Dimethyl maleate, reaction with nitronic

Although the [4- -2] cycloaddition of nitroalkenes is governed by inverse-electron-demand and requires an electron-rich 2ti-component, the [3 + 2] cycloadditions of nitronates engage both electron-rich and electron-poor dipolarophiles [118, 119]. Reactions with electron-poor dipolarophiles, however, are more facile [55]. It is difficult to compare the cycloaddition reactivity of different nitronates with dipolarophiles because nitronates are somewhat unstable. As a result, low yields of the nitroso acetals may reflect this instability rather than slow reaction rate. The example in Scheme 16.21 illustrates the higher reactivity of electron-deficient dipolarophiles in [3 - - 2] cycloadditions with nitronates [55]. In this competition experiment, nitro-styrene 44 undergoes inverse-electron-demand [4 + 2] cycloaddition selectively with the electron-rich ethyl vinyl ether even in the presence of dimethyl maleate. The intermediate nitronate reacts further with the electron-poor dimethyl maleate, even though both alkenes are present in large excess. The product 80 is isolated in 30% yield and... 

Cycloaddition reaction of nitrone (—)-(394) with dimethyl maleate D14 has been used for the synthesis of two new polyhydroxyl pyrrolizidines (687) and (688) (Schemes 2.293, 2.294). These compounds are analogs of alkaloids ros-marinecine and crotanecine, which were assayed for their inhibitory activities toward 22 commercially available glycosidase enzymes. One of them ((-)- a-epi-crotanecine) (—)-(688) is a potent and selective inhibitor of a-mannosidases (310). The reaction of (—)-(394) with dimethyl maleate gave a 9.6 6 1 mixture of cycloadducts (—)-(680), (+ )-(680), and (—)-(681), which arise from anti-exo,... 

The Stereoselectivity of 1,3-Dipolar Cycloadditions. There is no endo mle for 1,3-dipolar cycloadditions like that for Diels-Alder reactions. Stereoselectivity, more often than not, is low, as shown by the reactions of C,/V-diphenylnitrone—both regioisomers 6.238 and 6.239 (R=C02Et) from the reaction with ethyl acrylate are mixtures of exo and endo isomers, only a little in favour of the exo product. Similarly, the reactions of methyl crotonate with nitrones favour the exo product 6.242 over the endo 6.243. In contrast, other reactions are endo selective, as in the cycloaddition 6.244 of an azomethine ylid to dimethyl maleate giving largely the endo adduct 6.245. 

Since the discovery of the very remarkable 100% endo selectivity of the reactions of nitronic esters with dimethyl maleate, maleic anhydride and maleimides secondary orbital interactions involving the nitrogen atom of the 1,3-dipole and the substituents on the dipolarophile have been postulated as strong endo-orienting factors, able to overwhelm the contrasting steric factors (Figure 1). 

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