Restricted stereochemistry of solvation of allylic lithium compounds: Structural and dynamic consequences

Article abstract of DOI:10.1021/ja983047h

Several 1-sila allylic lithium compounds have been prepared with potential ligands for Li substituted at the 2-position. They are [2-[[cis-2,5-bis(methoxymethyl)-1-pyrrolidinyl]methyl]-1-(trimethylsilyl)allyl] lithium (22), [2-[[cis-2,5-bis(methoxymethyl)-1-pyrrolidinyl]methyl]-1-(dimethylethylsilyl) allyl]lithium(23), [2-[[bis-(2-methoxyethyl)amino]methyl]-1-(dimethylethylsilyl)allyl]lithium (24), [2-[[bis(2-methoxyethyl)amino]methyl]-1-(tert-butyldimethylsilyl)allyl]lithium (25), and [2-[2-[bis(2-methoxyethyl)amino]-1,1-dimethylethyl](ethyl-dimethylsilyl)] allyllithium (26). Using diethyl ether or THF solutions all these compounds exhibited one bond ¹³C, ⁷Li spin coupling of ～8 Hz, a 1:1:1:1 ¹³C NMR pattern indicating monomeric structures; all show ligand resonances to be magnetically nonequivalent and reveal C₁, C₃ ¹³C NMR shifts of about 40 and 75 δ which lie between those for model delocalized 1 and localized species 2. These compounds are concluded to be examples of the heretofore missing folded, internally tridentately coordinated partially delocalized structures with small detectable C, Li covalence. The exception is 25 which, in diethyl ether, consists of a rapidly interconverting equilibrium mixture of localized and delocalized more solvated forms, the former prevailing at 300 K and progressively converting mainly to the latter by 180 K. NMR line shape analysis of the diastereotopic gem methylsilyl ¹³C resonances as well as that due to the ligand carbons shows that all these line shape changes are due to the dynamics of inversion at lithium-bound carbon and that other ligand reorientation processes are slower than carbanide inversion; for inversion, ΔH? is found to be 6-9 kcal?mol^-1, respectively. Averaging with increasing temperature of the ¹³C, ⁷Li spin coupling in 24 provides the dynamics of bimolecular carbon lithium bond exchange with ΔH? of 12 kcal?mol^-1. Mechanisms are proposed on the basis of the data. We ascribe restricted stereochemistry of ligand lithium coordination to be responsible for these unusual internally coordinated structures.

Full text of DOI:10.1021/ja983047h

432
J. Am. Chem. Soc. 1999, 121, 432-443
Restricted Stereochemistry of Solvation of Allylic Lithium
Compounds: Structural and Dynamic Consequences
Gideon Fraenkel,* Joseph H. Duncan, and Jinhai Wang
Contribution from the Department of Chemistry, The Ohio State UniVersity, Columbus, Ohio 43210
ReceiVed August 24, 1998
Abstract: Several 1-sila allylic lithium compounds have been prepared with potential ligands for Li substituted
at the 2-position. They are [2-[[cis-2,5-bis(methoxymethyl)-1-pyrrolidinyl]methyl]-1-(trimethylsilyl)allyl]lithium
(22), [2-[[cis-2,5-bis(methoxymethyl)-1-pyrrolidinyl]methyl]-1-(dimethylethylsilyl)allyl]lithium (23), [2-[[bis-
(2-methoxyethyl)amino]methyl]-1-(dimethylethylsilyl)allyl]lithium (24), [2-[[bis(2-methoxyethyl)amino]methyl]-
1-(tert-butyldimethylsilyl)allyl]lithium (25), and [2-[2-[bis(2-methoxyethyl)amino]-1,1-dimethylethyl](ethyl-
dimethylsilyl)]allyllithium (26). Using diethyl ether or THF solutions all these compounds exhibited one bond
13C, 7Li spin coupling of ∼8 Hz, a 1:1:1:1 13C NMR pattern indicating monomeric structures; all show ligand
resonances to be magnetically nonequivalent and reveal C1, C3 13C NMR shifts of about 40 and 75 δ which
lie between those for model delocalized 1 and localized species 2. These compounds are concluded to be
examples of the heretofore missing folded, internally tridentately coordinated partially delocalized structures
with small detectable C, Li covalence. The exception is 25 which, in diethyl ether, consists of a rapidly
interconverting equilibrium mixture of localized and delocalized more solvated forms, the former prevailing
at 300 K and progressively converting mainly to the latter by 180 K. NMR line shape analysis of the
diastereotopic gem methylsilyl 13C resonances as well as that due to the ligand carbons shows that all these
line shape changes are due to the dynamics of inversion at lithium-bound carbon and that other ligand
reorientation processes are slower than carbanide inversion; for inversion, ∆Hq is found to be 6-9 kcal‚mol-1
,
respectively. Averaging with increasing temperature of the 13C, 7Li spin coupling in 24 provides the dynamics
of bimolecular carbon lithium bond exchange with ∆Hq of 12 kcal‚mol-1. Mechanisms are proposed on the
basis of the data. We ascribe restricted stereochemistry of ligand lithium coordination to be responsible for
these unusual internally coordinated structures.
Most solvated allylic lithium compounds adopt delocalized
ion-paired structures,1 some aggregated, as determined from
spectroscopic,2 X-ray crystallographic,3 and supporting calcu-
lational studies.4 Alternating 13C NMR chemical shifts with
shielding at the allyl termini, see 1 (shown without aggregation),
is quite consistent with a delocalized anion2. A good model for
an unsolvated allylic lithium, 2, displayed 13C shifts which
resembled those for an alkene and are assigned to a localized
structure.5 Until recently there were no reports of spin coupling
between 13C and directly bonded 6Li or 7Li in any allylic lithium
compound. Absence of the appropriate fine structure could be
the result of fast 7Li quadrupole-induced relaxation,7 “relaxation
of the second kind”, fast intermolecular C, Li bond exchange,8
or simply a very small coupling constant.
At low temperatures, <180 K, unexpected nonequivalences
(1) (a) Wardell, J. L. In ComprehensiVe Organometallic Chemistry;
Wilkinson, G., Stone, F. G. H., Abel, E. W., Eds.; Pergammon Press:
Oxford, 1982; Vol. 7, p 97. (b) Seyferth, D.; Julia, T. F. J. Organomet.
Chem. 1967, 8, C13. (c) Schlosser, M.; Stahle, N. Angew. Chem. 1980, 92,
477. (d) Stahle, M.; Schlosser, M. J. Organomet. Chem. 1981, 220, 277.
(e) Neugebauer, W.; Schleyer, P. v. R. J. Organomet. Chem. 1980, 198,
C1. (f) Brownstein, S.; Bywater, S.; Worsfold, D. J. J. Organomet. Chem.
1980, 199, 1.
(2) (a) West, P.; Purmort, J. I.; McKinley, S. V. J. Am. Chem. Soc. 1968,
90, 797. (b) O’Brian, D. H.; Hart, A. J.; Russell, C. R. J. Am. Chem. Soc.
1975, 97, 4410. (c) Benn, R.; Rufinska, A. J. Organomet. Chem. 1982,
239, C19. (d) Bates, R. B.; Beavers, W. J. Am. Chem. Soc. 1974, 96, 5001.
(e) Dolinskaya, E. R.; Poddabnyi, I. Ya; Tseretech, I. Yu. Dokl. Akad. Nauk.
SSSR 1970, 191, 802. (f) Thompson, T. B.; Ford, W. T. J. Am. Chem. Soc.
1974, 101, 5459.
(3) (a) Koster, H.; Weiss, E. Chem. Ber. 1982, 115, 3422. (b) Schumann,
U.; Weiss, E.; Dietrich, H.; Mahdi, W. J. Organomet. Chem. 1987, 322,
299. (c) Sebastian, J. F.; Grunwell, J. R.; Hsu, B. J. Organomet. Chem.
1974, 78, C1. (d) Boche, G.; Etzrodt, H.; Marsch, M.; Massa, H.; Baum,
G.; Dietrich, H.; Mahdi, W. Angew. Chem. 1986, 98, 84. (e) Boche, G.;
Fraenkel, G.; Cabral, J.; Harms, K.; Eikema-Hommes, N. J. P. Van.; Lorenz,
J.; Marsch, M.; Schleyer, P. v. R. J. Am. Chem. Soc. 1992, 114, 1562-
1565.
seen among 13C resonance in ion-paired allylic lithium com-
(4) (a) Erusalimski, C. B.; Kormer, V. H. Zh. Org. Khim. 1984, 20, 208.
(b) Tidwell, E. R.; Russell, B. R. J. Organomet. Chem. 1974, 80, 175. (c)
Boche, G.; Decher, G. J. Organomet. Chem. 1983, 259, 31. (d) Clarke, T.;
Jemmis, E. D.; Schleyer, P. v. R.; Binkley, J. S.; Pople, J. A. J. Organomet.
Chem. 1978, 150, 1. (e) Clarke, T.; Rhode, C.; Schleyer, P. v. R.
Organometallics 1983, 2, 1344. (f) Bushby, R. J.; Tytho, M. P. J.
Organomet. Chem. 1984, 270, 265. (g) Pratt, L. M.; Khan, I. M. J. Comput.
Chem. 1995, 16, 1070. (h) Eikemma-Hommes, N. J. R. Van; Bu¨hl, M.;
Schleyer, P. v. R. J. Organomet. Chem. 1991, 409, 307-320.
(5) (a) Fraenkel, G.; Halasa, A. F.; Mochel, V.; Stumpe, R.; Tate, D. J.
Org. Chem. 1985, 50, 4563-4565. (b) Glaze, W. H.; Jones. P. C. J. Chem.
Soc. 1969, 1434. (c) Glaze, W. H.; Hanicac, J. E.; Moore, M. L.; Chandpuri,
J. J. Organomet. Chem. 1972, 44, 39. (d) Glaze, W. H.; Hanicac, J. E.;
Chandpuri, J.; Moore, M. L.; Duncan, D. P. J. Organomet. Chem. 1973,
51, 13. (e) Bywater, S.; Lachance, P.; Worsfold, D. J. J. Phys. Chem. 1975,
79, 2142.
(6) Fraenkel, G.; Qiu, F. J. Am. Chem. Soc. 1996, 118, 5828-5829.
(7) Abragam, A. The Principles of Nuclear Magnetism; Oxford University
Press: London, 1961; p 309.
(8) Luz, Z.; Meiboom, S. J. Chem. Phys. 1963, 39, 366.
10.1021/ja983047h CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/29/1998

SolVation of Allylic Lithium Compounds
J. Am. Chem. Soc., Vol. 121, No. 2, 1999 433
pounds,9 for example, 3, showed for the first time that
coordinated TMEDA was unsymmetrically sited with respect
to the allyl loop and that ion pairs have energetically favored
structures. Then, signal-averaging effects observed with increas-
ing temperature were shown to result from the dynamics of
reorientation of coordinated lithium with respect to the anion
within the ion pair.9,10
fashion similar to the chemistry of 4, metalation of 10 is
facilitated by the pendant ligand.11 Diol 11, which was prepared
Recently, a long anticipated, third general structure of allylic
lithium compounds was reported that lies between the two
reference compounds, 1 and 2.6,11 In experiments to slow down
exchange of ions among ion pairs, to facilitate structure
determination, it was proposed to encapsulate the ions by means
of internal coordination to lithium using a pendant ligand.
However, instead of producing such an ion pair, metalation of
4 produced a species that, from its NMR spectra, is best
in four steps15-17 starting from adipic acid, was converted to
cis-2,5-bis(methoxymethyl)pyrrolidine (14), following the pro-
cedure of Enders for transforming (S)-(-)-2-(hydroxymethyl)-
pyrrolidine to the 2-methoxymethyl derivative;18 see 11-14.
Isobutenyl chloride (15), was conveniently aminated by both
described as 5, internally coordinated, partially delocalized with
small detectable C, Li covalence. The allyl 13C shifts lie between
those for the two reference compounds 1 and 2.11 Compound 5
7
exhibits 13C, Li scalar coupling of 8 Hz, far below the 42 Hz
common to many different monomeric organolithium com-
pounds. Line shape analysis of NMR data obtained as a function
of temperature provided dynamic information on inversion at
carbon-bound lithium, C, Li bond exchange, and 1,3 lithium
sigmatropic shifts.11
This article is addressed to the extent of the effects described
above. Is the structure of 5 unique or is there a continuum of
varying delocalization reflected by the 13C NMR shifts and 13C,
lithium coupling constants? The latter should increase with
decreasing delocalization. How would changing solvent, the
attached ligand, and its tether and substitution on allyl affect
the structure and dynamic behavior? Internally coordinated
structures might be in equilibrium with others, for example, of
general type 1.
bis(2-methoxyethyl)amine and cis-2,5-bis(methoxymethyl)pyr-
rolidine, the latter prepared as described above, forming,
respectively, aminoalkenes 16 and 17. Allylic metalation (n-
butyllithium) of 16 and 17 followed by silylation provided our
required starting materials, 18-21. It is interesting that while
metalation of allyl trimethylsilane is slow using n-butyllithum
in THF and proceeds readily only with sec-butyllithium in
THF,9b n-butyllithium readily deprotonates 16 and 17. Prelimi-
nary studies of N-methyl-N,N-bis(2-methoxyethyl)amine as a
catalyst for RLi metalation were disappointing;19 it is inferior
to TMEDA. Hence, the rapid metalations of 16 and 17 with
n-butyllithium owe their facility to the pendant ligand, most
likely due to its prior complexation with n-butyllithium thus
directing base to the site of deprotonation.
Results and Discussion
Following published procedures, ethyl-2-bromo-2-methyl-
propanoate was converted to 2,2,3-trimethyl-3-butenoic acid;12-14
see 6 and 7. Formation of the amide 8 followed by LAH
reduction provided the required unsaturated amine, 9. Allylic
metalation and silylation to give 10 proceeded smoothly. In a
(9) (a) Fraenkel, G.; Chow, A.; Winchester, W. R. J. Am. Chem. Soc.
1990, 112, 1382-1386. (b) Fraenkel, G.; Winchester, W. A.; Chow, A. J.
Am. Chem. Soc. 1990, 112, 2582-2585.
(10) (a) Fraenkel, G.; Cabral, J. A. J. Am. Chem. Soc. 1993, 115, 1551-
1557. (b) Fraenkel, G.; Cabral, J. A. J. Am. Chem. Soc. 1992, 114, 9007-
9015.
(11) Fraenkel, G.; Qiu, F. J. Am. Chem. Soc. 1997, 119, 3571-3579.
(12) Reformatsky, S.; Plesconossoff, B. Chem. Ber. 1895, 28, 2839.
(13) Kajikawaja, A. Tetrahedron Lett. 1978, 4135.
(15) Cignarella, G.; Nathansohn, G. J. Org. Chem. 1961, 26, 1500.
(16) Cignarella, G.; Nathansohn, G. Gazz. Chim. Ital. 1966, 90, 1495.
(17) Dr. Jinhai Wong, The Ohio State University, private communication,
1997.
(18) Kipphardt, H.; Enders, D. Org. Syn. 1957, 65, 173.
(19) Dr. Jose Cabral, The Ohio State University, Newark, private
communication, 1997.
(14) Karpf, M. HelV. Chim Acta 1984, 67, 73-85.

434 J. Am. Chem. Soc., Vol. 121, No. 2, 1999
Fraenkel et al.
by its mirror plane. In contrast, all carbons in the attached
ligands in 22-26 are magnetically nonequivalent at low
temperature, 180 K.
The 13C NMR data observed in this study also imply some
detectable covalence between C1 and lithium. The Fermi contact
interaction22 which is responsible for scalar coupling between
7
6
directly bonded 13C and Li or 13C and Li requires some “s”
character and degree of covalence associated with the bond. In
7
fact, all the samples show evidence of one-bond 13C, Li spin
coupling at low temperature, Table 2. 7Li has I ) 3/2. 13C NMR
for C1 of 23-26 consists of well-resolved equally spaced 1:1:
1:1 quartets which establishes that 13COH is bonded to one 7Li,
most likely in a monomer. The coupling constants are all ∼7
( 1 Hz. The splitting is only poorly resolved in the case of 22,
however;11 its 13C1 resonance width and shape is consistent with
7
the conclusions for the other compounds. Note that 13C, Li
coupling constants are averaged with increasing temperature due
to intermolecular C, Li exchange and also progressively on
cooling. The latter effect results from increasingly faster Li
Allylsilanes 10, 18-20, and 2 are cleanly and exclusively
metalated at allyl CH2Si using methyllithium in THF/Et2O20
resulting in compounds 26 and 22-25, respectively. Reaction
7
nuclear electric quadrupole-induced relaxation. Due to these
7
effects, 13C, Li coupling is sometimes not observed at all and
often only manifested by selective broadening of the 13C
resonance for lithium-bound carbon within a narrow temperature
range.23
Averaging of 13C, 7Li couplings due to 7Li quadrupole-
induced relaxation can be avoided by the use of samples
6
6
enriched in Li (I ) 1) since the quadrupole moment of Li is
lower than that of 7Li by a factor of 91.3.24 However since the
resonance ratio ν(7Li)/ν(6Li) is 2.64, that puts 1J(13C,6Li) at 2.5-
3.0 Hz, which is easily missed in the case of viscosity
broadening. This is difficult to use for NMR line shape analysis.
7
The 13C, Li coupling constants reported herein are very
at allyl CH2N is not detected. These compounds were transferred
into diethyl ether-d10 or THF-d8 for NMR study. Proton and
13C chemical shifts for these species obtained at <180 K are
listed around the structures in Table 1.
With the exception of 25 in diethyl ether, these samples gave
no evidence for more than one species present over the entire
temperature range investigated, 160-290 K.
similar to those found for some benzylic lithium compounds.25
These all hover around 6-8 Hz, much lower than the many
13C, 7Li coupling constants found for a wide variety of
monomeric organolithium constants, which are uniformally 42
Hz.26 The latter appear to be independent of the organic moiety.
A rationalization of this unexpected uniformity, based on the
treatment of Ramsey,22 Karplus,27 and Grant28,29 and its ac-
companying approximations, then requires that the product of
the “s” character and a function of the covalence, both associated
with the C-Li bond, be a constant. Current NMR theory does
As noted above, our model for a delocalized solvated (THF)
allylic lithium compound is 1-(trimethylsilyl)lithium with 13C
NMR shifts for C1, C2, and C3 of 53, 150, and 62 δ, respectively.
This is the alternating pattern typical of a delocalized carbanion
shielded at the termini due to negative charge.9b The shift values
are consistent with the well-known linearity of the sp2 13C shift
with charge on carbon.21 In contrast, the C1, C2, and C3 shifts
for unsolvated 3-(neopentylallyl)lithium are 22, 150, and 100
δ, respectively. These have the appearance of a 1-substituted
alkene and are considered as representing a localized allylic
lithium compound.5a
The allyl shifts for C1, C2, and C3 of 22-26 lie between those
for the model delocalized and localized 2 species described
above and should therefore be regarded as partially delocalized.
These shift values vary within a very narrow range. They appear
not to depend significantly on changes in the structure of ligand
from loose in 24 and 25 to constrained in 22 and 23 or with a
change in tether, 26.
1
not account for the failure of J(13C,7Li) values for allylic6,11
and benzylic25 lithium compounds to conform to the common
pattern found for most organolithium compounds.26 Perhaps the
conjugated nature of the former places them in a more ionic
category than the latter.
Taken together, all these data are most consistent with the
folded monomeric internally coordinated structures shown in
Table 1. These are different from allylic lithium compounds
described previously,2,3 most likely due to the restricted options
for stereochemistry of coordination of pendant ligand to lithium.
(22) Ramsay, N. F. Phys. ReV. 1953, 91, 303.
(23) Fraenkel, G.; Subramanian, S.; Chow, A. J. Am. Chem. Soc. 1995,
117, 6300-6307.
(24) Pople, J. A.; Schneider, W. G.; Berstein, H. J. High-Resolution
Nuclear Magnetic Resonance; McGraw-Hill Book Co.: New York, 1959;
p 48.
In precursors to the allylic lithium compounds studied here,
the two methoxyethyl moieties have the same 13C NMR as do
the two sides of cis-1,5-bis(methoxymethyl)pyrrolidine separated
(25) (a) Fraenkel, G.; Martin, K. V. J. Am. Chem. Soc. 1995, 117, 10336-
10344. (b) Ruhland, T.; Hoffmann, R. W.; Schade, S.; Boche, G. Chem.
Ber. 1995, 128, 551-556.
(20) Prior complexation of CH3Li to pendant ligand must be implicated
here also since CH3Li fails to deprotonate allyltrimethylsilane under the
same conditions.
(21) (a) Spiesecke, H.; Schneider, W. A. Tetrahedron Lett. 1961, 468.
(b) Tokuhiro, T.; Fraenkel, G. J. Am. Chem. Soc. 1969, 91, 5005. (c)
Lauterbur, P. C. J. Am. Chem. Soc. 1961, 83, 1838.
(26) Bauer, W.; Winchester, W. R.; Schleyer, P. v. R. Organometallics
1987, 6, 2371-2379.
(27) Karplus, M.; Grant, D. M. Proc. Nat. Acad. Sci. U.S.A. 1959, 45,
1269.
(28) Grant, D. M.; Litchman, W. M. J. Am. Chem. Soc. 1965, 87, 3994.
(29) Litchman, W. M.; Grant, D. M. J. Am. Chem. Soc. 1967, 89, 2228.

SolVation of Allylic Lithium Compounds
J. Am. Chem. Soc., Vol. 121, No. 2, 1999 435
Table 1
13C NMR Shifts, δ, Allylic Lithium Compounds 22-26, THF-d8 or
Diethyl Ether-d10 Solution at Different Temperatures
Table 2. 1J(13C,7Li) (Hz) Values for Allylic Lithium Compounds
The 13C1 NMR of 24 in diethyl ether-d solution provides just
the changes needed to measure the intermolecular C, Li bond
cpd
J (Hz)
solvent
T (K)
exchange and estimate the 7Li quadrupole relaxation rate.30 At
22
23
24
24
25
26
7.0a
7.0
7.8
8.2
6.8
6.0
Et2O-d10
Et2O-d10
THF-d8
Et2O-d10
THF-d8
THF-d8
240
235
240
250
245
235
7
low-temperature, one-bond 13C1, Li coupling is clearly seen.
Since quadrupole relaxation is already slow enough at 260 K
to reveal the 13C, 7Li coupling, it is unlikely to perturb the 13
C
line shapes at higher temperatures. Besides, the contribution due
7
to Li quadrupole relaxation will also be taken into account;
see below. The exchanging system, with 13C in natural
abundance is modeled as (eq 1) together with spin functions in
a Poorly resolved but line shape consistent with a monomer.
The only energetically favorable arrangement is with Li and N
in or near the allyl plane and the oxygens on two sides and
normal to this plane. Such an arrangement allows for “s”
character associated with some covalency to the C-Li bond,
hence detectable spin coupling. The published structures for
solvated allylic lithium compounds have lithium normal to the
allyl plane,3 which minimizes the possibilities for 13C, 7Li spin
coupling. Further, among our compounds internal coordination
encapsulates lithium, reduces its exchange rate with lithium in
other molecules compared to externally solvated allylic lithium
the product representation φ13Cφ7Li, so that the quantum mechan-
ics follows the chemistry. Here R, â are for 13C (I ) 1/2), l and
m for 7Li (I ) 3/2). The 13C transitions to be plotted are diagonal
7
in Li since this is a 13C first-order spectrum and are listed as
7
compounds, and improves the liklihood of observing 13C, Li
(30) Kaplan, J. I.; Fraenkel, G. NMR of Chemically Exchanging Systems;
spin coupling should the value be large enough to resolve.
Academic Press: New York, 1980; Chapters 4 and 6.

436 J. Am. Chem. Soc., Vol. 121, No. 2, 1999
Fraenkel et al.
R (3/2) f â (3/2), R (1/2) f â (1/2), R (-1/2) f â (-1/2), and R
(-3/2) f â (-3/2), where the states of 7Li are indicated by their
mz eigenvalues. The required elements of the density matrix
are
(10)
RφLi|F|âφLi ) FI
(2)
and are abbreviated as F1, F2, F3, and F4 for mz of 7Li,
respectively, 3/2, 1/2, -1/2, and -3/2. Then, given the FI elements,
the absorption is given in (3).
and then summed as in (3) to give the NMR absorption. Use of
trial values of k and r showed that Li quadrupole-induced
Abs(ν) ) -Im(F1 + F2 + F3 + F4)
(3)
7
The elements FI are obtained by solving the four coupled first-
order equations generated by taking the four elements of the
density matrix equation (eq 4) whose states are connected by a
relaxation does not contribute detectably to the NMR line shapes
above 260 K. Comparison of observed to calculated line shapes,
Figure 1, provided the pseudo-first-order rate constants. Result-
ing activation parameters are ∆Hq ) 12.5 kcal‚mol-1 and ∆Sq
) 6.4 eu; see Table 3.
At low temperature, 13C NMR of the geminal methyls on Si
in 22-26 in diethyl ether-d10 each give rise to a single 1:1
doublet. This splitting is not the result of slow interconversion
of rotamers with nonequivalent methyls by rotation around the
Si-allyl bonds since precursor propenes gave only a single line
each for these methyl pairs in 13C NMR at low temperature.
Rather the geminal methyl doublets in our allylic lithium
compounds are due to the chiral environments in these
compounds. With increasing temperature these doublets pro-
gressively average to single lines at their respective centers. The
line shapes are treated as due to two-site half-spin uncoupled
equally populated exchanging systems.
RφLi|l[F,H] - F/T + EF + RF|âφLi ) 0
(4)
13C transition, where E and R are exchange and relaxation
operators, respectively, 1/T is the 13C line width in the absence
of exchange, H is the Hamiltonian, and F is the density matrix.
Elements of EF are evaluated as follows. Consider the exchange
process again, eq 1. Before exchange, an element of the density
matrix of 13C 7Li is given by eq 5 since the trace of F is unity.
CLi
Rl,âl
CLi
Rl,âl
F
) F
FLi*
(5)
∑
m,m
m
After exchange, switching Li* for Li (in C Li) and m for l in
the spin products, we have eq 6. Since there are four spin states
The overall process responsible for these changes in line
shapes is inversion at lithium-bound carbon; it must be first
order since the appearance of the line shapes does not change
with the concentration of the allylic lithium compound. Some
proposals regarding the mechanism are made below. Compari-
sons of observed to calculated methylsilyl 13C line shapes for
23 (1H and 13C) and 24 provided the first-order rate constants
for inversion. The resulting activation parameters for all
compounds studied are listed in Table 3.
afterrex
Rl,âI
CLi
F
)
FCLi
F
Rm,âm l,l
∑
m
1
CLi
Rm,âm
)
F
(6)
∑
4
m
for 7Li, each diagonal element is equal to 1/4. Then, an element
of EF is given by eq 7 where k is the psuedo-first-order rate
As noted above, all carbons on the pendant ligands in 22-
26 are magnetically nonequivalent. With increasing temperature,
the equal 13C NMR doublets due to CH3O, CH2O, and NCH2C
in 24, for example, averaged to single lines at their respective
centers; similar effects were found for the pyrrolidino ligand in
23sdoublets due to CH3O, CH2O, ring CH2, and ring CH each
undergo signal averaging with increasing temperature.
Phenomenologically these line shape changes are the result
of ligand reorientation. Each doublet undergoing averaging was
calculated as a separate two-site equally populated uncoupled
exchanging system. Comparison of observed and calculated line
shapes provided the reorientational rate constants. Since the line
shapes were independent of concentration, the process respon-
sible for the changes must be first order. Line shape analysis of
the ligand 13C resonances for 23 (CH2CH2 and CH2O) and 24
(CH2O and CH3O) gave the activation parameters listed in Table
3.
In studies of allylic and benzylic lithium compounds9,10
complexed to external ligands such as TMEDA, reorientational
effects observed in NMR of the ligand were ascribed to rotation
or flip-flopping of the complexed ligand on one side of the
carbanionic plane (lateral motions), fast reversible N, Li
dissociation accompanied by inversion at nitrogen and rotation
around the NCH2 bond, and transfer of coordinated lithium
between two sides normal to the carbanionic face. Only the latter
process results in inversion.
1
[EFCLi
]
RI,âI ) k
FCRmLi,âm - FCLi
RI,âI
∑
(
(
)
4
1
m
3
) k
FCRmLi,âm - FCLi
(7)
∑
RI,âI
)
4m*1
4
constant.
Elements (RF)Rlâl have already been evaluated.31 In the
extreme narrowing approximation, τω , 1, the jR are simply
related and we are able to use a composite relaxation parameter,
r, shown in eq 8, with q the electric field gradient, Q the
r ) [(e2qQ)/4I(2I - 1)h]2τ
(8)
quadrupole moment, h Planck’s constant, I the spin, and τ the
correlation time.
Finally, we display the spin Hamiltonian in the rotating frame
where νS is the resonance frequency of 13C, ν is a point on the
frequency axis, the operators have their usual meanings, and
JCLi is J(13C7Li), henceforth abbreviated as “J”; see eq 9.
1
H ) 2π(νs - ν)IzC + JC,LiICz ILz i
(9)
The resulting four coupled equations (10), displayed in matrix
form, are solved for the F elements as a function of the frequency
(31) A. Chow, M. S. Thesis, The Ohio State University, 1982.

SolVation of Allylic Lithium Compounds
J. Am. Chem. Soc., Vol. 121, No. 2, 1999 437
Figure 2. C1 and C3 13C NMR shifts of 25, in diethyl ether-d10 at
different concentrations, plotted versus temperature.
Figure 1. 13C NMR of 24, 0.25 M in diethyl ether-d10 (left) C1 part,
observed, different temperatures; (right) calculated, with rate constants.
Table 3. Activation Parameters for Allylic Lithium Compounds
∆Hq
∆Sq
cpd
process
resonance
OCH3
CH2
Si(CH3)2
OCH3
OCH2
CH2
Si(CH3)2
OCH3
(kcal/mol)a
(eu)b
22 inversion
9.3
8.9
9.3
9.4
9.1
9.4
6.1
5.9
6.2
5.8
12.5
8.5
8.9
7.8
8.6
12.0
11.9
-6.5
-8.0
-7.3
-6.2
-8.1
-6.9
-17.6
-18.4
-17.2
-15.8
-6.4
-4.5
-3.1
-21.0
-15.0
-2.0
-8.0
23 inversion
24 inversion
OCH2
Si(CH3)2 (1H)
Li-C bond exchange 7Li-C1
25 inversion
Si(CH3)2
OCH3
NCH2C
OCH3
Si(CH3)2
C(CH2)2
ligand reorientation
26 inversion
a (5%. b (10%.
1
Figure 3. 13C and H NMR of 25 in diethyl ether-d-10 at different
Due to the tridentate and attached nature of the ligand in 22-
26, ligand lithium dissociation would be a disfavored reorienta-
tion route compared to systems with external ligands. Further,
with attached ligand, lateral motion would require a 1,3 lithium
sigmatropic shift, already known to be slow6 (∆Hq ) 18
kcal‚mol-1), and would lead to thermodynamically unstable
products. It is not surprising then that all the activation
parameters determined for reorientation of the pendant ligands
temperatures with C(1)H and C(3)H2 resonances indicated. (left) 13C
NMR; (right) H NMR; C(3)H2 to left in each stack.
1
delocalization as evidenced by the C1 and C3 13C shifts. An
exception is the behavior of 25. In THF solution, 25 shows the
same C1, C3 13C shifts as the other compounds largely
independent of temperature between 180 and 290 K. In contrast,
while the room-temperature 13C NMR spectrum of 25 in diethyl
ether was identical to that in the THF solution, on lowering the
temperature, the C1 and C3 shifts approach each other, that of
C1 increasing and C3 decreasing in almost linear fashion (see
Figure 2). By 210 K, the C1 and C3 shifts resemble those for a
typical ion-paired delocalized allylic metal compound such as
[1-(trimethylsilyl)allyl]lithium.9a Similar results were observed
in proton NMR, Figure 3. These observations were independent
of concentration of 26; see Figure 2. Within the entire
temperature range over which 25 in diethyl ether was investi-
gated, no more than one NMR spectrum was observed. The
only reasonable explanation for these observations is that 25 in
are essentially identical to inversion values that come from 13
C
geminal methyl resonances, i.e., the other ligand reorientation
processes must be much slower than inversion. The exception
is 26 with the two-carbon tether. Possibly this is a looser bonding
arrangement which might facilitate the dissociation reorientation
process, hence ligand reorientation is considerably faster than
inversion; see Table 3.
It might have been expected that the electronic structures of
these internally solvated partially delocalized allylic lithium
compounds would respond sensitively to changes in the ligand,
its tether, substituent, and solvent. So far none of these
modifications has shown significant influence on the degree of

438 J. Am. Chem. Soc., Vol. 121, No. 2, 1999
Fraenkel et al.
diethyl ether consists of a rapidly interconverting equilibrium
mixture of two or more species. The more covalent species)
would prevail at higher temperatures, converting mainly to the
ionic more delocalized species at lower temperatures.32,33 Since
the results appear to be independent of concentration, the
aggregation of the different kinds of species must be the same.
Taken together, the shifts and 13C, 7Li spin coupling data for
compounds studied here all support the folded partially de-
localized internally coordinated structures with detectable C,
Li covalence, proposed in structures 22-26.
These compounds undergo several interesting fast equilibrium
exchange and rearrangement processessvery fast ionic a
covalent interconversions, inversion at carbon bound lithium
measurable on the NMR time scale, and somewhat slower
bimolecular C,Li bond exchange, the latter evidenced by
averaging of the 13C, 7Li coupling constant for 24. The system
was simulated as in (1). The dynamic parameter, k, obtained
Qualitatively the results for 25 have parallels in the extensive
literature on equilibria between contact and solvent-separated
ion-paired metal salts.32,33 The latter are favored at lower
temperatures due to exothermicity associated with coordinating
extra ligand molecules to metal ion in the solvent-separated ion
pairs, compared to the contact ion pairs.32,33 The analogy is
qualitative since the higher temperature form of 25 is regarded
as a partially covalent species. Similar results have been
observed for neopentylallyllithium, which interconverts rapidly
between covalent and ionic forms with the latter predominant
only at lower temperatures.5a Why 25 behaves in this way while
the others described herein do not must be ascribed to the tertiary
butyl group in silicon. Steric interactions between the tertiary
butyl group in the (internally solvated) localized structure and
the pendant ligand may be responsible for destablizing the higher
temperature species.
It is also interesting that the rate of interconversion between
the more covalent and more ionic forms of 25 is too fast to
allow observation of NMR resonances due to the individual
species. At the lowest temperature at which 25 in diethyl ether
was investigated, being the slowest interconversion rate, only
one species, the ionic one is present. Midrange at 260 K with
similar concentrations of at least two species present, as
evidenced by the observed shifts, still only one spectrum was
observed.
As noted above, in the past allylic lithium compounds were
reported to adopt two main structures, the delocalized ion-paired
ones (see 1), recognized by their alternating 13C shifts with
shielding at the termini, and the unsolvated species, for example,
2, considered localized because their 13C shifts resembled those
for an alkene. In principle, one might expect there should be
other structures between 1 and 2; delocalized to different
degrees, the less delocalized the greater the C, Li covalency.
Two such structures reported recently6,11 are favored only due
to the strategic attachment of a coordinating ligand, which has
the effect of severely restricting the stereochemistry of lithium
coordination.
13C7Li + 12C7Li* [k
\
]
13C7Li* + 12C7Li
(1)
2
from fitting the line shapes is the pseudo-first-order rate constant
k2(13C7Li) as defined by Grunwald et al.35 While there is no
evidence for any particular mechanism, the process has to be
second order in ground-state organolithium compound. Transi-
tion states dimeric with respect to ground state may resemble
higher aggregated ground-state structures for many organo-
lithium compounds.3 Thus, C, Li bond exchange between
monomers (the state of 24) could be written, neglecting
solvation, as (11) for a system with 13C in natural abundance.
(11)
While 13C NMR shifts for 22-26 do not vary much, there
are differences among the dynamic results for inversion. Among
compounds with a one-carbon tether, the reorientation param-
eters derived from the 13C NMR ligand resonance are very
similar to those from the geminal methyl pairs. Since the latter
line shapes have to result from inversion, so must the line shape
changes of the ligand resonances. In these cases, C1 inversion
is the fastest mode of ligand reorientation. The exception is 26
with a two-carbon tether wherein ligand reorientation is faster
than inversion. Perhaps the complex in 26 is just weaker than
in the other four compounds with a one-carbon tether. Ligand
reorientation was found to be faster than inversion in cases of
allylic lithium compounds complexed to external ligands.
Development of a mechanism for inversion in 22-26 requires
taking into account the following observations. It is a first-order
process. The results with the loose ligand bis(2-methoxyethyl)-
amino compared to the constrained cis-2,5-bis(methoxymethyl)-
pyrrolidino are not very different and in both cases ligand
reorientation is driven by the inversion process. This suggests
that fast reversible ligand lithium dissociation with nitrogen
inversion is not a feature of the inversion process about C1 (it
is slower); i.e., lithium ligand coordination retains its integrity
throughout inversion.
In the present study, we have investigated the extent of the
structural and dynamic consequences of internal coordination
of lithium by varying the nature of the ligand, its tether, and
substitution.
All the species reported here (except 25 at low temperature
in diethyl ether) exhibit similar sets of allylic 13C shifts,
intermediate between those for reference localized and de-
localized species. Extension of the tether from one to two
carbons changes the shifts only a little. This applies also to the
ligand carbon shifts. Similarly, replacing the floppy bis(2-
methoxyethyl)amino ligand by the more constrained cis-2,5-
bis(methoxymethyl)pyrrolidino moiety causes only minor changes
in the 13C allyl shifts. These changes are too small to interpret
further.
Inversion is slower than localized/delocalized allylic lithium
interconversion and is much faster than rotation around the
allylic bond, the latter with ∆Hq of 12-20 kcal‚mol-1 2f
A
.
mechanism for inversion consistent with the above observations
involves (1) a 90° anticlockwise rotation of coordinated Li
around C1 with ionization and planarization, (2) transfer of
coordinated Li+ between the two faces of the anion, and (3)
90° clockwise rotation with deplanarization around C1. The
overall result is inversion at C1; see Figure 4. If step 1 and its
reverse (2) are fast, that would account for the rapid localized/
(32) (a) Davies, C. E. Ion Association; Butterworth: Washington, DC,
1962. (b) Swarc, M., Ed. Ions and Ion-pairs in Organic Reactions; Wiley-
Interscience: New York, 1972 and 1974; Vols. 1 and 2. (c) Streitwieser,
A. Acc. Chem. Res. 1984, 17, 353-357. (d) Reichert, C. SolVents and
SolVent Effects in Organic Chemistry; VCH: Weinheim, 1990.
(33) (a) Fraenkel, G.; Hallden-Abberton, M. P. J. Am. Chem. Soc. 1981,
103, 5657-5664. (b) Paquette, L. A.; Bauer, W.; Sivik, M. R.; Bu¨hl, M.;
Feigel, M.; Schleyer, P. v. R. J. Am. Chem. Soc. 1990, 112, 8767-8789.
(34) (a) Ronsberg, F. E.; Gilchrist, J. A.; Colum, D. B. J. Am. Chem.
Soc. 1991, 113, 5751-5757. (b) Jackman, L. M.; Scarmoutzos, L. M.;
Porter, W. J. Am. Chem. Soc. 1987, 109, 5624.
(35) Grunwald, E.; Loewenstein, A.; Meiboom, S. J. Chem. Phys. 1957,
27, 630.

SolVation of Allylic Lithium Compounds
J. Am. Chem. Soc., Vol. 121, No. 2, 1999 439
The tube was flame-dried under vacuum and then flushed with argon
three times consecutively. After the NMR tube cooled to room
temperature, an aliquot of the prepared organolithium solution was
syringed into it. The solvent was removed under vacuum, and the NMR
tube was flushed with argon. The stopcock was closed and the stopper
removed before the tube was attached to a high-vacuum line (10-6 Torr)
trapped with liquid nitrogen. The side of the stopcock adapter that was
open to the air during attachment to the high-vacuum line was allowed
to pump down before the stopcock was opened to pump out the
organolithium sample. After 0.5 h under high vacuum, the organolithium
sample in the NMR tube was frozen in liquid nitrogen and deuterated
solvent (0.8-1.0 mL) was vacuum transferred to the NMR tube. The
contents were allowed to thaw and then were frozen again with liquid
nitrogen before the NMR tube was sealed under vacuum at the hard
glass portion. Samples thus prepared had a concentration of 0.25 M
and were stored in dry ice before the low-temperature NMR studies.
Ethyl 2,2,3-Trimethyl-3-butenoate (7). Into a 250-mL three-necked
flask were introduced Zn dust (4.0 g, 0.61 mol) and 50 mL of freshly
distilled benzene. The mixture was heated to reflux, the heat source
was removed, and a mixture of ethyl 2-bromoisobutyrate (10 g, 0.051
mol) and acetone (3.0 g, 0.051 mol) was added dropwise at a rate
consistent with maintaining the reaction temperature at 80-85 °C. After
addition was complete, the mixture was heated for 2 h and then cooled
to room temperature.
Figure 4. Proposed mechanism for inversion of allylic lithium
compounds.
Then, 60 mL of 12 N sulfuric acid was added. The resulting mixture
was stirred vigorously for 1 h. After the two phases had separated, the
lower aqueous layer was extracted with 50 mL of benzene. The
combined benzene layers were washed with 100 mL of water, saturated
NaHCO3, and water again. The mixture was then dried over Na2SO4,
evaporated to dryness in vacuo, and then distilled in vacuo to give 7.9
g of 3-hydroxy-2,2,3-trimethylbutyrate12 in 89% yield: bp 40-45 °C/
delocalized interconversion observed for 25 in diethyl ether.
The rate determining step for inversion is (2), the transfer of
coordinated Li+ between two faces of the anion.
In sum, we have demonstrated the generality that our
internally solvated allylic lithium compounds adopt partially
delocalized structures with detectable C, Li covalence. They
undergo fast inversion, the dynamics of which have been
monitored using NMR line shape analysis as well as intermo-
lecular C, Li bond exchange.
1
40 Torr; H NMR (CDCl3, 200 MHz) δ 4.08 (q, 2H); 3.68 (s, 1H),
1.18 (t, 3H), 1.11 (s, 6H), 1.07 (s, 6H); 13C NMR (CDCl3, 50.0 MHz)
δ 178.3, 73.2, 60.5, 49.3, 24.9, 21.1, 13.9.
A mixture of 3-hydroxy-2,3,3-trimethylbutyrate (16.2 g, 0.093 mol)
and 70 mL of pyridine was cooled to 0 °C in an ice bath. To the cooled
solution was added slowly with vigorous stirring POCl3 (14.2 g, 0.092
mol). White crystals formed almost immediately. The mixture was
allowed to stand for 5 h at room temperature and was finally heated
for 1.5 h using a heating mantle. It was then cooled to room temperature,
treated with 100 mL of water, followed by 100 mL of diethyl ether,
and stirred. After the layers were separated, the aqueous layer was
extracted twice with 50 mL of ether. The ether layers were combined
and washed with 2 × 100 mL of 2 N of HCl to remove pyridine, and
excess HCl was removed by washing with 100 mL of water. The clear
ether solution was dried over Na2SO4, and solvent was removed in
vacuo. The residue was distilled to give 12.5 g of ethyl-3-chloro-2,3,3-
We attribute the unusual structures to the confined stereo-
chemistry of lithium coordination and the encapsulated site of
lithium.
Experimental Section
General Procedures. Solvents and common reagents were purchased
from Ohio State University stores. Deuterated solvents were purchased
from Cambridge Isotopes. Enriched 6Li was purchased from Oak Ridge
National Laboratory. Alkyllithiums (7Li) and all other chemicals were
purchased from the Aldrich Chemical Co.
Conventional FT-NMR spectra were recorded using a Bruker AC-
200 spectrometer in the Chemistry Department or a Bruker Avance
300 spectrometer of The Ohio State University Central Campus
Instrumentation Center (CCIC). Variable-temperature NMR spectra
were recorded at the CCIC on a Bruker MSL 300 spectrometer or a
Bruker Avance 300 spectrometer. Accurate mass spectra were obtained
from a VG-250S or Kratos MS-30 mass spectrometer at the CCIC.
TMEDA was distilled from calcium hydride under argon and stored
under argon in darkness. Diethyl ether, tetrahydrofuran, and pentane
were freshly distilled from sodium benzophenone ketyl under industrial-
grade argon. Reactions forming or using organolithium compounds were
carried out under an argon atmosphere.
Handling of Organolithium Compounds. Organolithium com-
pounds are very moisture and air sensitive. All glassware used for
preparation or reaction of organolithium compounds was washed in a
base bath, dried in an oven overnight, and then flame-dried under
vacuum before flushing with argon. All syringes were dried in an oven
overnight and flushed with argon while cooling before use.
Preparation of NMR Samples. All NMR tubes used for variable-
temperature studies were sealed to a hard glass tube connected to a
female 14/20 ground joint. This tube was then fitted with an adapter
consisting of two male 14/20 joints joined by a 2-mm-straight bore
glass stopcock. Caution was taken to avoid excess grease on all joints.
A rubber serum stopper was fitted on the exposed end of the stopcock
adapter and attached to a Schlenk line by a needle and Tygon tubing.
1
trimethylbutyrate in 86% yield:13 bp 100-105 °C/40 Torr; H NMR
(CDCl3, 200 MHz) δ 4.76 (m, 2H), 4.07 (q, 2H), 1.62 (q, 3H), 1.20 (s,
6H), 1.12 (t, 3H); 13C NMR (CDCl3, 50.0 MHz) δ 176.3, 147.7, 110.2,
60.4, 47.5, 24.4, 19.8, 13.9.
A mixture of ethyl 3-chloro-2,3,3-trimethylbutyrate (9.1 g, 0.058
mol) with 10 g of KOH in 15 mL of water and 50 mL of absolute
ethanol was heated under reflux for 2 h and then cooled. Water (100
mL) was added, and the mixture was acidified by adding concentrated
HCl dropwise. After 100 mL of ether was added, layers were separated.
The aqueous layer was extracted twice with ether. The ether extracts
were combined and washed with 50 mL of water and dried over
Na2SO4. After removal of solvent in vacuo, the residue was distilled
to give 6.0 g of the title compound,14 7, in 81% yield:13 bp 135-138
°C/40 Torr; 1H NMR (CDCl3, 200 MHz) δ 11.0 (b, 1H), 4.92 (m, 2H),
1.77 (m, 3H), 1.40 (s, 6H); 13C NMR (CDCl3, 50.0 MHz) δ 183.2,
146.9, 111.1, 47.5, 24.3, 19.9.
N,N-Bis(2-methoxyethyl)-2,3,3-trimethyl-3-butenamide (8). Thio-
nyl chloride (5.2 mL, 0.071 mol) was added dropwise to 7 (6.0 g, 0.047
mol). The mixture was heated at 85 °C (water bath) for 1 h. Excess of
thionyl chloride was removed by distillation, and the remaining mixture
was cooled to 0 °C. Then, 14 mL of bis(2-methoxyethyl)amine (12.7
g, 0.12 mol) was added and the mixture was stirred for 3 h. At this
point, 15 mL of water and 50 mL of ether were added. After separation,
the aqueous layer was extracted with 2 × 30 mL portions of ether.

440 J. Am. Chem. Soc., Vol. 121, No. 2, 1999
Fraenkel et al.
Ether layers were combined, washed with water, and dried over Na2SO4.
After removal of solvent, the residue was distilled to give 8.3 g of title
compound 4 in 73% yield: bp 108-112 °C/40 Torr; 1H NMR (CDCl3,
200 MHz) δ 4.74 (m, 2H), 3.50 (t, 4H), 3.36 (t, 4H), 3.36 (t, 4H), 3.17
(s, 6H), 1.60 (m, 3H), 1.15 (s, 6H); 13C NMR (CDCl3, 50.0 MHz) δ
175.2, 149.6, 108.9, 70.8, 70.1, 58.5, 58.3, 47.9, 47.5, 46.2, 26.3, 19.5.
N,N-Bis(2-methoxyethyl)-2,3,3-trimethyl-3-butenylamide (9). To
a solution of LiAlH4 (1.4 g, 0.036 mol) in 100 mL of THF was added
8 (8.0 g, 0.033 mol) in 15 mL of THF. The mixture was refluxed
overnight. The excess LiAlH4 was hydrolyzed by dropwise addition
of 15 mL of 15% aqueous NaOH at 0 °C. The resulting precipitate
was filtered. The solvent was removed in vacuo, and the residue was
distilled to give 6.0 g of amine 9 in 80% yield: bp 83-84 °C/0.8 Torr;
1H NMR (CDCl3, 200 MHz) δ 4.72 (m, 2H), 3.38 (t, 4H), 3.28 (s,
6H), 2.65 (t, 4H), 2.41 (s, 2H), 1.70 (m, 3H), 0.99 (s, 6H); 13C NMR
(CDCl3, 50.0 MHz) δ 151.5, 110.0, 71.5, 65.4, 58.6, 55.6, 40.6, 25.4,
19.8.
followed by rotary evaporation yielded the product as a waxy, colorless
solid (129 g, 0.34 mol, 51%): mp 63-65 °C (lit.15 mp 65-66 °C); 1H
NMR (CDCl3, δ ) 7.26 ppm) 4.21 (m, 6H), 2.15 (m, 4H), 1.28 (t, J
) 7.0, 6H); 13C NMR (CDCl3, δ ) 77.0) 169.13, 62.20, 44.66, 32.41,
13.91.
cis-2,5-Dicarbethoxy-N-benzylpyrrolidine. A 1-L three-necked
round-bottom flask was equipped with a condenser, an argon inlet, an
addition funnel, and a magnetic stir bar. meso-Diethyl 2,5-dibromo-
adipate (129 g, 0.34 mol) was dissolved in benzene (400 mL) and heated
to a gentle reflux. The heat was removed, and then benzylamine (129
mL, 1.18 mol) was added dropwise to maintain the reflux. After addition
was complete, the mixture was refluxed overnight. Upon cooling to
room temperature, the mixture was vacuum filtered to remove as much
of the benzylamine hydrobromide salt as possible. To prevent isomer-
ization, the product was not washed with base and some of the
hydrobromide salt remained even after distillation due to sublimation
as is evident in the NMR spectrum. The benzene was removed by rotary
evaporation, and the product was distilled to give the product as a clear
liquid in 74% (77.0 g, 0.25 mol): bp 170-174° C (2 Torr) (lit.35 bp
145-148 °C/0.3 Torr); 1H NMR (CDCl3, δ ) 7.24 ppm) 7.28 (m, 5H),
4.05 (m, 4H), 3.79 (s, 2H), 3.65 (m, 2H), 2.04 (m, 4H), 1.146 (m, 6H);
13C NMR (CDCl3, δ ) 77.0 ppm) 173.36, 137.51, 129.48, 128.0,
127.16, 65.53, 63.43, 60.51, 57.77, 53.99, 28.6, 14.11.
3-[(Ethyldimethylsilyl)methyl]-N,N-bis(2-methoxyethyl)-2,2-di-
methyl-3-butenylamine (10). Under an atmosphere of argon, a solution
of amine 9, (2.95 g, 0.013 mol) at 0 °C in 25 mL of THF was reacted
with n-butylllithium (5.3 mL, 2.5 M, 0.013 mol) in pentane. The mixture
was allowed to warm to room temperature and stirred for 2 h. After
cooling the mixture to -78 °C, 1.82 mL (0.013 mol) of dimethylethyl-
chlorosilane was added. The mixture was warmed to room temperature
and stirred for 2 h after which 5 mL of water was added. THF was
removed and 50 mL of ether was added. After separation of phases,
the aqueous layer was extracted twice with 20 mL of ether. The
combined ether layers were washed with 50 mL of water and dried
over Na2SO4. After removal of solvent, the residue was distilled to
cis-2,5-Dicarbethoxypyrrolidine. cis-2,5-Dicarbethoxy-N-benzyl-
pyrrolidine (23.6 g, 77.3 mmol) and absolute ethanol (100 mL) were
introduced into the glass liner of a Parr high-pressure reactor. Palladium
on carbon (10%, 2.36 g) was added and the reactor assembled. The
reactor was flushed four times by filling with hydrogen to 400 psi and
venting before finally being filled to 1200 psi. The reaction vessel was
then heated at 40 °C overnight with vigorous stirring. The mixture was
removed from the reactor and filtered through Celite to remove the
catalyst. The filter cake was washed thoroughly with absolute ethanol.
Rotary evaporation of the ethanol followed by distillation yielded the
product (15.9 g, 73.4 mmol, 95%): bp 127-130 °C/2 Torr (lit.36 bp
1
give 1.6 g of product 10 in 39% yield: bp 120-125 °C/1.0 Torr; H
NMR (CDCl3, 200 MHz) δ 4.73-4.56 (m, 2H), 3.37 (t, 4H), 3.28 (s,
6H), 2.65 (t, 4H), 2.38 (s, 2H), 1.45 (m, 2H), 0.94 (s, 6H), 0.89 (t,
3H), 0.50 (q, 2H), -0.04 (s, 6H); 13C NMR (CDCl3, 50.0 MHz) δ
152.9, 108.1, 71.6, 65.6, 58.6, 55.8, 41.4, 25.2, 19.5, 7.69, 7.29, -2.88.
GC indicated 50% of 9 (1.5 g) remained unreacted.
1
95-96 °C/0.3 Torr); H NMR (CDCl3, δ ) 7.24 ppm) 4.10 (q, J )
N-[2-[2-[Bis(2-methoxyethyl)amino]-1,1-dimethylethyl](ethyldi-
methylsilyl)]allyllithium (26). To a solution of amine 10 (233 mg,
0.74 mmol) in 3.0 mL of THF was added methyllithium (0.65 mL, 1.4
M, 0.91 mmol) in ether at -78 °C. The mixture was then warmed to
room temperature and stirred for 2 h.
An NMR tube with a ground joint connected to an adapter with a
glass stopper was flame-dried under vacuum and flushed with argon.
An aliquot of 1 mL of the above prepared solution was syringed into
the NMR tube. The solvent was removed under vacuum, and the NMR
tube was flushed with argon before it was transferred to a high-vacuum
line (10-6 Torr) trapped with liquid nitrogen to remove all volatile
impurities. After about 1 h, THF-d8 (0.4 mL) was vacuum transferred
to the NMR tube. While frozen with liquid nitrogen and under vacuum,
the tube was sealed with a torch. This sample was stored in dry ice
prior to NMR investigation.
meso-Diethyl 2,5-Dibromoadipate. A 500-mL three-neck round-
bottom flask was equipped with an addition funnel, a condenser, and
an HCl/HBr trap. The flask was charged with adipic acid, (100 g, 0.68
mol) and thionyl chloride (122.6 mL, 1.68 mol). The mixture was then
heated to 65-70 °C with a hot water bath for 2.5 h until the evolution
of HCl gas was complete. Bromine (80.5 mL, 1.56 mol) was added to
the addition funnel. After heating the solution to 85-95 °C, the bromine
was added as fast as it would react while under irradiation from a flood
lamp. After the addition was complete (5 h), the solution was maintained
at 85-90 °C for 1 h and then allowed to cool to room temperature.
Absolute ethanol (500 mL) in a 2-L beaker equipped with a magnetic
stir bar was chilled in an ice bath. The reaction mixture was cautiously
poured into the vigorously stirring ethanol and allowed to stir overnight
in a fume hood, resulting in the formation of a large amount of crystals.
The product was collected in a Buchner funnel and washed with a small
amount of cold ethanol. The ethanolic mother liquor was then allowed
to stir overnight in a fume hood for a second crop of crystals. The
crystals were dissolved in diethyl ether, and the solution was washed
with saturated NaHSO3 (aqueous, 250 mL), H2O (250 mL), saturated
NaHCO3 (aqueous, 2 × 250 mL), and saturated NaCl (aqueous, 250
mL). The solution was then dried over anhydrous Na2SO4. Filtration
7.10, 4H), 3.70 (m, br, 2H), 2.06 (m, br, 2H), 1.84 (m, br, 2H), 1.18 (t,
J ) 7.10, 6H); 13C NMR (CDCl3, δ ) 77.0 ppm) 173.9, 60.82, 60.14,
29.68, 13.95.
cis-2,5-Bis(hydroxymethyl)pyrrolidine (11). A 250-mL three-neck
round-bottom flask was equipped with an addition funnel, a condenser,
an argon inlet, and a magnetic stir bar. Lithium aluminum hydride (5.6
g, 0.148 mol) was charged into the flask, and cis-2,5-dicarbethoxy-
pyrrolidine (12.75 g, 59 mmol) and diethyl ether (50 mL) were loaded
into the addition funnel. The apparatus was flooded with argon and
chilled to 0 °C before the addition of diethyl ether (50 mL) to the LiAlH4
by syringe. The cis-2,5-dicarbethoxypyrrolidine solution was then added
dropwise over a period of 20 min. The cooling bath was removed, and
the mixture was stirred at room temperature for 1 h. Once again the
mixture was cooled to 0 °C before quenching by extremely cautious
incremented addition of H2O (15 mL). The amount of water is very
critical to the successful isolation of the product. Since the product is
insoluble in diethyl ether, the ether was filtered off and the product
and aluminum salts were collected on a Buchner funnel. The product
was then washed from the aluminum salts by stirring the mixture in
hot ethanol (100 mL) for 15 min and then filtering once again on a
Buchner funnel. The process was repeated two additional times. The
crude product (7.09 g, 54 mmol, 91%) was obtained by rotary
evaporation in a tared 250-mL round-bottom flask and was not purified
further before proceeding to the next step.
cis-2,5-Bis(hydroxymethyl)-N-formylpyrrolidine (12). The synthe-
sis of the title compound was based on the synthesis of (S)-(-)-1-
formyl-2-(hydroxymethyl)pyrrolidine published by Kipphardt et al.18
cis-2,5-Bis(hydroxymethyl)pyrrolidine (15.5 g, 0.118 mol) was trans-
ferred (by dissolving in ethanol followed by rotary evaporation to
remove the ethanol) to a 250-mL three-neck round-bottom flask
equipped with an argon inlet, an addition funnel, a reflux condenser,
and a magnetic stir bar. The flask was cooled in an ice/water bath.
Methyl formate (8.18 g, 0.136 mol) was then added dropwise. The
mixture initially dissolves and then becomes viscous upon stirring
(36) O’Neil, B. T.; Watson, H. A. J. Org. Chem. 1990, 55, 2950.

SolVation of Allylic Lithium Compounds
J. Am. Chem. Soc., Vol. 121, No. 2, 1999 441
overnight. The excess methyl formate and methanol were removed
under vacuum to yield a foamy semisolid that was not purified further
before proceeding to the next step.
was fractionated to give the title compound (6.5 g, 30.5 mmol) in 62%
yield as a clear colorless liquid: bp 110-115 °C/1 Torr; 1H NMR
(CDCl3, δ ) 7.26 ppm) 4.81 (s, br, 1H), 4.65 (s, br, 1H), 3.23 (m,
8H), 3.10 (s, 2H), 3.04 (m, 2H), 2.76 (m, 2H), 1.80 (m, 2H), 1.66 (s,
3H), 1.52 (m, 2H). 13C NMR (CDCl3, δ ) 77.0 ppm) 145.35, 111.39,
77.08, 64.96, 62.75, 58.78, 27.91, 20.49; MS M+/e calcd for C12H23-
NO2 213.172 889, obsd 213.172 637 9, base peak C10H18NO+
168.139 938 4.
cis-2,5-Bis(methoxymethyl)-N-formylpyrrolidine (13). The syn-
thesis of the title compound was based on the synthesis of (S)-(-)-1-
formyl-2-(methoxymethyl)pyrrolidine published by Kipphardt et al.18
The 250-mL three-neck round-bottom flask containing the crude cis-
2,5-bis(hydroxymethyl)-N-formylpyrrolidine from the previous step was
fitted with an argon inlet, a reflux condenser, and a magnetic stir bar.
THF (150 mL) was added and the mixture cooled in a dry ice/acetone
bath. cis-2,5-Bis(hydroxymethyl)-N-formylpyrrolidine was not very
soluble in THF, but became brittle when cooled and was broken with
a metal spatula to allow proper stirring. The cold bath was removed,
and methyl iodide (24.0 mL, 0.386 mol) followed by sodium hydride
(8.6 g, 0.356 mol) was added. The reaction was then allowed to warm
slowly. At some point, large gray-brown clumps form in the solution.
These clumps begin to break up with strong evolution of hydrogen at
room temperature. It was necessary to control this reaction by
occasionally cooling the flask in an ice bath. After the evolution of
hydrogen abated, the mixture was refluxed for 20 min before the heat
source was removed and the reaction was quenched by dropwise
addition of 6 M HCl (26.5 mL). The THF was removed by rotary
evaporation to yield the crude product in water. The product was not
further purified before being carried on to the next step.
cis-2,5-Bis(methoxymethyl)pyrrolidine (14). The synthesis of the
title compound was based on the synthesis of (S)-(+)-2-methoxy-
methylpyrrolidine published by Kipphardt et al.18 The aqueous solution
containing the N-formyl-cis-2,5-bis(methoxymethyl)pyrrolidine from
the previous step was transferred to a 500-mL Erlenmeyer flask. A
solution of KOH (53 g, 0.94 mol) in water (210 mL) was added, and
the mixture was stirred overnight. Potassium carbonate (150 g, 1.09
mol) was added causing precipitation of potassium salts which were
removed from the solution by vacuum filtration on a Buchner funnel
and washed with diethyl ether. The solution was extracted with diethyl
ether (3 × 100 mL). The ether layers were combined and washed with
saturated NaCl (aqueous, 50 mL) and dried over anhydrous Na2SO4
before removal of the ether by rotary evaporation. Distillation yielded
the product (6.5 g, 41 mmol, 35% based on cis-2,5-bis(hydroxymethyl)-
pyrrolidine): bp 65-70 °C/0.2 Torr; 1H NMR (CDCl3, δ ) 7.26 ppm)
3.15 (m, 12H), 2.04 (s, 1H), 1.61 (s, br, 2H), 1.24 (s, br, 2H); 13C
NMR (CDCl3, δ ) 77.0 ppm) 76.74, 58.53, 57.59, 26.99.
2-[[Bis(2-methoxyethyl)amino]methyl]-1-(dimethylethylsilyl)pro-
pene (18). A 100-mL three-necked round-bottomed flask equipped with
a magnetic stir bar, an argon inlet tube, a stopcock stopper, and a 25-
mL addition funnel was flame-dried under vacuum and, after cooling
to room temperature, was flushed twice with prepurified argon. Into
the flask was introduced 2-[[bis(2-methoxyethyl)amino]methyl]propene
(4.0 g, 21.4 mmol) and dry THF (20 mL) freshly distilled from sodium-
benzophenone ketyl under argon. The mixture was cooled in a dry ice/
acetone bath for 30 min, and n-butyllithium in hexanes (2.5 M, 8.6
mL, 22 mmol) was added dropwise via syringe. After stirring for 30
min at this temperature, the mixture was allowed to warm to room
temperature and stirred for an additional 2 h, during which a bright
yellow precipitate formed. The mixture was then cooled again in a dry
ice/acetone bath and stirred for 30 min before the dropwise addition
of chlorodimethylethylsilane (2.58 g, 21 mmol) from the addition funnel
over 30 min, during which time the previously observed precipitate
dissolved. On warming the mixture to room temperature and stirring
for 3 h, a white precipitate of LiCl developed. The mixture was
transferred to a 250-mL round-bottomed flask, and most of the solvent
was removed by rotary evaporation. Saturated aqueous sodium chloride
solution (75 mL) was added, and the mixture was transferred to a
separatory funnel. The flask was washed with diethyl ether (75 mL),
and the washings were added to the separatory funnel. The aqueous
layer was additionally extracted with diethyl ether (2 × 75 mL) before
the ether layers were combined and dried over anhydrous sodium
sulfate. Solvent was removed by rotary evaporation before the residue
was distilled under vacuum to afford 4.2 g of the desired title compound
in 72% yield: bp 85-90 °C/0.7 Torr; 1H NMR (CDCl3, δ ) 7.26 ppm)
4.79 (s, br, 1 H), 4.59 (s, br, 1 H), 3.42 (t, J ) 6.0 Hz, 4 H), 3.29 (s,
6 H), 2.94 (s, 2 H), 2.65 (t, J ) 6.0 Hz, 4 H), 1.55 (s, 2 H), 0.90 (t, J
) 7.9 Hz, 3 H), 0.47 (q, J ) 7.9 Hz, 2 H), -0.051 (s, 6 H); 13C NMR
(CDCl3, δ ) 77.00 ppm) 145.34, 109.63, 71.30, 62.79, 58.67, 53.80,
21.92, 7.14, 7.04, -3.62. MS M+/e calcd for C14H31NO2Si 273.212 420,
obsd 273.212 768 6, base peak C12H26NOSi+ 228.175 445 6.
2-[[Bis(2-methoxyethyl)amino]methyl]propene (16). Under an
argon atmosphere, bis(2-methoxyethyl)amine (29.4 g, 220 mmol) and
2-methyl-3-chloropropene (10.0 g, 110 mmol) were introduced into a
flame-dried 100-mL round-bottomed flask equipped with a magnetic
stir bar and a reflux condenser. The mixture was heated to ap-
proximately 80 °C and stirred overnight. The mixture was cooled to
room temperature resulting in precipitation of ammonium salts. After
50 mL of water was added, the mixture was poured into a separatory
funnel and extracted with diethyl ether (3 × 50 mL). The ether layers
were combined and washed with saturated aqueous sodium chloride
solution and dried over sodium sulfate. After gravity filtration, the
solvent was removed by rotary evaporation and the residue was
fractionated to give 15.0 g of the title compound in 80% yield as a
clear colorless liquid: bp 74-76 °C/4 Torr (lit.16 bp 64 °C/2 Torr); 1H
NMR (CDCl3, δ ) 7.26 ppm) 4.82 (s, br, 1 H), 4.75 (s, br, 1H), 3.40
(t, J ) 6.1 Hz, 4 H), 3.28 (s, 6 H), 2.98 (s, 2 H), 2.62 (t, J ) 6.1 Hz,
4 H), 1.67 (s, br 2 H); 13C NMR (CDCl3, δ ) 77.0 ppm) 143.90, 112.32,
71.24, 62.41, 58.56, 53.68, 20.50.
cis-2,5-Bis(methoxymethyl)-1-(2-methylallyl)pyrrolidine (17). Un-
der an argon atmosphere, cis-2,5-bis(methoxymethyl)pyrrolidine (15.6
g, 98 mmol) and 3-chloro-2-methylpropene (4.8 mL, 49 mmol) were
introduced into a flame-dried 50-mL round-bottomed flask equipped
with a magnetic stir bar and a reflux condenser. The mixture was heated
to approximately 80 oC and stirred overnight. The mixture was cooled
to room temperature resulting in a precipitate of ammonium salts. After
25 mL of water was added, the mixture was poured into a separatory
funnel and extracted with diethyl ether (3 × 50 mL). The ether layers
were combined and washed with saturated aqueous sodium chloride
solution (25 mL) and dried over anhydrous sodium sulfate. After gravity
filtration, the solvent was removed by rotary evaporation and the residue
2-[[Bis(2-methoxyethyl)amino]methyl]-1-(tert-butyldimethylsilyl)-
propene (19). A 100-mL three-necked round-bottomed flask equipped
with a magnetic stir bar, an argon inlet tube, a stopcock stopper, and
a 25-mL addition funnel was flame-dried under vacuum and, after
cooling to room temperature, was flushed twice with prepurified argon.
Into the flask was introduced 2-[[bis(2-methoxyethyl)amino]methyl]-
propene (4.0 g, 21.4 mmol) and dry THF (20 mL) freshly distilled
from sodium-benzophenone ketyl under argon. The mixture was cooled
in a dry ice/acetone bath for 30 min, and n-butyllithium in hexanes
(2.5 M, 8.6 mL, 22 mmol) was added dropwise via syringe. After
stirring for 30 min at this temperature, the mixture was allowed to warm
to room temperature and stirred for an additional 2 h, during which
time a bright yellow precipitate formed. The mixture was then cooled
again in a dry ice/acetone bath and stirred for 30 min before the
dropwise addition of tert-butyldimethylsilyl chloride (3.17 g, 21 mmol)
in THF (20 mL) from the addition funnel over 30 min, during which
time the previously observed precipitate dissolved. The mixture was
then warmed to room temperature and stirred for 3 h, during which
time a white precipitate of LiCl formed. The mixture was transferred
to a 250-mL round-bottomed flask and most of the solvent was removed
by rotary evaporation. Saturated aqueous sodium chloride solution (75
mL) was added, and the mixture was transferred to a separatory funnel.
The flask was washed with diethyl ether (75 mL) which was added to
the separatory funnel. The aqueous layer was additionally extracted
with diethyl ether (2 × 75 mL) before the ether layers were combined
and dried over anhydrous sodium sulfate. The solvent was removed
by rotary evaporation before the residue was subjected to bulb-to-bulb
distillation (3 Torr) to afford 2.03 g of the desired title compound in
31% yield: 1H NMR (CDCl3, δ ) 7.26 ppm) 4.81 (s, br, 1 H), 4.62 (s,

442 J. Am. Chem. Soc., Vol. 121, No. 2, 1999
Fraenkel et al.
br, 1 H), 3.44 (t, J ) 6.2 Hz, 4 H), 3.31 (s, 6 H), 2.95 (s, 2 H), 2.67
(t, J ) 6.2 Hz, 4 H), 1.58 (s, 2 H), 0.86 (s, 9 H), -0.04 (s, 6 H); 13C
NMR (CDCl3, δ ) 77.00 ppm) 145.5, 109.9, 71.4, 62.7, 58.7, 53.8,
26.4, 19.1, 16.7, -5.983; MS M+/e calcd for C16H35NO2Si 301.243 710,
obsd 301.247 268 7, base peak C14H28NOSi+ 256.182 830 8.
64.83, 63.33, 58.80, 27.89, 23.75, -1.44; MS M+/e calcd for C15H31-
NO2Si 285.212 420, obsd 285.211 996 4, base peak C13H26NOSi+
240.177 795 4.
[2-[[cis-2,5-Bis(methoxymethyl)-1-pyrrolidinyl]methyl]-1-(tri-
methylsilyl)allyl]lithium (22). A 35-mL Schlenk tube equipped with
a magnetic stir bar and an argon inlet tube was flame-dried under
vacuum and then flushed with argon. Freshly distilled dry diethyl ether
(2.15 mL) and cis-2,5-bis(methoxymethyl)-1-[2-[(trimethylsilyl)methyl]-
allyl]pyrrolidine (0.200 g, 0.70 mmol) were introduced into the tube.
cis-2,5-Bis(methoxymethyl)-1-[2-[(dimethylethylsilyl)methyl]allyl]-
pyrrolidine (20). A 50-mL three-necked round-bottomed flask equipped
with a magnetic stir bar, an argon inlet tube, a stopcock stopper, and
a 25-mL addition funnel was flame-dried under vacuum and, after
cooling to room temperature, was flushed twice with prepurified argon.
Into the flask was introduced cis-2,5-bis(methoxymethyl)-1-(2-methyl-
allyl)pyrrolidine (2.78 g, 13.0 mmol) and dry THF (5 mL) freshly
distilled from sodium-benzophenone ketyl under argon. The mixture
was cooled in a dry ice/acetone bath for 30 min, and butyllithium in
hexanes (1.6 M, 10.6 mL, 17 mmol) was added dropwise via syringe.
After stirring for 30 min at this temperature, the mixture was allowed
to warm to room temperature and stirred for an additional 2 h, during
which time a bright yellow precipitate formed. The mixture was then
cooled again in a dry ice/acetone bath and stirred for 30 min before
the dropwise addition of chlorodimethylethylsilane (1.91 g, 2.19 mL,
15.6 mmol) from the addition funnel over 30 min, during which time
the previously observed precipitate dissolved. The mixture was then
warmed to room temperature and stirred for 3 h. During this time, a
white precipitate of LiCl developed. The mixture was transferred to a
250-mL round-bottomed flask, and most of the solvent was removed
by rotary evaporation. Saturated aqueous sodium chloride solution (50
mL) was added, and the mixture was transferred to a separatory funnel.
The flask was washed with diethyl ether (50 mL), and the washings
were added to the separatory funnel. The aqueous layer was additionally
extracted with diethyl ether (2 × 50 mL) before the ether layers were
combined and dried over anhydrous sodium sulfate. After removal of
solvent by rotary evaporation, the residue was distilled under vacuum
to afford the desired title compound (1.40 g, 4.67 mmol) in 36%
o
After the solution was chilled to -78 C with a dry ice/acetone bath
under argon, a solution of methyllithium in diethyl ether (1.4 M, 0.65
mL, 0.92 mmol) was added slowly by syringe. The temperature was
allowed to warm to room temperature, and then the mixture was stirred
for 1 h.
An NMR sample with a concentration of 0.25 M was prepared as
previously described: 1H NMR (Et2O-d10, δ ) 1.07 ppm) 4.16 (d, J )
3.2 Hz, 1H), 4.13 (d, J ) 3.2 Hz, 1H), 3.43 (s, 6H), 3.36 (m, 2H), 3.01
(s, 2H), 2.82 (s, br, 2H), 1.83 (m, br, 4H), 0.82 (s, 1H), -0.003 (s,
9H); 13C NMR (Et2O-d10, δ ) 14.5 ppm) 158.82, 74.58, 69.13, 67.40,
58.81, 43.79, 27.69, 1.95.
[2-[[cis-2,5-Bis(methoxymethyl)-1-pyrrolidinyl]methyl]-1-(di-
methylethylsilyl)allyl]lithium (23). A 35-mL Schlenk tube equipped
with a magnetic stir bar and an argon inlet tube was flame-dried under
vacuum and then flushed with argon. Freshly distilled dry diethyl ether
(2.15 mL) and cis-2,5-bis(methoxymethyl)-1-[2-[(dimethylethylsilyl)-
methyl]allyl]pyrrolidine (0.200 g, 0.67 mmol) were introduced into the
tube. After the solution was chilled to -78 °C with a dry ice/acetone
bath under argon, a solution of methyllithium in diethyl ether (1.4 M;
0.62 mL; 0.87 mmol) was added slowly by syringe. The temperature
was allowed to warm to room temperature and then the mixture was
stirred for 1 h.
An NMR sample with a concentration of 0.25 M was prepared as
previously described: 1H NMR (Et2O-d10, δ ) 1.07 ppm) 4.15 (d, J )
3.4 Hz, 1H), 4.12 (d, J ) 3.4 Hz, 1H), 3.41 (s, 6H), 3.33 (m, 2H), 3.07
(s, 2H), 2.80 (s, br, 2H), 1.81 (m, 4H), 0.92 (t, J ) 7.9 Hz, 3H), 0.51
(q, J ) 7.9 Hz, 2H), -0.06 (s, 6H); 13C NMR (Et2O-d10, δ ) 14.5
ppm) 159.09, 74.70, 73.76, 69.19, 67.35, 58.87, 42.80, 27.77, 10.36,
9.12, 0.50.
[2[[Bis(2-methoxyethyl)amino]methyl]-1-(dimethylethylsilyl)allyl]-
lithium (24). A 35-mL Schlenk tube equipped with a magnetic stir
bar and an argon inlet tube was flame-dried under vacuum and then
flushed with argon. Freshly distilled dry THF (1.5 mL) and 2-[[bis(2-
methoxyethyl)amino]methyl]-1-(dimethylethylsilyl)propene (0.200 g,
0.77 mmol) were introduced into the tube. After the solution was chilled
to -78 °C with a dry ice/acetone bath under argon, a solution of
methyllithium in diethyl ether (1.4 M, 0.66 mL, 0.92 mmol) was added
slowly by syringe. The temperature was allowed to warm to room
temperature, and then the mixture was stirred for 1 h. This procedure
was also repeated using n-butyllithium (6Li).
Samples were prepared using diethyl ether-d10 and THF-d8 as
solvents. This sample had a concentration of 0.25 M and was stored in
dry ice prior to the NMR studies: 1H NMR (Et2O-d10, δ ) 1.07 ppm)
3.29 (t, J ) 5.3 Hz, 4 H), 3.04 (s, 6 H), 2.97 (s, 1 H), 2.93 (s, 1 H),
2.54 (s, 2 H), 2.41 (t, J ) 5.3 Hz, 4 H), 0.60 (t, J ) 7.8 Hz, 3 H), 0.33
(s, 1 H), 0.20 (q, J ) 7.8 Hz, 2 H), -0.39 (s, 6 H); 13C NMR (Et2O-
d10, δ ) 65.3 ppm) 157.8, 76.00, 70.84, 69.24, 58.45, 56.74, 40.22,
10.41, 9.16, -0.52.
[2-[[Bis(2-methoxyethyl)amino]methyl]-1-(tert-butyldimethyl-
silyl)allyl]lithium (25). A 35-mL Schlenk tube equipped with a
magnetic stir bar and an argon inlet tube was flame-dried under vacuum
and then flushed with argon. Freshly distilled dry THF (1.5 mL) and
2-[[bis(2-methoxyethyl)amino]methyl]-1-(tert-butyldimethylsilyl)pro-
pene (0.232 g, 0.77 mmol) were introduced into the tube. After the
solution was chilled to -78 oC with a dry ice/acetone bath under argon,
a solution of methyllithium in diethyl ether (1.4 M, 0.66 mL, 0.92
mmol) was added slowly by syringe. The temperature was allowed to
warm to room temperature, and then the mixture was stirred for 1 h.
NMR samples with a concentration of 0.25 M were prepared with
THF-d8 and Et2O-d10 as previously described. Two other samples with
concentrations of 0.50 and 0.125 M in Et2O-d10 were also prepared:
1H NMR (THF-d8, δ ) 1.73 ppm) 3.59 (t, J ) 5.3 Hz, 4 H), 3.35 (s,
1
yield: bp 135-140 °C/0.8 Torr; H NMR (CDCl3, δ ) 7.26 ppm)
4.77 (s, br, 1H), 4.48 (s, br, 1H), 3.23 (m, 8H), 3.03 (m, 4H), 2.74 (m,
2H), 1.78 (m, 2H), 1.51 (m, 4H), 0.87 (t, J ) 7.8 Hz, 3H), 0.43 (q, J
) 7.8 Hz, 2H), -0.08 (s, 6H); 13C NMR (CDCl3, δ ) 77.0 ppm)
146.67, 109.12, 77.20, 64.88, 63.43, 58.87, 27.98, 22.00, 7.29, 6.98,
-3.67; MS M+/e calcd for C16H33NO2Si 299.228 060, obsd
299.226 470 9, base peak C14H28NOSi+ 254.194 351 2.
cis-2,5-Bis(methoxymethyl)-1-[2-[(trimethylsilyl)methyl]allyl]pyr-
rolidine (21). A 50-mL three-necked round-bottomed flask equipped
with a magnetic stir bar, an argon inlet tube, a stopcock stopper, and
a 25-mL addition funnel was flame-dried under vacuum and, after
cooling to room temperature, was flushed twice with prepurified argon.
Into the flask was introduced cis-2,5-bis(methoxymethyl)-1-(2-methyl-
allyl)pyrrolidine (2.65 g, 12.4 mmol) and dry THF (5 mL) freshly
distilled from sodium-benzophenone ketyl under argon. The mixture
was cooled in a dry ice/acetone bath for 30 min, and butyllithium in
hexanes (1.6 M, 10.0 mL, 16 mmol) was added dropwise via syringe.
After stirring for 30 min at this temperature, the mixture was allowed
to warm to room temperature and stirred for an additional 2 h, during
which a bright yellow precipitate formed. The mixture was then cooled
again in a dry ice/acetone bath and stirred for 30 min before the
dropwise addition of chlorotrimethylsilane (1.62 g; 1.89 mL; 14.9
mmol) from the addition funnel over 30 min. During this time, the
previously observed precipitate dissolved. The mixture was then warmed
to room temperature and during stirring over 3 h a white precipitate of
LiCl formed. The mixture was transferred to a 250-mL round-bottomed
flask, and most of the solvent was removed by rotary evaporation.
Saturated aqueous sodium chloride solution (50 mL) was added, and
the mixture was transferred to a separatory funnel. The flask was washed
with diethyl ether (50 mL) which was added to the separatory funnel.
The aqueous layer was additionally extracted with diethyl ether (2 ×
50 mL) before the ether layers were combined and dried over anhydrous
sodium sulfate. The solvent was removed by rotary evaporation before
the residue was distilled under vacuum to afford the desired title
compound (2.46 g, 8.6 mmol) in 69% yield: bp 130-140 °C/0.8 Torr;
1H NMR (CDCl3, δ ) 7.26 ppm) 4.77 (s, br, 1H), 4.47 (s, br, 1H),
3.23 (m, 8H), 3.03 (m, 4H), 2.76 (m, 2H), 1.79 (m, 2H), 1.52 (m, 4H),
0.045 (s, 9H); 13C NMR (CDCl3, δ ) 77.0 ppm) 146.63, 109.00, 77.14,

SolVation of Allylic Lithium Compounds
J. Am. Chem. Soc., Vol. 121, No. 2, 1999 443
6 H), 3.22 (s, br, 2 H), 2.84 (s, 2 H), 2.74 (t, J ) 5.3 Hz, 4 H), 0.87
(s, 9 H), 0.85 (s, 1 H), -0.06 (s, 6 H); 13C NMR (THF-d8, δ ) 67.4
ppm) 158.3, 73.8, 70.9, 69.7, 68.3, 58.7, 56.1, 28.7, 20.6, -2.8.
Instrumentation Center, who provided invaluable advice and
assistance on NMR technology.
Supporting Information Available: Observed and calcu-
lated NMR line shapes and Eyring plots. See any current
masthead page for ordering information and Web access
instructions.
Acknowledgment. This research was generously supported
by the National Science Foundation, Grant CHE9615116, as
was acquisition in part of the NMR equipment used in this work.
We are grateful to Dr. Charles Cottrell, Central Campus
JA983047H