Complex-induced proximity effects and dipole-stabilized carbanions: kinetic evidence for the role of complexes in the .alpha.'-lithiations of carboxamides

Abstract

The kinetics of the '-lithiations of /V,Ai-dimethyl-2,4,6-triisopropylbenzamide (4) and (V,7V-diethyl-2,4,6-triisopropylbenzamide (5) by seobutyllithium (j-BuLi) in cyclohexane have been investigated. Direct observation of the reactant amide, the intermediate amide-lithium reagent complex(es), and the '-lithiated products by stopped-flow infrared spectroscopy was used to investigate the initial rate constants as a function of reactant concentrations. At constant amide concentration the initial rate constant decreases sharply with increasing concentration of J-BuLi. This behavior is also observed in the presence of tetramethylethylenediamine (TMEDA). The major interaction of TMEDA with s-BuLi in cyclohexane is shown by cryoscopic measurements to be an addition of TMEDA to aggregated J-BuLi. Semiquantitative schemes constructed on the basis of the kinetic data suggest the presence of at least two reactive complexes and that complexes with more ligands are more reactive. The implications of these results are discussed.

Beyond Thermodynamic Acidity: A Perspective on the Complex‐Induced Proximity Effect (CIPE) in Deprotonation Reactions

“…[50] The reaction was shown to involve rapid formation of differentially complexed sBuLi tetramers with favorable equilibrium constants consistent with profile 1 e. Structure 33, which shows only one complete amide structure for clarity, contains three amide substrates complexed to the tetrameric organolithium complex and is the most reactive by a factor of 1000 relative to differentially complexed tetramers. A surprising decrease in the initial rate constant for the formation of 35 with an increase in sBuLi concentration is attributable to the fact that the concentration of this critical species decreases as the concentration of sBuLi is increased.…”

Certain applications of heteroatom directed ortho-metalation in sulfur heterocycles

“…25 Anionic carboannulation was utilised by others 27 to annulate a quinone ring carrying a phenylthio substituent on a thiophene ring.…”

Bidirectional Metalation of Hydrobenzoin: Direct Access to New Chiral Ligands and Auxiliaries

“…Support for pre-complexation of the alkyllithium to the DMG was given by the work of Beak and co-workers 38 who directly observed a complexed species upon reaction of the dimethyl carboxamide 148 with s-BuLi in cyclohexane using stopped-flow IR spectroscopy (Scheme 27). It was shown that the s-BuLi tetramer 149, which was formed in rapid equilibrium with 148, is a thousand times more reactive compared to differentially complexed tetramers.…”