J. Am. Chem. Soc. 1997, 119, 5567-5572
5567
Lithium Diisopropylamide Solvated by Monodentate and
Bidentate Ligands: Solution Structures and Ligand Binding
Constants
Julius F. Remenar, Brett L. Lucht, and David B. Collum*
Contribution from the Department of Chemistry, Baker Laboratory, Cornell UniVersity,
Ithaca, New York 14853-1301
ReceiVed January 3, 1997X
Abstract: 6Li and 15N NMR spectroscopic studies of lithium diisopropylamide ([6Li]LDA and [6Li,15N]LDA) in
toluene/pentane solutions containing a variety of mono- and polydentate ligands are reported. LDA forms exclusively
dimers in the presence of n-BuOMe, Et2O, t-BuOMe, THF, 2-methyltetrahydrofuran, 2,2-dimethyltetrahydrofuran,
tetrahydropyran, dimethoxyethane, N,N,N′,N′-tetramethylethylenediamine, and MeOCH2CH2NR2 (NR2 ) NMe2, NEt2,
pyrrolidino). Addition of 1,2-dipyrrolidinoethane and (2-pyrrolidinoethyl)dimethylamine provides monomer-dimer
mixtures. Treatment of LDA with trans-N,N,N′,N′-tetramethylcyclohexanediamine (TMCDA) or trans-1-(dimethyl-
amino)-2-isopropoxycyclohexane in hydrocarbons afford exclusively monomers. Sparteine binds only reluctantly,
giving a mixture of unsolvated oligomers and monomer. Competitions of the ethereal ligands vs TMCDA afford
binding constants and associated free energies for dimer solvation which are correlated with those obtained previously
for lithium hexamethyldisilazide.
Introduction
investigation of mono- and polydentate ligands is a logical ex-
tension of previous investigations of lithium amide solvation
and aggregation. It also provides important structural and
thermochemical foundations for detailed rate studies of LDA-
mediated dehydrohalogenations described in the second portion
of the study.8
Despite the importance of organolithium reagents in organic
chemistry,1 our understanding of precisely how ligand structure
affects lithium ion coordination is still limited.2 Ligand-
dependent reactivities, selectivities, and other empirical observa-
tions are often suggested to reflect ligand binding constants
without adequate justification. We submit that an understanding
of reactivities requires a knowledge of (1) the reactant structures
and stabilities, (2) the aggregation and solvation events leading
up to the rate limiting transition structure, and (3) the influence
of organolithium reagent, solvent, and substrate on the stabilities
of the transition structures. Computational studies of the
possible transition structures become more important once
structure and rate studies establish the transition structure
stoichiometry.
(4) Solution structural studies of LDA: (a) Bernstein, M. P.; Romesberg,
F. E.; Fuller, D. J.; Harrison, A. T.; Williard, P. G.; Liu, Q. Y.; Collum, D.
B. J. Am. Chem. Soc. 1992, 114, 5100. (b) Kim, Y.-J.; Bernstein, M. P.;
Galiano-Roth, A. S.; Romesberg, F. E.; Williard, P. G.; Fuller, D. J.;
Harrison, A. T.; Collum, D. B. J. Org. Chem. 1991, 56, 4435. (c)
Romesberg, F. E.; Bernstein, M. P.; Gilchrist, J. H.; Harrison, A. T.; Fuller,
D. J.; Collum, D. B. J. Am. Chem. Soc. 1993, 115, 3475. (d) Galiano-
Roth, A. S.; Collum, D. B. J. Am. Chem. Soc. 1989, 111, 6772. (e) Galiano-
Roth, A. S.; Kim, Y.-J.; Gilchrist, J. H.; Harrison, A. T.; Fuller, D. J.;
Collum, D. B. J. Am. Chem. Soc. 1991, 113, 5053. (f) Romesberg, F. E.;
Gilchrist, J. H.; Harrison, A. T.; Fuller, D. J.; Collum, D. B. J. Am. Chem.
Soc. 1991, 113, 5751.
(5) Solid state structural studies of LDA: Mair, R. S.; Clegg, W.; O’Neil,
P. A. J. Am. Chem. Soc. 1993, 115, 3388. Williard, P. G.; Hintze, M. J. J.
Am. Chem. Soc. 1987, 109, 5539. Williard, P. G.; Hintz, M. J. J. Am. Chem.
Soc. 1990, 112, 8602. Zarges, W.; Marsch, M.; Harmes, K.; Boche, G.
Angew. Chem., Int. Ed. Engl. 1989, 28, 1392. Barnett, N. D. R.; Mulvey,
R. E.; Clegg, W.; O’Neil, P. A. J. Am. Chem. Soc. 1991, 113, 8187. Williard,
P. G.; Salvino, J. M. J. Org. Chem. 1993, 58, 1. Henderson, K. W.; Dorigo,
A. E.; Liu, Q.-Y.; Williard, P. G.; Schleyer, P. v. R.; Bernstein, P. R. J.
Am. Chem. Soc. 1996, 118, 1339. Also, see ref 4a.
(6) Other physicochemical studies of LDA: (a) Romesberg, F. E.;
Collum, D. B. J. Am. Chem. Soc. 1992, 114, 2112. (b) Bernstein, M. P.;
Collum, D. B. J. Am. Chem. Soc. 1993, 115, 789. (c) Bernstein, M. P.;
Collum, D. B. J. Am. Chem. Soc. 1993, 115, 8008. (d) Romesberg, F. E.;
Collum, D. B. J. Am. Chem. Soc. 1994, 116, 9187. (e) Romesberg, F. E.;
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Collum, D. B. J. Am. Chem. Soc. 1995, 117, 2166. (f) Renaud, P.; Fox,
M. A. J. Am. Chem. Soc. 1988, 110, 5702. (g) Xie, L.; Saunders, W. H.,
Jr. J. Am. Chem. Soc. 1991, 113, 3123. (h) Newcomb, M.; Varick, T. R.;
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T. S. Tetrahedron Lett. 1986, 27, 331. (j) Kopka, I. E.; Fataftah, Z. A.;
Rathke, M. W. J. Org. Chem. 1987, 52, 448. (k) Newcomb, M. A.; Burchill,
M. T. J. Am. Chem. Soc. 1984, 106, 8276. (l) Mass, R. J.; Rickborn, B. J.
Org. Chem. 1986, 51, 1992. (m) Ahlbrecht, H.; Schneider, G. Tetrahedron
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(7) Reviews of lithium amide structural studies: (a) Gregory, K.;
Schleyer, P. v. R.; Snaith, R. AdV. Inorg. Chem. 1991, 37, 47. (b) Mulvey,
R. E. Chem. Soc. ReV. 1991, 20, 167. (c) Collum, D. B. Acc. Chem. Res.
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We describe a two-part investigation of lithium diisopropyl-
amide (LDA).3 In this paper we will present NMR spectro-
scopic investigations of LDA in the presence of a variety of
monodentate and bidentate ligands.4-7 While ethereal ligands
provide dimeric LDA, several diamines afford the first examples
of monomeric LDA. We will show how a strongly coordinating
diaminestrans-N,N,N′,N′-tetramethyl-1,2-cyclohexanedi-
aminescan be used to determine the relative binding constants
of the ethereal ligands on the LDA dimer fragment. This
X Abstract published in AdVance ACS Abstracts, May 1, 1997.
(1) (a) Klumpp, G. W. Recl. TraV. Chim. Pays-Bas 1986, 105, 1. (b)
Polyamine-Chelated Alkali Metal Compounds; Langer, A. W., Jr., Ed.;
American Chemical Society: Washington, 1974. (c) Ions and Ion Pairs
in Organic Reactions; Szwarc, M., Ed.; Wiley: New York, 1972; Vols. 1
and 2. (d) Jackman, L. M.; Bortiatynski, J. In AdVances in Carbanion
Chemistry; JAI: New York, 1992, Vol. 1, pp 45-87.
(2) Seebach, D. Angew. Chem., Int. Ed. Engl. 1988, 27, 1624.
(3) LDA and related lithium dialkylamides are important reagents in
synthetic organic chemistry. For reviews, see: d’Angelo, J. Tetrahedron
1976, 32, 2979. Heathcock, C. H. In ComprehensiVe Carbanion Chemistry;
Buncel, E., Durst, T., Eds.; Elsevier: New York, 1980; Vol. B, Chapter 4.
Cox, P. J.; Simpkins, N. S. Tetrahedron: Asymmetry 1991, 2, 1. Asymmetric
Synthesis; Morrison, J. D., Ed.; Academic Press: New York, 1983; Vols.
2 and 3. Evans, D. A. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic Press: New York, 1983; Vol. 3, Chapter 1. Snieckus, V. Chem.
ReV. 1990, 90, 879.
S0002-7863(97)00029-2 CCC: $14.00 © 1997 American Chemical Society