Inorganic chemistry, anelectrocyclic reaction is a type ofpericyclic,rearrangement reaction where the net result is onepi bond being converted into onesigma bond or vice versa.[1] These reactions are usually categorized by the following criteria:
TheNazarov cyclization reaction is a named electrocyclic reaction converting divinylketones to cyclopentenones.
A classic example is the thermalring-opening reaction of 3,4-dimethylcyclobutene. Thecis isomer exclusively yields cis,trans-hexa-2,4-diene whereas the trans isomer gives the trans,trans diene:[2]
This reaction course can be explained in a simple analysis through thefrontier-orbital method: the sigma bond in the reactant will open in such a way that the resultingp-orbitals will have the same symmetry as theHOMO of the product (ahexadiene). The only way to accomplish this is through aconrotatory ring-opening which results in opposite phases for the terminal lobes.
When performing an electrocyclic reaction, it is often desirable to predict thecis/trans geometry of the reaction's product. The first step in this process is to determine whether a reaction proceeds throughconrotation or disrotation. The table below shows the selectivity rules for thermal and photochemical electrocyclic reactions.
| System | Thermally induced (ground state) | Photochemically induced (excited state) |
|---|---|---|
| Even # of conjugation | Conrotatory | Disrotatory |
| Odd # of conjugation | Disrotatory | Conrotatory |
For the example given below, thethermal reaction of (trans,cis,trans)-octa-2,4,6-triene will happen through a disrotatory mechanism. After determining the type of rotation, whether the product will be cis or trans can be determined by examining the starting molecule. In the example below, the disrotation causes both methyls to point upwards, causing the product to becis-dimethylcyclohexadiene.
In addition, thetorquoselectivity 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 inenantiomeric excess.
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 thetransition 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 through 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 ofvitamin 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 (below left) was rearranged into the benzocycloheptatriene diterpenoid isosalvipuberlin (right) by boiling a methylene chloride solution. This transformation can be envisaged as a disrotatory electrocyclic reaction, followed by two suprafacial 1,5-sigmatropic hydrogen shifts, as shown below.[6]
An often studied electrocyclic reaction is the conrotatory thermal ring-opening ofbenzocyclobutene. The reaction product is a very unstable ortho-quinodimethane but this molecule can be trapped in anendo addition with a strongdienophile such asmaleic anhydride to theDiels-Alder adduct. Thechemical yield for the ring opening of the benzocyclobutane depicted inscheme 2 is found to depend on the nature of thesubstituent R.[7] With a reactionsolvent such astoluene and a reaction temperature of 110 °C, the yield increases going frommethyl to isobutylmethyl to(trimethylsilyl)methyl. The increasedreaction rate for thetrimethylsilyl compound can be explained bysilicon hyperconjugation as the βC-Si bond weakens the cyclobutane C-C bond by donating electrons.
Abiomimetic electrocycliccascade 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 4πNazarov reaction; asymmetric catalysis of both reactions have been controlled by use of achiral auxiliary, and the Nazarov reaction has been performedcatalytically using chiralLewis acids,Brønsted acids and chiral amines.[11]