Biocatalytic Construction of Chiral Pyrrolidines and Indolines via Intramolecular C(sp)-H Amination.

Nature harnesses exquisite enzymatic cascades to construct -heterocycles and further uses these building blocks to assemble the molecules of life. Here we report an enzymatic platform to construct important chiral -heterocyclic products, pyrrolidines and indolines, via abiological intramolecular C(sp)-H amination of organic azides. Directed evolution of cytochrome P411 (a P450 enzyme with serine as the heme-ligating residue) yielded variant , capable of catalyzing the insertion of alkyl nitrene into C(sp)-H bonds to build pyrrolidine derivatives with good enantioselectivity and catalytic efficiency.

Programmable late-stage functionalization of bridge-substituted bicyclo[1.1.1]pentane bis-boronates.

Modular functionalization enables versatile exploration of chemical space and has been broadly applied in structure-activity relationship (SAR) studies of aromatic scaffolds during drug discovery. Recently, the bicyclo[1.1.