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...

3-Halo-5,6-dihydro-4H-1,2-oxazine N-oxides as synthetic equivalents of unsaturated nitrile oxides in the [3 + 2]-cycloaddition with arynes: synthesis of substituted 3-vinyl-1,2-benzisoxazoles

“…Following previous studies on the [4 + 2]-cyclofragmentation of 1,2-oxazine N -oxides to unsaturated oxime derivatives, 14 as well as reactions of 1,2-oxazine N -oxides with arynes, 15 we envisioned 3-halo-substituted 1,2-oxazine N -oxides as viable surrogates of unsaturated nitrile oxides. It relies on the possibility of base-promoted cyclofragmentation/elimination of HBr (Scheme 1, (4)).…”

“…The reaction is initiated by the fluoride-induced formation of aryne and its [3 + 2]-cycloaddition with nitronate. 15,19 Next, the fluoride ion acts as a base and HBr is eliminated, possibly assisted by the anomeric effect from the nitrogen lone electron pair (n N → σ* C–Br ). This results in the formation of the key intermediate, N , N -bis(oxy)enamine 6 , that can undergo [4 + 2]-cyclofragmentation of the 5,6-dihydro-2 H -1,2-oxazine ring 20,21 leading to vinylbenzisoxazoles 3 and a carbonyl compound (acetone).…”