Enhanced reactivity of electron-deficient enynes in the palladium-catalyzed homo-benzannulation of conjugated enynes

Article abstract of DOI:10.1021/jo0006876

We report the high reactivity of electron-deficient enynes in the homo-benzannulation of conjugated enynes in the presence of Pd(PPh₃)₄. The introduction of electron-withdrawing groups enabled us to carry out the benzannulation of 1-substituted enynes as well as 1,2- and 2,4-disubstituted enynes. Polysubstituted benzenes were prepared in a highly regioselective manner in good to excellent yields.

Full text of DOI:10.1021/jo0006876

5350
J . Org. Chem. 2000, 65, 5350-5354
En h a n ced Rea ctivity of Electr on -Deficien t En yn es in th e
P a lla d iu m -Ca ta lyzed h om o-Ben za n n u la tion of Con ju ga ted En yn es
Shinichi Saito,*,† Yukiyasu Chounan,‡ Tsutomu Nogami,‡ Tomoko Fukushi,‡ Norie Tsuboya,¶
Yasuyuki Yamada,¶ Haruo Kitahara,‡ and Yoshinori Yamamoto*,¶
Institute for Chemical Reaction Science, Tohoku University, Sendai, 980-8578, J apan,
Department of Natural Science, Faculty of Education, Hirosaki University, Hirosaki 036-8560, J apan,
and Department of Chemistry, Graduate School of Science, Tohoku University, Sendai, 980-8578, J apan
yoshi@yamamoto1.chem.tohoku.ac.jp
Received May 4, 2000
We report the high reactivity of electron-deficient enynes in the homo-benzannulation of conjugated
enynes in the presence of Pd(PPh3)4. The introduction of electron-withdrawing groups enabled us
to carry out the benzannulation of 1-substituted enynes as well as 1,2- and 2,4-disubstituted enynes.
Polysubstituted benzenes were prepared in a highly regioselective manner in good to excellent
yields.
Polysubstituted benzenes are useful synthetic inter-
benzenes. For example, 2-substituted enynes always
cyclodimerize to give the corresponding 1,4-disubstituted
benzenes, and no isomeric 1,3-disubstituted benzenes are
isolated. While di- or trisubstituted enynes were used as
the substrates for the cross-benzannulation reaction,5,6
only monosubstituted enynes cyclodimerized in the homo-
benzannulation reaction: the reaction did not proceed
when a 1,2- or 2,4-dialkyl enyne was employed as the
substrate (eq 2).
mediates in organic synthesis, and the development of
efficient synthetic methods for such compounds is very
important. The preparation of polysubstituted benzenes
has been mainly carried out by stepwise introduction of
functional groups into the benzene ring via electrophilic1
or nucleophilic2 substitution. Careful choice of param-
eters such as synthetic route and reaction condition is
necessary to achieve highly regioselective syntheses of
polysubstituted benzenes. Recently, we reported the
palladium-catalyzed homo-benzannulation reaction (cy-
clodimerization) of 2-substituted enynes (eq 1).3 The
Our recent study of the substituent effects on the
reactivity of substituted enynes revealed that the reactiv-
ity of electron-deficient enynes was much higher com-
pared to that of alkyl enynes. The introduction of an
electron-withdrawing group into the conjugated enynes
enabled the homo-benzannulation of polysubstituted
enynes to proceed.7 In this paper we report details of the
palladium-catalyzed homo-benzannulation of electron-
deficient enynes (eq 3).8
homo-benzannulation of 4-substituted enynes also pro-
ceeded to yield 2,6-disubstituted styrenes (eq 1).4 These
reactions have been applied to the synthesis of many
functionalized benzenes such as paracyclophanes and
phenols.5 A common and useful feature of these reactions
is the highly regioselective formation of substituted
† Institute for Chemical Reaction Science, Tohoku University.
‡ Hirosaki University.
¶
Department of Chemistry, Graduate School of Science, Tohoku
University.
(1) March, J . Advanced Organic Chemistry, 4th ed.; Wiley: New
York, 1992; Chapter 11, pp 501-568.
(2) Snieckus, V. Chem. Rev. 1990, 90, 879-933.
(3) Saito, S.; Salter, M. M.; Gevorgyan, V.; Tsuboya, N.; Tando, K.;
Yamamoto, Y. J . Am. Chem. Soc. 1996, 118, 3970-3971.
(4) Gevorgyan, V.; Tando, K.; Uchiyama, N.; Yamamoto, Y. J . Org.
Chem. 1998, 63, 7022-7025.
(5) Reviews: (a) Saito, S.; Yamamoto, Y. Chem. Rev. in press. (b)
Gevorgyan, V.; Yamamoto, Y. J . Organomet. Chem. 1999, 576, 232-
247.
10.1021/jo0006876 CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/01/2000

Enhanced Reactivity of Electron-Deficient Enynes
J . Org. Chem., Vol. 65, No. 17, 2000 5351
Ta ble 1. h om o-Ben za n n u la tion of Electr on -Deficien t
Ta ble 2. h om o-Ben za n n u la tion of Electr on -Deficien t
En yn es (1)
En yn es (2)
temp time
yield
(%)
temp time
yield
R1
(°C)
(h) product
entry enyne
EWG
R1
(°C)
(h) product (%)
entry enyne
EWG
1
2
3
3a
3b
3c
COOEt
COOEt n-C6H13
CN n-C5H11
H
80
80
80
2
3
5
4a
4b
4c
43
38
53
1
2
3
4
5
1a
1b
1c
1d
1d
COOEt
COOEt
CN
CONMe2
CONMe2
H
rt
80
80
45
80
2
2
1.5
4
1
2a
2b
2c
2d
2d
88
73
84
62
53
n-C6H13
n-C5H11
H
H
reaction temperature (80 °C) was required (compare
Table 1, entry 1 and Table 2, entry 1). A similar tendency
was observed in the reaction of other enynes such as 3b
and 3c (Table 2, entries 2 and 3). The stereochemistry
of the olefinic moiety was again unaffected in these
reactions. We applied the reaction of (E)-enynes to the
synthesis of a naphthalenone derivative. Thus, the cyclic
carbonyl enyne 5 cyclodimerized efficiently in the pres-
ence of Pd(PPh3)4 to give 6 in 72% yield (eq 4).
Resu lts
Ben za n n u la tion of Con ju ga ted (Z)-En yn es. (Z)-1-
Ethoxycarbonyl-1-butene-3-yne (1a ) cyclodimerized in the
presence of a catalytic amount of Pd(PPh3)4 to give the
1,3-disubstituted benzene (2a ) in good yield (Table 1,
entry 1). It is noteworthy that the reactivity of this enyne
was significantly higher compared to that of other alkyl
enynes,3,4 and the reaction proceeded smoothly at room
temperature. The stereochemistry of the olefinic moiety
was unaffected during the reaction, and we did not isolate
the regioisomeric (E)-styrene derivative from the reaction
mixture. The enhanced reactivity of enynes in the ben-
zannulation in the presence of an alkoxycarbonyl group
was also demonstrated in the reaction of 1,2-disubsti-
tuted enynes. Thus, the homo-benzannulation of (Z)-1-
ethoxycarbonyl-2-hexyl-1-butene-3-yne 1b also proceeded
smoothly in the presence of Pd(PPh3)4 at 80 °C to give
the 1,2,4-trisubstituted benzene 2b in 73% yield (Table
1, entry 2). When a cyano group was introduced in the
C-1 position of the enyne, a similar rate acceleration of
the reaction was observed, and the reaction of 1c
proceeded at 80 °C to give the 1,2,4-trisubstituted
benzene 2c (Table 1, entry 3). The homo-benzannulation
of enyne 1d bearing a dimethylaminocarbonyl group,
which is a less electron-withdrawing group, at the C-1
position proceeded smoothly (Table 1, entries 4 and 5).
However, the reactivity of the enyne 1d was much lower
compared to that of 1a , and it was necessary to carry
out the reaction at higher temperature for the complete
conversion in a short period.9
While 2,4-dialkylenynes did not undergo homo-ben-
zannulation, the reaction of an electron-deficient 2,4-
disubstituted enyne proceeded rapidly under very mild
conditions. Thus, the palladium-catalyzed cyclodimer-
ization of the methoxycarbonylenyne 7 proceeded at 30
°C to give the 1,2,3,5-tetrasubstituted benzene 8 in good
yield (eq 5). On the other hand, we previously reported
Ben za n n u la tion of Con ju ga ted (E)-En yn es a n d
2,4-Disu bstitu ted En yn es. The reactivity of (E)-enynes
was lower compared to that of (Z)-enynes in the homo-
benzannulation reaction. Thus, the homo-benzannulation
of the (E)-ethoxycarbonylenyne 3a proceeded in the
presence of Pd catalyst (Table 2, entry 1), though the
yield of the product 4a was lower (43%) and a higher
(6) (a) Gevorgyan, V.; Takeda, A.; Homma, M.; Sadayori, N.;
Radhakrishnan, U.; Yamamoto, Y. J . Am. Chem. Soc. 1999, 121, 6391-
6402. (b) Gevorgyan, V.; Sadayori, N.; Yamamoto, Y. Tetrahedron Lett.
1997, 38, 8603-8604.
(7) The enhanced reactivity of alkoxycarbonylenynes in the cross-
benzannulation was reported. See: ref 6.
(8) Preliminary results of this study have been communicated. See:
Saito, S.; Tsuboya, N.; Chounan, Y.; Nogami, T.; Yamamoto, Y.
Tetrahedron Lett. 1999, 40, 7529-7532.
(9) We monitored these reactions by TLC and quenched the reaction
when the starting material disappeared. Therefore, the results de-
scribed in Tables 1 and 2 would reflect the difference of the reactivity
of the enynes to some extent.
that the benzannulation of the cyanoenyne 9a and
perfluorohexylenyne 9b gave the expected polysubsti-
tuted benzenes 10a and 10b, respectively, together with

5352 J . Org. Chem., Vol. 65, No. 17, 2000
Saito et al.
the zipper annulated products 11a and 11b (eq 6).10 It
F igu r e 1. Electronic effects of the substitutents (electron-
withdrawing groups) on the enynes.
other benzannulation reactions, the reactivity of polysub-
stituted enynes was lower compared to that of monosub-
stituted enynes, probably because of steric effects.
A similar rate-acceleration effect was also observed in
the reactions of 1-cyanoenynes, 1-alkoxycarbonylenynes,
and 1-ketoenynes, in which only the benzannulation
products were obtained, whereas a rate-acceleration
effect and the formation of the zipper annulation products
(bicyclic compounds) were observed in the reaction of
2-cyanoenyne 9a and 2-perfluorohexylenyne 9b.10 The
formation of these bicyclic compounds might be explained
in terms of the different electronic properties of the
substituents present in the C-2 position. Thus, the
ethoxycarbonyl group has the relatively stronger conju-
gation effect (field value (F) ) 0.34, resonance value (R)
) 0.11),14 while the cyano group has the stronger induc-
tive effect (F ) 0.51) and a relatively weak resonance
effect (R ) 0.15).15 The perfluoroalkyl group also has a
similar electronic effect (F ) 0.42, R ) 0.06).14,15 The
difference of the electronic properties of the substituents
should play an important role in the reaction of 2-sub-
stituted enynes, and it is likely that the enyne with a
substituent that has a stronger field effect cyclodimerizes
to give the bicyclic compound in addition to the benzene
derivative in the presence of palladium catalysts. Con-
sidering the electronic structures of the enynes, the
activation of the C-1 and/or C-4 carbon might be impor-
tant for the benzannulation to proceed (Figure 1 (b)-(d)).
On the other hand, the activation of C-3 carbon might
be important for the zipper annulation to proceed (com-
pare Figure 1a and b).16 The nature of the electron-
withdrawing substituents had no influence on the reac-
tion pathway of 1-substituted enynes.
should be noted that a nearly 1:1 mixture of the ordinary
benzannulation product and nonordinary zipper annu-
lation product was obtained in the presence of Pd
catalyst, though the use of Ni catalyst resulted in the
formation of zipper annulation products in some reac-
tions.10
Discu ssion
On the basis of the results mentioned above, it is now
obvious that the reactivity of electron-deficient enynes
is much higher compared to that of alkylenynes: the very
mild condition (rt, 2 h) required for the cyclodimerization
of 1a is remarkable compared to the reaction conditions
required for the reaction of 2-substituted enynes and
4-substituted enynes (65 °C, 1 h3 or 100 °C, 24 h,4
respectively). Comparing the reaction conditions of 1a
and 1d (Table 1), we assume that the rate of the reaction
depends on the electron-withdrawing ability of the sub-
stituent: the reactivity of the less electron-deficient
enyne 1d was lower compared to that of more electron-
deficient 1a . Currently the precise mechanism of this
benzannulation is not clear, and therefore the role of the
electron-withdrawing group in the reaction is difficult to
understand. Since it has been shown that the interaction
of palladium(0) species with electron-deficient alkynes is
much stronger than that with electron-rich alkynes,11 the
increased reactivity of the enynes might be explained in
terms of stronger interaction of the electron-deficient
enynes with the Pd catalyst.
The isomerization of the less reactive (E)-enynes to
more reactive (Z)-enynes has been suggested as a possible
pathway for the benzannulation reaction.6 However, this
isomerization process is unlikely to occur during the
reaction, since the formation of a single isomer was
observed in all of the reactions we carried out. Further-
more, the successful benzannulation of the cyclic enyne
5 clearly shows that the isomerization of (E)-enyne to (Z)-
enyne is not a requirement for the reaction to proceed.
The reactions of (Z)-enynes proceeded under milder
conditions compared to those of (E)-enynes, probably
because the rate of the formal [1,3]-migration of the
hydrogen atom is quite different.12,13 As is the case for
(12) The rate of the reaction may also be controlled by the steric
effect. The lower yields of the products in the reaction of (E)-enynes
may be explained in terms of the formation of polymeric compounds.
(13) Exclusive hydrogen migration from E-position of conjugated
enynes has been reported in the cross-benzannulation reaction. See:
ref 6a.
(14) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165-
195.
(10) Saito, S.; Tanaka, T.; Koizumi, T.; Tsuboya, N.; Itagaki, H.;
Kawasaki, T.; Endo, S.; Yamamoto, Y. J . Am. Chem. Soc. 2000, 122,
1810-1811.
(11) Greaves, E. O.; Lock, C. J . L.; Maitlis, P. M. Can. J . Chem. 1968,
46, 3879-3891.
(15) Values of n-perfluoropropyl group.
(16) Though the C-2 carbon is most activated by the field effect of
the electron-withdrawing group attached to the C-2 position (Figure
1 (a), no intermolecular C-C bond between C-2 carbons was formed
in the zipper annulation.

Enhanced Reactivity of Electron-Deficient Enynes
J . Org. Chem., Vol. 65, No. 17, 2000 5353
cm-1; HRMS calcd for C7H9NO 123.0684, found 123.0687.
Anal. Calcd for C7H9NO: C, 68.27; H, 7.37; N, 11.37. Found:
C, 67.99; H, 7.55; N, 11.18.
In summary, we found that some electron-deficient
enynes are highly reactive substrates for the palladium-
catalyzed homo-benzannulation. We succeeded in extend-
ing the scope of the benzannulation reaction, and some
disubstituted enynes also cyclodimerized in the presence
of a Pd catalyst. Useful functional groups such as cyano
group and alkoxycarbonyl group were introduced to the
benzene ring under mild conditions. This reaction pro-
vides another efficient method for the regioselective
synthesis of functionalized polysubstituted benzenes.
(E)-3-Hexyl-p en t-2-en -4-yn oic a cid eth yl ester (3b): pale
1
yellow oil; H NMR (270 MHz, CDCl3) δ 6.10 (s, 1H), 4.15 (q,
2H, J ) 7.2 Hz), 3.15 (s, 1H), 2.71 (t, 2H, J ) 7.7 Hz), 1.56
(quint, 2H, J ) 7.5 Hz), 1.2-1.6 (m, 9H), 0.86 (t, 3H, J ) 6.7
Hz); 13C NMR (67.8 MHz, CDCl3) δ 165.5, 141.8, 125.7, 84.3,
81.6, 60.1, 32.0, 31.6, 28.9, 28.3, 22.6, 14.2, 14.0; IR (neat) 3304,
2959, 2930, 2860, 2097, 1717, 1614, 1466, 1369, 1219, 1178,
1146, 1038, 878, 635 cm-1; HRMS calcd for C13H20O2 208.1463,
found 208.1476. Anal. Calcd for C13H20O2: C, 74.96; H, 9.68.
Found: C, 74.94; H, 9.52.
1
Exp er im en ta l Section
(E)-3-P en tyl-p en t-2-en -4-yn en itr ile (3c): yellow oil; H
NMR (270 MHz, CDCl3) δ 5.56 (s, 1H), 3.40 (s, 1H), 2.47 (t, J
) 7.6 Hz, 2H), 1.64-1.55 (m, 2H), 1.33-1.28 (m, 4H), 0.88 (t,
J ) 6.9 Hz, 3H); 13C NMR (67.8 MHz, CDCl3) δ 146.7, 115.7,
105.0, 86.3, 81.3, 35.4, 30.8, 27.4, 22.3, 13.8; IR (neat) 3292,
3059, 2959, 2932, 2862, 2220, 2098, 1589, 1466, 1458, 1379,
1339, 827, 650 cm-1; HRMS calcd for C10H13N 147.1047, found
147.1044. Anal. Calcd for C10H13N: C, 81.59; H, 8.90; N, 9.51.
Found: C, 81.19; H, 8.82; N, 9.28.
2-Meth ylen e-oct-3-yn oic a cid m eth yl ester (7): colorless
oil; 1H NMR (270 MHz, CDCl3) δ 6.50 (d, J ) 1.5 Hz, 1H),
5.99 (dt, J ) 1.5 Hz, 0.7 Hz, 1H), 3.80 (s, 3H), 2.37 (t, J ) 7.0
Hz, 2H), 1.63-1.36 (m, 4H), 0.93 (t, J ) 7.3 Hz, 3H); 13C NMR
(67.8 MHz, CDCl3) δ 165.1, 132.9, 124.2, 93.9, 76.6, 52.6, 30.5,
22.0, 19.1, 13.6; IR (neat) 2957, 2932, 2359, 1736, 1435, 1213
cm-1; HRMS calcd for C10H14O2: 166.0994, found 166.0978.
Because of the limited stability of 7, we carried out the
benzannulation reaction without completely removing the
impurity.
Rep r esen ta tive P r oced u r e for th e P a lla d iu m -Ca ta -
lyzed Ben za n n u la tion of Electr on -Deficien t En yn es. To
a yellow solution of Pd(PPh3)4 (11.6 mg, 0.01 mmol) in dry
toluene (1.0 mL) was added 1c (73.6 mg, 0.5 mmol) at room
temperature, and the mixture was stirred at 80 °C for 1 h
under Ar. The mixture was passed through a short alumina
column (ether) and evaporated. The residue was further
purified by column chromatography (silica gel, hexane/ethyl
acetate ) 20:1) to give 2c as a yellow oil (57.4 mg, 0.78 mmol,
78%). The reaction conditions and the isolated yields for the
reaction of 1, 3, 5, and 7 are described in Tables 1 and 2 and
eqs 5 and 6.
5-((Z)-2-E t h oxyca r b on yl-1-h exylvin yl)-2-h exylb en zo-
ic a cid eth yl ester (2a ): pale yellow oil; 1H NMR (270 MHz,
CDCl3) δ 8.15 (bs, 1H), 8.00 (bd, J ) 8.1 Hz, 1H), 7.80 (bd, J
) 7.7 Hz, 1H), 7.42 (t, J ) 7.7 Hz, 1H), 6.98 (d, J ) 12.5 Hz,
1H), 6.01 (d, J ) 12.5 Hz, 1H), 4.38 (q, J ) 7.0 Hz, 2H), 4.17
(q, J ) 7.0 Hz, 2H), 1.39 (t, J ) 7.0 Hz, 3H), 1.23 (t, J ) 7.0
Hz, 3H); 13C NMR (67.8 MHz, CDCl3) δ 166.2, 165.9, 141.8,
135.2, 133.6, 130.7, 130.3, 129.8, 128.0, 121.1, 61.0, 60.4, 14.3,
14.0. IR (neat) 1717, 1633, cm-1; HRMS calcd for C14H16O4
248.1048, found 248.1055. Anal. Calcd for C14H16O4: C, 67.73;
H, 6.50. Found: C, 67.59; H, 6.51.
Syn th esis of th e Con ju ga ted En yn es. Monosubstituted
enynes 1a ,17 1d , and 3a 17 were prepared by the Sonogashira
reaction18 of (Z)-ethyl 3-bromopropenate,19 (E)-ethyl 3-bro-
mopropenate,19 or (Z)-2-bromopropenoic acid dimethylamide20
with (trimethylsilyl)acetylene, followed by the removal of the
trimethylsilyl group (KF/MeOH). The synthesis of 1,2-disub-
stituted enynes 1b and 3b was carried out by the Horner-
Wadsworth-Emmons reaction of the (trimethylsilyl)ethynyl
ketones21 with triethyl phosphonoacetate,22 isolation of the
isomers by column chromatography, and deprotection (KF/
MeOH). The synthesis of 1,2-disubstituted enynes 1c and 3c
was carried out by the Horner-Wadsworth-Emmons reaction
of the ethynyl ketones23 with diethyl (cyanomethyl)phospho-
nate,22 and isolation of the isomers by column chromatography.
Cyclic ketoenyne 523 was prepared according to the published
method. The synthesis of 7 was carried out by the Sonogashira
reaction18 of methyl 1-bromovinylacrylate25 with 1-hexyne.
Compound 7 has limited stability, and the polymerization
proceeded easily in the absence of a radical inhibitor such as
BHT (2,6-di-tert-butyl-4-methylphenol).
(Z)-3-H exyl-p en t -2-en -4-yn oic a cid et h yl est er (1b ):
yellow oil; 1H NMR (270 MHz, CDCl3) δ 6.03 (m, 1H), 4.17 (q,
J ) 7.1 Hz, 2H), 3.57 (d, J ) 0.7 Hz, 1H), 2.25 (ddd, J ) 7.5,
7.5, 1.0 Hz, 2H), 1.56 (quint, J ) 7.1 Hz, 2H), 1.2-1.3 (m, 9H),
0.85 (t, J ) 6.8 Hz, 3H); 13C NMR (67.8 MHz, CDCl3) δ 164.8,
138.6, 125.7, 88.4, 81.2, 60.2, 38.7, 31.5, 28.5, 27.7, 22.5, 14.2,
14.0; IR (neat) 3256, 2957, 2932, 2860, 2095, 1732, 1622, 1456,
1373, 1350, 1283, 1205, 1142, 1099, 1040, 862, 640 cm-1
;
HRMS calcd for C13H20O2 208.1463, found 208.1467. Anal.
Calcd for C13H20O2: C, 74.96; H, 9.68. Found: C, 74.64; H,
9.35.
1
(Z)-3-P en tyl-p en t-2-en -4-yn en itr ile (1c): yellow oil; H
NMR (300 MHz, CDCl3) δ 5.53 (m, 1H), 3.62 (s, 1H), 2.30 (ddd,
J ) 7.6, 7.6, 1.4 Hz, 2H), 1.63-1.53 (m, 2H), 1.37-1.26 (m,
4H), 0.90 (t, J ) 6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
146.4, 116.2, 104.5, 88.4, 79.8, 37.2, 30.8, 27.2, 22.2, 13.8; IR
(neat) 3298, 3057, 2959, 2932, 2862, 2222, 2098, 1684, 1593,
1466, 1458, 1379, 1169, 1101, 818, 648 cm-1; HRMS calcd for
C
10H13N 147.1047, found 147.1058.
(Z)-P en t-2-en -4-yn oic a cid d im eth yla m id e (1d ): yellow
1
oil; H NMR (300 MHz, CDCl3) δ 6.43 (d, J ) 11.9 Hz, 1H),
5.84 (dd, J ) 11.7, 2.6 Hz, 1H), 3.28 (d, J ) 2.6 Hz, 1H), 3.04
(s, 3H), 3.00 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 166.0, 134.2,
115.0, 85.2, 79.4, 37.5, 34.7; IR (neat) 3217, 2934, 1634, 706
5-((Z)-2-E t h oxyca r b on yl-1-h exylvin yl)-2-h exylb en zo-
ic a cid eth yl ester (2b): yellow oil; 1H NMR (270 MHz,
CDCl3) δ 7.65 (m, 1 H), 7.21 (m, 2 H), 5.88 (m, 1 H), 4.34 (q, J
) 7.3 Hz, 2 H), 3.98 (q, J ) 7.3 Hz, 2 H), 2.97-2.91 (m, 2 H),
2.45-2.40 (m, 2 H), 1.62-1.54 (m, 2 H), 1.41-1.25 (m, 15 H),
1.05 (t, J ) 7.3 Hz), 0.91 - 0.84 (m, 6 H); 13C NMR (CDCl3,
67.8 MHz) δ 167.7, 166.0, 158.7, 144.0, 137.6, 130.7, 130.3,
129.4, 129.2, 117.6, 60.8, 59.8, 40.3, 34.4, 31.8, 31.78, 31.5, 29.5,
28.7, 27.3, 22.7, 22.5, 14.3, 14.1, 14.0, 13.9; IR (neat) 1722,
1639 cm-1; HRMS calcd for C26H40O4 416.2926, found 416.2915.
5-((Z)-2-Cya n o-1-p e n t ylvin yl)-2-p e n t ylb e n zon it r ile
(17) Barrett, A. G. M.; Hampercht, D.; Okubo, M. J . Org. Chem.
1997, 62, 9376-9378.
(18) Brandsma, L.; Vasilevsky, S. F.; Verkruijsse, H. D. Application
of Transition Metal Catalysts in Organic Synthesis; Springer: Berlin,
1999; pp 210-213.
(19) Weir, J . R.; Patel, B. A.; Heck, R. F. J . Org. Chem. 1980, 45,
4926-4931.
(20) Ma, S.; Lu, X.; Li, Z. J . Org. Chem. 1992, 57, 709-713. We
prepared 1d by the reaction of ethyl (E)-2-bromoacrylate with dim-
ethylamine.
1
(2c): yellow oil; H NMR (300 MHz, CDCl3) δ 7.62-7.59 (m,
2H), 7.38 (d, J ) 7.9 Hz, 1H), 5.43 (s, 1H), 2.85 (t, J ) 7.6 Hz,
2H), 2.53 (t, J ) 6.9 Hz, 2H), 1.71-1.66 (m, 2H), 1.40-1.26
(m, 10H), 0.92-0.83 (m, 6H); 13C NMR (75 MHz, CDCl3) δ
163.6, 148.1, 135.8, 131.6, 131.1, 129.9, 117.4, 116.8, 112.9,
96.5, 37.8, 34.4, 31.3, 31.0, 30.3, 27.1, 22.3, 22.2, 13.9, 13.8;
IR (neat) 2224, 1612 cm-1; HRMS calcd for C20H26N2 294.2095,
found 294.2097. Anal. Calcd for C20H26N2: C, 81.59; H, 8.90;
N, 9.51. Found: C, 81.55; H,8.95; N, 9.38.
(21) Brandsma, L. Preparative Acetylenic Chemistry, 2nd ed.; Elsevi-
er: Amsterdam, 1988; pp 105-107.
(22) Pettit, G. R.; Dias, J . R. J . Org. Chem. 1971, 36, 3207-3211.
(23) Brandsma, L. Preparative Acetylenic Chemistry, 2nd ed.; Elsevi-
er: Amsterdam, 1988 pp 281-282.
(24) Cheng, M.; Hulce, M. J . Org. Chem. 1990, 55, 964-975.
(25) Rachon, J .; Goedken, V.; Walborsky, H. M. J . Org. Chem. 1989,
54, 1006-1012.

5354 J . Org. Chem., Vol. 65, No. 17, 2000
Saito et al.
3-((Z)-2-Dim et h ylca r b a m oylvin yl)-N,N-d im et h ylb en -
za m id e (2d ): red purple oil; 1H NMR (300 MHz, CDCl3) δ
7.36-7.31 (m, 4H), 6.61 (d, J ) 12.6 Hz, 1H), 6.08 (d, J ) 12.5
Hz, 1H), 3.08 (s, 3H), 2.96 (s, 3H), 2.94 (s, 3H), 2.85 (s, 3H);
13C NMR (67.8 MHz, CDCl3) δ 170.9, 168.4, 136.6, 135.4, 132.4,
129.0, 128.5, 126.9, 126.7, 124.2, 39.4, 37.4, 35.2, 34.3; IR (neat)
2932, 1684, 1393, 750 cm-1; HRMS calcd for C14H18N2O2
246.1368, found 246.1370.
1H), 5.51 (s, 1H), 2.84 (t, J ) 7.7 Hz, 4H), 1.70-1.65 (m, 2H),
1.45-1.29 (m, 10H), 0.92-0.84 (m, 6H); 13C NMR (75 MHz,
CDCl3) δ 162.6, 148.6, 136.0, 130.35, 130.28, 130.1, 117.4,
116.7, 113.2, 96.9, 34.3, 33.6, 31.3, 31.2, 30.4, 28.0, 22.3, 22.2,
13.9, 13.8; IR (neat) 2860, 2216, 1603 cm-1; HRMS calcd for
C
20H26N2 294.2095, found 294.2096. Anal. Calcd for C20H26N2:
C, 81.59; H, 8.90; N, 9.51. Found: C, 81.63; H, 9.20; N, 9.38.
3,5-Dibu tyl-4-(1-m eth oxyca r bon ylvin yl)ben zoic a cid
m eth yl ester (8): pale yellow oil; 1H NMR (CDCl3, 270 MHz)
δ 7.74 (s, 2H), 6.71 (d, J ) 1.7 Hz, 1H), 5.62 (d, J ) 1.7 Hz,
1H), 3.91 (s, 3H), 3.73 (s, 3H), 2.59-2.37 (m, 4H), 1.57-1.21
(m, 8 H), 0.89 (t, J ) 7.2 Hz, 6H); 13C NMR (CDCl3, 67.8 MHz)
δ 167.3, 166.9, 141.5, 140.5, 138.6, 129.9, 129.4, 127.4, 52.3,
52.0, 33.4, 33.1, 22.7, 13.9; IR (neat) 1724, 1435 cm-1; HRMS
calcd for C20H28O4 332.1987, found 332.1991.
7-(3-Oxocycloh ex-1-en yl)-3,4-d ih yd r o-2H-n a p h th a len -
1-on e (10): colorless powder, mp 71-74 °C; 1H NMR (270
MHz, CDCl3) δ 8.21 (d,J ) 2.2 Hz, 1H) 7.66 (dd, J ) 2.2, 8.1
Hz, 1H), 7.32 (d, J ) 8.1 Hz, 1H), 6.44 (t, J ) 1.5 Hz, 1H),
3.01 (t, J ) 6.1 Hz, 2H), 2.80 (ddd, J ) 1.5, 6.1, 6.1 Hz, 2H),
2.69 (t, J ) 6.1 Hz, 2H), 2.50 (t, J ) 6.2 Hz, 2H), 2.17 (m, 4
H); 13C NMR (67.8 MHz, CDCl3) δ 199.8, 197.9, 158.6, 146.2,
137.2, 132.7, 130.6, 129.5, 125.6, 124.9, 39.0, 37.2, 29.6, 28.0,
23.0, 22.7; IR(KBr) 1670, 1600, 1409, 1328, 1257, 1203, 1178
cm-1; HRMS calcd for C16H16O2 240.1150, found 240.1148.
Anal. Calcd for C16H16O2: C, 79.97; H, 6.71. Found: C, 79.96;
H, 6.87.
3-((Z)-2-Eth oxyca r bon ylvin yl)ben zoic a cid eth yl ester
1
(4a ): pale yellow oil; H NMR (270 MHz, CDCl3) δ 8.21 (bs,
1H), 8.05 (ddd, J ) 7.7 Hz, 1.3 Hz, 1.5 Hz, 1H), 7.72 (d, J )
15.8 Hz, 1H), 7.72-7.76 (m, 1H), 7.47 (dd, J ) 7.7 Hz, 7.7 Hz,
1H), 6.52 (d, J ) 15.8 Hz, 1H), 4.40 (q, J ) 7.0 Hz, 2H), 4.28
(q, J ) 7.0 Hz, 2H), 1.41 (t, J ) 7.0 Hz, 3H), 1.35 (t, J ) 7.0
Hz, 3H); 13C NMR (67.8 MHz, CDCl3) δ 166.7, 166.0, 143.4,
134.8, 132.1, 131.3, 131.0, 128.98, 128.95, 119.6, 61.3, 60.7,
14.34, 14.32; IR (neat) 1717, 1641 cm-1; HRMS calcd for
C14H16O4 248.1048, found 248.1053. Anal. Calcd for C14H16O4:
C, 67.73; H, 6.50. Found: C, 67.53; H, 6.59.
5-((E)-2-E t h oxyca r b on yl-1-h exylvin yl)-2-h exylb en zo-
ic a cid eth yl ester (4b): pale yellow oil; 1H NMR (CDCl3,
270 MHz) δ 7.90 (d, J ) 2.0 Hz, 1H), 7.47 (dd, J ) 2.0, 8.1 Hz,
1 H), 7.24 (d, J ) 8.1 Hz, 1H), 6.03 (s, 1H), 4.38 (q, J ) 7.1
Hz, 2H), 4.21 (q, J ) 7.1 Hz, 2H), 3.10-3.05 (m, 2H), 3.00-
2.90 (m, 2H), 1.64-1.54 (m, 4H), 1.43-1.25 (m, 18H), 0.93-
0.82 (m, 6H); 13C NMR (CDCl3, 67.8 MHz) δ 167.71, 166.45,
159.66, 145.12, 138.82, 131.12, 130.28, 129.60, 128.70, 117.29,
61.03, 59.88, 34.29, 31.75, 31.72, 31.56, 30.84, 29.45, 29.40,
29.02, 22.63, 22.58, 14.34, 14.32, 14.09, 14.04. IR (neat) 1717,
1624 cm-1; HRMS calcd for C26H40O4 416.2926, found 416.2916.
5-((E )-2-Cya n o-1-p e n t ylvin yl)-2-p e n t ylb e n zon it r ile
(4c): yellow oil; 1H NMR (300 MHz, CDCl3) δ 7.62 (d, J ) 2.0
Hz, 1H), 7.52 (dd, J ) 8.2, 2.0 Hz, 1H), 7.36 (d, J ) 8.2 Hz,
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
compounds 1c, 2b, 2d , 4b, 7, and 8 (PDF). This material is
available free of charge via the Internat at http://pubs.acs.org.
J O0006876