Construction of Saturated Oxazolo[3,2-b][1,2]oxazines via Tandem [3+2]-Cycloaddition/[1,3]-Rearrangement of Cyclic Nitronates and Ketenes

Abstract

Reaction of six-membered cyclic nitronates with disubstituted ketenes affords hitherto unknown saturated oxazolo­[3,2-b]­[1,2]­oxazines possessing up to four contiguous stereogenic centers. The process involves a tandem of [3+2]-cycloaddition across the CO bond of ketene, followed by a spontaneous [1,3]-rearrangement of transient vinylidene-substituted bicyclic nitrosoacetals. DFT calculations of the mechanism suggest that the [1,3]-O,C-shift proceeds through a recyclization of a biradical intermediate formed by an unusually mild homolytic cleavage of the N–O bond. The resulting products can be utilized as precursors of other fused 1,2-oxazines derivatives, in particular 1,2-oxazino-1,2,4-triazin-3-ones.

Regio- and diastereoselective access to densely functionalized ketonesviathe Boekelheide rearrangement of isoxazolineN-oxides

“…Ketenes may undergo dimerization and side reactions involving N-oxides 3. 8 Unlike nitrostyrenes 1, aliphatic nitroalkenes are labile upon isolation and storage. Recently, we developed the synthesis of 3-alkyl substituted isoxazoline N-oxides 8 from vicinal nitroalcohols 6, in which the isolation of aliphatic nitroalkenes is avoided (Scheme 3, part A).…”

Renewed «Isoxazoline Route» for the Synthesis of Densely Functionalized Ketones

“…Ketenes may undergo dimerization and side reactions involving N-oxides 3. [8] Unlike nitrostyrenes 1, aliphatic nitroalkenes are labile upon isolation and storage that limits their synthetic application. Recently, we developed the synthesis of 3alkyl substituted isoxazoline-N-oxides 8 from vicinal nitroalcohols 6, in which isolation of aliphatic nitroalkenes is avoided (Scheme 3, Part A).…”

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

“…4-(4-Methoxyphenyl)-6,6-dimethyl-5,6-dihydro-4H-1,2-oxazine 2-Oxide (1a). Prepared according to a known method 29 (E)-1-methoxy-4-(2-nitrovinyl)benzene 30 (2.69 g, 15.0 mmol) and 2methylpropene (2.5 g, 45 mmol). Yield: 3.3 g (94%).…”

“…31 6,6-Dimethyl-4-phenethyl-5,6-dihydro-4H-1,2-oxazine 2-Oxide (1c). Prepared according to a known method 29 from (E)-(4nitrobut-3-en-1-yl)benzene 33 (482 mg, 2.72 mmol) and 2-methylpropene (760 mg, 13.6 mmol taken as a 5 M solution in CH 2 Cl 2 ). Yield: 408 mg (64%).…”

“…Prepared according to a known method 29 from (E)-1methoxy-4-(2-nitrovinyl)benzene 30 (1.5 g, 8.4 mmol) and racemic camphene (2.28 g, 16.8 mmol). Yield: 1.8 g (68%).…”