[5]Helicenes by tandem radical cyclisation

Article abstract of DOI:10.1016/S0040-4039(02)01720-3

A new and rapid approach to [5]helicenes is described. A central feature is the use of a sequential, non-reducing radical cyclisation reaction of (Z,Z)-1,4-bis(2-iodostyryl)benzene derivatives, viz. 3→1, mediated by tributyltin hydride.

Full text of DOI:10.1016/S0040-4039(02)01720-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7345–7347
[5]Helicenes by tandem radical cyclisation
David C. Harrowven,a,* Michael I. T. Nunna and David R. Fenwickb
aDepartment of Chemistry, The University of Southampton, Southampton SO17 1BJ, UK
bDiscovery Chemistry, Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ, UK
Received 27 June 2002; accepted 16 August 2002
Abstract—A new and rapid approach to [5]helicenes is described. A central feature is the use of a sequential, non-reducing radical
cyclisation reaction of (Z,Z)-1,4-bis(2-iodostyryl)benzene derivatives, viz. 3“1, mediated by tributyltin hydride. © 2002 Elsevier
Science Ltd. All rights reserved.
For many years helicenes were regarded as little more
than an academic curiosity. More recently their
extraordinary optical and electronic properties have
rekindled an interest in these non-planar condensed
aromatics in fields as diverse as liquid crystals,1 sen-
sors,2 asymmetric synthesis and polymer synthesis.3,4
Helicenes are commonly prepared by oxidative photo-
cyclisation.5,6 Though useful, the method can give rise
to complex product mixtures due to poor regiocontrol
in the photocyclisation step and competitive side reac-
tions such as photo-induced dimerisation or benzo-
[ghi]perylene formation.6 Several alternative strategies
have therefore been developed for the synthesis of
helicenes,7 including methods based on Diels–Alder
cycloaddition reactions and carbenoid insertion reac-
tions.8,9
helicenes,12 it seemed likely that the two processes could
be run in parallel. In this letter we report our realisation
of that objective.
The first target we decided to address was the parent
[5]helicene 1. To that end, p-xylylene dibromide 4 was
transformed into the corresponding bis-phosphonium
salt 5 by treatment with triphenylphosphine.6a,13
A
tandem Wittig reaction was then effected with o-
iodobenzaldehyde, giving a 1:1 mixture of (Z,E)- and
(Z,Z)-1,4-bis(2-iodostyryl)benzenes 7 and 3 in 77%
yield. These were readily separated by column chro-
matography. Pleasingly, treatment of 3 with tributyltin
hydride under standard radical forming conditions,
gave [5]helicene 1 in 58% yield (Scheme 2).
With the viability of the approach established, we next
sought to extend the method to other [5]helicenes. A
series of iodobenzaldehyde derivatives 11a–d were thus
prepared using standard protocols (Scheme 3). Each
Our interest in radical additions to aromatic and het-
eroaromatic ring systems,10 prompted us to explore an
alternative entry to helicenes based on a tandem radical
cyclisation strategy (Scheme 1). Having shown that
6-endo/exo-trig cyclisations of aryl radicals to arenes
provide a high yielding route to phenanthrenes,11 and
that related cyclisations to phenanthrenes can give
was then coupled to
6
to give 1,4-bis(2-
iodostyryl)benzenes 12a–d, respectively. In each case
the major product formed was the desired (Z,Z)-isomer
and this could be separated from the product mixture
by a combination of column chromatography and
recrystallisation. The (Z,E)-isomers were found to be
significant byproducts while the (E,E)-isomers
accounted for little more than 5% of the total mass
balance (Scheme 3).
The stage was now set to examine the generality of the
reaction in more detail. Pleasingly, each of the (Z,Z)-
1,4-bis(2-iodostyryl)benzenes 12a–d, gave the corre-
sponding [5]helicene as the major product on treatment
with tributyltin hydride under standard radical forming
conditions (4.4 equiv. Bu3SnH, 0.4 equiv. AIBN,
Scheme 1.
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01720-3

7346
D. C. Harrow6en et al. / Tetrahedron Letters 43 (2002) 7345–7347
Table 1. Radical cyclisation reactions leading to helicenes
Scheme 2.
Scheme 3.
low solubility in toluene and ethyl acetate, combined
with our employment of an aqueous KF work-up pro-
cedure, led to substantial mechanical losses of these
byproducts.
PhMe, 90°C). Yields ranged from 35 to 49% (Table 1).
These helicenes were accompanied by the correspond-
ing dibenzo[a,h]anthracene, arising from cycli-
sations of the aryl radical intermediates to the C2
and C5 centres of the central arene. Though these
were isolated in yields ranging from 3 to 27%, they
were undoubtedly formed in greater quantity—their
In conclusion, we have developed a new route to
[5]helicenes based on a tin mediated, non-reducing
tandem radical cyclisation of (Z,Z)-1,4-bis(2-
iodostyryl)benzene derivatives. The approach is short

D. C. Harrow6en et al. / Tetrahedron Letters 43 (2002) 7345–7347
7347
and easy to effect, with the key step providing helicenes
in 35–58% yield. We are presently seeking to extend the
method to higher helicenes and related structures that
are difficult to prepare by traditional methods.
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