Rules for anionic and radical ring closure of alkynes

Area of Science:

• Organic Chemistry
• Reaction Mechanisms
• Stereochemistry

Background:

• The Baldwin's rules predict favored cyclization modes based on ring size and attack trajectory.
• Stereoelectronic factors governing nucleophilic and radical cyclizations of alkynes are reexamined.

Purpose of the Study:

• To reevaluate the stereoelectronic basis of favored attack trajectories in alkyne cyclizations.
• To compare intrinsic stereoelectronic preferences with thermodynamic stability in product formation.

Main Methods:

• Dissection of activation barriers into intrinsic and thermodynamic components using Marcus theory.
• Computational analysis of cyclization selectivities for various nucleophiles.
• Comparison with experimental observations of known cyclization reactions.

Main Results:

• Obtuse attack trajectories (exo-dig) are stereoelectronically favored over acute trajectories (endo-dig) for intrinsic bond formation.
• Thermodynamic stability of endo-products can mask the intrinsic preference for smaller rings.
• Predictions align with experimental data for 3-exo-dig and 4-exo-dig cyclizations, contradicting Baldwin's rules.
• Calculated selectivities for carbon-, nitrogen-, and oxygen-centered nucleophiles show exo-dig preference.

Conclusions:

• The intrinsic stereoelectronic preference favors exo-dig closures, challenging traditional Baldwin's rules.
• Thermodynamic factors play a significant role, especially in smaller ring formation.
• The findings provide a more accurate stereoelectronic model for alkyne cyclizations, applicable to both nucleophilic and radical pathways.