6-Endo-dig versus 5-exo-dig: Exploring Radical Cyclization Preference with First-, Second-, and Third-row Linkers...

Area of Science:

• Computational Chemistry
• Organic Synthesis

Background:

• The Baldwin rules predict cyclization pathways in organic reactions.
• Understanding factors influencing radical cyclization is crucial for synthetic chemistry.

Purpose of the Study:

• To investigate the cyclization preferences of hex-5-yn-1-yl radical systems with diverse linkers.
• To provide fundamental insights for the rational design of cyclic compounds.
• To develop a predictive tool for cyclization preference.

Main Methods:

• High-level computational modeling using the coupled cluster singles, doubles, and triples (CCSD(T)) method.
• Application of the SMD(benzene)-G4(MP2) thermochemical protocol.
• Analysis of stereoelectronic effects, cyclization barriers, and intrinsic barriers.

Main Results:

• Systems with B, Si, P, S, Ge, As, and Se linkers favor 6-endo-dig cyclization, unlike C, O, and N linkers.
• Cyclization preference is primarily influenced by changes in 5-exo-dig reaction barriers.
• A strong correlation was identified between radical attack trajectory angle and reaction barrier heights, predicting cyclization preference.

Conclusions:

• Computational modeling reveals distinct cyclization preferences based on linker type.
• A new tool for predicting cyclization preference has been developed based on radical structural parameters.
• Stereoelectronic effects significantly influence cyclization pathways, particularly in hypervalent silicon systems.