Journal of the American Chemical Society
ARTICLE
J. Org. Chem. 1991, 56, 4435. (b) Collum, D. B. Acc. Chem. Res. 1993,
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(28) Competitive and intramolecular isotope effects can be used to
examine post-rate-limiting proton transfer. They differ in that the intra-
molecular isotope effect demands a symmetry-equivalent choice of H
versus D within the same molecule whereas the competitive isotope effect
requires an exchange mechanism to establish the choice of H versus D.
(29) (a)Carpenter, B. K. Determination of Organic Reaction Mechanisms;
Wiley: New York, 1984. (b) Whisler, M. C.; MacNeil, S.; Snieckus, V.; Beak,
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(30) The calculated isotope effects in eqs 6 and 7 derive from the
regioselectivities derived from 1-2-d1, and 1-6-d1. If the isotope effects
are calculated using 1-2,6-d2 instead of 1, the isotope effects are
calculated as follows:
6
(12) 6Li is spin 1. For a review of Li NMR spectroscopy, see:
G€unther, H. J. Braz. Chem. Soc. 1999, 10, 241.
(13) (a) Espinet, P.; Albeniz, A. C.; Casares, J. A.; Martinez-Ilarduya,
J. M. Coord. Chem. Rev. 2008, 252, 2180. (b) Gakh, Y. G.; Gakh, A. A.;
Gronenborn, A. M. Magn. Reson. Chem. 2000, 38, 551. (c) McGill, C. A.;
Nordon, A.; Littlejohn, D. J. Process Anal. Chem. 2001, 6, 36. (d) Espinet,
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(14) Krasovskiy, A.; Knochel, P. Angew. Chem., Int. Ed. 2004, 43, 3333.
(15) Frisch, M. J.; et al. Gaussian 03, revision B.04; Gaussian, Inc.:
Wallingford, CT, 2004.
kHð2Þ=kDð2Þ ¼ ðkHð2Þ=kDð6ÞÞðkDð6Þ=kDð2ÞÞ ¼ 50
kHð6Þ=kDð6Þ ¼ ðkHð6Þ=kDð2ÞÞðkDð2Þ=kDð6ÞÞ ¼ 12
(16) (a) Ramirez, A.; Candler, J.; Bashore, C. G.; Wirtz, M. C.; Coe,
J. W.; Collum, D. B. J. Am. Chem. Soc. 2004, 126, 14700. (b) Riggs, J. C.;
Ramirez, A.; Cremeens, M. E.; Bashore, C. G.; Candler, J.; Wirtz, M. C.;
Coe, J. W.; Collum, D. B. J. Am. Chem. Soc. 2008, 130, 3406. (c) Kottke,
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(d) Reich, H. J.; Green, D. P.; Medina, M. A.; Goldenberg, W. S.;
(31) The method used to prepare 1-2,6-d2, which involves initial
metalation by LDA and quenching with MeOD (1.0 equiv) followed by
alternating pulses of n-BuLi without intermediate workups, may have a
general utility for exhaustive deuteration of the acidic sites on arenes.
(32) (a) Stegelmann, C.; Andreasen, A.; Campbell, C. T. J. Am.
Chem. Soc. 2009, 131, 8077. (b) Maniscalco, S. J.; Tally, J. F.; Fisher,
H. F. Arch. Biochem. Biophys. 2004, 425, 165.
(33) (a) Isotopic perturbation is insufficient to resolve the reso-
nances of 1 and 1-2,6-d2 by 19F NMR spectroscopy.33bꢀd The IR
absorbances of 1 (1428 cmꢀ1) and 1-2,6-d2 (1384 cmꢀ1) could be
monitored, but with some error introduced by absorbances of the
aryllithiums. (b) Hindermann, D. K.; Cornwell, C. D. J. Chem. Phys.
1968, 48, 4148. (c) Forsyth, D. A.; Yang, J.-R. J. Am. Chem. Soc. 1986,
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€
Gudmundsson, B. O.; Dykstra, R. R.; Phillips, N. H. J. Am. Chem. Soc.
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(17) 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.
(18) Snaith and co-workers underscored the merits of R3NHX salts
as precursors to anhydrous LiX salts. See: Barr, D.; Snaith, R.; Wright,
D. S.; Mulvey, R. E.; Wade, K. J. Am. Chem. Soc. 1987, 109, 7891.
Also see: Hall, P. L.; Gilchrist, J. H.; Collum, D. B. J. Am. Chem. Soc.
1991, 113, 9571.
(19) Zhao, P.; Collum, D. B. J. Am. Chem. Soc. 2003, 125, 14411 and
references cited therein.
(20) Rein, A. J.; Donahue, S. M.; Pavlosky, M. A. Curr. Opin. Drug
Discovery Dev. 2000, 3, 734.
(34) For an attempted comprehensive bibliography of anionic triple
ions of lithium salts (XꢀLiꢀXꢀ), see: Ma, Y.; Ramirez, A.; Singh, K. J.;
Keresztes, I.; Collum, D. B. J. Am. Chem. Soc. 2006, 128, 15399.
(35) The computations use the Gaussian standard state of 1.0 atm. If
the THF concentration is corrected to neat THF (approximately 12 M),
each solvation step benefits from approximately 2.0 kcal/mol of addi-
tional stabilization at ꢀ78 °C (195 K). Pratt, L. M.; Merry, S.; Nguyen,
S. C.; Quan, P.; Thanh, B. T. Tetrahedron 2006, 62, 10821.
(36) Frey, P. A.; Hegeman, A. D. Enzymatic Reaction Mechanisms;
Oxford University Press: New York, 2007; Chapter 2.
(21) (a) Espenson, J. H. Chemical Kinetics and Reaction Mechanisms,
2nd ed.; McGraw-Hill: New York, 1995; Chapter 2, p 44. (b) Atkins,
P. W.; Jones, L. L. Chemical Principles: The Quest for Insight, 2nd ed.; W
H. Freeman: New York, 2002. (c) Rae, M.; Berberan-Santos, M. N.
J. Chem. Educ. 2004, 81, 436.
(22) Determining initial rates (slopes) of a curved decay can be
strongly dependent on the percent conversion, requiring a compromise
between adequate sample size and loss of linearity. This problem is
mitigated by fitting a significant part of the decay, a portion that includes
some curvature, to a third-order polynomial (at2 þ bt þ c), making sure
not to include too much curvature. The parameter b represents the rate
at time zero. (One may verify this by taking the first derivative with
respect to t and setting t = 0. Initial rate = f0(0) = b.) The experimental
observable (NMR intensity, IR absorbance, etc.) is converted to
concentration to ensure a valid comparison between initial rates of
varying concentrations.
(23) For a review of rate studies of LDA-mediated reactions see:
Collum, D. B.; McNeil, A. J.; Ramirez, A. Angew. Chem., Int. Ed. 2007,
46, 3002.
(24) The concentration of LDA, although expressed in units of
molarity, refers to the concentration of the monomer unit (normality).
The concentration of THF is expressed as total concentration of free
(uncoordinated) ligand.
(37) LDA-mediated ortholithiations of 2-fluoropyridines also show
a second-order catalysis by LiCl.6c
(38) (a) Ma, Y.; Collum, D. B. J. Am. Chem. Soc. 2007, 129, 14818.
(b) Depue, J. S.; Collum, D. B. J. Am. Chem. Soc. 1988, 110, 5524. (c)
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(39) Laurence, C.; Nicolet, P.; Dalati, M. T.; Abboud, J.-L. M.;
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(41) Equation 17 appears to become undefined at [LiClT] = 0, but
this is not the case as described previously.3
(42) (a) Besson, C.; Finney, E. E.; Finke, R. G. J. Am. Chem. Soc.
2005, 127, 8179. (b) Besson, C.; Finney, E. E.; Finke, R. G. Chem. Mater.
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(e) Tanj, S.; Ohno, A.; Sato, I.; Soai, K Org. Lett. 2001, 3, 287.
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(25) The minor deviation above first order has the appearance of
experimental error. A forthcoming study, however, describes experi-
mental evidence of LDA-tetramer-based reactivities.
(26) We define the idealized rate law as that obtained by rounding
the observed reaction orders to the nearest rational order.
(27) Open dimers were first proposed for the isomerization of
oxiranes to allylic alcohols by mixed metal bases. See: Mordini, A.;
Rayana, E. B.; Margot, C.; Schlosser, M. Tetrahedron 1990, 46, 2401. For
a bibliography of lithium amide open dimers, see: Ramirez, A.; Sun, X.;
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therein.
(43) (a) Depue, J. S.; Collum, D. B. J. Am. Chem. Soc. 1988,
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7150
dx.doi.org/10.1021/ja200906z |J. Am. Chem. Soc. 2011, 133, 7135–7151