Intramolecular [4+2] Cycloadditions of iminoacetonitriles: A New Class of Azadienophiles for Hetero Diels-Alder Reactions

A recent paper from Danheiser et al describes the preparation and intramolecular Diels-Alder reactions of iminoacetonitriles, a class of electron deficient imines whose cycloadditions have not previously been described.  As a result iminoacetonitriles can be considered as valuable building blocks for the synthesis of nitrogen heterocycles.  Iminoacetonitriles are readily prepared by a Mitsunobu reaction between an alcohol and HN(Tf)CH₂CN, followed by base catalysed elimination of trifluoromethane sulphinate.  Cycloadditions are carried out at 85-120oC in toluene in a sealed tube using BHT as a radical scavenger.  E- and Z-imines seem to react at similar rates, in most cases giving a product with an exo-oriented cyano group.  It is believed that the initially formed epimeric cycloadducts equilibrate to give the axial cyano isomer, which is favoured as a result of the “a–amino nitrile anomeric effect”.  (J. Am. Chem. Soc., 2003, 125, 4970-4971).