
(95:5 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.14 (dt,
J=8.0, 1.2 Hz, 2H), 7.51-7.45 (m, 4H), 7.10 (dt, J=8.0, 1.2 Hz,
2H), 6.91-6.75 (m, 4H), 6.62 (s, 1H), 3.80 (s, 3H), 3.79 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 161.8, 159.9, 159.0, 146.8,
142.4, 130.2, 127.4, 126.8, 126.1, 116.2, 115.6, 115.1, 114.3,
114.1, 55.3, 55.2; IR (neat) νmax 2930, 2843, 1608, 1342, 1242,
1176, 1032, 833 cm-1; MS (EI) m/z (%) 378 (Mþ þ 1, 52), 271
(100), 240 (3). Anal. calcd for C22H19NO5: C, 70.02; H, 5.07; N,
3.71. Found: C, 69.95; H, 5.12; N, 3.76.
(Z)-1-Methyl-4-(oct-4-en-4-yloxy)benzene (3cc): 172 mg, 79%
yield; colorless thick liquid; Rf=0.71 (hexane); H NMR (400
1
(Z)-4-(1,2-Bis(4-chlorophenyl)vinyloxy)benzonitrile (3ie): 250
mg, 68% yield; colorless thick liquid; Rf =0.40 (49:1 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.54 (dt, J=6.8, 2.0 Hz,
2H), 7.51-7.44 (m, 4H), 7.32 (dt, J=6.8, 2.0 Hz, 2H), 7.27 (dt,
J=6.8, 2.0 Hz, 2H), 7.05 (dt, J=6.8, 2.0 Hz, 2H), 6.68 (s, 1H);
13C NMR (101 MHz, CDCl3) δ 159.3, 147.9, 135.0, 134.4, 133.7,
133.1, 132.1, 130.2, 129.2, 128.9, 126.9, 118.6, 116.8, 116.52,
116.51, 106.1; IR (neat) νmax 3335, 3067, 2926, 2856, 2226, 1901,
1601, 1494, 1091, 831 cm-1; MS (EI) m/z (%) 366 (Mþ þ 1, 61),
298 (76), 279 (96), 211 (100), 185 (20), 149 (40). Anal. calcd for
C21H13Cl2NO: C, 68.87; H, 3.58. Found: C, 68.92; H, 3.91.
(Z)-1-Methoxy-4-(1-(4-nitrophenoxy)-2-phenylvinyl)benzene
(6a) and (Z)-1-Methoxy-4-(2-(4-nitrophenoxy)-2-phenylvinyl)-
benzene (6a0): 326 mg, 94% yield; yellow thick liquid; Rf=0.40
(49:1 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) olefin-H for
6a/6a0 δ 6.73 (s, 1H, 31%; minor)/6.64 (s, 1H, 69%; major);
HPLC analysis (Daicel Chiralpak AS-H column, hexane/i-
PrOH=97:3 for elution, flow rate=1.0 mL/min; λ=254 nm)
for 6a/6a0=tR (7.87 min, 37%; minor)/(8.47 min, 63%; major);
1H NMR (400 MHz, CDCl3) for 6a þ 6a0 δ 8.12 (br d, J=9.2 Hz,
4H; 2H (for major) þ 2H (for minor)), 7.58-7.44 (m, 8H; 4H
(for major) þ 4H (for minor)), 7.36-7.28 (m, 4H; 2H (for major) þ
2H (for minor)), 7.22-7.18 (m, 2H; 1H (for major) þ 1H (for
minor)), 7.12-7.05 (m, 4H; 2H (for major) þ 2H (for minor)),
6.89-6.80 (m, 4H; 2H (for major) þ 2H (for minor)), 6.73 (s, 1H,
minor), 6.64 (s, 1H, major), 3.78 (s, 3H, major), 3.77 (s, 3H,
MHz, CDCl3) δ 7.09 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H),
5.02 (t, J=7.2 Hz, 1H), 2.32 (s, 3H), 2.11 (t, J=7.2 Hz, 2H), 2.03
(q, J = 7.2 Hz, 2H), 1.53-1.43 (m, 2H), 1.43-1.33 (m, 2H),
0.96-0.87 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 154.6, 150.6,
130.5, 129.9, 115.9, 34.3, 27.2, 22.8, 20.6, 20.1,13.9, 13.6; IR
(neat) νmax 3028, 2962, 2868, 1684, 1506, 1222, 1167, 920, 815
cm-1; MS (EI) m/z (%) 219 (Mþ þ 1, 100), 178 (3), 161 (5), 143
(67), 129 (14). Anal. calcd for C15H22O: C, 82.52; H, 10.16.
Found: C, 82.61; H, 10.10.
(Z)-4-(Oct-4-en-4-yloxy)biphenyl (3sc): 268 mg, 96% yield;
colorless liquid; Rf=0.6 (hexane); 1H NMR (400 MHz, CDCl3)
δ 7.62-7.50 (m, 4H), 7.44 (t, J=7.2 Hz, 2H), 7.37-7.31 (m, 1H),
7.03 (dt, J=6.8, 2.0 Hz, 2H), 5.08 (t, J=7.2 Hz, 1H), 2.16 (t, J=
7.2 Hz, 2H), 2.05 (q, J = 7.6 Hz, 2H), 1.58-1.48 (m, 2H),
1.47-1.38 (m, 2H), 0.98-0.89 (m, 6H); 13C NMR (101 MHz,
CDCl3) δ 156.4, 150.5, 140.8, 134.4, 128.7, 128.2, 126.8, 126.7,
116.3, 116.2, 34.4, 27.2, 22.7, 20.1, 13.9, 13.6; IR (neat) νmax
2959, 2928, 2868, 1684, 1606, 1514, 1230, 1167, 835, 761, 696
cm-1; MS (EI) m/z (%) 281 (Mþ þ 1, 100), 161 (7), 143 (76), 129
(19). Anal. calcd for C20H24O: C, 85.67; H, 8.63. Found: C,
85.61; H, 8.70.
(Z)-1-Methoxy-3-(oct-4-en-4yloxy)benzene (3kc): 217 mg,
93% yield; colorless liquid; Rf=0.44 (hexane); H NMR (400
1
MHz, CDCl3) δ 7.16 (t, J=8.4 Hz, 1H), 6.57-6.48 (m, 3H), 5.01
(t, J=6.4 Hz, 1H), 3.78 (s, 3H), 2.10 (t, J=7.2 Hz, 2H), 1.99 (q,
J = 7.2 Hz, 2H), 1.54-1.41 (m, 2H), 1.41-1.31 (m, 2H),
0.94-0.84 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 160.9,
158.0, 150.4, 129.8, 116.3, 108.3, 106.8, 102.1, 55.2, 34.4, 27.2,
22.7, 20.1, 13.9, 13.6; IR (neat) νmax 2959, 2872, 1684, 1602,
1454, 1280, 1143, 962, 850, 688 cm-1; MS (EI) m/z (%) 235
(Mþ þ 1, 100), 143 (63), 125 (5). Anal. calcd for C15H22O2: C,
76.88; H, 9.46. Found: C, 76.95; H, 9.39.
13
minor); C NMR (101 MHz, CDCl3) for 6a þ 6a0 δ 161.5,
160.1, 148.4, 142.4, 134.0, 130.6, 128.7, 128.5, 127.5, 127.0,
125.9, 125.2, 116.2, 114.2, 55.2 (for major regioisomer); and
159.2, 146.7, 134.8, 130.6, 128.8, 128.5, 127.0, 126.4, 126.0,
125.2, 116.8, 116.0, 115.4, 114.0, 55.1 (for minor regioisomer);
IR (neat) for 6a þ 6a0 νmax 3080, 2934, 2837, 1637, 1591, 1342,
1238, 1022, 846 cm-1; MS (EI) m/z (%) for 6a þ 6a0 348 (Mþ þ 1,
100), 241 (97), 209 (11), 165 (3). Anal. calcd for C21H17NO4: C,
72.61; H, 4.93; N, 4.03. Found (as a mixture of 6a þ 6a0): C,
72.55; H, 4.88; N, 4.07.
(Z)-1-Fluoro-4-(oct-4-en-4-yloxy)benzene (3ec): 210 mg, 95%
yield; colorless liquid; Rf=0.55 (hexane); 1H NMR (400 MHz,
CDCl3) δ 6.99-6.91 (m, 2H), 6.89-6.82 (m, 2H), 4.99 (t, J=7.2
Hz, 1H), 2.06 (t, J = 7.6 Hz, 2H), 1.98 (q, J = 7.2 Hz, 2H),
(Z)-1-Nitro-4-(1-phenylprop-1-en-2-yloxy)benzene (6b) and
(Z)-1-Nitro-4-(1-phenylprop-1-enyloxy)benzene (6b0): 237 mg,
1.52-1.41 (m, 2H), 1.41-1.31 (m, 2H), 0.93-0.86 (m, 6H); 13
C
1
NMR (101 MHz, CDCl3) δ 158.8, 156.4, 152.74, 152.72, 150.7,
117.0, 116.9, 116.1, 115.9, 115.7, 34.2, 27.2, 22.7, 20.1, 13.8, 13.5;
19F NMR (376 MHz, CDCl3) δ -123.4; IR (neat) νmax 2959,
2928, 1682, 1502, 1201, 922, 829 cm-1; MS (EI) m/z (%) 223 (Mþ
93% yield; yellow thick liquid; H NMR (400 MHz, CDCl3)
olefin-H for 6b and 6b0 δ 6.06 (s, 1H, 30%; minor) 6.02 (q, J=7.2
Hz, 1H, 70%; major); HPLC analysis (Daicel Chiralcel OD-H
column, hexane/i-PrOH=99:1 for elution, flow rate=1.0 mL/min;
2256 J. Org. Chem. Vol. 75, No. 7, 2010

Kuram et al.
JOCArticle
λ=267 nm) for 6b/6b0=tR (4.33 min, 32%;minor)/(4.62 min, 68%;
major).
13C NMR (101 MHz, CDCl3) for 6d þ 6d0 δ 160.9, 159.8, 157.6,
149.4, 134.9, 130.4, 130.1, 130.0, 128.8, 128.6, 127.4, 115.1,
114.0, 108.7, 107.4, 102.7, 55.3, 55.2 (for major regioisomer);
and 158.9, 147.8, 136.2, 130.4, 130.1, 128.8, 128.5, 128.0, 127.5,
127.4, 127.1, 125.6, 116.3, 114.0, 108.5, 102.6, 55.3, 55.2 (for
minor regioisomer); IR (KBr) for 6d þ 6d0 νmax 2926, 2852, 1604,
1510, 1251, 1141, 835, 692 cm-1; MS (EI) m/z (%) for 6d þ 6d0
333 (Mþ þ 1, 100), 241 (38), 209 (5), 165 (3). Anal. calcd for
C22H20O3: C, 79.50; H, 6.06. Found (as a mixture of 6d þ 6d0): C,
79.44; H, 6.12.
(Z)-1-Nitro-4-(1-phenylprop-1-enyloxy)benzene (6b0, major):
light yellow thick liquid; Rf = 0.60 (49:1 hexane/EtOAc); 1H
NMR (400 MHz, CDCl3) δ 8.14 (d, J=8.8 Hz, 2H), 7.42 (d, J=
7.6 Hz, 2H), 7.33-7.24 (m, 3H), 7.03 (d, J=9.2 Hz, 2H), 6.02 (q,
J=7.2 Hz, 1H), 1.73 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 162.4, 149.2, 142.2, 134.3, 128.7, 128.4, 126.1, 124.8,
115.5, 113.2, 11.4; IR (neat) νmax 3080, 2989, 2920, 1666, 1591,
1342, 1109, 750 cm-1; MS (EI) m/z (%) 256 (Mþ þ 1, 100), 240
(22), 149 (46), 135 (3). Anal. calcd for C15H13NO3: C, 70.58; H,
5.13; N, 5.49. Found: C, 70.49; H, 5.10; N, 5.55.
(Z)-4-(2-Phenyl-1-(3-(trifluoromethyl)phenyl)vinyloxy)biphe-
nyl (6e) and (Z)-4-(1-Phenyl-2-(3-(trifluoromethyl)phenyl)vinyl-
oxy)biphenyl (6e0): 147 mg, 35% yield; pale yellow thick liquid;
Rf=0.17 (hexane); 1H NMR (400 MHz, CDCl3) olefin-H for 6e/
6e0 δ 6.79 (s, 1H, 31%; minor)/6.73 (s, 1H, 69%; major); HPLC
analysis (Daicel Chiralcel OD-H column, hexane/i-PrOH=19:1
for elution, flow rate=1.0 mL/min; λ=254 nm) for 6e/6e0=tR
(5.58 min, 30%; minor)/(5.99 min, 70%; major); 1H NMR (400
MHz, CDCl3) for 6e þ 6e0 δ 7.96 (br s, 2H; 1H (for major) þ 1H
(for minor)), 7.92 (d, J=7.6 Hz, 1H; major), 7.80 (d, J=8.0 Hz,
1H, minor), 7.74 (d, J=7.6 Hz, 1H, major), 7.68 (d, J=6.8 Hz,
2H, major), 7.60-7.25 (m, 25H; 11H (for major) þ 14H (for
minor)), 7.13 (t, J = 8.4 Hz, 4H; 2H (for major) þ 2H (for
minor)), 6.79 (s, 1H, minor), 6.73 (s, 1H, major); 13C NMR (101
MHz, CDCl3) for 6e þ 6e0 δ=155.7, 151.4, 140.5, 135.5, 135.4,
131.8, 129.2, 129.0, 128.8, 128.6, 128.5, 128.0, 126.9, 126.8,
126.2, 125.9, 123.9, 118.4, 116.6 (for major regioisomer); and
155.5, 148.2, 137.0, 134.2, 131.4, 131.0, 130.7, 129.0, 128.8,
128.5, 128.0, 126.8, 126.2, 125.1, 122.8, 122.7, 116.6, 115.2 (for
(Z)-1-Nitro-4-(1-phenylprop-1-en-2-yloxy)benzene (6b, minor):
light yellow thick liquid; Rf = 0.58 (49:1 hexane/EtOAc); 1H
NMR (400 MHz, CDCl3) δ 8.19 (d, J=8.0 Hz, 2H), 7.39 (d, J=
7.6 Hz, 2H), 7.28-7.20 (m, 2H), 7.17 (d, J=7.6 Hz, 1H), 7.07 (d,
J=8.8 Hz, 2H), 6.06 (s, 1H), 2.04 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 160.7, 147.5, 142.7, 134.0, 128.5, 128.3, 127.3, 126.1,
117.4, 116.5, 19.7; IR (neat) νmax 3082, 2922, 2849, 1682, 1591,
1340, 1240, 1109, 748 cm-1; MS (EI) m/z (%) 256 (Mþ þ 1, 36),
241 (10), 154 (55), 138 (100). Anal. calcd for C15H13NO3: C, 70.58;
H, 5.13; N, 5.49. Found: C, 70.65; H, 5.10; N, 5.43.
(Z)-1-Nitro-4-(1-phenylhex-1-en-2-yloxy)benzene (6c) and
(Z)-1-Nitro-4-(1-phenylhex-1-enyloxy)benzene (6c0): 241 mg,
81% yield; yellow thick liquid; Rf=0. 40 (49:1 hexane/EtOAc);
1H NMR (400 MHz, CDCl3) olefin-H for 6c/6c0 δ 6.08 (s, 1H,
57%; major)/5.95 (s, 1H, 43%; minor); HPLC analysis (Daicel
Chiralpak AS-H column, hexane/i-PrOH = 97:3 for elution,
flow rate=1.0 mL/min; λ=254 nm) for 6c/6c0 =tR (6.96 min,
38%; minor)/(7.45 min, 62%; major); 1H NMR (400 MHz,
CDCl3) for 6c þ 6c0 δ 8.25-8.15 (m, 4H; 2H (for major) þ 2H
(for minor)), 7.48-7.38 (m, 4H; 2H (for major) þ 2H (for
minor)), 7.32-7.20 (m, 4H; 2H (for major) þ 2H (for minor)),
7.18-7.12 (m, 2H; 1H (for major) þ 1H (for minor)), 7.08-6.99
(m, 4H; 2H (for major) þ 2H (for minor)), 6.08 (s, 1H, major),
5.95 (t, J=7.6 Hz, 1H, minor), 2.33 (t, J=7.2 Hz, 2H; 1H (for
major) þ 1H(forminor)), 2.17(q, J=7.2 Hz, 2H; 1H (for major) þ
1H (for minor)), 1.68-1.50 (m, 4H; 2H (for major) þ 2H (for
minor)), 1.49-1.27 (m, 4H; 2H (for major) þ 2H (for minor)),
0.96-0.81 (m, 6H; 3H (for major) þ 3H (for minor)); 13C NMR
(101 MHz, CDCl3) for 6c þ 6c0 δ 160.9, 151.4, 142.5, 133.9,
128.7, 128.5, 128.4, 126.1, 124.9, 116.3, 33.2, 29.1, 22.1, 13.9 (for
major regioisomer); and 162.7, 148.3, 142.1, 134.2, 128.4, 127.3,
119.1, 117.7, 116.7, 115.6, 31.2, 25.6, 22.4, 13.9 (for minor
regioisomer); IR (neat) for 6c þ 6c0 νmax 3082, 3026, 2957,
19
minor regioisomer); F NMR (376 MHz, CDCl3) for 6e/6e0
δ -62.67/-62.75; IR (neat) for 6e þ 6e0 νmax 3061, 3034, 2959,
1892, 1641, 1604, 1514, 1446, 1168, 908, 761, 694 cm-1; MS (EI)
m/z (%) for 6e þ 6e0 417 (Mþ þ 1, 89), 315 (7), 279 (100), 265 (9),
247 (2). Anal. calcd for C27H19F3O: C, 77.87; H, 4.60. Found (as
a mixture of 6e þ 6e0): C, 77.92; H, 4.56.
1,4-Bis[(Z)-1,2-diphenylvinyloxy]benzene (8a): 256 mg, 55%
yield; colorless solid; mp 197-199 °C; Rf=0.36 (95:5 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J=7.2 Hz, 4H),
7.56 (d, J=7.2 Hz, 4H), 7.34-7.25 (m, 10H), 7.24-7.17 (m, 2H),
6.86 (br s, 4H), 6.58 (s, 2H); 13C NMR (101 MHz, CDCl3) δ
151.1, 150.0, 136.0, 134.8, 128.9, 128.5, 128.3, 127.3, 126.1,
117.2, 116.5; IR (KBr) νmax 2924, 2849, 1494, 1197, 1020, 758,
690 cm-1; MS (EI) m/z (%) 467 (Mþ þ 1, 46), 430 (8), 411 (11),
313 (11), 289 (13), 211 (100), 143 (14). Anal. calcd for C34H26O2:
C, 87.52; H, 5.62. Found: C, 87.61; H, 5.58.
2930, 1668, 1591, 1516, 1342, 1242, 1111, 850, 750 cm-1
;
1,3-Bis[(Z)-1,2-diphenylvinyloxy]benzene (8b): 440 mg, 94%
yield; colorless solid; mp 116-117 °C; Rf=0.45 (95:5 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J=7.2 Hz, 4H),
7.51-7.46 (m, 4H), 7.30-7.18 (m, 12 H), 7.02 (t, J=8.4 Hz, 1H),
6.75 (t, J=2.4 Hz, 1H), 6.61 (br s, 3H), 6.58 (d, J=2.0 Hz, 1H);
13C NMR (101 MHz, CDCl3) δ 157.6, 149.7, 135.9, 134.6, 130.3,
129.0, 128.6, 128.5, 128.4, 127.4, 126.0, 116.6, 110.1, 105.6; IR
MS (EI) m/z (%) for 6c þ 6c0 296 (Mþ - 1, 86), 278 (11), 154
(17), 138 (100). Anal. calcd for C18H19NO3: C, 72.71; H, 6.44;
N, 4.71. Found (as a mixture of 6c þ 6c0): C, 72.65; H, 6.41;
N, 4.76.
(Z)-1-Methoxy-3-(1-(4-methoxyphenyl)-2-phenylvinyloxy)-
benzene (6d) and (Z)-1-Methoxy-3-(2-(4-methoxyphenyl)-1-phenyl-
vinyloxy)benzene (6d0): 101 mg, 63% yield; pale yellow solid; Rf=
0.26 (95:5 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) olefin-
H for 6d/6d0 δ 6.58 (s, 2H; 1H (for major) þ 1H (for minor));
HPLC analysis (Daicel Chiralpak AS-H column, hexane/
i-PrOH = 19:1 for elution, flow rate = 0.3 mL/min; λ = 254
nm) for 6d/6d0 = tR (13.9 min, 91%; major)/(14.49 min, 9%;
minor); 1H NMR (400 MHz, CDCl3) for 6d þ 6d0 δ 7.67-7.59
(m, 6H; 3H (for major) þ 3H (for minor)), 7.55 (d, J=8.0 Hz,
2H; 1H (for major) þ 1H (for minor)), 7.36-7.25 (m, 4H; 2H (for
major) þ 2H (for minor)), 7.21 (t, J=8.0 Hz, 2H; 1H (for major) þ
1H (for minor)), 7.14 (t, J=8.0 Hz, 2H; 1H (for major) þ 1H (for
minor)), 6.87 (d, J = 8.0 Hz, 4H; 2H (for major) þ 2H (for
minor)), 6.65 (br s, 4H; 2H (for major) þ 2H (for minor)), 6.58 (s,
2H; 1H (for major) þ 1H (for minor)), 6.53 (d, J=8.0 Hz, 2H;
1H (for major) þ 1H (for minor)), 3.80 (s, 6H; 3H (for major) þ
3H (for minor)), 3.75 (s, 6H; 3H (for major) þ 3H (for minor));
(KBr) νmax 3057, 2926, 1597, 1483, 1446, 1257, 1132, 690 cm-1
;
MS (EI) m/z (%) 467 (Mþ þ 1, 100), 357 (4), 315 (11), 289 (8),
211 (94), 197 (5). Anal. calcd for C34H26O2: C, 87.52; H, 5.62.
Found: C, 87.41; H, 5.66.
1,2-Bis[(Z)-1,2-diphenylvinyloxy]benzene (8c): 33 mg, 7%
yield; colorless solid; mp 142-143 °C; Rf=0.39 (95:5 hexane/
1
EtOAc); H NMR (400 MHz, CDCl3) δ 7.78 (dd, J=7.2, 4.4,
Hz, 7H), 7.42-7.32 (m, 10H), 7.31-7.25 (m, 3H), 6.87 (dd, J=
6.0, 2.0 Hz, 2H), 6.76 (s, 2H), 6.68 (dd, J=6.2, 3.4 Hz, 2H); 13
C
NMR (101 MHz, CDCl3) δ 149.9, 145.4, 135.9, 134.9, 129.1,
128.9, 128.7, 128.6, 128.5, 128.0, 127.5, 126.1, 125.6, 122.5,
121.3, 116.9, 116.2, 108.5; IR (KBr) νmax 3024, 1637, 1591,
1493, 1446, 1244, 1111, 1018, 920, 690 cm-1; MS (EI) m/z (%)
467 (Mþ þ 1, 6), 303 (22), 289 (69), 211 (59), 197 (100), 167 (4), 65
(13). Anal. calcd for C34H26O2: C, 87.52; H, 5.62. Found: C,
87.45; H, 5.66.
J. Org. Chem. Vol. 75, No. 7, 2010 2257

Kuram et al.
JOCArticle
(Z)-2-(1,2-Diphenylvinyloxy)phenol (8c0): 97 mg, 34% yield.
colorless thick liquid; Rf=0.18 (95:5, hexane/EtOAc); 1H NMR
(400 MHz, CDCl3) δ 7.65 (d, J=7.6 Hz, 2H), 7.57 (dt, J=6.8, 1.6
Hz, 2H), 7.41-7.25 (m, 6H), 7.10 (dd, J=8.0, 1.2 Hz, 1H), 6.92
(td, J=8.0, 1.6 Hz, 1H), 6.81 (dd, J=8.0, 1.6 Hz, 1H), 6.75 (s,
1H), 6.69 (td, J=7.6, 1.6 Hz, 1H), 6.01 (s, 1H, -OH); 13C NMR
(101 MHz, CDCl3) δ 149.1, 145.6, 143.0, 135.1, 134.3, 128.7,
128.7, 128.59, 127.6, 125.6, 123.0, 120.4, 117.2, 115.6, 114.9; IR
(neat) νmax 3524, 3055, 2976, 1641, 1448, 1203, 1018, 918, 740
cm-1; MS (EI) m/z (%) 289 (Mþ þ 1, 100), 287 (12), 225 (3), 211
(63), 197 (11), 179 (5). Anal. calcd for C20H16O2: C, 83.31; H,
5.59. Found: C, 83.21; H, 5.56.
1,3,5-Tris[(Z)-1,2-diphenylvinyloxy]benzene (8d): 38 mg, 6%
yield; colorless solid; mp 194-196 °C; Rf=0.21 (95:5 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.45 (br s, 6H), 7.33 (d,
J=7.2 Hz, 6H), 7.28-7.16 (m, 18H), 6.52 (s, 3H), 6.29 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 158.2, 149.6, 135.6, 134.5, 128.9,
128.4, 128.2, 127.2, 125.9, 116.3, 99.7; IR (KBr) νmax 2922, 2851,
1738, 1601, 1446, 1134, 761, 692 cm-1; MS (EI) m/z (%) 662
(Mþ þ 1, 100), 483 (47), 412 (35), 369 (16), 313 (24), 211 (51), 178
(14), 149 (9). Anal. calcd for C48H36O3: C, 87.25; H, 5.49. Found: C,
87.16; H, 5.54.
483 (Mþ þ 1, 100), 305 (5), 211 (8), 178 (8), 127 (3). Anal. calcd
for C34H26O3: C, 84.62; H, 5.43. Found: C, 84.71; H, 5.39.
(Z)-5-(1,2-Diphenylvinyloxy)benzene-1,3-diol (8d00): 99 mg,
32% yield; pale-brown thick liquid; Rf = 0.43 (60:40 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J=7.6 Hz, 2H),
7.56 (d, J=6.8 Hz, 2H), 7.37-7.17 (m, 6H), 6.64 (s, 1H), 6.14 (s,
2H), 5.85 (s, 1H), 5.65 (br s, 2H, -OH); 13C NMR (101 MHz,
CDCl3) δ 158.3, 157.4, 149.2, 135.7, 134.5, 128.9, 128.6, 128.5,
128.4, 127.5, 125.7, 116.8, 97.1, 96.6; IR (neat) νmax 3385
(-O-H), 2930, 1697, 1606, 1132, 1049, 825 cm-1; MS (EI)
m/z (%) 305 (Mþ þ 1, 100), 291 (4), 211 (8), 179 (8), 127 (8).
Anal. calcd for C20H16O3: C, 78.93; H, 5.30. Found: C, 78.85;
H, 5.26.
Acknowledgment. We gratefully acknowledge the Univer-
sity of Hyderabad, ACRHEM, and the DST (Grant No. SR/
S1/OC-34/2009) for support. M.R.K. and M.B. thank CSIR,
India, for graduate fellowships. We are grateful to Professor
S. Pal, Dr. P. Raghavaiah, and Mr. C. C. Gupta for solving
the X-ray crystallographic data for products 3aa and 8a. We
sincerely thank Professor T. P. Radhakrishnan for proof-
reading the manuscript. Professor K. C. Kumara Swamy is
thanked for the helpful discussion. This manuscript is dedi-
cated to Professor Tamejiro Hiyama, Kyoto University,
Japan, for his lifetime contribution to organic chemistry.
3,5-Bis((Z)-1,2-diphenylvinyloxy)phenol (8d0): 44 mg, 9%
yield; pale-brown thick liquid; Rf=0.18 (90:10 hexane/EtOAc);
1H NMR (400 MHz, CDCl3) δ 7.57 (d, J=7.6 Hz, 4H), 7.51 (d,
J=3.4 Hz, 4H), 7.34-7.18 (m, 13H), 6.62 (s, 2H), 6.38 (s, 1H,
-OH), 6.14 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 158.4,
157.6, 149.5, 135.7, 134.5, 129.0, 128.6, 128.5, 128.4, 127.4,
125.8, 116.7, 98.3, 97.9; IR (neat) νmax 3537, 3400 (-O-H),
2924, 1695, 1601, 1448, 1128, 916, 827 cm-1; MS (EI) m/z (%)
Supporting Information Available: Detailed experimental
procedures, spectra, and X-ray data. This material is available
free of charge via the Internet at http://pubs.acs.org.
2258 J. Org. Chem. Vol. 75, No. 7, 2010