Stereochemical Aspects of Enantiopure and Racemic Organolithium Aggregates Li4Ar4 {Ar = C6H4[CH(M)NM2]-2}

Article abstract of DOI:10.1002/ejoc.200300550

The compounds (R)- and rac-[1-(dimethylamino)ethyl]benzene, (R)-1 and rac-1, respectively, react quantitatively with tBuLi in a 1:1 molar ratio in pentane to give the corresponding (R)- and rac-{Li4[C6H4(CH(Me)NMe2)-2]4} (R)-2 and rac-2, respectively. The

Full text of DOI:10.1002/ejoc.200300550

FULL PAPER
Stereochemical Aspects of Enantiopure and Racemic Organolithium
Aggregates Li Ar {Ar ؍ C H [CH(Me)NMe ]-2}
4
4
6
4
2
[
a]
[a]
[a]
Claudia M. P. Kronenburg, Evelien Rijnberg, Johann T. B. H. Jastrzebski,
[b]
[b]
[b]
Huub Kooijman, Anthony L. Spek, and Gerard van Koten*
Dedicated to the memory of Dr. Ron Snaith and his great contribution to organolithium chemistry
Keywords: Lithiation / Lithium / Racemic compounds / Structure elucidation
The compounds (R)- and rac-[1-(dimethylamino)ethyl]ben-
zene, (R)-1 and rac-1, respectively, react quantitatively with
tBuLi in a 1:1 molar ratio in pentane to give the correspond-
tion, in non-coordinating hydrocarbon solvents, and in the
solid state. Detailed information about rac-2, which, in con-
trast to the high solubility of (R)-2, is essentially insoluble in
4 6 4 2 4
{C H [CH(Me)NMe ]-2}
], (R)-2 and rac- hydrocarbon solvents, was provided by 13C CP/MAS NMR
ing (R)- and rac-[Li
, respectively. The same reaction with nBuLi afforded a 1:1:1
aggregate of nBuLi, 2, and 1 according to the results of nuclear aggregate comprising a combination of two dimeric
2
spectra. We conclude that rac-2 is a self-assembled tetra-
1
13
7
quench experiments with H
2
O and D
2
O. The H, C, and Li
units, but in this case they are derived from the (R)- and (S)-
enantiomers, respectively.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
NMR spectra, as well as the single-crystal X-ray structure,
reveal that (R)-2 has a unique self-assembled tetranuclear
structure of two diastereoisomeric dimeric units both in solu-
Introduction
donor groups, which can be either solvent molecules or in-
ter- or intramolecularly coordinating substituents in the or-
[
2,12]
The use of organolithium reagents in chemical synthesis ganic monoanion.
These inter- and intramolecular do-
has increased enormously during the last 30 years.[1,2] Their nor groups are known to affect the synthesis and reactivity
[
13Ϫ17]
relatively simple synthesis and high reactivity make organ- of organolithium reagents.
For the synthesis of ortho-
olithium compounds often more attractive reagents in or- lithiated aryl compounds, direct lithiation is commonly
ganic synthesis than are the corresponding Grignard re- used by hydrogenϪlithium exchange (deprotonation) of the
agents. The most widely used organolithium compound, ortho-substituted arene with a suitable alkyllithium com-
nBuLi, is currently applied to both laboratory-scale synth- pound (nBuLi, sBuLi, or tBuLi). In this reaction [the so-
eses and large-scale industrial processes. Aryllithium com- called Directed ortho Metallation (DoM) reaction] the or-
pounds, especially ortho-lithiated ones, have proven to be tho-substituent acts as an ortho-directing group (oDG),
important reagents in the synthesis of functionalized aro- which leads to the regioselective formation of the ortho-li-
[
3,4,18Ϫ20]
matic compounds and are of great interest to organic chem- thiated product.
[
3,4]
ists.
Furthermore, they are frequently used in transmet-
In our studies we frequently make use of oDG-arenes, in
allation reactions that lead to catalytically active organome- which the oDG is a CH(Z)NR substituent, e.g., [(1-di-
2
[
5]
tallic complexes, e.g., arylϪplatinum metal complexes and methylamino)methyl]benzene, 1,3-bis[(dimethylamino)me-
related copper and zinc species.[
6Ϫ11]
thyl]benzene, and chiral derivatives (at the benzylic-C or
In general, organolithium species associate through their -N centers) thereof. In several cases, we have observed that
electron-deficient carbonϪlithium bonds. The type of ag- ortho-lithiation of these oDG-arenes with nBuLi in a 1:1
gregation that these compounds undergo is governed by molar ratio did not proceed beyond 50% conversion, leaving
steric factors and the presence of heteroatom-containing unchanged nBuLi and oDG-arene, where subsequent
quench experiments still indicated the presence of reactive
[
a]
[21,22]
Debye Institute, Department of Metal-Mediated Synthesis, butyl anions.
We believe that the unchanged BuLi be-
Utrecht University,
comes incorporated in mixed (nBu/oDG-aryl)lithium aggre-
Bijvoet Center for Biomolecular Research, Crystal and gates and, in that way, becomes inaccessible for further re-
Padualaan 8, 3584 Utrecht, The Netherlands
[
b]
Structural Chemistry, Utrecht University,
action with free oDG-arene. Indeed, isolated examples of
such mixed aggregates have been characterized.
existence is of importance, for example, when in situ-lithi-
Padualaan 8, 3584 CH Utrecht, The Netherlands
[
23Ϫ26]
Their
Fax: (internat.) ϩ 31-30-2523615
E-Mail g.vankoten@chem.uu.nl
Eur. J. Org. Chem. 2004, 153Ϫ159
DOI: 10.1002/ejoc.200300550
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
153

G. van Koten et al.
FULL PAPER
ated oDG-arenes are used in subsequent transmetallation
reactions; the presence of mixed (butyl/oDG-aryl)lithium
aggregates, rather than quantitative lithiated oDG-arenes,
will give rise to the formation of a mixture of butyl and
oDG-aryl metal species instead of a pure oDGϪaryl metal
compound.
This paper descibes the factors that determine the forma-
tion and structural features of an enantiopure oDG-arylli-
thium compound, (R)-[Li {C H [CH(Me)NMe ]-2} ], and
4
6
4
2
4
its racemic analog, rac-[Li {C H [CH(Me)NMe ]-2} ]. We
4
6
4
2
4
will detail the synthesis of mixed (butyl/oDG-aryl)lithium
aggregates in a future paper.
Results and Discussion
Synthesis
Scheme 1
Reaction of (R)-[1-(dimethylamino)ethyl]benzene [(R)-1]
with nBuLi in a 1:1 molar ratio in diethyl ether at room
temperature for 24 h, followed by quenching the reaction
mixture with D O, afforded a 1:1 mixture of (R)-1 and (R)-
2
cemic rac-2 is essentially insoluble (Ͻ 1 mg/mL) in them. In
this respect, it should be noted that the achiral analog of 2,
1-orthoD, which indicates that ortho-lithiation occurred to
50% completion (see Scheme 1). Based on this ‘‘chemical
[
Li {C H (CH NMe )-2} ], which is isostructural with (R)-
4 6 4 2 2 4
[
27]
evidence,’’ earlier we had proposed the formation of a spec-
ies consisting of the ortho-lithiated arene, unchanged
2, is also insoluble in hydrocarbon solvents.
nBuLi, and the complexed parent oDG-arene in a 1:1:1 ra-
Structural Aspects of (R)- and rac-[Li {C H [CH(Me)-
tio.[
21,22]
4
6
4
The structural characterization of this species, i.e.,
NMe ]-2} ]
2
4
[
(nBu)(oDG-aryl)Li (oDG-arene)], is still under investi-
2
gation. In contrast, we found that the reaction of (R)-1 with
Crystals of (R)-2 that were suitable for X-ray crystal-
tBuLi instead of nBuLi[ in pentane proceeded to com- lography were obtained by treating (R)-1 with tBuLi in pen-
21]
pletion and gave the pure oDG-aryllithium compound tane without stirring. Similar attempts to obtain suitable
[
Li {C H [CH(Me)NMe ]-2} ] [(R)-2], which was isolated crystals of rac-2 failed, invariably resulting in the formation
4 6 4 2 4
as a white solid in an almost-quantitative yield (see of pure, but amorphous, rac-2.
Scheme 1). According to the same procedure, the racemic
The molecular geometry of (R)-2 in the solid state reveals
oDG-aryllithium compound rac-2 was prepared starting a tetranuclear aggregate in which the four lithium atoms are
from racemic [1-(dimethylamino)ethyl]benzene [rac-1].
arranged in an almost-regular tetrahedron. Each of the aryl
The very different solubility of (R)-2 and rac-2 in hydro- groups is bonded via Cipso (five-coordinate) to one of the
carbon solvents, such as benzene and toluene, is striking. faces of the Li tetrahedron, while the nitrogen atom of the
4
Whereas (R)-2 has an almost infinite solubility in these sol- ortho-amine substituent is coordinated to the apical posi-
vents, making structural studies by NMR spectroscopic tion of a lithium atom, rendering this lithium atom four-
techniques in solution relatively easy, the corresponding ra- coordinate. The overall structural geometry of (R)-2 is de-
2
Figure 1. Ball-and-stick model of (R)-2 in two different orientations; rotation (90°) of A along the y axis gives B; the C dimeric unit is
1
1
2
clearly visible in the upper half of the Li
4
tetrahedron of A, while the C dimeric unit can be seen in the lower half of B (for C and C ,
see Figure 4)
154
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Eur. J. Org. Chem. 2004, 153Ϫ159

Aspects of Enantiopure and Racemic Organolithium Aggregates
FULL PAPER
picted in Figure 1. Relevant bond lengths and angles are
given in Table 1.
˚
Table 1. Selected bond lengths [A] and torsion angles [°] for (R)-2
C1ϪLi1
C1ϪLi1a
C1ϪLi2
C6···Li1a
C11ϪLi1
C11ϪLi2
2.250(3) C11ϪLi2a
2.309(3) N1ϪLi1
2.341(3) N2ϪLi2a
2.414(3) Li1ϪLi2
2.347(2) Li1ϪLi1a
2.354(3) Li1ϪLi2a
Li2ϪLi2a
2.229(4)
2.040(3)
2.033(2)
2.591(3)
2.498(3)
2.588(4)
2.551(4)
Figure
3. Three
geometrically different
isomers of
[Li (C H [CH NMe ]-2) (THF) ]
2
6
4
2
2
2
2
C1ϪC2ϪC7ϪC8
C11ϪC12ϪC17ϪC18
180.0(2)
Ϫ96.5(2)
a ϭ 1 Ϫ x, Ϫy, z
In relation to the present study, it is important to note
that dimers A and C are present as pairs of enantiomers,
(S)C(i),(S)C(i) and (R)C(i),(R)C(i), respectively, while B is a
meso form (see Figure 3). This situation arises because each
of the bridging Cipso atoms of the two-electron, three-
center-bonded ortho-amino aryl groups in these aggragates
The basic structural features of (R)-2 in the solid state
closely resemble those reported earlier for
Li {C H [CH NMe ]-2} ]. A useful way to describe the
[27]
[
4
6
4
2
2
4
has become a chiral center, labelled (S)C(i) or (R)C(i), which
central Li (C ) core in both structures is in terms of a
[37,38]
4
ipso 4
is a topic that has been discussed in detail earlier.
In
distorted cube having alternating Li and C atoms, with the
C atoms being the two-electron, four-center-bonded Cipso
atoms. The four ortho-amine-chelated aryl ligands span four
edges of this cube, which can be realized in two different
ways as shown in Figure 2.
fact, arrangements of types I and II found in the solid state
comprise two associated dimers of type C. Furthermore, it
was concluded that in solution the NϪLi coordination is
rigid on the NMR spectroscopic time scale.
A different situation arises when a second chiral center
with a given configuration is added to the C,N-chelate ring
[
38]
(
chiral labelling approach).
Figure 4 presents two differ-
1
2
ent possibilities, C and C , which are diastereoisomers, for
a C-type dimer having a methyl-substituted benzylic carbon
center with an R configuration [labelled (R)C(b)], as is the
3
case in (R)-2. For rac-2, a third type of dimer, i.e., C in
Figure 4, should also be considered. The chiral benzylic car-
Figure 2. The two different ways in which the C,N-chelating ligands bon atoms have opposite configurations in this dimer. An
4 4
can span the edges of the Li C cube
interesting feature of this ‘‘racemic’’ dimer is the fact that
the two C,N-chelate ligands are diastereotopic, i.e., they
have different resonance patterns in NMR spectra.
While the four C,N-ligands in II are symmetry-related by
three perpendicular twofold axes, these four ligands in I are
symmetry-related by a fourfold inversion axis. Precedents
for both arrangements have been reported in the literature,
[
27]
e.g., [Li {C H [CH NMe ]-2} ]
and [Li {CH[Me]-
4
6
4
[
2
2
4
4
28]
CH CH OMe} ]
have arrangement
I
while [Li4-
2
2
4
[29,30]
(
CH CH CH NMe ) ]
and
[Li (CH CH CH
2
2
2
2 4
4
2
2
2-
[
31]
OMe)4] have arrangement II.
It is interesting to note that the central core of this type
of Li aggregate in both arrangements comprises an associ-
4
Figure 4. Three diastereoisomeric structures for a C-type dimer
having a chiral center in the five-membered chelate-ring
ation of two dimeric units. Previously, we reported that the
tetranuclear aggregate [Li {C H [CH NMe ]-2} ] breaks
4
6
4
2
2
4
down in THF into the corresponding THF-solvated dimers,
although little structural data were available for such dimers
[
27,32]
at the time.
More recently, an elegant multinuclear
These C-type diastereoisomers have different stereochem-
NMR spectroscopy study was conducted using these dimers ical features, in particular for the structural positioning of
and related compounds in polar solvents, such as THF, di- the benzylic methyl substituents in (R)-2. These substituents
1
2
ethyl ether, or a combination thereof. This study revealed are pointing towards each other in C , but in C they point
that such dimers exist in polar, coordinating solvents as an in opposite directions. It is obvious that steric congestion
equilibrium mixture of three geometrically different types in the latter type of dimer is lower, which most likely favors
of dimers: A, B, and C[
33Ϫ36]
(see Figure 3).
C over C .
2
1
Eur. J. Org. Chem. 2004, 153Ϫ159
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155

G. van Koten et al.
FULL PAPER
1
2
At this point it is worth noting that, in the case of (R)-2, dimers, C and C . Furthermore, this situation was con-
a type-I Li4 arrangement (cf. Figure 2) can only be as- firmed by the observation of two resonances in a 1:1 ratio
1
2
6
sembled by a combination of one C dimer and one C
of intensities at δ ϭ 0.09 and 0.14 ppm in the Li NMR
1
dimer, and consequently the Li aggregate contains two dia- spectrum of (R)-2. In the H NMR spectrum, a third reson-
4
stereoisomeric (dimeric) parts. Combination of either two ance pattern is also present, although with lower intensity
1
2
C or two C dimers always results in the formation of a (ca. 10%), which could not be seen in the corresponding
13
type-II Li arrangement. It is obvious that the latter will be
C NMR spectrum because of the low signal-to-noise ra-
4
the most favored one for steric reasons (vide supra).
tio. This additional resonance pattern displays an H(6) res-
The X-ray crystal structure of (R)-2 reveals a type-I ar- onance at δ ϭ 8.55 ppm, which is indicative of the presence
rangement [all four benzylic carbon centers have (R) con- of a CipsoϪLi bond, as well as an additional resonance of a
figuration]. For reasons outlined above, this tetranuclear ag- benzylic hydrogen atom at δ ϭ 3.05 ppm. We propose that
1
gregate contains two diastereoisomeric dimeric units, C
the latter resonance pattern is the result of the presence of
2
and C . This structural feature results in a rather-crowded minor amounts of (R)-2, e.g., in the form of a type-II aggre-
situation for the methyl groups at the side of the cube that gate. It should be noted, based on symmetry considerations,
1
comprises the C -type dimer. As a consequence of this that a type-II structure gives rise to only one resonance pat-
crowding, the aryl groups are tilted in such a way that the tern for all four ortho-amine-chelated aryl groups. This ob-
aryl carbon atom next to Cipso, i.e., C(6), lies in close prox- servation could indicate that an equilibrium exists between
˚
imity [2.418(3) A] to one of the lithium atoms.
the type-I and -II aggregates in solution, which in apolar
The ring pucker-conformations of the five-membered solvents lies predominantly to the side of the type-I aggre-
1
2
C,N-chelate rings in the C and C parts of (R)-2 are dis- gate. Precedents for the existence of such an equilibrium
2
[29,30]
tinctly different. In the C -type dimeric part the α-methyl have been documented for [Li (CH CH CH NMe ) ],
4
2
2
2
2 4
substituents are placed in the energetically favored antiper- which has a type-II structure in the solid state. H, 13C, and
iplanar conformation with respect to the corresponding aryl
ring [torsion angle Ϫ96.5(2)°]. In contrast, these α-methyl that in solution this compound exists as a 60:40 equilibrium
substituents in the C -type dimeric part are orientated in- mixture of type-I and type-II aggregates.
1
7
Li NMR spectra at Ϫ40 °C in [D ]toluene show, however,
8
1
[31]
Above Ϫ40 °C, the H and 13C NMR spectra of (R)-2
1
plane with respect to the corresponding aryl ring [torsion
angle 180.0(2)°], which is an energetically less favorable con- indicate coalescence of the two resonance patterns, resulting
former. It should be noted that in the latter situation, the in only one well-defined resonance pattern at 0 °C (see
opposite chelate ring puckering resulting in antiperiplanar- Table 2). Two resonances are still observed at this tempera-
orientated methyl substituents would bring these methyl ture for the diastereotopic NMe methyl groups, which indi-
2
groups in very close proximity. Most probably the energeti- cates that LiϪN coordination is inert on the NMR spectro-
cally less favored in-plane orientation in the solid state is scopic time scale. A possible explanation for this obser-
compensated for by a sterically less congested situation.
vation is a process involving simultaneous scrambling of the
[
15,21]
Earlier studies
showed that (R)-2 exists as tetrameric bonding of the Cipso atoms over the Li faces of the Li
3
4
1
aggregates in non-coordinating solvents, such as benzene tetrahedron. In fact, the C dimer undergoes site exchange
and toluene. The structure as observed for (R)-2 in the solid with the C dimer during such a process (cf. Figure 4). If
2
state is most likely retained in these solvents, as can be con- such a process becomes fast on the NMR spectroscopic
1
13
cluded from the observed H and C NMR spectra re- time scale it will result in magnetically equivalent aryl
corded at various temperatures (see Table 2). Below Ϫ40 groups, without rendering the NMe methyl groups enanti-
2
1
13
°
C, in both H and C NMR spectra, two distinctly differ- otopic. Finally, coalescence of the resonances of the dia-
ent resonance patterns are observed in a 1:1 ratio, which is stereotopic NMe methyl groups to a single resonance oc-
2
in agreement with the situation observed in the solid state curs at higher temperatures (Ͼ 40 °C), which points to a
structure for (R)-2, which comprises two diastereoisomeric process involving LiϪN dissociation/association that be-
Table 2. Relevant variable-temperature H and 13C NMR spectroscopic data for (R)-2[a]
1
T[a] [K]
δ ( H) [ppm]
1
δ ( C) [ppm]
13
NMe
2
α-Me
α-CH
o-Haryl
NMe
2
α-Me
α-C
C1
C2
3
2
2
63
98
73
1.89
1.78 and 1.92
1.78 and 1.98
1.32
1.28
1.30
3.27
3.47
3.64
(br. s)
Ϫ
8.27
8.57
8.79
(br. s)
Ϫ
42.4
38.9 and 44.0
38.4 and 44.0
18.6
16.2
Ϫ
70.9
69.5
68.3
176.1
176.9
175.9
157.5
157.2
157.2
[
b]
(br. s)
2
1
33
93
Ϫ[c]
Ϫ
43.2 and 45.7
22.5
8.4
73.4
64.4
176.3
183.1
159.2
156.9
35.6 and 42.9
1.38 and 1.67
1.17
1.93
3.28
4.83
9.01
9.01
1.93 and 2.30
[
[
a]
as an external standard in [D
8
]toluene as solvent. [b] Not observed.
All values are reported on the δ scale (ppm), relative to SiMe
Not measured.
4
c]
156
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Aspects of Enantiopure and Racemic Organolithium Aggregates
FULL PAPER
comes fast on the NMR spectroscopic time scale above
this temperature.
Further studies are underway directed to determine the
relative thermodynamic and kinetic stabilities of the tetra-
As has been mentioned before, we were unable to obtain nuclear assemblies of (R)-2 and rac-2. In particular, we ex-
crystals of rac-2 suitable for an X-ray crystallography. pect that these species have different rates for the
Moreover, the very limited solubility of rac-2 in apolar sol- tetramerϪdimer equilibria in polar, coordinating solvents
1
13
vents prevented H and C NMR spectroscopy studies to (THF, Et O), as well as different reactivities for the forma-
2
be undertaken in solution. For this reason we attempted to tion of mixed aggregates with other alkyl- or aryllithium
[
24Ϫ26]
gain structural information about rac-2 by comparison of species or even lithium salts.
the 1 C CP/MAS NMR spectra of rac-2 and (R)-2 (see Fig-
3
ure 5).
Experimental Section
General Remarks: All experiments were carried out under a dry,
oxygen-free, nitrogen atmosphere, using standard Schlenk tech-
niques. Solvents were dried and distilled from Na/benzophenone
prior to use. The nBuLi (1.6  in hexane) and tBuLi (1.5  in
pentane) solutions were ordered in 10-g nitrogen sure-sealed bottles
and used as received after determination of the exact concentration
by titration with 1,10-phenantroline in 2-butanol/m-xylene (1 ).
1
13
6
13
H, C, Li, and C CP/MAS NMR NMR spectra were recorded
on a Varian 300 MHz spectrometer at ambient temperature, unless
stated otherwise. Chemical shifts (δ) are given in ppm relative to
6
SiMe
4
as an external standard. The Li NMR spectra were refer-
enced to LiCl in D
2
O (1.0 ) as an external standard. Elemental
analyses were obtained from Dornis und Kolbe Mikroanalytisches
Laboratorium, Mülheim a.d. Ruhr, Germany.
Synthesis of [Li{(R)-C
was prepared according to a published procedure, starting from
R)-C CH(Me)NMe and tBuLi. Crystals suitable for X-ray
crystallography were obtained by performing the reaction without
stirring. When (S)-C CH(Me)NMe is subjected to the same li-
thiation reaction, the related analog, (S)-1, was obtained in a
6 4 2 4
H [CH(Me)NMe ]-2}] [(R)-2]: This species
[21]
(
6
H
5
2
6
H
5
2
Figure 5. 13C CP/MAS NMR spectra of (R)-2 and rac-2
1
straightforward manner. H NMR (C
6
D
6
, 300.105 MHz, 298 K):
δ ϭ 1.13 [d, J ϭ 6.71 Hz, 3 H, CH(Me)], 1.62 (br. s, 3 H, NMe ),
), 3.33 [br. s, 1 H, CH(Me)], 7.05 [d, J ϭ
3
2
Two distinct resonance patterns are observed for (R)-2
that are especially clear for Cipso, C(6), the benzylic carbon
3
1
.72 (br. s, 3 H, NMe
2
3
7.32 Hz, 1 H, ArH(3)], 7.20 [dt, 1 H, J ϭ 7.03 Hz, ArH(4)], 7.26
3
13
atom, and the benzylic methyl substituent (see Figure 5). [t, J ϭ 7.03 Hz, 1 H, ArH(5)], 8.47 [bd, 1 H, ArH(6)] ppm.
This spectrum is in full agreement with the structure ob- NMR ([D ]toluene, 75.469 MHz, 298 K): δ ϭ 17.5 (br. s, CCH
served for (R)-2 in the solid state (two geometrically differ- 38.9, 44.0 (br. s, NMe ), 69.4 (br. s, ArCH), 124.6, 125.2, 125.5,
C
8
3
),
2
6
1
2
13
140.9 [Ar(3,4,5,6)], 157.2, 175.9 [Ar(1,2) quaternary] ppm. Li
NMR ([D ]toluene, 44.165 MHz, 218 K): δ ϭ 0.09 and 0.14 ppm.
Li (600.5): calcd. C 77.41, H 9.09, N 9.03%; found C
7.28, H 8.93, N 9.01%.
ent C and C sites; vide supra). Interestingly, the C CP/
MAS NMR spectrum of rac-2 shows only one distinct res-
onance pattern, which is similar to one of the patterns of
8
C
40
H
56
N
4
4
7
1
3
(
R)-2. An explanation for the relatively simple C CP/MAS
NMR spectrum of rac-2 is that in the solid state rac-2 exist The rac-2 species was prepared in a similar way starting from rac-
as a type-I Li aggregate comprising a combination of one
CH(Me)NMe
C
6
H
5
2
.
4
2
1
1
C - and one C -type dimer. Furthermore, in the C -type
X-ray Crystal Structure Analyses of (R)-2: Pertinent data for the
structure determinations are collected in Table 3. X-ray data were
collected on a Nonius CAD-4T diffractometer. The data set was
dimeric unit of the Li aggregate, the configuration of the
4
2
two benzylic carbon centers is opposite to those in the C -
type dimer. It should be noted that all four organic moieties measured at 150 K, using graphite-monochromated Mo-Kα radi-
˚
in such an arrangement are symmetry-related by a fourfold ation (λ ϭ 0.71073 A) from a rotating anode source. Accurate unit
inversion axis (vide supra). The alternative, i.e., a type-II cell parameters and an orientation matrix were determined by least-
squares fitting of the setting angles of 25 well-centered reflec-
aggregate in which the four organic moieties all have the
same stereochemistry, is highly unlikely, because this ar-
rangement would in fact represent a structure like that of
tions.[
39]
The structure was solved by direct methods using
[
40]
2
SHELXS-86. Refinement on F was performed with SHELXL-
[41]
97.
Hydrogen atoms were included in the refinement on calcu-
(R)-2 [or its enantiomer, (S)-2], which is known to have a
lated positions riding on their carrier atoms. The non-hydrogen
atoms of the structure were refined with anisotropic displacement
parameters. The hydrogen atoms were refined with a fixed isotropic
displacement parameter related by a constant factor to the value
type-I structure (vide supra). Finally, we note that a ran-
dom distribution of R and S ligands over the Li tetra-
4
hedron would give rise to very complicated spectra as a re-
sult of the formation of a variety of diastereoisomeric ag- of the equivalent isotropic displacement parameter of their carrier
gregates.
atoms. Because of the absence of strong anomalous scatters, the
Eur. J. Org. Chem. 2004, 153Ϫ159
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
157

G. van Koten et al.
FULL PAPER
[
[
[
[
4]
5]
6]
7]
absolute configuration could not be determined experimentally.
The absolute configuration was therefore assigned in accordance
with the known configuration of the asymmetric carbon atoms of
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1
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(R)-2
[
[
[
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13]
14]
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40 4 4
C H56Li N
Mol. Weight
Crystal System
Space group
620.65
orthorhombic
P2 2 (No. 18)
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˚
a [A]
11.8653(8)
15.6471(11)
10.0929(8)
1873.8(3)
1.100
2
672
0.062
yellow
0.6 ϫ 0.6 ϫ 0.6
˚
[15]
[16]
b [A]
˚
c [A]
˚
3
V [A ]
D
calcd. [g cmϪ3
]
Z
[
17]
F(000)
µ [mmϪ1] Mo-K
α
Crystal color
Crystal size [mm]
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[18]
[19]
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1.3, 27.5
150
Ϫ15:15, Ϫ20:0, Ϫ13:0
4911
2241 [Rint ϭ 0.035]
1197Ϫ1218.
Temperature [K]
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[20]
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5
[
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223
[
a]
Final R
Final wR
1
0.0379 [2457 I Ͼ 2σ(I)]
[
b]
2
0.101
1.043
[
[
23]
24]
Goodness of Fit
Ϫ1[c]
2
2
2
w
σ (F ) ϩ (0.0537P) ϩ0.25P
Ͻ 0.001, Ͻ 0.001
(
∆
∆/σ)max, (∆/σ)av
max
[e AϪ3]
ρmin, ∆ρ
Ϫ0.15, 0.21
[
25]
[
[
a]
[b]
ϭ Σ[w(F 2
2)2/Σ[w(F ) ]]1/2.
2 2
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1
ϭΣ||F
o
| Ϫ |F
c
||/Σ|F
o
|. wR
c
2
o
Ϫ F
c
o
c]
2
2)/3.
P ϭ Max(F
o
,0) ϩ 2F
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[
[
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This work was supported in part (A.L.S.) by The Netherlands
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the Netherlands Organization for Scientific Research (NWO). Dr.
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Aspects of Enantiopure and Racemic Organolithium Aggregates
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The configuration of the bridging Cipso center in the rotamer
having the aryl plane perpendicular to the LiϪLi vector is de-
termined by the priority of the atoms connected to Cipso in
the C,N-chelate ring, viewing in the direction of the second
Li atom.
[42]
Eur. J. Org. Chem. 2004, 153Ϫ159
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
159