Imperial College London

Henry Rzepa

Paul Schleyer sent me an email about a pattern he had spotted, between
[my post on
F](http://www.ch.imperial.ac.uk/rzepa/blog/?p=11165 "The dimer of SF2: small is beautiful (and weird)."){target="_blank"}[~3~](http://www.ch.imperial.ac.uk/rzepa/blog/?p=11165 "The dimer of SF2: small is beautiful (and weird)."){target="_blank"}[SSF](http://www.ch.imperial.ac.uk/rzepa/blog/?p=11165 "The dimer of SF2: small is beautiful (and weird)."){target="_blank"}
and some work he and Michael Mauksch had done 13 years ago with the
intriguing title "*Demonstration of Chiral Enantiomerization in a
Four-Atom Molecule*".\[cite\]http://doi.org/d8g2nw\[/cite\] Let me
explain the connection, but also to follow-up further on what I
discovered in [that
post](http://www.ch.imperial.ac.uk/rzepa/blog/?p=11165 "The dimer of SF2: small is beautiful (and weird)."){target="_blank"}
and how a new connection
evolved.[![FSSF3-gen](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2013/09/FSSF3-gen.svg){.aligncenter
.size-full .wp-image-11247 decoding="async"
width="350"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2013/09/FSSF3-gen.svg)

The prologue (or prequel). Reaction **2** is the path for decomposing
the dimer of SF~2~ (X=F) to two monomers. In the previous post I
(eventually)
[found](http://www.ch.imperial.ac.uk/rzepa/blog/?p=11165&cpage=1#comment-63482){target="_blank"}
the transition state for this process, with a relatively low energy
barrier. As a mechanistic type, it is known as a reductive elimination
(the reverse would be a oxidative addition) since the S atom on the left
is reduced from a formal oxidation state of S(IV) to S(II) (or *vice
versa*). Analogues of this reaction are **1** and **3**. But before I
managed to locate the transition state for reaction **2**, I
accidentally found the transition state for reaction **4**. This retains
the S-S bond (at the transition state, this bond is actually shorter
than in reactant/product), and is what might be called a two-electron
pericyclic redox reaction, since the S on the left is reduced to S(II)
and the S on the right is oxidised to S(IV). I have not yet found
whether this actually represents a new mechanistic type or not; it does
not appear to have a name (should it be called *periredox*? Or
*redoxocyclic*?). The lesson to be learnt here is that nature normally
indulges in the (more or less) lowest energy route to a given target,
but quantum chemists have the advantage that they can discover
"chemistry in the clouds"; patterns of behaviour requiring too much
energy to be seen in the real world and hence permanently hidden from
us. But that does not mean we cannot learn chemistry from them.

Thus isomeric reaction **4** is very much higher in energy than **2**.
But it is what triggered Paul's memory. Reaction **5** is related both
to **4** in that it involves a \[1,2\] hydrogen shift of X (retaining
the S-S bond) followed by a second \[1,2\] shift of Y. It is also
related to **2** since it involves in effect an oxidative addition (by a
lone pair) to an S-X bond to generate S(IV), followed by a reductive
elimination back to S(II) to regenerate the enantiomer of the reactant
(it is thus a two-step redox reaction). Thus if X and Y are different in
**5**, then all three of the species shown above are themselves chiral,
and hence the reaction is indeed a "*Demonstration of Chiral
Enantiomerization in a Four-Atom Molecule".* The point here is that
enantiomerisations do not necessarily have to proceed through an achiral
transition state, but that the entire enantiomerisation pathway can be
[continuously
chiral](http://symmetry.hu/content/fowler-05-4.pdf){target="_blank"}.

That was the intro! Now follows my calculated intrinsic reaction
coordinate (ωB97XD/6-311G(d,p) for reaction
**5**.\[cite\]10.6084/m9.figshare.801866\[/cite\] My first attempt at
the transition state was to use **2** as a template (rather than **4**,
which was far higher in energy). Well, talk about unexpected! The
migration of X=Cl is 16.7 kcal/mol lower than X=F.  No problem there.
Next, the IRC for X=F. The overall process certainly enantiomerises the
two chiral *gauche* conformations, but without transposing X and Y, and
not involving an intermediate S(IV) species as shown in reaction **5**
(*i.e.* it goes directly, *via* reaction **6**). 

![FSSCl](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2013/09/FSSCl.gif){.aligncenter
.size-full .wp-image-11254 loading="lazy" decoding="async" width="415"
height="311"}

But look at that energy! Way too high (above the clouds in fact). And
although the start and end species are identical (apart from being
enantiomers) the energy profile is far from being symmetrical. 

![FSSClE](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2013/09/FSSClE.svg){.aligncenter
.size-full .wp-image-11256 decoding="async" width="400"}

As for the gradient norms, where to begin? The TS as always is at IRC
=0.0 But in between it and the start and end points one can see no less
than THREE "*hidden intermediates*". Two of them are in fact exactly
*cis* (IRC=3.5) and *trans* (IRC = 5.0) planar forms of F-S-S-Cl. At
these points, the pathway is clearly achiral! The third (IRC = 1.0) is a
fascinating species in which the S-S bond is largely broken and it is
bridged by an F. So this pathway involves S-S cleavage, just like **2**.
It is entirely serendipitous; no-one in their right mind would actually
set out to find it! 

![FSSClEG](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2013/09/FSSClEG.svg){.aligncenter
.size-full .wp-image-11255 decoding="async" width="400"}

Well, since **2** as a template led to the above, what happens when
**4** is used? For F
migrating\[cite\]10.6084/m9.figshare.803096\[/cite\] a barrier 11.6
kcal/mol higher is found than for Cl
migrating\[cite\]10.6084/m9.figshare.802822\[/cite\], similar to that
previously reported.\[cite\]http://doi.org/d8g2nw\[/cite\]

![FSSClpa](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2013/09/FSSClpa.gif){.aligncenter
.size-full .wp-image-11261 loading="lazy" decoding="async" width="415"
height="311"}

The energy and gradient norm profiles, in comparison to the previous,
are uneventful.\[cite\]10.6084/m9.figshare.802821\[/cite\] The S-S bond
stays intact throughout, and it is shorter at the transition state
(1.846Å) than at  the start (1.950Å) or the end (1.874Å). This reaction
has got its feet on the ground, rather than its head in the clouds!

[![FSSClpaG](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2013/09/FSSClpaG.svg){.aligncenter
.size-full .wp-image-11262 decoding="async"
width="400"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2013/09/FSSClpaG.svg)
![FSSClpaE](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2013/09/FSSClpaE.svg){.aligncenter
.size-full .wp-image-11263 decoding="async" width="400"}

I am reminded of stories our crystallographer here tells. Students bring
him synthesized molecules for their structures to be determined, and
quite frequently it's not at all the compound that was desired. For not
a few highly focused students, the compound is quickly forgotten, even
though it may have turned out to be very unusual. Likely it will not be
[deposited into a
repository](http://www.ch.imperial.ac.uk/rzepa/blog/?p=10998 "A two-publisher model for the scientific article: narrative+shared data."){target="_blank"}.
And how many compounds that might otherwise have been the catalyst for
new and unusual discoveries are thus lost?  So never throw away an
unexpected result (yes, even a calculation).  There is probably
something you could learn from it! 

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


Paul Schleyer sent me an email about a pattern he had spotted, between my post on F
<sub>
 3
</sub>
SSF and some work he and Michael Mauksch had done 13 years ago with the intriguing title “
<em>
 Demonstration of Chiral Enantiomerization in a Four-Atom Molecule
</em>
”.[cite]http://doi.org/d8g2nw[/cite] Let me explain the connection, but also to follow-up further on what I discovered in that post and how a new connection evolved.

Messaggi di Rogue Scholar

Patterns of behaviour: serendipity in action for enantiomerisation of F-S-S-Cl