Talk:Mod:3516464

FEEDBACK

Good introduction – the differences between molecular mechanics and DFT calculations are clearly stated.

Q1: Your calculations and structures are all good. The discussion of kinetic vs thermodynamic control is good although the following statement is not necessarily true: “Therefore it can be rationalized that compound 4 is the more stable dominant product, and the hydrogenation reaction is under thermodynamic control.” The hydrogenation reaction could still be under kinetic control and it could be that the thermodynamic product is the same as the kinetic product. This is in fact often the case and the D-A reaction is a bit of an oddity. So it is not possible to definitively say the reaction is under thermodynamic control or kinetic control without carrying out further calculations on the relevant transition states (not possible for MM2). Your analysis of the strain-contributors in the fully hydrogenated compound is valid, but it is not possible to compare the energy of this product to the monohydrogenated compounds because they are not isomeric.

Q2. Your energies are good and the “down” isomer is correctly identified as the lowest energy one. In fact your lowest energy for compound 9 is lower than expected! The atropisomerism has nothing to do with the hyperstability of the olefin; this type of isomerisim merely arises when there are conformational isomers which “don’t interconvert”. The non-interconversion is somewhat arbitrary and time-dependent: As you have said the isomers do interconvert, but only after a certain time period (usually of course, conformational isomers interconvert rapidly). The 6-ring is a good focus for structural optimisation because there are known conformations to look for; it would have been good to hear a brief description of other ways in which you optimised the structure. The definition of alkene hyperstability is right. The calculated energy of the hydrogenated form can’t strictly be compared to the energy of the alkene because you can only compare isomers with molecular mechanics. Structural analysis is still a valid method however and comparison of sp2 and sp3 bond deviations is a good approach.

Q3. Your calculations, MOs, and IR stretch values look good. The discussion of the pi-sigma* interaction is good and its impact on the vibrational energies is detailed well. NB: Anti-periplanar is a specific term which refers to a 180 deg dihedral angle between two groups; it should only be used when talking about atoms that are separated by 3 consecutive bonds.

Q4. The energy values you got are close to those expected and as you have found the A/B/C/D set is expected to be lower in energy than A’/B’/C’/D’. Methyl is the best choice of alkyl group for the reasons you stated and the semi-empirical method is more appropriate than molecular mechanics here. As you can see from your energy values and structures with MOPAC, A=C and B=D; the neighbouring group interaction is directly incorporated into a hybrid structure because MOPAC treats the system (more realistically) as a non-classical carbocation. The reason for the stereoselectivity is partly that the intermediate conformations A and B are the lowest in energy (compared to A’ and B’) and also that these intermediates have a better orientation for nucleophilic attack; hence these intermediates are favoured on both sides of the Curtin-Hammett kinetics dichotomy.

MP. This kind of attempt to distinguish diastereoisomers by calculating physical properties is exactly the right approach for a mini-project. The NMR data seems to be a good match to both isomers as indicated by your graph. Perhaps a clearer case could be made by graphically comparing the absolute differences from the calculated and lit values to see which isomer differs the most and whether it is a significant difference. On that point there are many error analyses which would give a more quantitative answer. The IR spectra, while worth including were unlikely to help you to distinguish between the isomers, but it is interesting that your optical rotation give a strong indication as to which isomer is formed. For your discussion of the diastereoselectivity, it is always useful to refer to a detailed reaction mechanism to help your analysis. Another point that would have been worth discussing is possible ways to tell these isomers apart experimentally and whether this was done by the authors of the synthesis.