Rapid Sp-Enriched Scaffold Generation Via a Selective Aziridine Amide Ring-Opening Reaction

Overview

Journal J Org Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2024 Feb 10

PMID 38340064

Authors

Masahito Abe

Jeremy S Coleman

Christopher C Presley

Nathan D Schley

Craig W Lindsley

Affiliations

Soon will be listed here.

Abstract

Sp-enriched small molecules play a critical role in developing drug candidates. While designing analogues with greater sp character, a methodology utilizing a less explored cyclic-aziridine amide ring-opening reaction to generate sp-enriched scaffolds has been developed and reported. This methodology enables rapid access to substructures with higher fsp values, attracting greater attention within the past few decades. The reaction exhibits a wide reaction scope, featuring a highly sterically hindered phenolic ether, thiophenolic ethers, protected aniline formations, and aliphatic/heteroaromatic ring-containing aziridine amides as substrates. Additionally, this reaction provides access to congested tertiary ether formations through regioselective transformation, applicable to an extensive range of drug discovery targets, construction of complex small molecules, and natural product syntheses. The scaffolds developed show improved physicochemical properties.

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