Aromatic molecules are key constituents of many pharmaceuticals, electronic materials, and commodity plastics. The utility of these molecules directly reflects the identity and pattern of ...substituents on the aromatic ring. Here, we report a palladium(II) catalyst system, incorporating an unconventional ortho-dimethylaminopyridine ligand, for the conversion of substituted cyclohexanones to the corresponding phenols. The reaction proceeds via successive dehydrogenation of two saturated carbon-carbon bonds of the six-membered ring and uses molecular oxygen as the hydrogen acceptor. This reactivity demonstrates a versatile and efficient strategy for the synthesis of substituted aromatic molecules with fundamentally different selectivity constraints from the numerous known synthetic methods that rely on substitution of a preexisting aromatic ring.
An efficient organocatalytic method for chemoselective aerobic oxidation of secondary benzylic alcohols within lignin model compounds has been identified. Extension to selective oxidation in natural ...lignins has also been demonstrated. The optimal catalyst system consists of 4-acetamido-TEMPO (5 mol %; TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl) in combination with HNO3 and HCl (10 mol % each). Preliminary studies highlight the prospect of combining this method with a subsequent oxidation step to achieve C–C bond cleavage.
Quinones are common stoichiometric reagents in organic chemistry. Para‐quinones with high reduction potentials, such as DDQ and chloranil, are widely used and typically promote hydride ion. In recent ...years, many catalytic applications of these methods have been achieved by using transition metals, electrochemistry, or O2 to regenerate the oxidized quinone in situ. Complementary studies have led to the development of a different class of quinones that resemble the ortho‐quinone cofactors in copper amine oxidases and mediate the efficient and selective aerobic and/or electrochemical dehydrogenation of amines. The latter reactions typically proceed by electrophilic transamination and/or addition‐elimination reaction mechanisms, rather than hydride ion pathways. The collective observations show that the quinone structure has a significant influence on the reaction mechanism and has important implications for the development of new quinone reagents and quinone‐catalyzed transformations.
Quinones are highly useful reagents for the dehydrogenation and oxidative functionalization of organic molecules, but they are often used in stoichiometric quantities. This Review highlights recent advances in quinone‐catalyzed reactions wherein the reduced quinone is regenerated by a more‐desirable stoichiometric oxidant. In many cases, O2 is capable of serving as the terminal oxidant (see scheme; Sub=substrate).
Lignin is a heterogeneous aromatic biopolymer that accounts for nearly 30% of the organic carbon on Earth and is one of the few renewable sources of aromatic chemicals. As the most recalcitrant of ...the three components of lignocellulosic biomass (cellulose, hemicellulose and lignin), lignin has been treated as a waste product in the pulp and paper industry, where it is burned to supply energy and recover pulping chemicals in the operation of paper mills. Extraction of higher value from lignin is increasingly recognized as being crucial to the economic viability of integrated biorefineries. Depolymerization is an important starting point for many lignin valorization strategies, because it could generate valuable aromatic chemicals and/or provide a source of low-molecular-mass feedstocks suitable for downstream processing. Commercial precedents show that certain types of lignin (lignosulphonates) may be converted into vanillin and other marketable products, but new technologies are needed to enhance the lignin value chain. The complex, irregular structure of lignin complicates chemical conversion efforts, and known depolymerization methods typically afford ill-defined products in low yields (that is, less than 10-20wt%). Here we describe a method for the depolymerization of oxidized lignin under mild conditions in aqueous formic acid that results in more than 60wt% yield of low-molecular-mass aromatics. We present the discovery of this facile C-O cleavage method, its application to aspen lignin depolymerization, and mechanistic insights into the reaction. The broader implications of these results for lignin conversion and biomass refining are also considered.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oxidation reactions are key transformations in organic chemistry because they can increase chemical complexity and incorporate heteroatom substituents into carbon-based molecules. This principle is ...manifested in the conversion of petrochemical feedstocks into commodity chemicals and in the synthesis of fine chemicals, pharmaceuticals, and other complex organic molecules. The utility and function of these molecules correlate directly with the presence and specific placement of oxygen and nitrogen heteroatoms and other functional groups within the molecules. Methods for selective oxidation of C–H bonds have expanded significantly over the past decade, and their role in the synthesis of organic chemicals will continue to increase. Our group’s contributions to this field are linked to our broader interest in the development and mechanistic understanding of aerobic oxidation reactions. Molecular oxygen (O2) is the ideal oxidant. Its low cost and lack of toxic byproducts make it a highly appealing reagent that can address key “green chemistry” priorities in industry. With strong economic and environmental incentives to use O2, the commmodity chemicals industry often uses aerobic oxidation reactions. In contrast, O2 is seldom used to prepare more-complex smaller-volume chemicals, a limitation that reflects, in part, the limited synthetic scope and utility of existing aerobic reactions. Pd-catalyzed reactions represent some of the most versatile methods for selective C–H oxidation, but they often require stoichiometric transition-metal or organic oxidants, such as CuII, AgI, or benzoquinone. This Account describes recent strategies that we have identified to use O2 as the oxidant in these reactions. In Pd-catalyzed C–H oxidation reactions that form carbon-heteroatom bonds, the stoichiometric oxidant is often needed to promote difficult reductive elimination steps in the catalytic mechanism. To address this challenge, we have identified new ancillary ligands for Pd that promote reductive elimination, or replaced Pd with a Cu catalyst that undergoes facile reductive elimination from a CuIII intermediate. Both strategies have enabled O2 to be used as the sole stoichiometric oxidant in the catalytic reactions. C–H oxidation reactions that form the product via β-hydride or C–C reductive elimination steps tend to be more amenable to the use of O2. The use of new ancillary ligands has also overcome some of the limitations in these methods. Mechanistic studies are providing insights into some (but not yet all) of these advances in catalytic reactivity.
Direct methods for stereoselective functionalization of sp³-hybridized carbon-hydrogen C(sp³)-H bonds in complex organic molecules could facilitate much more efficient preparation of therapeutics and ...agrochemicals. Here, we report a copper-catalyzed radical relay pathway for enantioselective conversion of benzylic C–H bonds into benzylic nitriles. Hydrogen-atom abstraction affords an achiral benzylic radical that undergoes asymmetric C(sp³)–CN bond formation upon reaction with a chiral copper catalyst. The reactions proceed efficiently at room temperature with the benzylic substrate as limiting reagent, exhibit broad substrate scope with high enantioselectivity (typically 90 to 99% enantiomeric excess), and afford products that are key precursors to important bioactive molecules. Mechanistic studies provide evidence for diffusible organic radicals and highlight the difference between these reactions and C–H oxidations mediated by enzymes and other catalysts that operate via radical rebound pathways.
Aerobic oxidation reactions have been the focus of considerable attention, but their use in mainstream organic chemistry has been constrained by limitations in their synthetic scope and by practical ...factors, such as the use of pure O2 as the oxidant or complex catalyst synthesis. Here, we report a new (bpy)CuI/TEMPO catalyst system that enables efficient and selective aerobic oxidation of a broad range of primary alcohols, including allylic, benzylic, and aliphatic derivatives, to the corresponding aldehydes using readily available reagents, at room temperature with ambient air as the oxidant. The catalyst system is compatible with a wide range of functional groups and the high selectivity for 1° alcohols enables selective oxidation of diols that lack protecting groups.
α,β-Unsaturated carbonyl compounds are versatile intermediates in the synthesis of pharmaceuticals and biologically active compounds. Here, we report the discovery and application of Pd(DMSO)2(TFA)2 ...as a catalyst for direct dehydrogenation of cyclohexanones and other cyclic ketones to the corresponding enones, using O2 as the oxidant. The substrate scope includes heterocyclic ketones and several natural-product precursors.
The "magic methyl" effect describes the change in potency, selectivity, and/or metabolic stability of a drug candidate associated with addition of a single methyl group. We report a synthetic method ...that enables direct methylation of C(sp
)-H bonds in diverse drug-like molecules and pharmaceutical building blocks. Visible light-initiated triplet energy transfer promotes homolysis of the O-O bond in di-
-butyl or dicumyl peroxide under mild conditions. The resulting alkoxyl radicals undergo divergent reactivity, either hydrogen-atom transfer from a substrate C-H bond or generation of a methyl radical via β-methyl scission. The relative rates of these steps may be tuned by varying the reaction conditions or peroxide substituents to optimize the yield of methylated product arising from nickel-mediated cross-coupling of substrate and methyl radicals.
Palladium-catalyzed aerobic oxidation reactions have been the focus of industrial application and extensive research efforts for nearly 60 years. A significant transition occurred in this field ...approximately 20 years ago, with the introduction of catalysts supported by ancillary ligands. The ligands play crucial roles in the reactions, including promotion of direct oxidation of palladium(0) by O2, bypassing the typical requirement for Cu salts or related redox cocatalysts to facilitate oxidation of the reduced Pd catalyst; facilitation of key bond-breaking and bond-forming steps during substrate oxidation; and modulation of chemo-, regio-, or stereoselectivity of a reaction. The use of ligands has contributed to significant expansion of the scope of accessible aerobic oxidation reactions. Increased understanding of the role of ancillary ligands should promote the development of new synthetic transformations, enable improved control over the reaction selectivity, and improve catalyst activity and stability. This review surveys the different ligands that have been used to support palladium-catalyzed aerobic oxidation reactions and, where possible, describes mechanistic insights into the role played by the ancillary ligand.
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