I. Solution and chelation properties of ortho-substituted phenyllithium derivatives. II. Solution and chelation properties of 3-substituted 2-thienyllithium derivatives. III. Development of a quantitative measure of chelation strength using alpha-trimethy

The use of organolithium reagents to form C--C bonds is one of the most important synthetic methodologies in organic chemistry. Knowledge of the solution structure of organolithium reagents is key to understanding and fully utilizing these important synthetic reagents. One of the most powerful properties of organolithium reagents is the ability of Lewis basic functional groups to coordinate either intermolecularly or intramolecularly with the lithium atom, a process commonly known as chelation. We have investigated the solution and chelation properties of several classes of organolithium reagents including phenyllithium, 2-thienyllithium and vinyllithium reagents using variable temperature, heteronuclear NMR spectroscopy in conjunction with the polar additives TMEDA, PMDTA, TMTAN and HMPA.; The ortho-substituted phenyllithium reagents and the 3-substituted 2-thienyllithium reagents that were studied exist in both monomeric and dimeric forms at low temperatures in ethereal solutions containing THF. Intramolecular chelation of the nitrogen atom of an ortho-oxazoline group in the phenyllithium series is relatively strong. Chelation in 2-thienyllithium reagents containing 5-membered ring ether and amine chelating groups is much weaker than the corresponding phenyllithium analogs; nearly quantitative dissociation from chelated dimers to non-chelated monomers occurred upon addition of just 1 equiv of PMDTA. 3-N,N-Dimethylaminomethyl-2-thienyllithium is >99% dimer (KMD > 31,000 M-1 at -136°C) in 3:2:1 THF:Me2O:Et2O while 3-methoxymethyl-2-thienyllithium is mostly monomer (KMD was 3.3 M-1 at -135°C) suggesting that chelation in the 5-membered ring amine is much stronger than in the 5-membered ring ether.; A method of quantitatively determining the relative chelation strength of two chelating groups was developed and tested using alpha-trimethylsilyl-substituted vinyllithium reagents. These reagents are monomeric below -70°C in 3:2 THF:Et2O, but entropically favored dimers were observed for several of the reagents at higher temperatures. Direct competition for lithium chelation between 5- and 7-ring ether chelates showed a ≥50:1 preference for the 5-ring ether chelate. Weaker chelation was observed for 7-membered ring ether and amine chelating groups.