10.1021/acs.joc.5b01136
The research focuses on reductive lithiation, a method for preparing organolithium compounds, typically involving the use of aromatic radical-anions or lithium metal in the presence of an aromatic electron transfer catalyst. The study explores the reductive lithiation of alkyl phenyl thioethers, alkyl chlorides, acrolein diethyl acetal, and isochroman using lithium dispersion as a source of lithium metal, absent of an electron transfer agent. The experiments involved various substrates with different alkyl group sizes to investigate the steric effect on the reaction's efficiency and selectivity. The analyses included DFT calculations to understand the bond dissociation energies and adsorption geometries on the lithium surface, as well as traditional organic chemistry techniques such as NMR spectroscopy and mass spectrometry to characterize the products and monitor the progress of the reactions. The results showed that lithium dispersion could achieve reductive lithiation efficiently and that the reactivity order was reversed when comparing the presence or absence of an electron transfer agent, with smaller alkyl groups exhibiting greater reactivity. This discovery challenges the prevailing understanding of reductive lithiation and highlights the significance of steric effects in these reactions.