The Synthesis of 2,5-Dioxaspiro[3.4]octane Building Blocks: Three-Dimensional Spirocyclic Analogs of 1,4-Dioxanes

A ring-closing metathesis (RCM) strategy was employed for the synthesis of spirooxetane compounds with a tetrahydrofuran (THF) core. The approach proposed relied on the preparation of an unsaturated spirooxetane from vinyl oxetanol. The reaction sequence involved the NaH-mediated О-alkylation with m...

Full description

Saved in:
Bibliographic Details
Main Authors: Bohdan V. Vashchenko, Eduard V. Litskan
Format: Article
Language:English
Published: National University of Pharmacy (Kharkiv) 2025-04-01
Series:Журнал органічної та фармацевтичної хімії
Subjects:
Online Access:https://ophcj.nuph.edu.ua/article/view/324901
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A ring-closing metathesis (RCM) strategy was employed for the synthesis of spirooxetane compounds with a tetrahydrofuran (THF) core. The approach proposed relied on the preparation of an unsaturated spirooxetane from vinyl oxetanol. The reaction sequence involved the NaH-mediated О-alkylation with methyl 2-(bromomethyl)acrylate in the presence of TBAI. The subsequent RCM reaction using the Grubbs’ II catalyst gave the dihydrofuran carboxylate with a yield of 70 %. The hydrogenation under high-pressure conditions using a Pearlman’s catalyst made it possible to obtain the saturated THF-derived carboxylate, which was then subjected to alkaline hydrolysis to give a stable lithium carboxylate. The corresponding alcohol obtained via LiAlH4-mediated reduction of the ester was oxidized to the corresponding aldehyde using DMP. The alcohol was further converted into a mesylate serving as a precursor for the corresponding amine and bromide. The set of dioxane analogs proposed can serve as promising building blocks readily available on a multigram scale for the scientific community.
ISSN:2308-8303
2518-1548