Pd-catalysed C-H functionalisation of free carboxylic acids

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Carboxylic acid groups are prevalent in pharmaceuticals and agrochemicals.
• Their coordinating ability in Pd-catalyzed C-H functionalization has been historically masked by directing groups.
• The roles of carboxylic acids as additives and steric inducers have been largely neglected.

Purpose of the Study:

• To systematically review the diverse roles of carboxylic acids in Pd-catalyzed C-H activation, excluding additive and steric effects.
• To highlight their application in proximal and distal C-H activation relevant to drug discovery and agrochemical development.
• To provide mechanistic insights and recent strategies for future research.

Main Methods:

• Literature review of Pd-catalyzed C-H functionalization reactions involving free carboxylic acids.
• Systematic analysis of carboxylic acid coordination and directing effects.
• Discussion of mechanistic pathways and recent synthetic advancements.

Main Results:

• Carboxylic acids play a crucial, often underestimated, role in directing Pd-catalyzed C-H activation reactions.
• Their coordinating ability enables both proximal and distal C-H functionalization.
• Recent strategies have emerged to leverage these effects in complex molecule synthesis.

Conclusions:

• Carboxylic acids are versatile directing groups in Pd-catalyzed C-H functionalization.
• Understanding their coordinating role is key for developing efficient synthetic methodologies in pharma and agrochem.
• This review provides a foundation for future research in this area.