Carbon-Carbon Bond Cleavage for Late-Stage Functionalization

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Late-stage functionalization (LSF) is crucial for modifying complex molecules like natural products and drugs.
• Efficient synthesis of diverse chemical libraries is vital for drug discovery.
• Carbon-carbon (C-C) bond activation offers a powerful strategy for molecular editing, surpassing traditional C-C bond construction.

Purpose of the Study:

• To review recent strategies for carbon-carbon bond cleavage in the context of late-stage functionalization.
• To provide a comprehensive overview of selective C-C bond cleavage methods.
• To highlight the application of these methods in drug discovery and chemical biology.

Main Methods:

• Focus on catalytic approaches, including transition metal and organocatalysis.
• Discussion of C-C bond cleavage across various bond types: C-C(sp), C-C(sp2), C-C(sp3) single bonds, double bonds, and triple bonds.
• Inclusion of ring-opening reactions involving C-C bond cleavage in small rings (3- to 6-membered).

Main Results:

• Recent advancements in selective C-C bond activation strategies have been compiled.
• The applicability of these methods to late-stage functionalization is demonstrated.
• Exemplar applications in complex bioactive molecules and drug discovery are showcased.

Conclusions:

• Selective carbon-carbon bond cleavage is a key enabler for late-stage functionalization.
• These methods significantly impact the efficiency and scope of drug discovery and chemical biology.
• Future research directions in late-stage C-C bond functionalization are proposed.