Intermolecular cycloadditions alkyl nitronates

Elsewhere, Heaney et al. (313-315) found that alkenyloximes (e.g., 285), may react in a number of ways including formation of cyclic nitrones by the 1,3-APT reaction (Scheme 1.60). The benzodiazepinone nitrones (286) formed by the intramolecular 1,3-APT will undergo an intermolecular dipolar cycloaddition reaction with an external dipolarophile to afford five,seven,six-membered tricyclic adducts (287). Alternatively, the oximes may equilibrate to the corresponding N—H nitrones (288) and undergo intramolecular cycloaddition with the alkenyl function to afford five,six,six-membered tricyclic isoxazolidine adducts (289, R = H see also Section 1.11.2). In the presence of an electron-deficient alkene such as methyl vinyl ketone, the nitrogen of oxime 285 may be alkylated via the acyclic version of the 1,3-APT reaction and thus afford the N-alkylated nitrone 290 and the corresponding adduct 291. In more recent work, they prepared the related pyrimidodiazepine N-oxides by oxime-alkene cyclization for subsequent cycloaddition reactions (316). Related nitrones have been prepared by a number of workers by the more familiar route of condensation with alkylhydroxylamines (Scheme 1.67, Section 1.11.3). 

The intermolecular alkylation of metallo nitronates with various alkyl halides is limited. The addition of methyl iodide to the silver salt of an aryl nitro-methane provides the corresponding methyl nitronate in moderate yield (Eq. 2.13) (150), which has also been extended to the silver salt of trinitromethane (Scheme 2.16) (151-153). However, in the case of primary halides, both O- and C-alkylation are observed. For secondary and tertiary halides, only O-alkylation is observed, but in low yields. Unfortunately, under the reaction conditions, the starting alkyl halide can undergo dehydrohalogenation to provide the corresponding alkene, which then undergoes [3+2] cycloaddition with the alkyl nitronate. 

The use of mediators to improve reactivity or selectivity in nitrone cycloaddition chemistry begins with the nitrone generation step. As is well known, the N-alkyla-tion of oximes provides one of the most direct and convenient synthetic routes to N-alkylated nitrones from readily available aldehydes and ketones. Electrophilic mediators have been employed to activate alkenes for N-alkylation, both in intramolecular and intermolecular reactions. They include activation of the internal alkene function by the action of (a) strong nonmetallic electrophiles such as phenyl-selenenyl sulfate (159), and (b) metallic catalysts such as Ag(I) (160) and Pd(II) ions... 

I. Intermolecular [3+2]-Addition of Nitronates to Olefins Of all known types of nitronates (see Section 3.2), alkyl- and silyl nitronates as well as cyclic C5-C6 nitronates are involved in [3+ 2]-cycloaddition reactions. Detailed comparative kinetic studies for different types of nitronates have not been reported. However, a few data (162, 336, 337) allow one to deduce some sequences (Chart 3.10). 

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