Chen Gang, Shigenari Toshihiko, Jain Pankaj, Zhang Zhipeng, Jin Zhong, He Jian, Li Suhua, Mapelli Claudio, Miller Michael M, Poss Michael A, Scola Paul M, Yeung Kap-Sun, Yu Jin-Quan
Department of Chemistry, The Scripps Research Institute , 10550 N. Torrey Pines Road, La Jolla, California 92037, United States.
J Am Chem Soc. 2015 Mar 11;137(9):3338-51. doi: 10.1021/ja512690x. Epub 2015 Mar 3.
Pd-catalyzed β-C-H functionalizations of carboxylic acid derivatives using an auxiliary as a directing group have been extensively explored in the past decade. In comparison to the most widely used auxiliaries in asymmetric synthesis, the simplicity and practicality of the auxiliaries developed for C-H activation remains to be improved. We previously developed a simple N-methoxyamide auxiliary to direct β-C-H activation, albeit this system was not compatible with carboxylic acids containing α-hydrogen atoms. Herein we report the development of a pyridine-type ligand that overcomes this limitation of the N-methoxyamide auxiliary, leading to a significant improvement of β-arylation of carboxylic acid derivatives, especially α-amino acids. The arylation using this practical auxiliary is applied to the gram-scale syntheses of unnatural amino acids, bioactive molecules, and chiral bis(oxazoline) ligands.
在过去十年中，使用辅助基团作为导向基团的钯催化羧酸衍生物的β-C-H官能化反应已得到广泛研究。与不对称合成中使用最广泛的辅助基团相比，为C-H活化而开发的辅助基团的简单性和实用性仍有待提高。我们之前开发了一种简单的N-甲氧基酰胺辅助基团来指导β-C-H活化，尽管该体系与含有α-氢原子的羧酸不兼容。在此，我们报道了一种吡啶型配体的开发，该配体克服了N-甲氧基酰胺辅助基团的这一局限性，从而显著改善了羧酸衍生物尤其是α-氨基酸的β-芳基化反应。使用这种实用辅助基团的芳基化反应应用于非天然氨基酸、生物活性分子和手性双（恶唑啉）配体的克级合成。
