Harnessing the ambiphilicity of silyl nitronates in a catalytic asymmetric approach to aliphatic β3-amino acids

• Published in: Nature catalysis Vol. 4; no. 12; pp. 1043 - 1049
• Main Authors: Das, Sayantani, Mitschke, Benjamin, De, Chandra Kanta, Harden, Ingolf, Bistoni, Giovanni, List, Benjamin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-12-2021
• Subjects: 639/638/403/933; 639/638/77/883; 639/638/77/889; Catalysis; Chemistry; Chemistry and Materials Science
• ISSN: 2520-1158; 2520-1158
• DOI: 10.1038/s41929-021-00714-x

Nitronate anions, formally generated by α-deprotonating the corresponding nitroalkanes, are highly nucleophilic and versatile intermediates in many carbon–carbon bond-forming reactions. In contrast, the corresponding silyl nitronates are ambiphilic and react, at the same carbon atom, with both electrophiles and nucleophiles. However, while their nucleophilicity has been well exploited in catalytic enantioselective reactions with imines and aldehydes, utilizing the electrophilicity of silyl nitronates in asymmetric synthesis has remained elusive. Here we report the facile, efficient and general reactivity of readily available silyl nitronates with silyl ketene acetals, catalysed by highly Lewis-acidic and confined silylium imidodiphosphorimidate catalysts. The products of this reaction, so-called nitroso acetals, are obtained in excellent enantioselectivity and can be easily converted into
N
-Boc-β
3
-amino acid esters in a single step.
Utilizing the electrophilicity of ambiphilic silyl nitronates in asymmetric synthesis has remained elusive. Now, silylium-based Lewis acids are used for their activation, achieving the catalytic asymmetric nucleophilic addition of silyl ketene acetals to silyl nitronates for the synthesis of β
3
-amino acids.