3 Cycloaddition and Cycloreversion Reactions

Introduction Cycloaddition reactions Reactions in which at least two new bonds are formed simultaneously, so as to convert two or more open-chain molecules or portions of molecules into rings Cycloreversion reactions are the reverse of cycloadditions Classification of two reactions The number of electrons in each reacting molecule that change locations during reactions

Introduction In a more general sense, all reactions with TS involving closed cyclic arrays of electrons, even if new rings are not formed, can be regarded.

Suprafacial and Antarafacial Addition Two possible ways to form bonds Suprafacial addition (s) – addition to lobes on the same side of a p system Antarafacial addition (a) – addition to lobes on opposite

Suprafacial and Antarafacial Addition Two possible ways to form bonds Suprafacial addition (s) – addition to lobes on the same side of a p system Antarafacial addition (a) – addition to lobes on opposite

Selection Rules for Cycloaddition and Cycloreversion Woodward-Hoffmann Rules Governing the stereochemistry of cycloaddition and cycloreversion reactions - Thermal cycloaddition or cycloreversions involving 4n + 2 electrons are allowed if they proceed with an even number (or zero) of antarafacial interactions of reacting unit. - Thermal cycloaddition or cycloreversions involving 4n electrons are allowed if they proceed with an odd number of antarafacial interactions of reacting unit.

Selection Rules for Cycloaddition and Cycloreversion Derivations of the Rules The Woodward-Hoffmann rules for cycloaddition reactions can be derived from frontier orbital. - The HOMO of one reacting unit may interact with LUMO of another to form bonds

Selection Rules for Cycloaddition and Cycloreversion Derivations of the Rules The Woodward-Hoffmann rules for cycloaddition reactions can be derived from frontier orbital. - The HOMO of one reacting unit may interact with LUMO of another to form bonds

Selection Rules for Cycloaddition and Cycloreversion Derivations of the Rules

Selection Rules for Cycloaddition and Cycloreversion Derivations of the Rules The rules also apply to cycloadditions of systems with odd numbers of atomic orbitals. - Supurafacial addition of an allylic anion would be allowed. But allylic cation is forbidden.

Examples of Thermal Cycloaddition Reactions [2 + 2] Reactions (Diradical reactions) Orbital overlap in TS for a theoretically allowed [2a + 2s] would be extremely poor because the reaction give rise to twisted cyclobutane.

Examples of Thermal Cycloaddition Reactions Cycloreversions of cyclobutane into alkenes at high temperature are common reactions

Examples of Thermal Cycloaddition Reactions There are a few types of alkenes that will easily add to form cyclobutane derivatives – highly reactive double bond such as strained or twisted one.

Examples of Thermal Cycloaddition Reactions

Examples of Thermal Cycloaddition Reactions

Examples of Thermal Cycloaddition Reactions Tetrafluoroethene and other polyfluoroalkenes can react with other alkenes to form four-membered rings.

Examples of Thermal Cycloaddition Reactions Tetrafluoroethene and other polyfluoroalkenes can react with other alkenes to form four-membered rings.

Examples of Thermal Cycloaddition Reactions Tetrafluoroethene and other polyfluoroalkenes can react easily with other alkenes to form four-membered rings. Why?? (1) The p bonds in polyfluoroalkenes were calculated to be about 17 kcal/mol weaker than other unstrained double bond because strong repulsions between the unshared electrons on the fluorine atoms and electrons of the p bonds. (2) The bond energies are lowered by resonance stabilization of the radical fragments formed when p bonds of the polyfluoroalkenes are broken.

Examples of Thermal Cycloaddition Reactions [2 + 2] Reactions – Cycloaddition with ketenes Stereospecific reaction Concerted [p2a + p2s] mechanism

Examples of Thermal Cycloaddition Reactions [2 + 2] Reactions - Polar mechanism Alkenes substituted with powerful EWG can react with electron-rich alkenes to form cyclobutanes

Examples of Thermal Cycloaddition Reactions [2 + 2] Reactions - Polar mechanism Alkenes substituted with powerful EWG can react with electron-rich alkenes to form cyclobutanes Evidences of polar mechanism (1) The rate of these reactions increase with increasing solvent polarity (2) The reactions are not completely stereospecific (3) The mixtures of stereoisomers are formed increases with increasing polarity of the solvents (4) Open-chain products are formed in addition to the cyclobutanes in hydroxylic solvents

Examples of Thermal Cycloaddition Reactions [2 + 2] Reactions - Polar mechanism Alkenes substituted with powerful EWG can react with electron-rich alkenes to form cyclobutanes Zwitterionic intermediates

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions – Diels-Alder reaction Thermal [p4s + p2s] cycloaddition reactions occur readily (electron-rich dienes and electron-poor dienophile)

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions – Diels-Alder reaction Anthracene and furan can readily undergo Diels-Alder reactions, but cycloreversion processes (retro-Diels-Alder reactions) are likely to occur at reasonable temperature

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions – Diels-Alder reaction In the case of cycloaddition reaction of butadiene with polyfluoroalkenes six-membered rings as well as the four- membered rings as major product

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions – Endo rule Unsaturated substituents on the dienophile are cis to the double bond of the newly formed cyclohexene ring

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions – Endo rule Unsaturated substituents on the dienophile are cis to the double bond of the newly formed cyclohexene ring

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions – Endo rule Diels-Alder reactions are usually obtained in higher yields than exo products (Endo isomer is thermodynamically less stable than exo isomer)

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions – Endo rule Woodward-Hoffmann rationalized by frontier orbital theory

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions –Reactivity in Diels-Alder reactions The rate was affected by both steric and electronic effect - s-cis Conformation was required - Slowly undergo when substituents at C1 and C4 are cis to the other double bond - Substituents at C2 of diene increase its reactivity - Fast reaction between dienes with EDG and dienophiles EWG

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions –Reactivity in Diels-Alder reactions Catalysis by strong Lewis acids increases the rates of many Diels-Alder reactions

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions –Regioselectivity The principal isomer formed will result from connecting the atoms with the largest coefficients in the frontier orbitals of the two components “Major product will arise from the TS that resembles the most stable of the possible diradical intermediates that might be formed in the reaction”

Examples of Thermal Cycloaddition Reactions [4 + 2] Cycloadditions –Regioselectivity

Examples of Thermal Cycloaddition Reactions [2 + 2 + 2] Cycloadditions – [p2s + p2s + p2s] reactions Theoretically allowed, but reactions would suffer from a large negative entropy effect. Thus, reactions would be unfavorable at the high temperature. Cycloreversion Concerted [s2s + s2s + s2s] reaction

Examples of Thermal Cycloaddition Reactions [2 + 2 + 2] Cycloadditions – The Alder “Ene Reaction” Alkenes can form addition products, resulting from the transfer of hydrogen atoms, on reaction with strong dienophiles. Concerted [p2s + s2s + p2s] mechanism

Examples of Thermal Cycloaddition Reactions [2 + 2 + 2] Cycloadditions – The Alder “Ene Reaction” Carbonyl groups, in aldehydes, can act as “enophiles” in ene reactions – allylic hydrogen of alkenes are transferred to carbonyl oxygen Catalytic reaction

Examples of Thermal Cycloaddition Reactions Other Thermal Cycloaddition Reactions Suprafacial eight-electron [4s + 4s] or [6s + 2s] are forbidden by the Woodward-Hoffmann rules.

Examples of Thermal Cycloaddition Reactions Other Thermal Cycloaddition Reactions [p8s + p2s] reactions are thermally allowed by the Woodward-Hoffmann rules.

Examples of Thermal Cycloaddition Reactions Other Thermal Cycloaddition Reactions [p6s + p4s] reactions are thermally allowed by the Woodward-Hoffmann rules.

Examples of Thermal Cycloaddition Reactions Other Thermal Cycloaddition Reactions [p12s + p2s] reactions are thermally allowed by the Woodward-Hoffmann rules. [p14s + p2a] reactions proceeds antarafacially

Photochemical Cycloadditions [2 + 2] reactions

Photochemical Cycloadditions [2 + 2] reactions

Photochemical Cycloadditions Reactions from Singlet and Triplet States Singlet photoaddition reactions of alkenes tend to be inefficient processes, but alkenes can undergo photo- chemical cycloaddition reactions efficiently in close proximity of the double bonds.

Photochemical Cycloadditions Reactions from Singlet and Triplet States Singlet-state cycloaddition reactions of open-chain alkenes proceed by stereospecific [p2s + p2s] paths.

Photochemical Cycloadditions Reactions from Singlet and Triplet States Photochemical [2 + 2] cycloreversions have been shown to proceed suprafacially

Photochemical Cycloadditions Reactions from Singlet and Triplet States Triplet states of alkenes are more likely to undergo cycloaddition reaction with other alkenes. Photocycloaddition reactions are often assisted by the addition of photosensitizers

Photochemical Cycloadditions Reactions from Singlet and Triplet States Cyclobutane formation via triplet states is typically not a Stereospecific reaction