Directed C−H functionalization has been realized as a complementary tool to the traditional approaches for a straightforward access of non‐proteinogenic amino acids; albeit such a process is restricted mostly up to the γ‐position. In the present work, we demonstrate the diverse (hetero)arylation of amino acids and analogous aliphatic amines selectively at the remote δ‐position by tuning the reactivity controlled by ligands. An organopalladium δ‐C(sp3)−H activated intermediate has been isolated and crystallographically characterized. Mechanistic investigations carried out experimentally in conjunction with computational studies shed light on the difference in the mechanistic picture depending on the substrate structure.

Covalent organic frameworks (COFs) are ideal host matrices for biomolecule immobilization and biocatalysis due to their high porosity, various functionalities, and structural robustness. However, the porosity of COFs is limited...

Peptide-based biomimetic catalysts are promising materials for efficient catalytic activity in various biochemical transformations. However, their lack of operational stability and fragile nature in non-aqueous media limit their practical applications. In this study, we have developed a cladding technique to stabilize biomimetic catalysts within porous covalent organic framework (COF) scaffolds. This methodology allows for the homogeneous distribution of peptide nanotubes inside the COF (TpAzo and TpDPP) backbone, creating strong noncovalent interactions that prevent leaching. We synthesized two different peptide-amphiphiles, C10FFVK and C10FFVR, with lysine (K) and arginine (R) at the C-termini, respectively, which formed nanotubular morphologies. The C10FFVK peptide-amphiphile nanotubes exhibit enzyme-like behavior and efficiently catalyze C–C bond cleavage in a buffer medium (pH 7.5). We produced nanotubular structures of TpAzo–C10FFVK and TpDPP–C10FFVK through COF cladding by using interfacial crystallization (IC). The peptide nanotubes encased in the COF catalyze C–C bond cleavage in a buffer medium as well as in different organic solvents (such as acetonitrile, acetone, and dichloromethane). The TpAzo–C10FFVK catalyst, being heterogeneous, is easily recoverable, enabling the reaction to be performed for multiple cycles. Additionally, the synthesis of TpAzo–C10FFVK thin films facilitates catalysis in flow. As control, we synthesized another peptide-amphiphile, C10FFVR, which also forms tubular assemblies. By depositing TpAzo COF crystallites on C10FFVR nanotubes through IC, we produced TpAzo–C10FFVR nanotubular structures that expectedly did not show catalysis, suggesting the critical role of the lysines in the TpAzo–C10FFVK.

Directed CÀHfunctionalization has been realized as ac omplementary tool to the traditional approaches for as traightforwarda ccess of non-proteinogenic amino acids; albeit such aprocess is restricted mostly up to the g-position. In the present work, we demonstrate the diverse (hetero)arylation of amino acids and analogous aliphatic amines selectively at the remote d-position by tuning the reactivity controlled by ligands.Anorganopalladium d-C(sp 3 )ÀHactivated intermediate has been isolated and crystallographically characterized. Mechanistic investigations carried out experimentally in conjunction with computational studies shed light on the difference in the mechanistic picture depending on the substrate structure.