Intramolecular Catalytic Hydrogen Atom Transfer (CHAT).

Intramolecular catalysis ( IntraCat ) is the acceleration of a process at one site of a molecule catalyzed by a functional group in the same molecule; an external agent such as a solvent typically facilitates it. Here, we report a general first-principles-based IntraCat mechanism, which strictly occurs within a single molecule with no coreagent being involved─we call it intramolecular catalytic transfer of hydrogen atoms ( CHAT ). A reactive part of a molecule ( chat catalyst moiety or chat agent, represented by -OOH, -COOH, -SH, -CH 2 OH, -HPO 4 , or another bifunctional H-donor/acceptor group) catalyzes an interconversion process, such as keto-enol or amino-imino tautomerization, and cyclization in the same molecule, while being regenerated in the process. It can thus be regarded as an intramolecular version of the intermolecular H atom transfer processes mediated by an external molecular catalyst, e.g., dihydrogen, water, or a carboxylic acid. Earlier, we proposed a general mechanistic systematization of intermolecular processes, illustrated in the simplest case of the H 2 -mediated reactions classified as dihydrogen catalysis [Asatryan, R.; et al. Catal. Rev.: Sci. Eng. , 2014, 56, 403-475]. Following this systematization, the CHAT catalysis belongs to the category of relay transfer of H atoms, albeit in an intramolecular manner. A broader class of intramolecular processes includes all types of H-transfer reactions stimulated by an H-migration, which we call self-catalyzed H atom transfer (SC-HAT). The CHAT mechanism comprises a subset of SC-HAT in which the catalytic moiety is regenerated (i.e., acts as a true catalyst and not a reagent). We provide several characteristic examples of CHAT mechanism based on detailed analysis of the corresponding potential energy surfaces. All such cases showed a dramatically reduced activation barrier relative to the corresponding uncatalyzed H-transfer reactions. For example, we show that CHAT can facilitate long-range H-migration in larger molecules and can occur multiple times in one molecule with multiple interconverting groups. It also facilitates amino-imino tautomerization of unsaturated GABA-analogues and peptides, as well as intramolecular cyclization processes to form heterocycles, e.g., oxygenated rings. CHAT pathways may also explain the pH-dependent increase of mutarotation rate of glucose-6-phosphate demonstrated in pioneering experiments that introduced the classical IntraCat concept. In addition, we identify a ground electronic state CHAT pathway as an alternative to the UV-promoted long-range molecular crane keto-enol conversion with a remarkably low activation energy. To initially assess the possible impact of the new keto-enol conversion pathway on combustion of n -alkanes, we present a detailed kinetic analysis of isomerization and decomposition of pentane-2,4-ketohydroperoxide (2,4-KHP). The results are compared with key alternative reactions, including direct dissociation and Korcek channels (for which a new alkyl group migration channel is also identified), revealing the competitiveness of the CHAT pathway across a range of conditions. Taken together, this work provides insight into a general class of reaction pathways that has not previously being systematically considered and that may occur in a broad range of contexts from combustion to atmospheric chemistry to biochemistry.