Distal C(sp³)-H Amidation via Ind*Rh^III Catalyzed Nitrene Transfer.

Area of Science:

• Organometallic Chemistry
• Catalysis
• Organic Synthesis

Background:

• Direct C-H functionalization offers a powerful strategy for streamlining synthetic routes.
• Amides are versatile functional groups, but their direct incorporation via C-H activation remains challenging.
• Indium-Rhodium (Ind*Rh^III) catalysis presents a novel avenue for C-H functionalization.

Purpose of the Study:

• To explore Ind*Rh^III catalyzed distal amidation of C(sp³)-H sites using amides as directing groups.
• To enhance catalytic activity for functionalizing primary and secondary β-C(sp³)-H bonds.
• To demonstrate the utility in late-stage functionalization and polymer modification.

Main Methods:

• Utilized an Ind*Rh^III complex in conjunction with a 2-pyridone ligand.
• Employed nitrene transfer catalysis for C-H amidation.
• Applied the methodology to pharmaceutical derivatives and polymer side chains.

Main Results:

• Achieved enhanced catalytic activity for distal amidation of C(sp³)-H sites.
• Successfully functionalized both primary and secondary β-C(sp³)-H bonds.
• Demonstrated late-stage functionalization of drug molecules and post-polymerization modification of poly(2-alkyl-2-oxazoline)s and poly(2-alkyl-2-oxazines).

Conclusions:

• Ind*Rh^III catalysis provides an efficient method for distal C-H amidation.
• The developed method broadens the scope of late-stage functionalization and polymer modification.
• This catalysis enables the synthesis of complex molecules and functionalized polymers.