Imperial College London

Henry Rzepa

The mechanism of the reaction of alkenes known as ozonolysis was first
set out in its modern form by
[Criegee](http://dx.doi.org/10.1002/anie.197507451 "Mechanism of Ozonolysis"){target="_blank"}.
The crucial steps, (a), (b) and (d), are all pericyclic
cycloaddition/eliminations. The last step (e) is known as reductive
ozonolysis, and this step is often treated as an afterthought, part of
the work-up of the reaction if you like (it is not illustrated in
Criegee's review for example). Here, I will attempt to show that it is
actually a very interesting mechanistic step.

[![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/ozonolysis.svg "ozonolysis"){.aligncenter
.wp-image-6709 loading="lazy" decoding="async" width="420"
height="193"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/ozonolysis.svg)

Step (e) reminded me of a mechanism we had recently investigated,
involving *[desulfurization of epidithiodioxopiperazine fungal
metabolites](http://dx.doi.org/10.1002/chem.201101129 "On the determination of the stereochemistry of semi-synthetic natural product analogues using chiroptical spectroscopy: Desulfurization of epidithiodioxopiperazine fungal metabolites"){target="_blank"}* in
which an S-S bridge is reduced by one sulfur atom by the action of
triphenyl phosphine. Dimethyl sulfide in turn is used to reduce a O-O
fragment of the trioxolane intermediate produced from ozonolysis by one
oxygen. The [transition
state](http://hdl.handle.net/10042/to-13960 "InChIKey=LFPFHOKCPSUFKU-UHFFFAOYSA-N"){target="_blank"} for
path (e) is shown below (ωB97XD/6-311G(d)/SCRF=dichloromethane).

::: {#attachment_6711 .wp-caption .aligncenter style="width: 372px"}
![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/ozonolysis.jpg "ozonolysis"){.wp-image-6711
loading="lazy" decoding="async"
aria-describedby="caption-attachment-6711"
onclick="jmolInitialize('../Jmol/');jmolSetAppletColor('white');jmolApplet([450,450],'load wp-content/uploads/2012/05/ozonolysis.log;frame 3; zoom 100;connect (atomno=4) (atomno=6) partial;connect (atomno=4) (atomno=15) partial;connect (atomno=5) (atomno=16) partial;connect (atomno=1) (atomno=4) partial;vectors on;vectors 4;vectors scale 5.0; color vectors yellow; vibration 20;animation mode loop;');"
width="362" height="158"}

Transition state geometry for step (e). Click for 3D.
:::

The reaction IRC for this step is shown below

|                                                                                                                                                                                                                                                                    |                                                                                                                                                                                                                                                                       |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| [![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/ozone1.svg "ozone1"){.aligncenter .wp-image-6714 loading="lazy" decoding="async" width="220" height="142"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/ozone1.svg) | [![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/ozone1g.svg "ozone1g"){.aligncenter .wp-image-6715 loading="lazy" decoding="async" width="225" height="142"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/ozone1g.svg) |
| [![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/oz.gif "oz"){.aligncenter .wp-image-6726 loading="lazy" decoding="async" width="351" height="276"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/oz.gif)             |                                                                                                                                                                                                                                                                       |

1.  Notice how the sulfur atom approaches more or less along the axis of
    the O-O bond.
2.  At the transition state (IRC=0) the three atoms are almost
    collinear. This might have some steric consequences for sterically
    congested alkenes.
3.  At IRC = -4, cleavage of the O-O bond is almost complete, an the
    system is starting to resemble the zwitterion shown below (the
    calculation is done with a solvent continuum field applied, to help
    stabilise any ionic intermediates that might form). One might be
    tempted to ask how this species could be stabilised to the extent of
    having a less transient existence.  
    [![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/ozonolysis1.svg "ozonolysis1"){.aligncenter
    .wp-image-6719 loading="lazy" decoding="async" width="88"
    height="94"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2012/05/ozonolysis1.svg)
4.  Still, it is highly transient, since there is no actual minimum in
    the IRC energy profile. Instead, between IRC -4 and -15, the
    remaining bonds cleave to form the final product shown in the scheme
    above. As with the [previous
    post](http://www.ch.imperial.ac.uk/rzepa/blog/?p=6618 "The mechanism of the Baeyer-Villier rearrangement."){target="_blank"},
    which illustrated the Baeyer-Villiger rearrangement, this reductive
    elimination is also very asynchronous, with the pair of C-O bonds
    cleaving after the O-O.

This again illustrates the reactions where several bonds are either
forming or cleaving, the relative dynamics can be quite unpredictable.
It may even be strongly influenced by substituents and solvation. All
text books of organic chemistry  I know of rarely if ever address this
aspect of mechanism. With new generations of interactive and dynamic
text books about to [spring upon
us](http://www.ch.imperial.ac.uk/rzepa/blog/?p=5881 "Mobile-friendly solutions for viewing (WordPress) Blogs with embedded 3D molecular coordinates"){target="_blank"},
it might be time to rethink what goes into them. I would hope it is not
just a rehash of  what one might call the classical arrow pushing
representations of mechanism.

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


The mechanism of the reaction of alkenes known as ozonolysis was first set out in its modern form by Criegee. The crucial steps, (a), (b) and (d), are all pericyclic cycloaddition/eliminations.

Messaggi di Rogue Scholar

Reductive ozonolysis: the interesting step.