α-Vinylation of 1,3-Dicarbonyl Compounds with Alkenyl(aryl)iodonium Tetrafluoroborates: Effects of Substituents on the Aromatic Ring and of Radical Inhibitors

Article abstract of DOI:10.1021/jo962007y

Direct α-vinylations of enolate anions derived from 1,3-dicarbonyl compounds with 4-teri-butyl-1- cyclohexenyl(aryl)iodonium 2 and 1-cyclopentenyl(aryl)iodonium tetrafluoroborates 3 are reported. Frequently, α-phenylations compete with the vinylations in the reaction of 1,3-dicarbonyl compounds with alkenyl(phenyl)iodonium salts 2a and 3a. Use of alkenyl(p-methoxyphenyl)iodonium salts 2b and 3b, however, leads to selective α-vinylation at the expense of the competing arylation of 1,3-dicarbonyl compounds. Use of an efficient aryl radical trap, 1,1-diphenylethylene, inhibits radical-induced decomposition of the alkenyl(aryl)iodonium salts, thereby improving the yields of α-vinylations of enolate anions derived from 1,3-dicarbonyl compounds.

Full text of DOI:10.1021/jo962007y

2130
J . Org. Chem. 1997, 62, 2130-2138
r-Vin yla tion of 1,3-Dica r bon yl Com p ou n d s w ith
Alk en yl(a r yl)iod on iu m Tetr a flu or obor a tes: Effects of Su bstitu en ts
on th e Ar om a tic Rin g a n d of Ra d ica l In h ibitor s
Masahito Ochiai,* Toshifusa Shu, Takema Nagaoka, and Yutaka Kitagawa
Faculty of Pharmaceutical Sciences, University of Tokushima, 1-78 Shomachi, Tokushima 770, J apan
Received October 28, 1996X
Direct R-vinylations of enolate anions derived from 1,3-dicarbonyl compounds with 4-tert-butyl-1-
cyclohexenyl(aryl)iodonium 2 and 1-cyclopentenyl(aryl)iodonium tetrafluoroborates 3 are reported.
Frequently, R-phenylations compete with the vinylations in the reaction of 1,3-dicarbonyl compounds
with alkenyl(phenyl)iodonium salts 2a and 3a . Use of alkenyl(p-methoxyphenyl)iodonium salts
2b and 3b, however, leads to selective R-vinylation at the expense of the competing arylation of
1,3-dicarbonyl compounds. Use of an efficient aryl radical trap, 1,1-diphenylethylene, inhibits
radical-induced decomposition of the alkenyl(aryl)iodonium salts, thereby improving the yields of
R-vinylations of enolate anions derived from 1,3-dicarbonyl compounds.
Simple unactivated vinyl halides tend to be nonreactive
elegant synthesis of (+)-isocarbacyclin relied on this
direct vinylation of â-keto esters as a key step.11
in bimolecular displacement reactions and, consequently,
fail to react with metal enolates under standard experi-
mental conditions.1,2 Multistep R-vinylations of metal
enolates using a masked vinyl cation equivalent as an
electrophile are now possible3 because of the availability
of such electrophiles as R-trimethylsilyl aldehydes,4
R-phenylseleno aldehydes,5 and enol ethers.6
Recently, Pinhey and co-workers demonstrated that
alkenyllead tricarboxylates, generated in situ by a metal
(Hg, Sn, or Zn)-lead (Pb) exchange reaction, served as
useful reagents for the R-vinylation of carbonyl com-
pounds.7 Alkenyllead triacetates are highly labile and
undergo relatively fast reductive elimination of lead(II)
acetate, yielding an alkyne or an enol acetate.8,9 Rapid
generation of alkenyllead triacetates (<2 min in most
cases), however, makes the R-vinylation of carbonyl
compounds possible.10 Ikegami and Hashimoto in their
Because of an excellent nucleofugality of a phenyli-
odonio group, which shows a leaving group ability about
106 times greater than triflate,12 alkenyl(phenyl)iodonium
salts serve as the highly activated species of alkenyl
halides in nucleophilic vinylic substitution reactions with
a number of nucleophiles, such as organocuprates, sul-
finates, thiolates, nitrites, halides, cyanides, azides, and
phosphines.13-16 Few studies of the reaction of alken-
ylphenyliodonium salts with enolate anions are available.
Vinylation of the sodium enolate of 2-phenyl-1,3-indan-
dione (4a ) with (2-chloro-2-phenylethenyl)iodonium tet-
rafluoroborate has been reported by Beringer and Galton
to give 2-(2-chloro-2-phenylethenyl)-2-phenyl-1,3-indan-
dione in 67% yield.17 We have already reported the
reaction of 2-hexyl-1,3-indandione with (4-tert-butyl-1-
cyclohexenyl)phenyliodonium tetrafluoroborate (2a ) in
the presence of potassium tert-butoxide in THF, which
affords 2-(4-tert-butyl-1-cyclohexenyl)-2-hexyl-1,3-indan-
dione in 64% yield.13a We now report in detail the scope
and the limitation of this direct R-vinylation of â-dicar-
bonyl compounds with alkenyl(aryl)iodonium salts. Also
presented here are substituent effects of alkenyl(aryl)-
iodonium salts on selectivity of vinylation versus aryla-
tion as well as the effects of radical inhibitors.
* Address correspondence to: Masahito Ochiai, Faculty of Pharma-
ceutical Sciences, University of Tokushima, 1-78 Shomachi, Tokushima
770, J apan. Tel: 886-33-5187. Fax: 886-33-5187. E-mail: mochiai@
ph.tokushima-u.ac.jp.
X Abstract published in Advance ACS Abstracts, March 1, 1997.
(1) Caine, D. Carbon-Carbon Bond Formation; Marcel Dekker: New
York, 1979; Chapter 2.
(2) Enolate anions undergo photostimulated reaction with vinyl
halides to give R-vinylated products by SRN1 mechanism. See: Bun-
nett, J . F.; Creary, X.; Sundberg, J . E. J . Org. Chem. 1976, 41,
1707.
(3) For transition metal-catalyzed direct R-vinylations of enolates,
see: (a) Millard, A. A.; Rathke, M. W. J . Am. Chem. Soc. 1977, 99,
4833. (b) Kosugi, M.; Hagiwara, I.; Sumiya, T.; Migita, T. Bull. Chem.
Soc. J pn. 1984, 57, 242. (c) Fauvarque, J . F.; J utland, A. J . Organomet.
Chem. 1979, 177, 273.
(4) Hudrlik, P. F.; Kulkarni, A. K. J . Am. Chem. Soc. 1981, 103,
6251.
(5) (a) Kowalski, C. J .; Dung, J .-S. J . Am. Chem. Soc. 1980, 102,
7950. (b) Clive, D. L. J .; Russell, C. G. J . Chem. Soc., Chem. Commun.
1981, 434.
(6) (a) Chang, T. C. T.; Rosenblum, M.; Samuels, S. B. J . Am. Chem.
Soc. 1980, 102, 5930. (b) Chang, T. C. T.; Rosenblum, M. J . Org. Chem.
1981, 46, 4103.
(10) For reviews, see: Pinhey, J . T. Aust. J . Chem. 1991, 44, 1353.
(11) Hashimoto, S.-I.; Shinoda, T.; Ikegami, S. J . Chem. Soc., Chem.
Commun. 1988, 1137.
(12) Okuyama, T.; Takino, T.; Sueda, T.; Ochiai, M. J . Am. Chem.
Soc. 1995, 117, 3360.
(13) (a) Ochiai, M.; Sumi, K.; Takaoka, Y.; Kunishima, M.; Nagao,
Y.; Shiro, M.; Fujita, E. Tetrahedron 1988, 44, 4095. (b) Ochiai, M.;
Sumi, K.; Nagao, Y.; Shiro, M.; Fujita, E. Tetrahedron Lett. 1985, 26,
2351.
(14) Ochiai, M.; Oshima, K.; Masaki, Y. J . Am. Chem. Soc. 1991,
113, 7059.
(15) (a) Ochiai, M.; Oshima, K.; Masaki, Y. Tetrahedron Lett. 1991,
32, 7711. (b) Ochiai, M.; Oshima, K.; Masaki, Y.; Kunishima, M.; Tani,
S. Tetrahedron Lett. 1993, 34, 4829. (c) Ochiai, M.; Oshima, K.;
Masaki, Y. Chem. Lett. 1994, 871. (d) Zefirov, N. S.; Kozmin, A. S.;
Kasumov, T.; Potekhin, K. A.; Sorokin, V. D.; Brel, V. K.; Abramkin,
E. V.; Struchkov, Y. T.; Zhdankin, V. V.; Stang, P. J . J . Org. Chem.
1992, 57, 2433.
(16) For reviews, see: (a) Koser, G. F. The Chemistry of Functional
Groups, Supplement D; Wiley: New York, 1983; Chapter 25. (b)
Varvoglis, A. The Chemistry of Polycoordinated Iodine; VHC Publish-
ers: New York, 1992. (c) Stang, P. J . Angew. Chem., Int. Ed. Engl.
1992, 31, 274. (d) Koser, G. F. The Chemistry of Functional Groups,
Supplement D2; Wiley: New York, 1995. (e) Stang, P. J .; Zhdankin,
V. V. Chem. Rev. 1996, 96, 1123.
(7) (a) Parkinson, C. J .; Pinhey, J . T.; Stoermer, M. J . J . Chem. Soc.,
Perkin Trans. 1 1992, 1911. (b) Moloney, M. G.; Pinhey, J . T. J . Chem.
Soc., Chem. Commun. 1984, 965. (c) Moloney, M. G.; Pinhey, J . T. J .
Chem. Soc., Perkin Trans.
1 1988, 2847. (d) Hashimoto, S.-I.;
Miyazaki, Y.; Shinoda, T.; Ikegami, S. Tetrahedron Lett. 1989, 30, 7195.
(8) (a) Corey, E. J .; Wollenberg, R. H. J . Am. Chem. Soc. 1974, 96,
5581. (b) Larock, R. C.; Oertle, K.; Beatty, K. M. J . Am. Chem. Soc.
1980, 102, 1966. (c) Moloney, M. G.; Pinhey, J . T.; Stoermer, M. J . J .
Chem. Soc., Perkin Trans. 1 1990, 2645. (d) Pinhey, J . T.; Stoermer,
M. J . J . Chem. Soc., Perkin Trans. 1 1991, 2455.
(9) Isolation of vinyllead triacetates is very difficult; however,
evidences for the formation of vinyllead triacetates by metal-Pb
exchange are obtained from a 1H NMR spectroscopic study.7c,8b
(17) Beringer, F. M.; Galton, S. A. J . Org. Chem. 1965, 30, 1930.
S0022-3263(96)02007-5 CCC: $14.00 © 1997 American Chemical Society

R-Vinylation of 1,3-Dicarbonyl Compounds
J . Org. Chem., Vol. 62, No. 7, 1997 2131
Ta ble 1. Rea ction of 1,3-Dica r bon yl a n d Rela ted
Sch em e 1
Com p ou n d s w ith Alk en yl(p h en yl)iod on iu m Sa lts 2a a n d
3a a
product (yield,b %)
iodonium time,
entry substrate
salt
h
vinylation phenylation ratioc
1
2
3
4
5
6
7
8
9
4a
5a
6a
7a
8a
2a
2a
2a
2a
2a
2a
2a
2a
2a
3a
3a
4
1
56
4
1
26
4b (86)
5b (86)
6b (14)
7b (47)
8b (19)d
9b (46)e
4c (1)
5c (10)
6c (0)
7c (0)
8c (8)
9c (19)
10c (7)
11c (0)
12c (48)
4c (64)
5c (29)
99:1
90:10
100:0
100:0
71:29
71:29
88:12
100:0
43:57
33:67
50:50
9a
10a
11a
12a
4a
2.5 10b (53)f
23
2
20
44
11b (86)
12b (36)
4d (32)
5d (29)
10
11
5a
a
Reactions were carried out at room temperature under argon.
Isolated yields. c Ratios of vinylation versus phenylation. A 2:1
b
d
Resu lts a n d Discu ssion
mixture of diastereoisomers. e A 4:1 mixture of diastereoisomers.
f A 1:1 mixture of diastereoisomers.
Syn th esis of Alk en yl(a r yl)iod on iu m Tetr a flu or o-
bor a tes. 4-tert-Butyl-1-cyclohexenyl(aryl)iodonium tet-
rafluoroborates 2 were prepared by the BF3-catalyzed
silicon-iodine(III) exchange reaction of 4-tert-butyl-1-
(trimethylsilyl)cyclohexene18 with iodosylbenzene (1a ),
p-methoxyiodosylbenzene (1b), or p-chloroiodosylbenzene
(1c), as described previously.12,13 In general, purification
of 2 was carried out by recrystallization in dichloro-
methane-hexane (or diethyl ether): 2a , 96%; 2b, 83%;
2c, 44%. The BF3-catalyzed exchange reaction of 1-(tri-
methylsilyl)cyclopentene18 with iodosylarenes 1a and 1b
afforded 1-cyclopentenyliodonium salts 3a (81%) and 3b
(73%), respectively (Scheme 1). 1-Cyclohexenyliodonium
salts 2 are relatively labile and, therefore, should be kept
below 0 °C. 1-Cyclopentenyliodonium salts 3, however,
remain stable for more than 1 month at ambient tem-
perature. The very high nucleofugality of aryliodonio
groups has been measured by kinetic studies of solvolysis
of 2, which generates 1-cyclohexenyl cation.12 Thus, the
reduced stability of 2 as compared with 3 would appear
to reflect its tendency to dissociate to the corresponding
vinyl cation, i.e., 1-cyclohexenyl cation. Generation of
1-cyclopentenyl cation has not been observed, probably
because of its high energy.19
longed treatment, gave 6b in only 14% yield (Table 1,
entry 3). It is to be noted that in the reaction with
enolate anions of â-keto esters 8a , 9a , and 10a , which
afforded diastereoisomeric mixtures of R-vinylation prod-
ucts, the competing side reaction became serious and the
undesired R-phenylation products were obtained in 7-19%
yields (Table 1, entries 5-7). This situation also held
true for the reaction with nitrocyclohexane (12a ) with
2a , in which R-phenylation was found to be a relatively
major reaction process. Cyclopentenylation of â-dike-
tones 4a and 5a with cyclopentenyl(phenyl)iodonium salt
3a showed a similar tendency and produced a large
amount of phenylation products 4c and 5c. Furthermore,
compared to the reaction of 2a , a longer reaction time
was required for the cyclopentenylation using 3a (Table
1, entries 1, 2, 10, and 11). The structure of 5b was
determined by spectroscopy using two-dimensional (2D)
NMR techniques, i.e., H, H-COSY, 13C, H-COSY, and
nuclear Overhauser enhancement spectroscopy (NOESY),
which indicated that the nucleophilic substitution of
vinyliodonium salt 2a with 5a takes place regioselectively
at the vinylic ipso position.
1
1
1
Rea ction of Cycloh exen yl- (2a ) a n d Cyclop en ten -
ylp h en yliod on iu m Sa lts (3a ). Exposure of the potas-
sium enolate (1.1 equiv) of 2-phenyl-1,3-indandione (4a ),
generated by the reaction with freshly sublimed potas-
sium tert-butoxide in THF for 1 h at room temperature
under argon, to cyclohexenyl(phenyl)iodonium salt 2a (1
equiv) for 4 h at room temperature resulted in nucleo-
philic vinylic substitutions at the ipso position. This
direct R-vinylation of the â-diketone gave 2-(4-tert-butyl-
1-cyclohexenyl)-2-phenyl-1,3-indandione (4b) in 86% yield.
Formation of a trace amount of R-phenylation product
4c (1%) was also detected in this reaction. The results
of direct R-vinylation of 1,3-dicarbonyl compounds with
cyclohexenyl-(2a) and cyclopentenyl(phenyl)iodonium salts
(3a ) are summarized in Table 1.
This nucleophilic vinylic substitution of 2a with â-di-
carbonyl compounds is very sensitive to the nature of the
enolate anions. With indandiones 4a and 5a , the R-vi-
nylation occurred smoothly, whereas the reaction with
1,3-cyclopentanedione 6a was sluggish and, after pro-
(18) Paquette, L. A.; Fristad, W. E.; Dime, D. S.; Bailey, T. R. J .
Org. Chem. 1980, 45, 3017.
(19) (a) Hanack, M.; Bentz, H.; Markl, R.; Subramanian, L. R.
Liebigs Ann. Chem. 1978, 1894. (b) Pfeifer, W. D.; Bahn, C. A.;
Schleyer, P. R.; Bocher, S.; Harding, C. E.; Hummel, K.; Hanack, M.;
Stang, P. J . J . Am. Chem. Soc. 1971, 93, 1513.
Not unexpectedly, â-diketones with an active methyl-
ene group undergo divinylation by reaction with vinyli-

2132 J . Org. Chem., Vol. 62, No. 7, 1997
Ochiai et al.
Sch em e 2
Sch em e 4
Ta ble 2. Effects of Su bstitu en ts on th e Ar om a tic Rin g of
Alk en yl(a r yl)iod on iu m Sa lts 2 a n d 3
conditions
Sch em e 3
iodonium
salt
temp,
°C
time,
h
product
entry
substrate
(yield,a %)
1
2
3
4
5
6
7
8
9
5a
9a
9a
10a
10a
10a
12a
4a
2b
2b
2c
2b
2b
2c
2b
3b
3b
25
50
25
25
50
25
50
50
50
35
9
1
38
2.5
69
24
3
5b (72)
9b (61)b
9b (44)b
10b (51)c
10b (60)c
10b (36)c
12b (34)d
4d (51)e
5d (51)
odonium salts. Thus, treatment of potassium enolate of
13a with 2a (1 equiv) afforded 2,2-bis(4-tert-butyl-1-
cyclohexenyl)indandione (13b) in 9% yield (see Scheme
2). On the other hand, acetylacetone (14a ) gave the
desired olefin 14b in 53% yield.
5a
14
a
b
Isolated yields. A 4:1 mixture of diastereoisomers. c A 1:1
mixture of diastereoisomers. 12e (5%) was obtained. e 4e (9%)
d
was obtained.
Alkenylphenyliodonium salts with a hydrogen atom
attached to the R-vinylic carbon atom undergo a facile
R-elimination by the reaction with a weak base such as
Et3N, NaHCO3, and n-Bu4NF to generate alkylidenecar-
benes, which further undergo 1,5-carbon-hydrogen in-
sertions, providing a useful route for the construction of
substituted cyclopentenes.20 This R-elimination pathway
leading to the generation of alkylidenecarbenes appears
to compete with the direct R-vinylation of 1,3-dicarbonyl
compounds using alkenylphenyliodonium salts with an
R-vinylic hydrogen, since enolate anions of 1,3-dicarbonyl
compounds may also act as a base for R-vinylic hydrogen
abstraction. Such competition between the direct R-vi-
nylation of 1,3-dicarbonyl compounds and the R-elimina-
tion leading to the generation of alkylidenecarbenes was
observed in the reaction of (Z)-(2-benzenesulfonyl-1-
decenyl)iodonium salt with 4a , in which a considerable
amount of the alkylidenecarbene-derived 1-benzene-
sulfonylcyclopentene20b (14%) was produced along with
formation of the vinyl sulfone 4g (42%) (Scheme 3). The
direct R-vinylation yielding 4g is highly stereoselective
with exclusive formation of the retained Z-isomer. The
stereochemistry of 4g was established by the observation
of a nuclear Overhauser effect (NOE) enhancement
between the vinylic and allylic protons.
arylation of dimedone enolate 15a with (o-nitrophenyl)-
phenyliodonium salt has been shown to give 2-(o-nitro-
phenyl)dimedone (15b) selectively without formation of
2-phenyldimedone.21 The presence of an electron-releas-
ing p-methoxy group decelerates the nucleophilic aro-
matic ipso substitution (Scheme 4); for instance, ther-
molysis of 16a affords a mixture of 16b and 16c in a ratio
of 81:19.22 For this reason, we sought to determine
whether this substituent effect observed in the nucleo-
philic substitutions of diaryliodonium salts holds for those
of alkenyl(aryl)iodonium salts.
Compared to the reactions of alkenyl(phenyl)iodonium
salt 2a , use of alkenyliodonium salt 2b with a p-
methoxyphenyl group as a ligand on the iodine(III) was
found to increase the selectivity for R-vinylation at the
expense of the competing R-arylation of 1,3-dicarbonyl
compounds (Table 2). Thus, in marked contrast to the
reaction of 2a with enolate anions of 5a , 9a , and 10a that
produces 10-29% of undesired phenylation (Table 1,
entries 2, 6, and 7), reactions with 2b resulted in a highly
selective R-vinylation with no sign of p-methoxyphenyl-
ation. R-Phenylation is a major process both for reactions
of nitrocyclohexane (12a ) with 2a and for those of
â-diketone 4a with 3a ; however, use of (p-methoxyphen-
yl)iodonium salts 2b and 3b resulted in a significant
selectivity for R-vinylation, although the yields were
moderate (Table 2, entries 7 and 8). The presence of a
p-methoxy group in 2b and 3b tends to decrease the
reactivity toward the nucleophilic substitutions and,
Su bstitu en t Effects of Alken yl(ar yl)iodon iu m Salts
on Selectivity of Vin yla tion ver su s Ar yla tion . In the
nucleophilic ipso substitution of unsymmetrical diaryli-
odonium salts (ArAr′I+X-), the electronic effects of sub-
stituents on the aromatic rings play an essential role in
determining selectivity in that the nucleophile tends to
attack the more electron-deficient aromatic ring.16 Thus,
(21) (a) Beringer, F. M.; Forgione, P. S.; Yudis, M. D. Tetrahedron
1960, 8, 49. (b) Beringer, F. M.; Falk, R. A. J . Chem. Soc. 1964, 4442.
(22) (a) Lancer, K. M.; Wiegand, G. H. J . Org. Chem. 1976, 41, 3360.
(b) Yamada, Y.; Kashima, K.; Okawara, M. Bull. Chem. Soc. J pn. 1974,
47, 3179. (c) Yamada, Y.; Okawara, M. Bull. Chem. Soc. J pn. 1972,
45, 1860. (d) Beringer, F. M.; Brierley, A.; Drexler, M.; Gindler, E.
M.; Lumpkin, C. C. J . Am. Chem. Soc. 1953, 75, 2708.
(20) (a) Ochiai, M.; Takaoka, Y.; Nagao, Y. J . Am. Chem. Soc. 1988,
110, 6565. (b) Ochiai, M.; Kunishima, M.; Tani, S.; Nagao, Y. J . Am.
Chem. Soc. 1991, 113, 3135. (c) Ochiai, M.; Uemura, K.; Masaki, Y.
J . Am. Chem. Soc. 1993, 115, 2528.

R-Vinylation of 1,3-Dicarbonyl Compounds
Ta ble 3. Effects of Ra d ica l In h ibitor s on Dir ect Vin yla tion of 1,3-Dica r bon yl a n d Rela ted Com p ou n d s
conditions
product (yield,a %)
J . Org. Chem., Vol. 62, No. 7, 1997 2133
entry
substrate
iodonium salt
additive (equiv)
temp, °C
time, h
vinylation
phenylation
ratiob
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
6a
7a
8a
8a
8a
8a
9a
9a
10a
10a
10a
12a
12a
4a
2a
2a
2a
2a
2a
2b
2a
2b
2a
2b
2c
2a
2b
3b
3a
3b
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
galvinoxyl (1)
25
25
25
25
25
25
25
25
25
25
25
25
50
50
25
50
2
1.5
1.5
1
0.5
1.5
0.5
7
0.5
18
2
0.5
3
6b (63)
7b (73)
6c (0)
7c (0)
8c (14)
8c (27)
8c (26)
8e (4)
100:0
100:0
63:37
72:28
74:26
95:5
79:21
100:0
82:18
100:0
100:0
35:65
96:4
8b (23)c
8b (70)c
8b (74)c
8b (79)c
9b (72)d
9b (48)d
10b (65)e
10b (66)e
10b (51)e
12b (28)
12b (58)
4d (66)
TEMPO (1)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
1,1-diphenylethylene (2)
9c (19)
9e (0)
10c (14)
10e (0)
10f (0)
12c (53)
12e (2)
4e (24)
5c (24)
5e (0)
3
24
14
74:26
69:31
100:0
5a
5a
5d (52)
5d (58)
a
b
d
Isolated yields. Ratios of vinylation versus phenylation. c A 2:1 mixture of diastereoisomers. A 4:1 mixture of diastereoisomers.
e A 1:1 mixture of diastereoisomers.
therefore, to attain a reasonable rate; the reactions were
generally carried out at 50 °C.
of vinylation and phenylation products 8b and 8c were
only slightly increased27 (compare Table 1, entry 5, and
Table 3, entry 3). On the other hand, use of 2,2,6,6-
tetramethylpiperidine-N-oxyl (TEMPO, 1 equiv) or 1,1-
diphenylethylene (2 equiv) as an additive improved the
yield of 8b dramatically up to 70-74% and that of 8c
(26-27%), but did not affect the selectivity on vinylation
versus phenylation. The best results, in terms of yields
and selectivity, for the direct vinylation of 8a were
obtained by using cyclohexenyl(p-methoxyphenyl)iodo-
nium salt (2b) in the presence of 1,1-diphenylethylene
(Table 3, entry 6). Similarly, the addition of 1,1-diphen-
ylethylene was found to considerably increase the yields
of vinylation of â-diketones 6a and 7a , and â-keto ester
9a in the reaction with 2a . Use of this radical trap also
improved the yields of cyclopentenylation of 4a and 5a
(Table 3, entries 14-16). More than 80 mol % of 1,1-
diphenylethylene is generally recovered unchanged in
these reactions. Unexpectedly, conflicting results on the
effects of this radical trap were obtained from the
vinylation of nitrocyclohexane (12a ); that is, the reaction
of 12a with 12b was much improved with added 1,1-
diphenylethylene, but the yield of 12b was decreased in
the reaction with 2a . In addition, we found that the use
of this trap decreased the yield of the reaction of 9a with
2b.
To gain a better understanding of the effects of this
radical inhibitor, product analysis was carried out in
detail for the vinylation of 8a with 2a in the presence
and absence of the inhibitor. It is clear from the data
presented in Scheme 5 that, in addition to the phenyla-
tion yielding 8c, the formation of benzene (19) as well
as 4-tert-butylcyclohexene (20) is a major competing
reaction. Thus, in the absence of 1,1-diphenylethylene
as an additive, benzene (19) and 4-tert-butylcyclohexene
(20) are produced in 45% and 39% yields, respectively.
In the presence of 2 equiv of 1,1-diphenylethylene,
however, the yields of 19 and 20 drop to 27% and 7%,
respectively.
Interestingly, but for reasons not quite clear to us,
alkenyliodonium salt 2c with an electron-withdrawing
chloro substituent at the para position showed selectivity
similar to that of 2b. Specifically, only R-vinylation
products 9b and 10b were obtained in the reaction of 2c
with 9a and 10a , albeit in moderate yields (Table 2,
entries 3 and 6).
Effects of Ra d ica l In h ibitor s on Dir ect r-Vin yla -
tion . The extensive studies conducted by Beringer and
his co-workers on arylation of enolate anions derived from
1,3-dicarbonyl compounds with diaryliodonium salts sug-
gests that the generation of the aryl radicals by electron
transfer from enolates to iodonium salts, with subsequent
decomposition of the resulting 9-I-2 intermediate, are
involved in this arylation reaction.21,23,24 Barton and his
co-workers,25 however, employing spin trapping experi-
ments using 1,1-diphenylethylene, clearly demonstrated
that the reaction involves two competing mechanisms:
an induced radical-chain process producing aromatic
hydrocarbons and a nonradical process yielding arylation
products. 1,1-Diphenylethylene is an efficient phenyl
radical trap that inhibits the radical-induced decomposi-
tion of diphenyliodonium salts into benzene; accordingly,
use of this trap in the reaction with enolate anions
improves the yields of phenylated products.25,26
To investigate the occurrence of a radical process in
this vinylation reaction using alkenyl(aryl)iodonium salts
as well as to improve the yields of the vinylation, effects
of radical inhibitors were examined. The results are
summarized in Table 3. When â-keto ester 8a was
treated with cyclohexenyl(phenyl)iodonium salt 2a in the
presence of galvinoxyl (1 equiv) as an additive, the yields
(23) (a) Beringer, F. M.; Galton, S. A.; Huang, S. J . J . Am. Chem.
Soc. 1962, 84, 2819. (b) Beringer, F. M.; Forgione, P. S. Tetrahedron
1969, 19, 739. (c) Tanner, D. D.; Reed, D. W.; Setiloane, B. P. J . Am.
Chem. Soc. 1982, 104, 3917.
(24) (a) Chen, K.; Koser, G. F. J . Org. Chem. 1991, 56, 5764. (b)
Hampton, K. G.; Harris, T. M.; Hauser, C. R. J . Org. Chem. 1964, 29,
3511.
As described above, these hydrocarbons 19 and 20
appear to be radical products. The 9-I-2 intermediate
21 (Scheme 6), probably produced by electron transfer
from the enolate to iodonium salt 2a , can decompose to
(25) Barton, D. H. R.; Finet, J .-P.; Giannotti, C.; Halley, F. J . Chem.
Soc., Perkin Trans. 1 1987, 241.
(26) (a) Lubinkowski, J . J .; Knapczyk, J . W.; Calderon, J . L.; Petit,
L. R.; McEwen, W. E. J . Org. Chem. 1975, 40, 3010. (b) Lubinkowski,
J . J .; Gomez, M.; Calderon, J . L.; McEwen, W. E. J . Org. Chem. 1978,
43, 2432. (c) Lubinkowski, J . J .; Arrieche, C. G.; McEwen, W. E. J .
Org. Chem. 1980, 45, 2076. (d) Singh, P. R.; Khanna, R. K. Tetrahe-
dron Lett. 1982, 23, 5355.
(27) The effects of galvinoxyl as a radical trap in the reaction are
relatively small. This is probably because this radical can react with
bases, in this case, enolate anions.28

2134 J . Org. Chem., Vol. 62, No. 7, 1997
Ochiai et al.
Sch em e 5
Sch em e 6
Sch em e 7
hexenyl)-2-phenyl-1,3-indandione or 2-(5-tert-butyl-1-cy-
clohexenyl)-2-methyl-1,3-indandione among the products
in the reactions of 4a or 5a with 2a , in spite of our careful
search, would seem to eliminate the possibility that
cyclohexyne intermediates are involved. As mentioned
above, nucleophilic substitutions of alkenyliodonium salt
2a take place only at the vinylic ipso position, and
furthermore, involvement of the highly labile cyclopen-
tyne intermediate seems to be unlikely.
Solvolysis of 2 generates 1-cyclohexenyl cation even at
25 °C.12 This vinyl cation pathway, however, cannot be
applied to the direct vinylation of â-dicarbonyl com-
pounds, because 1-cyclopentenylation with 3 also occurs
smoothly even at 25-50 °C (Table 1-3). We know of no
evidence verifying the generation of 1-cyclopentenyl
cation.19 Strongly bent vinyl cations, such as cyclopen-
tenyl cations, are strained too much to be formed as an
intermediate. Furthermore, the stereochemical outcome
of R-vinylation of 4a with (Z)-(2-benzenesulfonyl-1-dece-
nyl)iodonium salt, leading to exclusive formation of the
retained Z-isomer 4g (Scheme 3), is not compatible with
this vinyl cation pathway, which might expect formation
of stereoisomeric mixtures.
An addition-elimination sequence at the R-vinylic
carbon atoms of alkenyliodonium salts has been proposed
for nucleophilic vinylic substitutions with tetrabutylam-
monium halides and sodium benzenesulfinate substitu-
tions that proceed with exclusive retention of configura-
tion (Scheme 7).15 This mechanism nicely explains
stereoselective formation of the retained Z-isomer 4g.
Although this pathway is the most common in nucleo-
philic vinylic substitutions, the presence of a highly
electron-withdrawing group such as a benzene sulfonyl
group promotes the formation of betaine 25. The alk-
enyliodonium salts 2 and 3 do not bear substituents
associated with the stabilization of betaine intermediates.
An alternative possibility, illustrated in Scheme 8,
involves the intermediate formation of hypervalent or-
ganoiodane 27 and/or 28 by ligand exchange on the
iodine(III). Subsequent ligand coupling on the iodine-
(III) of 27 or 28 would give rise to vinylation products.22a,32
Koser and Chen have suggested the formation of similar
intermediates in their elegant regiocontrolled reactions
of silyl enol ethers with diphenyliodonium fluoride.24a
Furthermore, the reported structure of crystalline diben-
generate 4-tert-butylcyclohexenyl radical 22 and iodo-
benzene (17) (path a), or to generate phenyl radical (23)
and 4-tert-butyl-1-iodocyclohexene (18) (path b). These
radicals would be responsible for the formation of 19 and
20. Of these two pathways for the decomposition of 21,
path a would be favored over path b because of the higher
stability associated with the combination of the vinyl
radical 22 and 17 compared to that of the phenyl radical
(23) and the vinyl iodide 18.13a,29 Clearly, 1,1-diphenyl-
ethylene is functioning as an inhibitor of a radical
reaction which produces 19 and 20, presumably by
capturing the vinyl and the phenyl radicals.25,26,28 The
extent of the changes in the yield of benzene (19) in the
presence and absence of the inhibitor suggests that some
process other than a phenyl radical mechanism is re-
sponsible for the formation of 19. It is evident from Table
3, entry 4, that the presence of TEMPO in the reaction
mixture also inhibits the radical reactions.
On the basis of these findings as well as the great
improvement of the yields of vinylation and phenylation
products, we believe, with Barton,25 that vinyl and phenyl
radical mechanisms are not involved in either the vinyl-
ation or the phenylation reactions.
Rea ction Mech a n ism . Many mechanisms have been
recognized in nucleophilic vinylic substitutions.30 Among
them, the elimination-addition mechanism via the in-
termediate formation of 4-tert-butyl-1-cyclohexyne from
2 should be considered. Nucleophilic substitutions of
1-chlorocyclohexene in the presence of NaNH2-t-BuONa
have been shown to involve initial formation of cyclohex-
yne via syn-â-elimination, followed by nucleophilic addi-
tion.31 Our inability to detect any 2-(5-tert-butyl-1-cyclo-
(28) (a) Lai, C. C.; McEwen, W. E. Tetrahedron Lett. 1971, 3271.
(b) Leardini, R.; Tundo, A.; Zanardi, G. J . Chem. Soc., Perkin Trans.
2 1983, 285.
(29) The value of ∆H° for the following reaction has been calculated
to be 2.4 kcal/mol. See: Golden, D. M.; Benson, S. W. Chem. Rev. 1969,
69, 125.
C6H5I + H2CdCH• f C6H5• + H2CdCHI
(30) For reviews, see: (a) Rappoport, Z. Adv. Phys. Org. Chem. 1969,
7, 1. (b) Modena, G. Acc. Chem. Res. 1971, 4, 73. (c) Miller, S. I.
Tetrahedron 1977, 33, 1211. (d) Rappoport, Z. Acc. Chem. Res. 1981,
14, 7. (e) Rappoport, Z. Recl. Trav. Chim. Pays-Bas 1985, 104, 309.
(f) Shainyan, B. A. Usp. Khim. 1986, 55, 942. (g) Rappoport, Z. Acc.
Chem. Res. 1992, 25, 474.
(32) (a) Oae, S. Acc. Chem. Res. 1991, 24, 202. (b) Grushin, V. V.;
Shcherbina, T. M. J . Organomet. Chem. 1985, 292, 105.
(31) Caubere, P. Acc. Chem. Res. 1974, 7, 301.

R-Vinylation of 1,3-Dicarbonyl Compounds
J . Org. Chem., Vol. 62, No. 7, 1997 2135
Sch em e 8
releasing p-methoxy group in 2b and 3b improves the
selectivity of the ipso vinylation over the arylation.
Exp er im en ta l Section
Gen er a l. For general experimental detail, see ref 12.
Potassium tert-butoxide was freshly sublimed repeatedly (two
times) in vacuo prior to use. 2-Phenyl-1,3-indandione (4a ),
2-methyl-1,3-cyclopentanedione (6a ), 2-methyl-1,3-cyclohex-
anedione (7a ), methyl 2-oxocyclopentanecarboxylate (9a ),
2-acetylbutyrolactone (10a ), 2,2,5-trimethyl-1,3-dioxane-4,6-
dione (11a ), nitrocyclohexane (12a ), and 1,3-indandione (13a )
are commercially available. 2-Methyl-1,3-indandione (5a ) and
2-carbomethoxyindanone (8a ) were prepared according to
literature procedure.38,39
(4-ter t-Bu tyl-1-cycloh exen yl)ph en yliodon iu m Tetr aflu -
or obor a te (2a ) a n d (4-ter t-Bu tyl-1-cycloh exen yl)(p-ch lo-
r op h en yl)iod on iu m Tetr a flu or obor a te (2c). The BF3-
catalyzed silicon-iodonium exchange reaction between 4-tert-
butyl-1-(trimethylsilyl)cyclohexene and iodosylbenzene (1a ) or
p-chloroiodosylbenzene (1c) was carried out in the same way
as described previously.12 The yields of 2a and 2c were 96%
and 44%, respectively.
Sch em e 9
(4-ter t-Bu tyl-1-cycloh exen yl)(p-m eth oxyp h en yl)iod o-
n iu m Tetr a flu or obor a te (2b). To a stirred suspension of
p-methoxyiodosylbenzene (1b) (38 mg, 0.15 mmol) and 4-tert-
butyl-1-(trimethylsilyl)cyclohexene40 (20 mg, 0.10 mmol) in
dichloromethane (3 mL) was added BF3‚Et2O (22 mg, 0.15
mmol) at 0 °C under nitrogen, and the mixture was stirred
for 3 h at 0 °C and for an additional 2 h at room temperature.
After the addition of a saturated aqueous sodium tetrafluo-
roborate solution (3 mL), the mixture was stirred for 5 min.
The reaction mixture was poured into water and extracted
with dichloromethane. The organic layer was concentrated
under an aspirator vacuum to give an oil, which was washed
several times with hexane-diethyl ether by decantation at
-78 °C. Recrystallization from hexane-diethyl ether gave the
alkenyliodonium salt 2b (36 mg, 83%) as a powder: mp 84-
ziodolium 1,3-diphenyl-1,3-propanedionate prepared by
the reaction of dibenziodolium salt with â-diketone, in
which the enolate anion serves as a chelate ligand for
the iodonium cation, suggests that the oxygen-coordi-
nated iodane 27 may serve as an intermediate.33,34
The conclusions of Moriarty and Koser that the R-oxy-
sulfonylation or R-hydroxylation of ketones with [hy-
droxy(tosyloxy)iodo]benzene or iodosylbenzene (1a ) under
both basic and acidic conditions probably involves forma-
tion of R-aryliodonio ketones as reactive intermediates
have been generally accepted.35 In fact, 2-dimedonyl-
phenyliodonium tosylate (29) has been isolated from the
reaction of dimedone with [hydroxy(tosyloxy)iodo]benzene
in acetonitrile at room temperature (Scheme 9).36 Fur-
ther, reaction of diphenyliodonium salts with phenyl-
lithium has been shown to give triphenyliodine(III).37
These results suggest that another possible structure, 28,
in which the â-diketone is coordinated as a carbon (CR)
ligand on the iodine(III), may serve as an intermediate.
In conclusion, reactions of alkenyl(aryl)iodonium tet-
rafluoroborates 2 and 3 with enolate anions derived from
2-substituted 1,3-dicarbonyl compounds afford 2-alkenyl-
1,3-dicarbonyl compounds. Use of 1,1-diphenylethylene
inhibits the radical-induced decomposition of these iodo-
nium salts and, thereby, improves the yield of the vinyl-
ated products. Furthermore, the presence of an electron-
87 °C dec; IR (KBr) 1570, 1490, 1175, 1060 cm-1
;
1H NMR
(CDCl3) δ 7.92 (br d, J ) 8.9 Hz, 2H), 7.01 (br d, J ) 8.9 Hz,
2H), 7.00-6.87 (m, 1H), 3.87 (s, 3H), 2.80-2.11 (m, 3H), 2.01-
1.66 (m, 2H), 1.60-1.11 (m, 2H), 0.84 (s, 9H); FAB MS m/z
371 [(M - BF4)+]. Anal. Calcd for C17H24OBF4I: C, 44.57; H,
5.28. Found: C, 44.40; H, 5.11.
(1-Cyclop en ten yl)p h en yliod on iu m Tetr a flu or obor a te
(3a ). To a stirred suspension of iodosylbenzene (1a) (2.1 g,
9.6 mmol) and 1-(trimethylsilyl)cyclopentene40 (840 mg, 6.0
mmol) in dichloromethane (30 mL) was added BF3‚Et2O (1.4
g, 9.6 mmol) at 0 °C under nitrogen, and the mixture was
stirred for 1 h at 0 °C and for an additional 0.5 h at room
temperature. After the addition of a saturated aqueous
sodium tetrafluoroborate solution, the mixture was stirred for
15 min. The reaction mixture was poured into water and
extracted with dichloromethane. The organic layer was
concentrated under an aspirator vacuum to give an oil, which
was washed several times with hexane-diethyl ether by
decantation at -78 °C. Recrystallization from dichloro-
methane-diethyl ether gave the alkenyliodonium salt 3a (1.39
g, 81%) as colorless crystals: mp 78-79 °C; IR (KBr) 2954,
1
1475, 1446, 1055, 770, 745 cm-1; H NMR (CDCl3) δ 8.00 (br
(33) (a) Greidanus, J . W.; Rebel, W. J .; Sandin, R. B. J . Am. Chem.
Soc. 1962, 84, 1504. (b) Lee, P. E.; Soderberg, R. H. J . Am. Chem.
Soc. 1972, 94, 4132.
d, J ) 7.5 Hz, 2H), 7.65 (br t, J ) 7.5 Hz, 1H), 7.49 (br t, J )
7.5 Hz, 2H), 6.94 (m, 1H), 2.78-2.61 (m, 4H), 2.03 (quint, J )
7.5 Hz, 2H); 13C NMR (CDCl3) δ 150.7 (d), 135.6 (d), 132.7 (d),
132.4 (d), 109.5 (s), 108.8 (s), 37.9 (t), 33.8 (t), 23.1 (t); FAB
MS m/z 271 [(M - BF4)+]. Anal. Calcd for C11H12BF4I: C,
36.91; H, 3.38. Found: C, 37.12; H, 3.39.
(34) For the formation of S-O sulfurane intermediates in the
reaction of sulfonium salts with enolate anions, see: (a) Kobayashi,
M.; Umemura, K.; Watanabe, N.; Matsuyama, H. Chem. Lett. 1985,
1067. (b) Kobayashi, M.; Umemura, K.; Matsuyama, H. Chem. Lett.
1987, 327. (c) Umemura, K.; Matsuyama, H.; Watanabe, N.; Koba-
yashi, M.; Kamigata, N. J . Org. Chem. 1989, 54, 2374. (d) Umemura,
K.; Matsuyama, H.; Kobayashi, M.; Kamigata, N. Bull. Chem. Soc. J pn.
1989, 62, 3026.
(1-Cyclop en t en yl)(p -m et h oxyp h en yl)iod on iu m Tet -
r a flu or obor a te (3b). To a stirred suspension of p-methoxy-
iodosylbenzene (1b) (143 mg, 0.57 mmol) and 1-(trimethylsilyl)-
cyclopentene40 (50 mg, 0.36 mmol) in dichloromethane (5 mL)
(35) (a) Moriarty, R. M.; Prakash, O. Acc. Chem. Res. 1986, 19, 244.
(b) Moriarty, R. M.; Vaid, R. K.; Koser, G. F. Synlett 1990, 365. (c)
Moriarty, R. M.; Vaid, R. K. Synthesis 1990, 431.
(36) Koser, G. F.; Relenyi, A. G.; Kalos, A. N.; Rebrovic, L.; Wettach,
R. H. J . Org. Chem. 1982, 47, 2487.
(37) (a) Wittig, G.; Rieber, M. Ann. Chem. 1949, 562, 187. (b) Claus,
K. Chem. Ber. 1955, 88, 268. (c) Beringer, F. M.; Chang, L. L. J . Org.
Chem. 1971, 36, 4055.
(38) Mosher, W. A.; Soeder, R. W. J . Org. Chem. 1971, 36, 1561.
(39) (a) Wynberg, H.; Helder, R. Tetrahedron Lett. 1975, 16, 4057.
(b) House, H. O.; Hudson, C. B. J . Org. Chem. 1970, 35, 647.
(40) Paquette, L. A.; Fristad, W. E.; Dime, D. S.; Bailey, T. R. J .
Org. Chem. 1980, 45, 3017.

2136 J . Org. Chem., Vol. 62, No. 7, 1997
Ochiai et al.
was added BF3‚Et2O (81 mg, 0.57 mmol) at 0 °C under
nitrogen, and the mixture was stirred for 3 h at 0 °C and for
an additional 3 h at room temperature. After the addition of
a saturated aqueous sodium tetrafluoroborate solution (5 mL),
the mixture was stirred for 5 min. The reaction mixture was
poured into water and extracted with dichloromethane. The
organic layer was concentrated under an aspirator vacuum to
give an oil, which was washed several times with hexane-
diethyl ether by decantation at -78 °C. Further purification
by decantation using diethyl ether gave the alkenyliodonium
salt 3b (101 mg, 73%) as an oil: IR (Nujol) 1570, 1485, 1180,
IR (CHCl3) 1740, 1705 cm-1; 1H NMR (CDCl3) δ 8.10-8.0 (m,
2H), 7.95-7.84 (m, 2H), 7.39-7.25 (m, 5H), 1.72 (s, 3H); MS
m/z (relative intensity) 236 (100, M+), 104 (26), 77 (16); HRMS
calcd for C16H12O2 (M+) 236.0837, found 236.0834.
2-(1-Cyclop en ten yl)-2-m eth yl-1,3-in d a n d ion e (5d ): pale
yellow crystals; mp 94-96 °C (recrystallized from diethyl
1
ether-hexane); IR (CHCl3) 1740, 1705, 1590 cm-1; H NMR
(CDCl3) δ 8.06-7.92 (m, 2H), 7.92-7.76 (m, 2H), 5.65-5.52
(m, 1H), 2.40-2.12 (m, 4H), 1.90-1.70 (m, 2H), 1.48 (s, 3H);
MS m/z (relative intensity) 226 (100, M+), 211 (51), 197 (21),
105 (32), 77 (24). Anal. Calcd for C15H14O2: C, 79.62; H, 6.24.
Found: C, 79.35; H, 6.31.
1
1060, 1025, 830 cm-1; H NMR (CDCl3) δ 7.91 (br d, J ) 8.9
Hz, 2H), 6.99 (br d, J ) 8.9 Hz, 2H), 6.91-6.80 (m, 1H), 3.86
(s, 3H), 2.77-2.55 (m, 4H), 2.03 (quint, J ) 7.6 Hz, 2H); FAB
MS m/z 301 [(M-BF4)+]; HRMS (FAB) calcd for C12H14OI [(M
- BF4)+] 301.0089, found 301.0107.
2-(4-ter t-Bu tyl-1-cycloh exen yl)-2-m eth yl-1,3-cyclop en -
ta n ed ion e (6b): colorless plates; mp 129-131 °C (recrystal-
lized from diethyl ether-hexane); IR (CHCl3) 1760, 1720 cm-1
;
1H NMR (CDCl3) δ 5.59-5.48 (m, 1H), 3.04-2.54 (m, 4H),
2.20-1.68 (m, 5H), 1.34-1.01 (m, 2H), 1.19 (s, 3H), 0.84 (s,
9H); MS m/z (relative intensity) 248 (12, M+), 220 (100), 163
(42), 136 (39), 79 (35), 57 (38); HRMS calcd for C16H24O2 (M+)
248.1776, found 248.1777. Anal. Calcd for C16H24O2: C, 77.38;
H, 9.74. Found: C, 77.29; H, 9.77.
Gen er a l P r oced u r e for Dir ect Vin yla tion of 1,3-Dica r -
bon yl Com p ou n d s w ith Alk en yl(a r yl)iod on iu m Sa lts 2
a n d 3. To a stirred solution of freshly sublimed potassium
tert-butoxide (15 mg, 0.13 mmol) in THF (2 mL) was added a
1,3-dicarbonyl compound (0.13 mmol) under argon at room
temperature, and the mixture was stirred for 1 h. A solution
of an alkenyl(aryl)iodonium salt 2 or 3 (0.12 mmol) in THF (3
mL) was added to this mixture at room temperature or at 50
°C, and the mixture was stirred for the periods shown in Tables
1 and 2. Water was added, the mixture was extracted with
diethyl ether three times, and the combined organic phase was
washed with water and brine. The solution was dried over
anhydrous Na2SO4 and concentrated to give an oil, which was
purified by preparative TLC. The yields of pure products are
given in Tables 1 and 2.
2-(4-ter t-Bu tyl-1-cycloh exen yl)-2-m eth yl-1,3-cycloh ex-
a n ed ion e (7b): colorless plates; mp 145-147 °C (recrystallized
1
from diethyl ether-hexane); IR (CHCl3) 1720, 1690 cm-1; H
NMR (CDCl3) δ 5.45-5.34 (m, 1H), 2.94-2.67 (m, 2H), 2.58-
2.35 (m, 2H), 2.23-1.64 (m, 7H), 1.30-1.00 (m, 2H), 1.25 (s,
3H), 0.85 (s, 9H); MS m/z (relative intensity) 262 (1, M+), 206
(100), 149 (21). Anal. Calcd for C17H26O2: C, 77.82; H, 9.99.
Found: C, 77.60; H, 9.94.
2-(4-tert-Bu t yl-1-cycloh exen yl)-2-ca r b om et h oxy-1-in -
d a n on e (8b): a 2:1 mixture of diastereoisomers; colorless oil;
IR (CHCl3) 1710, 1655, 1605, 1230, 1080 cm-1 1H NMR
;
2-(4-ter t-Bu t yl-1-cycloh exen yl)-2-p h en yl-1,3-in d a n d i-
on e (4b): pale yellow needles; mp 102-104 °C (recrystallized
from diethyl ether-hexane); IR (CHCl3) 1735, 1705, 1595, 1230
(CDCl3) δ 7.79 (br d, J ) 7.7 Hz, 1H), 7.61 (br t, J ) 7.7 Hz,
1H), 7.44 (br d, J ) 7.7 Hz, 1H), 7.38 (br t, J ) 7.7 Hz, 1H),
5.69-5.59 (m, a major isomer), 5.59-5.50 (m, a minor isomer),
3.98 (d, J ) 17.7 Hz, a minor isomer), 3.92 (d, J ) 17.7 Hz, a
major isomer), 3.76 (s, a minor isomer), 3.76 (s, a major
isomer), 3.26 (d, J ) 17.7 Hz, a major isomer), 3.22 (d, J )
17.7 Hz, a minor isomer), 2.50-1.64 (m, 5H), 1.40-1.10 (m,
2H), 0.83 (s, 9H); MS m/z (relative intensity) 326 (74, M+), 267
(100), 210 (47), 182 (77), 57 (31); HRMS calcd for C21H26O3
(M+) 326.1882, found 326.1867.
2-Ca r bom eth oxy-2-p h en yl-1-in d a n on e (8c): colorless
oil; IR (CHCl3) 1720, 1610, 1230 cm-1; 1H NMR (CDCl3) δ 7.84
(br d, J ) 7.7 Hz, 1H), 7.62 (br t, J ) 7.7 Hz, 1H), 7.57-7.18
(m, 7H), 4.24 (d, J ) 17.3 Hz, 1H), 3.75 (s, 3H), 3.56 (d, J )
17.3 Hz, 1H); MS m/z (relative intensity) 266 (55, M+), 238
(90), 207 (100), 178 (100); HRMS calcd for C17H14O3 (M+)
266.0942, found 266.0936. Anal. Calcd for C17H14O3: C, 76.67;
H, 5.30. Found: C, 76.47; H, 5.34.
2-(4-ter t-Bu tyl-1-cycloh exen yl)-2-ca r bom eth oxycyclo-
p en ta n on e (9b): a 4:1 mixture of diastereoisomers; colorless
oil; IR (CHCl3) 1740, 1720, 1360, 1220 cm-1; 1H NMR (CDCl3)
δ 5.58-5.54 (m, a major isomer), 5.54-5.52 (m, a minor
isomer), 3.74 (s, a minor isomer), 3.73 (s, a major isomer),
2.58-2.42 (m, 1H), 2.42-2.18 (m, 3H), 2.18-1.74 (m, 7H),
1.33-1.09 (m, 2H), 0.86 (s, a major isomer), 0.85 (s, a minor
isomer); MS m/z (relative intensity) 278 (8, M+), 250 (100), 222
(21), 166 (20); HRMS calcd for C17H26O3 (M+) 278.1882, found
278.1895.
cm-1 1H NMR (CDCl3) δ 8.06-7.97 (m, 2H), 7.90-7.78 (m,
;
2H), 7.41-7.20 (m, 5H), 5.61-5.50 (m, 1H), 2.16-1.69 (m, 5H),
1.37-1.08 (m, 2H), 0.82 (s, 9H); MS m/z (relative intensity)
358 (100, M+), 301 (15), 287 (46). Anal. Calcd for C25H26O2:
C, 83.76; H, 7.31. Found: C, 83.68; H, 7.44.
2,2-Dip h en yl-1,3-in d a n d ion e (4c):23a pale yellow prisms;
mp 117-119 °C (recrystallized from ethanol); IR (CHCl3) 1740,
1720, 1700 cm-1; 1H NMR (CDCl3) δ 8.11-8.07 (m, 2H), 7.92-
7.87 (m, 2H), 7.29 (m, 10H); MS m/z (relative intensity) 298
(100, M+), 241 (31), 165 (32).
2-(1-Cyclop en ten yl)-2-p h en yl-1,3-in d a n d ion e (4d ): pale
yellow needles; mp 134-138 °C (recrystallized from diethyl
1
ether-hexane); IR (CHCl3) 1735, 1700, 1590 cm-1; H NMR
(CDCl3) δ 8.10-7.98 (m, 2H), 7.92-7.82 (m, 2H), 7.40-7.28
(m, 5H), 5.72-5.60 (m, 1H), 2.43-2.23 (m, 4H), 1.87 (quint, J
) 7.1 Hz, 2H); MS m/z (relative intensity) 288 (100, M+), 259
(13), 231 (16), 202 (15). Anal. Calcd for C20H16O2: C, 83.31;
H, 5.59. Found: C, 83.06; H, 5.81.
2-P h en yl-2-(p-m eth oxyp h en yl)-1,3-in d a n d ion e (4e): col-
1
orless oil; IR (CHCl3) 1740, 1725, 1700, 1595 cm-1; H NMR
(CDCl3) δ 8.14-8.04 (m, 2H), 7.95-7.84 (m, 2H), 7.36-7.26
(m, 5H), 7.21 (d, J ) 9.0 Hz, 2H), 6.84 (d, J ) 9.0 Hz, 2H),
3.77 (s, 3H); MS m/z (relative intensity) 328 (100, M+), 271
(13), 228 (14); HRMS calcd for C22H16O3 (M+) 328.1099, found
328.1095.
2-(4-ter t-Bu t yl-1-cycloh exen yl)-2-m et h yl-1,3-in d a n d i-
on e (5b): colorless plates; mp 102-104 °C (recrystallized from
diethyl ether-hexane); IR (CHCl3) 1750, 1710, 1600 cm-1; 1H
NMR (CDCl3) δ 8.04-7.94 (m, 2H), 7.92-7.80 (m, 2H), 5.70-
5.62 (m, 1H), 2.15-1.70 (m, 5H), 1.41 (s, 3H), 1.28-1.04 (m,
2H), 0.81 (s, 9H); 13C NMR (CDCl3) δ 203.6 (s), 202.8 (s), 141.4
(s), 141.3 (s), 135.8 (d), 135.8 (d), 133.9 (s), 126.7 (d), 123.7
(d), 123.5 (d), 59.6 (s), 43.3 (d), 32.1 (s), 27.2 (t), 27.2 (t), 27.1
(q), 24.1 (t), 16.9 (q); MS m/z (relative intensity) 296 (100, M+),
239 (15), 225 (42), 161 (38); HRMS calcd for C20H24O2 (M+)
296.1776, found 296.1794. Anal. Calcd for C20H24O2: C, 81.04;
H, 8.16. Found: C, 80.61; H, 8.25.
2-Ca r bom eth oxy-2-p h en ylcyclop en ta n on e (9c): color-
less oil; IR (CHCl3) 1750, 1720, 1220 cm-1; 1H NMR (CDCl3) δ
7.40-7.28 (m, 5H), 3.71 (s, 3H), 2.89 (dt, J ) 13.6, 6.4 Hz,
1H), 2.54 (dt, J ) 13.6, 6.4 Hz, 1H), 2.54-2.31 (m, 2H), 2.08-
1.86 (m, 2H); MS m/z (relative intensity) 218 (100, M+), 190
(12), 175 (15), 159 (10); HRMS calcd for C13H14O3 (M+)
218.0943, found 218.0943.
2-Ace t yl-2-(4-t er t -b u t yl-1-cycloh e xe n yl)b u t yr ola c-
ton e (10b): a 1:1 mixture of diastereoisomers; colorless
crystals; IR (CHCl3) 1760, 1710, 1360 cm-1; 1H NMR (CDCl3)
δ 5.99-5.90, 5.90-5.78 (each m, total 1H), 4.30-4.06 (m, 2H),
3.00, 2.93 (each t, J ) 7.7 Hz, total 1H), 2.36, 2.34 (each s,
total 3H), 2.21-1.57 (m, 6H), 1.35-1.00 (m, 2H), 0.87 (s, 9H);
MS m/z (relative intensity) 264 (1, M+), 222 (100), 207 (18),
138 (43). Anal. Calcd for C16H24O3: C, 72.69; H, 9.15.
Found: C, 72.48; H, 9.08.
2-Meth yl-2-ph en yl-1,3-in dan dion e (5c):41 colorless plates;
mp 159-161 °C (recrystallized from diethyl ether-hexane);
(41) Henze, H. R.; Leanza, W. J . J . Org. Chem. 1952, 17, 4.

R-Vinylation of 1,3-Dicarbonyl Compounds
J . Org. Chem., Vol. 62, No. 7, 1997 2137
2-Acetyl-2-p h en ylbu tyr ola cton e (10c): colorless oil; IR
(CHCl3) 1760, 1715, 1360 cm-1; 1H NMR (CDCl3) δ 7.48-7.28
(m, 5H), 4.38-4.14 (m, 2H), 3.34 (ddd, J ) 12.9, 7.6, 6.3 Hz,
1H), 2.37 (ddd, J ) 12.9, 7.0, 6.4 Hz, 1H), 2.21 (s, 3H); MS
m/z (relative intensity) 182 (10), 162 (100), 117 (73), 77 (34).
5-(4-ter t-Bu t yl-1-cycloh exen yl)-2,2,5-t r im et h yl-1,3-d i-
oxa n e-4,6-d ion e (11b): white needles; mp 79-80 °C (recrys-
tallized from diethyl ether-hexane); IR (CDCl3) 1780, 1740,
1385, 1295 cm-1; 1H NMR (CDCl3) δ 5.91-5.80 (m, 1H), 2.36-
1.79 (m, 5H), 1.76 (s, 3H), 1.73 (s, 3H), 1.66 (s, 3H), 1.33-1.03
(m, 2H), 0.86 (s, 9H); MS m/z (relative intensity) 294 (3, M+),
279 (1), 208 (100), 152 (41), 124 (20); HRMS calcd for C17H26O4
(M+) 294.1831, found 294.1826. Anal. Calcd for C17H26O4: C,
69.36; H, 8.90. Found: C, 69.12; H, 8.83.
1-(4-t er t -Bu t yl-1-cycloh e xe n yl)-1-n it r ocycloh e xa n e
(12b): colorless plates; mp 77-79 °C (recrystallized from
diethyl ether-hexane); IR (CDCl3) 1530, 1445, 1365 cm-1; 1H
NMR (CDCl3) δ 5.98-5.91 (m, 1H), 2.56-2.40 (m, 2H), 2.20-
2.04 (m, 2H), 2.00-1.73 (m, 5H), 1.73-0.98 (m, 8H), 0.85 (s,
9H); MS m/z (relative intensity) 219 [100, (M - NO2)+], 163
(26), 123 (53), 109 (38), 81 (44), 67 (32), 57 (78). Anal. Calcd
for C16H27O2N‚1/4H2O: C, 71.20; H, 10.27; N, 5.19. Found: C,
71.28; H, 9.98; N, 4.99.
(71), 161 (33), 137 (41), 57 (40), 43 (100). Anal. Calcd for
C15H24O2: C, 76.23; H, 10.23. Found: C, 75.85; H, 10.13.
Rea ction of 4a w ith (Z)-P h en yl(2-ben zen esu lfon yl-1-
d ecen yl)iod on iu m Tetr a flu or obor a te. To a stirred solu-
tion of freshly sublimed potassium tert-butoxide (17 mg, 0.15
mmol) in THF (1.5 mL) was added the diketone 4a (33 mg,
0.15 mmol) under argon at room temperature, and the mixture
was stirred for 1.5 h. A solution of (Z)-phenyl(2-benzenesulfo-
nyl-1-decenyl)iodonium tetrafluoroborate20b (76 mg, 0.13 mmol)
in THF (1.5 mL) was added to this mixture at room temper-
ature, and the mixture was stirred for 24 h. Water was added,
the mixture was extracted with diethyl ether three times, and
the combined organic phase was washed with water and brine.
The solution was dried over anhydrous Na2SO4 and concen-
trated to give an oil, which was purified by preparative TLC
(dichloromethane-hexane (2:1) and ethyl acetate-hexane (2:
8)) to give (Z)-2-phenyl-2-(2-benzenesulfonyl-1-decenyl)-1,3-
indandione (4g) (28 mg, 42%) and 1-benzenesulfonyl-3-
pentylcyclopentene20b (5 mg, 14%). 4g: colorless needles; mp
114-115 °C (recrystallized from dichloromethane-hexane); IR
(CHCl3) 1740, 1700, 1585, 1295, 1245, 960, 900 cm-1; 1H NMR
(CDCl3) δ 8.02-7.96 (m, 2H), 7.86 (br d, J ) 7.3 Hz, 2H), 7.77-
7.72 (m, 2H), 7.61 (br t, J ) 7.3 Hz, 1H), 7.53 (br t, J ) 7.3
Hz, 2H), 7.46 (br d, J ) 7.3 Hz, 2H), 7.33 (br t, J ) 7.3 Hz,
2H), 7.27 (br t, J ) 7.3 Hz, 1H), 6.26 (t, J ) 1.7 Hz, 1H), 2.16
(dt, J ) 1.7, 7.3 Hz, 2H), 1.39 (quint, J ) 7.3 Hz, 2H), 1.30-
1.10 (m, 10H), 0.86 (t, J ) 7.3 Hz, 3H); 13C NMR (CDCl3) δ
197.3 (s), 142.7 (s), 141.5 (s), 139.8 (s), 138.7 (s), 138.5 (d), 135.1
(d), 133.7 (d), 129.4 (d), 129.1 (d), 128.3 (d), 128.2 (d), 127.3
(d), 123.6 (d), 66.0 (s), 32.1 (t), 31.7 (t), 29.0 (t), 28.9 (t), 28.8
(t), 22.6 (t), 14.0 (q); MS m/z (relative intensity) 500 (15, M+),
359 (100), 222 (43), 71 (51); HRMS calcd for C31H32O4S (M+)
500.2021, found 500.2018. Anal. Calcd for C31H32O4S‚1/
4H2O: C, 73.71; H, 6.48. Found: C, 73.82; H, 6.44. The
stereochemistry of 4g was established by the observation of
an NOE enhancement between vinylic (δ 6.26) and allylic
protons (δ 2.16).
1-Nitr o-1-p h en ylcycloh exa n e (12c):42 colorless oil; IR
(CHCl3) 1535, 1445, 1345 cm-1; 1H NMR (CDCl3) δ 7.52-7.30
(m, 5H), 2.94-2.75 (m, 2H), 2.25-1.99 (m, 2H), 1.76-1.26
(m, 6H); MS m/z (relative intensity) 159 [93, (M - NO2)+], 91
(100).
1-Nitr o-1-(p-m eth oxyp h en yl)cycloh exa n e (12e):43 color-
less oil; IR (CHCl3) 1530 cm-1; 1H NMR (CDCl3) δ 7.45 (d, J )
9.2 Hz, 2H), 6.88 (d, J ) 9.2 Hz, 2H), 3.81 (s, 3H), 2.90-1.10
(m, 10H); MS m/z (relative intensity) 189 [100, (M - NO2)+],
121 (100), 81 (25).
Rea ction of 1,3-In d a n d ion e (13a ) w ith 2a . To a stirred
solution of freshly sublimed potassium tert-butoxide (8 mg,
0.07 mmol) in THF (1.5 mL) was added the diketone 13a (11
mg, 0.07 mmol) under argon at room temperature, and the
mixture was stirred for 1 h. A solution of (4-tert-butyl-1-
cyclohexenyl)phenyliodonium salt 2a (31 mg, 0.07 mmol) in
THF (1.5 mL) was added to this mixture at room temperature,
and the mixture was stirred for 2 h. Water was added, the
mixture was extracted with diethyl ether three times, and the
combined organic phase was washed with water and brine.
The solution was dried over anhydrous Na2SO4 and concen-
trated to give an oil, which was purified by preparative TLC
(8:2 hexane-diethyl ether) to give 2,2-bis(4-tert-butyl-1-cyclo-
hexenyl)-1,3-indandione (13b) (2.8 mg, 9%) as colorless crys-
tals: mp 144-146 °C (recrystallized from diethyl ether-
hexane); IR (KBr) 1735, 1700, 1590, 780 cm-1; 1H NMR (CDCl3)
δ 8.03-7.87 (m, 2H), 7.87-7.71 (m, 2H), 5.69-5.55 (m, 2H),
2.33-1.69 (m, 10H), 1.23-1.00 (m, 4H), 0.85 (s, 18H); MS m/z
(relative intensity) 418 (100, M+), 361 (26), 57 (26); HRMS
calcd for C29H38O2 (M+) 418.2872, found 418.2859. Anal.
Calcd for C29H38O2: C, 83.21; H, 9.15. Found: C, 82.94; H,
9.06.
1-Ben zen esu lfon yl-3-pen tylcyclopen ten e. The title com-
pound showed spectral properties identical with those of the
compound previously synthesized.20b
Gen er a l P r oced u r e for Vin yla tion of 1,3-Dica r bon yl
Com p ou n d s in th e P r esen ce of Ra d ica l In h ibitor s. To a
stirred solution of freshly sublimed potassium tert-butoxide
(15 mg, 0.13 mmol) in THF (2 mL) was added a 1,3-dicarbonyl
compound (0.13 mmol) under argon at room temperature, and
the mixture was stirred for 1 h. A radical inhibitor (galvinoxyl
(0.12 mmol), 2,2,6,6-tetramethylpiperidine-N-oxyl (0.12 mmol),
or 1,1-diphenylethylene (0.24 mmol)) and subsequently a
solution of an alkenyl(aryl)iodonium salt 2 or 3 (0.12 mmol)
in THF (3 mL) were added to this mixture at room temperature
or at 50 °C, and the mixture was stirred for the periods shown
in Table 3. Water was added, the mixture was extracted with
diethyl ether three times, and the combined organic phase was
washed with water and brine. The solution was dried over
anhydrous Na2SO4 and concentrated to give an oil, which was
purified by preparative TLC. The yields of pure products are
given in Table 3.
2-Car bom eth oxy-2-(p-m eth oxyph en yl)-1-in dan on e (8e):
colorless oil; IR (neat) 1715, 1600, 1255 cm-1; 1H NMR (CDCl3)
δ 7.82 (d, J ) 7.7 Hz, 1H), 7.68-7.24 (6H), 6.87 (d, J ) 8.7
Hz, 2H), 4.19 (d, J ) 17.3 Hz, 1H), 3.78 (s, 3H), 3.74 (s, 3H),
3.55 (d, J ) 17.3 Hz, 1H); MS m/ z (relative intensity) 296 (34,
M+), 268 (26), 253 (27), 237 (100), 165 (69); HRMS calcd for
C18H16O4 (M+) 296.1049, found 296.1064.
Rea ction of 2,4-P en ta n ed ion e (14a ) w ith 2a . To a
stirred solution of freshly sublimed potassium tert-butoxide
(148 mg, 1.3 mmol) in THF (25 mL) was added the diketone
14a (130 mg, 1.3 mmol) under argon at room temperature,
and the mixture was stirred for 1 h. A solution of (4-tert-butyl-
1-cyclohexenyl)phenyliodonium salt (2a ) (512 mg, 1.2 mmol)
in THF (25 mL) was added to this mixture at room tempera-
ture, and the mixture was stirred for 8 h. Water was added,
the mixture was extracted with diethyl ether three times, and
the combined organic phase was washed with water and brine.
The solution was dried over anhydrous Na2SO4 and concen-
trated to give an oil. Flash chromatography of the crude
product using hexane-diethyl ether (9:1) yielded the olefin 14b
(149 mg, 53%) as colorless needles: mp 77-78 °C (recrystal-
lized from methanol); IR (CHCl3) 1695, 1590, 1360, 975, 910
Bypr odu ct An alysis for Vin ylation of 2-Car bom eth oxy-
in d a n on e (8a ) w ith 2a . (a ) With ou t Ad d itive. To a stirred
solution of freshly sublimed potassium tert-butoxide (9 mg,
0.08 mmol) in THF (0.5 mL) was added a solution of the â-keto
ester 8a (15 mg, 0.08 mmol) in THF (1 mL) under argon at
room temperature, and the mixture was stirred for 1 h.
A
cm-1 1H NMR (CDCl3) δ 16.35 (s, 1H), 5.63-5.57 (m, 1H),
;
solution of the iodonium salt 2a (31 mg, 0.07 mmol) in THF
(1.5 mL) was added to this mixture at room temperature, and
the mixture was stirred for 1 h. Water was added, the mixture
was extracted with pentane, and the combined organic phase
was washed with water and brine. The yields of byproducts
were determined by analytical GC using a column of 20%
2.22-1.84 (m, 5H), 2.04 (s, 6H), 1.34-1.16 (m, 2H), 0.90 (s,
9H); MS m/ z (relative intensity) 236 (70, M+), 221 (14), 179
(42) Kornblum, N.; Taylar, H. J . J . Org. Chem. 1963, 28, 1424.
(43) Kozyrod, R. P.; Pinhey, J . T. Aust. J . Chem. 1985, 38, 713.

2138 J . Org. Chem., Vol. 62, No. 7, 1997
Ochiai et al.
silicone GE SF-96 on Chromosorb W-AWDMCS: benzene (19,
45%) (50 °C, heptane as the internal standard), iodobenzene
(17, 55%), 4-tert-butylcyclohexene (20, 39%)12 (120 °C, dode-
cane as the internal standard), and 4-tert-butyl-1-iodocyclo-
hexane (18, 25%)13a (180 °C, pentadecane as the internal
standard). For the yields of 8b and 8c, see entry 5 in Table 1.
(b) In th e P r esen ce of 1,1-Dip h en yleth ylen e. To a
stirred solution of freshly sublimed potassium tert-butoxide
(9 mg, 0.08 mmol) in THF (0.5 mL) was added a solution of
the â-keto ester 8a (15 mg, 0.08 mmol) in THF (1 mL) under
argon at room temperature, and the mixture was stirred for 1
h. 1,1-Diphenylethylene (26 mg, 0.14 mmol)] and subsequently
a solution of the iodonium salt 2a (31 mg, 0.07 mmol) in THF
(1.5 mL) was added to this mixture at room temperature, and
the mixture was stirred for 0.5 h. Water was added, the
mixture was extracted with pentane, and the combined organic
phase was washed with water and brine. The yields of
byproducts were determined by analytical GC using a column
of 20% silicone GE SF-96 on Chromosorb W-AWDMCS:
benzene (19, 27%), iodobenzene (17, 46%), 4-tert-butylcyclo-
hexene (20, 7%), and 4-tert-butyl-1-iodocyclohexene (18, 16%).
For the yields of 8b and 8c, see entry 5 in Table 3.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
3b, 4e, 4g, 8b, 8e, 9b, 9c, and 10c and the 13C NMR spectrum
for 4g (9 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O962007Y