Continued Progress towards Efficient Functionalization of Natural and Non‐natural Targets under Mild Conditions: Oxygenation by C−H Bond Activation with Dioxirane

Abstract

The successful isolation and characterization of a dioxirane species in 1988 opened up one of the most attractive methods for the efficient oxidation of simple and/or structurally complex molecules. Dioxirane today rank among the most powerful tools in organic chemistry, with numerous applications in commercially important processes. They were quickly recognized as efficient oxygen transfer agents, especially for epoxidations and for a wide range of O‐insertion reactions into C−H bonds. Dioxirane possess catalytic activity and appear as highly (chemo‐, regio‐, and stereo‐) selective oxidants, despite their reactivity under mild and strictly neutral conditions being controlled by a combination of steric and electronic factors. In this review, we discuss some of the most recent and significant developments in the selective homogeneous and heterogeneous oxyfunctionalization of non‐activated C−H bonds in hydrocarbons of natural and non‐natural targets by using isolated dioxirane or, more generally, by using the ketones (i.e., the dioxirane precursors) as organocatalysts.

One-Stage Catalytic Oxidation of Adamantane to Tri-, Tetra-, and Penta-Ols

“…The oxidation of 0 with O 2 C(CF 3 )CH 3 demonstrates the unique properties of this system, which is out of competition, potentially capable of oxidizing 0 not only to 4a but also to 5a with high yields with an increase in reaction time [57,58].…”

“…With one-stage oxidation of 0 to 3a and 4a, the best results were obtained when methyl(trifluoromethyl)dioxirane O 2 C(CF 3 )CH 3 as an oxidizer was used, with which the sequential oxidation of 0 to 2a, 3a, and 4a with high yields 93, 90, and 78% occurred in 40 min, 2 and 3 h, respectively [57]. The unique properties of this catalytic system during the oxidation of various substrates are systematized in the review [58].…”

“…In one-stage syntheses of 3a and 4a, as well as in multi-stage syntheses, in fact, the scheme of sequential oxidation of 0 is realized, but without the stages of isolation of intermediate products. For example, since 3a is an intermediate product in the series 2a, 3a, 4a, its synthesis using different chemical reagents means searching for optimal conditions in which the target product has the highest yield [49,[57][58][59][60][61][62][63]. It was in this way that work was carried out to find the conditions for the oxidation of 0 to 3a and 4a.…”

Novel Strategies in C-H Oxidations for Natural Product Diversification—A Remote Functionalization Application Summary

“…They are quickly recognized as efficient oxygen transfer agents, especially for epoxidations and for a wide range of O-insertion reactions into C-H bonds. ( Fusco et al, 2020 )…”

Electronic control over site-selectivity in hydrogen atom transfer (HAT) based C(sp3)–H functionalization promoted by electrophilic reagents

“…Different HAT reagents have been employed for this purpose (Scheme 7), namely heteroatom-centered radicals such as alkoxyl, 11,12 acyloxyl, 13,14 aminoxyl, 15,16 amidyl, 17 iodanyl, 18 halogens, 19 and radical ions such as aminium radicals 20,21 and sulfate radical anion, 22 as well as radical-like HAT reagents such as photocatalysts (for example, polyoxometalates 23 or excited arylketones 24 ), bioinspired catalysts (like metalloporphyrins and other metal complexes) 25,26 and dioxiranes. 27,28 Among the latter class of reagents, biocatalysts such as cytochrome P450 enzymes and their mutants, in the so-called ''directed evolution'' approach have received great attention for the possibility they offer to ensure outstanding site-and stereoselectivities in C-H bond functionalization processes through the appropriate positioning of the substrate in the active site via non covalent interactions. 29 A new class of HAT reagents that offers the opportunity to broadly diversify both structure and reactivity has been recently developed, and consists in N-ammonium amidyl radicals that can be conveniently generated electrochemically by oxidation of N-ammonium ylide precursors (Scheme 8).…”