4.5- Dimethylthiazole, deprotonation

The deprotonation of 4,5-dimethylthiazole and addition of the resulting anion to aldehydes was demonstrated as early as 1948 (48HCA652) and 2-lithiothiazoles were later shown to react with aldehydes, ketones, methyl iodide, and epoxides... 

The treatment of thiazole with n-butyl- or phenyllithium leads to exclusive deprotonation at C-2. When the 2-position is blocked, deprotonation occurs selectively at C-5. However, if the substituent at C-2 is an alkyl group, the kinetic acidities of the protons at the a-position and at the 5-position are similar. The reaction of 2,4-dimethylthiazole with butyllithium at -78°C yields the 5-lithio derivative (289) as the major product but if the reaction is carried out at higher temperature the thermodynamically more stable 2-lithiomethyl derivative (290) is obtained (Scheme 37). The metallation at these two positions is also dependent on the strength and bulk of the base employed (74JOC1192) lithium diisopropylamide is preferred for selective deprotonations at the 5-position. 

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