Dynamics in Catalytic Asymmetric Diastereoconvergent (3+2) Cycloadditions with Isomerizable Nitrones and α-Keto Ester Enolates

Reaction design in asymmetric catalysis has traditionally been predicated on a structurally robust scaffold in both substrates and catalysts, to reduce the number of possible diastereomeric transition states. Herein, we present the stereo-chemical dynamics in the Ni(II)-catalyzed diastereoconvergent (3 + 2) cycloadditions of isomerizable nitrile-conjugated nitrones with alpha-keto ester enolates. Even in the presence of multiple equilibrating species, the catalytic protocol displays a wide substrate scope to access a range of CN-containing building blocks bearing adjacent stereocenters with high enantio- and diastereoselectivities. Our computational investigations suggest that the enantioselectivity is governed in the deprotonation process to form (Z)-Ni-enolates, while the unique syn addition is mainly controlled by weak noncovalent bonding interactions between the nitrone and ligand.

Automated summary

This study explores stereo-chemical dynamics in Ni(II)-catalyzed reactions, demonstrating a wide substrate scope and high selectivity in forming CN-containing building blocks with adjacent stereocenters. Computational investigations indicate that enantioselectivity is governed by the deprotonation process, while unique syn addition is controlled by noncovalent interactions between the nitrone and ligand.