Solution Structure and Chelation Properties of 2-Thienyllithium Reagents

Abstract

[reaction: see text] The solution and chelation properties of 2-thienyllithium reagents with potential amine and ether chelating groups in the 3-position and related model systems have been investigated using low temperature 6Li, 7Li, 13C, and 31P NMR spectroscopy, 15N-labeling, and the effect of solvent additives. In THF-ether mixtures at low temperature 3-(N,N-dimethylaminomethyl)-2-thienyllithium (4) is ca. 99% dimer (which is chelated) and 1% monomer (unchelated), whereas 3-(methoxymethyl)-2-thienyllithium (5) is <10% dimer. Compound 5 crystallizes as a THF-solvated dimer, but there is no indication that the ether side chain is chelated in solution. Both 4 and 5 form PMDTA-complexed monomers almost stoichiometrically, similar to the model compound 2, in sharp contrast to phenyl analogues, which show very different behavior. The barriers to dimer interconversion are ca. 2 kcal/mol lower and chelation is significantly weaker in the 2-thienyllithium reagents than in their phenyl analogues.

Advanced NMR Methods and DFT Calculations on the Regioselective Deprotonation and Functionalization of 1,1′‐Methylenebis(3‐methylimidazole‐2‐thione)

“…The 13 C– 7 Li coupling of 35.9 Hz is very similar to those of other monomeric ArLi reagents such as phenyllithium or thienyllithium derivatives . The 1 J ( 13 C, 7 Li) coupling is typically 10–14 Hz in tetramers, 20 Hz in dimers and 40 Hz in monomers; therefore, on the basis of our findings, we ascribe a monomeric structure to 5 in THF solution, as will be shown below.…”

Metalated heterocycles in organic synthesis: Recent applications

“…The solution structure and chelation properties of some of these 2-thienyllithiums have being studied recently by NMR techniques. 29 In some cases, temperature-dependent behaviors have been observed, as in the LDA-promoted lithiation of 2-bromothiophene at -78 ºC which afforded the expected 5-substituted-2-bromothiophene.…”

Metalated Heterocycles in Organic Synthesis: Recent Applications

“…The solution structure and chelation properties of some of these 2-thienyllithiums have being studied recently by NMR techniques. 29 In some cases, temperature-dependent behaviors have been observed, as in the LDA-promoted lithiation of 2-bromothiophene at -78 ºC which afforded the expected 5-substituted-2-bromothiophene. However, the same process at room temperature or 0 ºC gave a 5-alkylated-2,4-dibromothiophene according to a halogen-transfer-based halogen dance process.…”