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

Bohdan V. Vashchenko; Eduard V. Litskan

doi:10.24959/ophcj.25.324901

Authors

Bohdan V. Vashchenko Taras Shevchenko National University of Kyiv; Enamine Ltd, Ukraine https://orcid.org/0000-0003-4575-2065
Eduard V. Litskan Taras Shevchenko National University of Kyiv; Enamine Ltd, Ukraine https://orcid.org/0009-0003-8026-3467

DOI:

https://doi.org/10.24959/ophcj.25.324901

Keywords:

oxetanes, dioxanes, spirocycles, building blocks

Abstract

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.

Supporting Agency

The work was funded by the internal Enamine grant.

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