Electrocyclic reaction Information & Electrocyclic reaction Links at HealthHaven.com

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:

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.

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.

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.

[edit] 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.

[edit] 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.

[edit] 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]

[edit] 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]:

Electrocyclization in Endrianic acids synthesis

[edit] References

^ IUPAC Gold Book
^ The preparation and isomerization of - and -3,4-dimethylcyclobutene. Tetrahedron Letters, Volume 6, Issue 17, 1965, Pages 1207-1212 Rudolph Ernst K. Winter doi:10.1016/S0040-4039(01)83997-6
^ The conservation of orbital symmetry. Acc. Chem. Res., Volume 1, Issue 1, 1968, Pages 17–22 Roald Hoffmann and Robert B. Woodward doi:10.1021/ar50001a003
^ Fleming, Ian. Frontier Orbitals and Organic Chemical Reactions. 1976 (John Wiley & Sons, Ltd.) ISBN 0-471-01820-1
^ Biosynthetic and Biomimetic Electrocyclizations. Chem. Rev., Volume 105, Issue 12, 2005, Pages 4757-4778 Christopher M. Beaudry, Jeremiah P. Malerich, and Dirk Trauner doi:10.1021/cr0406110
^ J. T. Arnason, Rachel Mata, John T. Romeo. Phytochemistry of Medicinal Plant(2nd Edition).1995 (Springer) ISBN 0306451816, 9780306451812
^ Accelerated Electrocyclic Ring-Opening of Benzocyclobutenes under the Influence of a -Silicon Atom Yuji Matsuya, Noriko Ohsawa, and Hideo Nemoto J. Am. Chem. Soc.; 2006; 128(2) pp 412 - 413; (Communication) DOI: 10.1021/ja055505+ Abstract
^ The endiandric acid cascade. Electrocyclizations in organic synthesis. 4. Biomimetic approach to endiandric acids A-G. Total synthesis and thermal studies K. C. Nicolaou, N. A. Petasis, R. E. Zipkin J. Am. Chem. Soc., 1982, 104 (20), pp 5560–5562 doi:10.1021/ja00384a080
^ Inspirations, Discoveries, and Future Perspectives in Total Synthesis K. C. Nicolaou J. Org. Chem., 2009 Article ASAP doi:10.1021/jo802351b

[0] IUPAC Gold Book

[1] The preparation and isomerization of - and -3,4-dimethylcyclobutene. Tetrahedron Letters, Volume 6, Issue 17, 1965, Pages 1207-1212 Rudolph Ernst K. Winter doi:10.1016/S0040-4039(01)83997-6

[2] The conservation of orbital symmetry. Acc. Chem. Res., Volume 1, Issue 1, 1968, Pages 17–22 Roald Hoffmann and Robert B. Woodward doi:10.1021/ar50001a003

[3] Fleming, Ian. Frontier Orbitals and Organic Chemical Reactions. 1976 (John Wiley & Sons, Ltd.) ISBN 0-471-01820-1

[4] Biosynthetic and Biomimetic Electrocyclizations. Chem. Rev., Volume 105, Issue 12, 2005, Pages 4757-4778 Christopher M. Beaudry, Jeremiah P. Malerich, and Dirk Trauner doi:10.1021/cr0406110

[5] J. T. Arnason, Rachel Mata, John T. Romeo. Phytochemistry of Medicinal Plant(2nd Edition).1995 (Springer) ISBN 0306451816, 9780306451812

[6] Accelerated Electrocyclic Ring-Opening of Benzocyclobutenes under the Influence of a -Silicon Atom Yuji Matsuya, Noriko Ohsawa, and Hideo Nemoto J. Am. Chem. Soc.; 2006; 128(2) pp 412 - 413; (Communication) DOI: 10.1021/ja055505+ Abstract

[7] The endiandric acid cascade. Electrocyclizations in organic synthesis. 4. Biomimetic approach to endiandric acids A-G. Total synthesis and thermal studies K. C. Nicolaou, N. A. Petasis, R. E. Zipkin J. Am. Chem. Soc., 1982, 104 (20), pp 5560–5562 doi:10.1021/ja00384a080

[8] Inspirations, Discoveries, and Future Perspectives in Total Synthesis K. C. Nicolaou J. Org. Chem., 2009 Article ASAP doi:10.1021/jo802351b

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Contents

[edit] Woodward-Hoffman Rules

[edit] Frontier molecular orbital Theory

[edit] Excited state electrocyclizations

[edit] Electrocyclic Reactions in Biological Systems

[edit] Scope

[edit] References