Breaking the tert-Butyllithium Contact Ion Pair: A Gateway to Alternate Selectivity in Lithiation Reactions

The effects of Lewis basic phosphoramides on the aggregate structure of t-BuLi have been investigated in detail by NMR and DFT methods. It was determined that hexamethyl­phosphoramide (HMPA) can shift the equilibrium of t-BuLi to include the triple ion pair (t-Bu–Li–t-Bu)−/HMPA4Li+ which serves as a...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2023-05, Vol.145 (19), p.10743-10755
Main Authors: Crockett, Michael P., Piña, Jeanette, Gogoi, Achyut Ranjan, Lalisse, Remy F., Nguyen, Andrew V., Gutierrez, Osvaldo, Thomas, Andy A.
Format: Article
Language:English
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Summary:The effects of Lewis basic phosphoramides on the aggregate structure of t-BuLi have been investigated in detail by NMR and DFT methods. It was determined that hexamethyl­phosphoramide (HMPA) can shift the equilibrium of t-BuLi to include the triple ion pair (t-Bu–Li–t-Bu)−/HMPA4Li+ which serves as a reservoir for the highly reactive separated ion pair t-Bu–/HMPA4Li+. Because the Li-atom’s valences are saturated in this ion pair, the Lewis acidity is significantly decreased; in turn, the basicity is maximized which allowed for the typical directing effects within oxygen heterocycles to be overridden and for remote sp3 C–H bonds to be deprotonated. Furthermore, these newly accessed lithium aggregation states were leveraged to develop a simple γ-lithiation and capture protocol of chromane heterocycles with a variety of alkyl halide electrophiles in good yields.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.2c13047