Strategic Synthesis of γ-Nitroketones between Nitroalkanes and Cyclopropanols: Harnessing Free-Radical Nucleophilic Substitution for Chemical Innovation

Abstract

The alkylation of nitro compounds is an efficient technique to augment molecular complexity, as exemplified by the Henry reaction and Michael addition involving sp²-hybridized carbon. However, a challenge arises in the alkylation of nitro compounds with sp³-hybridized carbon due to competing nonproductive O-alkylation. In this study, we have developed a manganese-promoted oxidative alkylation of nitroalkanes using cyclopropyl alcohols via a solvent-caged free-radical nucleophilic substitution pathway. This process yields a variety of γ-nitroketones, including sterically hindered tertiary nitroalkanes, thereby introducing a novel approach for the C-alkylation of nitroalkanes. Subsequent reduction facilitates the efficient synthesis of pyrroline and pyrrolidine derivatives.