Remote Oxidation of Aliphatic CH Bonds with Biologically Inspired Catalysts

Bromoacetic Acid-Promoted Nonheme Manganese-Catalyzed Alkane Hydroxylation Inspired by α-Ketoglutarate-Dependent Oxygenases

“…These results imply that the catalytic activity of 1 depends on the acidity of the carboxylic acids . More interestingly, sterically bulky carboxylic acids, which have been frequently used to ameliorate the activity and enantioselectivity in nonheme manganese- and iron-catalyzed olefin epoxidation and C–H oxidation reactions, were found to be inefficient for the catalytic oxidation reaction (Table , entries 8–11). Moreover, addition of stronger Brønsted acids was also demonstrated to be detrimental to the reaction (Table , entries 12–14).…”

“…Inspired by the structures and functions of metalloenzymes, tremendous efforts have been exerted to develop site-selective C–H bond oxidation reactions utilizing biomimetic nonheme manganese and iron complexes combined with a variety of artificial oxidants, such as H 2 O 2 , iodosylbenzene (PhIO), and peracids . Notably, White and co-workers have detailed elegant results employing nonheme iron and manganese complexes possessing rigid tetradentate nitrogen ligands (PDP and CF 3 -PDP; PDP = 1,1′-bis­(pyridin-2-ylmethyl)-2,2′-bipyrrolidine, CF 3 -PDP = 1,1′-bis­((5-(2,6-bis­(trifluoromethyl)­phenyl)­pyridin-2-yl)­methyl)-2,2′-bipyrrolidine) that are capable of oxidizing the distal methine C–H bonds in a predictable manner on the basis of a combination of electronic, steric, and stereoelectronic differences of multiple C–H bonds and the methylene C–H bonds through catalyst control. , More recently, polarity reversal and noncovalent interactions between catalysts and substrates have been utilized to modulate the selectivity in nonheme iron- and manganese complex-catalyzed site- and/or stereoselective C–H bond oxidations. , Despite significant recent advances, , some drawbacks of currently available methods for C­(sp 3 )–H oxidation are the laborious synthesis of the chelating ligand, low turnover numbers, superstoichiometric amounts of oxidant, long reaction time, and recycling and recovery of starting material to obtain satisfactory product yields.…”

“…Interestingly, the role(s) of the succinate ligand, such as the effect(s) on the formation of high-valent iron­(IV)–oxo species and/or the modulation of the reactivity of the iron­(IV)–oxo intermediates in oxidation reactions, has never been discussed in the enzymatic reactions . In CC epoxidation and C–H oxidation reactions enabled by synthetic iron and manganese complexes and H 2 O 2 , the use of carboxylic acids as an additive is mandatory to achieve the regio-, stereo-, and enantioselective oxidation reactions with improved product yields; the roles of the carboxylic additive have been proposed to facilitate the O–O bond cleavage of a metal­(III)–OOH complex to produce a high-valent metal–oxo carboxylate intermediate as active oxidants and to modulate the electrophilicity of the metal–oxo species due to the interaction between carboxylic acid and the postulated iron– and manganese–oxo intermediates in the second-coordination sphere, despite that the high-valent metal­(V)–oxo species binding carboxylic acids have never been captured in biomimetic oxidation reactions …”

Direct Photocatalyzed Hydrogen Atom Transfer (HAT) for Aliphatic C–H Bonds Elaboration

“…Upon suitable conditions, a moiety embedded in the molecular scaffold can be activated and triggers the hydrogen abstraction at a specific site in an intramolecular fashion thus inducing a remote activation of a C–H bond ( r -HAT). ,− Typically, such site-selectivity is granted by the formation of a favorable six-membered cyclic transition state, which results in the occurrence of a 1,5-HAT step, despite the fact that the 1,n-HAT mode ( n ≥ 6) may compete in some cases …”

Enzyme-Like Hydroxylation of Aliphatic C–H Bonds From an Isolable Co-Oxo Complex

“…In addition to biological systems, there has been concerted effort in discovering catalysts that mediate C–H hydroxylation reactivity in a synthetic context. − Many of these systems invoke transition metal-oxo intermediates, ,,− and selectivity is noted to be greater in systems that have an extremely fast rebound step that avoids long-lived radical intermediates that can engage in side reactions. ,, In parallel, there has been significant interest in the detailed study of C–H activation by isolable, well-characterized transition metal-oxo complexes in order to better understand what factors govern the reactivity of enzymatic and synthetic catalysts. , However, in most of these cases, the activation of strong bonds, such as aliphatic C–H bonds, is rarely observed or slow, in direct contrast to the rates of C–H oxidation by P450s. This muted reactivity with strong C–H bonds by well-defined systems is often attributed to free energy considerations.…”