Imperial College London

Henry Rzepa

Most representational chemistry generated on a computer requires the
viewer to achieve a remarkably subtle transformation in their mind from
two to three dimensions (we are not quite yet in the era of the 3D
iPad!). The
[Cahn-Ingold-Prelog](http://en.wikipedia.org/wiki/Cahn–Ingold–Prelog_priority_rules){target="_blank"}
convention was a masterwork (which won the Nobel prize). It is shown in
action for the molecule on the left below. The CIP notation was actually
generated by Chemdraw, and required a fair sprinkling of wedged and
hashed bonds to (try to) remove stereoambiguity and generate the labels
(try it for yourself). As part of a lecture course on pericyclic
reactions, I tell the students that the reaction involves a \[1,3\]
sigmatropic migration of the red carbon and that this migration proceeds
with ***inversion of configuration*** at this migrating carbon (as the
selection rules require). Perceiving what the correct CIP product label
should be (with inferred stereochemical labels, resolving ? into either
R or S) is IMHO one of the most difficult conceptual experiences in all
of organic chemistry. I have over the years struggled to find a way of
revealing this in lecture notes (these struggles with the "lecture
notes" will be the topic of a future post here). However, I think I may
have finally cracked it; my solution is set out below!

::: {#attachment_5167 .wp-caption .aligncenter style="width: 320px"}
[![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/10/13.jpg "13"){.size-full
.wp-image-5167 loading="lazy" decoding="async"
aria-describedby="caption-attachment-5167" width="310"
height="164"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/10/13.jpg)

A 1,3 sigmatropic methyl migration.
:::

A short-cut to the answer might be to reason that if the CIP label for
the reactant is (S), and we are told that the carbon migrates with
inversion, we should label the product (R). Unfortunately, CIP does not
work like that. Because the key carbon in the product is not connected
to *exactly the same four surrounding ligands* as the reactant, all bets
are off! Having got that one out of the way, I now uncover my new
diagram.

::: {#attachment_5176 .wp-caption .aligncenter style="width: 317px"}
![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/10/13Me.gif "13Me"){.size-full
.wp-image-5176 loading="lazy" decoding="async"
aria-describedby="caption-attachment-5176"
onclick="jmolInitialize('../Jmol/');jmolSetAppletColor('yellow');jmolApplet([450,450],'load wp-content/uploads/2011/10/13Me.log; frame 3; zoom 100; connect (atomno=12) (atomno=4) PARTIAL;connect (atomno=12) (atomno=2) PARTIAL;vectors on;vectors 4;vectors scale 5.0; color vectors green; vibration 20;animation mode loop;');"
width="307" height="311"}

Intrinsic reaction coordinate (IRC) for the 1,3 carbon migration. Click
for transition state mode.
:::

Keep an eye out for the CIP labels, which are generated dynamically as
the IRC proceeds. It starts (S), but then the label goes as the
[bond](http://www.ch.imperial.ac.uk/rzepa/blog/?p=5104){target="_blank"}
to the atom gets disconnected (formally), and reappears as (R) when the
atom is reconnected to its new home. If you look carefully at the
breaking and forming bond, you will perceive in effect an S~N~2 reaction
taking place, with the required inversion at the carbon. The hydrogen on
that carbon conveniently swings around to reinforce the perception of an
inversion.

It is worth considering how the [IRC
representation](http://hdl.handle.net/10042/to-9510){target="_blank"}
might improve upon the perception compared with the [imaginary
(transition state) vibrational
mode](http://hdl.handle.net/10042/to-9509){target="_blank"}. The latter
in effect represents only a small part of that IRC, the so-called
harmonic part. Most reactions deviate from such a [harmonic
oscillator](http://en.wikipedia.org/wiki/Harmonic_oscillator){target="_blank"},
and the IRC captures that deviation. The stereochemical perception can
be enhanced by showing the full
([anharmonic](http://en.wikipedia.org/wiki/Anharmonicity){target="_blank"})
motion of the atoms during the reaction.

Finally, a bonus. Below you can see a \[1,9\] sigmatropic methyl
migration. It proceeds both with inversion at the methyl, and from top
to bottom faces  (antarafacially) of the nonatetraene. A double-twist
Möbius transition state.

::: {#attachment_5186 .wp-caption .aligncenter style="width: 294px"}
[![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/10/19.gif "19"){.size-full
.wp-image-5186 loading="lazy" decoding="async"
aria-describedby="caption-attachment-5186" width="284"
height="208"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/10/19.gif)

1,9 methyl migration with double antarafaciality.
:::

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


Most representational chemistry generated on a computer requires the viewer to achieve a remarkably subtle transformation in their mind from two to three dimensions (we are not quite yet in the era of the 3D iPad!). The Cahn-Ingold-Prelog convention was a masterwork (which won the Nobel prize). It is shown in action for the molecule on the left below.

Publicaciones de Rogue Scholar

The perception of stereochemistry. A challenging case.