Dearomative syn-Dihydroxylation of Naphthalenes with a Biomimetic Iron Catalyst.

Arenes are interesting feedstocks for organic synthesis because of their natural abundance. However, the stability conferred by aromaticity severely limits their reactivity, mostly to reactions where aromaticity is retained. Methods for oxidative dearomatization of unactivated arenes are exceedingly rare but particularly valuable because the introduction of Csp3-O bonds transforms the flat aromatic ring in 3D skeletons and confers the oxygenated molecules with a very rich chemistry suitable for diversification. Mimicking the activity of naphthalene dioxygenase (NDO), a non-heme iron-dependent bacterial enzyme, herein we describe the catalytic syn-dihydroxylation of naphthalenes with hydrogen peroxide, employing a sterically encumbered and exceedingly reactive yet chemoselective iron catalyst. The high electrophilicity of hypervalent iron oxo species is devised as a key to enabling overcoming the aromatically promoted kinetic stability. Interestingly, the first dihydroxylation of the arene renders a reactive olefinic site ready for further dihydroxylation. Sequential bis-dihydroxylation of a broad range of naphthalenes provides valuable tetrahydroxylated products in preparative yields, amenable for rapid diversification.

Nickel-Catalyzed Decarbonylative Amination of Carboxylic Acid Esters.

The reaction of carboxylic acid derivatives with amines to form amide bonds has been the most widely used transformation in organic synthesis over the past century. Its utility is driven by the broad availability of the starting materials as well as the kinetic and thermodynamic driving force for amide bond formation. As such, the invention of new reactions between carboxylic acid derivatives and amines that strategically deviate from amide bond formation remains both a challenge and an opportunity for synthetic chemists. This report describes the development of a nickel-catalyzed decarbonylative reaction that couples (hetero)aromatic esters with a broad scope of amines to form (hetero)aryl amine products. The successful realization of this transformation was predicated on strategic design of the cross-coupling partners (phenol esters and silyl amines) to preclude conventional reactivity that forms inert amide byproducts.

Characterized cis-FeV(O)(OH) intermediate mimics enzymatic oxidations in the gas phase.

FeV(O)(OH) species have long been proposed to play a key role in a wide range of biomimetic and enzymatic oxidations, including as intermediates in arene dihydroxylation catalyzed by Rieske oxygenases. However, the inability to accumulate these intermediates in solution has thus far prevented their spectroscopic and chemical characterization. Thus, we use gas-phase ion spectroscopy and reactivity analysis to characterize the highly reactive [FeV(O)(OH)(5tips3tpa)]2+ (32+) complex. The results show that 32+ hydroxylates C-H bonds via a rebound mechanism involving two different ligands at the Fe center and dihydroxylates olefins and arenes. Hence, this study provides a direct evidence of FeV(O)(OH) species in non-heme iron catalysis. Furthermore, the reactivity of 32+ accounts for the unique behavior of Rieske oxygenases. The use of gas-phase ion characterization allows us to address issues related to highly reactive intermediates that other methods are unable to solve in the context of catalysis and enzymology.

Mechanistically Driven Development of an Iron Catalyst for Selective Syn-Dihydroxylation of Alkenes with Aqueous Hydrogen Peroxide.

Product release is the rate-determining step in the arene syn-dihydroxylation reaction taking place at Rieske oxygenase enzymes and is regarded as a difficult problem to be resolved in the design of iron catalysts for olefin syn-dihydroxylation with potential utility in organic synthesis. Toward this end, in this work a novel catalyst bearing a sterically encumbered tetradentate ligand based in the tpa (tpa = tris(2-methylpyridyl)amine) scaffold, [FeII(CF3SO3)2(5-tips3tpa)], 1 has been designed. The steric demand of the ligand was envisioned as a key element to support a high catalytic activity by isolating the metal center, preventing bimolecular decomposition paths and facilitating product release. In synergistic combination with a Lewis acid that helps sequestering the product, 1 provides good to excellent yields of diol products (up to 97% isolated yield), in short reaction times under mild experimental conditions using a slight excess (1.5 equiv) of aqueous hydrogen peroxide, from the oxidation of a broad range of olefins. Predictable site selective syn-dihydroxylation of diolefins is shown. The encumbered nature of the ligand also provides a unique tool that has been used in combination with isotopic analysis to define the nature of the active species and the mechanism of activation of H2O2. Furthermore, 1 is shown to be a competent synthetic tool for preparing O-labeled diols using water as oxygen source.

Oxidation of alkane and alkene moieties with biologically inspired nonheme iron catalysts and hydrogen peroxide: from free radicals to stereoselective transformations.

The selective oxidation of hydrocarbons is a challenging reaction for synthetic chemists, but common in nature. Iron oxygenases activate the O-O bond of dioxygen to perform oxidation of alkane and alkenes moieties with outstanding levels of regio-, chemo- and stereoselectivity. Along a bioinspired approach, iron coordination complexes which mimic structural and reactivity aspects of the active sites of nonheme iron oxygenases have been explored as oxidation catalysts. This review describes the evolution of this research field, from the early attempts to reproduce the basic reactivity of nonheme iron oxygenases to the development of effective iron oxidation catalysts. The work covers exclusively nonheme iron complexes which rely on H2O2 or O2 as terminal oxidants. First, it delineates the key steps and the essential catalyst design principles required to activate the peroxide bond at nonheme iron centers without (or at least minimizing) the release of free-diffusing radicals. It follows with a critical description of the mechanistic pathways which govern the reaction between iron complexes and H2O2 to generate the oxidizing species. Eventually, the work presents a state-of-the-art report on the use of these catalysts in aliphatic C-H oxidation, olefin epoxidation and alkene syn-dihydroxylation, under substrate-limiting conditions. A special focus is given on the main strategies elaborated to tune catalyst activity and selectivity by modification of its structure. The work is concluded by a concise discussion on the essential progresses of these oxidation catalysts together with the challenges that remain still to be tackled.