CO₂ or SO₂: Should It Stay, or Should It Go?

Area of Science:

• Computational Chemistry
• Organic Chemistry
• Radical Reactions

Background:

• Radical formation is crucial in organic synthesis, particularly for cross-coupling reactions.
• Dissociative processes involving loss of CO2 or SO2 from RXO2 precursors are key radical generation pathways.
• Understanding the thermodynamics of these processes is essential for reaction design.

Purpose of the Study:

• To computationally analyze and compare carbon-centered radical formation from carboxylates (loss of CO2) and sulfinates (loss of SO2).
• To investigate factors influencing the thermodynamic favorability of C-S bond scission in sulfinate precursors.
• To elucidate the role of substituents, especially fluorination, on radical generation pathways.

Main Methods:

• Broad computational analysis of reaction pathways and energy profiles.
• Thermodynamic calculations (enthalpy and entropy) for C-C and C-S scission processes.
• Investigation of substituent effects, including varying degrees of fluorination.

Main Results:

• C-C scission with CO2 loss from carboxylates is generally exothermic.
• C-S scission with SO2 loss from sulfinates is typically endothermic but can be driven by entropy.
• Stereoelectronic effects and the degree of fluorination significantly impact the exothermicity/endothermicity of C-S fragmentation.

Conclusions:

• Significant thermodynamic differences exist between radical formation from carboxylates and sulfinates.
• Subtle structural and electronic factors, particularly fluorination, are critical for controlling the feasibility of sulfinate-based radical generation.
• These findings provide insights into optimizing radical cross-coupling strategies using sulfinate and carboxylate precursors.