Ir(?)-Catalyzed Aryl C-H Bond Carbenoid Functionalization Cascade: Access To 1,3-Dihydroindole-2-Ones

Transitin metal-catalyzed direct C-H bond functionalization is a most effective tool to construct carbon-carbon bonds,which provides an atom-and step-economic transformation platform for the synthesis of complex organic molecules.Functionalized indolone skeleton is a common structural unit in many bioactive molecules,natural products and synthetic intermediates.For example,some ketone structure-containing organic molecules often have anti-inflammatory and anti-tumor biological activity,so developing concise synthetic methods to construct indole ketone skeleton has aroused many concerns.In this paper,N-pyridyl-substituted aromatic amines were designed and synthesized,in which the pyridine ring was employed as the chelate-oriented functional group,and we systematically investgated the effects of reaction parameters such as catalysts,additives,solvents and temperature et al on the cascade cyclization of N-(2-pyridyl)aniline with diazotized Meldrum's acid.Then,we tested the substrate scope of this transformation under the optimized reaction conditions,and found that both electron-withdrawing and electron-donating substituent groups on the benzene ring or pyridine ring could be smoothly converted to the corresponding ketone compounds in moderate to good yields.However,the ortho-or meta-substituted benzene ring only produced a single C-H carbenoid inserted products due to the steric hindrance.The synthetic application for this transformation indicates that indolone compounds can be further transformed into small molecule hematopoietic growth factor analogues.Meanwhile,the related control experiments and kinetic isotope effect were carried out to demonstrat the possible mechanism,in which twice aryl C-H carbenoid insertion were involved in this transformation.