Asymmetric Organocatalyzed Transfer Hydroxymethylation of Isoindolinones Using Formaldehyde Surrogates

Warning

This publication doesn't include Faculty of Education. It includes Faculty of Pharmacy. Official publication website can be found on muni.cz.
Authors

ŠVESTKA David BOBÁĽ Pavel OTEVŘEL Jan WASER Mario

Year of publication 2024
Type Article in Periodical
Magazine / Source Organic Letters
MU Faculty or unit

Faculty of Pharmacy

Citation
Web https://pubs.acs.org/doi/10.1021/acs.orglett.4c00818?src=getftr
Doi http://dx.doi.org/10.1021/acs.orglett.4c00818
Keywords ALDOL REACTIONENANTIOSELECTIVE HYDROXYMETHYLATIONALPHA-HYDROXYMETHYLATIONOXINDOLESALDEHYDESCHEMISTRYTOOL
Description The piperidine-based Takemoto catalyst has been successfully employed in a novel asymmetric transfer hydroxymethylation of activated isoindolinones, allowing us to prepare the enantioenriched hydroxymethylated adducts in good to excellent yields (48–96%) and enantiopurities (81:19–97:3 e.r.). To increase the reaction rate without compromising the selectivity, carefully optimized formaldehyde surrogates were employed, providing a convenient source of anhydrous formaldehyde with a base-triggered release. The substrate scope, including 34 entries, showed the considerable generality of the asymmetric transformation, and most entries exhibited complete conversions in 24–48 h. A scale-up experiment and multiple enantioselective downstream transformations were also carried out, suggesting the prospective synthetic utility of the products.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.