Sunlight‐ or UVA‐Light‐Mediated Synthesis of Hydroxamic Acids from Carboxylic Acids

Abstract

AbstractThe development of light‐mediated methods for synthetic applications is increasingly attracting high interest. We present herein a new photochemical protocol for the synthesis of hydroxamic acids, which constitute an important class of medicinal agents, mainly due to their anticancer properties. The method is mediated by UVA‐light or sunlight and its key point is the generation of a charge transfer complex by the interaction of 4‐dimethylaminopyridine with a halomethane. Various carboxylic acids were directly coupled with O‐protected hydroxylamines, upon irradiation with either LED 370 nm or solar light. A detailed study of the mechanism was carried out by the employment of direct infusion–high resolution mass spectrometry (DI‐HRMS), providing experimental evidence for the formation of various activated species, which may lead to the desired product. The light‐mediated protocol was applied in the synthesis of the drugs Vorinostat and Bufexamac.