Direct Synthesis of Unprotected Indolines Through Intramolecular sp C-H Amination Using Nitroarenes as Aryl Nitrene Precursors.

Given the prevalence of molecules containing nitro groups in organic synthesis, innovative methods to expand the reactivity of this functional group are of interest in both industrial and academic settings. In this report, a metal-free intramolecular benzylic sp C-H amination is disclosed using aryl nitro compounds as aryl nitrene precursors. Organosilicon reagent N,N'-bis(trimethylsilyl)-4,4'-bipyridinylidene (Si-DHBP) served as an efficient reductant in the transformation, enabling the in situ generation of aryl nitrene species for the direct, metal-free synthesis of unprotected 2-arylindolines from the corresponding nitroarene compounds.

Deaminative coupling of benzylamines and arylboronic acids.

A metal-free deaminative coupling of non-prefunctionalised benzylamines and arylboronic acids is reported. In this operationally simple reaction, a primary amine in benzylamine is converted into a good leaving group using inexpensive and commercially available isoamyl nitrite as a nitrosating reagent. Lewis-acidic arylboronic acids are shown to replace mineral acids such as HCl or HBF that are conventionally used in the preparation of aryl diazonium salts.

Late-stage stitching enabled by manganese-catalyzed C─H activation: Peptide ligation and access to cyclopeptides.

Bioorthogonal late-stage diversification of structurally complex peptides bears enormous potential for drug discovery and molecular imaging. Despite major accomplishments, these strategies heavily rely on noble-metal catalysis. Herein, we report on a manganese(I)-catalyzed peptide C─H hydroarylation that enabled the stitching of peptidic and sugar fragments, under exceedingly mild and racemization-free conditions.

Late-stage peptide C-H alkylation for bioorthogonal C-H activation featuring solid phase peptide synthesis.

Methods for the late-stage diversification of structurally complex peptides hold enormous potential for advances in drug discovery, agrochemistry and pharmaceutical industries. While C-H arylations emerged for peptide modifications, they are largely limited to highly reactive, expensive and/or toxic reagents, such as silver(I) salts, in superstoichiometric quantities. In sharp contrast, we herein establish the ruthenium(II)-catalyzed C-H alkylation on structurally complex peptides.

Late-Stage Diversification through Manganese-Catalyzed C-H Activation: Access to Acyclic, Hybrid, and Stapled Peptides.

Bioorthogonal C-H allylation with ample scope was accomplished through a versatile manganese(I)-catalyzed C-H activation for the late-stage diversification of structurally complex peptides. The unique robustness of the manganese(I) catalysis manifold was reflected by full tolerance of sensitive functional groups, such as iodides, esters, amides, and OH-free hydroxy groups, thereby setting the stage for the racemization-free synthesis of C-H fused peptide hybrids featuring steroids, drug molecules, natural products, nucleobases, and saccharides.

Nitrosonium ion catalysis: aerobic, metal-free cross-dehydrogenative carbon-heteroatom bond formation.

Catalytic cross-dehydrogenative coupling of heteroarenes with thiophenols and phenothiazines has been developed under mild and environmentally benign reaction conditions. For the first time, NOx+ was applied for catalytic C-S and C-N bond formation. A comprehensive scope for the C-H/S-H and C-H/N-H cross-dehydrogenative coupling was demonstrated with >60 examples.

Covalent Post-assembly Modification Triggers Multiple Structural Transformations of a Tetrazine-Edged FeL Tetrahedron.

Covalent post-assembly modification (PAM) reactions are useful synthetic tools for functionalizing and stabilizing self-assembled metal-organic complexes. Recently, PAM reactions have also been explored as stimuli for triggering supramolecular structural transformations. Herein we demonstrate the use of inverse electron-demand Diels-Alder (IEDDA) PAM reactions to induce supramolecular structural transformations starting from a tetrazine-edged FeL tetrahedral precursor.