Philicities, Fugalities, and Equilibrium Constants.

Area of Science:

• Organic Chemistry
• Physical Organic Chemistry
• Reaction Mechanisms

Background:

• Traditional organic chemistry posits strong bases are poor nucleofuges, with exceptions like iodide ions.
• The Leffler-Hammond parameter (α) was historically used to determine transition state position (early vs. late).
• Bordwell's "nitroalkane anomaly" questioned the interpretation of α, particularly for proton transfer reactions.

Purpose of the Study:

• To investigate general relationships between Lewis basicities, nucleophilicities, nucleofugalities, and their Lewis acidic counterparts.
• To propose new terminology: "protophilicity" for kinetic basicity and "protofugality" for kinetic acidity.
• To challenge the interpretation of the Leffler-Hammond parameter as solely indicative of transition state position.

Main Methods:

• Utilized benzhydrylium ions with varied substituents as reference compounds to systematically alter Lewis acidity and electrophilicity.
• Correlated rate constants of reactions with nucleophiles against the Lewis acidities of benzhydrylium ions.
• Analyzed kinetic and thermodynamic data for various reaction series, including SN2 reactions and solvolysis.

Main Results:

• Demonstrated linear correlations between rate constants and Lewis acidities for benzhydrylium ions, spanning early to late transition states.
• Showed that differences in intrinsic reaction barriers cause deviations from linear rate-equilibrium correlations and lead to counterintuitive phenomena.
• Identified cases where stronger nucleophiles/nucleofuges (e.g., DABCO over DMAP) and exceptions to common reactivity rules occur.

Conclusions:

• The Leffler-Hammond parameter (α) is not a reliable measure of transition state position within closely related reaction series.
• Intrinsic reaction barriers play a crucial role in determining reactivity, leading to phenomena that defy simple thermodynamic or kinetic predictions.
• Revisiting and systematically analyzing intrinsic barriers is essential for a comprehensive understanding of organic reaction mechanisms.