Deoxygenative Arylation of 5,6-Dihydro-4H-1,2-oxazine-N-oxides with Arynes

Abstract

Six-membered cyclic nitronates (5,6-dihydro-4H-1,2-oxazine-N-oxides) react with Kobayashi's aryne precursors producing 3-(2-hydroxyaryl)-substituted 1,2-oxazines via deoxygenative C−H arylation. The process involves a hitherto unknown 1,3-dipolar cycloaddition of nitronate to the aryne to give an unusual tricyclic nitroso acetal, in which the N−O bond of the isoxazoline ring is selectively cleaved upon the action of a base (CsF) or an acid (TFA). The transient cycloadducts were isolated and characterized in some cases. The synthetic potential of the obtained 3-(2-hydroxyaryl)-substituted 1,2-oxazines was demonstrated by their stereoselective reduction to 1,4-amino alcohols and reductive 1,2-oxazine ring contraction to tetrahydrofuran derivatives.

[3+3]-Annulation of Cyclic Nitronates with Vinyl Diazoacetates: Diastereoselective Synthesis of Partially Saturated [1,2]Oxazino[2,3-b][1,2]oxazines and Their Base-Promoted Ring Contraction to Pyrrolo[1,2-b][1,2]oxazine Derivatives

“…We attribute it to two main reasons. First, N–O bonds in nitroso acetals are also susceptible to basic cleavage (e.g., Scheme 4 , path b) [ 76 , 77 ], which can lead to the formation of side products. The use of alcohol promotes the elimination of the hydroxyl group from intermediate E via hydrogen bonding, thus facilitating pyrrole formation (path a).…”

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

“…Albeit cycloadditions of arynes with various N-oxide-based 1,3dipoles (nitrones, 10 nitrile oxides, 11 heterocyclic N-oxides 12 ) have been extensively studied in recent years, nitronates remain unexplored in these reactions. In our recent communication, 13 we reported that the reaction of C(3) unsubstituted 5,6-dihydro-4H-1,2-oxazine N-oxides 1 (R = H) with Kobayashi's aryne precursors 14 9 produced 3-(2-hydroxyaryl)-substituted 1,2-oxazines 10, which were likely formed by a spontaneous fragmentation of the five-membered ring in the initially generated cycloadducts 5. In this work, we succeeded in preparing stable tricyclic nitroso acetals of types 5 and 6 by blocking the ring fragmentation through incorporation of a non-hydrogen substituent R at the C(4a) position (Scheme 1).…”