Re-catalyzed Synthesis Of Phthalides From Benzamides And Aldehydes Via C-H Functionalization

The rapid growth of the field of C-H bond functionalization over the past few decades might significantly streamline the organic synthesis. In principle, the direct transformations of C-H bonds as a robust and efficient means for forming new chemical bonds widely occurring in organic molecules can obviate the pre-activation of reaction substrates, diminish the generation of undesired waste, thus improving the atom and step economy of the whole event. So far, noble transition-metal(e.g., Rh, Pd, Ir and Ru) catalysts have played a leading role in the area of C-H bond activation reactions. In order to make the C-H functionalization more applicable, the development of novel, efficient catalysts is highly desirable. As our continuous interest in rhenium catalysis, we have devoted ourselves to expanding the Re catalyst to improve the selectivity and versatility of these transformations,and make a better progress in the C-H activation field.We herein report the Re-catalyzed C-H bond activation and addition of benzamides to aldehydes to afford biologically important phthalides. As we all know, this is the first example of rhenium catalyze benzamides as directing group that enables C-H bond activation and addition to aldehydes, it provides a useful and new types of catalytic reactions for the synthesis of phthalides derivatives. This reaction shows broad scope with a high level of functional group compatibility and is applicable to aromatic or aliphatic aldehydes to obtain the desired phthalides in good yields. The proposed mechanism via C-H bond activation, insertion of the aldehyde, reductive elimination, intramolecular nucleophilic cyclization, and elimination of methanamine.