Mild metal-catalyzed C-H activation: examples and concepts

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Direct functionalization of non-activated carbon-hydrogen (C-H) bonds offers superior atom and step economy.
• Traditional C-H activation often requires harsh conditions, limiting its synthetic utility.
• Recent mechanistic insights have driven the development of milder C-H activation protocols.

Purpose of the Study:

• To review the state-of-the-art in mild C-H activation transformations.
• To highlight C-H activation methods developed since 2011 that operate under mild conditions.
• To provide a conceptual overview of strategies enabling milder C-H functionalization.

Main Methods:

• Literature review of C-H activation transformations reported since 2011.
• Focus on reactions proceeding at or below ambient temperature.
• Analysis of protocols avoiding strong acids, bases, or oxidants.

Main Results:

• Identification of numerous C-H activation reactions that proceed under mild conditions.
• Demonstration of improved functional group tolerance and selectivity in these mild protocols.
• Compilation of key strategies enabling these advancements.

Conclusions:

• Significant progress has been made in developing mild C-H activation methods.
• These milder methods enhance the applicability of C-H functionalization in complex molecule synthesis.
• The review aims to inspire future research in developing novel, mild C-H transformations.