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] or vice-versa. These reactions are usually unnamed, being categorized by the following criteria:
The torquoselectivity in an electrocyclic reaction refers to the direction of rotation. For example, a reaction that is conrotatory can still rotate in two directions, producing enantiomeric products. A reaction that is torquoselective restricts one of these directions of rotation (partially or completely) to produce a product in enantiomeric excess.
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.
| system | Thermally Induced (ground state) | Photochemically Induced (excited state) |
|---|---|---|
| "4n" e- | Conrotatory | Disrotatory |
| "4n + 2" e- | Disrotatory | Conrotatory |
The stereospecificity is then determined by whether the reaction proceeds through a conrotatory or disrotatory process.
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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.
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.
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 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]
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]:
Asymmetric electrocyclic reactions are an emerging field in contemporary organic synthesis. The most commonly-studied reactions in this field are the 4π Staudinger β-lactam synthesis[10] and the 4π Nazarov reaction; asymmetric catalysis of both reactions have been controlled by use of a chiral auxiliary, and the Nazarov reaction has been performed catalytically using chiral Lewis acids, Brønsted acids and chiral amines.[11]