Late-Stage Modification of Peptides with Maleimides through Palladium-Catalyzed β-C(sp)-H Alkylation.

Transition-metal-catalyzed C-H activation has proven to be a powerful tool for the late-stage modification of peptides. We herein report a method for site-selective alkylation of peptides with maleimides through Pd-catalyzed β-C(sp)-H activation. In this protocol, the methionine residues within peptides serve as the directing groups, which circumvented the preinstallation and subsequent removal of the directing groups.

Methionine-enabled peptide modification through late-stage Pd-catalyzed β-C(sp)-H olefination/cyclization.

We present a method for site-selective diversification of peptides Pd-catalyzed β-C(sp)-H olefination/cyclization. In this protocol, the native methionine residue acts as a directing group, enabling site-specific olefination/cyclization of peptides. This chemistry demonstrates broad substrate scope, offering a versatile tool for peptide ligation.

Backbone-Enabled and Ester Groups Switched δ-C(sp)-H Amination/Fluorination: Cyclic Dipeptides Synthesis.

An efficient and concise strategy for the synthesis of cyclic dipeptides via Pd-catalyzed site-selective δ-C(sp)-H amination/fluorination and N-to-C cyclization is disclosed. The backbone amides within the dipeptides serves as endogenous directing groups, while the desired products were switched by the C-terminal ester group. This chemistry presents a novel and robust alternative to construct cyclodipeptide fragments.

Backbone-enabled modification of peptides with benzoquinone palladium-catalyzed δ-C(sp)-H functionalization.

Backbone-enabled site-selective modification of peptides with benzoquinone Pd-catalyzed δ-C(sp)-H functionalization has been achieved. The amide groups of peptides serve as internal directional groups, facilitating C-H functionalization through a kinetically less favored six-membered palladacycle. This methodology presents novel opportunities for the late-stage site-selective diversification of peptides.

Relay Copper-Catalyzed Synthesis of Imidazo[1,5-]pyridine Scaffolds from Phenylalanine and Halohydrocarbon.

An efficient and straightforward strategy to synthesize imidazo[1,5-]pyridine compounds from phenylalanine and halohydrocarbon has been successfully developed. The protocol features a relay copper-catalyzed reaction involving intermolecular C-O coupling and intramolecular C-N cyclization, providing an approach to access a diverse range of imidazo[1,5-]pyridine derivatives with unique aza quaternary carbon centers.

Late-Stage Diversification of Peptides via Pd-Catalyzed Site-Selective δ-C(sp)-H Fluorination and Amination.

Site-selective C-H fluorination is an attractive strategy for directly transforming inert C-H bonds into C-F bonds, yet it remains a significant challenge. Herein, we have developed an efficient and versatile strategy for site-selective fluorination and amination of phenylalanine-containing peptides via late-stage Pd-catalyzed δ-C(sp)-H activation, providing a valuable tool for the in situ synthesis of fluorinated indoline scaffolds within peptides.

Site-Selective Modification of Peptides via Late-Stage Pd-Catalyzed Tandem Reaction of Phenylalanine with Benzoquinone.

An efficient and straightforward approach for site-selective functionalization of phenylalanine and phenylalanine-containing peptide via a Pd-catalyzed tandem reaction has been developed. The robust method underwent dual C-H activation, including C-C coupling with benzoquinone and intramolecular C-N cyclization, providing a feasible and rapid synthetic route to incorporate 4-benzoquinone-indoline fragments into peptides.

Copper-Catalyzed Chemodivergent Synthesis of Oxazoles and Imidazolidones by Selective C-O/C-N Cyclization.

Efficient synthesis of phenylalanine-derived oxazoles and imidazolidones can be achieved by copper-catalyzed reactions that are controlled by directing groups and proceed by selective C-O or C-N coupling. This strategy employs inexpensive commercial copper catalysts and readily available starting materials. It uses a convenient reaction procedure and provides a reliable approach to the versatile and flexible assembly of heterocyclic building blocks.