DOI: 10.1002/asia.201200201
Ruthenium-Catalyzed Intramolecular [2+2+2] Cyclization of Allene–Yne–
Enes: Construction of Fused-Tricyclic Skeletons
Nozomi Saito,* Taisuke Ichimaru, and Yoshihiro Sato*[a]
A transition metal-catalyzed [2+2+2] three-component
cycloaddition is one of the most powerful methodologies for
construction of a polycyclic skeleton in a one-pot opera-
tion.[1,2] Numerous examples of an intermolecular or intra-
molecular [2+2+2] cycloaddition with alkynes or alkenes, as
an unsaturated bond component, have been reported to
date.[1] However, [2+2+2] cycloaddition of substrates includ-
ing an allene as a coupling partner is still limited to several
examples.[3–8]
We have previously reportedc a ruthenium(II)-catalyzed
cyclodimerization of allenynes 1 that afford pentacyclic
compounds 3.[9] The reaction proceeds through the forma-
tion of ruthenacyclopentene intermediate 2, from which re-
Scheme 1. Ruthenium-catalyzed cyclization of allenyne through ruthena-
cyclopentene intermediate.
ductive elimination followed by dimerization of the resulting
cyclobutene derivative affords 3. In this regard, we envis-
aged that if the reaction of allenyne 1, which possesses an
unsaturated bond as an R1 substituent, was carried out in
the presence of a ruthenium catalyst, insertion of the unsa-
turated bond into the ruthenium–carbon bond of 2 would
proceed to give ruthenacycle 4, and subsequent reductive
elimination would afford tricyclic compound 5 (Scheme 1).
Here, we report ruthenium(II)-catalyzed intramolecular
[2+2+2] cyclization of allene–yne–ene, which affords 5,6,5-
fused tricyclic skeletons.[10,11]
Scheme 2. ACHTNUTRGENNUG[Cp*RuClACHTUNGTREN(NUNG cod)]-catalyzed [2+2+2] cyclization of allene–yne–
ene 1a.
To study the feasibility of the above method, the simple
substrate 1a was treated with 5 mol% of [Cp*RuClACTHNUTRGNEUG(N cod)] in
toluene at 508C (Scheme 2). As a result, an expected 5,6,5-
fused tricyclic compound 5a was obtained in 95% yield as
a single diastereomer.
tricyclic compound 5c was produced in low yield (Table 1,
entry 2). Allene-yne-enes 1d–1 f were also subjected to the
same reaction conditions, however, no desired cyclic com-
pounds were obtained and only starting materials were re-
covered (Table 1, entries 3–5). The reaction of allene-yne-
ene 1g with a methyl group on the allene moiety gave the
corresponding tricyclic compound 5g in 36% yield along
with the triene derivative 6, which was obtained through b-
hydride elimination from ruthenacycloheptene intermediate
4 (Table 1, entry 6).
Next, we turned our attention to investigation of the
effect of the linker structure (Table 2). When the substrate
1h containing a fluorenyl group between the alkyne and
alkene moieties was subjected to the above-mentioned reac-
tion conditions, the cyclized product 5h was obtained in
83% yield (Table 2, entry 1). The reaction of allene-yne-
enes 1i and 1j containing a nitrogen atom and an oxygen
atom, respectively, in the linker between the alkyne and
alkene moieties proceeded stereoselectively to give the cor-
responding tricyclic compounds 5i and 5j (Table 2, entries 2
Encouraged by this result, we set out to investigate the
scope and limitations of the [2+2+2] cyclization of allene–
yne–enes. First, the effects of substituents on the allene and
alkene moieties were examined (Table 1). Cyclization of 1b
with a methallyl group instead of an allyl group afforded the
corresponding cyclized product 5b in quantitative yield as
a single stereoisomer (Table 1, entry 1). On the other hand,
when the substrate 1c bearing an E-crotyl group as a teth-
ered alkene was treated with [Cp*RuClACTHNUTRGNEUNG(cod)] catalyst, the
[a] Dr. N. Saito, T. Ichimaru, Prof. Dr. Y. Sato
Faculty of Pharmaceutical Sciences
Hokkaido University
Sapporo 060-0812 (Japan)
Fax : (+81)11-706-4982
Supporting information for this article is available on the WWW
Chem. Asian J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
&
&
&
Saito, Nozomi
