[3 + 3] Formal Cycloadditions of Nitrones from Isatins and Azaoxyallyl Cations for Construction of Spirooxindoles

Abstract

A [3＋3] formal cycloaddition reaction between in situ formed azaoxyallyl cations and nitrones from isatins has been developed, furnishing a spectrum of spiro[1,2,4-oxadiazinan-5-one]oxindoles in good to excellent yields with excellent diastereoselectivity. This method provides direct and efficient access to potentially bioactive spirooxindoles incorporating a six-membered heterocyclic scaffold.

A Computational Study on Cycloaddition Reactions between Isatin Azomethine Imine and in situ Generated Azaoxyallyl Cation

“…Azaoxyallyl cations, generated in situ from α‐halohydroxamates in the presence of a base, have been widely applied as three‐atom synthons to the assembly of diverse heterocycles [1–3] . These highly reactive intermediates have been engaged in [3+ m ] ( m =1∼4) cycloaddition reactions [4] with a variety of partners, such as sulfur ylides, [5,6] indoles, [7] imines, [8] carbonyl compounds, [9] 1,3‐dipoles, [10,11] dienes, [12,13] and so on [14–19] . Expanding the scope of cycloaddition reactions involving an azaoxyallyl cation intermediate has been a hot research issue in modern organic synthesis.…”

Rapid Access to Hindered α-Amino Acid Derivatives and Benzodiazepin-3-ones from Aza-Oxyallyl Cations

“…The azaoxyallyl cation intermediates mentioned above have attracted considerable attention as ideal three-atom synthons for the synthesis of heterocycles. A variety of biologically important heterocycles were sequentially prepared by the valuable [3+2], [3+3], and [4+3] cycloadditions of azaoxyallyl cations with indole, 2-methylfuran, dienes, carbonyl compounds, 1,3-dipoles, cyclopentadiene, etc. − Remarkably, the direct coupling of nucleophilic partners with α-halohydroxamates via an in situ-generated azaoxyallyl cation intermediate at either of the α-carbonyl positions is rarely reported . Herein, we report an economical and efficient method for the synthesis of a wide range of α-aminocarbonyl compounds from the reaction of various α-halohydroxamates with amines in the presence of a mild base without using any catalyst .…”

“…Excellent yields were obtained when the benzyloxy group in the α-halohydroxamates was replaced by other N-protecting groups such as methoxy, allyloxy, and tert -butyloxy groups ( 7a–7c , respectively). As expected, N -benzyl-2-bromo-2-methylpropanamide participates in this α-substitution ( 7d , 0%), indicating that the benzyl group on the N atom is not sufficient to stabilize the azaoxyallyl cation and that an alkoxy group is necessary for the reaction. − Cyclopentyl- and cyclohexyl-substituted hydroxamates worked well for this reaction, delivering the desired products 7e and 7f in 89% and 78% yields, respectively. Remarkably, various monoalkyl and monoaryl hydroxamates successfully underwent this reaction, giving the desired products ( 7g–7o ) in good to excellent yields (60–83%).…”

“…On the basis of the previously reported cycloaddition of in situ-formed aza-oxyallyl cations − and the results mentioned above, we proposed a plausible mechanism of our aza/aza-[4+3] cycloaddition, as illustrated in Scheme . First, azaoxyallyl cation intermediate A was generated from α-halohydroxamate 1a under basic conditions.…”

Synthesis of 2-Aminoimidazolones and Imidazolones by (3 + 2) Annulation of Azaoxyallyl Cations

“…11,12 Recently, our group and Jeffrey’s, 13,14 followed by Liao’s, 15 published a novel method for the dearomative (3+2) annulation reaction between 3-substituted indoles and azaoxyallyl cations to give pyrroloindolines. In the intervening time, others have expanded upon our initial work, thus reporting the (3+3), (3+2), and (3+1) reactions of azaoxyallyl cations with nitrones, 16–19 carbonyls, 20–24 isothiocyanates, 25,26 alkynes, 27 sulfur ylides, 28 thiocyanates, 29 and other coupling partners. 30 In this manuscript, we report for the first time annulation reactions between azaoxyallyl cations and nitriles and cyanamides to give imidazolones and 2-aminoimidazolones (Scheme 1).…”