CH Hydroxylation Using a Heterocyclic Catalyst and Aqueous H₂O₂

Abstract

Catalytic reaction processes for selective C À H bond hydroxylation are at the fore of modern synthetic chemical methods development. Such technologies attempt to mimic the extraordinary performance and precision of enzymatic systems. [1] Following this approach, most inventions have relied on transition-metal based complexes to support reactive metaloxo or metal-peroxo species that can effect the desired C À H oxidation event. [2,3] Far fewer catalytic methods make use of strained, electrophilic organic heterocycles (e.g., dioxiranes and oxaziridines). [4,5] We have capitalized on the unique properties of oxaziridines-ease of synthesis, modularity of design, tunable reactivity-and have described the first example of an oxaziridine-based catalytic process for C À H hydroxylation. [6,7] In contrast to most metal-mediated hydroxylation reactions, for which the high, indiscriminant reactivity of the oxidant often limits product selectivity and catalyst turnover, our first-generation oxaziridine system is hampered by its modest activity, thus restricting its use to a very small number of substrates. As such, we have sought new catalyst designs with enhanced performance and application potential. Mechanistic insights gained through computational and kinetics experiments have made possible the advent of a catalyst for CÀH hydroxylation that: 1) can be employed with a number of architecturally diverse substrates; 2) displays positional selectivity towards tertiary C À H bonds; and 3) functions under aqueous conditions with H 2

Metal-Catalyzed Nitrogen-Atom Transfer Methods for the Oxidation of Aliphatic C–H Bonds

“…Notably, cyclization reactions of α -branched, N -Boc sulfamide derivatives favor formation of the anti -isomer with moderate levels of stereocontrol. 19 This preference can be rationalized using the same cyclic transition state model in which A 1,3 -strain between the N -Boc group and the α -substituent forces the latter into a pseudoaxial alignment, thereby favoring the anti -diastereomer.…”

“…2,3 In this Account, we discuss our investigations of both intra- and intermolecular catalytic C–H and π -bond amination, focusing on our efforts to develop chemoselective and diastereoselective insertion reactions and to understand operative mechanisms for N-atom transfer and catalyst inhibition. An exhaustive overview of the historical traces of this technology and the salient contributions from many others who work in this field has been presented elsewhere and will be largely omitted from this text.…”

Enantioselective Organocatalytic Oxaziridination of N‐Tosyl Aldimine Catalyzed by Cinchona Alkaloid‐Ester Derivatives

“…The chemical shifts are reported in ppm with the solvent signal as a reference (7.26 ppm). The splitting patterns of the signals are reported as s singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; td, triplet of doublets; m, multiplet; bs, broad signal …”

Metal‐Free Oxidative Carbon‐Heteroatom Bond Formation Through C–H Bond Functionalization

“…A remarkable C–H hydroxylation of methine C–H bonds under oxidative organocatalytic conditions was achieved by Du Bois and co‐workers (Scheme ) 79. Benzoxathiazine‐based heterocyclic catalyst 155 together with H 2 O 2 in aqueous AcOH under ambient conditions provided various tertiary alcohols such as 154 in good yields.…”