One-Pot Direct Oxidation of Primary Amines to Carboxylic Acids through Tandem ortho-Naphthoquinone-Catalyzed and TBHP-Promoted Oxidation Sequence.

Biomimetic oxidation of primary amines to carboxylic acids has been developed where the copper-containing amine oxidase (CuAO)-like o-NQ-catalyzed aerobic oxidation was combined with the aldehyde dehydrogenase (ALDH)-like TBHP-mediated imine oxidation protocol. Notably, the current tandem oxidation strategy provides a new mechanistic insight into the imine intermediate and the seemingly simple TBHP-mediated oxidation pathways of imines. The developed metal-free amine oxidation protocol allows the use of molecular oxygen and TBHP, safe forms of oxidant that may appeal to the industrial application.

One-Pot Tandem ortho-Naphthoquinone-Catalyzed Aerobic Nitrosation of N-Alkylanilines and Rh(III)-Catalyzed C-H Functionalization Sequence to Indole and Aniline Derivatives.

The nitroso group served as a traceless directing group for the C-H functionalization of N-alkylanilines, ultimately removed after functioning either as an internal oxidant or under subsequent reducing conditions. The unique ability of o-NQ catalysts to aerobically oxidize the N-alkylanilines without using solvents and stoichiometric amounts of oxidants has rendered the new opportunity to develop the telescoped catalyst systems without a need for directly handling the hazardous N-nitroso compounds.

Oxidation Potential-Guided Electrochemical Radical-Radical Cross-Coupling Approaches to 3-Sulfonylated Imidazopyridines and Indolizines.

Oxidation potential-guided electrochemical radical-radical cross-coupling reactions between N-heteroarenes and sodium sulfinates have been established. Thus, simple cyclic voltammetry measurement of substrates predicts the likelihood of successful radical-radical coupling reactions, allowing the simple and direct synthetic access to 3-sulfonylated imidazopyridines and indolizines. The developed electrochemical radical-radical cross-coupling reactions to sulfonylated N-heteroarenes boast the green synthetic nature of the reactions that are oxidant- and metal-free.

Correction: Recent advances in the copper-catalyzed aerobic Csp3-H oxidation strategy.

Correction for 'Recent advances in the copper-catalyzed aerobic Csp3-H oxidation strategy' by Hun Young Kim et al., Org. Biomol. Chem., 2021, DOI: .

Recent advances in the copper-catalyzed aerobic Csp3-H oxidation strategy.

The interplay between copper catalysts and molecular oxygen provides the opportunity to control the promiscuous catalytic behaviors in aerobic Csp3-H bond oxidations without using stoichiometric amounts of oxidants. This mini-review aims to cover the Cu-catalyzed aerobic benzylic and α-carbonyl Csp3-H oxidations and that of the carbon next to an amine group in the past five years. The development of tandem multicomponent reactions employing aerobic Csp3-H bond oxidations will be discussed to highlight the controlled catalyst behaviors and the catalyst interactions between multiple reaction components.

Visible-Light [4+2] Homodimerization of Decomposition-Prone Styrenes via Electron Transfer Catalysis of Diaryl Diselenides.

The facile electron transfer catalysis of diaryl diselenides was utilized for the visible-light [4+2] homodimerization of decomposition-prone styrenes. The reaction required only 0.5 mol % TPT+BF4- photocatalyst and 1.5 mol % electron transfer catalyst (ArSe)2. The spontaneous electron transfer capability of diaryl diselenides was demonstrated for the first time, leading to the sequestration of redox-prone radical cation intermediates via electron transfer processes. A variety of polymerization-prone styrenes smoothly underwent the visible-light-promoted [4+2] homodimerization to tetralin derivatives.

Photoredox-Catalyzed 1,4-Peroxidation-Sulfonylation of Enynones: A Three-Component Radical Coupling Approach for the Synthesis of Highly Functionalized Allenes.

An Eosin Y-catalyzed visible light-promoted 1,4-peroxidation-sulfonylation of enynones was achieved to give tetrasubstituted allenes. The photoredox catalysis of Eosin Y allowed the concomitant formation of peroxy and sulfonyl radicals, where the preferential peroxy radical addition to the alkene moiety of enynones resulted in the subsequent α-keto radical-sulfonyl radical cross couplings. The developed photoredox catalysis of Eosin Y demonstrates a regioselective 1,4-diradical addition strategy, opening up a new possibility of diradical functionalization of conjugate systems.

Efficient approaches to the stereoselective synthesis of cyclopropyl alcohols.

Cyclopropanes occur in a diverse array of natural products, including pheromones, steroids, terpenes, fatty acid metabolites, and amino acids, and compounds that contain cyclopropanes exhibit interesting and important pharmacological properties. These valuable synthetic intermediates can be functionalized, or their rings can be opened, and the synthetic utility and unique biological activity of cyclopropanes have inspired many investigations into their preparation. One of the most powerful methods to generate cyclopropanes is the Simmons-Smith cyclopropanation. Since the original studies in the late 1950s reported that IZnCH(2)I could transform alkenes into cyclopropanes, researchers have introduced various modifications of the original procedure. Significantly, Furukawa demonstrated that diethylzinc and CH(2)I(2) react to generate carbenoids, and Shi described more reactive zinc carbenoids that contain electron-withdrawing groups on zinc (XZnCHI(2)). Despite these advances, the development of catalytic asymmetric Simmons-Smith reactions remains challenging. Although researchers have achieved catalytic asymmetric cyclopropanation of allylic alcohols, these reactions have had limited success. One attractive approach to the synthesis of cyclopropanes involves tandem reactions, where researchers carry out sequential synthetic transformations without the isolation or purification of intermediates. Such a synthetic strategy minimizes difficulties in the handling and purification of reactive intermediates and maximizes yields and the generation of molecular complexity. This Account summarizes our recent effort in the one-pot enantio- and diastereoselective synthesis of cyclopropyl alcohols. In one approach, an asymmetric alkyl addition to α,ß-unsaturated aldehydes or asymmetric vinylation of aliphatic or aromatic aldehydes generates allylic zinc alkoxide intermediates. Directed diastereoselective cyclopropanation of the resulting alkoxide intermediates using in situ generated zinc carbenoids provides cyclopropyl or halocyclopropyl alcohols with high enantio-, diastereo-, and chemoselectivity. Other strategies employ bimetallic reagents such as 1-alkenyl-1,1-heterobimetallics or CH(2)(ZnI)(2) and provide access to di- and trisubstituted cyclopropyl alcohols. These methods enable facile access to skeletally diverse chiral cyclopropyl alcohols in high yields and stereoselectivities without the isolation or purification of the intermediates.

One-Pot Tandem Nickel-Catalyzed α-Vinyl Aldol Reaction and Cycloaddition Approach to [1,2,3]Triazolo[1,5-a]quinolines.

A one-pot tandem approach to [1,2,3]triazolo[1,5-a]quinolines was developed from (E)-ß-chlorovinyl ketones and 2-azidoaryl carbonyls using a sequence of α-vinyl aldol and azide-alkyne cycloaddition reactions. In particular, the intramolecular azide-alkyne cycloaddition of allenol intermediates was readily promoted by a synergistic action of NEt3 and nickel catalysts. Given that the [1,2,3]triazolo[1,5-a]quinolines are useful synthetic precursors to α-diazoimines through ring-chain isomerization process, the subsequent denitrogenative transformations should provide ready access to valuable heterocyclic compounds.

Chemodivergent Sulfonylation of Enynones via Ionic and Radical Addition Modes of Sulfinic Acids.

Different addition modes of sulfinic acids were developed for the chemodivergent sulfonylation of enynones, where the ionic sulfonylation to an alkyne moiety of enynones was effected through a salt-controlled syn-addition pathway. The radical sulfonylation of an alkene moiety also provided the stereodefined sulfonylated alkenes. A one-pot tandem sequence of the Ti(Oi-Pr)4-catalyzed α-vinyl aldol condensation of (E)-ß-chlorovinyl ketones followed by the chemodivergent sulfonylations was also explored, allowing for ready access to highly substituted dienes and enynes.

Catalytic Aerobic N-Nitrosation by Secondary Nitroalkanes in Water: A Tandem Diazotization of Aryl Amines and Azo Coupling.

Secondary nitroalkanes underwent oxygen-mediated nitro-nitrite isomerization, serving as versatile N-nitrosating agents under aerobic conditions. To capitalize on the newly discovered aerobic nitro-nitrite isomerization phenomenon, a phase-transfer catalysis system employing KSeCN and TBAI was developed, in which the tandem diazotization and azo coupling with nitroalkanes as well as N-nitrosation of amines were accomplished. The current tandem diazotization and azo coupling strategy provides a facile synthesis of areneazo-2-(2-nitro)propane derivatives, a safe synthetic alternative to aryl diazonium salts.

Visible-Light-Promoted Aryl Cation Formation: Aromatic SN1 Reactions of Areneazo-2-(2-nitro)propanes.

The visible light excitation of areneazo-2-(2-nitro)propane·HCl salts generated the singlet aryl cation that readily underwent aromatic SN1 reactions with a variety of nucleophiles. The in situ generated singlet aryl cation was stabilized by a counter nitronate anion that prevented other intersystem crossing and single electron transfer processes. With the improved safety features of neutral areneazo-2-(2-nitro)propane derivatives, the current visible-light-promoted aromatic SN1 reactions provide an alternative aryl Csp2-X bond forming strategy.

Studies on elimination pathways of ß-halovinyl ketones leading to allenyl and propargyl ketones and furans under the action of mild bases.

The elimination pathway of stereochemically defined ß-halovinyl ketones has been investigated using a mild base, NEt(3), leading to the formation of allenyl ketones and propargyl ketones. A preferential α-vinyl enolization of (E)-ß-chlorovinyl ketones has been observed where a nonplanar s-cis conformation is proposed as a dominant conformation as opposed to a planar s-cis conformation of (Z)-ß-chlorovinyl ketones. Other eliminative pathways, such as concerted syn- and anti-E2 as well as γ-deprotonation, are excluded on the basis of the deuterium isotope studies. The synthetic utility of the elimination reaction of ß-chlorovinyl ketones was further demonstrated for a one-pot synthesis of 2,5-disubstituted furans in the presence of 1 mol % CuCl.

Bioinspired o-Naphthoquinone-Catalyzed Aerobic Oxidation of Alcohols to Aldehydes and Ketones.

A biomimetic alcohol dehydrogenase (ADH)-like oxidation protocol was developed using an ortho-naphthoquinone catalyst in the presence of a catalytic amount of base. The developed organocatalytic aerobic oxidation protocol proceeds through the intramolecular 1,5-hydrogen atom transfer of naphthalene alkoxide intermediates, a mechanistically distinctive feature from the previous alcohol dehydrogenase mimics that require metals in the active form of catalysts. The ADH-like aerobic oxidation protocol should provide green alternatives to the existing stoichiometric and metal-catalyzed alcohol oxidation reactions.

Continuous Flow Synthesis of 1,4-Benzothiazines Using Ambivalent Reactivity of (E)-ß-Chlorovinyl Ketones: A Point of Reaction Control Enabled by Flow Chemistry.

A continuous flow system to 1,4-benzothiazines was developed using the point of reaction control, where the ambivalent (E)-ß-chlorovinyl ketones and 2,2'-dithiodianilines were confined in a diffusion controlled flow setting. The successful segregation of reactive chemical species in a flow setting allowed more defined reaction pathways that are not feasible in traditional batch reaction conditions. The point of reaction control in flow systems helps to execute the reactions often plagued with the concurrent generation of multiple chemical species.

Silver-Catalyzed Asymmetric Desymmetrization of Cyclohexadienones via Van Leusen Pyrrole Synthesis.

A catalytic asymmetric desymmetrization of cyclohexadienones was accomplished via Van Leusen pyrrole synthesis in the presence of a chiral silver catalyst. The ready access to chiral-fused pyrrole derivatives is attributed to the identification of a suitable isocyanomethyl sulfone surrogate, NasMIC. The current Ag(I)-chiral phosphino-carboamide ligand system can be extended to the kinetic resolution of racemic cyclohexadienones, capitalizing on the differentiated reactivity of chiral quaternary complexes from AgSbF6, chiral ligand (L*), cyclohexadienone, and NasMIC.

One-Pot Synthesis of N-Hydroxypyrroles via Soft α-Vinyl Enolization of (E)-ß-Chlorovinyl Ketones: A Traceless Arylsulfinate Mediator Strategy.

A traceless arylsulfinate mediator strategy has been developed to switch the reaction course of ß-chlorovinyl ketones with N-hydroxyamine. The soft α-vinyl enolization of (E)-ß-chlorovinyl ketones was conducted in the presence of sodium arylsulfinate to give transient alkenyl sulfones that in turn reacted with NH2OH to give novel access to N-hydroxypyrroles. The mechanistic studies revealed the initial formation of oxazine intermediates that rearranged to thermodynamically stable aromatic products, N-hydroxypyrroles, under microwave-assisted heating conditions.

ortho-Naphthoquinone-Catalyzed Aerobic Hydrodeamination of Aryl Amines via in Situ De-diazotization of Aryl Diazonium Species.

The catalytic diazotization of aryl amines was developed using ortho-naphthoquinone catalyst under aerobic conditions, where the 2-nitropropane served as a source of nitrosonium ion. The catalytic generation of diazonium species from aryl amines was further explored in the hydrode-diazotization to give the corresponding products. The mechanistic studies indicated the involvement of aryl radical species that readily underwent the radical cyclization to alkenes as well as the halogen abstraction reactions.

Visible-Light-Promoted Photoaddition of N-Nitrosopiperidines to Alkynes: Continuous Flow Chemistry Approach to Tetrahydroimidazo[1,2-a]pyridine 1-Oxides.

The photoaddition of N-nitrosopiperidines to terminal alkynes was effected under visible-light irradiation, in which a novel synthetic access to tetrahydroimidazo[1,2-a]pyridine 1-oxides was achieved via the dehydrogenative cycloisomerization of ß-nitroso enamine intermediates. The decomposition pathways of N-nitrosamines, alkynes, and ß-nitroso enamine intermediates were better handled in a continuous flow setting through the diffusion control of chemical species that negatively affected the formation of tetrahydroimidazo[1,2-a]pyridine 1-oxides under batch reaction conditions.

Visible-Light-Induced Three-Component Selenofunctionalization of Alkenes: An Aerobic Selenol Oxidation Approach.

A photocatalyst-free visible-light-induced selenofunctionalization of alkenes has been developed using a variety of nucleophiles. The homolytic scission of diselenides under visible-light conditions coupled with the aerobic selenol oxidation to diselenides allowed the successful implementation of three-component selenofunctionalization under visible-light irradiation in open-air conditions. The mechanistic studies revealed the critical role of oxygen content in a reaction medium, where the electron transfer process from the carbon-based radicals to either molecular oxygen or selenyl radicals was controlled.