Intermolecular Aminocarbonylation of Alkenes using Concerted Cycloadditions of Iminoisocyanates

The
aminocarbonylation of alkenes is a powerful method for accessing
the β-amino carbonyl motif that remains underdeveloped. Herein,
the development of intermolecular aminocarbonylation reactivity of
iminoisocyanates with alkenes is presented. This includes the discovery
of a fluorenone-derived reagent, which was effective for many alkene
classes and facilitated derivatization. Electron-rich substrates were
most reactive, and this indicated that the LUMO of the iminoisocyanate
is reacting with the HOMO of the alkene. Computational and experimental
results support a concerted asynchronous [3 + 2] cycloaddition involving
an iminoisocyanate, which was observed for the first time by FTIR
under the reaction conditions. The products of this reaction are complex
azomethine imines, which are precursors to valuable β-amino
carbonyl compounds such as β-amino amides and esters, pyrazolones,
and bicyclic pyrazolidinones. A kinetic resolution of the azomethine
imines by enantioselective reduction (s = 13–43)
allows access to enantioenriched products. Overall, this work provides
a new tool to convert alkenes into β-amino carbonyl compounds.