Nitrones nitrone-alkene

The Ti(IV) TADDOL catalyst Q leads to moderate enantioselectivity in nitrone-alkene cycloaddition.158... 

Finally, the reversibility of the nitrone/alkene [3+2] cycloaddition, mainly used to access the hexahydro-isoxa-zolo[2,3- ]pyridine ring system (see Section 11.10.3.7), can be used to functionalize these heterocycles. Accordingly, Holmes et al. found that a cycloreversion-cycloaddition reaction could be performed from 65 by simple heating in toluene at 190 °C. Under these conditions, the product of the reaction was found to be the exo-adduct 67 (Scheme 21) <2002J(P1)1494>. 

The products of nitrone-alkene cycloadditions are isoxazolines, and the oxygen-nitrogen bond can be cleaved by reduction, leaving both an amino and a hydroxy function in place. 

As with the Diels-Alder reaction, it is possible to achieve enantioselective cycloaddition in the presence of chiral catalysts.89 The Ti(IV) catalyst C with chiral diol ligands leads to moderate to high enantioselectivity in nitrone-alkene cycloadditions.90... 

The in situ formation of nitrones from oximes by 1,3-APT or 1,2-prototropy is clearly a powerful synthetic strategy but conventional nitrone generation, in particular hydroxylamine-carbonyl condensation, has been applied to numerous syntheses, in intra- and intermolecular mode (258). Accordingly, the ring systems similar to those synthesized using 1,3-APT/intramolecular nitrone-alkene cycloaddition (INAC) methodology by Heaney (313-315) (see Section 1.11.2) or Padwa and Norman (340) have been made using conventionally prepared nitrones (Scheme 1.67). As with the previous examples, once formed, the nitrones are suitably placed for a spontaneous intramolecular cycloaddition reaction with the... 

Tricyclic P-lactams not having a bridgehead nitrogen atom have been obtained by intramolecular Friedel-Crafls reactions <99T5567> and from the intramolecular Diels-Alder reactions of 1,3-dienes generated from a mesylate 79 <99TL1015>. Other tricyclic P-lactams e.g., 80 have been obtained by intramolecular nitrone-alkene cycloaddition <99TL5391>. 

In an approach to the clavine alkaloids [170] based on intramolecular nitrone-alkene cycloaddition, the condensed tetracyclic system is probably favored by steric factors. Equilibration at higher temperature leads to predominantly a bridged oxabicyclo-[3.2.1]nonae derivative in which a portion of the molecule contains polarity alternation sequence (OCOC=0, N-C-C-C=0). 

Scheme 29 Preparation of tricyclic [1-lactams 86-89 using nitrone-alkene(alkyne) cycloadditions...

They have also reported a direct route to optically pure, fused, or bridged tricyclic (3-lactams (III and IV, Fig. 18) as further advances in the intramolecular nitrone-alkene cycloaddition reactions of monocyclic 2-azetidinone-tethered alkenyl-aldehydes [289]. 

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