Talk:Mod:holbein16
Q1. Your calculated energies for the dimers and hydrogenated compounds are all correct. Your discussion of thermodynamic/kinetic control is a little confused. I think you are saying that the highest energy endo-product is formed but the text then says the endo product is the thermodynamic product. Be careful to clearly state answers to questions in the script, such as: the highest energy endo-isomer predominates, therefore the reaction must proceed under kinetic control. Thermodynamic control applies to reversible reactions and after equilibrium is reached, the most stable product is preferentially formed. Kinetic control applies to irreversible reactions and depends on the difference in energy between transition states: The lowest energy TS will lead to the favoured product, but this could be the higher energy product (as in cyclopentadiene dimerization) or the lower energy product. Therefore it is not possible to label one product the “kinetic product” if all that is known about the possible products are the energies and the TS-energies are not known. In the case of dimerisation, selectivity is indeed due to the secondary orbital interaction possible in the endo-TS but not in the exo-TS. As you say, the difference in energy between the monohydrogenated dimers is mainly due to difference in bending strain. It is true to say that this difference is due to the loss of strain after hydrogenation: Specifically, the alkene in compound 3 is more strained than that in compound 4 because its bond angles deviate from the ideal for sp2 centres to a greater degree. You say that the lower energy product should be the likely product of hydrogenation, but you could only say this for sure if the reaction is under thermodynamic control. If the reaction is under kinetic control it could be either product. In actual fact, compound 4 is formed preferentially and this could be due to thermodynamic control OR kinetic control. Alkene hydrogenation is usually carried out with a metal catalyst (e.g. palladium on charcoal) and hydrogen gas; under these conditions, reactions are usually under kinetic control (i.e. the products are not in equilibrium with the starting materials) and selective hydrogenation of alkenes is due to the steric effects that allow coordination of one alkene more easily than another.
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Q2. Your calculated energies are all very good again, indicating that you found the true lowest energy conformations. The method of randomly moving around atoms to find different starting points is reasonable, but in some cases you can use chemical intuition to look for different possibilities – i.e. 6-ring chair or twist-boat. The origin for stereocontrol in both cases is well described. I’m not sure about the pericyclic mechanism though – seems to me that the driving force of the reaction is relief of the positively charged nitrogen – the metal could just be coordinated by a dative bond and then the Grignard attacks. Magnesium is indeed the problem for carrying out an MM2 calculation on the reaction intermediate: it is not supported specifically, because MM2 has a set of parameters defined for different element types (e.g. sp3 C, H, Cl) but magnesium isn’t included. Some different force fields include different element types and it is also possible to manually change/expand them.
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Q3. Your calculated energy for molecule 10 is good and this is the more stable form, but for molecule 9 it is possible to get a lower energy conformation if the 6-ring is in the twist-boat form. Since 6-membered rings have well-known favoured conformations (chair, twist-boat, boat are all possible depending on the substituents) it is worth analysing those options for a problem such as this. The alkene is indeed a hyperstable alkene – the key thing is that the alkane that would be made by hydrogenation would be unstable (have more strain than the parent olefin).
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Q4. Your and although your MOs look a bit weird, you correctly say that the syn-alkene is more nucleophilic as demonstrated by its reaction with dichlorocarbene. Your IR stretch values are all correct and the discussion about how the bond strength differs with various electro-donating and electron-withdrawing substituents is very good. You mentioned the pi-sigma* interaction of the anti-alkene and the C-Cl bond; this affects the molecule by making the alkene stronger and the C-Cl bond weaker. It can be seen from your result with the anti-double bond hydrogenated, that the C-Cl bond becomes stronger in this case, where no interaction is possible.
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MP. The choice of reaction is good because the isomeric products are rigid structures suitable for computational calculations and the various possible reaction pathways show the importance of clearly and unambiguously assigning chemical structures using spectroscopy and other tools. The various possibilities in selectivity are well described and the analysis of MOs was a good extension of the techniques learnt in the first half of the course.The graphical representation of the NMR data makes the spread of error clear. The accuracy is actually pretty good – but as you said the problem is the difference in shift for the isomers is so small that it you can’t differentiate. Errors in the NMR are due to the fact that the molecule has conformation freedom in reality and different conformers contribute to the NMR shifts. You point out that some of the shifts overlap due to similarity – more than this, some of the shifts are chemically equivalent. In practical terms they have the same shift therefore, but the calculation is carried out only on one frozen picture of the molecule so the chemically equivalency is not apparent. The error in the IR calculation is largely due to the calculation being carried out in the gas phase whereas the experimental data is obtained on the compound in its ambient state (i.e. solid or liquid). You are correct in identifying X-ray crystallography as the definitive method in structure elucidation and as you say NOESY is spectroscopic technique that is useful here.