高效绿色的酰胺合成方法一直是当前有机合成, 尤其是制药行业所关注的重要问题. 本工作发展了一种通过光催化C—N键裂解的叔胺脱烷基酰化反应, 无需额外添加剂, 使用廉价的吖啶盐作为光敏剂, 即可在室温下由酸酐和叔胺合成酰胺. 本研究为酰胺的高效合成提供了一种不需金属和添加剂, 绿色、温和、经济、高效的方法, 该方法具有广泛的底物适用范围和良好的官能团耐受性.

The amide moiety is unarguable importance due to its widespread presence in numerous biologically active molecules, including agrochemicals, insecticides, pharmaceutical agents, peptides, proteins, polysaccharides and nucleic acids. The condensation of a carboxylic acid and an amine using a coupling reagent or metal/boronic catalyst represents the most common approach in amide synthesis and is frequently employed in producing modern pharmaceuticals. However, the use of stoichiometric amounts of coupling agents, oxidants, or catalytic amounts of metal catalysts often involves challenges such as toxicity and high cost. In connection with our studies on photoredox acylations, we herein report an efficient photoredox dealkylative acylation of tertiary amines with acid anhydrides using a commercially available and inexpensive acridine salt-based photocatalyst, which enables the preparation of a wide range of amides from tertiary amines under mild reaction conditions. To an oven dried Schlenk-tube, benzoic anhydride (45.2 mg, 0.20 mmol), triethylamine (60.7 mg, 0.60 mmol), $\mathrm{Mes}-\mathrm{Acr}^{+} \mathrm{ClO}_{4}^{-}$ (1.6 mg, 0.004 mmol) and MeCN (2 mL) were added under argon atmosphere. The reaction mixture was stirred under the irradiation of 20 W Blue LED (450 nm) at room temperature. After completion of the reaction, the reaction mixture was concentrated by vacuum, purified by silica gel chromatography, and eluted by petroleum ether/ethyl acetate to obtain products. With the optimized reaction conditions in hand, we investigated the scope of anhydrides and tertiary amines in the present dealkylative acylation. In general, all tested substrates were suitable for yielding amidation products, all of the aliphatic, aromatic anhydrides and tertiary amines are suitable reactants for the transformations to afford the corresponding amides in moderate to excellent yields. The successful gram-scale reaction and late-stage functionalization of drug molecule in mild conditions under room temperature have qualified the protocol to be practical, cost-effective, and environmentally friendly. The mechanistic studies have verified the single-electron oxidation of tertiary amine by the photosensitiser and the generation of an acyl radical via single electron reduction of anhydride.