Herein, a new strategy for the synthesis of monofluoroalkenes via employing α-fluoroacrylic acids and N-hydroxyphthalimide (NHPI) redox-active esters as coupling partners has been developed. This decarboxylative reaction enabled the formation of C­(sp2)–C­(sp3) bonds to provide a practical and efficient approach for the construction of a variety of monofluoroalkenes, which are key structural motifs in organic chemistry, under mild reaction conditions. The protocol exhibited excellent functional group compatibility and delivered monofluoroalkene products with excellent Z-stereoselectivity. This work also provides a platform for the modification of complex biologically active molecules containing carboxylic acids.

Herein, an iron(II)-catalyzed decarboxylative and oxidative decarbonylative cross-coupling of α-fluoroacrylic acids with aliphatic aldehydes is presented. This methodology provided a novel and practical strategy for the construction of the monofluoroalkenes...

A protocol for the copper-catalyzed decarboxylative cross-coupling of α-fluoroacrylic acids with N-tosyl oxaziridines was reported. A series of substituted α-fluoroacrylic acids, and primary, secondary and tertiary substituted oxaziridines were suitable reaction substrates. The decarboxylation reaction exhibited good functional group compatibility and excellent Z-stereoselectivity. This method provides a novel and practical strategy for the construction of monofluoroalkenes, which are key functional groups in the pharmaceutical and material sciences. In addition to α-fluoroacrylic acids, βfluoroacrylic acid could also participate in the reaction smoothly, which provides a protocol to access various substituted monofluoroalkenes. This methodology also provides a platform for the modification of complex biologically active molecules. Keywords fluoroacrylic acids; oxaziridines; copper-catalyzed; monofluoroalkene; decarboxylative 有机分子中嵌入氟原子可以引起其亲脂性、代谢稳 定性、膜通透性、生物利用度以及与生物靶点的结合能 力等物理、 化学及生物活性方面性质的变化 [1] . 因此, 含 氟有机化合物在医药、农药及材料科学等领域中得到了 广泛地应用 [2] . 据统计, 市面上大约 40%的农药分子和 大约 25%的医药分子至少含有一个氟原子 [3] . 特别地, 在含氟有机化合物中, 单氟烯烃与肽键是生物电子等排 体, 对肽酶稳定性强、空间构象稳定 [4] . 因此, 在医药化 学和材料领域, 单氟烯烃是理想的肽键模拟物. 在生物 医药、药物研究等方面, 单氟烯烃已经得到了广泛的应 用 [5] . 鉴于单氟烯烃在化学医药及材料方面的重要性, 近来已有很多课题组报道了很多实用的合成策略 [6] . 例 如, 卡宾插入反应、Wittig 反应、Julia-Kocienski 烯化反 应、偕二氟环丙烷的开环偶联反应 [7] 、氟卤代烯烃的交 叉偶联反应 [8] 以及偕二氟烯烃的脱氟偶联反应 [9][10][11][12] . 除 此之外, 我们课题组近来发展了一系列以氟代丙烯酸为 原料的脱羧偶联用于合成单氟烯烃化合物的策略. 例 如, 光诱导氟代丙烯酸与活性酯之前的双脱羧偶联反应 (Scheme 1a) [13] ; 铁催化氟代丙烯酸与烷基醛类化合物 的脱羧、脱羰反应(Scheme 1b) [14] ; 铜催化通过氟代丙烯