关键词: 叔胺, 脱烷基, 酰化, 酰胺, 光催化

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.

Key words: tertiary amines, dealkylation, acylation, amide, photocatalysis