Imperial College London

Henry Rzepa

Much like climbing Mt. Everest because its there,  some hypothetical
molecules are just too tantalizing for chemists to resist attempting a
synthesis. Thus in 1964, Edgar Heilbronner  speculated on whether a
conjugated annulene ring might be twistable into a  Möbius strip. It was
essentially a fun thing to try to do, rather than the effort being based
on some anticipated  (and useful) property it might have. If you read
the original article (rumour has it the idea arose during a lunchtime
conversation, and the manuscript was completed by the next day), you
will notice one aspect of these molecules that is curious by its
absence. There is no mention
([10.1016/S0040-4039(01)89474-0](http://dx.doi.org/10.1016/S0040-4039(01)89474-0){target="new"})
that such Möbius systems will be **chiral**. By their nature, they have
only axes of symmetry, and no planes of symmetry, and such molecules
therefore cannot be superimposed upon their mirror image; as is required
of a **chiral** system (for a discussion of the origins and etymology of
the term, see
[10.1002/chir.20699](http://dx.doi.org/10.1002/chir.20699){target="new"}).

::: {#attachment_364 .wp-caption .aligncenter style="width: 164px"}
![The 16-annulene synthesized by Herges and his
team.](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2009/04/herges.jpg "herges"){.size-full
.wp-image-364 loading="lazy" decoding="async"
aria-describedby="caption-attachment-364"
onclick="jmolInitialize('../Jmol/');jmolSetAppletColor('yellow');jmolApplet([450,450],'load wp-content/uploads/2009/04/BEMLIP.mol;zoom 120;');"
width="154" height="288"}

The 16-annulene synthesized by Herges and his team. Click for 3D.
:::

Heilbronner's little vignette had little overt effect on the synthetic
community until around 2003, when Rainer Herges announced that a
crystalline annulene following this recipe had been rationally
synthesized
([10.1038/nature02224](http://dx.doi.org/10.1038/nature02224){target="new"}).
This time, the chemical community really sat up and took notice. The
synthesis was hailed as a major achievement, ranking (chemically) as
similar to climbing Everest. But if you read Herges' article carefully,
yet again you will note the absence of any discussion of the chirality
of their molecule. Their synthesis was of course racemic, in other words
an equal proportion of both enantiomers was made. Indeed, it is not
obvious how a non-racemic synthesis could be carried out, although
resolution of the product might be an easier task. So in the absence of
any pure enantiomer of this molecule, can one speculate on its chiral
properties? One obvious such property is the optical rotation, and in
particular the \[α\]D value in chloroform. Most optically pure molecules
with molecular weights of \< 500 Daltons  tend to have rotations also \<
500°. Few molecules have values \> 1000°. Now it should be said at the
outset that a molecule with a large optical rotation is not *more
chiral* than a molecule with a smaller value; indeed it seems generally
agreed that the question "how chiral is this molecule" is either fairly,
or even completely meaningless. But it seems a useful task of having a
value to hand which is at least approximately accurate, so that some
idea of whether any attempted resolution of the enantiomers has produced
optically pure product or not. Fortunately, in the last decade or so,
computing a value for \[α\]D has been entirely viable using the standard
programs
(see [10.1002/chir.20466](http://dx.doi.org/10.1002/chir.20466){target="new"}
and [10.1021/jo070806i](http://dx.doi.org/10.1021/jo070806i) for a
discussion). This is also useful for two reasons:

 

1.  If the magnitude of the rotation is \> 100°, then the sign of this
    rotation can be very reliably matched to either enantiomer. This
    allows the absolute configuration to be assigned with a lot of
    confidence, and probably much more easily than trying to do it by
    other methods.
2.  The magnitude itself can be reliably predicted to within 10% of the
    true value if the molecule is conformationally rigid. However, if it
    has any rotatable groups (and that even includes e.g. OH groups),
    then the result can be enormously sensitive to that conformation (or
    Boltzmann mixture of conformations). Put the other way, calculating
    the optical rotation could be regarded as a very sensitive way of
    determining conformations!

So what of the 16-annulene synthesized by Herges and co-workers. Well at
the B3LYP/6-311G(2df,2pd) and SCRF(CPCM,solvent=chloroform) level of
theory (which is reasonably accurate, although one can do better of
course), the enantiomer shown by clicking on the graphic above is
predicted to have a rotation of **-1355°** (for the digital repository
entry for the calculation, see
[10042/to-2176](http://hdl.handle.net/10042/to-2176)). That is indeed a
large value for such a relatively small molecule, and is probably more
reliable because of the lack of conformational ambiguity. Well, you saw
the prediction here! Anyone up for testing it experimentally?

::: {.wp_orcid_field}
[https://orcid.org/0000-0002-8635-8390](https://orcid.org/0000-0002-8635-8390){target="_blank"
rel="author"}
:::


Much like climbing Mt. Everest because its there,  some hypothetical molecules are just too tantalizing for chemists to resist attempting a synthesis. Thus in 1964, Edgar Heilbronner  speculated on whether a conjugated annulene ring might be twistable into a  Möbius strip. It was essentially a fun thing to try to do, rather than the effort being based on some anticipated  (and useful) property it might have.

Messaggi di Rogue Scholar

The chirality of Möbius annulenes