Angewandte
Chemie
spectroscopic analysis and a yield of 90% of the isolated
product 6 was obtained in just 25 min. Heating with catalyst 4
at 408Cfor 24 h provided a yield of 52% of the isolated
product (55% conversion; entry 1). These results for the two
metathesis protocols are quite general in that the microwave
protocol tends to give excellent conversions and yields,
whereas the protocol which employs 4 at 408Cis gentler,
albeit giving generally lower yields. Substituents at the 7,7’-
positions of the binaphthyl skeleton also had little affect on
the outcome of the ring-closing event (entries 2 and 3). The
ring closure of dimethyl ether 7 was performed on the largest
scale possible (which was limited because of the volume of the
microwave vessel; scale: ꢀ 350 mg of 7; entry 2). The micro-
wave could reach a maximum temperature of 1208Con this
scale. Following irradiation for 120 min, 7 underwent 95%
conversion, and 57% yield of the isolated helicene 8 was
obtained. Treatment of 7 with 4 at 408Cin a sealed tube
resulted in a conversion of 40% and a similar yield of 22% for
the isolated product 8 (55% yield based on the recovered
starting material). The dibenzyl ether 9 also provided a
conversion of 100% after 25 min under microwave heating
conditions (entry 3). However, some benzyl deprotection was
observed and a yield of 61% was obtained for the isolated
product 10. The milder cyclization using 4 resulted in only
41% conversion, but cleavage of the benzyl group was not
observed and the yield of the isolated product 10 (22% vs
49% yield based on the recovered starting material) was
nearly identical to that observed for the methoxy derivative 8.
To improve the efficiency of the reaction, the microwave
protocol was repeated, but catalyst 3 was replaced with 4. As
expected 100% conversion was observed after 25 min;
however, some cleavage of the benzyl group was again
observed, although the yield of the isolated product was
slightly higher than the previous run with 3 (68 vs 61%).
Substituents at the 8,8’-positions were expected to be
problematic, as they result in increased ring strain in the
helicene products. Consequently, the first substrate inves-
tigated possessed the smallest substituent possible, an extra
hydrogen atom (entry 4). 5,5’-6,6’-7,7’-8,8’-Octahydro-1,1’-bi-
2-naphthol was transformed into 11 and subjected to micro-
wave irradiation with 3; although 100% conversion of 11 was
obtained, 140 minutes were required for complete conver-
sion. Surprisingly, 50% conversion (45% yield of the isolated
product) was obtained with catalyst 4, thus prompting a
second trial with 4 under microwave irradiation. Gratifyingly,
75% conversion was obtained after only 25 min, and the
saturated helicene 12 was isolated in 68% yield (86% yield
based on recovered 11).
Subsequent experiments sought to further investigate the
effect of the substituents which would result in increased
strain in the helicene products. Consequently, the [6]helicene
precursor 15 underwent smooth conversion (100%) to the
corresponding [6]helicene 16 after 60 min under microwave
irradiation, which was isolated in 80% yield (entry 6).
Treatment with catalyst 4 at 408Cin a sealed tube resulted
in 100% conversion and 70% yield of the isolated product.
Similar results were obtained for the preparation of [7]hel-
icene (entry 7). For example, substrate 17 required 60 min of
microwave irradiation with 2 to undergo complete conversion
into 18 (81% yield of isolated product). Milder conditions
with catalyst 4 also resulted in 100% conversion and 80%
yield of isolated [7]helicene.
In summary, we have developed a novel synthesis of
substituted [5]helicenes and [6]- and [7]helicenes through
ring-closing olefin metathesis. Conditions have been opti-
mized using two separate protocols: catalyst 3/CH2Cl2 under
microwave irradiation or catalyst 4/PhH at 408C, when a
sensitive functionality may be present. A highlight of this
method is the facile formation of various substituted [5]hel-
icenes and [6]- and [7]helicenes from the readily modifiable
1,1’-binaphthyls. For example, substituted [6]helicenes could
be formed from mixed oxidative couplings between 3-
phenanthrol and various 2-naphthols. This ease of function-
alization suggests that these methods should be of significant
interest in the fields of materials science and medicinal
chemistry. These studies reinforce that olefin metathesis
catalysts can be remarkably effective in generating strained
molecular architectures and emphasize that ring-closing
olefin metathesis can be a powerful route to the preparation
of aromatic compounds. In contrast to other methods for
helicene formation which utilize reactive radical or carbene
intermediates, these olefin-metathesis conditions are gentle
and the possibility of an asymmetric route to helicenes
through a kinetic-resolution route is currently being pursued.
Received: November 21, 2005
Published online: March 28, 2006
Keywords: arenes · helical structures · helicenes ·
microwave irradiation · olefin metathesis
.
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Higher helicenes were also accessible using the above
protocols. The first attempt involved the conversion of 2-
phenanthrol into the corresponding divinyl precursor 13
through the same series of transformations used for 1
(entry 5).[15] The resulting helicene 14 was expected to form
readily under conditions optimized for [5]helicene. Indeed,
following microwave irradiation for 25 min in the presence 3,
100% conversion of 13 was observed and 75% yield of the
helicene product 14 was obtained. Strangely, heating 13 in a
sealed tube with 4 gave a conversion of 45% and a yield of
55% (based on the recovered starting material) for 14.
[4] a) S. Honzawa, H. Okubo, S. Anzai, M. Yamaguchi, K. Tsumoto,
I. Kumagai, Bioorg. Med. Chem. 2002, 10, 3213; b) Y. Xu, X. Y.
Zhang, H. Sugiyama, T. Umano, H. Osuga, K. Tanaka, K . J. Am .
Chem. Soc. 2004, 126, 6566 – 6567.
Angew. Chem. Int. Ed. 2006, 45, 2923 –2926
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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