Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

Abstract

SummaryStrained azirinium ylides derived from 2H-azirines and α-diazoketones under Rh(II)-catalysis can undergo either irreversible ring opening across the N–C2 bond to 2-azabuta-1,3-dienes that further cyclize to 2H-1,4-oxazines or reversibly undergo a 1,5-cyclization to dihydroazireno[2,1-b]oxazoles. Dihydroazireno[2,1-b]oxazoles derived from 3-aryl-2H-azirines and 3-diazoacetylacetone or ethyl diazoacetoacetate are able to cycloadd to acetyl(methyl)ketene generated from 3-diazoacetylacetone under Rh(II) catalysis to give 4,6-dioxa-1-azabicyclo[3.2.1]oct-2-ene and/or 5,7-dioxa-1-azabicyclo[4.3.1]deca-3,8-diene-2-one derivatives. According to DFT calculations (B3LYP/6-31+G(d,p)), the cycloaddition can involve two modes of nucleophilic attack of the dihydroazireno[2,1-b]oxazole intermediate on acetyl(methyl)ketene followed by aziridine ring opening into atropoisomeric oxazolium betaines and cyclization. Azirinium ylides generated from 2,3-di- and 2,2,3-triaryl-substituted azirines give rise to only 2-azabuta-1,3-dienes and/or 2H-1,4-oxazines.

Recent advances in ketene chemistry

“…The precursor of a ketene in the Wolff rearrangement, an acylcarbene (or carbenoid), can so react, as was recently reported by Russian workers. 134 The diazodiketone 251 in the presence of dirhodium tetraacetate or tetraoctanoate is suggested to generate a rhodium carbenoid which reacts with the 2H-azirine 252 in a [3+2] cycloaddition forming the intermediate 254, which rearranges to 255, and reacts further with acetyl methyl ketene 253, also formed by rearrangement of the carbenoid, by 1,2-and 1,4-cycloadditions, forming 256-258. (Scheme 94) A number of analogous reactions were studied.…”

Single‐Step Modular Synthesis of Unsaturated Morpholine N‐Oxides and Their Cycloaddition Reactions

“…To the best of our knowledge, 2 H ‐1,4‐oxazine N ‐oxides 6 and 7 have not previously been reported, and discussions of oxazines similar to 10 are rare and limited to their use as latent azadienes ,. Due to the demand for new heterocycles for medicinal and material applications, we decided to explore the reactivity of 6 and 7 to determine how they might be applied in the preparation of new structurally diverse libraries.…”

“…Oxazine 19 similarly underwent a [4+2] cycloaddition with the same dienophile but the initial cycloaddition product rearranged to the corresponding pyridine 21 under the reaction conditions. These transformations are in contrast to the reactivity reported for similar oxazines generated from 2 H ‐azirines and diazoesters, which favor ring opening and rearrangement ,. The preparation of cycloaddition products 20 and 21 also further supports the unique utility of oxazines such as 6 – 8 and 10 for the diversity‐oriented synthesis of new heterocyclic structures.…”

An Efficient Synthesis of Functionalized 2H-1,3,5-Oxadiazines via Metal-Carbenoid-Induced 1,2,4-Oxadiazole Ring Cleavage

“…Aryl-, benzoyl-, and tosyl-substituted -diazoacetic esters 2c-f as well as 3-diazopentane-2,4-dione (2j) were decomposed by both Rh 2 (OAc) 4 and Rh 2 (Piv) 4 without any conversion of oxadiazole 1a (Table 1, entries [3][4][5][6][7][8][9][10][11][12][13][14][15][16]12). The reason for the failure is probably the low nucleophilicity of the oxadiazole.…”

“…The reason for the failure is probably the low nucleophilicity of the oxadiazole. As a result, the carbenoids derived from diazo compounds 2c-f,j much more rapidly react in intramolecular fashion, for example, via CH insertion 14 or Wolff rearrangement 15 which lead to oxetane or ketene derivatives and the products of their transformations. High yields of 1,3,5-oxadiazines were achieved using ethyl 2-cyano-2-diazoacetate (2g), ethyl 2-diazo-3,3,3-trifluoropropanoate (2h), and dimethyl 2-diazomalonate (2i) (entries 7, 8, 10).…”