Naslov
Organocatalytic stereoselective synthesis of β,β- diaryl ketones with β-tetrasubstituted stereogenic center

Autori
Matišić, Mateja ; Gredičak, Matija

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
ESOC 2021 European Symposium on Organic Chemistry : Virtual Mini Symposium

Mjesto i datum
Online, 05.07.2021. - 06.07.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Organocatalysis ; Stereoselective synthesis ; β, β-diaryl ketones

Sažetak
Organocatalytic stereoselective synthesis of β, β- diaryl ketones with β-tetrasubstituted stereogenic center incorporated into isoindolinone moiety is described. Gem-diaryl-alkyl isoindolinone derivatives are key skeletons present in numerous naturally occurring and synthetic biologically active molecules. In this context, optically active isoindolinone-derived β, β-diaryl ketones show great potential as the synthetic intermediates of diarylalkyl-containing molecules due to the versatile transformations of the carbonyl and lactame group [1]. The enantioselective Mannich-type reactions of isoindolinone-derived ketimines with carbon nucleophiles – α-azoesters [2], cyclohexenone [3], N-acetyl enamides [4] and difluoroenoxysilanes [5] – provide a direct access to these compounds bearing a chiral tetrasubstituted stereogenic center. The main drawbacks of these methodologies are inherent restrictions for the construction of vicinal α, β-stereogenic centers, including the control of its diastereo- and enantioselectivity. Herein we report a chiral Brønsted acid-catalyzed stereoselective addition of ketones to benzophenone-ketimines for the construction of isoindolinone-derivedβ, β-diaryl ketones comprising tetrasubstituted stereogenic center. Key to the success of this transformation is the generation of reactive N-acyl ketiminuim species in situ from 3-hydroxy isoindolinones mediated by (R)-TRIP catalyst (Scheme 1). A broad range of ketimines and ketones afforded isoindolinone derivatives comprisingβ-tetrasubstituted center of chirality in high yields and enantioselectivities. The methodology was successfully employed in the construction of α, β- vicinal stereogenic centers in high diastereomeric and enantiomeric ratios. The mechanism of stereochemical induction will also be discussed.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA