Probing the Free Energy Landscape of Organophotoredox Catalyzed Anti-Markovnikov Hydrofunctionalization of Alkenes

Abstract

Experimental 13C kinetic isotope effects (KIEs) provide unprecedented mechanistic insight into three intermolecular anti-Markovnikov alkene hydrofunctionalization reactions – hydroesterification, hydroamination, and hydroetherification – enabled by organophotoredox catalysis. All three reactions are found to proceed via initial oxidation of the model alkene (anethole) to form a radical cation intermediate followed by sequential nucleophilic attack and hydrogen-atom transfer to deliver the hydrofunctionalized product. A normal 13C KIE on the olefinic carbon that undergoes nucleophilic attack provides qualitative evidence for rate-limiting nucleophilic attack in all three reactions. Comparison to predicted 13C KIE values obtained from DFT calculations for this step reveals that alkene oxidation has partial rate-limiting influence in hydroesterification and hydroamination, while the nucleophilic attack is solely rate-limiting in the hydroetherification reaction. The basic additive (2,6-lutidine) activates the nucleophile via deprotonation and is an integral part of the transition state for nucleophilic attack on the radical cation – providing an important design principle for the development of asymmetric versions of these reactions.

Divergent Functionalization of Alkynes Enabled by Organic Photoredox Catalysis

“…We propose that the alkyne functionalization shares similar features with the alkene hydrofunctionalization. 11,35 Initial oxidation of the diphenylacetylene by photoexcited catalyst A leads the formation of a high energy vinyl cation radical intermediate. 25 Reversible nucleophilic addition by pyrazole and subsequent hydrogen atom transfer would afford alkene intermediate 5.…”