Development of diastereoconvergent (3 + 2) cycloadditions

June 10, 2021

From "lock and key" to "induced fit"

A research team of RIKEN CSRS developed Ni-catalyzed diastereoconvergent (3 + 2) cycloadditions of isomerizable nitrones with α-keto ester enolates.

Inspired by induced-fit or conformational selection in enzymes, the research team aimed to explore an artificial synthetic workflow, in which both the catalyst and substrates are dynamically responsive in the transitions state. This reaction involves rather complex pathways compared with classical catalytic reactions using structurally constrained reactants. However, the developed catalytic protocol is operationally simple to selectively provide desired heterocycles with three contiguous stereocenters. Furthermore, experimental and computational investigations show the plausible mechanism to explain how the nickel complex selectively produces the major product even in the presence of multiple equilibrating species.

Insight into the stereochemical dynamics can be extrapolated to other equilibrating substrates, and it should contribute to access to highly functionalized chiral building blocks containing adjacent stereocenters.

Original article
Journal of the American Chemical Society doi:10.1021/jacs.1c02833
T. Ezawa, Y. Sohtome, D. Hashizume, M. Adachi, M. Akakabe, H. Koshino, M. Sodeoka,
"Dynamics in Catalytic Asymmetric Diastereoconvergent (3 + 2) Cycloadditions with Isomerizable Nitrones and α-Keto Ester Enolates".
Yoshihiro Sohtome; Senior Research Scientist
Mikiko Sodeoka; Group Director
Catalysis and Integrated Research Group