Uracil and its derivatives are core structural motifs in the fields of biomedicine, life sciences, and agricultural sciences, and their structural modification holds significant research and application value. Traditional modification methods, such as condensation cyclization and nucleophilic substitution, often rely on harsh conditions including high temperatures, strong acids, or strong bases. These approaches suffer from poor site selectivity, low atom economy, narrow substrate scopes, and environmental unfriendliness, failing to meet the demands of modern late-stage drug modification and industrial production. In recent years, direct C-H functionalization has emerged as a novel strategy for the efficient and green modification of uracil compounds, leveraging advantages such as the avoidance of pre-functionalization, high step economy, and excellent atom economy. This review systematically summarizes the progress in C-H functionalization of uracil and its derivatives over the past six years, covering various transformation types including alkylation, arylation, trifluoromethylation, acylation, amination, sulfidation/selenization, silicidation, alkenylation, and boronation. This article provides an in-depth comparison of substrate scopes, reaction mechanisms, and application potentials. By also incorporating relevant work from our research group, we aim to offer researchers in related fields a systematic and detailed reference framework to facilitate innovative applications of uracil-based molecules in drug discovery and life sciences.
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