Palladium-catalyzed alkylation of vinyl oxiranes with substituted allenes. Direct access to bifunctionalized allylic alcohols

Article abstract of DOI:10.1021/jo040139i

The first palladium-catalyzed alkylation of vinyl oxiranes with substituted allenes to form functionalized allylic alcohols is described. The reaction of activated allenes 5 with vinyl oxiranes 1 in the presence of catalytic amounts of Pd(PPh₃)

Full text of DOI:10.1021/jo040139i

P a lla d iu m -Ca ta lyzed Alk yla tion of Vin yl Oxir a n es w ith
Su bstitu ted Allen es. Dir ect Access to Bifu n ction a lized Allylic
Alcoh ols
Perli Nanayakkara and Howard Alper*
Centre for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, 10 Marie
Curie, Ottawa, Ontario K1N 6N5, Canada
halper@science.uottawa.ca
Received February 18, 2004
The first palladium-catalyzed alkylation of vinyl oxiranes with substituted allenes to form
functionalized allylic alcohols is described. The reaction of activated allenes 5 with vinyl oxiranes
1 in the presence of catalytic amounts of Pd(PPh3)4 (10 mol %) and 1,3-bis(diphenylphosphino)-
propane (dppp) (20 mol %) in THF at 60 °C gave the corresponding allylic alcohols 6 in good to
excellent yields. The allylic alcohols were obtained in different ratios of trans/ cis isomers.
A great deal of attention has recently been paid to the
palladium-catalyzed ring opening of vinyl oxiranes.1 A
number of publications have appeared on the regio- and
stereoselective formation of five-, six-, and seven-mem-
bered ring heterocycles by the palladium-catalyzed ring
opening and cycloaddition reactions of vinyl oxiranes with
heterocumulenes.2
It is known that the palladium(0)-catalyzed reaction
of vinyl oxiranes with nucleophiles (NuH) gives allylic
alcohols via π-allylpalladium intermediates (eq 1). Stable
carbon pronucleophiles, such as CH2(CO2Et)2, CH2(COPh)-
(CO2H), and CH2(CO2Me)(COCH3), are used as NuH,3
giving the corresponding carbon chain elongated allylic
alcohols in good yields. The ring opening of vinyl oxiranes
by organometallic reagents such as Pd(OAc)2,4 Pd-
(PPh3)4,5 and Pd2(dba)3‚CHCl36 to form allylic alcohols is
a versatile reaction in organic synthesis.7 The reactivity
of allyllithium compounds with vinyl oxiranes has also
been studied as a route to synthesize allylic alcohols.8
These metal-catalyzed reactions prompted us to explore
the synthesis of new functionalized compounds by the
palladium complex catalyzed reaction of vinyl oxiranes
and allenes.
In this reaction, effected under neutral conditions,
nucleophilic attack takes place selectively at the terminal
carbon, giving the 1,4-adduct. It has been shown that
C-C bond formation proceeds without adding a base
since the π-allylpalladium complex 2 behaves as a base
to pick up a proton.9 Although there are several examples
for the ring expansion, cycloaddition, and alkylation of
vinyl oxiranes with heterocumulenes and a variety of
pronucleophiles, no attempt has been made to use al-
lenes. Due to the unique arrangement of the two sets of
π-orbitals, the reactivity of electron-deficient 1,2 dienes
should be higher than that of the corresponding alkynes.
Herein, we wish to report a convenient palladium-
catalyzed reaction (Pd(PPh3)4/dppp) of vinyl oxiranes 1
with allenes possessing different substituents, to form
functionalized allylic alcohols 6, in good to excellent
yields. Neutral conditions are used because in situ
generated alcoholate is basic enough to deprotonate the
pronucleophilic entity (allene). A wide variety of func-
tional groups are tolerated in this reaction.
(1) Larock, R. C.; Stolz-Dunn, S. K. Tetrahedron Lett. 1989, 30, 3487.
(2) (a) Larksarp, C.; Alper, H. J . Am. Chem. Soc. 1997, 199, 3709.
(b) Larksarp, C, Alper, H. J . Org. Chem. 1998, 63, 6229.
(3) (a) Tsuji, J .; Kataoka, H.; Kobayashi, Y. Tetrahedron Lett. 1981,
22, 2575. (b) Takahashi, T.; Ootake, A.; Tsuji, J . Tetrahedron Lett. 1984,
25, 1921. (c) Takahashi, T.; Kataoka, H.; Tsuji, J . J . Am. Chem. Soc.
1983, 105, 147.
(4) Elliott, M.; Dhimane, A. L.; Malacria, M. Tetrahedron Lett. 1998,
39, 8849.
(5) Koizumi, T.; Sakamoto, J .; Gondo, Y.; Endo, T. Macromolecules
2002, 35, 2898.
(6) Trost, B.; J iang, C. J . Am. Chem. Soc. 2001, 123, 12907.
(7) (a) Mukaiyama, T.; Yamada, T.; Suzuki, K. Chem. Lett. 1983, 1,
5. (b) Candan, S. Turkish J . Chem. 2002, 26, 783. (c) Simic, M.; Hayon,
E. J . Phys. Chem. 1973, 77, 2662.
(8) Tsuji, J .; Kataoka, H.; Kobayashi, Y. Tetrahedron Lett. 1981, 22,
2575.
(9) (a) Trost, B. M.; Vos, B. A.; Brezezowski, C. M.; Martina, D. P.
Tetrahedron Lett. 1992, 33, 717. (b) Trost, B. M.; Molander, G. A. J .
Am. Chem. Soc. 1981, 103, 5969. (c) Shim, J .-G.; Yamamoto, Y. J . Org.
Chem. 1998, 63, 3067.
10.1021/jo040139i CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/15/2004
4686
J . Org. Chem. 2004, 69, 4686-4691

Palladium-Catalyzed Alkylation of Vinyl Oxiranes
TABLE 1. P r ep a r a tion of r-Allen ic Ester s by th e Wittig Rea ction a
entry
X
R1
R2
yieldc (%)
1
2
3
4
5
6
7
8
9
Ph
H
H
H
H
H
H
H
H
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
5a , 66
5b, 63
5c, 51
5d , 53
5e, 47
5f, 64
5g, 23
5h , 65
5i, 83
5j, 52
o-Br-Ph
p-Br-Phb
p-Cl-Ph
p-F-Ph
2-(2-naphthyl)
m,m-CF3-Phb
p-OMe-Ph
o,m-OMe-Ph
Ph
H
C2H5
CH2CH(CH3)2
C2H5
10
a
b
Reaction conditions: acid chloride (1 equiv), phosphorane (1 equiv), Et3N (1 equiv). Prepared from the acid using SOCl2. c Isolated
yield of the pure product.
SCHEME 1
Resu lts a n d Discu ssion
substituents were present on the arene ring (Table 1, e.g.,
entries 4 and 5). This could be due to the fact that
electron-withdrawing substituents lower the electron
density, which reduces the rate of formation of the
intermediates.
We started this study using commercially available
allenes such as 2,3-ethylbutadienoate, and 3-methyl-1,2-
butadiene with vinyl oxirane. Absence of the expected
products prompted us to use trisubstituted allenes.
Although there are a number of methods known for the
synthesis of allenes,10 the requisite substituted allenes
used in this study were prepared through the application
of a slightly modified procedure to that described by
Balme and co-workers (Table 1).11 The preparation of
R-allenic esters was accomplished by the reaction of
resonance-stabilized phosphoranes with isolable ketenes,12
ketene13 itself, and with acid chlorides in CH2Cl2 in the
presence of a second equivalent of the phosphoranes.
Disadvantages of the above methods have led to the
development of the acylation of Wittig reagents to
synthesize trisubstituted allenes in good yield. It was
found that the acylation of a Wittig reagent provides the
most convenient means for the preparation of allenes
substituted with various electron-withdrawing substit-
uents in good yields.
The mild reaction conditions used in the modified
method avoids the base-catalyzed isomerization of the
conjugated allenes to acetylenes. The reaction presum-
ably involves in situ formation of ketene and its capture
by the stabilized ylide. To obtain the allene in good purity
it was crucial to use freshly distilled acid chlorides, since
these decompose on storage. The ready availability of acid
chlorides allowed us to prepare a wide range of allenes
by this method.
Entry 9 was prepared using literature methods out-
lined in Scheme 1.14 The formation of the Wittig reagent
was best accomplished through the reaction of triphen-
ylphosphine and isobutyl 2-chloropropionate in the pres-
ence of triethylamine. Treatment of the intermediate
phosphonium salt with aqueous base yielded the Wittig
reagent as a pale yellow precipitate, which then reacted
with the corresponding acid chloride to form the allene.
The reaction of vinyl oxirane 1a (1 mmol) with mono-
and disubstituted allenes 5 was first investigated by
using reaction conditions similar to those described for
the reaction of vinyl oxiranes with heterocumulenes.
Mono- and disubstituted allenes are not suitable for the
present reaction, as the reaction of 1a with 5 in the
presence of different palladium catalysts and ligands in
THF under N2 gave none of the expected products.
According to the mechanism, â-H is necessary to form
the active allene intermediate, which will be stabilized
by other three substituents. In the case of mono- and
(10) (a) Lang, R. W.; Hansen, H.-J . Org. Synth. 1984, 202. (b) Trost,
B. M.; Pinkerton, A. B.; Seidel, M. J . Am. Chem. Soc. 2001, 123, 12466.
(c) Lang, R. W.; Hansen, H. Helv. Chim. Acta 1980, 63, 438.
(11) Balme, G.; Doutheau, A.; Gore, J .; Malacria, M. Synthesis 1979,
508, 202.
(12) (a) Wittig, G.; Hagg, A. Chem. Ber. 1963, 96, 1535. (b) Best-
mann, H. -J .; Hartung, H. Chem. Ber. 1966, 99, 1198.
(13) Hamlet, Z.; Barker, W. D. Synthesis 1970, 543.
(14) (a) Brown, F. J .; Matassa, V. G. US Patent 4,894,386, 1990.
(b) Giner, J .-L. Tetrahedron Lett. 2002, 43, 5457.
A number of R-allenic esters were synthesized in good
yields, and yields were lower when electron-withdrawing
J . Org. Chem, Vol. 69, No. 14, 2004 4687

Nanayakkara and Alper
TABLE 2. Op tim ized Con d ition s for th e Rea ction of Vin yl Oxir a n e 1a w ith Tr isu bstitu ted Allen es, Ca ta lyzed by
P a lla d iu m a
palladium/liganda
(mol %)
T
(°C)
yield of 6b
entry
(%)
trans/cisc
1
2
3
4
5
6
Pd2(dba)3 (10/20)
Pd(PPh3)4 (10/20)
Pd(PPh3)4 (10/20)
Pd(PPh3)4 (5/10)
Pd(PPh3)4 (10)d
e
60
60
rt
rt
85
60
50
74
71
58
-
50/50
43/57
44/56
44/56
-
a
b
Palladium catalyst and dppp were premixed for 30 min in 3.0 mL of dry degassed THF followed by addition of 1a and 5a . Isolated
yield of 6. c Ratio of trans/cis was determined by 1H NMR. In the absence of ligand. e In the absence of catalyst and ligand.
d
disubstituated allenes, stabilization of the negatively
charged allene intermediate would be difficult compare
to the trisubstituted allenes.
amount of catalyst was decreased to 5 mol % the product
yield was reduced (entry 4). We also found that the
reaction of vinyl oxirane with allene alone in THF at
ambient temperature does not proceed to give the allylic
alcohol (entry 6). Both catalyst and the ligand are
required for the reaction, as the use of catalyst without
ligand did not afford the product (entry 5). Also, THF
was found to be the best solvent for the alkylation of vinyl
oxirane with allenes.
We next examined the reactivity of trisubstituted
allenes (Table 2). The reaction of vinyl oxirane with
trisubstituted allenes proceeded rapidly under mild
conditions with 5-10 mol % of the palladium catalyst.
The reaction is totally regioselective giving only the 1,4-
adduct. According to similar work done in the past with
a variety of heterocumulenes, we expected to see the five-
membered ring cycloadduct. The present investigation
shows that the product consisted of a mixture of trans
and cis isomers of allylic alcohols. We concluded that the
trisubstituted allenes are important for the alkylation of
vinyl oxiranes.
When we examined the temperature effect for the
alkylation reaction, 60 °C was found to be the optimum
temperature for the present reaction. Alkylation occurs
even at room temperature, but the isolated yield is poor
compared to the reaction at 60 °C (Table 2, entry 3).
To understand the effect of substituents on the reactiv-
ity of allenes, we used electron-withdrawing and -donat-
ing substituents as well as bulky substituents present
on the arene ring (Table 3). Under the usual reaction
conditions, monosubstituted aryl allenes were converted
to the corresponding allylic alcohol in higher yields (entry
9). It should be noted that disubstituted aryl allenes gave
moderate yields compared to monosubstituted aryl al-
lenes, indicating that the steric bulkiness of the substit-
uents may have a significant effect on the reaction (entry
10).
Next, the effect of the catalyst system was examined.
1,2-Bis(diphenylphosphino)ethane (dppe), 1,2-bis(diphen-
ylphosphino)butane (dppb), and 1,2-bis(diphenylphosphi-
no)ferrocene (dppf) were tested as ligands, in addition to
dppp. The use of Pd2(dba)3 as a catalyst, instead of Pd-
(PPh3)4, in THF, gave poor results (entry 1). Other
catalyst systems, such as Pd(PPh3)4-dppe and Pd(PPh3)4-
2dppf, were also tested, but Pd(PPh3)4-2dppp was the
best among the catalyst systems examined. In addition,
catalysts such as Pd(OAc)2 and PdCl2(PhCN)2 were
totally ineffective. Based on the above reaction conditions,
we concluded that the catalytic system consisting of Pd-
(PPh3)4 and dppp is preferred for the present reaction.
The amount of catalyst-to-ligand ratio was next inves-
tigated, and the best results were obtained using Pd-
(PPh3)4/dppp in a 10:20 mol % ratio (entry 2). When the
In all the reactions investigated, allenes with an
electron-withdrawing group on the phenyl ring afford the
product as a mixture of E, Z isomers, in good to excellent
conversion. It also showed that the stereochemistry of
the resultant double bond is predominantly Z. This
4688 J . Org. Chem., Vol. 69, No. 14, 2004

Palladium-Catalyzed Alkylation of Vinyl Oxiranes
TABLE 3. P a lla d iu m -Ca ta lyzed Rea ction s of Vin yl Oxir a n e 1a w ith Su bstitu ted Allen es 5 in THF a
entry
allene
T (°C)
yieldb (%)
trans/cisc
1
2
3
4
5
6
7
8
9
10
11
12
13
5b
5b
5c
5d
5e
5f
70
rt
6b, 80
6b, 72
6c, 73
6d , 69
6e, 71
6f, 62
6f, 23
6g, 58
6h , 67
6i, 64
39/61
46/54
40/60
38/62
44/56
41/59
45/55
31/69
51/49
54/46
60
60
60
60
rt
60
60
60
60
100
120
5f
5g
5h
5i
5jd
5j
5j
a
Pd(PPh3)4 and dppp (10/20 mol %) were premixed for 30 min in 3.0 mL of dry, degassed THF followed by addition of 1a and 5 under
10 psi of N2 at the specified temperature in a glass autoclave. Isolated yield is based on the allene 5 used. c Ratio of trans/cis was
b
determined based on 1H and GC. Tetrasubstituted allene.
d
feature reflects the greater stability of the intermediate
syn complexes compared to the anti isomers. Some of the
advantages of the present reaction are that it can be
carried out in a comparatively shorter time and in some
cases at a relative low temperature (entry 2).
showed aromatic protons at δ 7.53-7.36, two multiplets
at δ 5.8 (4H) and δ 4.2 (8H), a dd at δ 2.8, two singlets at
δ 1.49 and 1.51 (6H), and a multiplet at δ 1.29-0.122,
which integrates to 8H instead of 6H. The integration at
δ 1.29-1.22 did not match with the number of protons,
which indicated that there could be an OH group
We also examined the reaction of a substituted vinylic
oxirane, 2-methyl-2-vinyloxirane (1b). The reaction was
performed under similar reaction conditions to 5e and
5h (Scheme 2). Although the reaction of 2-methyl-2-
vinyloxirane 1b was sluggish in comparison with that of
1a , presumably due to the steric congestion of the
π-allylpalladium intermediate 2, the alkylation products
were obtained in quite good yields.
1
underneath the multiplet. The H NMR analysis of 6c
in benzene resolved this problem, indicating that the
compound has an OH group adjacent to a methylene
center. A 2-D COSY experiment showed correlation
between that methylene center and the alkene protons.
(2) 13C NMR spectrum gave a signal at 172.8 ppm, which
corresponds to the ester carbonyl carbon. The two qua-
ternary carbons in the nonaromatic region (80-90 ppm)
suggest the presence of an alkyne functional group in the
product. (3) Mass spectral data for compound 6c sup-
ported the molecular formula (C17H19O3Br1) proposed for
the estimated value. (4) An intense absorption band at
1732 cm-1 region, typical of ester carbonyls, was present
in the IR spectrum and the absence of the characteristic
allene bond in the 1946 cm-1 region was observed after
The structural assignment of the products was made
on the basis of NMR and mass spectral results. We also
investigated the stereoselectivity of the reaction by using
5c as the allene. The latter was a mixture of trans and
cis isomers (inseparable by GC and TLC). This led us to
use preparative HPLC to separate the two isomers. The
data obtained for compound 6c in CDCl3 are discussed
below: (1) The 1H NMR spectrum of the trans/cis mixture
J . Org. Chem, Vol. 69, No. 14, 2004 4689

Nanayakkara and Alper
SCHEME 2
SCHEME 3
received. THF was dried over sodium/benzophenone and
distilled prior to use. All NMR spectra were recorded using
CDCl3 as the solvent with reference to residual CHCl3 (1H at
7.2 ppm and 13C at 77.0 ppm) except for 6c.
Separation of two isomers of 6c and 7c was achieved using
a HPLC equipped with a Nova-Pak Silica analytical, Nova-
Pak Silica preparative column with hexanes/ethyl acetate as
the mobile phase.
the reaction. A weak IR absorption was observed at 2340
and 2358 cm-1, which corresponds to the alkyne bond.
Esterification of 6a was performed to confirm the
presence of the allylic alcohol functionality (Scheme 3).
Benzoyl chloride and a catalytic amount of 4-(dimethyl-
amino)pyridine (DMAP) were added to a solution of 6a
in CH2Cl2 to give 7a in 53% yield.
Sp ectr a l Da ta . 6-Hyd r oxy-2-m eth yl-2-p h en yleth yn yl-
4-h exen oic a cid eth yl ester (6a ) (X ) H): light yellow oil;
1H NMR (300 MHz, CDCl3) δ 7.42-7.25 (m, 10H), 5.83-5.68
(m, 4H), 4.23-4.02 (m, 8H), 2.78-2.47 (m, 4H), 1.54 (s, 3H),
1.51 (s, 3H), 1.39-1.21 (m, 8H); 13C NMR (75 MHz, CDCl3) δ
172.8, 172.7, 133.2, 131.7, 131.4, 128.0, 127.9, 127.8, 127.7,
126.6, 126.4, 122.8, 122.7, 89.9, 89.7, 83.2, 62.9, 61.5, 61.3, 58.0,
43.1, 43.0, 42.4, 37.3, 25.1, 24.6, 13.9, 13.8; MS m/e 272 (M+);
EIHRMS calcd for C17H20O3 272.1412, found 272.1422.
2-(2-Br om op h en yleth yn yl)-6-h yd r oxy-2-m eth yl-4-h ex-
A possible mechanism for the Pd-catalyzed reaction is
outlined in Scheme 4. Initial oxidative addition of the Pd-
(0) catalyst to vinyl oxirane 1 may give the π-allylpalla-
dium intermediate 2. Addition of the activated allene to
the π-allylpalladium intermediate would produce 6 as a
mixture of trans and cis isomers.
In conclusion, we have observed the first regioselective
palladium-catalyzed ring opening and alkylation of vinyl
oxiranes with substituted allenes. The reaction is cata-
lyzed by 10 mol % of Pd(PPh3)4 and 20 mol % dppp
affording the corresponding funtionalized allylic alcohols
in good to excellent yields. The reaction tolerates a wide
range of functionality on the arene ring of the allylic
alcohols. This reaction provides a convenient new syn-
thetic route to allylic alcohols.
1
en oic a cid eth yl ester (6b) (X ) o-Br ): light yellow oil; H
NMR (300 MHz, CDCl3) δ 7.54 (d, J ) 8.0 Hz, 2H), 7.44 (d, J
) 1.68 Hz, 2H), 7.22-7.10 (m, 4H), 5.91-5.73 (m, 4H), 4.28-
4.13 (m, 4H), 4.11 (d, J ) 5.1 Hz, 4H), 2.82-2.65 (m, 2H),
2.56-2.03 (m, 2H), 1.54 (s, 3H), 1.52 (s, 3H), 1.44-1.23 (m,
8H); 13C NMR (75 MHz, CDCl3) δ 172.7, 172.4, 133.3, 133.1,
133.0, 132.1, 132.0, 131.6, 129.0, 128.9, 126.8, 126.7, 126.6,
126.5, 125.4, 124.9, 124.8, 94.7, 94.5, 81.9, 63.1, 61.6, 61.4, 58.1,
58.0, 43.4, 43.3, 42.3, 37.2, 25.1, 24.5, 14.0, 13.9; MS (m/e) 350
(M+); EIHRMS calcd for C17H19O3Br1 350.0518, found 350.0514.
2-(4-Br om op h en yleth yn yl)-6-h yd r oxy-2-m eth yl-4-h ex-
en oic a cid eth yl ester (6c) (X ) p-Br ): yellow oil; 1H NMR
(300 MHz, CDCl3) δ 7.53 (d, J ) 8.49 Hz, 4H). 7.36 (d, J )
8.42 Hz, 4H), 5.83-5.27 (m, 4H), 4.22-4.08 (m, 8H), 2.75-
Exp er im en ta l Section
All reactions and manipulations of chemicals were carried
out using standard Schlenk techniques under an atmosphere
of nitrogen. 2,3-Butadienoate, Pd(PPh3)4, and dppp were
purchased from commerical suppliers and were used as
4690 J . Org. Chem., Vol. 69, No. 14, 2004

Palladium-Catalyzed Alkylation of Vinyl Oxiranes
SCHEME 4
2.44 (m, 4H), 1.51 (s, 3H), 1.49 (s, 3H), 1.29-1.22 (m, 8H); 13
C
43.5, 42.5, 37.4, 25.3, 24.8, 14.2, 14.1; MS (m/e) 408 (M+);
EIHRMS calcd for C19H18O3F6 408.1160 found 408.1156.
6-H yd r oxy-2-(4-m et h oxyp h en ylet h yn yl)-2-m et h yl-4-
h exen oic a cid eth yl ester (6h ) (X ) o-OMe): light yellow
NMR (75 MHz, CDCl3) δ 172.1, 133.8, 133.1, 132.4, 131.8,
131.4, 128.0, 127.7, 127.3, 126.4, 126.0, 122.3, 122.2, 121.9,
121.1, 91.7, 91.4, 82.5, 62.9, 61.5, 61.3, 58.2, 43.4, 43.2, 42.6,
37.4, 25.1, 24.6, 13.9, 13.8; MS (m/e) 351 (M+); EIHRMS calcd
for C17H19O3Br1 350.0518, found 350.0515.
1
oil; H NMR (300 MHz, CDCl3) δ 7.33 (d, J ) 8.59 Hz, 4H),
6.78 (d, J ) 8.48 Hz, 4H), 5.80-5.66 (m, 4H), 4.21-4.08 (m,
8h), 3.77 (s, 6H), 2.74-2.44 (m, 4H), 1.50 (s, 3H), 1.48 (s, 3H),
1.29-1.22 (m, 8H); 13C NMR (75 MHz, CDCl3) δ 173.0, 172.8,
159.2, 159.1, 133.1, 132.8, 131.6, 127.1, 126.8, 115.0, 114.8,
113.6, 113.5, 88.4, 88.3, 83.0, 63.1, 61.5, 61.3, 58.1, 43.1, 43.0,
42.5, 37.3, 25.3, 24.7, 13.9, 13.8; MS (m/e) 302 (M+); EIHRMS
calcd for C18H22O4 302.1518, found 302.1607.
2-(2,5-Dim eth oxyp h en yleth yn yl)-6-h yd r oxy-2-m eth yl-
4-h exen oic a cid isobu tyl ester (6i) (X ) o,o-OMe): light
yellow oil; 1H NMR (300 MHz, CDCl3) δ 6.89 (s, 2H), 6.77 (dd,
J ) 3.77 Hz, 4H), 5.90-5.67 (m, 4H), 4.09 (d, J ) 5.18 Hz,
4H), 3.91 (d, J ) 6.84 Hz, 4H), 3.75 (d, J ) 17.87 Hz, 6H),
2.79-2.46 (m, 4H), 2.04-1.90 (m, 2H), 1.54 (s, 3H), 1.52 (s,
3H), 1.2-0.94 (m, 8H); 13C NMR (75 MHz, CDCl3) δ 173.2,
173.0, 154.6, 154.4, 153.2, 153.1, 133.3, 131.9, 127.5, 127.3,
118.3, 118.2, 115.4, 115.3, 113.1, 112.9, 112.5, 112.4, 94.1, 94.0,
79.8, 79.7, 71.6, 71.5, 63.6, 58.4, 56.6, 56.5, 55.8, 43.9, 43.7,
42.7, 37.5, 27.8, 25.7, 25.0, 19.0; MS (m/e) 360 (M+); EIHRMS
calcd for C21H28O5 360.1937, found 360.1959.
Ben zoic acid 5-eth oxycar bon yl-5-m eth yl-7-ph en ylh ept-
2-en -6-yn yl ester (7a ) (X ) H): light yellow oil; 1H NMR (300
MHz, CDCl3) δ 8.16-7.24 (m, 20H), 6.03-5.78 (m, 4H), 4.92
(d, J ) 5.09 Hz, 2H), 4.79 (d, J ) 5.86 Hz, 2H), 4.21 (m, 4H),
2.84-2.49 (m, 4H), 1.55 (s, 3H), 1.52 (s, 3H), 1.31-1.25 (m,
8H); 13C NMR (75 MHz, CDCl3) δ 172.8, 172.7, 166.4, 166.3,
133.7, 132.9, 131.7, 130.3, 130.2, 129.6, 129.5, 128.4, 128.3,
128.2, 128.1, 128.0, 126.9, 123.0, 122.9, 89.9, 89.8, 83.6, 83.5,
65.1, 61.7, 61.6, 60.9, 43.2, 43.1, 42.7, 37.7, 25.2, 25.0, 14.1,
14.0; MS (m/e) 376 (M+); EIHRMS calcd for C24H24O4, 376.1675
found 376.1695.
2-(4-Ch lor op h en yleth yn yl)-6-h yd r oxy-2-m eth yl-4-h ex-
1
en oic a cid eth yl ester (6d ) (X ) p-Cl): light yellow oil; H
NMR (300 MHz, CDCl3) δ 7.32 (d, J ) 8.05 Hz, 4H), 7.24 (d,
J ) 5.69 Hz, 4H), 5.85-5.59 (m, 4H), 4.27-4.11 (m, 8H), 2.77-
2.45 (m, 4H), 1.54 (s, 3H), 1.51 (s, 3H), 1.30-1.25 (m, 8H); 13
C
NMR (75 MHz, CDCl3) δ 172.9, 172.6, 134.2, 134.1, 133.5,
133.0, 132.0, 128.6, 128.5, 127.2, 127.0, 121.7, 121.5, 118.6,
91.3, 91.1, 82.5, 63.4, 61.8, 61.6, 58.5, 43.5, 43.3, 42.8, 42.7,
37.5, 25.4, 24.9, 14.2, 14.1; MS (m/e) 306 (M+); EIHRMS calcd
for C17H19O3Cl 306.1023, found 306.0992.
2-(4-F lu or op h en yleth yn yl)-6-h yd r oxy-2-m eth yl-4-h ex-
1
en oic a cid eth yl ester (6e) (X ) p-F ): light yellow oil; H
NMR (300 MHz, CDCl3) δ 7.37 (dd, J ) 6.5 Hz, 4H), 6.97 (t, J
) 8.30 Hz, 4H), 5.85-5.64 (m, 4H), 4.26-4.04 (m, 8H), 2.77-
2.45 (m, 4H), 1.51 (s, 3H), 1.49 (s, 3H), 1.39-1.21 (m, 8H); 13
C
NMR (75 MHz, CDCl3) δ 173.0, 172.8, 164.0, 163.9, 160.6,
160.5, 133.5, 133.47, 133.4, 131.9, 126.9, 126.6, 119.1, 119.05,
119.0, 118.9, 115.5, 115.4, 115.2, 115.1, 89.7, 89.6, 82.4, 63.2,
61.7, 61.6, 58.3, 43.3, 43.2, 42.6, 37.4, 25.3, 24.8, 14.1, 14.0;
MS (m/e) 290 (M+); EIHRMS calcd for C17H19O3F 290.1318
found 290.1307.
6-Hyd r oxy-2-m eth yl-2-n a p h th a len -2-yleth yn yl-4-h ex-
en oic a cid eth yl ester (6f) (X ) n a p h th yl): light yellow oil;
1H NMR (300 MHz, CDCl3) δ 7.93 (s, 2H), 7.79-7.72 (m, 6H),
7.47-7.42 (m, 6H), 5.88-5.69 (m, 4H), 4.29-4.08 (m, 8H),
2.83-2.519 (m, 4H), 1.58 (s, 3H), 1.56 (s, 3H), 1.32-1.27 (m,
8H); 13C NMR (75 MHz, CDCl3) δ 173.1, 172.9, 133.5, 132.8,
131.9, 131.4, 131.3, 128.5, 128.4, 127.8, 127.7, 127.6, 127.5,
126.8, 126.5, 126.43, 126.4, 126.3, 120.3, 120.2, 90.5, 90.3, 83.8,
63.2, 61.8, 61.6, 58.3, 43.4, 43.3, 42.7, 37.5, 25.4, 24.9, 14.1,
14.0; MS (m/e) 322 (M+); EIHRMS calcd for C21H22O3 322.1569,
found 322.1545.
Ack n ow led gm en t. We are grateful to the Natural
Sciences and Engineering Research Council of Canada
for supporting this research.
2-(3,5-Bis(tr iflu or om eth yl)p h en yleth yn yl)-6-h yd r oxy-
2-m eth yl-4-h exen oic a cid eth yl ester (6g) (X ) m ,m -
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 6a -i and 7a ; 1H COSY spectra of
1
CF 3): light yellow oil; H NMR (300 MHz, CDCl3) δ 7.83 (s,
4H), 7.76 (s, 2H), 5.84-5.62 (m, 4H), 4.28-4.05 (m, 8H), 2.79-
1
compounds 6c (cis) in C6D6, 7a (cis), and 7a (trans); H-13C
2.48 (m, 4H), 1.55 (s, 3H), 1.53 (s, 3H), 1.31-1.22 (m, 8H); 13
C
HMQC spectra of compound 7a (cis). This material is available
free of charge via the Internet at http://pubs.acs.org.
NMR (75 MHz, CDCl3) δ 172.4, 172.2, 135.0, 133.8, 132.4,
132.2, 132.0, 131.6, 131.5, 131.1, 126.7, 126.3, 125.4, 125.3,
124.7, 121.5, 121.1, 94.0, 93.8, 80.9, 63.3, 62.1, 61.9, 58.4, 43.6,
J O040139I
J . Org. Chem, Vol. 69, No. 14, 2004 4691