Nitrones nitrile oxide intermolecular cycloadditions

For intramolecular 1,3-dipolar cycloadditions, the application of nitrones and nitrile oxides is by far most common. However, in increasing frequency, cases intramolecular reactions of azomethine ylides (76,77,242-246) and azides (247-259) are being reported. The previously described intermolecular approach developed by Harwood and co-workers (76,77) has been extended to also include intramolecular reactions. The reaction of the chiral template 147 with the alkenyl aldehyde 148 led to the formation of the azomethine ylide 149, which underwent an intramolecular 1,3-dipolar cycloaddition to furnish 150 (Scheme 12.49). The reaction was found to proceed with high diastereoselectivity, as only one diaster-eomer of 150 was formed. By a reduction of 150, the proline derivative 151 was obtained. 

Modifying the aldehyde function in the pyrroles 1162 into 1,3-dipoles 1163 (nitrone) and 1167 (nitrile oxide) furnished tricyclic heterocycles 1164 and 1168 via intramolecular 1,3-dipolar cycloaddition reactions (Scheme 226) <2000T3013>. None of the isomeric bridged product 1165 is produced despite the preference for that regiochem-istry in the intermolecular reaction. Generated in situ (from the oximes 1166) nitrile oxides 1167 cyclized spontaneously to the dihydroisooxazole 1168 in quantitative yield at room temperature. 

Dipolar cycloaddition reactions occurreadily even with non-activated dipo-larophiles, such as isolated alkenes. This contrasts with the Diels-Alder reaction, particularly for intermolecular reactions, in which an activated alkene as the dienophile is required. Like the Diels-Alder reaction, [3+2] cycloaddition reactions of 1,3-dipoles are reversible, although in most cases it is the kinetic product that is isolated. For the intermolecular cycloaddition of nitrile oxides or nitrones, two of the most frequently used 1,3-dipoles, to monosubstituted or 1,1-disubstituted alkenes (except highly electron-deficient alkenes), the oxygen atom of the 1,3-dipole becomes attached to the more highly substituted carbon atom of the alkene double bond. Hence the 5-substituted isoxazolidine 206 is generated from the cycloaddition of the cyclic nitrone 205 with propene (3.136). Reductive... 

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