RESUMEN
The design of N-oxyl hydrogen atom transfer catalysts has proven challenging to date. Previous efforts have focused on the functionalization of the archetype, phthalimide-N-oxyl. Driven in part by the limited options for modification of this structure, this strategy has provided only modest improvements in reactivity and/or solubility. Our previous mechanistic efforts suggested that while the electron-withdrawing carbonyls of the phthalimide are necessary to maximize the O-H bond dissociation enthalpy of the HAT product hydroxylamine and overall reaction thermodynamics, they undergo nucleophilic substitution leading to catalyst decomposition. In an attempt to minimize this vulnerability, we report the characterization of N-oxyl catalysts wherein the aryl ring in PINO is replaced with the combination of a substituted heteroatom and quaternary carbon. By rendering one carbonyl carbon less electrophilic and the other less sterically accessible, the corresponding N1-aryl-hydantoin-N3-oxyl radical showed significantly higher stability than PINO as well as a modest improvement in reactivity. This proof-of-principle in new scaffold design may accelerate future HAT catalyst discovery and development.
RESUMEN
Four-membered nitrogen-containing heterocycles are highly desirable functional groups with synthetic and biological applications. Unsaturated four-membered N-heterocycles, 1- and 2-azetines, are historically underexplored, but have recently been gaining interest due to the development of new synthetic methods to access these compounds, and to their potential as reactive intermediates. This review covers both the synthesis and applications of azetines, with a focus on synthetic methods to access azetines developed since 2018, and a comprehensive review of the reactivity and applications of azetines as starting materials or intermediates to access both other heterocycles and complex products.