Asymmetric Organocatalyzed Transfer Hydroxymethylation of Isoindolinones Using Formaldehyde Surrogates
| Authors | |
|---|---|
| Year of publication | 2024 |
| Type | Article in Periodical |
| Magazine / Source | Organic Letters |
| MU Faculty or unit | |
| 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: |