Chemistry 324 - Spring 2008

On Fri (Feb 1) we used transition state models to follow atoms from reactants to products in Diels-Alder reactions. This exercise had several goals and you might reflect on how well it worked:

• Learn 2 techniques for building transition state models
  • Build reactants or products, define bond changes, search transition state library
  • Build reactants or products, constrain (a part of) the geometry to resemble the transition state, calculate best positions for the remaining atoms
• Learn the basic structural features of the Diels-Alder transition state
• Learn to differentiate endo positions from exo positions in the transition state

Another goal of the exercise was to learn how to correlate reactant geometry with product geometry. You may not have realized that the Diels-Alder reaction can produce a large number of isomers and there is a correlation between transition state geometry and product geometry.

A non-specific cycloaddition between a heavily substituted diene and a heavily substituted dienophile can generate as many as 32 possible cyclohexenes. There are 2 possible regioisomers, and there are 4 chiral carbons in each regioisomer, so there are 2^4 (= 16) stereoisomers of each regioisomer.

The Diels-Alder reaction is stereospecific. Groups that are effectively cis in the starting materials (G & e, B & c, etc.) must end up cis in the product. Therefore, the Diels-Alder reaction can only generate 8 possible isomers, and only 4 stereoisomers of each regioisomer.

Each of the products shown above comes from a different transition state. You can see this more easily by looking at the 4 “ortho” regioisomers derived from E-1,3-pentadiene and acrylonitrile (CH2=CHCN).

As the following models reveal, each of the “ortho” products comes from a different transition state geometry. The cis products are derived from endo transition states that bring together different faces of the starting materials. The trans products are derived from exo transition states.

One last thought: if either starting material is symmetric, the number of possible product isomers will decrease, but the number of possible transition state geometries will stay exactly the same. This means you will need to consider more than transition state geometry for each product.