2,2’- 4 -dihydrooxazole cycloaddition reactions

This regioselectivity is practically not influenced by the nature of subsituent R. 3,5-Disubstituted isoxazolines are the sole or main products in [3 + 2] cycloaddition reactions of nitrile oxides with various monosubstituted ethylenes such as allylbenzene (99), methyl acrylate (105), acrylonitrile (105, 168), vinyl acetate (168) and diethyl vinylphosphonate (169). This is also the case for phenyl vinyl selenide (170), though subsequent oxidation—elimination leads to 3-substituted isoxazoles in a one-pot, two-step transformation. 1,1-Disubstituted ethylenes such as 2-methylene-1 -phenyl-1,3-butanedione, 2-methylene-1,3-diphenyl- 1,3-propa-nedione, 2-methylene-3-oxo-3-phenylpropanoates (171), 2-methylene-1,3-dichlo-ropropane, 2-methylenepropane-l,3-diol (172) and l,l-bis(diethoxyphosphoryl) ethylene (173) give the corresponding 3-R-5,5-disubstituted 4,5-dihydrooxazoles. 

Dihydrooxazoles such as 263 have also been prepared <2004T7591> via an oxidative decarboxylation and elimination of the corresponding oxazolidine -carboxylic acid 262 (Scheme 77). The oxazolidine-4-carboxylic acids were in turn derived from L-serine. The thermal oxidative decarboxylation using lead tetraacetate was reported to be higher yielding and more practical than the analogous electrochemical version. Dihydrooxazoles 263 have been extensively used as chiral olefmic components in cycloaddition reactions and these reactions are discussed in Section 4.04.6.2.1. 

The 2-methyl-4,5-dihydrooxazoles (358 Z = O) or 2-methyl-4,5-dihydrothiazole (358 Z = S) undergo 1,3-dipolar cycloaddition reactions with benzonitrile A -oxide to give the corresponding 7a-methyl-3-phenyl-5,6-dihydro-7a//-oxazolo[3,2- ][l,2,4]oxadiazoles (16) or -thiazolo[3,2-c ]-[l,2,4]oxadiazoles (17) (Equation (121)) <92T7703>. 

Cycloadditions have been carried out to 37/-indoles (222, 223) (125,126), N-arylmaleimides (224) (127,128), l,2), -azaphospholes (225) (129), 5(47/)-oxazo-lones (226) (130), and 4,5-dihydrooxazoles (230) (131). The primary cycloadducts from the reaction of oxazolones (e.g., 226 with diaryl nitrile imines), derived from tetrazoles in refluxing anisole, do not survive. They appear to lose carbon dioxide and undergo a dimerization-fragmentation sequence to give the triazole 228 and the diarylethene 229 as the isolated products (130). In cases where the two aryl substituents on the oxazole are not the same, then, due to tautomerism, isomeric mixtures of products are obtained. 

In all the reactions discussed so far in this section, the heterocyclic nucleus reacts via an endocyclic carbon-carbon double bond. However, recently Koch et a/.183,184 reported the (2 + 2)-cycloaddition via a carbon-nitrogen double bond. 3-Ethoxyisoindol-l-one yielded (2 + 2)-cycloadducts (162) with both electron-rich and electron-neutral olefins, but not with electron-deficient olefins.183 2-Phenyl-4,5-dihydrooxazol-4-... 

Starting from the hydroxy amino acids serine and threonine, several oxazolidines 11 and 12 and dihydrooxazoles 13 and 14 were prepared6, which are useful in acyliminium ion reactions (Section D.l.4.5.) and in [1+2] cycloadditions (Section B.l.6.1.5.). 

Further C2-symmetric ligands containing bridged dihydrooxazoles 22 and 23 were obtained from rm-leucinol by the reaction with aliphatic dicarboxylic acid esters and used as ligands for copper in catalytic [1+2] cycloadditions (Section D. 1.6.1.5.)16-17. 

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