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

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-β3-amino acid esters in a single step.

Recent Advances in the Synthesis and Chemistry of Nitronates

Due to their availability and versatile reactivity, nitronates have become important building blocks in the stereoselective synthesis of bioactive molecules. This short review provides a summary of recent developments on the synthesis, chemistry and applications of O-alkyl and O-silyl nitronates.1 Introduction2 Approaches to the Synthesis of Nitronates2.1 Synthesis of Six-Membered Cyclic Nitronates2.1.1 Formal [4+2] Approaches2.1.2 Formal [3+3] Approaches2.1.3 Other Approaches2.2 Synthesis of Five-Membered Cyclic Nitronates2.2.1 Formal [3+2] Approaches2.2.2 Formal [4+1] Approaches2.2.3 Oxidation Approaches3 Chemistry of Nitronates3.1 Nitronates as α-C-Nucleophiles3.2 Nitronates as α-C-Electrophiles3.3 Nitronates in [3+n]-Annulation Reactions3.4 Reactions Involving the β-Carbon Atom of Nitronates3.5 Miscellaneous Transformations4 Conclusion