Ultrafast amidation of esters using lithium amides under aerobic ambient temperature conditions in sustainable solvents

Fairley, Michael and Bole, Leonie J. and Mulks, Florian F. and Main, Laura and Kennedy, Alan R. and O'Hara, Charles T. and García-Álvarez, Joaquin and Eva, Hevia (2020) Ultrafast amidation of esters using lithium amides under aerobic ambient temperature conditions in sustainable solvents. Chemical Science, 11 (25). pp. 6500-6509. ISSN 2041-6520 (https://doi.org/10.1039/D0SC01349H)

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Lithium amides constitute one of the most commonly used classes of reagents in synthetic chemistry. However, despite having many applications, their use is handicapped by the requirement of low temperatures, in order to control their reactivity, as well as the need for dry organic solvents and protective inert atmosphere protocols to prevent their fast decomposition. Advancing the development of air- and moisture-compatible polar organometallic chemistry, the chemoselective and ultrafast amidation of esters mediated by lithium amides is reported. Establishing a novel sustainable access to carboxamides, this has been accomplished via direct C-O bond cleavage of a range of esters using glycerol or 2-MeTHF as a solvent, in air. High yields and good selectivity are observed while operating at ambient temperature, without the need for transition-metal mediation, and the protocol extends to transamidation processes. Pre-coordination of the organic substrate to the reactive lithium amide as a key step in the amidation processes has been assessed, enabling the structural elucidation of the coordination adduct [{Li(NPh2)(OCPh(NMe2))}2] (8) when toluene is employed as a solvent. No evidence for formation of a complex of this type has been found when using donor THF as a solvent. Structural and spectroscopic insights into the constitution of selected lithium amides in 2-MeTHF are provided that support the involvement of small kinetically activated aggregates that can react rapidly with the organic substrates, favouring the C-O bond cleavage/C-N bond formation processes over competing hydrolysis/degradation of the lithium amides by moisture or air.