Computational Technique In predicting Diastereoselectivity

My research project for this j-term is to predict the Diastereoselectivity of (4+2) Cycloaddition addition reaction. Diels-Alder is (4+2) Cycloaddition reaction. I am testing the Diels- Alder reaction to predict Diastereoselectivity using computational modeling. We are using the computer generated program Gauss to calculate the energy of the system. The Gaussian program describes the different theories of computational chemistry that are useful in predicting several properties of a molecule like orientation, bond angle, energy of reactants and  products, vibration within molecule. It is even useful in calculating the frequency that occurs within the molecule.

Gauss program is a semi empirical method whose parameters are proved from experiment. Researchers who are working on computational chemistry can use Hartree Fork, B3LYP, MP2 and MP4 methods to predict the different properties of the molecule.  Among these B3LYP is commonly used method to predict the different structures of molecule. Along with the method it’s equally important to use basis set (describe where molecule is located) to get the reasonable result. The commonly used basic is 6-31G (d) which was proved best among others.

In my project I am using the 6-31G (d) basic set and B3LYP method to predict the Diastereoselectivity of Diels- Alder reaction.   This method is useful to characterize the transition state of the molecule.  Diels -Alder’s reaction usually contains two diastereomers. This can be done by optimization and frequency calculation.  One can use optimization followed by frequency calculation to calculate the free energy of the system. However, the Gaussian program also consists of optimization and frequency calculation at the same time which gives results about enthalpy and Gibbs free energy of the system, which helps in calculating the enthalpy of the system. Moreover, frequency calculation can predict the transition structure of the molecule.  

Any student doing research at computational chemistry especially in predicting the transition state of the molecule or predicting the diastereoselctivity of any reaction, frequency calculation should done  on a molecule on both reactants and products. The reliable method used in computational chemistry is B3LYP with basic set 6-31G (d).   So, after frequency calculation, one can calculate the bond order at transition state which is critical step to determine whether it is located at stationary points. It also conforms whether it lies within the imaginary line which confirms the selectivity by calculating the energy of both diastereomers.

Some reactions take hours to give the results even days to get desired result. So, I suggest others not to get frustration while using computational model to find results. Also, by change if anyone forget to change the basic set (describes where molecules are located), he/she can pull out the old file and can use that structure. It’s not necessary to create another structure of that molecule.

Reference:

James B.Forstman and AEleen Frisch," Exploring Chemistry with Electronic Structure Methods".