Imidazoles 3,3 -sigmatropic rearrangements

In another example using the isomeric amidoxime substrate 61, the formation of the expected [3,3]-rearrangement product 63 was not observed (Scheme 6.22). Instead the Z-adduct 62Z cyclized to oxadiazoline 64. Interestingly, the E-adduct 62E rearranged to hydroxypyrimidinone 60 and imidazole 66 instead of 63. The rearrangement of the substrate 62E was proposed to occur via intermediate 65 via a [l,3]-sigmatropic rearrangement which, after cyclization, led to the observed products 60 and 66. 

Lantos and colleagues reported a different imidazole synthesis via hetero-Cope rearrangement. Oximes 116 reacted with benzenecarboxidoyl chloride affording adducts 117 that readily underwent a [3,3]-sigmatropic rearrangement at high temperatures (equation 35) to substituted imidazoles 118. 

Similar enamine cyclization processes occur in several other successful heterocycle syntheses, e.g. in the Fischer indole synthesis. In this case, however, a labile N—N bond of a l-aryl-2-vinylhydrazine is cleaved in a [3,3]-sigmatropic rearrangement, followed by cyclization and elimination of ammonia to yield the indole (B. Robinson, 1963, 1969 R. J. Sundberg, 1970). Regioselectivity is only observed if R2 contains no enolizable hydrogen, otherwise two structurally isomeric indoles are obtained. Other related cyclization reactions are found in the Pechmann synthesis of triazoles (T.L. Gilchrist, 1974) and in G. Bredereck s (1939) imidazole synthesis (M.R. Grimmett, 1970). 

The reaction of 5,5-dimethyl-l-pyrroline 1-oxide with dimethylketene N-phenylimine leading to pyrrolo[l,2-a]imidazol-2(3H)-ones (190) proceeds via initial formation of zwitterion (188). Subsequent sigmatropic rearrangement of (188) gives zwitterion (189), capable of undergoing ring closure to (190) (79JOC4543). 

A Claisen rearrangement of the adduct (17) of an aromatic aldoxime and a propiolate ester provides a new and direct route to imidazole-4-carboxylates (see Scheme 5) in 61-72% yields. This new synthesis apparently involves a [l,3]-sigmatropic shift. 

A detailed reexamination of the thermal rearrangement of 1-methyl-imidazole originally reported by Wallach has been extended to encompass a wide range of 1-substituted imidazoles. The reaction appears to be of potential synthetic utility since it leads easily to 2-alkyl- and 2-arylimidazoles. It is an irreversible reaction, uncatalyzed, intramolecular, and does not involve radicals [l,5]-sigmatropic shifts, as shown in Scheme 40, are probably implicated. The major product is the 2-substituted imidazole (134), but small amounts of the 4- (or 5-) isomer (135) are also formed. A 1-allyl substituent migrates with equal facility to both 2- and 4(or 5)-positions, suggesting that a Cope-type rearrangement may also be involved for this substituent. ... 

---