Inverting Steric Effects: Using "Attractive" Noncovalent Interactions To Direct Silver-Catalyzed Nitrene Transfer

Area of Science:

• Catalysis
• Organic Chemistry
• Computational Chemistry

Background:

• Nitrene transfer (NT) reactions are vital for C-H amination, crucial in pharmaceuticals and chemicals.
• Transition-metal catalysts are developed for selective NT, but understanding site-selectivity remains challenging.

Purpose of the Study:

• Investigate the selectivity of Ag(tpa)OTf in activating α-conjugated C-H bonds over tertiary alkyl C(sp3)-H bonds.
• Elucidate the role of noncovalent interactions (NCIs) in directing C-H amination selectivity.
• Apply insights to optimize reactions and design novel catalysts.

Main Methods:

• Experimental studies to probe catalyst-substrate interactions.
• Computational modeling (DFT) to analyze transition states and reaction pathways.
• Development of a predictive model based on Hess's law for selectivity.

Main Results:

• Ag(tpa)OTf preferentially activates α-conjugated C-H bonds.
• Noncovalent interactions, including π···π and Ag···π, significantly influence selectivity.
• Computational studies confirm the role of NCIs in stabilizing directed transition states.
• A Hess's law-based approach accurately predicts selectivity for new substrates.

Conclusions:

• Noncovalent interactions are key determinants of site-selectivity in Ag-catalyzed NT reactions.
• Understanding these interactions facilitates rational catalyst design for C-H functionalization.
• The findings provide a framework for developing selective C-H amination strategies.