Catalytic Enantioselective α-Fluorination of Carbonyl Compounds Using Chiral Transition Metal Complexes
Catalytic Enantioselective α-Fluorination of Carbonyl Compounds Using Chiral Transition Metal Complexes
复制标题
DOI：
10.5059/yukigoseikyokaishi.65.1099
复制
发表时间：
2007-11
影响因子：
0.2
通讯作者：
Y. Hamashima;M. Sodeoka
中科院分区：
文献类型：
--
作者：
Y. Hamashima;M. Sodeoka
发展了两种高效催化羰基化合物不对称α-环己基化反应的催化体系。阳离子钯配合物被发现是有效的活性次甲基和亚甲基化合物的氟化，和各种底物，包括β-酮酯，β-酮膦酸酯，和其他相关的化合物在环境友好的醇溶剂中氟化（高达99%ee）。该体系也适用于3-取代吲哚酮衍生物的反应。此外，我们还成功地开发了一种新的三元体系NiCl_2-binap/R_3SiOTf/2，6-二甲基吡啶，用于低酸性α-芳基乙酸衍生物的反应，反应顺利进行，得到了相应的单氟代化合物，具有较高的对映选择性（高达88%ee）。我们的手性反应是通用的，适用于立体选择性合成的手性氟化类似物的基本构件和催化不对称合成的BMS 204352，一个有前途的治疗中风的代理。
Two catalytic systems were developed for efficient catalytic enantioselective α-fluorination reactions of carbonyl compounds. Cationic Pd complexes were found to be effective for fluorination of active methine and methylene compounds, and various substrates including β-ketoesters, β-ketophosphonates, and other related compounds were fluorinated in environmentally friendly alcoholic solvents (up to 99% ee). This system was also applicable to the reaction of 3-substituted oxindole derivatives. In addition, we succeeded in developing a novel trinary system NiCl2-binap/R3SiOTf/2, 6-lutidine for the reaction of less acidic α-aryl acetic acid derivatives, and the desired reaction proceeded smoothly to give the corresponding monofluorinated compounds in a highly enantioselective manner (up to 88% ee). Our fluorination reactions are versatile, being applicable to stereoselective synthesis of chiral fluorinated analogues of fundamental building blocks and catalytic asymmetric synthesis of BMS204352, a promising agent for the treatment of stroke.