Hemilabile Ligands in Organolithium Chemistry: Substituent Effects on Lithium Ion Chelation

The lithium diisopropylamide-mediated 1,2-elimination of 1-bromocyclooctene to provide cyclooctyne is investigated using approximately 50 potentially hemilabile polyethers and amino ethers. Rate
laws for selected ligands reveal chelated monomer-based pathways. The dependence of the rates on ligand
structure shows that anticipated rate accelerations based on the gem-dimethyl effect are nonexistent and
that substituents generally retard the reaction. With the aid of semiempirical and DFT computational studies,
the factors influencing chelation are discussed. It seems that severe buttressing within chelates of the
substitutionally rich ligands precludes a net stabilization of the chelates relative to nonchelated (η1-solvated)
forms. One ligandMeOCH2CH2NMe2appears to promote elimination uniquely by a higher-coordinate
monomer-based pathway.