t-Butoxymethyllithium: Direct preparation from t-butyl methyl ether and applications as a hydroxymethyl anion equivalent
✍ Scribed by E.J. Corey; Thomas M. Eckrich
- Publisher
- Elsevier Science
- Year
- 1983
- Tongue
- French
- Weight
- 198 KB
- Volume
- 24
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
t-Butyl methyl ether can be metallated directly to afford a reactive and synthetically useful hydroxymethyl anion equivalent. t-Butyl methyl ether (TBME), a cheap @. $'l/iiter) commercial chemical, can be metallated by s-butyllithium -potassium t-butoxide reagent' as evidenced by formation of t-butoxyacetic acid upon subsequent treatment with CO2:
The metallation takes place readily at -78" using neat TBME (ca. 28 equiv), 1 equiv of s-BuLi and 0.7 equiv of KOtBu and after a 2 hr reaction period carbonation affords 75% yield of t-butoxyacetic acid (based on s-BuLi).
The active metallating agent is presumably s-BuK. 1 In the case of ketones having alpha hydrogens the reactions of t-BuOCH2Met formed in this way are complicated by the strongly basic character of the initial mixture, but this problem is readily obviated by the addition of 2 equiv of LiBr in THF solution which precipitates potassium and leaves t-butoxymethyllithium in solution. By this means solutions of the reagent t-BuOCH2Li in TBME-THF & can be generated conveniently in one operationally simple step. The foregoing paper describes a general route to alkoxymethyllithium reagents frcan alkyl chloromethyl ethers. 2 Although this route is applicable to the efficient synthesis of& the direct preparation &om TBME discussed herein would appear to be more practical for large scale work with this specific reagent.