Stereochemistry Of Pericyclic Reactions : A Basic To Advanced Guide

Pericyclic reactions are one of a set of organic reactions where electrons perform concerted cyclic reorganization without the involvement of intermediates. Such reactions are highly stereoselective; the stereochemical outcome depends on the nature of the participating orbitals and the symmetry property of the transition state. The role of stereochemistry is very essential in pericyclic reactions since it can predict and even control outcomes in terms of stereochemistry arising from such reactions. We shall briefly cover the stereochemistry of pericyclic reactions, which are divided into three important types: cycloadditions, electrocyclic reactions, and sigmatropic rearrangements.

Cycloaddition Reaction:

Cycloaddition are pericyclic reactions in which two or more unsaturated molecules combine and produce a cyclic product. The stereochemistry of cycloadditions is controlled by the symmetry of the interacting orbitals and conservation of orbital symmetry. One of the well-known classical example of the cycloaddition reaction is the Diels-Alder reaction, in which the formation of a new ring is a concerted process involving a conjugated diene and a dienophile.

In the Diels-Alder reaction, configuration of both diene and dienophile dominant it. Products thus are endo or exo depending on which part of diene or dienophile the substituents appear. Therefore, stereochems in transition states have specific types of stereoisomer formation, depending upon the arrangements of orbitals being reacted relative to one another.

Electrocyclic Reactions:

Electrocyclic reactions are known to be the reorganization of σ and π bonds within a cycle. The classification of electrocyclic reactions is primarily based on the number of electrons involved in the process of ring closure. In case of a conrotatory electrocyclic reaction, it has been observed that the orbital symmetry is preserved in the process of ring closure, and hence, the stereochemistry is preserved. On the other hand, the disrotatory electrocyclic reaction would result in the inversion of stereochemistry due to the participation of anti-symmetric orbitals.

The stereochemistry of electrocyclic reactions is controlled by the orientation of the orbitals that participate in the reaction. Transition state in an electrocyclic reaction is a major determinant of the stereochemical outcome; it is controlled by the orientation of the orbital interactions when the ring closes to yield the product. This principle of conservation of orbital symmetry is used to predict the stereochemical outcome of electrocyclic reactions.

Sigmatropic Rearrangements: Sigmatropic migrations involve the movement of σ bonds with attendant π bond rearrangement. Rearrangements are classified based on the number of atoms, and their method of bond rearrangement. In a [3,3] sigmatropic rearrangement, the migration of a σ bond results in the formation of one new σ bond and the rearrangement of two π bonds. The stereochemistry of the sigmatropic rearrangement depends upon the orbital involved in the migration as well as the symmetry of transition state. These reactions therefore can take place either with retention of stereochemistry or inversion, depending upon the geometry of overlap of the orbitals participating. Woodward-Hoffman rule tell us a generalization to predict the stereochemistry of sigmatropic rearrangements based on the orbital symmetry. In conclusion, the stereochemistry of pericyclic reactions is very close to the symmetry properties of the reacting orbitals and the transition states. Knowledge regarding the interaction of molecular orbitals and their conservation in a pericyclic reaction thus helps chemists predict the outcome of such a reaction regarding its stereochemistry, hence controlling it. That's why it's particularly important in designing an effective synthetic route and getting specific stereochemical results in organic synthesis.