A new entry to carbocycles: Synthesis of cyclopentene and cyclohexene derivatives through endo-mode ring closure of allenyl sulfones

Article abstract of DOI:10.1016/S0040-4039(03)00067-4

Treatment of dimethyl 4-(phenylsulfonyl)-4,5-hexadiene-1,1-dicarboxylate with potassium tert-butoxide in tert-butanol at room temperature effected successive endo-mode ring closure at the sp-hybridized carbon center and demethoxycarbonylation of the resulting malonate derivative leading to the exclusive formation of methyl 2-methyl-3-(phenylsulfonyl)-1-cyclopentenecarboxylate. An additional seven allenyl sulfones having a 1,3-dicarbonyl functionality gave the corresponding cyclopentene or cyclohexene derivatives in high yields.

Full text of DOI:10.1016/S0040-4039(03)00067-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1583–1586
A new entry to carbocycles: synthesis of cyclopentene and
cyclohexene derivatives through endo-mode ring closure of
allenyl sulfones
Chisato Mukai,* Rie Ukon and Norikazu Kuroda
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Kanazawa 920-0934, Japan
Received 8 December 2002; revised 27 December 2002; accepted 27 December 2002
Abstract—Treatment of dimethyl 4-(phenylsulfonyl)-4,5-hexadiene-1,1-dicarboxylate with potassium tert-butoxide in tert-butanol
at room temperature effected successive endo-mode ring closure at the sp-hybridized carbon center and demethoxycarbonylation
of the resulting malonate derivative leading to the exclusive formation of methyl 2-methyl-3-(phenylsulfonyl)-1-cyclopentenecar-
boxylate. An additional seven allenyl sulfones having a 1,3-dicarbonyl functionality gave the corresponding cyclopentene or
cyclohexene derivatives in high yields. © 2003 Elsevier Science Ltd. All rights reserved.
The construction of five- and six-membered carbocycles
is a fundamental process in synthesis, and enormous
procedures have been developed for preparing them.
The classical intramolecular Michael-type conjugate
addition1 of carbanionic organometallic species to acti-
vated alkenes and alkynes with an electron-withdrawing
group (i.e. Michael acceptors) is still one of the most
frequently used methods, although recent progress in
the field of organotransition metal chemistry has
enabled the efficient metal-catalyzed intramolecular
addition of enolates, derived from active methine
derivatives, to unactivated alkynes2 and allenes3 as well.
In contrast to the many examples of intramolecular
conjugate addition of carbanion species to alkenes and
alkynes1 having an electron-withdrawing group, rela-
tively few examples of the corresponding allene
derivatives4 have been reported. During our own
studies5 toward the development of a convenient and
efficient procedure for the preparation of oxacycles, we
were able to show that the endo-mode intramolecular
ring closure of allenes6 having a phenylsulfonyl func-
tionality with a terminal hydroxyl group proceeded
very efficiently. This letter describes our preliminary
results on the novel intramolecular ring closure reaction
of the allenyl sulfones 1 with suitable internal carbon
nucleophiles7 in an endo-mode manner8 leading to the
intriguing direct formation of the 1,2,3-trisubstituted-
cyclopentene and cyclohexene derivatives 2 (Scheme 1).
Thus, to the best of our knowledge, this would be the
first example dealing with the endo-mode intramolecu-
lar Michael-type reaction of allenes with the active
methine moiety.
The required starting allenes 7 and 8 for the ring
closure reaction were prepared by conventional means
in a straightforward manner as depicted in Scheme 2.
Condensation of the iodo derivatives 39 and 410 with
the active methine species under basic conditions was
followed by acid hydrolysis to give the condensed prod-
ucts 5 and 6 with a propargyl alcohol moiety. Exposure
of the methine derivatives 5 and 6 to benzenesulfenyl
chloride11 in THF in the presence of triethylamine
effected successive sulfenic ester formation and the
[2,3]-sigmatropic rearrangement to afford the corre-
sponding sulfoxides, which were subsequently oxidized
with mCPBA to furnish the sulfone derivatives 7 and 8.
Scheme 1.
Keywords: carbocycle; endo-mode ring closure; allenyl sulfone; car-
bon nucleophile; Michael-type reaction.
* Corresponding author. E-mail: cmukai@kenroku.kanazawa-u.ac.jp
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(03)00067-4

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C. Mukai et al. / Tetrahedron Letters 44 (2003) 1583–1586
67% yield (entry 4).14 These results are summarized in
Table 1.
The fascinating formation of 9a from 7a can tenta-
tively be rationalized in terms of the intermediacy of
the products 10a and/or 11a, which would collapse to
9a through demethoxycarbonylation.15 In order to
obtain more information on the mechanism of this
transformation, several experiments were carried out
(Scheme 3). Treatment of 7a with triethylamine in
CH2Cl2 at room temperature for 2 h provided 10a
and 11a in 69% and 24% yield, respectively. Com-
pound 10a was isomerized to 11a in 15% yield when
it exposed to triethylamine at room temperature for
48 h along with starting 10a (68%). However, 11a
was found to be stable under the same conditions
and no isomerization to 10a could be detected. It
turned out that these malonate derivatives 10a and
11a easily underwent demethoxycarbonylation with
alkoxides to provide 9a. Thus, independent treatment
of 10a and 11a with potassium tert-butoxide in
tBuOH at room temperature for 5 min furnished 9a
in 79% and 63% yield, respectively. On the basis of
these experiments, it could be concluded that the
Michael-type ring closure of 7a under the basic con-
ditions first occurred at the sp-hybridized carbon cen-
ter of the allenyl moiety in an endo-mode manner, as
anticipated, resulting in the formation of 10a, which
might be in part susceptible to the base-catalyzed iso-
merization to 11a. The final step of this transforma-
tion must be the demethoxycarbonylation of 10a
and/or 11a with the alkoxide species leading to the
production of 9a, although the exact mechanism of
the demethoxycarbonylation is so far unclear.16
Scheme 2. Reagents and conditions: (a) NaH, DMF, 0°C–rt;
(b) p-TsOH, MeOH, rt, 5a (86%), 5b (86%), 5c (34%), 5d
(90%), 6a (88%), 6b (83%), 6c (41%), 6d (98%); (c) PhSCl,
Et3N, THF, −78°C; (d) mCPBA, CH2Cl2, 0°C, 7a (85%), 7b
(81%), 7c (77%), 7d (50%), 8a (91%), 8b (74%), 8c (66%),
8d (88%).
At the beginning of this study, we investigated the
transformation of 7a to the corresponding ring-closed
products. Treatment of the allenyl sulfone 7a with
sodium methoxide in MeOH at room temperature
immediately led to complete consumption of the start-
ing material as well as production of three new spots
on TLC, which needed a prolonged reaction time (26
h) to converge into one product. The isolated product
from the reaction mixture was the cyclopentenecar-
boxylate derivative 9a12 (96%) instead of the expected
cyclopentene-1,1-dicarboxylate derivatives 10a and/or
11a (Table 1, entry 1). A similar result was observed
when 7a was exposed to potassium methoxide in
MeOH for a shorter reaction time (2 h) (entry 2). In
contrast to these two cases, rapid conversion of 7a
into 9a (84%) was realized within 5 min upon treat-
t
ment with potassium tert-butoxide in BuOH at room
The next phase of this program involved the applica-
tion of this newly developed procedure to the con-
temperature (entry 3). The ring closure of 7a with
potassium hydroxide in THF also furnished 9a in
Table 1. Ring closure reaction of 7aa
entry
base
equiv.
solvent
time
yield (%)
1
2
3
4
MeONa
MeOK
4.5b
4.5b
1.5
MeOH
MeOh
tBuOH
THF
26 hc
2 hc
96
95
84
67
tBuOK
5 mind
6 hc
aq. KOH
1.5
\\67
a Reaction was monitored by TLC. Complete consumption of 7a was observed within 5 min in each case.
b It took more prolonged reaction time when 1.5 equiv. of base was used.
c Three new spots gradually converged to 9a.
d No other products could be detected on TLC.

C. Mukai et al. / Tetrahedron Letters 44 (2003) 1583–1586
1585
t
Table 2. Ring closure reaction of 7 and 8 with BuOK in
tBuOHa
Scheme 3.
struction of other carbocycles. We chose potassium
t
tert-butoxide in BuOH (Table 1, entry 3) for further
investigation, since rapid conversion involving dealkoxy-
carbonylation would be anticipated. The results obtained
from the reactions of 7b–d and 8a–d under standard
conditions, in combination with the result of 7a, are
summarized in Table 2. There are several features that
should be pointed out. (i) All reactions, except for entries
3 and 7, afforded the corresponding cyclized-products
accompanied with dealkoxycarbonylation in high yields.
(ii) Contrary to our prediction, 7c and 8c produced 9b
and 12b, respectively, via debenzoylation instead of
deethoxycarbonylation (entries 3 and 7). This observa-
tion might provide additional information concerning
the mechanism.16,17 (iii) In the case of 7d and 8d, longer
time as well as higher temperature (60°C) were required
to complete the reaction, although rapid consumption of
the starting materials was observed within 5 min (entries
4 and 8).
In summary, we have developed a simple and conve-
nient procedure for the preparation of the cyclopentene
and cyclohexene frameworks having three distinguish-
able functionalities via the endo-mode ring closure of
the allenyl sulfone derivatives. Application of this inter-
esting method to the construction of other carbocycles,
like cycloheptene and cyclooctene skeletons, as well as
further investigation on the mechanism of the decar-
bonylation process is now in progress.
References
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Acknowledgements
This work was supported in part by Nagase Science and
Technology Foundation and by a Grant-in Aid for
Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan, to
which the authors’ thanks are due.

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also examined, but were found to be inferior to the ones
listed in Table 1.
15. Similar demethoxycarbonylation was reported by Balme
and co-workers2b during their investigation on the palla-
dium-catalyzed exo-mode cyclization of dimethyl 5-
hexyne-1,1-dicarboxylate and its analogues in the
t
presence of BuOK.
16. The simple explanation for demethoxycarbonylation of
10a and 11a might involve nucleophilic attack of the
alkoxide on the cationic carbonyl center. However, the
fact that a more sterically hindered tert-butoxide reacted
much faster than methoxide and hydroxide can not be
rationalized by the above assumption.
17. Debenzoylation preferentially occurred over deethoxycar-
bonylation (entries 3 and 7). Therefore, the other plausi-
ble mechanism for decarbonylation of the 1,3-dicarbonyl
functionality, which would involve the attack of the
alkoxide on the alkyl group of the ester functionality with
liberation of carbon monoxide, can be ruled out. In
addition, preferential deacetylation over demethoxycar-
bonylation was also reported under the palladium-cata-
lyzed exo-mode cyclization of alkyne derivatives in the
7. The intermolecular Michael-type reaction between the
1,2-allenyl ketones with the active methine derivatives
t
presence of BuOK.2b