The Design of Molecular Scaffolds for C-H Functionalization

Bond formation via metal-catalyzed selective C–H functionalization is well appreciated and often relies on the directing capability of the substrate. That is, the appropriate positioning of a Lewis basic functional group can present the metal catalyst center at a specific site, enabling activation of otherwise unreactive C–H bonds. The Lewis basicity of alcohols can be exploited to impart directing capabilities allowing for the capacity to induce metalation. For these reasons, free and masked alcohols have been utilized as directing groups for C–H functionalization. Through the design and synthesis of pyridyl- and quinolinyl-based acetals, our group demonstrated the ortho-olefination and arylation of arene alcohols via Pd-catalyzed C–H functionalization. The key highlight of these scaffolds is that they can be easily be attached and removed postfunctionalization in high yielding recovery. Although convenient and synthetically useful, the use of directing groups for C–H functionalization often results in a multistep process from attachment of the directing group to cleavage after functionalization. To improve this process overall, we have designed and synthesized molecular scaffolds allowing us to accomplish this process transiently. That is, we can attach, functionalize, and cleave the directing group in situ netting a one pot process. In addition, we can achieve this process using catalytic directing group.

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