Accessing rare α-heterocyclic aziridines via Brønsted acid-catalyzed Michael addition/annulation : scope, limitations, and mechanism
Abstract
We report an approach to the diastereoselective synthesis of 1,2-disubstituted heterocyclic aziridines. A Brønsted acid-catalyzed conjugate addition of anilines to trisubstituted heterocyclic chloroalkenes provides an intermediate 1,2-chloroamine. Diastereocontrol was found to vary significantly with solvent selection, with computational modelling confirming selective, spontaneous fragmentation in the presence of trace acids, proceeding through a pseudo-cyclic, protonated intermediate and transition state. These chloroamines can then be converted to the aziridine by treatment with LiHMDS with high stereochemical fidelity. This solvent-induced stereochemical enrichment thereby enables an efficient route to rare cis-aziridines with high dr. The scope, limitations, and mechanistic origins of selectivity are also presented
Citation
Hilton , T A , Leach , A , McKay , A P & Watson , A J B 2024 , ' Accessing rare α-heterocyclic aziridines via Brønsted acid-catalyzed Michael addition/annulation : scope, limitations, and mechanism ' , Chemistry - A European Journal , vol. Early View , e202303993 . https://doi.org/10.1002/chem.202303993
Publication
Chemistry - A European Journal
Status
Peer reviewed
ISSN
0947-6539Type
Journal article
Description
Funding: T.A.H. thanks the University of St Andrews for a PhD studentship. A.J.B.W. thanks the Leverhulme Trust for a Research Fellowship (RF-2022-014).Collections
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