Organolithium reagent

Organolithium reagents are a collection of organolithium compounds that are widely used in organic synthesis and polymer chemistry. These reagents are used to transfer the organic group or the lithium atom to diverse substrates, usually through nucleophilic addition or simple deprotonation. Organolithium reagents are used in industry as an initiator for anionic polymerization, which leads to the production of various elastomers.

Studies of organolithium reagents began in the 1930s and were pioneered by Karl Ziegler, Georg Wittig, and Henry Gilman. In comparison with Grignard (magnesium) reagents, organolithium reagents can often perform the same reactions with increased rates and higher yields, such as in the case of metalation. Since then, organolithium reagents have overtaken Grignard reagents in common usage.

Although simple alkyllithium species are often represented as monomer RLi, they exist as aggregates (oligomers) or polymers. The degree of aggregation depends on the organic substituent and the presence of other ligands. These structures have been elucidated by a variety of methods, notably ⁶Li, ⁷Li, and ¹³C NMR spectroscopy and X-ray diffraction analysis. Computational chemistry supports these assignments.

Due to the large difference in electronegativity between the carbon atom and the lithium atom, the C−Li bond is highly ionic. Owing to the polar nature of the C−Li bond, organolithium reagents are good nucleophiles and strong bases. For laboratory organic synthesis, many organolithium reagents are commercially available in solution form. These reagents are highly reactive, and are sometimes pyrophoric.

The relative electronegativities of carbon and lithium suggest that the C−Li bond will be highly polar. However, certain organolithium compounds possess properties such as solubility in nonpolar solvents that complicate the issue. While most data suggest the C−Li bond to be essentially ionic, there has been debate as to how much covalent character exists in it. One estimate puts the percentage of ionic character of alkyllithium compounds at 80 to 88%.

In allyl lithium compounds, the lithium cation coordinates to the face of the carbon π bond in an η³ fashion instead of a localized, carbanionic center, thus, allyllithiums are often less aggregated than alkyllithiums. In aryllithium complexes, the lithium cation coordinates to a single carbanion center through a Li−C σ type bond.

Like other species consisting of polar subunits, organolithium species aggregate. Formation of aggregates is influenced by electrostatic interactions, the coordination between lithium and surrounding solvent molecules or polar additives, and steric effects.

A basic building block toward constructing more complex structures is a carbanionic center interacting with a Li₃ triangle in an η³- fashion. In simple alkyllithium reagents, these triangles aggregate to form tetrahedron or octahedron structures. For example, methyllithium, ethyllithium and tert-butyllithium all exist in the tetramer [RLi]₄. Methyllithium exists as tetramers in a cubane-type cluster in the solid state, with four lithium centers forming a tetrahedron. Each methanide in the tetramer in methyllithium can have agostic interaction with lithium cations in adjacent tetramers. Ethyllithium and tert-butyllithium, on the other hand, do not exhibit this interaction, and are thus soluble in non-polar hydrocarbon solvents. Another class of alkyllithium adopts hexameric structures, such as n-butyllithium, isopropyllithium, and cyclohexanyllithium.