Copper-Catalyzed C(sp³ )-H Amidation: Sterically Driven Primary and Secondary C-H Site-Selectivity

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Undirected C(sp3)-H functionalization typically favors weaker tertiary C-H bonds due to lower bond dissociation energies (BDEs).
• Achieving selective functionalization of stronger primary and secondary C-H bonds over tertiary and benzylic sites remains a significant challenge in organic synthesis.

Purpose of the Study:

• To develop a catalyst system capable of selectively functionalizing primary and secondary C-H bonds over tertiary C-H bonds.
• To investigate the amidation of hydrocarbons using a novel copper catalyst and aroyl azides.

Main Methods:

• Utilized a copper (Cu) catalyst for the amidation of linear and cyclic hydrocarbons.
• Employed aroyl azides (ArC(O)N3) as the amidation reagent.
• Conducted mechanistic studies and Density Functional Theory (DFT) calculations to elucidate the reaction pathway.

Main Results:

• The developed Cu catalyst demonstrated high selectivity for primary and secondary C-H bond amidation over tertiary C-H bonds.
• Mechanistic studies revealed a pathway involving H-atom abstraction by nitrene intermediates, followed by radical capture by copper(II)amide species.
• Successful amidation of hydrocarbons was achieved in the absence of directing groups.

Conclusions:

• A novel Cu catalyst enables selective C-H amidation, prioritizing stronger primary/secondary bonds over weaker tertiary ones.
• The findings provide insights into catalyst design for achieving high site-selectivity in undirected C-H functionalization.
• This work offers a valuable tool for synthesizing functionalized hydrocarbons with enhanced control over regioselectivity.