Nitronates intermolecular cycloadditions

Cycloaddition of nitrone (508) to allyl alcohol at ambient temperature gave a mixture of four cycloadducts in a 23 5 4 1 ratio (Scheme 2.244). All of the adducts (509) are derived from the regiochemical approach opposite to the intramolecular pathway (Fig. 2.35). Formation of the cycloadduct in the intramolecular cycloaddition reaction is ascribed to a high preference for an endo-syn transition state, due to the constraint imposed by the short, three atom connecting chain (116). The major product in the intermolecular cycloaddition reaction was the exo-anti -(509) adduct (Scheme 2.244 and Fig. 2.35). 

Points b to d should be explained in more detail for intermolecular cycloaddition reactions of acyclic nitronates A with monosubstituted olefins. Regioselectivity of the process is determined by the character of the approach of olefin to the dipole (head-to-head or head-to-tail, (Chart 3.16, part (1)). In the former case, the substituent R is bound to the C-5 atom in the latter case, to the C-4 atom. 

It has long been recognized that nitrone cycloadditions may allow access to spirocyclic ring systems. Such systems are inherently difficult to synthesize by conventional methods, yet are a structural component of a number of biologically active natural materials. Two common strategies have emerged for spirocycle generation from exocyclic or endocyclic nitrones (Scheme 1.45). In the exocyclic version, the carbon atom (arrowed) of the nitrone C=N double bond of dipole 209 carries a cyclic substitutent and thus an intermolecular cycloaddition reaction will... 

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... 

The intermolecular cycloaddition route to spirocyclopropyl isoxazolidines and their subsequent rearrangement, used so widely by Brandi and co-workers (372-375) (Schemes 1.16 and 1.17, Section 1.5), has also been achieved in an intramolecular sense (Scheme 1.72). Cycloaddition of the alkenyl nitrone reagents (333a-c) afforded bicyclic isoxazolidinyl adducts 334, which rearranged under thermolysis in analogous fashion to the earlier work to give piperidinones (335) via... 

---