Asymmetric Organocatalyzed Transfer Hydroxymethylation of Isoindolinones Using Formaldehyde Surrogates

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14160%2F24%3A00136923" target="_blank" >RIV/00216224:14160/24:00136923 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Asymmetric Organocatalyzed Transfer Hydroxymethylation of Isoindolinones Using Formaldehyde Surrogates

Popis výsledku v původním jazyce

We developed a novel process for the asymmetric transfer hydroxymethylation between formaldehyde surrogates and activated isoindolinones. Bench-stable solid formaldehyde surrogates offer many advantages, such as no water presence, better solubility in organic solvents, and superior reactivity over conventionally used aqueous formalin, paraformaldehyde, or trioxane. However, they have never been systematically tested in asymmetric reactions. After the catalysts screening, the selection of the most suitable surrogate, and reaction conditions optimization, the enantioenriched hydroxymethylated adducts were delivered with good to excellent yields (48–96%) and enantiopurities (81:19 – 97:3 e.r). The substrate scope tested on 34 entries showed the considerable generality of the developed asymmetric transformation. A scale-up experiment and multiple enantioselective downstream transformations were also carried out, suggesting the prospective synthetic utility of the products.

Název v anglickém jazyce

Asymmetric Organocatalyzed Transfer Hydroxymethylation of Isoindolinones Using Formaldehyde Surrogates

Popis výsledku anglicky

We developed a novel process for the asymmetric transfer hydroxymethylation between formaldehyde surrogates and activated isoindolinones. Bench-stable solid formaldehyde surrogates offer many advantages, such as no water presence, better solubility in organic solvents, and superior reactivity over conventionally used aqueous formalin, paraformaldehyde, or trioxane. However, they have never been systematically tested in asymmetric reactions. After the catalysts screening, the selection of the most suitable surrogate, and reaction conditions optimization, the enantioenriched hydroxymethylated adducts were delivered with good to excellent yields (48–96%) and enantiopurities (81:19 – 97:3 e.r). The substrate scope tested on 34 entries showed the considerable generality of the developed asymmetric transformation. A scale-up experiment and multiple enantioselective downstream transformations were also carried out, suggesting the prospective synthetic utility of the products.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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