HFIP-driven Schmidt-type reaction enables chromone-3-carbonitriles and its applications

Mol Divers. 2024 Nov 23. doi: 10.1007/s11030-024-11027-z. Online ahead of print.

Abstract

Chromone-3-carbonitrile has been extensively studied in a panel of high-value transformations. However, existing protocols for the synthesis of this scaffold are often constrained by the structure of the starting materials and harsh conditions. To address these issues, we present a novel strategy that HFIP (hexafluoroisopropanol)-driven strategy, enables chromone-3-carbonitriles synthesis without undesirable side reactions. This protocol features readily available feedstocks, mild conditions, catalytic amount of acid and good to excellent yields. The utility of this chemistry is further demonstrated by amenable modifications of chromone-pyrimidines and imidazoles. Moreover, the analogous transformation of aldehydes is successfully constructed to achieve useful compounds such as 2-hydroxybenzonitriles, heterocyclic nitriles, and α, β-unsaturated nitriles. The HFIP-driven strategy offers an interesting access to different types of nitriles in a sustainably manner.

Keywords: Applications; Chromone-3-carbonitrile; HFIP; Nitrile; Schmidt-type reaction.