Bifunctional Activation in Ni(II)-Diamine-Acetate Catalysis: Structural and Mechanistic Insights

Since Shibasaki introduced the concept of asymmetric metal bifunctional activation, the integration of distinct activation modes within a single chiral catalyst has become a central strategy in asymmetric catalysis. However, despite the remarkable advances in computational chemistry, a precise mechanistic understanding of the origins of high reactivity and selectivity remains a critical bottleneck. In this Account, we present our mechanistic case studies on the catalytic asymmetric (3 + 2) cycloaddition of -keto esters with nitrones regulated by a Ni(II)diamine-acetate complex. By characterizing the distorted ground-state structures of the complex, we reveal a new bifunctional activation motif that unifies inner-sphere nucleophilic activation from the Ni(II)-enolate core with outer-sphere electrophile activation via ligand N-H hydrogen bonding. Combining experimental results with computational studies on nitrone reactions, we construct a coherent mechanistic framework that connects structural dynamics, coordination modes, and the emergence of both reactivity and stereoselectivity. These mechanistic interpretations account for both the enantioselectivity and unique dynamic diastereoselectivity, offering a foundation for the future design of asymmetric metal bifunctional catalysts. 1 Introduction 2 Ground-State Analysis of Ni(II)-Diamine-Acetate 3 Stereoselectivity in (3 + 2)