Abstract
This study provides a comprehensive mechanistic understanding of asymmetric THF α-O-arylation via Ni photochemical catalysis, leveraging enantioinduction data to refine
the reaction pathway. Originally reported in a racemic fashion by Molander and Doyle,
this transformation was re-examined using chiral bis(oxazoline) ligands, revealing
distinct enantioselectivity trends depending on the halogen present in the aryl halide
and Ni pre-catalyst. Stoichiometric experiments demonstrated that the Ni(II) oxidative
addition complex is primarily responsible for trapping the THF radical, while multivariate
linear regression modeling confirmed that the halide remains coordinated during the
enantiodetermining step. Time-course experiments uncovered an alternative initial
pathway when Ni(0) was used as the pre-catalyst, which ultimately converged to the
main Ni(II) pathway. EPR analysis further revealed rapid comproportionation between
Ni(0) and Ni(II), forming Ni(I) species that engage in radical trapping at early stages,
accounting for the observed reactivity differences. By integrating enantioselectivity
data with experimental techniques such as EPR spectroscopy, this study establishes
enantioinduction analysis as a powerful tool for mechanistic investigations in Ni
photochemical catalysis. The insights gained not only refine our understanding of
this transformation, but also provide a framework for probing similar Ni/Ir dual photocatalytic
systems.
1 Introduction
2 Enantioselectivity Data Highlights a Complex Mechanistic Scenario
3 Probing the Predominant Pathway with Stoichiometric Experiments
4 MLR Modeling to Understand the Halogen Effect on the Enantioinduction
5 Proposed Prevalent Mechanism
6 Initiation with Ni(0) Precatalyst
7 Conclusion
Key words
nickel - catalysis - asymmetric catalysis - organometallic reagents - free radicals
