Imperial College London

Henry Rzepa

A fascinating re-examination has
appeared\[cite\]10.1002/anie.201505482\[/cite\] of a reaction first
published\[cite\]10.1002/ange.19600721210\[/cite\] in 1960 by Wittig and
then\[cite\]10.1002/jlac.19646790106\[/cite\] repudiated by him in 1964
since it could not be replicated by a later student. According to the
new work, the secret to a successful replication seems to be the
presence of traces of a nickel catalyst (originally coming from *e.g.* a
nickel spatula?). In this recent
article\[cite\]10.1002/anie.201505482\[/cite\] a mechanism for the
catalytic cycle is proposed. Here I thought I might explore this
mechanism using calculations to see if any further insights might
emerge.

[![cyclopropanation](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/cyclopropanation.svg){.aligncenter
.size-full .wp-image-14606
decoding="async"}](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/cyclopropanation.svg)

In the mechanism above (I have retained the original numbering shown in
the article itself), L~n~ is set to 2PH~3~ as an initial approximation
and the solvent thf is approximated only by a continuum solvation field,
with no explicit thf molecules involved at this stage. At this level and
using ωB97XD/Def2-SVPD/SCRF=thf free energies, one can explore the cycle
quite quickly (\~2-3 days). It is also interesting that this reaction
unusually involved nine different elements (I wonder what the record is?
Not much greater I suspect).

|                              |          |                                                                          |
|------------------------------|----------|--------------------------------------------------------------------------|
| Species                      | ΔΔG~298~ | DataDOI                                                                  |
| 4+CH~2~NMe~3~+LiOTf + ethene | +23.9    | \[cite\]10.14469/ch/191545\[/cite\],\[cite\]10.14469/ch/191553\[/cite\]  |
| 5                            | 0.0      | \[cite\]10.14469/ch/191554\[/cite\]                                      |
| TS (5→ 9)                    | 12.7     | \[cite\]10.14469/ch/191536\[/cite\],\[cite\]10.14469/ch/191550\[/cite\]  |
| 9 + LiOTf + NMe~3~           | 0.2      | \[cite\]10.14469/ch/191555\[/cite\]                                      |
| TS (9 + ethene → 6)          | 7.2      | \[cite\]10.14469/ch/191547\[/cite\],\[cite\]/10.14469/ch/191546\[/cite\] |
| 6                            | 4.8      | \[cite\]10.14469/ch/191541\[/cite\]                                      |
| TS (6 → 7)                   | 11.2     | \[cite\]10.14469/ch/191540\[/cite\],\[cite\]10.14469/ch/191548\[/cite\]  |
| 7                            | -36.3    | \[cite\]10.14469/ch/191542\[/cite\]                                      |
| TS (7 → 4+8)                 | -18.8    | \[cite\]10.14469/ch/191537\[/cite\],\[cite\]10.14469/ch/191538\[/cite\]  |
| 4+8 + LiOTf + NMe~3~         | -29.7    | \[cite\]10.14469/ch/191545\[/cite\]                                      |

The structure of the complex **5** is more or less as shown in the
article. The mean single bonded Ni-C length in the Cambridge structure
database (CSD) is \~1.9Å, and (formally at least) Ni=C lengths are
shorter at \~1.80-1.85. There is one reasonable analogy to the
sub-structure shown
below\[cite\]10.5517/CCPV6C2\[/cite\],\[cite\]10.1021/om701275u\[/cite\]
with a C-Ni length of 1.90, Ni-Li = 2.51 and Li-C = 2.40 which is
reasonably similar to what is shown below. 

T

::: {#attachment_14625 .wp-caption .aligncenter style="width: 410px"}
![Click for
3D](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/5.jpg){.size-full
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sizes="(max-width: 1144px) 100vw, 1144px"}

Click for 3D
:::

The elimination of NMe~3~ reveals a reasonable thermal barrier,
resulting in the formation of the nickel-carbene product and the complex
between NMe~3~ and LiOTf. 

[![5a](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/5a.gif){.aligncenter
.size-full .wp-image-14614 decoding="async"
width="440"}](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/5a.gif)[![5-9](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/5-9.svg){.aligncenter
.size-full .wp-image-14620 decoding="async"
width="400"}](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/5-9.svg)

The Ni-carbene then reacts with alkene (modelled here by ethene) to form
a Ni-alkene π-complex, with a very low barrier to the exo-energic
reaction.

[![9-6a](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/9-6a.gif){.aligncenter
.size-full .wp-image-14615 decoding="async"
width="400"}](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/9-6a.gif)[![9-6](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/9-6.svg){.aligncenter
.size-full .wp-image-14621 decoding="async"
width="400"}](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/9-6.svg)

This complex then rearranges, again with a small barrier, to the
metallocyclobutane, with considerable release of energy.

[![6-7a](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/6-7a.gif){.aligncenter
.size-full .wp-image-14618 decoding="async"
width="400"}](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/6-7a.gif)[![6-7](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/6-7.svg){.aligncenter
.size-full .wp-image-14622 decoding="async"
width="400"}](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/6-7.svg)

Finally, the metallocyclobutane extrudes the nickel to form cyclopropane
bound to the Ni(PH~3~)~2~ as a pseudo-π/agostic complex, with this step
of the reaction being somewhat endo-energic (+6.6 kcal/mol). As
modelled, it produces a low-coordination Ni product **4**, which also
causes the initial reactants to be relatively high in energy (+23.9
relative to **5**). This suggests that the entire cycle should optimally
be repeated by including say two explicit thf solvent molecules, which
could coordinate to **4**, thus lowering its energy relative to the rest
of the cycle. 

[![7-4a](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/7-4a.gif){.aligncenter
.size-full .wp-image-14619 decoding="async"
width="400"}](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/7-4a.gif)[![7-4](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/7-4.svg){.aligncenter
.size-full .wp-image-14623 decoding="async"
width="400"}](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/09/7-4.svg)

Below is shown the NCI (non-covalent-interactions) surface for the
Ni-cyclopropane complex, revealing the relatively high density between
the Ni and the edge of the cyclopropane (high enough indeed to be
considered on the verge of being covalent density). No examples of this
motif are found in the CSD.

::: {#attachment_14642 .wp-caption .aligncenter style="width: 410px"}
![Click for
3D](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/10/Ni-NCI.jpg){.size-full
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aria-describedby="caption-attachment-14642"
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width="400"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/10/Ni-NCI.jpg 584w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2015/10/Ni-NCI-300x263.jpg 300w"
sizes="(max-width: 584px) 100vw, 584px"}

Click for 3D
:::

  
Overall, the reaction as shown shows entirely reasonable energetics and
activation free energy barriers (with the caveat that inclusion of
explicit solvent molecules might improve things, see above). We might
conclude from this that the catalytic cycle as proposed is entirely
reasonable. What we cannot comment on of course is the relative
energetics of any of the competing side reaction shown in the original
scheme,\[cite\]10.1002/anie.201505482\[/cite\] but it would be really
easy to include them in a more complete analysis if needed. I wanted to
show here that a simple *reality check* on a proposed reaction mechanism
can be quick to perform, and perhaps nowadays should be regarded as a
*sine qua non* of mechanistic speculation.

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:::


A fascinating re-examination has appeared[cite]10.1002/anie.201505482[/cite] of a reaction first published[cite]10.1002/ange.19600721210[/cite] in 1960 by Wittig and then[cite]10.1002/jlac.19646790106[/cite] repudiated by him in 1964 since it could not be replicated by a later student.

Rogue Scholar Beiträge

Yes, no, yes. Computational mechanistic exploration of (nickel-catalysed) cyclopropanation using tetramethylammonium triflate.