The Tandem Cope-type Hydroamination/[2,3]-rearrangement Sequence: A Strategy To Favor The Formation Of Intermolecular Hydroamination Productsand Enable Difficult Cyclizations

摘要

Given the prevalence and diversity of nitrogen-containing motifs in bioactive molecules, the development of efficient C-N bond-forming reactions is of paramount importance. The addition of a N-H bond across electron-rich, unsaturated C-C bonds stands out as one of the simplest and most desirable synthetic transformations for which no general solution currently exists. While significant progress has been achieved (primarily through transition metal catalysis), issues such as limited reaction scope, functional group compatibility, and challenges linked to unfavorable thermodynamics for reactions of alkenes continue to stimulate research directed at hydroamination reactivity. In recent efforts directed toward the development of metal-free alternatives, we reported that intermolecular reactions of hydroxylamine (aq. NH_2OH) and N-alkylhy-droxylamines with alkenes and alkynes can be performed simply upon heating at 95-140 ℃. Under our conditions, alcoholic solvents mediate a facile bimolecular proton transfer of the N-oxide intermediate and enable the efficient formation of the alkene hydroamination products.