Development of Ortho C−H Functionalization of Arenes Using Modifiable Silicon Tethered Directing Group

Transition metal-catalyzed directing group-assisted C−H functionalization has become one of the most powerful strategies for construction of carbon−carbon and carbon−heteroatom bonds in arenes. A variety of directing groups are commonly used for arene C−H functionalizations. Although, most directing groups are important functionalities by their own, difficulties of their further modification often limit the synthetic usefulness of these methods. Accordingly, our group has previously developed the modifiable silicon-tethered pyridyldiisopropylsilyl (PyDipSi) directing group for the palladium-catalyzed mono C−H oxygenation and halogenation reactions of arenes. However, PyDipSi-group was not efficient for synthetically more appealing double-fold C−H functionalizations reactions. Thus, we have developed a new modifiable pyrimidyldiisopropylsilyl PyrDipSi) directing group that allows for highly efficient diverse C−H functionalizations including double-fold oxygenation-, unsymmetrical oxygenation-, halogenation-, halogenation/oxygenation-, and iterative oxygenation reaction of various arenes. Subsequently, we were able to efficiently convert the PyrDipSi group into valuable functionalities after the C−H functionalization reaction. Construction of an alkyl−arene bond is one of the most challenging synthetic transformations. In recent years, transition metal-catalyzed directing group-assisted C−H alkylation becomes an increasingly important tool toward this goal. However, an efficient and general method for C−H alkylation reaction of arenes using modifiable directing group is still unknown. We successfully developed an efficient C−H alkylation reaction of arenes employing modifiable PyrDipSi group. Consequently, we were able to efficiently transform the PyrDipSi group to important functionalities after the C−H alkylation reaction.