Efficient phenanthrene, helicene, and azahelicene syntheses

Article abstract of DOI:10.1002/anie.200504287

Homolytic aromatic substitution reactions are used for the efficient regioselective synthesis of helicenes, phenanthrenes, and azahelicenes. The use of halo and alkoxy substituents to control the stereochemical outcome of this approach and X-ray studies o

Full text of DOI:10.1002/anie.200504287

Communications
Polyaromatic Compounds
DOI: 10.1002/anie.200504287
Efficient Phenanthrene, Helicene, and
Azahelicene Syntheses**
David C. Harrowven,* Ian L. Guy, and Lana Nanson
For many years, helicenes were regarded as little more than
an academic curiosity. More recently, their extraordinary
optical,[1] electronic,[2] and chelating[3] properties have re-
kindled an interest in these nonplanar condensed aromatic
compounds in fields as diverse as liquid crystals,[4] sensors,[5]
dyes,[5] asymmetric synthesis,[3,6,7] molecular recognition,[3,6,7]
polymer synthesis,[8] and materials science.[8] Helicenes have
classically been prepared by the oxidative photocyclization of
bis(stilbene)s.[9,10] Though useful, complex product mixtures
often arise as a result of poor regiocontrol in the photo-
cyclization step or competitive side reactions, such as photo-
induced dimerization or benzo[ghi]perylene formation.[10] The
challenge of developing efficient routes to helicenes that are
amenable to scale-up has inspired many imaginative
approaches,[11,12] including strategies based on Diels–Alder
cycloadditions,[13] carbenoid insertions,[14] radical cyclizations,
and metal-mediated cycloisomerizations.[15,16] Herein, we
report a short and efficient entry to helicenes, azahelicenes,
and phenanthrenes in which the use ofhalo and alkoxy
substituents to control both the stereochemical course of
Wittig reactions and the regiochemical course ofhomolytic
aromatic substitution reactions is a key feature.
The strategy developed is exemplified by the synthesis of
5-aza[5]helicene (4) outlined in Scheme 1.[17] This synthesis
relies on the use ofcooperative ortho effects to control the
stereochemical course ofa Wittig reaction [18] and the counter-
intuitive use ofa halide atom as a protecting group in a
homolytic aromatic substitution reaction. Thus, phosphonium
salt 2 and 2-chloroquinoline-3-carboxaldehyde were first
condensed under standard Wittig conditions to give azastil-
bene 3 in near quantitative yield as a 16:1 mixture of Z and
E isomers (as determined by 1H NMR spectroscopic integra-
tion[18a]). Isomer (Z)-3 was then exposed to 2.4 equivalents of
tributyltin hydride and 0.4 equivalents ofVAZO to induce
[19]
selective homolysis ofthe carbon–iodine bond.
Homolytic
substitution at C4 ofthe quinoline moiety followed to give 5-
aza[5]helicene 4 in 75% yield.[20] Notably, no products arising
from the addition of the aryl radical intermediate to C2 of the
[*] Prof. D. C. Harrowven, I. L. Guy, L. Nanson
School of Chemistry
University of Southampton
Highfield, Southampton, SO17 1BJ (UK)
Fax: (+44)238-059-6805
E-mail: dch2@soton.ac.uk
[**] Financial support from the EPSRC through the Doctoral Training
Account is gratefully acknowledged.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Scheme 3. Highly stereoselective syntheses of Z stilbenes and regiose-
lective syntheses of phenanthrenes.
Scheme 1. Synthesis of 6-chloro-5-aza[5]helicene. VAZO=1,1’-azobis-
(cyclohexanecarbonitrile).
quinoline moiety were observed,[20] as the attached chlorine
atom arrested that ortho-cyclization mode.
This method provides a powerful means of preparing all
kinds ofcondensed polyaromatic compounds with predictable
regiocontrol. For example, 1-chloro- and 1-bromophenan-
threne were readily prepared from phosphonium salts 5 and 6,
respectively, by condensation with 2-iodobenzaldehyde and
treatment ofthe resulting stilbenes 7 and 8 with 2.4 equiv-
alents oftributyltin hydride and 0.4 equivalents ofazoisobu-
tyronitrile (AIBN; Scheme 2).[21,22] In each case, the carbon–
Scheme 4. [5]Helicenes by tandem radical cyclization.
VAZO then gave 7,8-dimethoxy[5]helicene (18a) in 60%
yield (thus representing a 75% yield based on (Z,Z)-17a).
The related syntheses of2,3,7,8,12,13-hexamethoxy[5]heli-
cene (18b) and 1,7,8,14-tetramethoxy[5]helicene (18c) were
achieved in the same fashion in 73 and 46% overall yield,
respectively, from the respective phosphonium salts 11 and
15c.
Scheme 2. 1-Halophenanthres from 2-iodo-2’-halostilbenes.
The method was next extended to [7]helicenes by
conjoining bis(aldehyde) 16[23] with 2 equivalents ofphospho-
nium salt 2. The resulting 3:1 mixture of Z,Z and E,Z bis-
(stilbene)s 19 was separated by column chromatography, and
(Z,Z)-19 was treated with 5 equivalents oftributyltin hydride
and 0.4 equivalents ofVAZO in toluene at 90 8C to give 9,10-
dimethoxy[7]helicene (20) as large yellow needles in 75%
yield (Scheme 5).
iodine bond was homolyzed selectively to generate an aryl
radical donor,[19] thus leaving the second halide atom to serve
as a protecting group for the attached ortho-carbon atom in
the radical acceptor. The same two-step sequence was
effective over a broad range of substrates, as evidenced by
the examples outlined in Scheme 3 and the Supporting
Information.
The impressive degree of Z selectivity achieved in the
Wittig reaction when both the ylide and aldehyde contained
an ortho-halo or ortho-alkoxy substituent,[18] meant that the
method could be usefully employed in a bidirectional sense
for the synthesis of helicenes (Scheme 4). To that end, a
double Wittig reaction between bis(aldehyde) 16 and (ortho-
iodoaryl)triphenylphosphonium salt 15a gave the expected
bis(stilbene) 17a in near quantitative yield as an inseparable
4:1 mixture of Z,Z and E,Z isomers. Treatment with
4.4 equivalents oftributyltin hydride and 0.4 equivalents of
Further points ofinterest were noted ofllowing X-ray
crystallographic analysis ofhelicenes 18b, 18c, and 20 (see
Table 1 and the Supporting Information). Whereas crystal-
lization of 18b (from toluene/pentane) and 20 (from EtOAc)
led to racemic crystal forms, rac-18c (from EtOAc/hexane)
spontaneously formed enantiomorphous single crystals. This
phenomenon is extremely rare within the [5]helicene series,[24]
having been observed just once before with the condensed
[5]helicene
7:8,9:10-dibenzo-1,2,3,4-tetrafluorotripheny-
lene.[25] In addition, there appear to be two distinct helicene
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18b
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forms—type I in which the burden of torsional strain is mainly
accommodated by the central arene (exemplified by 18b),
and type II in which each ofthe internal arenes is distorted to
a similar extent (exemplified by 18c and 20).
In summary, concise and efficient routes to phenan-
threnes, helicenes, and azahelicenes have been achieved by
using homolytic aromatic substitution reactions. Points of
interest from a synthetic perspective are the use of halo and
alkoxy substituents to control the stereochemical course of
Wittig reactions which lead to stilbene and bis(stilbene)
precursors[18] and their subsequent role as protecting groups
in homolytic aromatic substitution reactions. Notable from a
structural perspective is the recognition oftwo distinct
helicene types and the spontaneous formation of enantio-
morphous single crystals on recrystallization of rac-18c from
ethyl acetate/hexane.
Received: December 2, 2005
Published online: February 28, 2006
Keywords: helicenes · homolytic aromatic substitution ·
.
polyaromatic compounds · protecting groups ·
radical cyclization
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