Enol ethers, addition 1,3-dipoles

Apart from the role of substituents in determining regioselectivity, several other structural features affect the reactivity of dipolarophiles. Strain increases reactivity norbornene, for example, is consistently more reactive than cyclohexene in 1,3-DCA reactions. Conjugated functional groups usually increase reactivity. This increased reactivity has most often been demonstrated with electron-attracting substituents, but for some 1,3-dipoles, enol ethers, enamines, and other alkenes with donor substituents are also quite reactive. Some reactivity data for a series of alkenes with several 1,3-dipoles are given in Table 10.6 of Part A. Additional discussion of these reactivity trends can be found in Section 10.3.1 of Part A. 

Most of the approaches outlined in Figure 15.10 have been successfully realized on insoluble supports, either with the alkene or alkyne linked to the support, or with support-bound 1,3-dipoles (Table 15.16). Nitrile oxides are highly reactive 1,3-dipoles and react smoothly with both electron-poor and electron-rich alkenes, including enol ethers [200]. The addition of resin-bound nitrile oxides to alkenes (Entries 5 and 6, Table 15.16) has also been accomplished enantioselectively under catalysis by diisopropyl tartrate and EtMgBr [201], The diastereoselectivity of the addition of nitrile oxides and nitrones to resin-bound chiral acrylates has been investigated [202], Intramolecular 1,3-dipolar cycloadditions of nitrile oxides and nitrones to alkenes have been used to prepare polycyclic isoxazolidines on solid phase (Entries 7 and 9, Table 15.16). 

A-Acyl imines of fluoroalkyl ketones react exothermically with kctcncs and under mild conditions with enol ethers and alkenes to fonn [4+2] cycloadducts (Table 9). They also react with dipoles. In contrast to reactions with sulfonyi imines, competitive [2 + 2] or [2 + 1] cycloadditions or additions onto the imine function are not observed. The strong heterodiene properties of A-acyl imines are illustrated by the reactions of methyl 3.3.3-trifluoro-2-(tri-fluoroacetyliniino)propanoate with dienes which al.so provide 1,3-oxazines as the major product. The minor product is the result of [4 + 2] cycloaddition of the diene with the imine function (Table 9. final entry). ... 

---