Modular Synthesis of Dihydropyranones through Cyclization and Organometallic Functionalization

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F25%3A00643874" target="_blank" >RIV/61389030:_____/25:00643874 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/25:73634642

Výsledek na webu

<a href="https://doi.org/10.1002/ejoc.202500848" target="_blank" >https://doi.org/10.1002/ejoc.202500848</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ejoc.202500848" target="_blank" >10.1002/ejoc.202500848</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Modular Synthesis of Dihydropyranones through Cyclization and Organometallic Functionalization

Popis výsledku v původním jazyce

Dihydropyranones are key structural motifs in biologically active polyketides. We report a reproducible and scalable method for synthesizing 3-methoxy-4,5-dihydropyran-2-ones (MeO-DHP-2-ones) via base-promoted cyclization of hydroxy alkynes. Mechanistic and computational studies revealed that water content and reaction time critically influence lactonization efficiency. Two optimized protocols – using potassium carbonate (K2CO3) or in situ generated sodium methoxide (MeONa) – enabled consistent yields across multiple substrates. Cyclization in deuterated methanol provided deuterium-enriched DHP-2-one scaffolds with high isotopic incorporation, valuable for mechanistic and medicinal applications. The transformation of DHP-2-ones into 4,5-dihydropyran-4-ones (DHP-4-ones) was achieved via organometallic addition followed by a tailored workup involving aqueous hydrochloric acid and boron trifluoride diethyl etherate (BF3·OEt2). This protocol proved robust and scalable, compatible with both organolithium and organomagnesium reagents, although the latter afforded lower yields. Mechanistic analysis highlighted key steps including hemiacetal formation, oxonium activation, and controlled hydrolysis. The methodology enables multigram-scale preparation of both DHP-2-one and DHP-4-one scaffolds and provides a streamlined route toward spiroacetal precursors.

Název v anglickém jazyce

Modular Synthesis of Dihydropyranones through Cyclization and Organometallic Functionalization

Popis výsledku anglicky

Dihydropyranones are key structural motifs in biologically active polyketides. We report a reproducible and scalable method for synthesizing 3-methoxy-4,5-dihydropyran-2-ones (MeO-DHP-2-ones) via base-promoted cyclization of hydroxy alkynes. Mechanistic and computational studies revealed that water content and reaction time critically influence lactonization efficiency. Two optimized protocols – using potassium carbonate (K2CO3) or in situ generated sodium methoxide (MeONa) – enabled consistent yields across multiple substrates. Cyclization in deuterated methanol provided deuterium-enriched DHP-2-one scaffolds with high isotopic incorporation, valuable for mechanistic and medicinal applications. The transformation of DHP-2-ones into 4,5-dihydropyran-4-ones (DHP-4-ones) was achieved via organometallic addition followed by a tailored workup involving aqueous hydrochloric acid and boron trifluoride diethyl etherate (BF3·OEt2). This protocol proved robust and scalable, compatible with both organolithium and organomagnesium reagents, although the latter afforded lower yields. Mechanistic analysis highlighted key steps including hemiacetal formation, oxonium activation, and controlled hydrolysis. The methodology enables multigram-scale preparation of both DHP-2-one and DHP-4-one scaffolds and provides a streamlined route toward spiroacetal precursors.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Organic Chemistry

ISSN

1434-193X

e-ISSN

1099-0690

Svazek periodika

28

Číslo periodika v rámci svazku

48

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

7

Strana od-do

e202500848

Kód UT WoS článku

001609848800001

EID výsledku v databázi Scopus

2-s2.0-105021262425