Boryl radical-mediated halogen atom transfer-induced radical cascade cyclization of N-(o-cyanobiaryl)acrylamides with alkyl halides

Abstract

We report a study on the use of ligated boryl radicals for the synthesis of nitrogen-containing polycyclic compounds under photocatalytic conditions through a halogen-atom-transfer (XAT) strategy. This approach leverages the fact that alkyl iodides are not capable of directly generating alkyl radical intermediates under photocatalytic conditions. Instead, the transformation proceeds via an XAT pathway involving boron-centered radical intermediates. A range of alkyl halides (1°, 2° and 3° C–I, C–Br) as well as alkyl iodide derivatives of biologically active molecules (such as ibuprofen, citronellol, geraniol, cholesterol, and estrone) are applicable in the strategy. Finally, a scale-up synthesis and late-stage modification through Sonogashira cross-coupling reactions of structurally complex molecules demonstrate the practicability of this methodology.