On the mechanism of lithiation of hydric aromatics: Direct NMR evidence for short H-Li contacts in mixed aggregates

Full text of DOI:10.1021/jo960570a

5194
J . Org. Chem. 1996, 61, 5194-5195
Sch em e 1. P r op osed Mech a n ism for th e
Lith ia tion of Hyd r ic Com p ou n d s
On th e Mech a n ism of Lith ia tion of Hyd r ic
Ar om a tics: Dir ect NMR Evid en ce for Sh or t
H-Li Con ta cts in Mixed Aggr ega tes1
J ose´ M. Saa´,* Gabriel Martorell, and
Antonio Frontera
Departament de Quı´mica, Universitat de les Illes Balears,
07071 Palma de Mallorca, Spain
Received March 27, 1996
Two relevant aspects of the mechanism of the hetero-
atom-directed lithiation of aromatics are the matter of
current debate.2 The first is concerned with the neces-
sity,2,3 or not,4 to invoke the formation of intermediate
complexes as a step prior to the actual rate-determining
deprotonation,5 while the second refers both to the actual
structure of such prelithiation complexes6 and the de-
tailed mechanism of activation3-5 of the ortho (or ap-
propriately located) hydrogens.7 A number of studies
have provided evidence, kinetic or otherwise, for such
prelithiation complexes.2,8,9 Unfortunately, direct NMR
evidence has not been found. The working mechanistic
models for lithiation of nonhydric10 and hydric11 aromat-
ics are based on theoretical MNDO studies according to
which ortho hydrogens are activated due to agostic inter-
action12 with spatially close lithium atoms.13 In particu-
lar, the lithiation of naphthols11 and related compounds14
has been rationalized on the basis of the mechanism
illustrated in Scheme 1 (COSA and COUSA stand for
coordinatively saturated and unsaturated mixed aggre-
gates). Key issues raised by this proposal were as
follows: (a) the lithiation of naphthols should involve a
mixed aggregate showing dissimilar degrees of agostic
interaction with ortho and peri protons, and (b) peri
lithiation is actually favored because agostic interaction
is stronger at this position. The NMR studies described
below provide clear-cut evidence for the intermediacy of
mixed aggregates of the general type [(ArOLi)m‚(RLi)n]
for the lithiation of hydric compounds. These mixed
clusters undergo perceivable lithiation at ca. 30 to 50 °C
at the most activated peri hydrogens,15 which according
to the7Li-1H HOESY NMR spectra are the closest to the
lithium atoms.16
NMR titration studies commenced with solution A,17
1
7
which showed one set of signals in the H, 13C, and Li
spectra corresponding to the expected lithium 1-naph-
tholate 1,18 a dimer according to the 7Li quadrupole
splitting constant (QSC ) 111 kHz).19,20
7
1D (1H, 13C,18 and Li) and 2D (7Li-1H HOESY) NMR
spectra of independently prepared B, C, and D solutions17
revealed the formation of mixed organolithium-lithium
naphtholate species 3,18 Scheme 2, as supported by (a)
the presence of a set of duplicated signals both in the
aromatic and aliphatic regions of 1H (Figure 1) and 13C18
NMR spectra of solutions B-E; (b) the appearance of
7
three lithium species in the Li NMR spectra (Figure 1)
corresponding to butyllithium homodimer (2; δ 1.09 ppm),
lithium naphtholate homodimer (1; δ -0.51 ppm), and
butyllithium-lithium naphtholate mixed dimer (3; δ 0.08
7
ppm), as proved by the Li-1H HOESY spectra (Figure
2) of 1 (cross peaks with H′-8 and H′-2 of the naphthalene
skeleton) and 3 (with H-8 only, and the R and â
hydrogens of the butyl chain), the 1H-1H COSY spec-
trum.18 Interestingly, both 2 and the mixed cluster 3
were also found to be dimers (m + n ) 2) as demonstrated
by the multiplicity (heptuplets J CLi ) 20, 21.5 Hz,
respectively) of the carbon-bearing lithium in the 13C
NMR spectra;18 the 7Li QSC value for 3 (QSC ) 135 kHz)
also agrees with 3 being a dimer in TMEDA. The
equilibrium illustrated in Scheme 2 is almost completely
displaced to the right when a 4:1 n-butyllithium:1-
naphthol ratio is reached (K ∼ 2.5), further addition of
n-butyllithium (up to 8:1 ratio) not inducing further
apparent changes.
(1) Dedicated to Prof. Fe´lix Serratosa “in memoriam”.
(2) (a) Wakefield, B. J . Chemistry of Organolithium Compounds;
Pergamon: Oxford, 1974. (b) Gschwend H. W.; Rodriguez, H. R. Org.
React. 1979, 26, 1. (c) Klumpp, G. W. Rec. Trav. Chim. Pays-Bas 1986,
105, 1. (d) Snieckus, V. Chem. Rev. 1990, 90, 879.
(3) Roberts, J . D.; Curtin, D. Y. J . Am. Chem. Soc. 1946, 68, 1658.
(4) (a) van Eikema Homes, N. J . R.; Schleyer, P. v. R. Tetrahedron
1994, 50, 5903 and references cited therein.
(5) Resek, J . E.; Beak, P. J . Am. Chem. Soc. 1994, 116, 405.
(6) Beak, P.; Meyers, A. I. Acc. Chem. Res. 1986, 19, 356.
(7) Remote metalations: (a) Fu, J .-m.; Zhao, B.-p.; Sharp, M. J .;
Snieckus, V. J . Org. Chem. 1991, 56, 1683. (b) Coll, G.; Morey, J .; Costa,
A.; Saa´ J . M. J . Org. Chem. 1988, 53, 5345. (c) Bashir-Hashemi, A.;
Arduengo, A. J . Chem. Abstr. 1981, 100, 103074q. See also ref 14.
(8) Hay, D.; Song, Z.; Smith, S. G.; Beak, P. J . Am. Chem. Soc. 1988,
110, 8145 and references cited therein. See also ref 5.
(9) (a) Meyers, A. I.; Fuentes, L. M.; Reiker, W. F. J . Am. Chem.
Soc. 1983, 105, 2082. (b) Meyers, A. I.; Dickman, D. A. J . Am. Chem.
Soc. 1987, 109, 1263. (c) Warmus, J . S.; Rodkin, M. A.; Barkley, R.;
Meyers, A. I. J . Chem. Soc., Chem. Commun. 1993, 1357.
(10) Bauer, W.; Schleyer, P.v.R. J . Am. Chem. Soc. 1989, 111, 7191
and references therein.
In agreement with previous MNDO calculations,11 the
7Li-1H HOESY spectrum of 3 (Figure 2) shows strong
contacts for the peri hydrogen (δ 8.5 ppm) only, thereby
suggesting that the ortho hydrogen must be further
(16) See: (a) Bauer, W.; Schleyer, P. v. R. In Advances in Carbanion
Chemistry; Snieckus, V., Ed.; J AI Press, Inc.: 1992; Vol. 1.
(17) Solutions containing 1:1 (A), 2:1 (B), 3:1 (C), 4:1 (D), and 8:1
(E) n-BuLi:1-naphthol ratios were prepared by adding 1-naphthol (1
mmol) in dry TMEDA (1 mL) to the appropriate amount of nBuLi in
TMEDA, at -20 to 0 °C, under argon. n-BuLi in TMEDA was prepared
from commercial 2.5M n-BuLi by removing the solvent with dry argon
and the residue dissolved in 1 mL of TMEDA. Solvent suppression
was achieved in all NMR spectra, except HOESY.
(11) Sun˜er, G. A.; Deya´, P. M.; Saa´, J . M. J . Am. Chem. Soc. 1990,
112, 1467. See also ref 14.
(12) Brookhart, M.; Green, M. L. H. J . Organomet. Chem. 1983, 250,
395.
(13) Bauer, W.; Clark, T.; Schleyer, P. v. R. J . Am. Chem. Soc. 1987,
109, 970 and references cited therein.
(14) Saa´, J . M.; Morey, J .; Frontera, A.; Deya´, P. M. J . Am. Chem.
Soc. 1995, 117, 1105.
(18) Supporting information available.
(19) J ackman, L. M.; Scarmoutzos, L. M.; De Brosse, C. W. J . Am.
Chem. Soc. 1987, 109, 5355 and references cited therein.
(20) The reliability of J ackman’s method19 depends on the uncer-
tainties regarding the anisotropic rotational diffusion. QSC values for
1 and 3 (111 and 135 kHz, respectively) lie close to the ideal 120 kHz.
(21) Because γS/γI is >2.38 and τC can be assumed to be ,1/ω. See:
Neuhaus, D.; Williamson, M. P. The Nuclear Overhauser Effect in
Structural and Conformational Analysis; VCH: New York, 1989.
(15) Caube`re, P. Chem. Rev. 1993, 93, 2317.
S0022-3263(96)00570-1 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 16, 1996 5195
F igu r e 1. 1H and 7Li spectra of 1-naphthol:n-butyllithium
mixtures A (1:1), B (1:2), C (1:3), D (1:4), and E (1:8) in
TMEDA18 at -20 °C.
Sch em e 2. Equ ilibr iu m F or m a tion of Mixed
Aggr ega tes fr om Alk yllith iu m a n d Lith iu m Ar yl
Oxid es
F igu r e 3. Peri lithiation of 1-naphthol:serial 1H NMR spectra
of a 1:4 1-naphthol:n-butyllithium mixture at increasing
temperatures.18
1-naphtholate.7b The structure of this compound is
consistent with 1D and 2D spectra (COSY, HMQC, and
HMBC),18 quenching experiments.7b
In summary, the present work provides the first
experimental evidence for the intermediacy of mixed
aggregates22 in the directed lithiation of hydric com-
pounds. The excess of lithiating agent is required to
displace the otherwise unfavorable equilibrium leading
to their formation.11,14 Close contacts observed in the
7Li-1H HOESY spectra of these mixed clusters show peri
hydrogens to be the closest to lithium atoms. Since
lithiation occurs on heating, it is tempting to conclude
that complex-induced proximity effects play a key role
in these reactions,6,14 perhaps by activating the closest
hydrogens by agostic interaction.12,13 The definitive
identification of the kinetically relevant species awaits
the realization of careful kinetic studies.
Ack n ow led gm en t. Financial support by the DGI-
CYT (Spain) is gratefully acknowledged. We thank Prof
G. Boche (U. Marburg) for his invaluable help.
Su p p or tin g In for m a tion Ava ila ble: 1D and 2D NMR
spectra of 1-naphthol:n-butylithium mixtures and a listing of
NMR data for 1-3 (7 pages).
J O960570A
F igu r e 2. 1H-7Li HOESY NMR spectrum (mixing time 300
ms) of solution B18 (see text) -20 °C. Assignments shown on
F1 are as follows: Hx for 3, H′x for 1, and H′′x for 2.
(22) McGarrity, J . F.; Ogle, C. A.; Brich, Z.; Loosli, H.-R. J . Am.
Chem. Soc. 1985, 107, 1810. Bates, T. F.; Thomas, R. D. J . Am. Chem.
Soc. 1988, 110, 5109. Williard P. G.; Hintze, M. J . J . Am. Chem. Soc.
1990, 112, 8062. Marsch, M.; Harms, K.; Lochmann, L.; Boche, G.
Angew. Chem., Int. Ed. Engl. 1990, 29, 308. Hanawalt, E. M.; Richey,
H. G. J r. J . Am. Chem. Soc. 1990, 112, 4893. Palmas, P.; Tekeley, P.;
J amart-Gregoire, B.; Caube`re, P.; Canet, D. J . Am. Chem. Soc. 1994,
116, 11604. Harder, S.; Lutz, M.; Streitwieser, A. J . Am. Chem. Soc.
1995, 117, 2361. Collum, D. B. Acc. Chem. Res. 1993, 26, 227. See also
ref 19.
away.21 Relevant to our objectives, peri lithiation can be
observed (Figure 3) in examining a series of NMR spectra
of solution D at different temperatures. Complete lithia-
tion is achieved at ca. 40 °C as shown by the disappear-
ance of the peri hydrogen, the final spectrum exhibiting
the expected AMX systems for 8-lithiated lithium