New perspectives and applications in organolithium chemistry: halocarbenoids and reductive lithiation

We report on the employment of 2-methyltetrahydrofuran and cyclopentyl methyl ether as alternative green solvents for the efficient generation of radical anions of Polycyclic Aromatic Hydrocarbons and their employment in the generation of organolithium reagents. 2-MeTHF was successfully employed as a solvent in the reductive lithiation of the benzylic C–O bond of phthalan, of the aromatic C–Cl bond of 4-chlorobenzyl methyl ether, and of the C–N bond ofN-phenylaziridine. Results obtained with N-phenylaziridine show that such a PAH mediated reductive lithiation of is strongly dependant on the solvent employed.We next investigated the reactivity of Weinreb amides with cyanomethyllithiums to access β-oxonitriles. Such a transformation occurs in the presence of primary, secondary and tertiary nitrile-containing carbanions. The study of the previously undisclosed15N- and17O-NMR data was correlated with analogous substrates thus, highlighting the spectroscopic effect of the β-oxonitrile group. Subsequently, the homologation of isocyanates with lithium carbenoids to reach α-halo or α,α-dihaloamides was realized: the protocol is high-yielding and no lose of optical purity was noticed in the presence of chiral materials. Finally, we studied the homologation of isatins derivatives with lithium carbenoids to access spiro-epoxyoxindoles.