Department of Chemistry , The Scripps Research Institute , 10550 N. Torrey Pines Road , La Jolla , California 92037 , United States.
Department of Chemical Development , Boehringer Ingelheim Pharmaceuticals Inc. , 900 Ridgebury Road , Ridgefield , Connecticut 06877 , United States.
J Am Chem Soc. 2018 Mar 14;140(10):3564-3568. doi: 10.1021/jacs.8b01359. Epub 2018 Mar 2.
We report the first example of Pd(II)-catalyzed γ-C(sp)-H activation of ketones directed by a practical 2,2-dimethyl aminooxyacetic acid auxiliary. 2-Pyridone ligands are identified to enable C(sp)-H activation for the first time. A rare six-membered palladacycle intermediate is isolated and characterized to elucidate the reaction mechanism. Both (hetero)arylation and vinylation of γ-C(sp)-H bonds are demonstrated. Sequential β- and γ-C(sp)-H (hetero)arylation of muscone showcases the utility of this method for late-stage diversification. A convenient Mn(II)-catalyzed auxiliary removal is also developed to further underscore the practicality of this transformation.
我们报告了首例钯（II）催化的酮的γ-C(sp)-H 活化反应，该反应由一种实用的 2,2-二甲基氨氧基乙酸辅助基导向。首次鉴定出 2-吡啶酮配体以实现 C(sp)-H 活化。分离并表征了罕见的六元钯环中间体以阐明反应机理。γ-C(sp)-H 键的（杂）芳基化和乙烯基化均得到了验证。麝香的β-和γ-C(sp)-H（杂）芳基化的级联反应展示了该方法在后期多样化中的实用性。还开发了一种方便的 Mn(II)催化辅助基去除方法，进一步强调了这种转化的实用性。
