Cyclization of aryl acyl radicals generated from S-(4-cyano)phenyl thiolesters by a nickel complex catalyzed electroreduction

Article abstract of DOI:10.1021/jo0268512

Aromatic acyl radicals generated from S-(4-cyano)phenyl 2-alkenylthiobenzoate by a nickel complex catalyzed electroreduction undergo 5- and 6-exo cyclization to give 1-indanone and dihydro-1-naphthalenone derivatives, respectively.

Full text of DOI:10.1021/jo0268512

cyclic ketones are isolated in modest to good yield on
subjecting the thiolesters to this electroreductive method.8
Herein, we report a study of the generation of aryl acyl
radicals from the S-(4-cyano)phenyl thiolesters and their
intramolecular additions reactions, which would proceed
according to the reaction path as shown in Scheme 1.
In the search for a precursors suitable to generation
of aryl acyl radicals, a thiolester A, composed of methyl
2-mercaptobenzoate and 2-(prop-2-enyl)benzoic acid, was
subjected to Ni(salen)-catalyzed electroreduction.10
Cycliza tion of Ar yl Acyl Ra d ica ls
Gen er a ted fr om S-(4-Cya n o)p h en yl
Th iolester s by a Nick el Com p lex Ca ta lyzed
Electr or ed u ction
Shigeko Ozaki,* Masashi Adachi, Sayaka Sekiya, and
Rie Kamikawa
Graduate School of Pharmaceutical Sciences, Osaka
University, 1-6, Yamadaoka, Suita, Osaka 565-0871, J apan
ozaki@phs.osaka-u.ac.jp
Received December 15, 2002
Abstr a ct: Aromatic acyl radicals generated from S-(4-
cyano)phenyl 2-alkenylthiobenzoate by a nickel complex
catalyzed electroreduction undergo 5- and 6-exo cyclization
to give 1-indanone and dihydro-1-naphthalenone derivatives,
respectively.
The electrolysis of A provided 30% of 2-(prop-2-enyl)-
benzyl alcohol as a major product and cyclized products
2-methylindanone and 3,4-dihydro-1(2H)-naphthalenone
in 13% and 4% yield, respectively. The yield of a
significant amount of the benzyl alcohol seemed to
indicate that the generated acyl radical would suffer from
further electroreductions, followed by attack with re-
sidual water in DMF (Scheme 1). When thiolester 1a , a
counterpart of A bearing an S-(4-cyano)phenyl group
instead of an S-(2-methoxycarbony)phenyl group, which
exhibits reductive peak of voltammetric measurement at
ca. 0.3 V less negative potential than A, was reductively
electrolyzed at 60 °C using Ni(tet a)2+ 9 as a catalyst, 5-exo
and 6-exo cyclizations of the generated acy radicals were
shown to be major reactions as shown in Table 1.
The comparison of results of the electrolysis in entry
1 with those of entries 3 and 4 suggests that cyclization
of aryl acyl radical onto an alkene proceeds more smoothly
at elevated temperature (60 °C) than at ambient tem-
perature. In previous papers, we have reported that alkyl
and vinyl radicals generated by similar catalytic elec-
troreduction undergo efficient inter- and intramolecular
carbon-carbon bond-forming reactions even at ambient
temperature.7 The present observation that the intramo-
lecular cyclizations of acyl radicals require heating seems
to indicate that the addition rates of acyl radicals onto
alkenes are significantly smaller than those of alkyl and
The generation of acyl radicals and their intra- and
intermolecular carbon-carbon bond-forming reactions
has long been recognized as a useful tool for homolytic
synthesis. The majority of the above reactions have been
achieved by employing acyl selenides,1 aryl acyl tel-
lurides,2 and S-acylxanthates3 as the acyl radical precur-
sors by means of organostannane-mediated chain reac-
tions. In the tin hydride method, the use of S-phenyl
thiolesters which are more stable under oxidizing condi-
tions and attractive as acyl radical precursors is known
not to be practical, since the reactions of stannyl radical
with simple S-phenyl thiolesters are too sluggish to set
the chain propagation viable.4 The tin-free methods such
as the photochemical method where the acylgermanes5
or acylcobalt(III)6 was used as acyl radical precursors
have also been developed and found useful applications
in synthesis of cyclic ketones and lactams, respectively.
We have developed a nickel complex catalyzed elec-
troreductive method as an organotin-free tool available
to conduct radical reactions.7 In our previous paper, we
demonstrated that the S-(2-methoxycarbonyl)phenyl thi-
olesters are a comvenient acyl radical precursor and that
(1) (a) Boger, D. L.; Mathvink, R. J . J . Am. Chem. Soc. 1990, 112,
4008-4011. (b) Boger, D. L.; Mathvink, R. J . J . Org. Chem. 1992, 57,
1429-1443. (c) Batty, D.; Crich. D. J . Chem. Soc., Perkin Trans 1, 1992,
3205-3209. (d) Bennasar, M.-L., Roca, T.; Griera, R.; Bosch, J . Org.
Lett. 2001, 3, 1697-1700.
(8) Ozaki, S.; Yoshinaga, H.; Matsui, E.; Adachi, M. J . Org. Chem.
2001, 66, 2503-2505.
(9) Thiolester A and 1a show reduction peak of voltammogram at
-2.08 and -1.78 V vs SCE, respectively. Ni(salen) exhibits its Ni(I)/
Ni(II) redox wave at -1.70/-1.60 V vs SCE and was found to catalyze
electroreduction of thiolester A , while Ni(tet a)(ClO4)2 exhibits its Ni-
(I)/Ni(II) redox wave at -1.36/-1.28 V vs SCE and was found to
catalyze electroreduction of 1a . For details, see ref 7b.
(2) Crich, D.; Chen, C.; Hwang, J .-T.; Yuan, H.; Papadatos, A.;
Walter, R. I. J . Am. Chem. Soc. 1994, 116, 8937-8951.
(3) Zard, S. Z. Angev. Chem., Int. Ed. Engl. 1997, 36, 672-685.
(4) Penn, J . H.; Liu, F. J . Org. Chem. 1994, 59, 2608-2618.
(5) (a) Kiyooka, S.; Kaneko, y.; Matsue, H.; Hamada, M.; Fujiyama,
R. J . Org. Chem. 1990, 55, 5562-5564. (b) Curran, D. P.; Liu, H. J .
Org. Chem. 1991, 56, 3463-3465. (c) Curran, D.; P.; Diederichsen, U.;
Palovich, M. J . Am. Chem. Soc. 1997, 119, 4797-4804.
(6) Gill, G. B.; Pattenden, G.; Reynolds, S. J . Chem. Soc., Perkin
Trans. 1 1994, 369-378.
(7) (a) Ozaki, S.; Matsushita, H,; Ohmori, H. J . Chem. Soc., Chem.
Commun. 1992, 1120-1122. (b) Ozaki, S.; Matsushita, H. ; Ohmori,
H.; J . Chem. Soc., Perkin Trans. 1 1993, 649-651. (c) Ozaki, S.;
Matsushita, H.; Ohomori, H. J . Chem. Soc., Perkin Trans. 1 1993,
2339-2344. (d) Ozaki, S.; Horiguchi, I.; Matsushita, H.; Ohmori, H.
Tetrahedron Lett. 1994, 35, 725-728. (e) Ozaki, S.; Matsui, E.; Waku,
J .; Ohmori, H. Tetrahedron Lett. 1997, 38, 2705-2708.
(10) Product 2c was accompanied by formation of compound 1cH
(5%), which was derived from reduction of the acceptor double bond
in 1c.
10.1021/jo0268512 CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/01/2003
4586
J . Org. Chem. 2003, 68, 4586-4589

SCHEME 1
TABLE 1. Electr or ed u ctive In tr a m olecu la r Cycliza tion of S-(4-Cya n o)p h en yl Th iolester a
substrate
R1
product, yield (%)
entry
1
R2
n
2
3
4
1b
2c
3
1a
1a
1a
1a
1b
1c
1c
1d
1e
1f
H
H
H
H
H
H
H
H
H
H
H
OMe
H
1
1
1
1
1
1
1
1
2
2
2a , 22
4
3a , trace
trace
2
4a , 42
80
0
11
4b, 19
0
0
4d , 14
0
4f, 6
8 (42)d
46
4e
5
trace
CH3
CO2Et
CO2Et
H
CO2Et
H
2b, 40
2c, 59
54g
2d , 63
2e, 44
2f, 41
3b,f trace
6
0
0
7e
8e
9e
10e
3d ,f trace
0
0
H
a
Electrolysis was conducted in DMF (20 mL) using a thiolester 1 (1 mmol), Ni(tet a)2+ (0.2 mmol), and tetraethylammonium
p-toluenesulfonate (2 mmol) at 60 °C. Electrolysis at room temperature. c Electrolysis without Ni(tet a)2+
.
Obtained as dimer of 2a .
b
d
e Electrolysis with 2 equiv of Ph2PH. f The existences of 3b and 3d are recognized by 1H NMR of the mixture with 2b and 2d , respectively.
g
Accompanied with a byproduct (5%) derived from reduction of the acceptor double bond in 1c.
vinyl radicals. Under the present reaction conditions, the
acyl radicals 1′ were also shown to provide products
resulting from 5-exo cyclization in much better yields
than those from 6-endo cyclization. Electroreduction of
1a without a catalyst Ni(tet a)2+ afforded a benzyl alcohol
4a in 80% yield and a trace amount of a cyclic ketone
2a . Electrolysis in entry 3 shows that a large part of the
cyclized radical was isolated as dimer 2a ′; i.e., the
trapping rate of the cyclized radical 2r (Scheme 1) by
hydrogen from the solvent DMF could not be fast enough
to prevent the coupling of the cyclized radical 2r derived
from 1a . The formation of the dimer 2a ′ was suppressed,
and 2-methylindanone 2a was provided in 46% yield on
addition of 2 equiv of diphenylphosphine as a hydrogen
donor (entry 4).7d As shown in entry 5, introduction of a
methyl group at the terminal of the acceptor also sup-
pressed the formation of the product from coupling of the
corresponding radicals 2r , however, it decreased yield of
2b to 40% and increased the yield of the corresponding
benzyl alcohol instead. These observations may suggest
that the decreased yield of 2b results from the decrease
in the rate of cyclization of the corresponding acyl radical
onto alkene. On the other hand, the introduction of an
electron-withdrawing group -CO2Et facilitated the 5-exo
cyclization of the acyl radical regardless of the presence
or absence of diphenylphosphine. The results in entries
5-7 seem to be consistent with the explanation that acyl
radicals exhibit nucleophilic character.11 Electrolysis of
a thiolester 1d prepared with 3-methoxybenzoic acid
provided a methylindanone 2d most effectively, probably
because the nucleophilic character of the acyl radical
derived from 1d is somewhat enhanced by the methoxy
11b
group.
The thiolesters 1e and 1f afforded dihydro-1-
naphthalenones 2e and 2f, respectively, via 6-exo cy-
clization in modest yield. 6-Exo cyclizations are slower
(11) (a) Brown, C. E.; Neville, A. G.; Rayner D. M.; Ingold, K. U.;
Lusztyk, J . Aust. J . Chem. 1995, 48, 363-379. (b) Crich, D.; Hao, X.
J . Org. Chem. 1997, 62, 5982-5988.
J . Org. Chem, Vol. 68, No. 11, 2003 4587

with brine, dried over MgSO4, and concentrated under reduced
pressure. Purification of the crude product by column chroma-
tography provided 4,4-dimethyl-2-[2(prop-2-enyl)]phenyl-2-ox-
azoline (5.47 g, 58%) as an oil. The oxazoline was converted to
the methiodide salt by stirring in excess MeI and DMSO
overnight at room temperature, and the volatiles were evapo-
rated under reduced pressure. The crude oxazoline methiodide
was added to 80 mL of 2 N NaOH and the mixture heated under
reflux for 8 h. The solution was washed with CH2Cl2 (35 mL ×
2), acidified to pH 1-2 with 10 N HCl, and extracted with CH2-
Cl2 (40 mL × 2). The extracts were washed with brine, dried
(MgSO4), and concentrated to leave 2-(prop-2-enyl)benzoic acid
as a yellow oil (2.54 g, 62%).
Meth od B: 5-Meth oxy-2-(p r op -2-en yl)ben zoic Acid . To
a solution of 2-bromo-5-methoxybenzoic acid (2.9 g, 12.6 mmol)
in MeOH (10 mL) was added 1.5 mL of concentrated H2SO4
dropwise at 0 °C, and the mixture was heated for 3 h. The
mixture was transferred into ice-cold water (25 mL), extracted
with AcOEt, washed successively with water (15 mL × 2), 5%
NaHCO3 (25 mL × 2), and 10 mL of brine, dried, and concen-
trated under reduced pressure. Purification of the crude product
by column chromatography afforded methyl 2-bromo-5-meth-
oxybenzoate (3.06 g, 99%). Methyl 2-bromo-5-methoxybenzoate
(3.06 g, 12.5 mmol), allyltributyltin (4.55 g, 13.75 mmol), and
Pd(PPh3)4 (0.144 g, 0.125 mmol) were added to 10 mL of benzene
in a sealed tube and the mixture heated at 120 °C for 20 h. The
mixture was transferred into 10 mL of water and extracted with
benzene. The extract was washed with water and dried. The
crude product obtained after concentration of the solution was
purified by column chromatography to provide methyl 5-meth-
oxy-2-(prop-2-enyl)benzoate (1.25 g, 57%) as a yellow oil. The
methyl benzoate (1.25 g, 6.1 mmol) was refluxed with 6 mL of
EtOH and 6 mL of 10% aqueous NaOH for 1 h. To the mixture
was added 10 mL of water, and the mixture washed with CH2-
Cl2 (15 mL × 2) and extracted with AcOEt (30 mL × 3) after
the pH was adjusted to pH 1-2 with 10 N HCl. The organic
layer was dried and concentrated under reduced pressure to
provide 5-methoxy-2-(prop-2-enyl)benzoic acid (0.92 g, 79%) as
a yellow oil.
Meth od C: 2-(Eth ylbu t-2-en oyl)ben zoic Acid . This ben-
zoic acid and the related benzoic acid 2-(ethyl pent-2-enoyl)-
benzoic acid were prepared according to the literature method.1b
Con d en sa tion of 4-Cya n oben zen eth iol w ith 2-(P r op -2-
en yl)ben zoic Acid To P r ovid e S-(4-Cya n o)p h en yl 2-(P r op -
2-en yl)ben zen eth ioa te (1a ). Diethyl cyanophosphonate (1.47
g, 9 mmol) was added dropwise to the 2-(prop-2-enyl)benzoic acid
in DMF dry (15 mL) at 0 °C and the mixture stirred for 30 min.
To the mixture were succesively added dropwise 4-cyanoben-
zenethiol in 4 mL of DMF and Et3N (0.90 g, 8.9 mmol) and the
mixture stirred for 2 h at 0 °C. The mixture was transferred to
150 mL of benzene and washed successively with 60 mL of 5%
citric acid, saturated NaHCO3, and brine. The crude product
obtained after concentration of the solvent was purified by
recrystallization from AcOEt-hexane to afford S-(4-cyano)-
phenyl 2-(prop-2-enyl)benzenethioate 1a (0.95 g, 39%) as a white
solid: mp 87-91 °C; 1H NMR δ 3.60 (2H, d, J ) 6.4), 4.98 (1H,
dd, J ) 1.6, 16.8), 5.05 (1H, dd, J ) 1.4, 10.0), 5.90-5.99 (1H,
m), 7.29-7.38 (2H, m), 7.51 (1H, td, J ) 1.1, 7.5), 7.63 (2H, d, J
) 8.4), 7.73 (2H, d, J ) 8.4), 7.89 (1H, d, J ) 7.7); 13C NMR δ
37.5, 113.0, 116.1, 126.4, 126.5, 128.6, 131.2, 132.5, 132.6, 132.7,
134.6, 139.2, 190.2; IR (Nujol) νmax 767, 915, 1004, 1205, 1220,
1635 (CdC), 1680 (SCdO), 2230 (CN) cm-1; FABMS m/e 280
(M+ + H); FABHRMS m/e 280.0777 (C14H17NOS requires
280.0796). Characterization based on the analytical and spectral
data of the benzoic acids prepared by one of the three different
methods A, B, and C and thiolesters 1b-f are given in the
Supporting Information.
than the related 5-exo cyclizations, and the intramolecu-
lar allylic hydrogen transfer to give hydrogenated prod-
ucts of the initial radicals usually becomes a serious
concern.12 However, the results of entries 9 and 10
suggest that 6-exo cyclization of the aryl acyl radicals
can compete with the intramolecular allylic hydrogen
transfer even with a thiolester 1f bearing unactivated
alkene under the present reaction conditions.1b,13 Definite
explanations for the observations in entries 9 and 10
seem to be unobtainable until mechanistic behaviors of
alk-6-enoyl radicals are fully investigated like the related
alk-5-enoyl radicals.11a,14 Under the present reaction
conditions, the rate of competitive decarbonylation of aryl
acyl radicals 1′ could be presumed to be significantly
smaller than those for 5-exo and 6-exo cyclizations of the
corresponding acyl radicals 1′ onto alkene acceptors
judging from the observation that the products derived
from the decarbonylation of acyl radical 1′ were not
detected.14
In summary, modification of the structure of radical
precursors, S-phenylthiolesters, was found to allow aryl
acyl radicals which are generated by nickel complex
catalyzed electroreductive methods to undergo 5- and
6-exo cyclization reactions similarly to alkyl acyl radi-
cals.8 This organotin-free methodology could be a useful
alternative to other methods available to conduct reac-
tions of acyl radicals due to the merits that reactions
could be driven by the use of stable starting materials
and harmless reagents with no need for desiccation of
the solvent.
Exp er im en ta l Section
Gen er a l Meth od s. 1H and 13C NMR spectra were recorded
as CDCl3 solutions at 300 and 75 MHz, respectively, using TMS
as internal reference. The J values are given in hertz (Hz).
Column chromatography was carried out on SiO2 (silica gel 60,
0.063-0.2 mm). Melting points are uncorrected. Cyclic voltam-
metry was performed with a three-elecrode system employing a
linear scanning unit (Huso Electronical System HECS 321B)
equipped with a potentiostat (Hokuto Denko PS-55B). Constant
current electrolysis was carried out with a potentio-galvanostat
(Hokuto Denko HA105S), and the quantity of electricity was
recorded with a coulometer (Hokuto Denko HF-201). All chemi-
cals used were commercially available.
Gen er a l P r oced u r e for th e P r ep a r a tion of S-(4-Cya n o)-
p h en yl Th iolester s 1. S-(4-Cyano)phenyl thiolesters were
prepared by condensation reaction of 4-cyanobenzenethiol with
the corresponding benzoic acids which were synthesized by one
of the three different methods A, B, and C. 4-Cyanobenzenethiol
was prepared from 4-cyanophenol according to the known
method for synthesis of 2-(prop-2-enyl)benzenethiol.15
Meth od A: 2-(P r op -2-en yl)ben zoic Acid . To a solution of
4,4-dimethyl-2-phenyl-2-oxazoline (7.71 g, 44 mmol) in dry THF
(130 mL) was added BuLi (37 mL of 1.6 M in hexane, 59 mmol)
dropwise at 0 °C, and the mixture was stirred for 3.5 h. The
solution was transferred to a suspension of cuprous bromide
(6.24 g, 43.5 mmol) in dry THF using a cannula (2 mm in
diameter) and nitrogen gas. The green mixture was stirred at 0
°C for 1.5 h, and then allyl bromide (4.84 g, 40 mmol) was added
and stirred overnight. To the mixture was added 45 mL of water
followed by 28% NH3 in water. The organic layer was washed
P r oced u r e for th e Electr or ed u ction of th e Th iolester s
1. The electroreduction was performed in DMF (10 or 20 mL)
using 0.5 or 1.0 mmol of a thiolester 1, 0.1 or 0.2 mmol of Ni(tet
a)(ClO4)2, 1 or 2 mmol of tetraethylammonium tosylate (TEATs)
as a supporting electrolyte, a graphite plate as a cathode, and
an aluminum rod as an anode in an undivided cell at 60 °C under
an atmosphere of nitrogen. A constant current (3 mA) was
(12) Curran, D. P. Synthesis 1988, 489-513 and references therein.
(13) Bachi, M. D.; Denenmark, D. Heterocycles 1989, 28, 583-588.
(14) Chatgilialoglu, C.; Ferreri, C.; Lucarini, M.; Venturini, A.;
Zavistas, A. A. Chem. Eur. J . 1997, 3, 376-387.
(15) Young, R. N.; Gauthier, J . Y.; Zamboni, R.; Belley, M. L. Eur.
Pat. Appl. EP 399,818, 1991.
4588 J . Org. Chem., Vol. 68, No. 11, 2003

passed until the substrate was consumed (determined by TLC).
The electricity passed was 3 F/mol of the substrate 1. The
solution from the electrolysis was transferred to a brine solution
(100 mL) and extracted with ether (40 mL × 3). The crude
product obtained after concentration under vacuum was purified
by silica gel column chromatography. Yields of products are
given in Table 1; their characterization data based on the
analytical and spectral data are given below.
CdO), 1730 (ester CdO) cm-1; EIMS m/e 232 (M+), 144 (M+
-
CH3CO2Et); EIHRMS m/e 232.1107 (C14H16O requires 232.1099).
3,4-Dih yd r o-2-m eth yl-1(2H)-n a p h th a len on e (2f): colorless
oil; 1H NMR δ 1.27 (3H, d, J ) 6.7), 1.89 (1H, ddd, J ) 5.1, 12.9,
24.9), 2.20 (1H, dq, J ) 4.4, 13.2), 2.53-2.75 (1H, m,), 2.94-
3.11 (2H, m,), 7.23 (1H, d, J ) 7.7), 7.30 (1H, t, J ) 7.5), 7.47
(1H, td, J ) 1.4, 7.3), 8.03 (1H, dd, J ) 1.2); 13C NMR δ 15.3,
28.7, 31.2, 42.5, 126.4, 127.2, 128.6, 132.3, 132.9, 144.0, 200.6;
IR (Nujol) νmax 740, 968, 1230, 1456, 1600, 1683 (ketone CdO),
2,3-Dih yd r o-2-m eth yl-1H-in d en -1-on e (2a ): colorless oil; 1H
NMR δ 1.21 (3H, d, J ) 7.1), 2.57-2.62 (1H, m), 2.63-2.67 (1H,
m), 3.25-3.34 (1H, m), 7.23-7.30 (1H, m), 7.33-7.36 (1H, m),
7.44-7.50 (1H, m), 7.63-7.67 (1H, m); 13C NMR δ 16.2, 34.9,
41.9, 123.9, 126.4, 127.3, 134.6, 136.3, 153.4, 209.4; IR (neat) ν
max 765, 1203, 1274, 1464, 1611, 1710 (CdO), 2950 (CH3) cm
-1; EIMS m/e 146 (M+), 131 (M+ - CH3); EIHRMS m/e 146.0744
(C10H10O requires 146.0732).
2930 cm-1; EIMS m/e 160 (M+), 145 (M+ - CH3), 118 (M+
C3H6); EIHRMS m/e 160.0913 (C11H12O requires 160.0888).
-
3,4-Dih yd r o-1(2H)-n a p h th a len on e (3a ): colorless oil; 1H
NMR δ 2.05-2.11 (2H, m), 2.57-2.61 (2H, m), 2.88-2.95 (2H,
m), 7.19-7.39 (2H,m), 7.50 (1H, t, J ) 7.5), 7.96 (1H, d, J )
7.5).
2-(Bu t-2-en yl)ben zyl a lcoh ol (4a ): colorless oil; 1H NMR δ
3.39 (2H, d, J ) 6.2), 4.63 (2H, s), 4.91 (1H, dd, J ) 1.2, 16.7),
4.98 (1H, dd, J ) 1.2, 10.0), 5.90-5.93 (1H, m), 7.12-7.21 (4H,
m).
1,2-Di(1-in d a n oyl)eth a n e (2a ′): colorless oil; 1H NMR δ
2.95-3.01 (4H, m, CH2CH2), 3.04-3.05 (1H × 2, m), 3.36-3.44
(1H × 2, dd, J ) 6.8, 16.7), 3.68 (1H × 2, d, J ) 9.1), 7.35-7.42
(3H, m), 7.44-7.47 (1H, m), 7.51-7.57 (2H, m), 7.58-7.63 (1H,
m), 7.73-7.75 (1H, m); 13C NMR δ 32.4, 33.7, 46.2, 124.1, 126.5,
127.3, 127.7, 132.3, 135.2, 205.5; EIMS m/e 290 (M+), 145 (1/2
M+).
5-Meth oxy-2-(p r op -2-en yl)ben zyl a lcoh ol (4d ): yellow oil;
1H NMR δ 1.58 (1H, t, J ) 6.0), 3.39 (2H, d, J ) 6.0), 3.80 (3H,
s), 4.67 (2H, d, J ) 5.8), 4.93-5.07 (2H, m), 5.91-6.04 (1H, m),
6.79 (1H, dd, J ) 2.7, 8.2), 6.98 (1H, d, J ) 2.5), 7.10 (1H, d, J
) 8.4,); 13C NMR δ 36.0, 55.2, 63.0, 113.1, 113.5, 115.5, 129.4,
130.9, 137.8, 140.0, 158.3; IR (neat) νmax 920, 1038, 1160, 1193,
1260, 1498, 1576, 1610, 1637, 2940 cm-1; EIMS m/e 178 (M+);
EIHRMS m/e 178.1000 (C11H14O2 requires 178.0994).
2,3-Dih yd r o-2-eth yl-1H-in d en -1-on e (2b): colorless oil; 1H
NMR δ 1.02 (3H, t, J ) 7.4), 1.23-1.34 (1H, m), 1.94-2.02 (1H,
m), 2.58-2.66 (1H, m), 2.83 (1H, dd, J ) 3.8, 17.1), 3.32 (1H,
dd, J ) 8.1, 17.1), 7.36 (1H, td, J ) 0.7, 7.3), 7.46 (1H, dt, J )
0.9, 8.6), 7.58 (1H, td, J ) 1.2, 7.4), 7.75 (1H, d, J ) 7.5); EIMS
m/e 160 (M+), 145 (M+ - CH3), 132, 131 (M+ - C2H5); EIHRMS
m/e 160.0918 (C11H12O requires 160.0888).
1
2-(Bu t-3-en yl)ben zyl a lcoh ol (4f): colorless oil; H NMR δ
1.26 (1H, t, J ) 7.1), 2.22 (2H, q, J ) 7.7), 2.79 (2H, t, J ) 7.9),
4.73 (2H, d, J ) 4.5), 4.97-5.09 (2H, m), 5.81-5.92 (1H, m),
7.25-7.35 (2H, m), 7.37-7.39 (1H, m), 7.48-7.53 (1H, m); EIMS
m/e 162 (M+); EIHRMS m/e 162.1056 (C11H14O requires 162.1045).
Eth yl 2-[2-(2,3-d ih yd r o-1-oxo-1H-in d en yl)]a ceta te (2c):
white solid; mp 40-41 °C; 1H NMR δ 1.21 (3H, t, J ) 7.1), 2.58-
2.67 (1H, m), 2.85-3.06 (3H, m), 3.46 (1H, dd, J ) 7.8, 16.9),
4.14 (2H, q, J ) 7.1), 7.38 (1H, t, J ) 7.4), 7.46 (1H, d, J ) 7.7),
7.56-7.62 (1H, m), 7.77 (1H, d, J ) 7.7); 13C NMR δ 14.0, 32.8,
35.1, 43.4, 60.6, 123.8, 126.4, 127.3, 134.7, 136.2, 153.2, 171.8,
206.7; IR (Nujol) νmax 770, 1183, 1228, 1410, 1607, 1710 (ketone
CdO), 1725 (ester CdO) cm-1; EIMS m/e 218 (M+), 172, 145 (M+
- CO2Et); EIHRMS m/e 218.0954 (C13H14O requires 218.0943).
2,3-Dih ydr o-6-m eth oxy-2-m eth yl-1H-in den -1-on e (2d): col-
orless oil; 1H NMR δ 1.31 (3H, J ) 7.3), 2.61-2.68 (1H, m,),
2.70-2.77 (1H, m), 3.32 (1H, dd, J ) 7.3, 16.2), 3.83 (3H, s),
7.16-7.19 (2H, m), 7.32-7.35 (1H, m); 13C NMR δ 16.3, 34.2,
42.7, 55.5, 105.1, 124.0, 127.1, 137.4, 146.2, 159.3, 209.4; IR
(neat) νmax 1027, 1245, 1280, 1490, 1617, 1710 (CdO), 2930, 2960
cm-1; FABMS m/e 177 (M+ + H), 149 (M+ + H - CO);
FABHRMS m/e 177.0919 (C11H12O2 requires 177.0916).
Eth yl 2-[2-(1,2,3,4-tetr a h yd r o-1-oxon a p h th a len yl)]a ce-
ta te (2e): white solid; mp 53-55 °C; 1H NMR δ 1.28 (3H, t, J )
7.1), 1.98 (1H, ddd, J ) 4.5, 12.9, 25.5), 2.20-2.29 (1H, m), 2.38-
2.51 (1H, m), 2.93-3.19 (4H, m), 4.19 (2H, q, J ) 7.1), 7.23 (1H,
d, J ) 7.5), 7.30 (1H, t, J ) 7.5), 7.47 (1H, td, J ) 1.4, 7.3), 8.03
(1H, dd, J ) 1.2, 7.8); 13C NMR δ 14.1, 29.1, 35.0, 44.6, 53.3,
60.4, 126.5, 127.3, 128.6, 132.4, 133.2, 143.9, 172.4, 198.3; IR
(Nujol) ν max 760, 900, 1176, 1200, 1290, 1320, 1600, 1674 (ketone
E t h yl
4-[2-[(4-cya n op h e n yl)t h ioca r b on yl]p h e n yl]-
bu ta n oa te (1cH): white solid; mp 76-79 °C; 1H NMR δ 1.23
(3H, t, J ) 7.1), 1.92 (2H, q, J ) 7.5), 2.32 (2H, t, J ) 7.5), 2.84
(2H, t, J ) 7.7), 4.10 (2H, q, J ) 7.1), 7.30-7.37 (1H, m), 7.47-
7.61 (2H, m), 7.65 (2H, d, J ) 8.0), 7.75 (2H, d, J ) 8.0), 7.90
(1H, d, J ) 7.7); IR (Nujol) νmax 907, 1200, 1263, 1638, 1657,
1683 (SCdO), 1730 (OCdO), 2225 (CN) cm-1; FABMS m/e 354
(M++H ), 219 (M+ - SAr); FABHRMS m/e 354.1167 (C20H20
NO3S requires 354.1164).
-
Ack n ow led gm en t. We are grateful to M. Pharm.
K. Okamoto for technical support of the Web submission
of this manuscript.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data (1H NMR, 13C NMR, MS) for thiolesters 1b-f and three
benzoic acids. Copies of 1H and 13C NMR spectra for com-
pounds 1a -f, 2a -f, and 1H NMR spectra of 4a ,b,f and 1cH.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O0268512
J . Org. Chem, Vol. 68, No. 11, 2003 4589