Screttas lithiation

What is Screttas lithiation?

Screttas reported this reaction in 1978. Screttas lithiation is one of the most commonly used methods for creating an organic lithium reagent by reductively lithiating an alkyl or aryl thioether with an aromatic radical anion, such as lithium naphthalene, in THF.

Screttas lithiation - general reaction scheme
Screttas lithiation

Screttas lithiation is useful for producing primary, secondary, tertiary, and even vinyl lithium species. It has been observed that the ease of generating the organic lithium species by reductive lithiation increases as the stability of the species decreases.

The lithium reagent that is produced can react with various electrophiles, including epoxides, aldehydes, ketones, α,β-unsaturated compounds, and alkyl halides. When titanium isopropoxide Ti[O-i-Pr]4 or cerium chloride CeCl3 is present, the addition of allyl lithium to aldehydes or ketones results in high stereoselectivity. The generated lithium species can also undergo intramolecular cyclization to form four- to six-membered ring structures. The reactivity order is:

secondary > tertiary > primary

with the secondary lithium reagent leading to the formation of cyclobutane or cyclopentane derivatives with exceptional stereoselectivity. However, the presence of a terminal olefinic methyl group inhibits such cyclization. Screttas lithiation is typically performed in THF, with dimethyl ether being the only exception.

References

Screttas, C. G. and Micha-Screttas, M., J. Org. Chem., 1978, 43, 1064

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