Work

Catalytic Enantioselective Aziridination of Z -Disubstituted Alkenes with Aspartyl β-Turn-Based Dirhodium(II) Metallopeptides and Assessment of Catalyst Scaffold Versatility

Year: 2026

Type: article

Abstract: We report an enantioselective aziridination of open-chain Z-disubstituted alkenes, enabled by a dirhodium(II) metallopeptide featuring finely tuned, β-turn-biased peptidyl ligands. This method affords cis-aziridines in up to 99:1 er and exhibits broad tolerance toward diverse aryl substitution patterns and peripheral functional groups. In conjunction, we explore a data science model that uncovers patterns in molecular features that reflect enantioselectivity across two nitrene transfer reactions catalyzed by dirhodium(II) metallopeptides: the aziridination reported here and a related benzylic amination reaction. This model is trained on molecular descriptors of both catalysts and substrates and used to interpret the differences between the two reactions. By linking a new synthetic methodology to cross-reaction, data science-driven modeling, this study offers both an efficient route to valuable aziridine scaffolds and a framework for analyzing enantioinduction across mechanistically diverse transformations.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.6c10875

Authors: Melissa Pighetti, Beck R. Miller, Annika K. Ehrlacher, Matthew S. Sigman, Scott J. Miller

Institutions: Yale University, University of Utah

Language: English

Topic: Synthesis and Catalytic Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Yale University, National Institutes of Health, National Institute of General Medical Sciences

Awards: G1547749889, G2525013255, G2921725335, G4280404505, G5925915286