Synthesis of Multisubstituted Arenes via PyrDipSi-Directed Unsymmetrical Iterative C-H Functionalizations

A modifiable or removable pyrimidyldiisopropylsilyl (PyrDipSi) directing group for double-fold symmetrical and unsymmetrical C-H functionalizations of arenes has been developed. The PyrDipSi directing group can be efficiently installed on arenes via the Rh-catalyzed cross-coupling reaction I of an aryl iodide with 2-(diisopropylsilyl)pyrimidine (PyrDip-SiH). This directing group allows for a highly efficient Pd-catalyzed C-H oxygenation and halogenation reaction of various arenes to produce a variety of symmetrically and unsymmetrically substituted arenes, including resorcinols, m-halophenols, and 1,3-dihaloarenes. Importantly, the PyrDipSi group can easily be removed or efficiently converted into valuable functionalities, which opens an access to densely substituted arene products from aryl iodides. Hence, the generality of this strategy was highlighted by the synthesis of up to hexasubstituted arene products from simple iodobenzene via iterative C-H functionalization reactions.