Organic Letters
Letter
for bis Me2O solvate). A closely related tetrahedral intermediate
(Ph2(Me2N)COLi) crystallizes from THF as a bis-solvated dimer.15a
(15) (a) Adler, M.; Marsch, M.; Nudelman, N. S.; Boche, G. Angew.
Chem., Int. Ed. 1999, 38, 1261. (b) Adler, M.; Adler, S.; Boche, G. J. Phys.
Org. Chem. 2005, 18, 193.
(16) High yields of ketones were obtained from addition of lithium
acetylides to δ-lactones. The tetrahedral intermediates were not
detected. Chabala, J. C.; Vincent, J. E. Tetrahedron Lett. 1978, 19, 937.
(17) Bender, M. L. J. Am. Chem. Soc. 1953, 75, 5986.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the NSF for financial support (CHE-0717954) and
funding for instrumentation (NSF CHE-9709065, CHE-
9304546).
(18) Fraenkel, G.; Watson, D. J. Am. Chem. Soc. 1975, 97, 231.
(19) Kinetically formed mixed aggregates have been detected for the
reaction of n-BuLi with benzaldehyde,3 deprotonation of trimethylsilyl-
acetylene with (n-BuLi)2,1a deprotonation of ketone with (LiNiPr)2,1d
aldol reaction of tetrameric and dimeric lithium enolate,1d and the
conjugate addition of LiNiPr2.20a
(20) (a) Ma, Y.; Hoepker, A. C.; Gupta, L.; Faggin, M. F.; Collum, D. B.
J. Am. Chem. Soc. 2010, 132, 15610. (b) Parsons, R. L., Jr.; Fortunak, J.
M.; Dorow, R. L.; Harris, G. D.; Kauffman, G. S.; Nugent, W. A.;
Winemiller, M. D.; Briggs, T. F.; Xiang, B.; Collum, D. B. J. Am. Chem.
Soc. 2001, 123, 9135. Qu, B.; Collum, D. B. J. Org. Chem. 2006, 71, 7117.
(c) Sun, X. F.; Kenkre, S. L.; Remenar, J. F.; Gilchrist, J. H.; Collum, D.
B. J. Am. Chem. Soc. 1997, 119, 4765. Zhao, P.; Condo, A.; Keresztes, I.;
Collum, D. B. J. Am. Chem. Soc. 2004, 126, 3113.
REFERENCES
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(3) McGarrity, J. F.; Ogle, C. A. J. Am. Chem. Soc. 1985, 107, 1805.
(4) Once the (n-BuLi)2 was consumed, the (n-BuLi)4 reacted at a
constant rate, corresponding to the rate of dissociation to the dimer (kTD
= 1.5 × 10−4 s−1 at −130 °C in 1:3 THF/Me2O).1a
(5) The complexity of RLi behavior is illustrated by the selectivity of
the Weinreb oxalamide Me(MeO)NC(O)C(O)OEt, where an
aryllithium reacts with the amide carbonyl, and n-BuLi reacts with the
ester, the opposite selectivity as observed in Scheme 1. Chiu, C. C.;
Jordan, F. J. Org. Chem. 1994, 59, 5763.
(21) (a) Abu-Hasanayn, F.; Streitwieser, A. J. Am. Chem. Soc. 1996,
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(22) Mixed aggregates have been frequently observed:20 (a) Hope, H.;
Power, P. P. J. Am. Chem. Soc. 1983, 105, 5320. (b) Jackman, L. M.;
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Chem. 2003, 68, 6387. (e) Sott, R.; Granander, J.; Hilmersson, G. J. Am.
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(6) Bender, M. L.; Ginger, R. D.; Unik, J. P. J. Am. Chem. Soc. 1958, 80,
1044.
(7) Solutions of 4-fluorophenyllithium were prepared by treatment of
trimethyl(4-fluorophenyl)stannane with n-BuLi. Like PhLi,1c,8 4-
fluorophenyllithium is a mixture of a monomer and dimer in THF-
containing solvents. In 1:3 THF/Me2O at −119 °C, KMD = [D]/[M]2 =
160 M−1. For conversion of the dimer to monomer, ΔH‡ = 6.4 kcal/mol,
ΔS‡ = −7.0 eu. At −110 °C kDM = 270 s−1. The 13C NMR shifts of the
(23) Grindley, T. B. Tetrahedron Lett. 1982, 23, 1757. Cain, D.; Pawar,
D. M.; Stewart, M.; Billings, H.; Noe, E. A. J. Org. Chem. 2001, 66, 6092.
(24) The reaction with ArLi was first-order in ester. Attempts to
determine order in ArLi gave significant scatter, but the results do
eliminate a zero-order reaction in ArLi. However, rate determining ester
E/Z isomerization cannot apply to both the ArLi reaction with 1 and the
much slower reaction (factor of 100) of 2,5-difluorophenyllithium.
(25) The NMR properties of 6·ArLi were very similar to those of 3·
ArLi. The same heterodimer was formed if the tertiary alcohol was
treated with excess ArLi at −110 °C. Monomeric 6 was not formed even
when deprotonated by a monomeric base at temperatures where the
dimerization of 6 is slow. We hypothesize that any (6)1 generated could
rapidly form the strongly hydrogen bonded dimer (RO−H−OR− Li+),
which is then deprotonated to form (6)2. Alternatively, the hydrogen
bonded alcohol could be deprotonated directly to form RO−H−OR−
Li+.
(26) Analysis of the concentration vs time curve shows that
monomeric ArLi is at least 3.5 times as reactive as the dimer towards 5.
(27) Addition of LiI in THF affects the 19F NMR shifts of 2 but not
those of 1 (see Supporting Information).
(28) Comparable nickel-catalyzed amide and ester hydrolysis rates of
an imidazole-substituted carboxylate have been reported: Suh, J.; Park,
T. H.; Hwang, B. K. J. Am. Chem. Soc. 1992, 114, 5141.
C−Li carbons for the dimer are δ 180.0 (1:2:3:4:3:2:1 septet, JC‑Li
=
19.5), and for the monomer, δ 187.9 (poorly resolved 1:1:1:1 quartet).
Compare δ 188.2 and 196.4 for the PhLi dimer and monomer.
(8) Bauer, W.; Winchester, W. R.; Schleyer, P. v. R. Organometallics
1987, 6, 2371.
(9) These observations support the structure assignment of 3·ArLi:
one of the 19F NMR signals is close to that of (ArLi)2, and the other two
are close to those of the homodimer (3)2; the 13C NMR signal of the C−
Li carbon shows a 1:2:3:4:3:2:1 septet at δ 180.9 (compare (ArLi)2 at δ
180.0), from coupling to two 7Li; an experiment with 13C enriched ester
showed a resonance at δ 102.7 for the acetal carbon.10 The molecular
weight of 3·ArLi in Me2O solution estimated by DOSY experi-
ments11−13 at −115 °C was 513 (calcd 464.4 for 3·ArLi ·Me2O).
(10) A tetrahedral intermediate (presumably stabilized by chelation)
was detected after addition of 1-methyl-2-lithiobenzimidazole to methyl
benzoate (13C signal of the acetal carbon at δ 101.9): Asakawa, K.;
Dannenberg, J. J.; Fitch, K. J.; Hall, S. S.; Kadowaki, C.; Karady, S.; Kii,
S.; Maeda, K.; Marcune, B. F.; Mase, T.; Miller, R. A.; Reamer, R. A.;
Tschaen, D. M. Tetrahedron Lett. 2005, 46, 5081.
(11) (a) Jerschow, A.; Muller, N. J. Magn. Reson. 1997, 125, 372.
(b) Hilmersson, G.; Davidsson, O. Organometallics 1995, 14, 912.
(12) (a) Keresztes, I.; Williard, P. G. J. Am. Chem. Soc. 2000, 122,
10228. (b) Li, D.; Kagan, G.; Hopson, R.; Williard, P. G. J. Am. Chem.
Soc. 2009, 131, 5627.
(13) Fernandez, I.; Martinez-Viviente, E.; Breher, F.; Pregosin, P. S.
Chem.Eur. J. 2005, 11, 1495.
(14) The structure assignment of (3)2 was based on its mode of
formation, its decomposition to ketone at −95 °C, and the observation
of the ketal carbon at δ 102.8 in the 13C enriched substrate.10 The dimer
aggregation state was inferred from a DOSY11−13 molecular weight
estimation in Me2O solution at −115 °C: 559 g/mol (calcd 632.5 g/mol
D
Org. Lett. XXXX, XXX, XXX−XXX