Benzocyclonone structures, represented by 4-chromanone and 1-indanone, are widely found in natural compounds and pharmaceuticals with important biological activities. Since cyano modification is an important strategy for structural modification and optimization in medicinal chemistry, the introduction of a cyano group into these structures is of great significance. Radical-driven cascade cyclization reactions have been developed as an effective means to build benzocyclones bearing various functional groups. However, existing methods for synthesizing cyanated 4-chromanone and 1-indanone are limited and often require harsh conditions. In this study, bromoacetonitrile was employed both as a radical precursor and a cyano source to develop an efficient photocatalytic radical cascade cyclization method for constructing cyano-substituted benzocyclonones. Under mild photocatalytic conditions, bromoacetonitrile generates a cyanomethyl radical that initiates a two-step addition and cyclization with 2-(allyloxy) aromatic aldehydes or its analogues, enabling the effective synthesis of cyano-modified 4-chromanone, 1-indanone, and dihydroquinolone derivatives. This reaction system demonstrates a wide substrate scope and enables the rapid construction of these structures under uniform standard conditions. Meanwhile, it shows good tolerance for various functional groups. Substrates containing iodine, bromine, ester, and sulfonyl groups all successfully undergo the desired transformations, producing target products in moderate to good yields. Notably, compared to previously used cyanide sources like trimethylsilyl cyanide and diazo compounds, bromoacetonitrile is safer and more readily accessible. Mechanistic investigations suggest the reaction proceeds through the addition of a cyanomethyl radical to a carbon-carbon double bond, forming an alkyl radical, which then undergoes intramolecular addition to the carbonyl group to create an oxygen radical intermediate. This intermediate undergoes an intramolecular 1,2-hydrogen atom transfer (1,2-HAT), which is then followed by single-electron oxidation and deprotonation, resulting in the final desired cyclization product. Overall, this research provides a mild and efficient method for simultaneously constructing benzocyclonone and performing cyano-modification, which is expected to advance the synthesis and discovery of related bioactive molecules.

Key words: photocatalysis, radical cyclization, bromoacetonitrile, cyanomethylation, 4-chromanone