Amide activation: an emerging tool for chemoselective synthesis.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Carboxamides possess a stabilized electrophilic carbonyl carbon, leading to lower reactivity compared to esters or acid chlorides.
• This reduced reactivity has historically limited the perception of amides as versatile synthetic handles.
• Despite this, recent decades have seen significant research into selective amide activation.

Purpose of the Study:

• To review the historical development of electrophilic amide activation.
• To highlight the synthetic applications of activated amides, particularly in natural product synthesis.
• To showcase the potential of amide activation strategies in modern organic synthesis.

Main Methods:

• Literature review of published research on amide activation.
• Analysis of synthetic transformations employing electrophilic amide activation.
• Case studies focusing on natural product synthesis utilizing these methods.

Main Results:

• Electrophilic activation strategies enable powerful chemical transformations of amides under mild conditions.
• Amide activation has proven valuable in the synthesis of complex natural products.
• A growing body of research demonstrates the utility and potential of these methods.

Conclusions:

• Electrophilic amide activation overcomes the inherent low reactivity of amides.
• These methods offer significant advantages for constructing complex molecular architectures.
• Amide activation is a key strategy with expanding applications in synthetic organic chemistry.