Talk:Mod:SergioGeorgini

Please make sure you put in references before submission, particularly for Figure 4.

Q1

• Torsion energy explanation: dihedral angles.
• Your analysis on the source of the difference in bend energies is correct, but Figure 6 and 7 are hard to see until I click on the picture. Tip: remove empty space.

Q2

• You seem to be fixed on 10 being more stable at the beginning even before showing the calculation results.
• "lowest totsl energy"
• Table 4: you need to clarify where the breakdown of energies come from. Are there any significant difference using MMFF94?
• You seem to understand the point I raised above with your comparison. However, the more corrected comparison between different techniques is the absolute difference in energy between 10 and 9. This is an observable quantity, which is directly related to the equilibrium constant between 9 and 10. Do MM2 and MMFF94 agree with each other?
• You were spot-on with hyperstable alkenes and the comparison in energy with hydrogenated product is appropriate. However, if you want to compare the energies of two different systems, you must BALANCE THE EQUATION.

Q3

• You might want to clearly explain how the structures were optimised and how the MOs were calculated. Instructions are included in the question, but we would still want to be absolutely certain which techniques students used. Sometime you guys even do a better job than we prescribed.
• Figure 14 -15: the main gripe is that there is too much empty space and the molecules I can see are consequently small. Clicking on the picture helps, but if you can please trim the pictures.
• Your MOs could be made smoother and nicer using Chem3D options. Talk to us if you don't know how.
• You talked about PM6 at the beginning, and then PM3 at the end. Please double check!
• Correct spotting of the ?*-? interaction, but you'll need to provide a better explanation for the selectivity. What is the carbene looking for to react? What's the mechanism?

Q4

• A' picture missing.
• A' MM2 and PM6 jmol missing. I do like it that you included the jmols from both methods.
• Please double check D and D'.
• You correctly spotted that energies of A and C are the same using PM6. Are the structures the same? and if MM2 gives different results, which method is wrong?
• From the energies for intermediate C/C' and D/D' can you calculate their equilibrium constants and predict the diastereoselectivity of the reactions?

Overall

I think you did a good job for week 1. Obviously more careful analysis and tuning to data presentation is required, but most of the data is solid. If you still aren't sure about something, do come and talk with us.

After Marking

Intro: Most of your comments here are good (e.g. the description of the different calculation methods). While it is fair to say that finding a very high energy transition state would suggest this is an unlikely pathway, this is not really the way in which synthetic chemists typically use computational chemistry. It breaks down more like this: There is a simple approach which is to embellish a report on a new reaction or facet of chemistry by calculating a feasible transition state (rather than just speculating with pen and paper mechanisms). A better approach is to compare energies found to empirical results (e.g. comparison of difference in calculated activation energy with observed ee) to add further weight to the model. The most sophisticated option (more like what you suggest) is to analyse computationally a wide range of different conditions (e.g. different catalysts in a known reaction mechanism) and then try out the system that gives the best results – this is usually done if carrying out all of the conditions is difficult (for example if catalysts are hard to make); it wouldn’t be done for example to find the best solvent (which is a cheap screen of conditions to perform).

Q1: Your energy values are all spot on – although it is not necessary to include so many decimal places in the results; consider that MM2 is an approximate method and there is also some random error in the calculation. Contributions to strain are correctly identified and discussed well. Using MM2 methods the more the structure starts to change (i.e. going from monounsaturated to saturated) the more inaccurate it becomes to compare the energies calculated – effectively the scale on which the energy values are measured changes. So overall, while your approach to calculating the energy balance for a second hydrogenation is correct, it would have been better to use a DFT calculation to get the energy values. What is still reasonable is the qualitative analysis you have given on the structure of the saturated product which suggest that it will be highly strained. The discussion of kinetic vs thermodynamic control is all correct.

Q2. Your approach to this question is good – analyse some different conformations and focus on features with well defined possibilities (6-ring conformations), but there are some problems with you structures: Your chair conformations have the wrong geometry at the ring junction (should be cis fused – i.e. hydrogens on the same side). It is very important to keep checking the structure you are working on because it can easily change from the correct form on manipulation. The discussion of hyperstable alkenes is very good. It is fine to make qualitative comparisons of the strain in the alkene and parent hydrocarbon as you have done. The comparison of energies is more problematic (with molecular mechanics) because the more a structure changes the more different is the scale on which the energy is calculated – you have the right approach though, including hydrogen in the energy balance; it would be interesting to see how the MM results compare to some calculated by DFT methods.

Q3. Your testing of different MOPAC methods to get more accurate, symmetrical MOs was a good step to take. The MOs look good and the explanation about the reactivity is all correct. The stretching frequencies are also correct as is the explanation for the differences that arise due to the pi-sigma* interaction. The only other comment I have to make about this question is that you should include all of the energies you get from different methods (e.g. MOPAC); this is useful because it can be used to assess the accuracy of your structures/energies.

Q4. R=methyl is indeed the best model to use here. Your energy values and structures are very good. As you recognised MOPAC gives A=C etc because the method can determine the bonding character between the carbonyl oxygen and the oxonium carbon when they are proximal; MM2 can’t do this because the bonds are set by the user at the start of the calculation. The selectivity is indeed largely governed by the relative distributions of C/C’ and D/D’; another factor is that the trajectory for nucleophilic attack is also better in the lower energy conformations.

MP. The introduction is good – setting out the questions you want to answer. Your NMR data looks fine and the approach in analysing your results is right – comparing two sets of calculated data to the lit values tells you whether you can differentiate between the isomers; this is often presented graphically (e.g. in a bar chart). The IR is also about as accurate as can be expected. I doubt that optical rotation was what the authors of the paper actually used to differentiate between the species – it would be necessary to already know which isomer has which rotation and compare the experimental result. I imagine they performed some additional 2D NMR experiments to determine which isomer they had – these type of experiments provide information about which Hs are close in space and which are a certain number of bonds apart. For the discussion of reactivity in the methylation reaction – it is reasonable to use this approach of looking at the structure of the starting material to determine possible factors affecting which side will be attacked. One thing to consider is whether the nucleophile in this case is actually bigger than the hydroxy group being formed (if the carbonyl oxygen is coordinated by Ce it will become even bigger). When the 1,2 addition takes place, the oxygen atom will be forced in one direction or the other, so the effect of this also needs to be considered. Overall, it is best to use a higher level of computation and look into transition state modelling to look at these issues in more depth (for example it can be difficult to predict the effect of dipole interactions and other non-steric factors).