Talk:Mod 1: Celeste van den Bosch

First week feedback

Overall it's hard to give a good assessment of your work, mainly because there's no indication as to which answer is completed. Consequently, I'm giving you the assessment of the page 'as is' on Friday night. Some of the comments probably will be addressed by you in due course, if not already.

• The presentation of the data is good and easy to follow/mark to me. I like to see a reaction/structure scheme with numbering for each questions so I don't have to flip between pages.
• You may find that a few of your pictures could be too big, depending on the width of the browser. This is due to the fact that wiki engine doesn't scale pictures along with text. An example of a code which will help you is shown below, in which the width of your picture is 500 pixels.

 [[Image:filename.jpg|alignment(right/left/middle)|500px|description]] 

• Question 1 - DiCy: Splitting Table 1 may help. You'll need to provide an analysis (what we really want to see!) to compare 1 with 2 and 3 with 4. Please pay attention to the source of the difference in energy, and if possible identify the part of the molecules responsible for it.
• Question 2 - Taxol: You'll need to rationalise the stability of the double bond. Pictures or Jmol to illustrate the structures in Table 2 is crucial here. MMFF94 calculation is still missing as is an explanation for the unusually stable double bond. You did notice that it's at the bridgehead and is normally strained though.
• Question 3 - MOPAC: Do we need LUMO+2? Your MO pictures looks OK, but a top-down point-of-view will probably be better. Most of your analysis is yet to be included, but what's the structure of the monoene?
• References: you've two in there. Obviously as you fill in the details and analysis, you'll need references to back your statements up.

FEEDBACK (After Week 2)

Q1: The energy values are all correct and the discussion of selectivity in the Diels-Alder reaction is good. It is not really possible to say whether the hydrogenation reaction is under thermodynamic or kinetic control; the kinetic product (lowest energy transition state) could be the same as the thermodynamic product (lowest energy product) and in fact this is usually the case – the Diels-Alder reaction is a bit of an odd case. So if you know the product is the higher energy molecule you can say for sure that the reaction is under kinetic control since it can’t be under thermodynamic control, but if the lower energy molecule is formed you still can’t say without further analysis (transition state calculations) and more information (reaction conditions etc). As a side note: most reductions of this sort are metal-catalysed, irreversible, and therefore under kinetic control. Your comparison of the contributions to strain correctly shows the major factors (the % analysis would have been better if it had shown difference as a % of total energy – or more simply the absolute difference in kcal). The reason bending strain is worse in 3 than in 4 is because the bond angles deviate more from the sp2 ideal in that compound – due to the constraints of having a double bond in the bicyclic half of the molecule.

Q2. Your energies are all good and the favoured isomer is correctly identified. You have a brief comment on the preference for the chair conformation for the 6-ring; a more complete analysis would also show the higher energy twist-boat for compound 9; you could also have briefly described the other ways in which you attempted structural optimisation. Hyperstable alkenes are correctly defined.

Q3. The MOs look good and the IR stretch frequencies are correct. The regioselectivity in the reaction with dichlorocarbene is well explained. The difference in the C-Cl stretching frequency when the double bond is removed is due to a pi-sigma* orbital interaction. When the double bond is removed it can no longer donate into the C-Cl antibonding orbital, so the bond is stronger.

Q4. The energy values and structures all look good. R=methyl is the correct choice here for a generic alkyl group and as you have discussed semi-empirical methods are best for this case. Your finding that A/B/C/D are lower in energy than A’/B’/C’/D’ is right. As your values show, for PM6 calculations, A=C and B=D; the calculation method is capable of incorporating the neighbouring group effect into a hybrid structure which is treated as a non-classical carbocation. The stereoselectivity in the reaction is due to two favourable effects, A/B are both lower in energy and more reactive (better orientation and trajectory for nucleophilic attack) than A’/B’.

MP. This looks like a good mini-project – a mixture of diastereomers with rigid looking structures. The NMR analysis is good and looking at different conformations is a good idea; if the energies of these conformations have been obtained, it should even be possible to look at the Boltzmann distribution at various temperatures and work out the expected contribution to physical properties of each. Another aspect that could have been looked at here is the RMS you get when comparing calculated values for the wrong isomer to lit data; if the wrong isomer has a significantly worse correlation to the data than the correct isomer this supports the use of predicted NMR as an analytical technique in this case. The optical rotation calculations seem to be good at getting the appropriate sign of the isomer if not the absolute value; in some cases this could be used to distinguish between isomeric products.