Preparation of carbocycles via base-catalyzed endo-mode cyclization of allenes

Article abstract of DOI:10.1021/jo050729w

A new and reliable procedure for constructing five- to seven-membered carbocycles via an endomode ring-closing reaction of 1-phenylsulfonylallenes with a substituent that has a terminal active methine moiety at the C ₁-position has been developed. Trisubstituted 1-phenylsulfonylallenes underwent a similar endo-mode ring-closing reaction to produce the corresponding five- to seven-membered carbocycles, while the formation of six- and seven-membered carbocycles from the corresponding tetrasubstituted allene was not realized. In addition, the introduction of an aromatic ring to the alkyl side chain of the starting allenes made possible the construction not only of normal-sized carbocycles but also an eight-membered framework.

Full text of DOI:10.1021/jo050729w

Preparation of Carbocycles via Base-Catalyzed Endo-Mode
Cyclization of Allenes
Chisato Mukai,* Norikazu Kuroda, Rie Ukon, and Rumiko Itoh
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology,
Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
cmukai@kenroku.kanazawa-u.ac.jp
Received April 12, 2005
A new and reliable procedure for constructing five- to seven-membered carbocycles via an endo-
mode ring-closing reaction of 1-phenylsulfonylallenes with a substituent that has a terminal active
methine moiety at the C1-position has been developed. Trisubstituted 1-phenylsulfonylallenes
underwent a similar endo-mode ring-closing reaction to produce the corresponding five- to seven-
membered carbocycles, while the formation of six- and seven-membered carbocycles from the
corresponding tetrasubstituted allene was not realized. In addition, the introduction of an aromatic
ring to the alkyl side chain of the starting allenes made possible the construction not only of normal-
sized carbocycles but also an eight-membered framework.
Introduction
m-chloroperbenzoic acid (m-CPBA), followed by a novel
base-catalyzed endo-mode ring closure of the resulting
allenyl sulfones 2 (R ) SO2Ph) (Scheme 1). A similar
The construction of carbocycles is a fundamental and
significant process in organic synthesis. Many useful
procedures have been developed for preparing mono- as
well as multicyclic carbon frameworks. The classical
intramolecular Michael-type conjugate addition of car-
banion species1 to activated alkenes and alkynes with an
electron-withdrawing group (i.e., Michael acceptors) is
still one of the most frequently used methods, despite
recent progress in the field of organotransition metal
chemistry.2,3 In contrast to the many examples of in-
tramolecular Michael-type addition of carbanions1 to
alkenes and alkynes possessing an electron-withdrawing
group, relatively few examples of the corresponding
allene derivatives have been reported.4-7 In previous
papers,8 we reported a novel and efficient method for the
preparation of five- to nine-membered oxacycles 3 (X )
O) via the endo-mode intramolecular ring-closing reaction
of allenes 2 (X ) OH) with a phenylsulfonyl functional-
ity.9,10 This procedure involves the known [2,3]-sigma-
tropic rearrangement of the propargyl alcohols 1 with
benzenesulfenyl chloride (PhSCl) and oxidation with
(2) For alkyne, see: (a) Fournet, G.; Balme, G.; Gore, J. Tetrahedron
1991, 47, 6293-6304. (b) Monteiro, N.; Gore, J.; Balme, G. Tetrahedron
1992, 48, 10103-10114. (c) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli,
F. Synlett 1993, 65-68. (d) Cruciani, P.; Aubert, C.; Malacria, M.
Tetrahedron Lett. 1994, 35, 6677-6680. (e) McDonald, F. E.; Olson,
T. C. Tetrahedron Lett. 1997, 38, 7691-7692. (f) Tsukada, N.; Yama-
moto, Y. Angew. Chem., Int. Ed. Engl. 1997, 36, 2477-2480. (g)
Kitagawa, O.; Suzuki, T.; Inoue, T.; Taguchi, T. Tetrahedron Lett. 1998,
39, 7357-7360. (h) Kadota, I.; Shibuya, A.; Gyoung, Y.; Yamamoto, Y.
J. Am. Chem. Soc. 1998, 120, 10262-10263. (i) Kitagawa, O.; Suzuki,
T.; Inoue, T.; Watanabe, Y.; Taguchi, T. J. Org. Chem. 1998, 63, 9470-
9475. (j) Bouyssi, D.; Monteiro, N.; Balme, G. Tetrahedron Lett. 1999,
40, 1297-1300. (k) Kitagawa, O.; Suzuki, T.; Fujiwara, H.; Fujita, M.;
Taguchi, T. Tetrahedron Lett. 1999, 40, 4585-4588. (l) Kitagawa, O.;
Fujiwara, H.; Suzuki, T.; Taguchi, T.; Shiro, M. J. Org. Chem. 2000,
65, 6819-6825 and references therein.
(3) For allene, see: (a) Besson, L.; Bazin, J.; Gore, J.; Cazes, B.
Tetrahedron Lett. 1994, 35, 2881-2884. (b) Yamamoto, Y.; Al-Masum,
M.; Asao, N. J. Am. Chem. Soc. 1994, 116, 6019-6020. (c) Trost, B.
M.; Gerusz, V. J. J. Am. Chem. Soc. 1995, 117, 5156-5157. (d) Meguro,
M.; Kamijo, S.; Yamamoto, Y. Tetrahedron Lett. 1996, 37, 7453-7456
and references therein.
(4) Ma, S. In Modern Allene Chemistry; Krause, N., Stephen, A.,
Hashmi, K., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 2, pp 595-684.
(5) Parsons and co-workers reported the intramolecular Michael-
type reaction of allene derivative with a terminal carbanion species.
Thus, the ring-closing reaction of dimethyl 4-methyl-6-(phenylsulfinyl)-
4,5-hexadiene-1,1-dicarboxylate resulted in the formation of seven-
membered oxacycles, instead of the expected carbocycles, presumably
due to exo-mode closure by the oxygen atom of the methoxycarbonyl
moiety at the sp-hybridized carbon center. The cyclopentane derivative,
which would be anticipated by the attack of the terminal carbanion
moiety in an exo-mode manner, could not be detected. Pairaudeau, G.;
Parsons, P. J.; Underwood, J. M. Chem. Commun. 1987, 1718-1720.
* To whom correspondence should be addressed. Tel: +81-76-234-
4411. Fax: +81-76-234-4410.
(1) For leading reviews, see: (a) Winterfeldt, E. Kontakte (Darm-
stadt) 1987, 37-56; Chem. Abstr. 1988, 109, 22316d. (b) Perlmutter,
P. Conjugate Addition Reactions in Organic Synthesis; Tetrahedron
Organic Chemistry Series Vol, 9; Pergamon: Oxford, 1992. (c) Little,
R. D.; Masjedizadeh, M. R.; Wallquist, O.; McLoughlin, J. I. Org. React.
1995, 47, 315-552.
10.1021/jo050729w CCC: $30.25 © 2005 American Chemical Society
Published on Web 07/13/2005
6282
J. Org. Chem. 2005, 70, 6282-6290

Base-Catalyzed Endo-Mode Cyclization of Allenes
SCHEME 1
SCHEME 2a
protocol using phosphorus reagents11 instead of PhSCl
provided oxacycles 3 (R ) POPh2, PO(OEt)2) with a
phosphoryl or a phosphono functionality, which should
be very useful for further manipulations.12,13 Further-
more, this newly developed method was shown to be
suitable for the preparation of not only five- to seven-
membered monocyclic nitrogen-containing heterocycles,
but also azabicyclic systems.14
a Reaction conditions: (a) NaH, DMF, 0 °C to rt; (b) p-TsOH,
MeOH, rt, 6a (86%), 6b (86%), 6c (31%), 6d (90%); (c) PhSCl, Et3N,
THF, -78 °C; (d) m-CPBA, CH2Cl2, 0 °C, 7a (85%), 7b (81%), 7c
(77%), 7d (50%).
TABLE 1. Base-Catalyzed Ring-Closing Reaction of 7aa
Next, we15 sought to synthesize carbocycles 3 (X )
active methine) using the base-catalyzed endo-mode ring-
closing reaction of allenes with a phenylsulfonyl group
as well as a terminal active methylene moiety. In this
paper, we describe the details of the novel intramolecular
ring-closing reaction of allenyl sulfones with suitable
internal carbon nucleophiles in an endo-mode manner
leading to substituted-cyclopentene, cyclohexene, and
cycloheptene derivatives. Preparation of benzocyclohex-
ene, benzocycloheptene, and benzocyclooctene skeletons
is also described.
entry
base
equiv
solvent
time
yield (%)
1
2
tBuOK
1.5
1.5
1.5
4.5d
4.5d
4.5d
1.5
1.5
1.5
1.5
tBuOH
tBuOH
tBuOH
MeOH
MeOH
MeOH
tBuOH
tBuOH
THF
5 minb
5 minb
9 hc
84
47
96
96
95
65
62
73
67
65
tBuONa
tBuOLi
MeOK
3
4
2 hc
5
MeONa
MeOLi
aq KOH
aq NaOH
aq KOH
aq NaOH
26 hc
5 minb
5 minb
30 minc
6 h
6
7
8
9
10
THF
6 h
Results and Discussion
a Reaction was monitored by TLC. Complete consumption of 7a
was observed within 5 min. b No other products could be detected
on TLC. c Three spots gradually converged to 8a. d A longer
reaction time was required when 1.5 equiv of base was used.
The required starting allenes for the ring-closing
reaction were prepared by conventional means in a
straightforward manner as depicted in Scheme 2. The
known propargyl alcohol derivative 416 was treated with
the active methylene species 5 in the presence of NaH
to give the condensed products, which were subsequently
exposed to acidic conditions (p-TsOH, MeOH) to afford 6
with a propargyl alcohol moiety. Conversion of 6 into the
desired allenes 7 with a phenylsulfonyl group was
realized by successive treatment of 6 with PhSCl17 in
THF at -78 °C in the presence of Et3N and m-CPBA in
CH2Cl2 at 0 °C (Scheme 2).
Initially, we investigated the transformation of 7a (Z1
) Z2 ) CO2Me) to the corresponding ring-closed product.
The results are summarized in Table 1. The ring-closing
reaction of 7a was first attempted according to the
previously optimized conditions8 for the ring-closing
reaction of allenyl sulfones 2 (R ) SO2Ph, X ) OH). Thus,
exposure of 7a to BuOK (1.5 equiv) in BuOH at room
temperature for 5 min (consumption of the starting
material was monitored by TLC) furnished the unex-
pected cyclopentene derivatives 8a18 in 84% yield (entry
1). When tBuONa (1.5 equiv) was used instead of tBuOK,
the starting 7a disappeared within 5 min, the same as
entry 1, but the chemical yield of 8a was much lower
(entry 2). Treatment of the allenyl sulfone 7a with MeOK
(4.5 equiv) in MeOH immediately led to not only complete
consumption of the starting material as in the case of
tBuOK (entries 1 and 2), but also to the production of
three spots on TLC, which after 2 h converged into 8a in
96% yield (entry 4). A similar result was obtained when
(6) Parsons, P. J.; Stefinovic, M. Synlett 1993, 931-932.
(7) The intermolecular Michael-type reaction between the 1,2-allenyl
ketones with the active methine derivatives has been reported. Ma,
S.; Yin, S.; Li, L.; Tao, F. Org. Lett. 2002, 4, 505-507.
(8) Mukai, C.; Yamashita, H.; Hanaoka, M. Org. Lett. 2001, 3, 3385-
3387.
(9) Parsons reported an exo-mode ring-closing reaction of allenyl
sulfoxide derivatives; see: (a) Pairaudeau, G.; Parsons, P. J.; Under-
wood, J. M. J. Chem. Soc., Chem. Commun. 1987, 1718-1720. (b) Gray,
M.; Parsons, P. J.; Neary, A. P. Synlett 1992, 597-598. (c) Gray, M.;
Parsons, P. J.; Neary, A. P. Synlett 1993, 281-282. (d) Parkes, K.;
Penkett, C. S.; Parsons, P. J. Synlett 1995, 709-710. (e) Edwards, N.;
Macritchie, J. A.; Parsons, P. J.; Drew, M. G. B.; Jahans, A. W.
Tetrahedron 1997, 53, 12651-12660. (f) Edwards, N.; Macritchie, J.
A.; Parsons, P. J. Tetrahedron Lett. 1998, 39, 3605-3608.
(10) Dai described an exo-mode ring-closing reaction of allenyl
sulfones resulting in the formation of five-membered oxacycles: Dai,
W.-M.; Lee, M. Y. H. Tetrahedron 1998, 54, 12497-12512.
(11) Mukai, C.; Ohta, M.; Yamashita, H.; Kitagaki, S. J. Org. Chem.
2004, 69, 6867-6873.
t
t
(12) An endo-mode ring-closing reaction of trisubstituted alle-
nylphosphine oxides, leading to the dihydrofuran skeleton, has been
reported: Pravia, K.; White, R.; Fodda, R.; Maynard, D. F. J. Org.
Chem. 1996, 61, 6031-6032.
(13) Brel reported an exo-mode cyclization of the allenylphosphonate
derivatives leading to a furan framework: Brel, V. K. Synthesis 2001,
1539-1545.
(14) Mukai, C.; Kobayashi, M.; Kubota, S.; Takahashi, Y.; Kitagaki,
S. J. Org. Chem. 2004, 69, 2128-2136.
(15) Part of this work was published as a preliminary communica-
tion: Mukai, C.; Ukon, R.; Kuroda, N. Tetrahedron Lett. 2003, 44,
1583-1586.
(17) Horner, L.; Binder, V. Liebigs Ann. Chem. 1972, 757, 33-68.
(18) The structure of 8a was unambiguously established on the basis
of its spectral evidence. In particular, the IR spectrum of 8a showed a
carbonyl absorption band at 1712 cm-1, which is in good accordance
with that of ethyl 1-cyclopentenecarboxylate (1710 cm-1) rather than
that of its regioisomer, ethyl 2-cyclopentenecarboxylate (1730 cm-1).19
(16) (a) Corey, E. J.; Niwa, H.; Knolle, J. J. Am. Chem. Soc. 1978,
100, 1942-1943. (b) Mukai, C.; Nomura, I.; Yamanishi, K.; Hanaoka,
M. Org. Lett. 2002, 4, 1755-1758.
J. Org. Chem, Vol. 70, No. 16, 2005 6283

Mukai et al.
TABLE 2. Isolation of Compounds 9 and 10
TABLE 3. Transformation of 9 to 8a
entry
base
equiv
solvent
time
8a (%)
1
2
3
tBuOK
1.5
1.5
4.5a
tBuOH
tBuOH
MeOH
5 min
5 min
20 h
63
64
93
tBuONa
MeONa
entry
base
equiv solvent time 8a (%) 9 (%) 10 (%)
a A longer reaction time was required when 1.5 equiv of base
was used.
1
2
3
4
5
tBuOK
tBuOK
tBuOK
tBuOK
Et3N
1.5
1.0
0.5
0.1
6.0
tBuOH 5 min
tBuOH 5 min
tBuOH 5 min
84
58
21
30
36
42
94
69
tBuOH 5 min trace trace
TABLE 4. Transformation of 10 to 8a
CH2Cl2 2 h
24
7a was exposed to MeONa (4.5 equiv) in MeOH for a
t
longer reaction time (26 h) (entry 5). Both BuOLi and
entry
base
equiv
solvent
time
8a (%)
MeOLi were also found to be effective for this ring-closing
reaction (entries 3 and 6). Aqueous bases, KOH and
NaOH, in tBuOH and THF could be used for this reaction
but gave slightly lower yields (entries 7-10). Thus,
tBuOK was found to be the best base for this transfor-
mation with regard to the reaction time and chemical
yield.
1
2
3
tBuOK
1.5
1.5
4.5a
tBuOH
tBuOH
MeOH
5 min
5 min
24 h
79
76
90
tBuONa
MeONa
a A longer reaction time was required when 1.5 equiv of base
was used.
TABLE 5. Base-Catalyzed Ring-Closing Reaction of
The formation of 8a from 7a can tentatively be
explained in terms of the intermediacy of the products 9
and/or 10, both of which would collapse to 8a through
demethoxycarbonylation. To confirm the plausible inter-
mediates 9 and/or 10 for the transformation of 7a into
8a, several experiments were carried out (Table 2).
Exposure of 7a to 1.0 equiv of tBuOK in tBuOH for 5 min
produced a new product 9, which had a bis(methoxycar-
bonyl) functionality, in 30% yield together with 8a (58%)
(entry 2). In addition, another cyclopentene derivative
10 possessing a bis(methoxycarbonyl) group was isolated
in 42% yield along with 8a (21%) and 9 (36%) when
treated with 0.5 equiv of base for 5 min (entry 3). Finally,
the exclusive formation of 10 (94%) was observed upon
7b-da
t
treatment of 7a with a catalytic amount of BuOK (0.1
equiv) (entry 4). Compounds 9 and 10 were both identical
t
to those observed in the reactions of 7a with BuOLi,
MeOM (M ) K, Na, Li), and aqueous KOH and NaOH
(see Table 1). The 1,2,3-trisubstituted cyclopentene de-
rivatives 9 and 10 were also obtained when 7a was
treated with Et3N instead of alkoxides in CH2Cl2 at room
temperature for 2 h (entry 5).
The interconversion between compounds 9 and 10 was
studied next. Compound 10 was partially isomerized to
9 (15%) when it exposed to Et3N in CH2Cl2 at room
temperature for 48 h, and the starting disubstituted
allene 10 was recovered (68%). On the other hand,
tetrasubstituted olefin 9 was stable under the same
conditions and no isomerization to 10 was detected. These
malonate derivatives 9 and 10 readily underwent
demethoxycarbonylation with several alkoxides to pro-
vide 8a in the yields shown in Tables 3 and 4.
a Allenes 7b-d were treated with tBuOK (1.5 equiv) in tBuOH
at rt. b The reaction was carried out in a combined solvent of
tBuOH and THF (1:1). c When 7d was exposed to aq KOH in THF
at rt for 5 min, compound 11 was obtained as a mixture of two
diastereoisomers (95:5).
8b (93%), but not the deethoxycarbonylated one (entry
2). Compound 7d was rather stable under the standard
basic conditions.20 Thus, the reaction mixture was heated
at 60 °C for 3 h to leave the demethoxycarbonylated
compound 8d in 98% yield (entry 3). When aqueous KOH
t
was used instead of BuOK, 7d exclusively provided 11
as a mixture of two diastereoisomers (95:5), the stereo-
chemistry of which was not determined (entry 4). Com-
pound 11 was easily converted into 8d in 71% yield by
We next investigated the ring-closing reaction of other
allenes 7b-d. Treatment of allene 7b with 1.5 equiv of
tBuOK in tBuOH at room temperature afforded the
corresponding cyclopentene derivatives 8b in 93% yield
as expected (Table 5, entry 1). Upon treatment with
tBuOK, compound 7c afforded the debenzylated product
t
exposure to BuOK at 60 °C for 3 h.
(19) Scharf, H.-D.; Korte, F. Chem. Ber. 1964, 97, 2425-2433.
(20) A mixed solvent of tBuOH and THF (1:1) was used for this
compound due to its solubility.
6284 J. Org. Chem., Vol. 70, No. 16, 2005

Base-Catalyzed Endo-Mode Cyclization of Allenes
TABLE 6. Base-Catalyzed Ring-Closing Reaction of
SCHEME 3
12a-da
alkoxy species, which leads to the exclusive production
of 20 (Scheme 3). The simple explanation for dealkoxy-
carbonylation and/or debenzoylation might involve initial
nucleophilic attack of the alkoxide on the carbonyl center.
In the cases of 7c and 14c, a more cationic carbonyl
moiety (benzoyl group) of two carbonyl functionalities was
attacked by tert-butoxide (Tables 5 and 6). Thus, deben-
zoylation preferentially occurred over deethoxycarbony-
lation (Table 5, entry 2, and Table 6, entry 3). On the
basis of these observations, the other plausible mecha-
nism for decarbonylation of the 1,3-dicarbonyl functional-
ity, which would involve the attack of the alkoxide at the
alkyl group of the ester functionality with liberation of
carbon dioxide, can be ruled out. Balme and co-workers2b
reported similar demethoxycarbonylation as well as
preferential deacetylation over demethoxycarbonylation
in their investigation of the palladium-catalyzed exo-
mode ring-closing reaction of alkyne derivatives with 1,3-
diacyl functionalities.
In addition, a more sterically hindered alkoxide (tert-
butoxide) reacted much faster than a sterically less-
hindered methoxide and hydroxide (Table 1). These
observations were in contrast to our prediction. Presum-
ably, the addition of tert-butoxide to a cationic carbonyl
moiety of 18 as a first step would result in the simulta-
neous formation of intermediate A, and serious nonbond-
ing steric congestion due to changing of hybridization
from sp2 to sp3 (120° to ca. 109°) might be encountered.
This inherent instability of A would irreversibly be
released by elimination of a bulky alkoxide moiety
leading to products 20. In the case of a sterically smaller
methoxide, for example, addition to a carbonyl group of
18 must be faster than that of tert-butoxide. However,
under less sterically congested conditions, intermediate
A′ might be stable enough, compared to A, and be in
equilibrium with the starting carbonyl compound 18. As
a result, collapse of intermediate A′ to the final products
20 would be much slower than that of intermediate A
(Scheme 4). A similar explanation might be possible for
the transformation of 19 into 20.
a Allenes 12a-d were treated with tBuOK (1.5 equiv) in tBuOH
at rt. b The reaction was carried out in a combined solvent of
tBuOH and THF (1:1). c When 12d was exposed to aq KOH in THF
at rt for 5 min, compound 16 was obtained as a mixture of two
diastereoisomers (84:16).
The ring-closing reaction of the C1-homologated allenes
1421 under the standard conditions (tBuOK in tBuOH at
room temperature) was examined next. The results are
summarized in Table 6. Allenes 14a,b gave the corre-
sponding 1-alkoxycarbonyl-2-methyl-3-phenylsulfonyl-2-
cyclohexene derivatives 15a,b (entries 1 and 2). Prefer-
ential debenzoylation over deethoxycarbonylation was
observed in the reaction of 14c (entry 3). Allene 14d20
behaved the same as 7d toward base leading to the
formation of 15d and 16 (entries 4 and 5). Thus, this
novel endo-mode ring-closing reaction of allenes, ac-
companied with deacylation, could be suitable for con-
structing a cyclopentene skeleton as well as a cyclohexene
framework.
Easy dealkoxycarbonylation and debenzoylation were
observed during the base-catalyzed endo-mode ring-
closing reaction of allenes 7 and 14 and resulted in the
exclusive formation of 1-alkoxycarbonyl (or phenylsulfo-
nyl)-2-methyl-3-phenylsulfonyl-2-cycloalkene derivatives
8 and 15. Considering both the results in Table 2 and
those in the base-catalyzed transformation of 9 and 10
into 8a (Tables 3 and 4), it can be concluded that the
Michael-type endo-mode ring-closing reaction of allenyl
sulfones 17 under basic conditions first occurred at the
sp-hybridized carbon center of the allenyl moiety, result-
ing in the formation of the exo-methylene derivative 18,
which might be in part susceptible to base-catalyzed
isomerization to the endo-olefin derivative 19, which has
a 1,3-diacyl moiety. The final step of this transformation
must be the deacylation of 18 and/or 19 with the aid of
To obtain more information on the conversion of 18
and/or 19 into 20 under basic conditions, additional
experiments were performed. Two allenes 7e and 14e22
with a fairly bulky ester group could be anticipated to
prevent the attack of bulky tert-butoxide. Thus, allenes
7e and 14e were exposed to the standard ring-closing
conditions (tBuOK (1.5 equiv) in tBuOH at room temper-
ature for 5 min), and this led to the isolation of 21 and
22 in respective yields of 88% and 99% (Scheme 5).
(21) Allenes 14 were prepared from the hexynyl iodide derivatives
12 via the corresponding active methine derivatives 13 (see the
Supporting Information).
(22) Compounds 7e and 14e were prepared according to the general
procedure (see the Supporting Information).
J. Org. Chem, Vol. 70, No. 16, 2005 6285

Mukai et al.
TABLE 7. Ring-Closing Reaction of 14a in the Presence
of 18-Crown-6
SCHEME 4
entry
18-crown-6 (equiv)
15a (%)
25 (%) (exo:endo)
1
2
3
92
51
58
1.5
6.0
24 (1:2)
41 (1:3)
SCHEME 5a
quantitative yield. This observation strongly suggested
that the mechanism for the deacylation step involves the
attack of alkoxides, used as a base, as depicted in Scheme
4.
As described in Table 7, entry 1, the cyclohexene
derivative 15a was exclusively formed from 14a by
t
t
a Reaction conditions: (a) BuOK, BuOH, rt, 5 min, 21 (88%)
t
t
t
t
treatment with 1.5 equiv of BuOK in BuOH at room
temperature. When a similar reaction was carried out
in the presence of 1.5 equiv of 18-crown-6, 15a was
isolated in 51% yield along with the cyclohexene deriva-
tives 25, which have a 1,3-bismethoxycarbonyl function-
ality, in 24% yield (Table 7, entry 2). Interestingly, an
increase in the amount of 18-crown-6 from 1.5 to 6.0
equiv changed the ratio of 15a to 25 (15a: 58%, 25: 41%)
(entry 3). The effect of 18-crown-6 on deacylation was
uncertain at this stage, but these results might be
tentatively interpreted in terms of the six-membered
cyclic intermediate 18 mediated by countercationic spe-
cies, which would help deacylation.
22 (99%); (b) BuOK, BuOH, rt, 24 h, 8e (11%).
SCHEME 6
No de(tert-butoxy)carbonyl products 8e and 15e were
detected in the reaction mixture. When 21 was treated
t
with BuOK for 24 h, de(tert-butoxy)carbonyl compound
8e was obtained in 11% yield as a minor product together
with recovery of the starting material 21 in 68% yield.
On the other hand, compound 22 was stable under these
conditions and 22 was completely recovered intact. These
experiments indirectly supported the proposed reaction
pathway in Scheme 4. Despite many efforts to isolate
RCO2But and RCO2Me, both of which should be byprod-
ucts of the base-catalyzed endo-mode ring-closing reaction
of 7 and 14 if the deacylation step proceeded as depicted
in Scheme 4, these byproducts could not be isolated. The
ring-closing reaction of 14c with the use of other bases
such NaOPh and NaSPh was examined because we
envisaged that the resulting tert-butyl benzoate and tert-
butyl benzothioate would be much easier to monitor by
TLC. However, independent treatment of 14c with
NaOPh and NaSPh brought an intractable mixture
presumably due to intermolecular Michael-type addition
of these bases to the allene 14c. When 14c was exposed
to Me3SiOK, the ring-closed product 23 with a 1,3-diacyl
moiety was obtained in 82% yield (Scheme 6). The
resulting 23 was subsequently treated with excess
amounts of NaOPh in THF at room temperature to
fortunately give the desired phenyl benzoate (24) in 12%
yield along with the cyclohexene derivative 15b in
The next phase of this study involved the application
of the endo-mode ring-closing reaction to the construction
of larger carbocycles. The allene 2823 was then exposed
t
t
to 1.5 equiv of BuOK in BuOH at rt for 20 min (Table
8, entry 1) to provide the seven-membered compound 30
(37%) and 32 (29%), accompanied with demethoxycarbo-
nylation, although the chemical yield (66%) was some-
what lower than in the formation of cyclopentene and
cyclohexene frameworks (see Tables 5 and 6). The mal-
onate derivative 31 was obtained in 53% yield (entry 2)
t
when 28 was treated with a catalytic amount of BuOK
for 12 h (0.5 equiv). The exo-methylene derivative 32,
which should have been derived from 31, was formed in
34% yield as a mixture of cis- and trans-isomers in a ratio
of 4 to 124 along with 31 (38%) upon treatment with 1.0
t
equiv of BuOK for 1 h (entry 3). It was shown that a
mixture of cis- and trans-32 underwent base-catalyzed
(23) Compound 28 was prepared from the known dimethyl malonate
derivative 26 (see the Supporting Information).
(24) The ratio of cis- and trans-32 was determined by 1H NMR
spectral analysis.
6286 J. Org. Chem., Vol. 70, No. 16, 2005

Base-Catalyzed Endo-Mode Cyclization of Allenes
TABLE 8. Base-Catalyzed Ring-Closing Reaction of 28
SCHEME 8
entry
base (equiv)
time
product (%)
1
2
3
1.5
1.0
0.5
20 min
1 h
12 h
30 (37), 32 (29)
31 (38), 32 (34)a
31 (53)
a A mixture of cis- and trans-32 was obtained in a ratio of 4:1.
case of disubstituted allenes 7, and the resulting ring-
closed product 42a had an (E)-ethylidene group.28 Simi-
larly, 40a27 furnished the six-membered product 43a in
high yield (87%),29 although it took a prolonged reaction
time (3 h) until the starting material was completely
consumed. In contrast to these results, the seven-
membered carbocycle 44a was formed in a low yield
(18%).30 By analogy to the ring-closing reaction of 39a,
40a, and 41a, the (p-methoxybenzyl)oxymethyl deriva-
tives 39b and 40b27 provided the corresponding five-and
six-membered carbocycles 42b and 43b in respective
yields of 92% and 68%, with a (Z)-(p-methoxybenzyl)-
oxyethylidene moiety31 when treated with tBuOLi (Scheme
8). Notably, the seven-membered product 44b was also
formed in moderate yield (53%). This result is different
from that of the simpler trisubstituted allene 41a, which
provided the corresponding seven-membered product 44a
in a rather lower yield (18%). Compounds 42b, 43b, and
44b have (Z)-stereochemistry,31 while 42a, 43a, and 44a
have (E)-stereochemistry.28 The difference in the stereo-
chemistry of these compounds would presumably reflect
the thermodynamic stability of each compound. Upon
exposure of allenes 39b, 40b, and 41b to the most
standard conditions (1.5 equiv of BuOK in BuOH at
room temperature), the ring-closing reaction proceeded
to afford the corresponding (Z)-(p-methoxybenzyl)oxy-
ethylidene derivatives 42b, 43b, and 44b along with the
demethoxycarbonylated compounds 46-48.32 An efficient
ring-closing reaction was also observed when tetrasub-
stituted allene 39c27 was exposed to basic conditions
(Scheme 9). However, this method was ineffective for the
ring-closing reaction of the tetrasubstituted allenes 40c
and 41c27 resulting in the formation of intractable
mixtures. In fact, the ring-closed products 43c and 44c
could never be detected in these reaction mixtures.
Several reaction conditions were used to attempt to
SCHEME 7
isomerization to furnish a mixture of cis-32 and the endo-
methylene derivative 30 in 40% yield (cis-32/30 ) ca.
3:2).25 The stereochemistry of cis-32 was determined by
a NOE experiment, which revealed 1.0% enhancement
between two allylic protons. This result should reflect the
fact that thermodynamically less stable trans-32 pre-
dominantly isomerized to more stable endo-olefin deriva-
tive 30, while the isomerization of rather stable cis-32
to 30, in comparison with the trans-congener, might be
much slower under the basic conditions used. In the case
of compound 29, no eight-membered carbocycles could be
detected in the reaction mixture under various basic
conditions.
We next looked at the scope and limitations of the
newly developed method for constructing carbocycles
based on the endo-mode ring-closing reaction. As shown
in Table 8, cycloheptene derivatives could be prepared
by the endo-mode ring-closing reaction of allenes, al-
though the chemical yields are moderate or lower,
compared to those for the preparation of cyclopentene and
cyclohexene congeners. However, we clarified that the C1-
homologated allene 2926 could not produce the corre-
sponding eight-membered derivatives at all.
t
t
Our next efforts focused on the effect of substituents
at the allenic terminus (tri- and tetrasubstituted 1-phe-
nylsulfonylallenes) in the ring-closing step. According to
the standard procedure, 39a27 was treated with BuOK
t
t
in BuOH at room temperature for 10 min to unexpect-
(28) The (E)-stereochemistry of 42a, 43a, and 44a was determined
by an NOE experiment. For instance, 1.4% enhancement of Ha of 43a
was observed upon irradiation of a vinyl proton.
edly give an intractable mixture (Scheme 7). The desired
ring-closed product 42a was obtained in 98% yield when
treated with BuOLi instead of BuOK for 10 min. No
demethoxycarbonylation was observed in contrast to the
t
t
(29) Compound 43a was obtained in 65% yield when 40a was
t
t
exposed to BuOK instead of BuOLi for 5 min.
(30) Compound 44a was obtained in 30% yield when 41a was
t
t
exposed to BuOK instead of BuOLi for 5 min.
(25) No peaks due to trans-32 could be detected by 1H NMR. The
ratio of cis-32 to 30 was determined by 1H NMR spectral analysis.
(26) Compound 29 was prepared from the known dimethyl malonate
derivative 27 (see the Supporting Information).
(27) Allenes 39-41 were prepared from the corresponding alkynes
33-35 via compounds 36-38 (see the Supporting Information).
(31) The (Z)-stereochemistry of 42b, 43b, and 44b was confirmed
as follows. Treatment of 42b, for example, with DDQ afforded the
allylic alcohol derivative 45 in 91% yield. An NOE experiment of 45
revealed a 9% enhancement of Ha when allylic protons were irradiated.
(32) Compounds 47 and 48 were obtained as a mixture of two
diastereoisomers in a ratio of ca. 1:1.
J. Org. Chem, Vol. 70, No. 16, 2005 6287

Mukai et al.
SCHEME 9
SCHEME 10a
TABLE 9. Ring-Closing Reaction of 51
a Reaction conditions: (a) NaH, THF, rt, 57 (67%), 58 (77%);
i
(b) propargyl alcohol, PdCl2(PPh3)2, Pr2NH, CuI, AcOEt, rt, 59
(87%), 60 (88%); (c) PhS(O)Cl, Et3N, CH2Cl2, -78 °C; (d) toluene
reflux, 61 (88%), 62 (88%); (e) tBuOK (1.0 equiv), tBuOH, rt, 63 (5
min, 66%), 64 (2 h, 29%).
entry
tBuOK (equiv)
52 (%)
53 (%)
54 (%)
sive demethoxycarbonylation and dephenylsulfinic acid.
In fact, when 52 was treated with BuOK for 5 min, the
1
2
3
2.0
1.5
0.1
10
23
86
9
15
14
58
53
t
naphthalene derivative 54 was obtained in 52% yield
together with double bond-isomerized product 53 (18%)
and recovery of the starting material 52 (27%). The
dihydronaphthalene framework 53 was rather stable,
compared to the exo-methylene framework 52, and af-
forded 54 in only 17% yield along with 52 (22%) and the
recovery of 53 (46%) under basic conditions.
overcome the difficulty encountered in the formation of
six- and seven-membered products by changing the
solvent, base, reaction temperature, and/or concentration;
however, no improvement was made.
In summary, the endo-mode ring-closing reaction of
1,1-disubstituted phenylsulfonylallenes possessing a ter-
minal active methine moiety produced five- to seven-
membered carbocycles, accompanied by deacylation, in
high yields. The efficient construction of cyclopentane and
cyclohexane skeletons from the corresponding tri- and
tetra-substituted allenes was also realized. This proce-
dure was not necessarily suitable for constructing seven-
membered carbocycles, although 41b afforded the corre-
sponding seven-membered framework in moderate yields
(Scheme 8).
We next focused on preparing larger benzocycloheptene
and benzocyclooctene skeletons. Condensation of the
diiodo derivative 5534 with dimethyl malonate gave the
condensed product 57 in 67% yield, which was subse-
quently converted into the propargyl alcohol derivative
59 in 87% yield by the Sonogashira coupling reaction.
Unexpectedly, the transformation of 59 into the allenyl
sulfone derivative 61 via [2,3]-sigmatropic rearrangement
of the sulfenic ester derivative was troublesome, and the
allene 61 was isolated in only 10% yield upon treatment
with PhSCl and m-CPBA. After we screened several
reagents and conditions, we found that benzenesulfinyl
chloride (PhS(O)Cl)35 instead of PhSCl was effective for
this transformation. As a result, 59 was reacted with
PhS(O)Cl in the presence of Et3N at -78°C to provide
the corresponding sulfinic ester derivative, which was
subsequently refluxed in toluene for 4.5 h to produce the
desired 61 in 88% yield. A similar protocol was applied
for the diiodo derivative 5634 to provide the C1-homolo-
gated allene derivative 62, via 58 and 60, in acceptable
yields (Scheme 10). Easy transformation of the allene 61
into benzocycloheptene derivative 63 under the standard
basic conditions (5 min) was realized in 66% yield, as
expected. The efficient formation of the seven-membered
ring of 63 may be attributed to the template effect of an
aromatic ring. However, the formation of an eight-
membered formation did not proceed as efficiently as we
had anticipated. In fact, exposure of the allene 62 to
Our endeavors were then turned to application of this
endo-mode ring-closing reaction to 1-alkyl (with a ter-
minal active methine moiety)-2-allenylbenzene deriva-
tives in which the template effect of the aromatic ring
would be expected to facilitate the ring-closing step. Thus,
t
t
upon exposure to BuOK (1.5 equiv) in BuOH at room
temperature for 20 min, 5133 underwent a ring-closing
reaction to give the two predictable products 52 and 53
in respective yields of 23% and 15%, in addition to the
unexpected naphthalene derivative 54 in 53% yield as a
major product (Table 9, entry 2). An increase in the
amount of tBuOK (2.0 equiv) brought a slightly high yield
of 54 (58%) as well as lower yields of 52 (10%) and 53
(9%) (entry 1). On the other hand, a catalytic amount of
tBuOK (0.1 equiv) provided 52 as a major product (86%)
along with 53 (14%) (entry 3). In this case, no formation
of the desulfonylated product 54 was observed. Com-
pound 54 must be derived from 52 and/or 53 via succes-
(34) Ripa, L.; Hallberg, A. J. Org. Chem. 1996, 61, 7147-7155.
(35) (a) Stirling, C. J. M. J. Chem. Soc., Chem Commun. 1967, 131-
131. (b) Smith, G.; Stirling, C. J. M. J. Chem. Soc. C 1971, 1530-
1535.
(33) Compound 51 was prepared form the known iodobenzene
derivative 49 via the propargyl alcohol derivative 50 (see the Support-
ing Information).
6288 J. Org. Chem., Vol. 70, No. 16, 2005

Base-Catalyzed Endo-Mode Cyclization of Allenes
tBuOK produced benzocyclooctene derivative 64 in a
rather lower yield (29%).
General Procedure for Ring-Closing Reaction of Com-
pounds 7 and 14. Typical Procedure. To a solution of 7a
t
t
(27.2 mg, 0.08 mmol) in BuOH (0.8 mL) was added BuOK
(13.5 mg, 0.12 mmol), and the mixture was stirred for 5 min
at rt. The reaction mixture was quenched by addition of
saturated aqueous NH4Cl, and extracted with AcOEt. The
extract was washed with water and brine, dried, and concen-
trated to dryness. The residue was chromatographed with
hexane-AcOEt (3:1) to give methyl 2-methyl-3-(phenylsul-
fonyl)-1-cyclopentene-1-carboxylate (8a) (18.8 mg, 84%).
Chemical yields are summarized in Tables 1, 2, and 5-7 and
Scheme 5.
In summary, we have developed a new and reliable
procedure for constructing of five- to seven-membered
carbocycles via an endo-mode ring-closing reaction of
1-phenylsulfonylallenes with an alkyl side chain, pos-
sessing a terminal active methine moiety, at the C1-
position. The resulting carbocycles readily underwent
deacylation under basic conditions. Trisubstituted 1-phe-
nylsulfonylallenes underwent a similar endo-mode ring-
closing reaction to produce the corresponding five- to
seven-membered carbocycles, although the formation of
the seven-membered frameworks was inefficient. In the
case of tetrasubstituted allenes, five-membered car-
bocycle was constructed in high yields, but the corre-
sponding six- and seven-membered compounds could not
be obtained. In addition, the introduction of an aromatic
ring to the alkyl side chain of the starting allenes made
possible the formation of not only normal-sized car-
bocycles (six-and seven-membered ones), but also an
eight-membered framework, although the yield of the
latter was rather low.
Methyl 2-methyl-3-(phenylsulfonyl)-1-cyclopentene-1-
carboxylate (8a): colorless solid; mp 104-107 °C (from Et2O);
1
IR 1712, 1647 cm-1; H NMR 7.88-7.51 (5H, m), 4.19-4.16
(1H, m), 3.70 (3H, s), 2.47-2.02 (4H, m), 2.28 (3H, br-s); 13C
NMR δ 165.3, 145.5, 137.3, 135.6, 134.0, 129.0, 128.9, 77.2,
51.4, 31.5, 25.0, 16.1; MS m/z 280 (M+, 0.5). Anal. Calcd for
C14H16O4S: C, 59.98; H, 5.75. Found: C, 59.74; H, 5.87.
Conversion of 7a into 9 and 10. A solution of 7a (51.5
mg, 0.15 mmol) and Et3N (0.13 mL, 0.91 mmol) in CH2Cl2 (1.5
mL) was stirred for 2 h. The reaction mixture was concentrated
to leave the residue, which was chromatographed with hex-
ane-AcOEt (3:1) to give dimethyl 2-methyl-3-(phenylsul-
fonyl)-2-cyclopentene-1,1-dicarboxylate (9) (12.5 mg, 24%)
and dimethyl 2-methylene-3-(phenylsulfonyl)cyclopen-
tane-1,1-dicarboxylate (10) (32.7 mg, 69%).
Experimental Section
Dimethyl 2-methyl-3-(phenylsulfonyl)-2-cyclopentene-
Dimethyl 6-Hydroxy-4-hexyne-1,1-dicarboxylate (6a).
To a solution of dimethyl malonate (0.18 mL, 1.59 mmol) in
DMF (9.0 mL) was added NaH (60% in oil, 50.4 mg, 1.27 mmol)
at 0 °C. After the mixture was stirred for 15 min at rt, a
solution of 4 (310 mg, 1.06 mmol) in DMF (1.0 mL) was added
to the mixture. The reaction mixture was stirred for 6 h,
quenched by addition of saturated aqueous NH4Cl, and
extracted with Et2O. The extract was washed with water and
brine, dried, and concentrated to dryness. p-TsOH (37.9 mg,
0.22 mmol) was added to a solution of the crude adduct in
MeOH (10 mL) at rt, and the mixture was stirred at the same
time for 24 h. The reaction mixture was concentrated to leave
the residue, which was chromatographed with hexane-AcOEt
(2:1) to give 6a36 (195 mg, 86%) as a colorless oil: IR 3609,
1
1,1-dicarboxylate (9): colorless oil; IR 1732, 1634 cm-1; H
NMR δ 7.93-7.50 (5H, m), 3.74 (6H, s), 2.69-2.59 (2H, m),
2.49-2.41(2H, m), 2.29 (3H, t, J ) 2.0 Hz); 13C NMR δ 169.5,
148.7, 140.3, 140.3, 133.5, 129.2, 127.3, 70.5, 53.0, 31.8, 31.4,
13.6; MS m/z 338 (M+, 10). Anal. Calcd for C16H18O6S: C, 56.79;
H, 5.36. Found: C, 56.46; H, 5.43.
Dimethyl 2-methylene-3-(phenylsulfonyl)cyclopentane-
1,1-dicarboxylate (10): colorless solid; mp 96-98 °C (from
Et2O); IR 1734 cm-1; 1H NMR δ 7.91-7.50 (5H, m), 5.73 (1H,
d, J ) 1.7 Hz), 5.44 (1H, d, J ) 1.7 Hz), 4.11-4.03 (1H, m),
3.71 (3H, s), 3.70 (3H, s), 2.55-2.10 (4H, m); 13C NMR δ 170.6,
169.1, 139.6, 136.8, 133.9, 129.7, 128.9, 122.6, 69.3, 63.7, 53.1,
53.0, 33.4, 26.4; MS m/z 338 (M+, 0.2). Anal. Calcd for
C16H18O6S: C, 56.79; H, 5.36. Found: C, 56.70; H, 5.48.
Isomerization of 10 into 9. A solution of 10 (43.0 mg, 0.13
mmol) and Et3N (0.05 mL, 0.39 mmol) in CH2Cl2 (1.3 mL) was
stirred for 48 h. The reaction mixture was concentrated to
leave the residue, which was chromatographed with hexane-
AcOEt (3:1) to give 9 (6.6 mg, 15%) along with recovery of 10
(29.2 mg, 68%).
1
3462, 2224, 1747 (sh), 1732 cm-1; H NMR δ 4.23 (2H, t, J )
2.0 Hz), 3.74 (6H, s), 3.58 (1H, t, J ) 7.3 Hz), 2.34 (1H, t, J )
2.0 Hz), 2.32 (2H, tt, J ) 2.0, 6.9 Hz), 2.16-2.05 (2H, m); 13C
NMR δ 169.4, 83.6, 79.1, 52.5, 50.9, 50.2, 27.4, 16.6; FABMS
m/z 215 (M+ + 1, 100). FABHRMS calcd for C10H15O5 215.0919,
found 215.0914.
Dimethyl 4-(Phenylsulfonyl)-4,5-hexadiene-1,1-dicar-
boxylate (7a). To a solution of 6a (270 mg, 1.26 mmol) in THF
(20 mL) was added Et3N (0.53 mL, 3.78 mmol) at -78 °C, and
the reaction mixture was stirred for 15 min. PhSCl (546 mg,
3.78 mmol) was added to the reaction mixture, which was
stirred for 3 h, quenched by addition of water, and extracted
with AcOEt. The extract was washed with water and brine,
dried, and concentrated to dryness. The residue was passed
through a short pad of silica gel with hexane-AcOEt (2:1) to
give the crude sulfoxide derivative. m-CPBA (261 mg, 1.51
mmol) was added to a solution of the crude sulfoxide in CH2-
Cl2 (13 mL) at 0 °C, and the mixture was stirred for 2.5 h.
The reaction mixture was quenched by addition of water and
extracted with CH2Cl2. The extract was washed with water
and brine, dried, and concentrated to dryness. The residue was
chromatographed with hexane-AcOEt (2:1) to give 7a (363
mg, 85%) as a colorless oil: IR 1969, 1938, 1747 (sh), 1732
Dimethyl (2Z)-(2-Hydroxyethylidene)-3-(phenylsulfo-
nyl)cyclopentane-1,1-dicarboxylate (45). DDQ (59.0 mg,
0.26 mmol) was added to a solution of 42b (61.9 mg, 0.13
mmol) in CH2Cl2 and H2O (1.3 mL, 20:1) and vigorously stirred
at rt for 1 h. The reaction mixture was quenched by addition
of saturated aqueous NaHCO3 and extracted with AcOEt. The
extract was washed with water and brine, dried, and concen-
trated to dryness. The residue was chromatographed with
hexane-AcOEt (1:1) to give 45 (42.3 mg, 91%) as a colorless
1
oil: IR 3605, 3526, 1732 cm-1; H NMR δ 7.94-7.53 (5H, m),
6.43 (1H, dt, J ) 1.3, 6.3 Hz), 4.54-4.47 (1H, m), 4.24-3.98
(2H, m), 3.78 (3H, s), 3.72 (3H, s), 2.73 (1H, br-s), 2.58-2.04
(4H, m); 13C NMR δ 171.2, 169.5, 138.3, 137.4, 134.1, 131.7,
129.4, 129.1, 67.2, 63.8, 61.3, 53.2, 53.0, 32.4, 27.5; MS m/z
368 (M+, 0.1); FABHRMS calcd for C17H21O7S 369.1008, found
369.1020.
1
cm-1; H NMR δ 7.91-7.50 (5H, m), 5.41 (2H, t, J ) 3.3 Hz),
Dimethyl 3-(o-Iodophenyl)propane-1,1-dicarboxylate
(57). To a solution of dimethyl malonate (55.4 mg, 0.42 mmol)
in THF (1.0 mL) was added NaH (60% in oil, 11.2 mg, 0.28
mmol) at 0 °C, and the mixture was stirred for 30 min at rt.
A solution of 55 (49.7 mg, 0.14 mmol) in THF (1.0 mL) was
added to the mixture. The reaction mixture was stirred for 12
h, quenched by addition of saturated aqueous NH4Cl, and
extracted with AcOEt. The extract was washed with water and
3.71 (6H, s), 3.36 (1H, t, J ) 7.6 Hz) 2.37-2.26 (2H, m), 2.11-
1.99 (2H, m); 13C NMR δ 207.5, 169.1, 139.8, 133.5, 129.1,
128.0, 112.1, 85.1, 52.6, 50.3, 26.5, 24.4; MS m/z 338 (M+, 48).
Anal. Calcd for C16H18O6S: C, 56.79; H, 5.36. Found: C, 56.49;
H, 5.47.
(36) Brillon, D.; Deslongchamps, P.Can. J. Chem. 1987, 65, 43-55.
J. Org. Chem, Vol. 70, No. 16, 2005 6289

Mukai et al.
brine, dried, and concentrated to dryness. The residue was
chromatographed with hexane-AcOEt (8:1) to give 57 (33.7
mg, 67%) as a colorless oil: IR 1749 (sh), 1732 cm-1; 1H NMR
δ 7.83-6.84 (4H, m), 3.75 (6H, s), 3.44 (1H, t, J ) 7.6 Hz),
2.81-2.71 (2H, m), 2.25-2.15 (2H, m); 13C NMR δ 169.4, 143.1,
139.4, 129.4, 128.3, 128.0, 100.3, 52.5, 50.8, 38.0, 28.9; MS m/z
362 (M+, 41); FABHRMS calcd for C13H16IO4 363.0093, found
363.0088.
169.4, 141.1, 139.5, 133.5, 131.2, 129.7, 129.5, 128.8, 128.6,
127.7, 126.2, 112.2, 83.0, 52.5, 51.4, 30.9, 30.1; MS m/z 414
(M+, 4.7); FABHRMS calcd for C22H23O6S 415.1215, found
415.1207.
Acknowledgment. We are grateful to Mr. Manabu
Honda for his technical assistance. This work was
supported in part by a Grant-in Aid for Scientific
Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan, for which we
are thankful.
Dimethyl 3-[2-{1-(Phenylsulfonyl)-1,2-propadienyl}-
phenyl]propane-1,1-dicarboxylate (61). To a solution of
sodium benzenesulfinate (400 mg, 2.40 mmol) was added a
solution of oxalyl chloride (0.25 M benzene solution, 8.00 mL,
2.00 mmol) at 0 °C. After being stirred for 1 h at rt, the reaction
mixture (2.80 mL, 0.70 mmol) was added to a solution of 59
(100 mg, 0.35 mmol) and Et3N (0.48 mL, 3.50 mmol) in CH2-
Cl2 at -78 °C. The reaction mixture was stirred for 10 min,
quenched by addition of water, and extracted with AcOEt. The
extract was washed with water and brine, dried, and concen-
trated to dryness. The crude sulfinic ester in toluene was
heated under reflux for 4 h. The reaction mixture was
concentrated, and the residue was chromatographed with
hexane-AcOEt (3:1) to give 61 (126 mg, 88%) as a colorless
Supporting Information Available: 1H and 13C NMR
spectra for compounds 6a-e, 12, 13b-e, 36a-c, 37a-c, 38a-
c, 39b, 40a-c, 41b,c, 42b, 43b, 44a,b, 46-48, 50-53, 57-
62, and 64, characterization data for compounds 6b-e, 7b-
e, 8b-e, 11, 13b-e, 14a-e, 15a-d, 16, 21-23, 25, 28-32,
36b,c, 37a-c, 38a-c, 39a-c, 40a-c, 41a-c, 42a-c, 43a,b,
44a,b, 46-48, 51-54, 58-60, and 62-64 and preparation of
compounds 12, 36a, and 50. This material is available free of
charge via the Internet at http://pubs.acs.org.
oil: IR 1967, 1931, 1749 (sh), 1732 cm-1 1H NMR δ 7.75-
;
7.08 (9H, m), 5.50 (2H, s), 3.74 (6H, s), 3.33 (1H, t, J ) 7.3
Hz), 2.48-2.39 (2H, m), 2.03-1.96 (2H, m); 13C NMR δ 208.9,
JO050729W
6290 J. Org. Chem., Vol. 70, No. 16, 2005