Site-predictable and chemoselective C–H bond functionalization
reactions offer synthetically powerful strategies for the step-economic
diversification of both feedstock and fine chemicals. Many transition-metal-catalyzed
methods have emerged for the selective activation and functionalization
of C–H bonds. However, challenges of regio- and chemoselectivity
have emerged with application to highly complex molecules bearing
significant functional group density and diversity. As molecular complexity
increases within molecular structures the risks of catalyst intolerance
and limited applicability grow with the number of functional groups
and potentially Lewis basic heteroatoms. Given the abundance of C–H
bonds within highly complex and already diversified molecules such
as pharmaceuticals, natural products, and materials, design and selection
of reaction conditions and tolerant catalysts has proved critical
for successful direct functionalization. As such, innovations within
transition-metal-catalyzed C–H bond functionalization for the
direct formation of carbon–carbon bonds have been discovered
and developed to overcome these challenges and limitations. This review
highlights progress made for the direct metal-catalyzed C–C
bond forming reactions including alkylation, methylation, arylation,
and olefination of C–H bonds within complex targets.