Cycloaddition Reactions: Why Is It So Challenging To Move from Six to Ten Electrons?

Abstract

High on cycloaddi(c)tions: The impact of the Woodward-Hoffmann [4n+2] rule for thermally allowed cycloaddition reactions and the challenges associated with moving from six to ten electrons are discussed in this Essay.

Catalytic Enantioselective [10+4] Cycloadditions

“…[3] Intermolecular higher-order cycloadditions remained elusive in asymmetric catalysis until the first metal-catalyzed [8+ +2] cycloaddition was reported in 2013. The highly stereoselective catalytic [10+ +4] cycloaddition exhibits ab road scope with high yields,r eflecting ar obust higher-order cycloaddition.…”

“…[3] Intermolecular higher-order cycloadditions remained elusive in asymmetric catalysis until the first metal-catalyzed [8+ +2] cycloaddition was reported in 2013. [1] Higher-order cycloadditions are relatively underexplored although the potential for elegant construction of complex cyclic scaffolds has been demonstrated by the syntheses of,f or example,c apnellene and azulenes.…”

“…[1] Higher-order cycloadditions are relatively underexplored although the potential for elegant construction of complex cyclic scaffolds has been demonstrated by the syntheses of,f or example,c apnellene and azulenes. [3] Intermolecular higher-order cycloadditions remained elusive in asymmetric catalysis until the first metal-catalyzed [8+ +2] cycloaddition was reported in 2013. [3] Intermolecular higher-order cycloadditions remained elusive in asymmetric catalysis until the first metal-catalyzed [8+ +2] cycloaddition was reported in 2013.…”

Catalytic Asymmetric [8+2] Annulation Reactions Promoted by a Recyclable Immobilized Isothiourea

“…On the other hand, the synthesis of medium and large rings through reactions involving more than six p electrons (the so called higher order cycloadditions [6] ) represents an interesting approach to build complex polycyclic compounds and bridge-containing carbocyclic products. However, this alternative [7] is often hampered by lack of periselectivity and other competing side reactions [8] which, along with the extra challenge of transferring chiral information across a number of bonds, can explain the lack of general methods to produce enantioenriched compounds via higher order cycloadditions.…”

“…On the other hand, the synthesis of medium and large rings through reactions involving more than six p electrons (the so called higher order cycloadditions [6] ) represents an interesting approach to build complex polycyclic compounds and bridge-containing carbocyclic products. However, this alternative [7] is often hampered by lack of periselectivity and other competing side reactions [8] which, along with the extra challenge of transferring chiral information across a number of bonds, can explain the lack of general methods to produce enantioenriched compounds via higher order cycloadditions. [9] Heptafulvenes [10] and their heteroanalogues (tropone, [11] tropothione [12] and the azaheptafulvenes [13] ), a subclass of the "non-benzenoid aromatic compounds" family, have been recognized as important synthons for higher order cycloadditions due to their conjugated cyclic polyolefin systems.…”