Branched-Selective Functionalization of 2-Alkyl Aziridines Through Ni-Catalyzed Dynamic Kinetic Activation

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Aziridines are strained heterocycles with inherent substrate-controlled regioselectivity.
• Developing methods to override this regioselectivity is crucial for accessing diverse nitrogen-containing products.
• Unlocking new synthetic disconnections from aziridines remains a significant challenge.

Purpose of the Study:

• To present a nickel-catalyzed dynamic kinetic activation of 2-alkyl and 2,2-dialkyl aziridines.
• To enable unconventional branched-selective alkyl Heck-type coupling and reductive defluorinative coupling.
• To establish a new reaction framework for remote desaturation of aziridines via ring-opening.

Main Methods:

• Nickel-catalyzed dynamic kinetic activation of aziridines.
• Coupling reactions with styrenes (Heck-type) and trifluoromethyl alkenes (reductive defluorinative).
• Mechanistic studies to elucidate the reaction pathway, including chain-walking processes.

Main Results:

• Achieved branched-selective functionalization of N-adjacent sites in aziridines.
• Demonstrated unprecedented remote desaturation via aziridine ring-opening.
• Identified a rare "self-terminated" chain-walking mechanism responsible for desaturation.
• Generated alkenyl amines with varying chain lengths.

Conclusions:

• Developed a modular and flexible approach for synthesizing diverse alkenyl amine derivatives.
• Overcame inherent regioselectivity limitations in aziridine activation.
• Established a novel catalytic strategy for remote desaturation in organic synthesis.