Electrocyclic reaction

In organic chemistry, an electrocyclic reaction is a type of pericyclic rearrangement reaction where the net result is one pi bond being converted into one sigma bond ^[1]. These reactions are usually unnamed, being categorized by the following criteria:

• electrocyclic reactions are photoinduced or thermal
• the number of pi electrons in the species with more pi bonds determines reaction mode
• electrocyclic reaction can be a ring closure (electrocyclization‎) or a ring opening reaction
• the stereospecifity is determined by conrotatory or disrotatory mode of transition state formation as predicted by the Woodward-Hoffmann rules.

The torquoselectivity in an electrocyclic reaction is the measure of selectivity in the direction of the conrotatory or disrotatory mode.

The Nazarov cyclization reaction is a named electrocyclic reaction converting divinylketones to cyclopentenones.

A classic example is the thermal ring-opening reaction of 3,4-dimethylcyclobutene. The cis isomer exclusively yields cis,trans-2,4-hexadiene whereas the trans isomer gives the trans,trans diene ^[2]:

This reaction course can be explained in a simple analysis through the frontier-orbital method: the sigma bond in the reactant will open in such a way that the resulting p-orbitals will have the same symmetry as the HOMO of the product (a butadiene). The only way to accomplish this is through a conrotatory ring-opening which results in opposite signs for the terminal lobes.

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

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.^[3]

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.^[4]

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.^[5] 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.^[6]

Scope

An often studied electrocyclic reaction is the conrotatory thermal ring-opening of benzocyclobutane. The reaction product is a very unstable ortho-quinodimethane but this molecule can be trapped in an endo addition with a strong dienophile such as maleic anhydride to the Diels-Alder adduct. The chemical yield for the ring opening of the benzocyclobutane depicted in scheme 2 is found to depend on the nature of the substituent R ^[7]. With a reaction solvent such as toluene and a reaction temperature of 110°C, the yield increases going from methyl to isobutylmethyl to trimethylsilylmethyl. The increased reaction rate for the trimethylsilyl compound can be explained by silicon hyperconjugation as the βC-Si bond weakens the cyclobutane C-C bond by donating electrons.

An biomimetic electrocyclic cascade reaction was discovered in relation to the isolation and synthesis of certain endiandric acids ^[8][9]:

References