Iron(II)‐Catalyzed Biomimetic Aerobic Oxidation of Alcohols

We report the first Fe^II‐catalyzed biomimetic aerobic oxidation of alcohols. The principle of this oxidation, which involves several electron‐transfer steps, is reminiscent of biological oxidation in the respiratory chain. The electron transfer from the alcohol to molecular oxygen occurs with the aid of three coupled catalytic redox systems, leading to a low‐energy pathway. An iron transfer‐hydrogenation complex was utilized as a substrate‐selective dehydrogenation catalyst, along with an electron‐rich quinone and an oxygen‐activating Co(salen)‐type complex as electron‐transfer mediators. Various primary and secondary alcohols were oxidized in air to the corresponding aldehydes or ketones with this method in good to excellent yields.     

A TEMPO‐Free Copper‐Catalyzed Aerobic Oxidation of Alcohols

The copper‐catalyzed aerobic oxidation of primary and secondary alcohols without an external N‐oxide co‐oxidant is described. The catalyst system is composed of a Cu/diamine complex inspired by the enzyme tyrosinase, along with dimethylaminopyridine (DMAP) or N‐methylimidazole (NMI). The Cu catalyst system works without 2,2,6,6‐tetramethyl‐l‐piperidinoxyl (TEMPO) at ambient pressure and temperature, and displays activity for un‐activated secondary alcohols, which remain a challenging substrate for catalytic aerobic systems. Our work underscores the importance of finding alternative mechanistic pathways for alcohol oxidation, which complement Cu/TEMPO systems, and demonstrate, in this case, a preference for the oxidation of activated secondary over primary alcohols.     

Iron(II)-Catalyzed Aerobic Biomimetic Oxidation of N-Heterocycles

Herein, an iron(II)-catalyzed biomimetic oxidation of N-heterocycles under aerobic conditions is described. The dehydrogenation process, involving several electron-transfer steps, is inspired by oxidations occurring in the respiratory chain. An environmentally friendly and inexpensive iron catalyst together with a hydroquinone/cobalt Schiff base hybrid catalyst as electron-transfer mediator were used for the substrate-selective dehydrogenation reaction of various N-heterocycles. The method shows a broad substrate scope and delivers important heterocycles in good-to-excellent yields.     

Development of an Iron(II)‐Catalyzed Aerobic Catechol Cleavage and Biomimetic Synthesis of Betanidin

An aerobic iron(II)‐catalyzed cleavage of catechols was developed. This reaction allows for the preparation of 2‐methoxy‐2 H‐pyrans that can be employed as versatile building blocks for synthesis. The utility of this biomimetic oxidative cleavage is featured in the synthesis of betanidin, a natural colorant with antioxidant properties.     

A Multitasking Vanadium‐Dependent Chloroperoxidase as an Inspiration for the Chemical Synthesis of the Merochlorins

The vanadium‐dependent chloroperoxidase Mcl24 was discovered to mediate a complex series of unprecedented transformations in the biosynthesis of the merochlorin meroterpenoid antibiotics. In particular, a site‐selective naphthol chlorination is followed by an oxidative dearomatization/terpene cyclization sequence to build up the stereochemically complex carbon framework of the merochlorins in one step. Inspired by the enzyme reactivity, a chemical chlorination protocol paralleling the biocatalytic process was developed. These chemical studies led to the identification of previously overlooked merochlorin natural products.     

A Convenient and Selective Palladium‐Catalyzed Aerobic Oxidation of Alcohols

An efficient procedure for the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively, with molecular oxygen under ambient conditions has been achieved. By applying catalytic amounts of Pd(OAc)₂ in the presence of tertiary phosphine oxides (O?PR₃) as ligands, a variety of substrates are selectively oxidized without formation of ester byproducts. Spectroscopic investigations and DFT calculations suggest stabilization of the active palladium(II) catalyst by phosphine oxide ligands.     

Iron‐Catalyzed Aerobic Oxidation of Aldehydes: Single Component Catalyst and Mechanistic Studies

An aerobic oxidation of aldehydes towards carboxylic acids in MeCN using 1 atm of pure oxygen or oxygen in air as the oxidant and a catalytic amount of single component catalyst, Fe(NO₃)₃ · 9H₂O, has been developed. Carboxylic acids with different synthetically useful functional groups were obtained at room temperature. Two mechanistic pathways have been proposed based on isotopic labeling, NMR monitoring, and control experiments. The practicality of this reaction has been demonstrated by conducting several 50 mmol‐scale reactions using pure oxygen or an air‐flow of ~30 mL/min.     

Binary Pd–Polyoxometalates and Isolation of a Ternary Pd–V–Polyoxomolybdate Active Species for Selective Aerobic Oxidation of Alcohols

Binary Pd–polyoxometalates [Pd(dpa)₂]₃[PW₁₂O₄₀]₂ ? 12 DMSO ( 2 ), [Pd(dpa)₂]₃[PMo₁₂O₄₀]₂ ? 12 DMSO ? 2 H₂O ( 3 ), and [Pd(dpa)(DMSO)₂]₂[HPMo₁₀V₂O₄₀] ? 4 DMSO ( 4 ) were synthesized by reaction of [Pd(dpa)(OAc)₂] ? 2 H₂O ( 1 ; dpa=2,2′‐dipyridylamine) with three Keggin‐type polyoxometalates and fully characterized by single‐crystal and powder XRD analyses, IR spectroscopy, and elemental analyses. The synthesis is facile and straightforward, and the complicated ligand‐modification procedure often used in the traditional charge‐transfer method can be omitted. In 2 – 4 , Pd complexes and polyoxometalate anions are coupled through electrostatic interaction. Compound 4 is more active than the other three compounds in the selective aerobic oxidation of alcohols at ambient pressure. Interestingly, during catalytic recycling of compound 4 , unprecedented ternary Pd–V–polyoxometalate [Pd(dpa)₂{VO(DMSO)₅}₂][PMo₁₂O₄₀]₂ ? 4 DMSO ( 5 ), which was captured and characterized by single‐crystal XRD, proved to be the true active species and showed high catalytic activity for the selective aerobic oxidation of aromatic alcohols (98.1–99.8 % conversion, 91.5–99.1 % selectivity). Moreover, on the basis of control experiments and EPR and UV/Vis spectra, a plausible reaction mechanism for the oxidation of alcohols catalyzed by 5 was proposed.     

Simple Copper Catalysts for the Aerobic Oxidation of Amines: Selectivity Control by the Counterion

We describe the use of simple copper‐salt catalysts in the selective aerobic oxidation of amines to nitriles or imines. These catalysts are marked by their exceptional efficiency, operate at ambient temperature and pressure, and allow the oxidation of amines without expensive ligands or additives. This study highlights the significant role counterions can play in controlling selectivity in catalytic aerobic oxidations.     

Direct Amidation from Alcohols and Amines through a Tandem Oxidation Process Catalyzed by Heterogeneous‐Polymer‐Incarcerated Gold Nanoparticles under Aerobic Conditions

We describe herein a highly elegant and suitable synthesis of amide products from alcohols and amines through a tandem oxidation process that uses molecular oxygen as a terminal oxidant. Carbon‐black‐stabilized polymer‐incarcerated gold (PICB‐Au) or gold/cobalt (PICB‐Au/Co) nanoparticles were employed as an efficient heterogeneous catalyst depending on alcohol reactivity and generated only water as the major co‐product of the reaction. A wide scope of substrate applicability was shown with 42 examples. The catalysts could be recovered and reused without loss of activity by using a simple operation.     

Palladium‐Catalyzed Intramolecular Hydroamination of Allenes Coupled to Aerobic Alcohol Oxidation

Taking the air! A Pd^II‐catalyzed intramolecular hydroamination of allenes coupled to alcohol oxidation has been developed. This reaction is performed by using a nitrogen‐based ligand under aerobic conditions, under which the molecular oxygen is used as the terminal oxidant for the reoxidation of Pd⁰ species to complete the catalytic cycle.

     

Palladium‐Catalyzed N‐Alkylation of Amides and Amines with Alcohols Employing the Aerobic Relay Race Methodology

Possibly because homogeneous palladium catalysts are not typical borrowing hydrogen catalysts and ligands are thus ineffective in catalyst activation under conventional anaerobic conditions, they had not been used in the N‐alkylation reactions of amines/amides with alcohols in the past. By employing the aerobic relay race methodology with Pd‐catalyzed aerobic alcohol oxidation being a more effective protocol for alcohol activation, ligand‐free homogeneous palladiums are successfully used as active catalysts in the dehydrative N‐alkylation reactions, giving high yields and selectivities of the alkylated amides and amines. Mechanistic studies implied that the reaction most probably proceeds via the novel relay race mechanism we recently discovered and proposed.     

Selectivity in the Aerobic Dearomatization of Phenols: Total Synthesis of Dehydronornuciferine by Chemo‐ and Regioselective Oxidation

We describe a selective aerobic oxidation of meta‐biaryl phenols that enables rapid access to functionalized phenanthrenes. Aerobic oxidations attract interest due to their efficiency, but remain underutilized in complex molecule settings due to challenges of selectivity. We discuss these issues in the context of Cu catalysis, and highlight the advantages of confining oxygen activation and substrate oxidation to the catalyst's inner‐coordination sphere. This gives rise to predictable selectivity that we use for a concise synthesis of the aporphine dehydronornuciferine.     

Base‐Catalyzed Hydrosilylation of Ketones and Esters and Insight into the Mechanism

Simple bases (KOtBu, KOH) catalyze the silane‐promoted reduction of ketones and esters to alcohols and of aldimines to amines. The inexpensive silane PMHS (polymethylhydrosiloxane) can be used as the reducing reagent. Double and triple bonds, as well as nitro‐ and cyano‐groups are tolerated. Careful dosing of the silane allows for chemoselective reduction of a more reactive group in the presence of a less reactive group (for example, aldehyde reduction in the presence of ketone/ketone reduction in the presence of ester group). Mechanistic studies showed that addition of base to silanes leads to silicate species, which are the acting reducing agents. Under basic conditions, hydrosiloxanes (tetramethyldisiloxane, TMDS; PMHS) convert into simple silanes (H₂SiMe₂, H₃SiMe), making this a practical method to generate these challenging silanes.