Palladium-catalyzed C(sp3)-H arylation using pyridinium ylide as a removable directing group.

Direct C–H bond functionalization is a useful synthetic method because it allows formation of C–C bonds directly from C–H bonds. However, directed functionalization of C(sp3)-H bonds is relatively rare. In this thesis, a method for palladium catalyzed, pyridinium ylide-directed C(sp3)-H bond aryaltion by aryl iodides has been developed. The reaction employs Pd(OAc)2 catalyst at 5-10 mol % loading and AgOAc or AgO2CCF3 as a halide-removal agent and hexafluoroisopropanol as solvent. A variety of functional groups, such as methoxy, bromo, ether, ester, aldehyde, trifluoromethoxy and fluoro are tolerated. Monoprotected amino acid ligands were found to significantly promote secondary C(sp3)-H bond arylation. Furthermore, we have also demonstrated that 4-pyrrolidinopyridinium ylide is able to activate methylene C(sp3)-H bonds without addition of external ligands. The pyridinium directing group can be easily removed through N-N bond cleavage using zinc or magnesium metals.