Lithiation of TMEDA and its higher homologous TEEDA: Understanding observed α- and β-deprotonation

Article abstract of DOI:10.1021/ja8058205

TMEDA and its ethyl-substituted analogue, TEEDA, show a different behavior toward the deprotonation with lithiumalkyls. While TMEDA mainly undergoes α-lithiation of its methyl group, TEEDA shows selective β-lithiation with following elimination of ethene. The crystal structure of the monomeric intermediate of this β-lithiation, tBuLi·TEEDA, and theoretical studies indicate kinetic favoritism for the β-lithiation. Copyright

Full text of DOI:10.1021/ja8058205

Published on Web 10/09/2008
Lithiation of TMEDA and its Higher Homologous TEEDA: Understanding
Observed r- and ꢀ-Deprotonation
Viktoria H. Gessner and Carsten Strohmann*
Anorganische Chemie, Technische UniVersit a¨ t Dortmund, Otto-Hahn-Str. 6, 44227 Dortmund, Germany
Received July 25, 2008; E-mail: mail@carsten-strohmann.de
The use of Lewis bases to increase the reactivity of lithium
organics is an important tool in synthetic chemistry. Thereby,
N,N,N′,N′-tetramethylethylenediamine (TMEDA, 1) belongs to the
most powerful and most often used Lewis bases in various types
1
of reactions. The increased reactivity is based on the deaggregation
of the lithiumalkyl, which has been shown in many examples by
2
X-ray diffraction analysis. However, besides the activation prop-
erty, these powerful metalating systems can easily attack solvents
or lead to intramolecular lithiation of the amine, resulting in side
products and loss of base. Among others, TMEDA (1) is known to
undergo a direct R-lithiation, the regioselectivity of which depends
3
on the used deprotonation agent. Another, but less often used,
Lewis base is the ethyl-substituted analogue of TMEDA, N,N,N′,N′-
Figure 2. Molecular structure of R-lithiated TMEDA (2) in the crystal
tetraethylethylenediamine (TEEDA, 4). Although there is less
known about this ligand, investigations show an increased reactivity
of lithium bases and higher selectivities by changing from TMEDA
(several hydrogens omitted). Selected bond lengths (Å) and angles (deg):
Li-C4, 2.174(2); Li′′′-C4, 2.148(2); Li-N1, 2.116(2); Li-N2, 2.037(2);
C4′′-Li-C4, 152.30(11); Li-C4-Li′′′, 88.26(11).
4
to TEEDA.
Scheme 1. R-Lithiation of TMEDA to the Tridentate Ligand 3
Figure 1. Lithiation of nonmetal functionalized alkyls (e.g., El ) R2N,
R2P, R3Si).
We present herein structural and mechanistic investigations of
the lithiation of TMEDA and TEEDA. Based on X-ray structures
we will give an explanation for the unexpected, selective ꢀ-lithiation
of TEEDA. While the deprotonation in the R-position to a nonmetal
is a well-known phenomenon, e.g. of phosphorus or nitrogen
compounds, the lithiation in the ꢀ-position to these elements is
highly exceptional (Figure 1), as a saturated hydrocarbon unit needs
Scheme 2. ꢀ-Lithiation of TEEDA 4 to Lithium Amide 5 and Amine
6 After Hydrolysis (75% Nonoptimized Yield)
3
to be directly lithiated by a lithiumalkyl. As TEEDA with its ethyl
groups bound to a heteroatom resembles diethylether, these results
hint to the mechanism of the decomposition of ether, which is of
5
,2
central interest in organolithium chemistry.
After intermediate warming to room temperature, R-lithiated
TMEDA (2) crystallizes at -78 °C from n-pentane out of a solution
of the amine and tBuLi (Figure 2). 2 crystallizes in the tetragonal
warmed reaction mixture of TEEDA and tBuLi yielded crystals of
the lithium amide 5 as result of the deprotonation of the ꢀ-hydrogen
atom and following elimination of ethene (Scheme 2). The same
6
7
crystal system, space group I4
Li atom possesses four contacts: two to the nitrogen atoms of the
ligand and two to the lithiated carbon centers. The Li-C distances
1
/a as an S
4
symmetric tetramer. Each
reaction was observed with nBuLi, sBuLi, and iPrLi as bases,
leading to the corresponding amine, N,N,N′-triethylethylenediamine
(6), after hydrolysis of 5 with water. Altogether, the deprotonation
of TEEDA is an unexpected example of a direct deprotonation of
a primary carbon unit by a lithiumalkyl. Such an elimination
reaction generally requires activated CH bonds and polar solvents
for the stabilization of intermediate species.
[
2.174(2) and 2.148(2) Å] and Li-N distances [2.116(2) and3
.037(2) Å] are comparable with known lithiated methylamines.
TMEDA is a rare example of a methylamine, which undergoes
2
3
f,g
direct R-lithiation of its methyl group.
However, competitive
lithiation of the ethylene bridge limits the yield of trapping reactions
of R-lithiated TMEDA. Nevertheless, it can be used synthetically
for the preparation of new ligands such as the tridentate ligand 3
This different lithiation behavior of TMEDA and TEEDA
prompted us to take a closer glance at the ongoing processes.
Therefore, we tried to isolate an intermediate species, based on
which the reaction behavior can be explained. Out of a mixture of
tBuLi and TEEDA, monomeric tBuLi·TEEDA (7) crystallizes in
(
Scheme 1).
An attempt to deprotonate the methylene group of TEEDA led
to a totally different result. Cooling to -78 °C of a previously
1
the monoclinic crystal system, space group P2 /n (Figure 3). The
1
4412 9 J. AM. CHEM. SOC. 2008, 130, 14412–14413
10.1021/ja8058205 CCC: $40.75  2008 American Chemical Society

C O M M U N I C A T I O N S
the lithiation of TEEDA suggest an analogous mechanism of this
reaction by precoordination of the ether to the lithiumalkyl.
In conclusion, we presented the structural and mechanistic
investigation of the lithiation of TMEDA and its ethyl-substituted
analogue, TEEDA (4). Hereby, we isolated R-lithiated TMEDA
(
2) as a tetrameric compound and monomeric tBuLi·TEEDA (7).
Based on 7 the unexpected favoritism for the ꢀ-lithiation of TEEDA
could be explained by means of DFT studies indicating a kinetic
favoritism for the ꢀ-lithiation in comparison to the R-deprotonation.
This favoritism according to the complex-induced proximity effect
is also indicated by the crystal structure of intermediate 7, showing
short distances and an arrangement of the ꢀ-hydrogen atom toward
the carbanionic center.
Figure 3. Molecular structure of tBuLi·TEEDA (7). Selected bond lengths
Å) and angles (deg): C1-Li, 2.101(3); Li-N1, 2.102(3); Li-N2, 2.094(3);
C1-H8c, 3.28(2); C1-H6c, 3.15(2); C1-H5b, 3.95(2); C1-Li-N1,
30.99(15); C1-Li-N2, 141.14(16); N1-Li-N2, 87.79(12).
(
Acknowledgment. We are grateful to the Deutsche Forschungs-
gemeinschaft and the Fonds der Chemischen Industrie for financial
support and the award of a scholarship (V.H.G.).
1
Supporting Information Available: Crystallographic (CIF), ex-
perimental and computational data, complete ref 9. This material is
available free of charge via the Internet at http://pubs.acs.org.
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4
). These results show a significant kinetic favoritism of the
ꢀ-lithiation over the R-lithiation of the methylene group. This is
also indicated in the crystal structure of tBuLi ·TEEDA (7), showing
closer contacts between the carbanionic center and the ꢀ-hydrogens
(
(
[
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5
lithiumalkyls occurs via a ꢀ-elimination reaction. The results of
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