Establish the Molecular Modelling Questions we'd like Answered

[mattodd]

Let's be sure what we're asking in the modelling, before we submit a request to e.g. Bun to resolve these matters. My first shot is below. Are these the interesting questions? Are these the relevant molecules? Overall, down the line, the question is whether we focus on one particular substrate for the catalyst search - one that will not epimerise. The answer to that might be best arrived at empirically (by getting the enantiopure stuff and cooking it with acid) but it's good to understand the results we'll get whatever.

[katb]

Maybe not the benzaldehyde product, but anisole? E-donating vs -withdrawing? I also starting thinking about more polar solvents. So, effect of MeOH or MeCN on TS?

[mattodd]

Yes, both good points. MeO not H for Series B and another realistic PS solvent with different polarity. Maybe MeCN better as something that might actually work? DCM/THF used in the literature, no?

[katb]

Yes. PhMe, DCM, THF (and other ethers) and MeOH often used. Sometimes water. Not necessarily catalytic, but those are common solvents.

[mattodd]

OK, let's see how much effort it'll be to examine other solvents, while getting values in toluene initially.

On 12 July 2013 13:46, Katrina Badiola notifications@github.com wrote:

Yes. PhMe, DCM, THF (and other ethers) and MeOH often used. Sometimes water. Not necessarily catalytic, but those are common solvents.

— Reply to this email directly or view it on GitHubhttps://github.com/opensourcecatalysis/KatOPS/issues/6#issuecomment-20856930 .

MATTHEW TODD | Senior Lecturer and Honours Coordinator School of Chemistry | Faculty of Science

THE UNIVERSITY OF SYDNEY Rm 519, F11 | The University of Sydney | NSW | 2006 T +61 2 9351 2180 | F +61 2 9351 3329 | M +61 415 274104 E matthew.todd@sydney.edu.au | W http://sydney.edu.au/science/chemistry/research/todd.html

CRICOS 00026A This email plus any attachments to it are confidential. Any unauthorised use is strictly prohibited. If you receive this email in error, please delete it and any attachments.

[mattodd]

Bun sent through numbers for the generation of carbanions, carbocations and radicals of A-D:

X–    X+  X•

A 200.7 471.5 265.6 B 278.6 444.2 274.3 C 199.4 496.6 268.2 D 338.4 447.0 292.0

The numbers are actually for going to the relevant species with the use of aqueous solvation energy for the proton, in the case of the carbanion:

X(toluene) -> X(-)(toluene) + H(+)(aq)

These are all DFT numbers, i.e., not taking experimental value for any species. The reactions leading to X- plus H+ should not be compared with those for X+ plus H- and the radicals, as the experimental aqueous solvation for H+ was used

Values for protonating the oxygen are as follows, but these were optimised to ring-opened structures (bottom right in the scheme):

A 185.9 B 158.9 C 195.1 D 160.0

Conclusion is that the MeO on the rings and the nitro are dominating, right? The aryl vs alkyl actually seems not to matter. However, the nitro on the aromatic ring is playing a big role. This seems to greatly destabilise the carbocation (essentially A vs B or D), implying that we should not expect the nitroaryl compound A to ring open in acid if the alkyl-subst does not, whereas the simple aryl-subst compound (B) is more likely. Most interesting. It should be noted, however, that these free energy changes (in kJ per mol) are very high, implying that perhaps any H+ assisted ring opening is unlikely

[mattodd]

Method: Standard DFT calculations were carried out with Gaussian 09. Geometries were obtained at the B3-LYP/6-31+G(d,p) level. The vibrational frequencies of stationary points were inspected to ensure that they corresponded to minima on the potential energy surface. Refined single-point energies were obtained with the M06-2X procedure with the 6-311+G(3df,2p) basis set. Zero-point vibrational energies and thermal corrections to enthalpy and entropies at 298 K, derived from scaled B3-LYP/6-31+G(d,p) frequencies, were incorporated into the total energies. The SMD continuum solvation model was used in conjunction with M05-2X/6-31G(d), which is a method recommended for use with the SMD model. The parameters for toluene were employed in the SMD calculations to reflect the experimental conditions. All relative energies are reported as solvation-corrected 298 K free energies in kJ mol–1.