Dipolarophiles methyl vinyl ketone

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). 

Scheme 1.64). The Ag(I)-mediated cyclization afforded dipole 306 for 1,3-dipolar cycloaddition with methyl vinyl ketone to yield adducts 307 and the C(2) epimer as a 1 1 mixture (48%). Hydrogenolytic N—O cleavage and simultaneous intramolecular reductive amination of the pendant ketone of the former dipolarophile afforded a mixture of alcohol 308 and the C(6) epimer. Oxidation to a single ketone was followed by carbonyl removal by conversion to the dithiolane and desulfurization with Raney nickel to afford the target compound 305 (299). By this methodology, a seven-membered nitrone (309) was prepared for a dipolar cycloaddition reaction with Al-methyl maleimide or styrene (301). 

Whereas 260 does not react with electron-rich dipolarophiles, the more delocalized isomiinchnone 261 does react with both electron-rich and -deficient dipolarophiles (154). A detailed FMO analysis is consistent with these observations and with the regiochemistry exhibited by diethyl ketene acetal and methyl vinyl ketone as shown in Scheme 10.36. The reaction of 261 with the ketene acetal to give 262 is LUMO-dipole HOMO-dipolarophile controlled (so-called lype III process). In contrast, the reaction of 261 with methyl vinyl ketone to give 263 is HOMO-dipole LUMO-dipolarophile controlled (so-called lype I process). In competition experiments using a mixture of A-phenylmaleimide and ketene acetal only a cycloadduct from the former was isolated. This result is consistent with a smaller energy gap for... 

Unsymmetrical dipolarophiles were found to undergo intermolecular cycloaddition with isomiinchnones with high regioselectivity [27]. For example, the decomposition of diazoimide 9 with Rh2(OAc)4 in the presence of methyl vinyl ketone resulted in the formation of two products identified as 27 and 28 in 27 %... 

Facile reaction of electron-deficient olefins (dipolarophiles) such as rra/i5-dibenzoylethylene, dimethyl fumarate, furanonitrile, methyl vinyl ketone, ethyl crotonate, ethyl acrylate, ethyl methacrylate, and dimethyl maleate with a mesoionic compound containing a masked thiocarbonyl ylide skeleton gives stable 1 1 cycloadducts. The structure of the cycloadduct was established by its carbonyl absorption in IR spectra and the molecular ion peak [M]. The stereochemistry of the cycloadducts was, however, secured by NMR spectra (74JOC3631) (Scheme 100). 

Pyrido[l,2-c]quinazolin-8-ones (215) were obtained from the cycloadducts (214) of anhydro 3-hydroxythiazolo[3,2-c]quinazolin-4-ium hydroxides (213) and alkynic (dimethyl acetylenedicarboxylate and ethyl propio-late) and alkenic dipolarophiles (fumaronitrile and methyl vinyl ketone) by extrusion of S or H2S (85JOC1666). A better yield could sometimes be... 

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