Department of Chemistry, University of Houston, Houston, Texas 77204-5003, USA.
J Am Chem Soc. 2010 Mar 24;132(11):3965-72. doi: 10.1021/ja910900p.
We have developed a method for auxiliary-directed, palladium-catalyzed beta-arylation and alkylation of sp(3) and sp(2) C-H bonds in carboxylic acid derivatives. The method employs a carboxylic acid 2-methylthioaniline- or 8-aminoquinoline amide substrate, aryl or alkyl iodide coupling partner, palladium acetate catalyst, and an inorganic base. By employing 2-methylthioaniline auxiliary, selective monoarylation of primary sp(3) C-H bonds can be achieved. If arylation of secondary sp(3) C-H bonds is desired, 8-aminoquinoline auxiliary may be used. For alkylation of sp(3) and sp(2) C-H bonds, 8-aminoquinoline auxiliary affords the best results. Some functional group tolerance is observed and amino- and hydroxy-acid derivatives can be functionalized. Preliminary mechanistic studies have been performed. A palladacycle intermediate has been isolated, characterized by X-ray crystallography, and its reactions have been studied.
我们开发了一种辅助导向的钯催化方法，用于羧酸衍生物中 sp(3)和 sp(2) C-H 键的β-芳基化和烷基化。该方法采用羧酸 2-巯基苯胺或 8-氨基喹啉酰胺底物、芳基或烷基碘化物偶联伙伴、醋酸钯催化剂和无机碱。通过使用 2-巯基苯胺辅助试剂，可以实现伯 sp(3) C-H 键的选择性单芳基化。如果需要芳基化仲 sp(3) C-H 键，则可以使用 8-氨基喹啉辅助试剂。对于 sp(3)和 sp(2) C-H 键的烷基化，8-氨基喹啉辅助试剂效果最佳。观察到一些官能团的耐受性，并且可以对氨基和羟基酸衍生物进行官能化。已经进行了初步的机理研究。分离得到了一个钯环中间体，并通过 X 射线晶体学进行了表征，研究了其反应。
