Electrocyclic reaction

Electrocyclic reactions are intramolecular ring closing/opening reactions of conjugated polyenes/cycloalkenes. They involve a cyclic transition state. A ring closing electrocyclic reaction typically results in the conversion of a π bond to a σ bond whereas the reverse ring opening reactions converts a σ bond to a π bond. ^[1]

The transition states arising in electrocyclic reactions can either be formed via a conrotatory or a disrotatory mode of transition state formation as dictated by symmetry requirements. These requirements are predicted by the Woodward-Hoffmann rules.

Whether the reaction is allowed to proceed in a conrotatory or disrotatory fashion depends on the number of electrons participating in the reaction and on whether or not the cyclization is induced thermally or photochemically.

The stereospecificity is then determined by whether the reaction proceeds through a conrotatory or disrotatory process.

Allowed and forbidden processes

A classic example is the thermal ring-opening reaction of 3,4-dimethylcyclobutene to 2,4-hexadiene^[2] compared to the thermal ring opening of 5,6-dimethylcyclohexa-1,3-diene to 2,4,6-octatriene.^[3]

The stereospecificity of these reactions can be explained by (1) the Woodward-Hoffman Rules and (2) Frontier Molecular Orbital Theory.

Woodward-Hoffman Rules

Correlation diagrams, which connect the molecular orbitals of the reactant to those of the product having the same symmetry, can then be constructed for the two processes.^[4]

These correlation diagrams indicate that only a conrotatory ring opening of 3,4-dimethylcyclobutene is symmetry allowed whereas only a disrotatory ring opening of 5,6-dimethylcyclohexa-1,3-diene is symmetry allowed. This is because only in these cases would maximum orbital overlap occur in the transition state. Also, the formed product would be in a ground state rather than an excited state.

Frontier molecular orbital Theory

According to the Frontier Molecular Orbital Theory, the sigma bond in the ring will open in such a way that the resulting p-orbitals will have the same symmetry as the HOMO of the product.^[5]

For the 5,6-dimethylcyclohexa-1,3-diene, only a disrotatory mode would result in p-orbitals having the same symmetry as the HOMO of hexatriene. For the 3,4-dimethylcyclobutene, on the other hand, only a conrotatory mode would result in p-orbitals having the same symmetry as the HOMO of butadiene.

Excited state electrocyclizations

If the ring opening of 3,4-dimethylcyclobutene were carried out under photochemical conditions the resulting electrocyclization would be occur via a disrotatory mode instead of a conrotatory mode as can be seen by the correlation diagram for the allowed excited state ring opening reaction.

Only a disrotatory mode, in which symmetry about a reflection plane is maintained throughout the reaction, would result in maximum orbital overlap in the transition state. Also, once again, this would result in the formation of a product that is in an excited state of comparable stability to the excited state of the reactant compound.

Electrocyclic Reactions in Biological Systems

Electrocyclic reactions occur frequently in nature.^[6] One of the most common such electrocyclizations is the biosynthesis of Vitamin D3.

The first step involves a photochemically induced conrotatory ring opening of 7-dehydrocholesterol to form pre vitamin D3. A [1,7]-hydride shift then forms Vitamin D3.

Another example is in the proposed biosynthesis of aranotin, a naturally occurring oxepine, and its related compounds.

Enzymatic epoxidation of phenylalanine-derived diketopiperazine forms the arene oxide, which undergoes a 6π disrotatory ring opening electrocyclization reaction to produce the uncyclized oxepine. After a second epoxidation of the ring, the nearby nucleophilic nitrogen attacks the electrophilic carbon, forming a five membered ring. The resulting ring system is a common ring system found in aranotin and its related compounds.

The benzonorcaradiene diterpenoid (A) was rearranged into the benzocycloheptatriene diterpenoid isosalvipuberlin (B) by boiling a methylene chloride solution. This transformation can be envisaged as a disrotatory electrocyclic reaction, followed by two suprafacial 1,5-simatropic hydrogen shifts, as shown bellow.^[7]

References