Nitronate-aryne cycloaddition as a concise route to stereochemically complex fused benzisoxazolines and amino alcohols

Abstract

The reaction of cyclic nitronates (isoxazoline N-oxides and 5,6-dihydro-4H-1,2-oxazine N-oxides) with Kobayashi's aryne precursors affords tricyclic benzene-fused nitroso acetals as a result of [3 + 2]-cycloaddition. The process is regio- and stereoselective in most cases and produces the target cycloadducts possessing up to four contiguous stereogenic centers. These nitroso acetals were shown to be convenient precursors of valuable polysubstituted aminodiols through catalytic hydrogenolysis of the N–O bonds. Also, the action of protic acids resulted in an unusual fragmentation of the cyclic nitroso acetal moiety through heterolytic N–O bond cleavage and Beckmann-type reaction. Using this acid-mediated reaction, the synthesis of a hitherto unknown hexahydrobenzo[4,5]isoxazolo[2,3-a]azepine scaffold was accomplished.