Tetrahedron Letters
Synthesis of benzofuran-containing spirolactones
from diarylcyclopropenones
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Jia-Ru Syu, Chi-Hui Lin, Chiao-Wen Kuo, Ding-Yah Yang
Department of Chemistry, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Xitun District, Taichung 40704, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Several novel benzofuran-containing spirolactones were synthesized and characterized using copper-
catalyzed heterodimerization of 1,2-diarylcyclopropenones, and followed by sequential intramolecular
cyclopropene ring opening and oxidative cyclization.
Received 16 November 2013
Revised 25 December 2013
Accepted 31 December 2013
Available online 8 January 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
1,2-Diarylcyclopropenone
Spirolactone
Dimerization
Benzofuran
Introduction
the synthesis and characterization of three o-hydroxyphenylcyc-
lopropenone-derived, benzofuran-containing spirolactones from
Ever since the synthesis of diphenylcyclopropenone was re-
ported half a century ago,1 the chemistry and properties of cyclop-
ropenone and its related cyclopropenylium derivatives2 have
inspired substantial research on account of the unusual aromatic-
1,2-diarylcyclopropenones.
Results and discussion
ity associated with this two-p-electron motif. Even today, this
Scheme 1 outlines the synthesis of the spirolactone 1. It started
with the coupling of p-methylanisole (2) with perchlorocycloprop-
1-ene (3) in the presence of aluminum chloride at low temperature
to give 2,3-bis(2-methoxy-5-methylphenyl)cycloprop-2-enone
(4).9 Compound 4 was then coupled with commercially available
1,2-diphenylcyclopropenone (5) under the influence of a catalytic
amount of copper bromide in 1,2-dichloroethane at 75 °C to obtain
the spirolactone 6.6 Selective demethylation of one of the two
methoxy groups on 6 with 1.2 equiv of tribromoborane followed
by in situ cyclopropene ring opening afforded the benzofuran 7.
The subsequent demethylation of the second methoxy group of 7
with tribromoborane induced the oxidative cyclization of the lac-
tone and phenol moiety to furnish the target spirolactone 1. The
molecular structures of 7, 1, and 6 were all elucidated by the X-
ray crystallography as shown in Figures 1 and 2.10
smallest Huckel aromatic continues to attract researchers’ atten-
tion for its unique aromatic cation properties. For instances, Peart
and Tovar3 have incorporated the cyclopropenium moiety into
p-conjugated polymers and found that the increased contributions
of cyclopropenium cation aromaticity restrict the quinoidal charge
carriers. Kelly and Lambert have recently reported the use of
diphenylcyclopropenone as a catalyst to catalyze cyclodehydration
of diols4 and to activate the substitution of alcohols with mesylate
ion.5 Our group was attracted by one of the unique properties of
diphenylcyclopropenone, that is, its ease of dimerization to the
corresponding cyclopropene spirolactone under the influence of
transition metal catalysts.6 We envision the resulting spirolactone,
in the presence of an intramolecular nucleophile, is prone to un-
dergo cyclopropene ring opening reaction due to its intrinsic
strained structure. The proposed ring-opened product is presum-
ably susceptible to oxidative cyclization to afford the benzofu-
ran-containing spirolactone. Since spirolactones are well-known
heterocycles that exhibit various biological7 and functional proper-
ties,8 the design and synthesis of spirolactones with novel molecu-
lar skeletons remain desirable. Here, we describe our effort toward
In the coupling reaction between 4 and 5, four possible
regioisomers were expected. To our delight, the desired product
6 was the major isomer with the ratio of the major product to other
combined three regioisomers to be approximately 7 to 1. The X-ray
crystal structure of the major coupling product
6 (Fig. 2)
unambiguously revealed that the two methoxyphenyl groups were
attached to the cyclopropene ring. Scheme 2 depicts the proposed
mechanism for the Cu(I)-catalyzed heterodimerization of 4 and 5
to 6. We envisioned that the first step involves the preferred
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0040-4039/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved.