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

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.