The equilibrium between 2-lithium-oxazole(-thiazole, -imidazole) derivatives and their acyclic isomers - A structural investigation

2-Metallated oxazoles, thiazoles and imidazoles are of interest for the preparation of derivatives of the respective heterocycles, and - especially in the case of metallated thiazoles - as acyllithium equivalents in organic syntheses. Metallation at C2 of these compounds, however, often leads (more so with Li-oxazoles than with Li-thiazoles and Li-imidazoles) to products derived from the acyclic isomers of the metallated heterocycles. In order to obtain more information on the positions of the relevant equilibria, we have carried out a C-13-NMR study of substituted Li-and ZnCl-oxazoles, Li-thiazoles and Li-imidazoles. In the case of Li-oxazoles, the equilibrium is completely on the side of the acyclic isomers. Addition of ZnCl2, however, leads to ring-closure, and, even in the case of 2-ZnCl-substituted benzoxazole, only the ring-closed isomer is observed. This demonstrates a dramatic gegenion effect on the equilibrium between two isomeric anions. In the case of Li-thiazoles, depending on the substitution pattern, either solely the ring-closed or an equilibrium with the ring-opened isomer is observed, In the series of Li-imidazoles, only the 2-lithiated benzimidazole is in equilibrium with its ring-opened isomer. The tendency of these compounds to undergo ring-opening parallels the leaving group properties of the various subunits [ROLi > RSLi > R2NLi, and phenyl-O(S,NR)Li > vinyl-O(S,NR)Li], The difference between the effects of Li+ vs. ZnCl+ in the (benz)oxazole series is in agreement with results of solid-state structure investigations of a 2-lithiated and a 2-zincated thiazole: in the Li compound the C-S bond is 2.9 pm longer than in the ZnCl species, indicating a more facile C-S bond cleavage with Li+ as the gegenion.