Mechanistic elucidation of the origins of the hydrogen-abstraction reactivity of hydroxyimide organocatalysts and its application in catalyst design

Highlights: • The origin of the different reactivity of hydroxyimide organocatalysts were elucidated. • The CH bond approaching and breaking occur via a cross-point structure in a H-abstraction process. • H-abstraction TS structures for NHPIs are reactant-like, but product-like for the case of TEMPO. • TEMPO has larger energetic LUMO-HOMO gap with substrate than that of NHPIs. • NHPIs require both CH bond approaching and distortion energies smaller than that of TEMPO. The mechanistic origin of the hydrogen-abstraction reactivity of hydroxyimide organocatalysts in three types has been theoretically explored by intrinsic reaction coordinate and distortion/interaction model. All these H-abstraction processes can be divided into two parts: CH bond approaching to catalyst and subsequent breaking via a cross-point structure. Generally, the H-abstraction reactivity increase when a catalyst has small LUMO_catalyst-HOMO_substrate gap, CH bond approaching energy and distortion energy required to achieve its transition state (TS) geometry, and large electron affinity. The TS structures for 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and N-methyl benzohydroxamic acid (NMBHA) are inclined to be product-like, but much reactant-like for N-hydroxyphthalimide (NHPI)-type catalysts.