Aggregation and Reactivity of Phenyllithium Solutions

Abstract

Phenyllithium forms a mixture of tetramer and dimer in ether. Complete conversion to dimeric solvates is achieved by the addition of THF, dioxolane, DME, or TMEDA in near stoichiometric amounts. The addition of 2,5-dimethyltetrahydrofuran favors dimer, but tetramer is still detectable at 14 equiv of cosolvent. PMDTA converts PhLi to monomer in ether. In THF, PhLi is a mixture of dimer and monomer. Addition of TMEDA forms a series of complexes, but the dimer/monomer ratio is essentially unaffected. PMDTA and HMPA form monomeric PhLi stoichiometrically. HMTTA and DMPU also result in monomer formation but several equiv are required. 12-Crown-4 shows no spectroscopically detectable complexation of PhLi in THF. All of the cosolvents tested increase the reactivity of PhLi in THF in a test metalation reaction: HMPA and 12-crown-4 show the largest effects, PMDTA is intermediate, and HMTTA and TMEDA result in the least activation. In two selectivity tests, HMPA and 12-crown-4 show a substantially lower selectivity than the other cosolvents. We postulate that a contribution from a highly reactive separated ion pair (SIP) intermediate is responsible for the lower selectivity.

On the deprotonation of 3,5-dichloropyridine using lithium bases: in situ infrared spectroscopic studies

“…It is known that phenyllithium is a mixture of dimer and monomer in THF; 11 concerning pyridyllithiums, such studies were not reported (Scheme 1).…”

Synthesis, Receptor Binding, Molecular Modeling, and Proliferative Assays of a Series of 17α‐Arylestradiols

“…The addition of TMEDA in THF has little if any effect on the monomer/dimer ratio, but forms a series of complexes with phenyllithium. [19] These changes in the structure of the phenyllithium may explain, in this case, the observed increase in reactivity. Thus, with three equivalents of TMEDA per aryllithium, condensation of the aryllithiums 4 d and 4 g onto the carbonyl at position 17 of estrones 1 and 2 occurs in 60 % yield to give the arylestradiols 7, 9, or 12.…”

“…The crude product was purified by silica gel column chromatography with toluene/ethyl acetate (4:96) as eluent and crystallized in ether/pentane (1:9) to give 17 as a white solid (32 mg, 76 %). 17a-(4'-Methoxyphenyl)estra-1,3,5(10)-trien-3,17b-diol (19): A mixture of 6 and estrone 1 (155 mg), resulting from preparation of 6, was dissolved in methanol (15 mL) and THF (4.5 mL) containing Pd/C 10 % (25 mg) in suspension. The reaction mixture was stirred under atmospheric pressure of hydrogen for 17 h. After filtration and evaporation of the solvents, the residues were crystallized from dichloromethane to give 19 as a white solid in 68 % yield (with low solubility in various solvents).…”

Carbanion Chemistry

“…The results 9 for 3,5-di-t-butyl-phenyl lithium, 1, are illustrative ( Figure 2). Reich and coworkers 10 have provided a benchmark study of the power of nmr to characterize organolithium solutions. They studied the monomer/dimer/tetramer equilibria of phenyl lithium as a function of solvent and temperature.…”

“…Studies of the solvation of phenyl lithium from the relative shifts of the ring carbons provides an excellent example. 10 The Schade and Boche study 34 of solvation of a benzyl lithium discussed under 2D methods is another.…”