Interrupted Nef Reaction of Cyclic Nitronates: Diastereoselective Access to Densely Substituted α-Chloronitroso Compounds

Abstract

The reaction of cyclic nitronic esters (isoxazoline- and 5,6-dihydro-4<i>H</i>-1,2-oxazine-<i>N</i>-oxides) with hydrochloric acid affords geminal chloronitroso compounds bearing a distant hydroxyl group. The reaction is usually diastereoselective, and in some cases stereodivergent formation of isomers at different temperatures is observed. The discovered process represents the first example of an interrupted Nef reaction of nitronic esters. DFT calculations support the initial formation of <i>N</i>,<i>N</i>-bis(oxy)iminium cations (key intermediates in the Nef reaction), which are intercepted by the chloride anion followed by ring opening. The synthetic utility of the resulting functionalized chloronitroso compounds in the Diels-Alder reaction with cyclopentadiene was demonstrated.