Distinguishing Competing Mechanistic Manifolds for C(acyl)-N Functionalization by a Ni/N-Heterocyclic Carbene...

Area of Science:

• Organometallic Chemistry
• Catalysis
• Synthetic Organic Chemistry

Background:

• Carboxylic acid derivatives, especially carboxamides, are attractive cross-coupling electrophiles due to their abundance and ease of handling.
• Current nickel-catalyzed carboxamide coupling methods often require high catalyst loadings and specific substrate features, limiting broad applicability.
• A lack of detailed mechanistic understanding hinders the development of more efficient and versatile carboxamide functionalization reactions.

Purpose of the Study:

• To elucidate the mechanistic pathways of acylative coupling reactions involving carboxamides catalyzed by the Ni/SIPr system.
• To identify the key nickel species and their roles (Ni(0), Ni(I), Ni(II)) during the catalytic cycle.
• To understand the factors controlling the selectivity between electrophile-first and nucleophile-first reaction mechanisms.

Main Methods:

• Detailed mechanistic investigation using stoichiometric organometallic studies.
• In situ spectroscopic measurements to monitor catalytic intermediates.
• Crossover experiments to probe reaction pathways and identify resting states.

Main Results:

• Demonstrated the accessibility of Ni(0), Ni(I), and Ni(II) resting states under reaction conditions.
• Identified that in situ precatalyst activation can limit overall reaction efficiency.
• Showed that low concentrations of active Ni(0) species favor an electrophile-first (closed-shell) mechanism over a nucleophile-first (open-shell) pathway.

Conclusions:

• The study provides critical experimental insights into the mechanistic intricacies of Ni/SIPr-catalyzed carboxamide cross-coupling.
• Understanding the nature and control of distinct mechanistic pathways is crucial for optimizing these coupling reactions.
• These findings will facilitate the rational design of improved cross-coupling methodologies for carboxamide substrates in fine chemical synthesis.