Solid-State and Solution Structures of Glycinimine-Derived Lithium Enolates

Abstract

A combination of crystallographic, spectroscopic, and computational studies was applied to study the structures of lithium enolates derived from glycinimines of benzophenone and (+)-camphor. The solvents examined included toluene and toluene containing various concentrations of tetrahydrofuran, N,N,N′,N′-tetramethylethylenediamine (TMEDA), (R,R)-N,N,N′,N′-tetramethylcyclohexanediamine [(R,R)-TMCDA], and (S,S)-N,N,N′,N′-tetramethylcyclohexanediamine [(S,S)-TMCDA]. Crystal structures show chelated monomers, symmetric disolvated dimers, S4-symmetric tetramers, and both S6- and D3d-symmetric hexamers. 6Li NMR spectroscopic studies in conjunction with the method of continuous variations show how these species distribute in solution. Density functional theory computations offer insights into experimentally elusive details.

Lithium Enolates Derived from Weinreb Amides: Insights into Five-Membered Chelate Rings

“…Mixtures of enolate 3c and 3d in THF at −80 °C showed the resonances of the two dominant homoaggregates along with 3:1, 2:2, and 1:3 heteroaggregate resonances characteristic of an ensemble of tetramers in rapid intraaggregate lithium exchange 15c (Figure 3). Monitoring of the relative concentrations of the five aggregates versus measured mole fraction 20 afforded a Job plot (Figure 4) displaying a nearly statistical distribution of homo- and heterotetramers.…”

“…Resonances corresponding to lithiums bearing substitutionally labile THF ligands shift markedly downfield, whereas unsolvated lithiums do not move appreciably. 15a,e,23 More highly solvated forms (often the lower aggregates) also increase in intensity relative that of the lesser-solvated forms owing to mass action. In the event, incremental addition of pyridine markedly shifted the 6 Li resonances of dimers and tetramers .…”

“…10b Spectral data do not distinguish D 2 d tetramer 8 from S 4 tetramer 7 : both should display a single 6 Li resonance and have ample precedent in the structural organolithium literature. 15c,26,27 We cannot exclude a fluctional stereochemical mixture; the facility of chelate exchange was suggested by the observed high symmetry of LDA mixed aggregate 6 .…”

“…Crystal structures of analogous tetrameric chelates show this same motif. 15,26,27 The critical observation is that five-membered-ring chelates with relatively small methoxy ligands allow for cooperative solvation by THF ( 19 ) and geminal chelation ( 20 ) . 29,30 …”

“…15a Unusual solvation numbers in the tetrameric enolates, if undetected, would wreak havoc on kinetics-derived mechanistic models owing to the incorrectly assigned reactant.…”