Cycloadditions are fascinating reactions where two π systems combine to form new σ bonds. The stereochemistry of these reactions is governed by orbital interactions, determining whether bonds form on the same or opposite faces of the reactants.

Understanding cycloaddition stereochemistry is crucial for predicting and controlling product formation. Factors like suprafacial vs antarafacial geometry, thermal vs photochemical conditions, and orbital symmetry all play key roles in determining reaction outcomes and product structures.

Stereochemistry of Cycloadditions

Suprafacial vs antarafacial geometries

• Suprafacial geometry
  • New bonds form on the same face of the π system maintains stereochemistry (cis-butadiene forms cis-cyclobutane)
  • Favored in most cycloaddition reactions due to better orbital overlap and lower activation energy
• Antarafacial geometry
  • New bonds form on opposite faces of the π system inverts stereochemistry (trans-butadiene forms cis-cyclobutane)
  • Less common due to geometric constraints requires a large distance between the termini of the π system (trans-cyclooctene)

Frontier orbital theory in cycloadditions

• Frontier Molecular Orbital (FMO) theory
  • Reactivity and stereochemistry determined by the interaction of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) explains regioselectivity and stereoselectivity
  • Orbital symmetry considerations play a crucial role in determining allowed and forbidden reactions
• Thermal cycloadditions
  • Electron flow from the HOMO of the electron-rich component (diene) to the LUMO of the electron-poor component (dienophile)
  • Favors suprafacial geometry due to better orbital overlap maximizes bonding interactions
  • Woodward-Hoffmann rules predict allowed reactions have a total of $(4n + 2)$ electrons in the participating π system ($6$ for Diels-Alder)
• Photochemical cycloadditions
  • One component is excited by light, promoting an electron from the HOMO to the LUMO changes frontier orbital interactions
  • Electron flow from the LUMO of the excited component to the LUMO of the ground-state component enables new reaction pathways
  • Allows for antarafacial geometry due to the involvement of antibonding orbitals reduces steric hindrance
  • Woodward-Hoffmann rules predict allowed reactions have a total of $4n$ electrons in the participating π system ($2$ for [2+2] cycloaddition)

Stereochemistry of cycloaddition reactions

• [4+2] cycloadditions (Diels-Alder reactions)
  • Thermally allowed, photochemically forbidden concerted mechanism with a cyclic transition state
  • Suprafacial geometry with respect to both the diene and the dienophile syn addition across both components
  • Endo rule: favors the transition state with maximum secondary orbital overlap (endo product over exo)
  • Stereochemistry of the diene is retained in the product (s-cis conformation required) enables stereospecific synthesis
  • Can create new chiral centers in the product, potentially leading to the formation of stereoisomers
• [2+2] cycloadditions
  • Thermally forbidden, photochemically allowed proceeds via a stepwise radical mechanism
  • Suprafacial geometry with respect to both components in photochemical reactions leads to syn addition
  • Antarafacial geometry possible in thermal reactions with highly constrained systems (trans-cyclooctene)
  • Stereochemistry of the components is retained in the product (head-to-head and tail-to-tail arrangement) allows stereocontrol

Pericyclic reactions and cycloadditions

• Cycloadditions are a subset of pericyclic reactions, which involve a concerted rearrangement of electrons through a cyclic transition state
• Pericyclic reactions are governed by orbital symmetry considerations, which determine their stereochemical outcomes
• Other examples of pericyclic reactions include electrocyclic reactions and sigmatropic rearrangements