Palladium(II)-Catalyzed Selective Arylation of Tertiary C-H Bonds of Cyclobutylmethyl Ketones Using Transient Directing Groups

We report the first example of selective Pd-II-catalyzed tertiary C-H activation of cyclobutylmethyl ketones using a transient directing group. An electron-deficient 2-pyridone ligand was identified as the optimal external ligand to enable tertiary C-H activation. A variety of cyclobutylmethyl ketones bearing quaternary carbon centers was readily accessed without preinstalling internal directing groups in up to 81 % yield and >95 : 5 regioisomeric ratios of tertiary C-H arylation to beta-methylene (beta-methyl) or gamma-C-H arylation.

Automated summary

In this study, we report the first example of selective Pd(II)-catalyzed tertiary C-H activation of cyclobutylmethyl ketones using a transient directing group. An electron-deficient 2-pyridone ligand was identified as the optimal external ligand to achieve tertiary C-H activation. Various cyclobutylmethyl ketones with quaternary carbon centers were obtained in high yields without the need for preinstalling internal directing groups, and showed high regioselectivity for tertiary C-H arylation.