Novel Sulfonium Reagents for the Modular Synthesis of Spiro[2.3]Hexanes and Heteroatom-Containing Analogues: Synthesis, Application, and Evaluation as Bioisosteres.

ABSTRACT: Molecular scaffolds with a high fraction of sp³-hybridized centers have attracted considerable attention in medicinal chemistry as bioisosteres for a wide range of aromatic and nonstrained heterocycles. In particular, strained spiro-heterocycles have garnered popularity for this purpose, although access to spiro[2.3]hexane analogues is underrepresented. We herein report modular access to nine different spiro[2.3]hexane analogues, including previously underdeveloped 5-oxa-1-azaspiro[2.3]hexane and 1,5-diazaspiro[2.3]hexane motifs. Our synthetic approach leverages novel cyclobutane-, oxetane-, and azetidine-substituted sulfonium salts, which can undergo Johnson-Corey-Chaykovsky type reactions with alkenes, carbonyls and imines to provide access to the desired spiro[2.3]hexanes. He

SUBMITTER: Natho P 

PROVIDER: S-EPMC12851011 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature