Cycloadditions with Capto-Dative Olefins, III. Addition of 2-Morpholino-Acrylonitrile to Various Aldonitrones

The captodative effect

“…The oxazolidines 61 cannot be isolated, as they undergo an eliminative ring-opening to pushpull amides 62. 50 The versatile a-(tert-butylthio)acrylonitrile (52) can even act as the 7r-4 component in (3 + 2) cycloadditions with electron-poor dienophiles, e.g., N-phenylmaleic imide, maleic anhydride, and acetylenedi~arboxylate.~~…”

“…The oxazolidines 61 cannot be isolated, as they undergo an eliminative ring-opening to pushpull amides 62. 50 The versatile a-(tert-butylthio)acrylonitrile (52) can even act as the ir-4 component in (3 + 2) cycloadditions with electron-poor dienophiles, e.g., IV-phenylmaleic imide, maleic anhydride, and acetylenedicarboxylate.51 61 Finally, captodative olefins and dienes react cleanly as 7t-2 components in Diels-Alder reactions.52 The a-(methylthio)acrylonitrile (63) exhibits more dienophilic character than acrylonitrile or a-chloroacrylonitrile.520 The captodative dienes, e.g., 65, react at the less substituted double bond with unactivated dienes.520 The cycloadducts (e.g., 67) of a-morpholinoacrylonitrile (59) are easily transformed to the corresponding ketones 68. Thus, this captodative olefin constitutes a new ketene equivalent.521* Owing to the numerous possi-bilities offered by variations of the captodative substitution and by their further transformations, the new concept provides a general approach for organic synthesis of polyfunctional compounds via radicals, especially in the field of selective reduction and oxidation, substitution, addition, and cycloaddition reactions.…”

Regio- and Stereoselectivity of Captodative Olefins in 1,3-Dipolar Cycloadditions. A DFT/HSAB Theory Rationale for the Observed Regiochemistry of Nitrones

“…In contrast, nitrones react with olefins bearing strong electron-withdrawing substituents, such as the nitro group, to give the C-4 substituted isoxazolidines, while the C-5 regioisomer was preferred when electron-releasing and moderate electron-withdrawing substituted olefins were added. 3a, Addition to 1,2-disubstituted olefins has proven to be regioselective as well, but they were restricted to have reverse electron-demand substituents . Although some studies have been devoted to captodative olefins in 1,3-dipolar additions, for most of the reports, they have been only treated as occasional examples. 6h, However, they have attracted especial interest in Diels−Alder reactions, because of the opposite electronic effect displayed by their geminally substituted functional groups …”

“…The high level ab initio calculations of transition structures and activation parameters of the regioisomeric approaches have satisfactorily accounted for the 1,3-dipolar additions between dipoles and dipolarophiles with diverse electron-demand. 1e, A less predictable behavior may be ascribed to captodative olefins, owing to the antagonic electronic effect upon the double bond, and to the steric hindrance generated around the disubstituted olefinic carbon. Indeed, FMO theory fails to rationalize the orientation observed with some captodative and disubstituted olefins. 1d,,8b,9a, Steric effects have been invoked as controlling the cycloaddition . The presence of a radicaloid or dipolaroid transition state generated by these strongly polarized dipoles at the ground state has also been suggested. 10a, …”

Efficient regioselective synthesis of 4‐ and 5‐substituted isoxazoles under thermal and microwave conditions

“…To ascertain the position of the amino moiety for the di-substituted isoxazoles 3a-3f, we compare these results with similar compound synthesized earlier. Döpp et al [8] reported the synthesis of the 4-(3-phenylisoxazol-5-yl)morpholine 3c by reacting benzonitrile oxide with 4-ethynylmorpholine. The authors found the signal for the ethylenic proton at 5.30 ppm whereas in our case we observed it at 5.35 ppm confirming that the amino moiety is in position 5.…”