Organocatalytic stereoselective cyanosilylation of small ketones
Enzymatic stereoselectivity has typically been unrivalled by most chemical catalysts, especially in the conversion of small substrates. According to the ‘lock-and-key theory’ 1 , 2 , enzymes have confined active sites to accommodate their specific reacting substrates, a feature that is typically abs...
Gespeichert in:
Veröffentlicht in: | Nature (London) 2022-05, Vol.605 (7908), p.84-89 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Enzymatic stereoselectivity has typically been unrivalled by most chemical catalysts, especially in the conversion of small substrates. According to the ‘lock-and-key theory’
1
,
2
, enzymes have confined active sites to accommodate their specific reacting substrates, a feature that is typically absent from chemical catalysts. An interesting case in this context is the formation of cyanohydrins from ketones and HCN, as this reaction can be catalysed by various classes of catalysts, including biological, inorganic and organic ones
3
–
7
. We now report the development of broadly applicable confined organocatalysts for the highly enantioselective cyanosilylation of aromatic and aliphatic ketones, including the challenging 2-butanone. The selectivity (98:2 enantiomeric ratio (e.r.)) obtained towards its pharmaceutically relevant product is unmatched by any other catalyst class, including engineered biocatalysts. Our results indicate that confined chemical catalysts can be designed that are as selective as enzymes in converting small, unbiased substrates, while still providing a broad scope.
The development of confined organocatalysts for the enantioselective cyanosilylation of small, unbiased substrates, including 2-butanone, is shown to lead to catalysts that are as selective as enzymes, with excellent levels of control. |
---|---|
ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/s41586-022-04531-5 |