Aminofluorene-Mediated Biomimetic Domino Amination–Oxygenation of Aldehydes to Amides

A conceptually novel biomimetic strategy based on a domino amination–oxygenation reaction was developed for direct amidation of aldehydes under metal-free conditions employing molecular oxygen as the oxidant. 9-Aminofluorene derivatives acted as pyridoxamine-5′-phosphate equivalents for efficient, chemoselective, and operationally simple amine-transfer oxygenation reaction. Unprecedented RNH transfer involving secondary amine to produce secondary amides was achieved. In the presence of ¹⁸O₂, ¹⁸O-amide was formed with excellent (95%) isotopic purity

Metal-Free Thermal Activation of Molecular Oxygen Enabled Direct α‑CH₂‑Oxygenation of Free Amines

Direct oxidation of α-CH₂ group of free amines is hard to achieve due to the higher reactivity of amine moiety. Therefore, oxidation of amines involves the use of sophisticated metallic reagents/catalyst in the presence or absence of hazardous oxidants under sensitive reaction conditions. A novel method for direct C–H oxygenation of aliphatic amines through a metal-free activation of molecular oxygen has been developed. Both activated and unactivated free amines were oxygenated efficiently to provide a wide variety of amides (primary, secondary) and lactams under operationally simple conditions without the aid of metallic reagents and toxic oxidants. The method has been applied to the synthesis of highly functionalized amide-containing medicinal drugs, such as O-Me-alibendol and -buclosamide

Direct β‑C(sp³)–H Functionalization of Aliphatic Amines to α,β-Unsaturated Imines, Aldehydes, and Chromenes

A metal-free method for direct β-C­(sp³)–H functionalization of aliphatic amine was developed. The method is based on a reaction that yields enamine directly from the corresponding aliphatic amine, which otherwise requires the aid of metallic reagent and/or external oxidant. The reaction is operationally simple, general, and highly efficient in functionalizing both cyclic and acyclic amines. Structurally diverse unsaturated imines were obtained from <i>N</i>-heterocycles, while acyclic amines provided 2-alkyl cinnamaldehyde and benzopyran derivatives with excellent <i>E</i>/<i>Z</i>-selectivity

Metal Free C–H Functionalization Enabled Diastereoselective Multicomponent Reaction of N‑Heterocycles to Fused Heteropolycycles

A novel C–H functionalization enabled multicomponent reaction involving N-heterocycles, dinucleophile, and dipolarophile has been developed. Direct α- and more challenging β-C­(sp3)–H functionalization of aliphatic N-heterocycles was achieved without the use of metallic reagents and oxidants under either conventional or microwave aided heating conditions. In a single operation, up to five carbon–carbon and carbon–heteroatom bonds are formed in a highly diastereoselective manner, providing the expeditious access to the complex heteropolycycles

Metal Free C–H Functionalization Enabled Diastereoselective Multicomponent Reaction of N‑Heterocycles to Fused Heteropolycycles

A novel C–H functionalization enabled multicomponent reaction involving N-heterocycles, dinucleophile, and dipolarophile has been developed. Direct α- and more challenging β-C­(sp3)–H functionalization of aliphatic N-heterocycles was achieved without the use of metallic reagents and oxidants under either conventional or microwave aided heating conditions. In a single operation, up to five carbon–carbon and carbon–heteroatom bonds are formed in a highly diastereoselective manner, providing the expeditious access to the complex heteropolycycles

Metal Free C–H Functionalization Enabled Diastereoselective Multicomponent Reaction of N‑Heterocycles to Fused Heteropolycycles

A novel C–H functionalization enabled multicomponent reaction involving N-heterocycles, dinucleophile, and dipolarophile has been developed. Direct α- and more challenging β-C­(sp3)–H functionalization of aliphatic N-heterocycles was achieved without the use of metallic reagents and oxidants under either conventional or microwave aided heating conditions. In a single operation, up to five carbon–carbon and carbon–heteroatom bonds are formed in a highly diastereoselective manner, providing the expeditious access to the complex heteropolycycles

Direct β‑C(sp³)–H Functionalization of Aliphatic Amines to α,β-Unsaturated Imines, Aldehydes, and Chromenes

A metal-free method for direct β-C­(sp³)–H functionalization of aliphatic amine was developed. The method is based on a reaction that yields enamine directly from the corresponding aliphatic amine, which otherwise requires the aid of metallic reagent and/or external oxidant. The reaction is operationally simple, general, and highly efficient in functionalizing both cyclic and acyclic amines. Structurally diverse unsaturated imines were obtained from <i>N</i>-heterocycles, while acyclic amines provided 2-alkyl cinnamaldehyde and benzopyran derivatives with excellent <i>E</i>/<i>Z</i>-selectivity

Metal Free C–H Functionalization Enabled Diastereoselective Multicomponent Reaction of N‑Heterocycles to Fused Heteropolycycles

A novel C–H functionalization enabled multicomponent reaction involving N-heterocycles, dinucleophile, and dipolarophile has been developed. Direct α- and more challenging β-C­(sp3)–H functionalization of aliphatic N-heterocycles was achieved without the use of metallic reagents and oxidants under either conventional or microwave aided heating conditions. In a single operation, up to five carbon–carbon and carbon–heteroatom bonds are formed in a highly diastereoselective manner, providing the expeditious access to the complex heteropolycycles

Metal-Free Sequential C(sp²)–H/OH and C(sp³)–H Aminations of Nitrosoarenes and <i>N</i>‑Heterocycles to Ring-Fused Imidazoles

Hydrogen bond assisted <i>ortho</i>-selective C­(sp²)–H amination of nitrosoarenes and subsequent α-C­(sp³)-H functionalization of aliphatic amines is achieved under metal-free conditions. The annulation of nitrosoarenes and 2-hydroxy-C-nitroso compounds with <i>N</i>-heterocycles provides a facile excess to a wide range of biologically relevant ring-fused benzimidazoles and structurally novel polycyclic imidazoles, respectively. Nucleophilic aromatic hydrogen substitution (S_NArH) was found to be preferred over classical S_NAr reaction during the C­(sp²)–H amination of halogenated nitrosoarenes