Influence of Ligand Structures on Chelate Stabilities
A R T I C L E S
Scheme 1
Chart 1. Relative Rate Constants (in parentheses) for the
Dehydrobromination of 1 by LDA Solvated by Unsubstituted
Ethanolamine-derived Amino Ethers
Results
The results are presented sequentially as follows: (1) Rate
studies establish the dominance of monomer-based eliminations;
(2) semiempirical (MNDO) computational studies address how
ligand structure influences the stabilities of chelates relative to
1
their open (η ) forms; (3) DFT methods probe nuances of the
LDA-mediated syn-elimination, including an elimination path-
way via a highly solvated LDA monomer.
General Methods. LDA was prepared as a white crystalline
solid.17 The ligands in Charts 1-3 are commercially available,
1
8
reported in the literature, or readily available from modified
6
15
syntheses (Supporting Information). Li and N NMR spec-
troscopic studies
1
9,20
6
15
17
show [ Li, N]LDA to be solvated by a
number of amino ethers and related polyfunctional ligands to
1
be η -solvated dimers. The distinction of O- rather than N-bound
to rephrase the original question: Why is there no gem-dimethyl
effect? This question leads us to consider the dominant and
complex steric effects that influence metal ion chelation. As
part of this study we revisit the long-standing problem of
choosing the appropriate reference state when studying the
chelate effect.1
coordination is consistent with previous studies showing that
ethers are superior to sterically demanding trialkylamines as
(
10) Beesley, R. M.; Ingold, C. K.; Thorpe, J. F. J. Chem. Soc. 1915, 107, 1080.
Ingold, C. K. J. Chem. Soc. 1921, 119, 305.
5,16
(11) Also, see the rigid group principle: Schmiegel, J.; Funke, U.; Mix, A.;
Gruetzmacher, H. F. Chem. Ber. 1990, 123, 1397. Voegtle, F.; Mayenfels,
P.; Luppertz, F. Synthesis 1984, 580. Rasshofer, W.; Oepen, G.; Mueller,
W. M.; Voegtle, F. Chem. Ber. 1978, 111, 1108. Siemeing, U. Polyhedron
1
997, 16, 1513.
(
12) Yamamoto, Y.; Takagishi, H.; Itoh, K. J. Am. Chem. Soc. 2002, 124, 28.
Hicks, F. A.; Buchwald, S. L.; J. Am. Chem. Soc. 1996, 118, 11688. Jung,
M. E.; Trifunovich, I. D.; Lensen, N. Tetrahedron Lett. 1992, 33, 6719.
Hill, E. A.; Link, D. C.; Donndelinger, P. J. Org. Chem. 1981, 46, 1177.
Eliel, E. L.; Knox, D. E. J. Am. Chem. Soc. 1985, 107, 2946. McIntyre, S.;
Sansbury, F. H.; Warren, S. Inorg. Chim. Acta 1984, 89, 157.
(
13) T u¨ z u¨ n, N. S.; Aviyente, V.; Houk, K. N. J. Org. Chem. 2002, 67, 5068.
Kende, A. S.; Journet, M. Tetrahedron Lett. 1995, 36, 3087.
14) Brown, R. F.; van Gulick, N. M. J. Org. Chem. 1956, 21, 1046.
15) (a) Frausto da Silva, J. J. R. J. Chem. Educ. 1983, 60, 390. (b) Simmons,
E. L. J. Chem. Educ. 1979, 56, 578. (c) Rosseinsky, D. R. J. Chem. Soc.,
Dalton Trans. 1979, 731. (d) Munro, D. Chem. Br. 1977, 13, 100. (e)
Hancock, R. D.; Marsicano, F. J. Chem. Soc., Dalton Trans. 1976, 1096.
(
(
(
f) Jones, G. R. H.; Harrop, R. J. Inorg. Nucl. Chem. 1973, 35, 173. (g)
Manhas, B. S. Res. J. Sci. 1974, 1, 16. (h) Bent, H. A. J. Phys. Chem.
1956, 60, 123.
(
8) Kirby, A. J. AdV. Phys. Org. Chem. 1980, 17, 183. Hammond, G. S. Steric
Effects in Organic Chemistry, Newman, M. S. Ed., Wiley: New York,
(16) Rutherford, J. L.; Hoffmann, D.; Collum, D. B. J. Am. Chem. Soc. 2002,
124, 264.
1956. Eliel, E. Stereochemistry of Carbon Compounds; McGraw-Hill Book
Comp.: New York, 1962; p 197. Capon, B.; McManus, S. P. Neighboring
Group Participation; Plenum Press: New York, 1976; Vol. I, p 43. See
also: Galli, C.; Mandolini, L. Eur. J. Org. Chem. 2000, 3117. Jung, M. E.
Synlett 1999, 843. Parrill, A. L.; Dolata, D. P. J. Mol. Struct. (THEOCHEM)
(17) Kim, Y.-J.; Bernstein, M. P.; Galiano-Roth, A. S.; Romesberg, F. E.; Fuller,
D. J.; Harrison, A. T.; Collum, D. B.; Williard, P. G. J. Org. Chem. 1991,
56, 4435.
(18) (a) A, B, F, G: Remenar, J. F.; Lucht, B. L.; Collum, D. B. J. Am. Chem.
Soc. 1997, 119, 5567. (b) C: Brown, H. C.; Zaidlewicz, M.; Dalvi, P. V.;
Narasimhan, S.; Mukhopadyay, A. Organometallics 1999, 18, 1305. (c)
D: Buøen, S.; Dale, J. Acta Chem. Scand. 1986, B40, 278. (d) E: Sammes,
P. G.; Smith, S. J. Chem. Soc., Perkin Trans. 1 1984, 2415; see also ref
1a. (e) H: Haarstad, V. B.; Domer, F. R.; Chihal, D. M.; Rege, A. B.;
Charles, H. C. J. Med. Chem. 1976, 19, 760. (f) I, J: Eckhardt, G. Org.
Mass. Spectrom. 1979, 14, 31. (g) L, M: Cope, A. C.; Kliegman, J. M.;
Friedrich, E. C. J. Am. Chem. Soc. 1967, 89, 287. (h) P: Seebach, D.;
Kalinowski, H.-O.; Bastani, B.; Crass, G.; Daum, H.; D o¨ rr, H.; DuPreez,
V. E.; Langer, W.; N u¨ ssler, C.; Dei, H.-A.; Schmidt, M. HelV. Chim. Acta
1977, 60, 301. (i) S, T: Di Vona, M. L.; Illuminati, G.; Lillocci, C. J.
Chem. Soc., Perkin Trans 2 1985, 1943. (j) U, V: Coote, S. J.; Davis, S.
G.; Goodfellow, C. L.; Sutton, K. H.; Middlemiss, D.; Naylor, A.
Tetrahedron: Asymmetry 1990, 1, 817. (k) W: Pine, S. H.; S a´ nchez, B.
L. J. Org. Chem. 1971, 36, 829. (l) X: Traynelis, V. J.; Dadura, J. G. J.
Org. Chem. 1961, 26, 686. (m) Y: Seebach, D.; Kalinowski, H.-O.; Bastani,
B.; Crass, G.; Daum, H.; D o¨ rr, H.; DuPreez, V. E.; Langer, W.; N u¨ ssler,
C.; Oei, H.-A.; Schmidt, M. HelV. Chim. Acta 1977, 60, 301. (n) Z: Shultz,
O. E.; Ziegler, A. Pharmazie 1970, 25, 472. (o) AA: Periasamy, M.;
Ramanathan, C. R.; Kumar, N. S. Tetrahedron: Asymmetry 1999, 10, 2307.
1
996, 370, 182. Lightstone, F. C.; Bruice, T. C. J. Am. Chem. Soc. 1994,
1
16, 10789. Parrill, A. L.; Dolata, D. P. Tetrahedron Lett. 1994, 35, 7319.
Keese, R.; Meyer, M. Tetrahedron 1993, 49, 2055. Jung, M. E.; Gervay,
J. J. Am. Chem. Soc. 1991, 113, 224. Schleyer, P. v. R. J. Am. Chem. Soc.
1
961, 83, 1368. Allinger, N. L.; Zalkow, V. J. Org. Chem. 1960, 25, 701.
Bruice, T. C.; Pandit, U. K. J. Am. Chem. Soc. 1960, 82, 5858.
1
0
(
9) The gem-dimethyl effect and affiliated Thorpe-Ingold effect have been
discussed in the context of organometallic chemistry: Bessel, C. A.;
Aggarwal, P.; Marschilok, A. C.; Takeuchi, K. J. Chem. ReV. 2001, 101,
1
1
031. Casey, C. P.; Klein, J. F.; Fagan, M. A. J. Am. Chem. Soc. 2000,
22, 4320. Faller, J. W.; Patel, B. P.; Albrizzio, M. A.; Curtis, M.
Organometallics 1999, 18, 3096. Barkley, J.; Ellis, M.; Higgins, S. J.;
McCart, M. K. Organometallics 1998, 17, 1725. Desper, J. M.; Gellman,
S. H.; Wolf, R. E., Jr.; Cooper, S. R. J. Am. Chem. Soc. 1991, 113, 8663.
Uemura, M.; Minami, T.; Hayashi, Y. J. Am. Chem. Soc. 1987, 109, 5278.
Shaw, B. L. J. Organomet. Chem. 1980, 200, 307. Shaw, B. L.; Weeks, B.
J. Chem. Soc., Dalton Trans. 1979, 1972. Shaw, B. L. J. Am. Chem. Soc.
1
975, 97, 3856. Al-Salem, N. A.; Empsall, H. D.; Markham, R.; Newman,
M. S.; Busch, D. H.; Cheney, G. E.; Gustafson, C. R. Inorg. Chem. 1972,
2, 2890.
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