Published on the web November 12, 2011
1343
Synthesis and Stereochemical Behavior of a New Chiral Oxa[7]heterohelicene
Ryo Irie,*1 Akihiro Tanoue,1 Suguru Urakawa,1 Tatsushi Imahori,2 Kazunobu Igawa,3 Taisuke Matsumoto,3
Katsuhiko Tomooka,3 Shinsuke Kikuta,4,5 Tatsuya Uchida,4,5 and Tsutomu Katsuki4,5
1Department of Chemistry, Graduate School of Science and Technology, Kumamoto University,
2-39-1 Kurokami, Kumamoto 860-8555
2Priority Organization for Innovation and Excellence, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555
3Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga, Fukuoka 816-8580
4Department of Chemistry, Graduate School of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581
5Institute for Advanced Study, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581
(Received September 1, 2011; CL-110728; E-mail: irie@scc.kumamoto-u.ac.jp)
A new chiral oxa[7]heterohelicene 1b was synthesized by
catalytic aerobic-oxidative tandem cyclization of the o-phenyl-
O
O
S
S
ene-linked bis(2-naphthol) derivative 3 with palladium acetate in
dimethyl sulfoxide. Optical resolution of 1b was possible on
chiral HPLC, but it was found stereochemically rather unstable
at ambient temperature. Kinetic analysis and DFT calculation for
the dynamics of racemization of 1b were also disclosed.
1a: benzo-fused type
1b: naphtho-fused type
2a
known
unknown
(stereochemically robust)
Because of their unique helical structures and chirality,
helicenes are fascinating targets in organic synthesis.1 Since
the pioneering work by Newman et al. on the preparation of
[6]helicene in an optically pure form,2 synthetic studies on chiral
helicenes have been accelerated.3 Besides typical carbohelicenes
composed of an all-carbon ring framework, heterohelicenes
incorporating one or more heteroaromatic units in the skeleton
have also gained increasing attention.1a-1d,4 Stereochemically
defined thiophene-containing helical ring systems are prime
examples.5 In contrast to this, the furan-alternatives have been
rarely focused on.6,7 That would be partially because oxa-
heterohelicenes are supposed to be stereochemically less stable
resulting from small overlapping at the helix termini.6c,6d,8
Moreover, it seems to pose another issue that synthetic methods
to embed furan into a helicene framework have not been well
elaborated. These points have inspired us to devise a novel
synthetic approach to chiral furan-containing heterohelicenes. To
begin with, we were intrigued by the fact that the thia[7]hetero-
helicene 2a6c,6d,8 holds a robust helicity, though the oxa[7]-
heterohelicene 1a is unknown (Figure 1). Thus, we launched
studies on the synthesis of 1b, an analog of 1a, to gain some
insight into the molecular design on optically active furan-
containing oxa-heterohelicenes as reliable chiral platforms.
o-Alkynylphenols are known to undergo palladium(II)-
catalyzed annulation to give 3-benzofuranylpalladium(II) inter-
mediates, which serve for further C-C coupling reactions in a
tandem fashion.9 Thus, we envisioned that the phenylenediyne-
linked bis(2-naphthol) 3 would be submitted to the serial C-O
and C-C bond formation under Wacker-type oxidation condi-
tions, leading to 1b (Scheme 1). The precursor 3 should be
accessible by assembling 2-naphthol, o-phenylene, and acetylene
segments through conventional Sonogashira coupling reactions.
Herein we report on the synthesis of a new oxa-heterohelicene 1b
and the evaluation of its stereochemical stability.
Figure 1. Oxa- and thia[7]heterohelicenes of interest.
How much stable is the helix?
oxidative tandem
C-O/C-C bond formations
HO
OH
O
O
1b
3
I
OH
+
+
Sonogashira coupling
H
TMS
I
I
Scheme 1. Synthetic strategy for 1b.
gave 4. The iodinated compound 4 underwent the Sonogashira
coupling reaction with trimethylsilylacetylene followed by the
desilylation with tetrabutylammonium fluoride to obtain 5. The
alkyne 5 was subjected to the double Sonogashira coupling with
o-diiodobenzene to give 6. Although deacetylation of 6 under
the conventional conditions with K2CO3 in methanol triggered
undesired nonoxidative cyclization into a naphthofuran deriva-
tive (see the Supporting Information24),9e,11 the desired 3 was
obtained by the treatment of 6 with aqueous hydrazine in
acetonitrile.12 Finally, aerobic-oxidative tandem cyclization
worked on 3 under catalysis with Pd(OAc)2 in DMSO13 at
room temperature to provide 1b in good yield.
The molecular structure of 1b was determined by X-ray
crystallography to prove the helicity induced in solid state
1
(Figure 2).14 Moreover, the H NMR spectrum of 1b in CDCl3
indicates a significant upfield shift (7.10 ppm) of an aromatic
proton located in the mutually overlapping naphthalene rings
as compared to the corresponding chemical shift (in a range
of 7.46-7.61 ppm) for planar naphtho[2,1-b]furan.15 This also
supports a helical form of 1b in solution. However, we noted
The target oxa-heterohelicene 1b was synthesized as shown
in Scheme 2. Regioselective iodination of 2-naphthol at C1
position10 and the subsequent acetylation of the hydroxy group
Chem. Lett. 2011, 40, 1343-1345
© 2011 The Chemical Society of Japan