Nitrones reaction with acrylonitrile

The reaction of -isopropyl-V(l-cyanoisobutyl)nitrone (lOe) has been extensively investigated.43 The orientation varies, and depends on the steric as well as electronic environment of the olefin. With olefins 5, such as acrylonitrile, lOe gives isoxazolidines I regiospecifically. With methyl methacrylate or methacrylonitrile, isoxazolidines of type III are obtained. However, the cycloadduct from crotonate ester or crotonitrile has reverse" orientation (type VUIt). The reactions with diethyl maleate or fumarate give adducts of types V and VII, respectively. 

The reaction of nitrone 101 with such olefins 5 as propylene, n-hexene, allyl alcohol, styrene, acrylic acid, methyl acrylate, acrylonitrile, and butadiene are all regiospecific to give S-substituted isoxazolidines of type l.77 The reaction with olefins 6 seems to be regio- and stereo-specific thus, nitrone 101 and methyl methacrylate give cycloadduct lilt as the sole product.77 Similarly, 101 and 1 -methyl-1-phenylethylene gives adduct Hit.77 In the reactions with olefins 7 or 8, the stereospecificity is more evident.77,78 The isoxazolidine obtained is always one of the two possible epimers. The reaction of nitrone 101 with trisubstituted olefins is highly stereoselective.64 Some results are summarized in Table III. 

Other than giving a very good account of the experimental qualitative behaviour, the above results probably offer a reasonable quantitative evaluation of the leacbon parameters. The apparent activation free enthdpy of the reaction of 1-pyrroline-1-oxide and 5,5-dimethyl-1-pyrroline-l-oxide with acrylonitrile have been meas-ured 2 in cyclohexane (20.4 0.4 and 21.7 0.4 kcal mol, respectively) and in di-chloromethane (22.4 0.2 and 23.010.8 kcal mol ) at 298K the rate constants for the reactions of H-nitrone have not been measured, but it can be stressed that N-monosubstituted nitrone, e.g, t-Bu-nitrone, exhibits a high reactivity in 1,3-dipolar cycloadditions, which is similar to that of 1-pyrroline-l-oxide so that the evaluations of Table 6 emerge to be surprisingly good. Moreover, the activation entropy of the reaction of 5,5-dimethyI-1-pyrroline-l-oxide with acrylonitrile in cyclohexane has been estimated -31,9 eu, a value which is well reproduced by our calculations in the gas-phase (-33.4, -31.1, footnote of Table 6). 

As a consequence of the complimentary electron demand of the nitroalkene and the product nitronate, there exists the possibility of a one-pot, tandem reaction. In this case, the nitroalkene will react preferentially with the electron-rich alkene to produce an intermediate nitronate. This nitronate can then react with a second alkene bearing an electron-withdrawing substituent. Therefore subjection of the nitroalkene 210 to both ethyl vinyl ether and acrylonitrile provides only the nitroso acetal 211 in moderate yield (Eq. 20) (70). Moreover, this also allows the possibility of intramolecular variants of the process. 

In a similar manner, nitrones 32c,133 32d,129 and 32e112 with various monosubstituted olefins afford the corresponding isoxazolizidines (33c-e). 4-Hydroxy-3-nitroisoxazoline-A(-oxide (321) is thoroughly investigated. With olefins 3, such as propylene, styrene, vinyl acetate, methyl acrylate and acrylonitrile, adducts 33f are formed.134 Reactions of alkoxy or alkoxycarbonyl derivatives of 32 are also known these include 32g,133 3 2h,13 32i,135 and 3 j135 32j is reactive enough to cyclize... 

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