Chemistry 324 - Spring 2008

One of you wrote “this sucks” next to your NMR assignments. I have to agree. A complete explanation of the 1H and 13C spectra is beyond me.

On other hand, while I wish I had chosen a more accessible set of data, these spectra are typical. Mother Nature is rarely kind. We just have to deal with that.

Here is my quick take on the NMR data along with some subtle relationships that should not be overlooked …

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Today’s paper contains a number of interesting issues. Rather than take several days to create one big long post, I am going to slice my ideas into small chunks and invite your comments.

Here’s one issue: diastereoselectivity in the reactions of 8 with dienes (Table I). Since this reaction involves three distinct steps, there are multiple points at which to stop and ponder selectivity.

• Conversion of 8 (diazo ester) into a metal carbenoid
• Cycloaddition of carbenoid and diene making a divinylcyclopropane
• Tautomerization of divinylcyclopropane to benzofuran

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NMR - General

As we discussed in class, always use the very best data tables you can find to predict chemical shifts and coupling constant, but remember that spectral data + assignments for a structurally analogous compound are even better than data tables. Some places you can look for spectral data on specific compounds:

• The same paper. Chemists tend to make a series of analogous molecules, replacing a methyl with a phenyl here, or a proton with a methoxy group there. If one of these molecules possesses an easily interpreted spectrum, you might be able to apply this same interpretation to your molecule’s spectra.
• Books. The Reed library contains several compilations of NMR (1H and 13C) and IR spectra (and more). Two favorites of mine are the various Aldrich Libraries (also available online) and “Tables of Spectra Data for Structure Determination of Organic Compounds,” by Pretsch et al. (QC462.85 .T313 1983).
• Online Tables. The Sigma-Aldrich site lets you look at high quality spectra for many of the compounds they sell. You get the spectra, but no interpretation. Another excellent site that actually provides assignments is maintained by Prof. Hans Reich, U. Wisconsin-Madison. I have listed links to four of his data tables, but his site contains much, much more:
  • ¹H chemical shifts
  • HH coupling constants
  • ¹³C chemical shifts
  • CH coupling constants

I have also added some other useful links for organic chemists to the site’s side bar. Check them out before the Qual.

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HW #5 (due next Monday) is based on two reactions that appear in paper #5 (to be discussed on Friday). So, even though we will discuss the paper before the homework is due, it probably would make sense to try the homework first.

Authors often file additional material with their papers that does not get published in the journal proper. This material is referred to as supporting (or supplementary) information and often contains important additions to the basic paper.

For example, the experiment-based papers that appear in a rapid-publication journal like Organic Letters usually contain only summaries of the research. Detailed experimental procedures, spectroscopic data, and crystallographic data, are published on-line as supplements.

Nearly all journals expect computational chemists to provide supporting information for their papers. At the very least, the chemist is expected to provide lists of the atomic Cartesian coordinates for each model, but other model properties may be demanded too.

A coordinate list can serve two purpose. First, it makes it possible for another scientist to repeat the calculation and check it for errors. Also, and from our point of view more important, a coordinate list can be converted into a “3-D” model so we don’t have to rely solely on the small flat figures in the journal to see what is going on.

You can use Spartan to view published models if you know how to convert the data in the supporting info into a file format that Spartan recognizes. The conversion procedure that I followed for paper #4 can be briefly summarized as:

1. Download & open supporting information
2. Copy atom coordinates to clipboard
3. Paste atom coordinates into a text file
4. Save text file with .xyz extension
5. Open file in Spartan

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Our discussion of solvent and salt effects was quite interesting, especially if you think about today’s lecture on rate constants. An endo/exo ratio of 2 means a tiny free energy difference (~ 0.4 kcal/mol) between the endo and exo transition states. Even a solvent effect of 1000 on the overall rate means that the barrier has changed by only ~4 kcal/mol (assuming room temperature reactions).

As part of our discussion, Sarah drew 4 different transition states, 2 forming the exo isomer and 2 forming the endo isomer. Here’s what they look like as tube models. (IN/OUT refers to the position of the C=O; s-cis and s-trans provides the same information.)

If the hydrophobic packing argument is correct, the surface area of these transition states should be a good bit smaller than the surface area of the separated reactants. According to Spartan, the transition states have surface areas between 153-156 A², while the reactants start with a total surface area of 194 A² (90 acrolein + 104 cyclopentadiene).

Space-filling models of the transition state show just how tightly these molecules snuggle together. Although the distance between reactants is >2 A (measured nucleus-to-nucleus), this is far less than the sum of two carbon van der Waals radii (2.9-3 A).

A few observations about our discussion of paper #1:

Even though the paper was short, we didn’t come close to covering it. This is normal. The gaps between 201/202-level of understanding and research-level of understanding are large and numerous. It takes a lot of time to bridge all of these gaps and that is more than we can do in just 50 minutes. Also, research publications are information-dense. A single paragraph may offer a lot to ponder.

Jr. Qual note: Please reflect on our discussion of the de?/activating? nature of the cyclopropylidene substituent. It illustrates how Pat and I expect you to analyze sophisticated ideas (if you can) by rigorous application of basic principles from 201/202. We routinely ask questions during the Qual that begin with something in the paper and end far away in a discussion of basic principles.

Please review the results of this paper regarding regio and stereoselectivity. The authors refer to endo selectivity, to diastereomeric excess (de) and diastereomeric ratios (dr). Given our subsequent discussions on Friday and your practice building endo and exo models, you should be able to draw the various product isomers that the authors are referring to. Try it. Of course, come see me if you have questions about this.

Finally, I gathered that the paper contained some terminology that was hard to fathom. This is normal. It is impossible to prepare you for everything that scientists might write. At least one of you mentioned that “Michael acceptor” was an unfamiliar term. You might have dealt with this (and perhaps you tried dealing with this) as follows:

1. Look up “Michael” in the index of your 201/202 textbook (Carey). You will see “Michael reaction,” but not “acceptor.” Read the section on “reactions” in Carey. It never mentions “acceptor,” but if you compare the structures of the reagents in the Michael reaction with the “acceptor” molecules in the paper, you ought to be able to sort this out.
2. Look up “Michael reaction/acceptor” in a more advanced text (or web page). Our library is loaded with books on chemical reactions, functional groups, you name it. It can be a little overwhelming. Therefore, I have compiled and posted a list of useful sources of information on this web site. Check it out. A permanent link to this page can be found on the Miscellaneous page.