Transition-Metal-Controlled α-C–H Acidity in Keto–Enol Tautomers: A DFT Study of Metal, Tautomer, and Substituent Effects
Year: 2026
Type: preprint
Abstract: Metal coordination provides an effective strategy for modulating the acidity of otherwise weak C–H bonds and controlling proton-transfer reactivity. Herein, we use density functional theory to investigate the effects of metal identity, tautomeric state, and substituent electronics on α-hydrogen acidity in metal-coordinated keto–enol systems. A systematic set of approximately 128 Au(III)-coordinated structures containing electron-donating and electron-withdrawing substituents was examined, with multiple coordination geometries and tautomeric forms considered to identify the thermodynamically preferred states. Au(III) coordination substantially enhances α-C–H acidity, with many systems exhibiting highly favorable deprotonation and strongly acidic computed pKa values. Electron-withdrawing substituents generally increase acidity, whereas electron-donating groups reduce it, although deviations observed for OMe and CF3 highlight the additional roles of charge delocalization and electrostatic stabilization. Kinetic analysis further reveals a strong dependence on tautomeric state: deprotonation of Au(III)-coordinated enol structures proceeds through barrierless pathways, whereas the corresponding keto structures require activation barriers of approximately 37–46 kcal mol−1. Comparative calculations with Co(III)-and Rh(III)-porphyrin complexes show substantially weaker acidification than Au(III), with both metals preferentially stabilizing the keto tautomer. These results demonstrate that metal identity, tautomeric structure, and substituent effects collectively govern α-C–H acidity and proton-transfer reactivity, highlighting the distinctive ability of Au(III) to promote α-hydrogen acidification in keto–enol systems.
Source: ChemRxiv
Authors: Amir Mahdian, Kari Laasonen
Institution: Aalto University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7220834908