: Structure based Mini project using DFT-based Molecular orbital methods

Many (most?) reactions carried out by synthetic chemists can (and do) give mixtures of products. Often, these products are isomers (for example stereoisomers, or regioisomers which can arise from reaction at more than one site in a molecule, or from different orientations of the reacting groups). Having isolated (and ideally having separated) these isomeric products, it is important to know which isomer(s) have been formed. Modern computational chemistry can provide an alternative: the ¹³C (also ¹⁵N,¹⁹F, ³¹P) spin-spin decoupled spectrum of a molecule can be predicted, often with acceptable accuracy. Computational chemistry also allows prediction of other useful spectroscopic properties, such as IR spectra and (for chiral compounds) optical rotations.

Choose a reaction to study. You will gain extra credit (+ 5%) for finding a suitable reaction from the literature yourself. In choosing reactions, bear in mind the comment below (in the section describing how to do the ¹³C prediction) about the need to choose molecules that are not highly conformationally flexible. A good starting point is to look at recent issues of journals containing synthetic chemistry (e.g.Journal of Organic Chemistry, Organic Letters, Organic and Biomolecular Chemistry, Tetrahedron).
Think about the following points and discuss them in your answer:
1. How would you differentiate spectroscopically between the isomeric products?
2. Calculate the predicted ¹³C spectra for the isomers using the GIAO method. Include a listing of the data and assignments in your report.
3. Compare your predicted data to the experimental ¹³C data in the paper. Do they match?
If you can, discuss the mechanism of the reaction and why the reaction shows (or doesn’t show) selectivity for one particular product isomer. Can any of the other computational techniques you’ve met in the course be used help to explain the selectivity?

Investigating the regioselectivity of the Baeyer-Villiger reaction

The Baeyer-Villiger reaction converts ketones into esters, effectively inserting an oxygen atom between the carbonyl group and the alpha-carbon. It is usually carried out using mCPBA. For unsymmetrical ketones, there are two possible regioisomeric products; usually it is possible to predict which isomer will predominate in line with the migratory aptitude of the ketone substituents. Investigate ONE of two recent literature examples where the reasons for the regiochemical outcome are not so obvious:

The Baeyer-Villiger reaction was used (DOI:10.1021/jo030377y ) in a recent synthesis of analogues of beta-lactam antibiotics. In Scheme 5, reaction of 10d gives 11d and 12d. Are the regiochemical assignments correct, and why is the regioselectivity low in this case?
During a total synthesis of the natural product (-)-kainic acid (DOI:10.1016/S0040-4020(02)00379-4 ), a neuropharmacological tool, a highly regioselective Baeyer-Villiger reaction was a key step (conversion of compound 14 into 15). Do the predicted ¹³C data fit with the reported ones? Why is this reaction so regioselective?

General Reference

K. Mori, The Chemical Record, 2005, ii5, 1-16. DOI:10.1002/tcr.20030