Lithiation 4-methyloxazole

By lithiation of 4-methyloxazole with n-BuLi and subsequent quenching with trimethyltin chloride, Dondoni et al. prepared 2-trimethylstannyl-4-methyloxazole [18], which was then coupled with 3-bromofuran to provide the expected furylthiazole. 

However, unlike the situation seen with 2-methyloxazole and 1,2-di-methylimidazole where side-chain metalation predominates, lithiation at C-5 can still be the predominant mode of reaction in certain cases, due to the stronger activating effect of the sulfur atom. The nature of the substituent at C-4, the type of electrophile employed, the temperature of the reaction, and the type of base used can all affect the product ratio (74JOC1192). 

The Stille coupling reaction is the most versatile method among all Pd-catalyzed crosscoupling reactions with organometallic reagents. By lithiation of 4-methyloxazole with H-BuLi and subsequent quenching with trimethyltin chloride, Dondoni et al. prepared 2-trimethylstannyl-4-methyloxazole [39], which was then coupled with aryl- and heteroaryl-halides to provide the expected 2-aryloxazole. Thus, 2-trimethylstannyl-4-methyloxazole was coupled with 3-bromo-pyridine to afford oxazolylpyridine 35. 

Dondoni s group also studied the synthesis and coupling reactions of 2-(stannyl)oxazoles. This work was part of their extensive investigations of the synthetic utility of stannylated and silylated azoles. Lithiation of 4-methyloxazole 3 followed by quenching with trimethyltin chloride gave the air- and moisture-sensitive 4-methyl-2-(trimethylstannyl)oxazole 993 in 60% yield after distillation... 

Dondoni s groups reported the first synthesis of a 2-(trimethylsilyl)oxazole (Scheme 1.269). Lithiation of 4-methyloxazole 3 and trapping with... 

Meyers and co-workers" also investigated lateral lithiation of a 2-methyloxazole derivative during their synthesis of the oxazole dienyl amine moiety 1203, common to 1183 and 1184. The authors proposed a retrosynthetic path, wherein selective functionalization of a 2-methyl-4-oxazolecarboxylic acid ester would be the starting point for 1203 (Scheme 1.305). 

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