Rh(III)-catalyzed C-H Activation of Aryl-Hydroxamates for the Synthesis of Isoindolinones.

: We report a Rh(III)-catalyzed C-H functionalization reaction yielding isoindolinones from aryl-hydroxamates and ortho-substituted styrenes. The reaction proceeds smoothly under mild conditions at room temperature, and tolerates a range of functional groups. Experimental and computational investigations support that the high regioselectivity observed for these substrates results from the presence of an ortho-substituent embedded in the styrene. The resulting isoindolinones are valuable building blocks for the synthesis of bioactive compounds. They provide  easy access to the natural product-like compounds, isoindolobenzazepines, in a one-pot-two-step reaction. Selected isoindolinones inhibited Hedgehog (Hh)-dependent differentiation of multipotent murine mesenchymal progenitor stem cells into osteoblasts.