Diastereoselective self-assembly of chiral diamine-chelated aryllithiums to dimeric aggregates

Article abstract of DOI:10.1021/ja045914q

Aryllithium compounds [LiC₆H₄(CH₂N(Et) CH₂CH₂NEt₂)-2]₂ (2b), [LiC ₆H₄(CH(Me)N(Me)CH₂-CH₂NMe ₂-(R))-2]₂ ((R)-3b),

Full text of DOI:10.1021/ja045914q

Published on Web 11/16/2004
Diastereoselective Self-Assembly of Chiral Diamine-Chelated
Aryllithiums to Dimeric Aggregates
Anne M. Arink,† Claudia M. P. Kronenburg,† Johann T. B. H. Jastrzebski,†
Martin Lutz,‡ Anthony L. Spek,‡,| Robert A. Gossage,§ and Gerard van Koten*,†
Contribution from the Debye Institute, Department of Metal-Mediated Synthesis,
Utrecht UniVersity, Padualaan 8, 3584 CH Utrecht, The Netherlands; BijVoet Center for
Biomolecular Research, Crystal and Structural Chemistry, Utrecht UniVersity,
Padualaan 8, 3584 CH Utrecht, The Netherlands; and The Chester Woodleigh Small Laboratory
of Organic Chemistry, Department of Chemistry, Acadia UniVersity,
WolfVille, NoVa Scotia, B4P 2R6 Canada
Received July 8, 2004; E-mail: g.vankoten@chem.uu.nl
Abstract: Aryllithium compounds [LiC6H4(CH2N(Et)CH2CH2NEt2)-2]2 (2b), [LiC6H4(CH(Me)N(Me)CH2-
CH2NMe2-(R))-2]2 ((R)-3b), and [LiC6H4(CH(Me)N(Me)CH2CH2NMe2-(rac))-2]2 ((rac)-3b) were synthesized
and characterized in the solid state and in solution. X-ray crystallographic studies of 2b and (R)-3b and
molecular weight determinations of 2b, (R)-3b, and (rac)-3b by cryoscopy in benzene showed that, both
in the solid state and in apolar, noncoordinating solvents such as benzene, these compounds exist as
discrete dimeric aggregates. For (R)-3b and (rac)-3b the aggregation process of two monomeric aryllithium
units to one dimer is highly diastereoselective.
Introduction
nitrogen atoms and Cipso that provides different chelation effects
and thus determines the structural features of the resulting
Aryllithium compounds with intramolecular heteroatom co-
ordination have proven to be very useful reagents and are of
great interest to organic chemists.1,2 Especially ortho-lithiated
aminoarenes, synthesized via so-called directed ortho metalation
(DoM), have been extensively used in organometallic chemistry
and catalysis.3-5 Monoanionic pincer ligands of the type C∧N
([C6H4(CH2NMe2)-2]-), N∧C∧N ([C6H3(CH2NMe2)2-2,6]-)
and C∧N∧N′ ([C6H4(CH2N(Me)CH2CH2NMe2)-2]-) are ex-
amples of aryl compounds with an ortho-amino substituent that
can act as an ortho directing group (oDG).3,4,6 Although in each
case the CH2NMe2 moiety is the same, it is the sequence of
aryllithium species. The present study deals with the C∧N∧N′
type of ortho-diamine aryl ligand which has two specific
features; i.e., the nitrogen atoms of the CH2N(Me)CH2CH2-
NMe2)-2 sidearm can coordinate both monodentate and bidentate
when chelating. In combination with Cipso-Li bonding this
results in terdendate C∧N∧N or bidentate C∧N bonding.
However, even when the -CH2CH2NMe2 part is noncoordi-
nating, its flexibility still enables the terminal nitrogen atom to
approach the metal and to become a spectator moiety.6
A unique feature of the C∧N∧N ligand is that N-Li
coordination of the benzylic nitrogen atom renders it a stereo-
genic center. Previous studies showed that [Li(C6H4(CH2N(Me)-
CH2CH2NMe2)-2)]2, [LiC∧N∧N′]2, occurs both in solution and
in the solid state as a dimeric species in which the ortho-diamine
substituent is chelate bonded.6 The (R)N(R)N and (S)N(S)N
enantiomeric pair is formed and isolated as the major isomer.
Recently we prepared, in connection with our studies of bromo-
and cyanocuprates,7 also the ethyl analogue [BrC6H4(CH2N(Et)-
CH2CH2NEt2)-2] and its corresponding aryllithium derivative.
It was found that this compound had a more favorable
conformational and configurational stability. In addition, we
recently observed that the aryllithium compounds derived from
the chiral monoanionic ligand [C6H4CH(Me)NMe2-2]- show
unique diastereoselective self-assembly to tetrameric aggre-
gates.8 This prompted us to prepare a chiral analogue of this
† Debye Institute, Department of Metal-Mediated Synthesis, Utrecht
University.
‡ Bijvoet Center for Biomolecular Research, Crystal and Structural
Chemistry, Utrecht University.
§ Acadia University.
| To whom correspondence on crystallographic studies should be
addressed.
(1) Gschwend, H. W.; Rodriguez, H. R. Org. React. 1979, 26, 1.
(2) (a) Snieckus, V. Chem. ReV. 1990, 90, 879 and references therein. (b)
Sotomayor, N.; Lete, E. Curr. Org. Chem. 2003, 7, 275. (c) Basu, A.;
Thayumanavan, S. Angew. Chem., Int. Ed. 2002, 41, 716. (d) Organolithi-
ums in EnantioselectiVe Synthesis; Topics in Organometallic Chemistry,
Vol. 5; Springer-Verlag: Heidelberg, 2003. (e) Patai Series: The Chemistry
of Functional Groups, The Chemistry of Organolithium Compounds;
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(3) Rietveld, M. H. P.; Grove, D. M.; van Koten, G. New J. Chem. 1997, 21,
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(4) Janssen, M. D.; Corsten, M. A.; Spek, A. L.; Grove, D. M.; van Koten, G.
Organometallics 1996, 15, 2810.
(5) (a) Belzner, J.; Scha¨r, D.; Dehnert, U.; Noltemeyer, M. Organometallics
1997, 16, 285. (b) Reich, H. J.; Goldenberg, W. S.; Sanders, A. W.;
Tzschucke, C. C. Org. Lett. 2001, 3, 33 and references cited therein. (c)
Reich, H. J.; Goldenberg, W. S.; Gudmundsson, B. O¨ .; Sanders, A. W.;
Kulicke, K. J.; Simon, K.; Guzei, I. A. J. Am. Chem. Soc. 2001, 123, 8067.
(d) Reich, H. J.; Gudmundsson, B. O¨ . J. Am. Chem. Soc. 1996, 118, 6074.
(e) Reich, H. J.; Goldenberg, W. S.; Sanders, A. W.; Jantzi, K. L.;
Tzschucke, C. C. J. Am. Chem. Soc. 2003, 125, 3509.
(6) Rietveld, M. H. P.; Wehman-Ooyevaar, I. C. M.; Kapteijn, G. M.; Grove,
D. M.; Smeets, W. J. J.; Kooijman, H.; Spek, A. L.; van Koten, G.
Organometallics 1994, 13, 3782.
(7) Kronenburg, C. M. P.; Jastrzebski, J. T. B. H.; Boersma, J.; Lutz, M.; Spek,
A. L.; van Koten, G. J. Am. Chem. Soc. 2002, 124, 11675.
9
10.1021/ja045914q CCC: $27.50 © 2004 American Chemical Society
J. AM. CHEM. SOC. 2004, 126, 16249-16258
16249

A R T I C L E S
Scheme 1
Arink et al.
sion at the benzylic nitrogen atoms is blocked as a result of
coordination to the lithium atoms, these nitrogen atoms are
stereogenic centers with a rigid configuration. In one-half of
the dimer, the nitrogen (NMe) atom has a (R)-configuration,
while in the other half the nitrogen (NMe) has a (S)-configu-
ration. Because the two halves of the dimer are symmetry related
by a center of symmetry, the dimer is a meso-compound.
The crystal structure of (R)-3b involves the packing of four
dimeric molecules in the acentric unit cell (space group P21).
The asymmetric unit contains two independent dimers A and
B which are chemically identical but which differ slightly,
though not significantly, in structure. The molecular geometry
of (R)-3b (dimer A) together with the adopted numbering
scheme is shown in Figure 1B, while bond distances and bond
angles for both molecules are given in Table 1.
ligand, i.e., [C6H4(CH(Me)N(Me)CH2CH2NMe2)-2]-, and to
study its stereoselective assembly during ortho-lithiation. Here
we report the synthesis, characterization, and stereochemical
features of these aryllithium compounds.
Results
The overall structural features of (R)-3b are closely related
to those of 2b. Also in this structure the two bridging aryl groups
are oriented in such a way that the benzylic nitrogen atoms
approach the C(11)-Li(1)-C(12)-Li(2) plane from opposite
sites. As outlined before for 2b, the benzylic nitrogen atoms
become rigid stereogenic centers as a consequence of Li-N
coordination, one adopting an (R)-configuration while the other
one has an (S)-configuration. Because the benzylic carbon atoms
by definition have a chosen (R)-configuration, the dimer consists
of two diastereoisomeric parts, having (R)C(R)N and (R)C(S)N
stereochemistry, respectively. Furthermore, it is notable that in
the (R)C(R)N part of the dimer the benzylic methyl group is
oriented anti-periplanar with respect to the aryl group, while in
the (R)C(S)N moiety this methyl group is in an energetically
slightly less favorable in-plane conformation.
The observed 13C CP-MAS NMR spectrum of 2b is in
agreement with the crystal structure; i.e., only one resonance
pattern is observed. The observation of three Me resonances at
4.7, 6.1, and 13.5 ppm (for the NEt2 and NEt groupings,
respectively) is a consequence of the fact that the terminal NEt2
groups are diastereotopic and thus give rise to two Et-resonance
patterns (Figure 2). Unfortunately, no crystals suitable for an
X-ray structure determination of (rac)-3b could be obtained.
Therefore, the 13C CP-MAS NMR spectra of (R)-3b and (rac)-
3b were compared, see Figure 2.
Synthesis of Aryllithium Compounds [Li(C∧N∧N′)]2 1b,
2b, (R)-3b, and (rac)-3b. Aryllithium compounds [LiC6H4-
(CH2N(Me)CH2CH2NMe2)-2]2 (1b), [LiC6H4(CH2N(Et)CH2-
CH2NEt2)-2]2 (2b), [LiC6H4(CH(Me)N(Me)CH2CH2NMe2-(R))-
2]2 ((R)-3b), and [LiC6H4(CH(Me)N(Me)CH2CH2NMe2-(rac))-
2]2 ((rac)-3b) were prepared quantitatively via a lithium-
bromine exchange reaction of the corresponding aryl bromides
1a, 2a, (R)-3a, and (rac)-3a, respectively, with n-BuLi in
pentane at -78 °C (see Scheme 1). Aryl bromides 1a and 2a
were prepared according to a procedure reported earlier,6,7 while
(R)-3a and (rac)-3a were prepared following an improved
literature procedure.9 (R)-3a was obtained with an enantiomeric
purity of 98%.
The aryllithium compounds are colorless solids, which are
sensitive toward moisture and oxygen, and are soluble in
common organic solvents such as benzene and diethyl ether.
Molecular weight determinations by cryoscopy in benzene
indicated that 2b, (R)-3b, and (rac)-3b exist as dimeric
aggregates in solution, as already has been reported for 1b.6
Crystals, suitable for X-ray crystal structure determination, of
2b and (R)-3b were obtained by crystallization of crude 2b and
(R)-3b, respectively, from diethyl ether at -30 °C.
Structures of [LiC6H4(CH2N(Et)CH2CH2NEt2)-2]2 (2b),
(R)-[LiC6H4(CH(Me)N(Me)CH2CH2NMe2)-2]2 ((R)-3b), and
(rac)-[LiC6H4(CH(Me)N(Me)CH2CH2NMe2)-2]2 ((rac)-3b) in
the Solid State. The molecular geometry of 2b together with
the adopted numbering scheme is shown in Figure 1A, while
bond distances and bond angles are given in Table 1. The
molecular structure of 2b in the solid state consists of a
centrosymmetric dimeric aggregate in which the two aryl units
are bridge-bonded (C(1)-Li(1) 2.2707(19), C(1)-Li(1i) 2.208(2)
Å) via two-electron three-center bonds of Cipso between two
lithium atoms. The two lithium atoms and the two bridging Cipso
atoms are arranged in a perfectly planar arrangement. The two
nitrogen atoms of each ethylenediamine substituent are coor-
dinated to the same lithium atom (N(1)-Li(1) 2.1148(19),
N(2)-Li(1) 2.1062(19) Å). One of the aryl units is oriented in
such a way that its nitrogen atoms bind to the corresponding
lithium atom from above the Li(1)-C(1)-Li(1i)-C(1i) plane,
while for the other aryl unit the nitrogen atoms bind to the
lithium atom from below this plane. Because pyramidal inver-
The 13C CP-MAS NMR spectrum of (R)-3b is rather
complicated. This is not unexpected because the dimer contains
two diastereoisomeric parts, (R)C(R)N and (R)C(S)N. Moreover,
the asymmetric unit contains two independent molecules.
Therefore, in the solid-state in principle four sets of resonances
are expected for the four different ligand environments.
However, as shown in Figure 2, a number of peaks are
overlapping. For the R-Me groups four resonances are indeed
observed at 9.2, 11.6, 24.9, and 25.4 ppm. For the Cipso atoms
two broad resonances are observed at 182.7 and 190.5 ppm.
7
Due to line broadening, most likely as a consequence of Li-
13C quadrupolar coupling, the splitting due to the two indepen-
dent molecules in the unit cell is not observed.
The observed 13C CP-MAS NMR spectrum of (rac)-3b is
much less complicated; see Figure 2. Only one resonance pattern
is observed of which seven resonances lie in the aliphatic range
(25.1, CMe; 39.6, NMe; 47.1 and 48.8, NMe2; 52.3, NCH2;
64.9, NCH2 and 72.0, benzyl-C). In the aromatic region four
resonances are observed (183.5, C(1); 157.6, C(2); 142.4, C(6);
and 124.5, C(3), C(4), and C(5)). The presence of only one
(8) Kronenburg, C. M. P.; Rijnberg, E.; Jastrzebski, J. T. B. H.; Kooijman,
H.; Spek, A. L.; van Koten, G. Eur. J. Org. Chem. 2004, 153.
(9) Rodriguez, G.; Albrecht, M.; Schoenmaker, J.; Ford, A.; Lutz, M.; Spek,
A. L.; van Koten, G. J. Am. Chem. Soc. 2002, 124, 5127.
9
16250 J. AM. CHEM. SOC. VOL. 126, NO. 49, 2004

Self-Assembly of Chiral Diamine-Chelated Aryllithiums
A R T I C L E S
Figure 1. (A) Displacement ellipsoid plot of 2b. Ellipsoids are drawn at the 50% probability level. Hydrogen atoms are omitted for clarity. Symmetry
operation i: 1 - x, 1 - y, 1 - z. (B) Displacement ellipsoid plot of one of the two independent molecules in the crystal structure of compound (R)-3b.
Ellipsoids are drawn at the 50% probability level. Hydrogen atoms are omitted for clarity.
Table 1. Selected Bond Lengths [Å] and Angles and Torsion
Angles [deg] for 2ba and (R)-3b
2b
(R)-3b (molecule A)
Bond Distances (Å)
Bond Distances (Å)
Li(1)-N(2)
2.1062(19) Li1-N11
2.1148(19) Li1-N21
2.2707(19) Li2-N12
2.119(4)
2.084(4)
2.130(4)
2.125(4)
2.236(4)
2.157(4)
2.212(4)
2.230(4)
Li(1)-N(1)
Li(1)-C(1)
Li(1i)-C(1)
2.208(2)
Li2-N22
Li1-C11
Li1-C12
Li2-C11
Li2-C12
Bond Angles (deg)
Bond Angles (deg)
N(1)-Li(1)-N(2)
C(1)-Li(1)-C(1i)
C(1i)-Li(1)-N(1)
Li(1)-C(1)-Li(1i)
C(6)-C(1)-C(2)
C(1)-Li(1)-N(1)
C(1)-Li(1)-N(2)
88.26(7)
N11-Li1-N21
88.75(16)
87.25(16)
116.26(19)
114.26(18)
64.25(14)
65.23(15)
115.89(8) N12-Li2-N22
128.31(9) C11-Li1-C12
64.11(8)
112.73(9) Li1-C11-Li2
87.08(7)
C11-Li2-C12
Li1-C12-Li2
114.74(8)
Torsion Angles (deg)
C11-C21-C71-C101
C12-C22-C72-C102
-66.1(3)
174.2(2)
a Symmetry operation i: 1 - x, 1 - y, 1 - z.
resonance pattern points to a highly symmetrical structure for
(rac)-3b in the solid state. Most likely this is a dimeric structure
in which a center of symmetry is present, like in 2b, vide supra,
suggesting that again a meso compound is formed; i.e., the dimer
consists of a (R)C(R)N/(S)C(S)N combination. However, by
definition such a symmetry element cannot be present in
(R)-3b.
Figure 2. 13C CP-MAS NMR spectra of (rac)-3b and (R)-3b; × symbols
are spinning sidebands.
are broad. Below 0 °C decoalescence occurs indicating the
diastereotopicity of these Et-groups. The presence of two
different species in solution was furthermore confirmed by the
observation of two resonances (0.46 ppm (major) and 0.36 ppm
1
A H and 13C NMR Study of the Structural Features of
6
(minor)) in a 2:1 intensity ratio in the Li spectrum of 2b.
1
1b,6 2b, (R)-3b, and (rac)-3b in Toluene Solution. The H
The observation of two resonance patterns in the 1H and 13
C
and 13C NMR spectra of 2b show two resonance patterns in an
approximately 2:1 intensity ratio, indicating the presence of two
different species in solution. This is especially obvious in the
1H NMR spectrum by the observation of two H(6) resonances
at 8.21 (major) and 8.27 ppm (minor) and two AB patterns (3.45
and 4.21 ppm for the major resonance pattern, 3.23 and 4.29
ppm for the minor) for the benzylic CH2 protons. At room
temperature the 1H and 13C NMR resonances of the NEt2 groups
NMR spectra of 2b prompted us to reinvestigate the data for
1b, which have been reported earlier.6 It appeared that also for
this compound, both in the 1H and 13C NMR spectra two
resonance patterns are present in an approximately 6:1 intensity
ratio. The chemical shift differences are significantly less than
those found for 2b, but in the 1H NMR spectrum of 1b a second
(low intensity) AB pattern for the benzylic protons is clearly
observable.
9
J. AM. CHEM. SOC. VOL. 126, NO. 49, 2004 16251

A R T I C L E S
Arink et al.
The 1H and 13C NMR spectra of (R)-3b show two resonance
patterns in a 1:1 intensity ratio. The diastereotopicity of the
terminal NMe2 methyl groups is reflected in the observation of
two resonances for each pattern. At approximately 25 °C
coalescence of each of these resonances begins. At a much
higher temperature (100 °C) subsequent coalescence of the
remaining two resonance patterns occurs.
Surprisingly, for (rac)-3b a simple, single resonance pattern
is observed at room temperature, in both the 1H and 13C NMR
spectra. Below 20 °C decoalescence of the NMe2 resonance
occurs into two resonances at 1.20 and 1.40 ppm. Apart from
the major H(6) resonance at 8.25 ppm, additional resonances
with low intensity (<5%) are observable, which point to the
presence of minor amounts of (R)-3b (δ H(6) ) 8.30 and 8.16
ppm) and its enantiomer (S)-3b in solution.
the lithium atom, and (iii) the presence (or absence) of
coordinating solvent or additional donor molecules. For example,
the presence of an ortho-CH(R)NMe2 (R ) H or Me) substituent
produces a tetrameric [LiC6H4CH(R)NMe2-2]4 structure,8,13f of
which the central aryllithium (hetero-cubane) structural motif
is similar to that of [LiPh(OEt2)]4,12 but with the coordinating
diethyl ether molecules replaced by intramolecular coordinating
NMe2 groups. Recently we reported that [LiC6H4CH(Me)-
NMe2-2]4 reacts with n-BuLi to give a [Li4(C6H4CH(Me)NMe2-
2)2(n-Bu)2] hetero-aggregate also having a hetero-cubane struc-
tural motif comprising two assembled dimeric subunits, one
aryllithium dimer and one butyllithium dimer.17 Due to the
presence of the chiral C6H4CH(Me)NMe2-2 ligand, the self-
assembly process leading to this structure is highly diastereo-
selective. In this respect it should be noted that it was shown
earlier that the lithiation of the benzylic carbon atom in
1-[(benzyldimethylsilyl)-(S)-2-methoxymethylpyrrolidine] is highly
diastereoselective,18 as was evidenced by the X-ray structures
of the TMEDA and DABCO complexes of the lithiated
products.19
Furthermore, it has been shown that strongly coordinating
solvents such as THF or additional donor molecules such as
TMEDA11,20c,d and PMDTA20d are capable of breaking down
such aggregates. Also in this case the presence of potentially
intramolecular-coordinating substituents (oDG) will influence
the remaining degree of aggregation. For example, considerable
amounts of monomeric PhLi are present either in a THF solution
of PhLi at low temperature20 or in the presence of PMDTA.20d
In the latter case, its monomeric structure has been established
by an X-ray crystal structure determination.21 In contrast, THF,
TMEDA, or PMDTA are only capable of breaking down
tetrameric [LiC6H4CH2NMe2-2]4 into dimeric species,5d,13f,h
indicating that in this process the ortho-(dimethylamino)methyl
substituent plays a crucial role as an oDG.
Discussion
It has been well-established that aryllithium compounds both
in the solid-state and in (apolar) solution are aggregated species.
The driving force for aggregation is the strong tendency of
lithium to attain a tetrahedral coordination geometry, or in
exceptional cases a trigonal one. Aggregation occurs via
electron-deficient Cipso-Lin (n ) 2 or 3) multicenter bonding,
while often coordination saturation at lithium is reached by the
coordination of additional coordinating solvent molecules or
intramolecular coordination of heteroatom-containing substit-
uents (oDG).
Phenyllithium in the solid state is a polymer, consisting of
[PhLi]2 dimeric units as a leading structural motif, linked to
infinite chains via η6-coordination of lithium to the π-charge
density of a phenyl group of an adjacent [LiPh]2 dimeric unit.10
Deaggregation of the polymer by donor molecules to discrete
species is dependent on the donor strength and type of the
specific donor molecule. For example in the presence of
TMEDA a discrete dimer [PhLi(TMEDA)2]2 is formed,11 while
the presence of the more weakly coordinating diethyl ether gives
rise to the formation of a tetramer [LiPh(OEt2)]4,12 in which
the four aryl groups are two-electron four-center bonded to each
face of a central Li4 tetrahedron and the fourth coordination
site of each lithium atom is occupied by a coordinating diethyl
ether molecule.
X-ray crystallographic studies of 1b,6 2b, and (R)-3b and
molecular weight determinations of 1b,6 2b, (R)-3b, and (rac)-
3b by cryoscopy in benzene showed that both in the solid state
and in apolar, noncoordinating solvents such as benzene these
compounds exist as discrete dimeric aggregates. The overall
structural motif as observed in the solid-state of these com-
pounds, vide supra, closely resembles that of [LiPh(TME-
Aryllithium compounds containing one or more potentially
coordinating heteroatoms, so-called ortho directing groups
(oDG), may form of a variety of structural motifs, i.e.,
dimers,5a-c,6,13 trimers,14 tetramers,13f,15 or higher aggregates.16
Important factors that control the structure of the actual
aggregate formed are (i) the nature of the potentially coordinat-
ing substituent, (ii) the position of this substituent relative to
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(19) (a) Strohman, C.; Lehmen, K.; Wild, K.; Schildbach, D. Organometallics
2002, 21, 3079. (b) Strohman, C.; Buchold, D. H. M.; Seibel, T.; Wild,
K.; Schildbach, D. Eur. J. Inorg. Chem. 2003, 3453.
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(11) Thoennes, D.; Weiss, E. Chem. Ber. 1978, 111, 3157.
(12) Hope, H.; Power, P. P. J. Am. Chem. Soc. 1983, 105, 5320.
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Lutz, M.; Mu¨ller, G. Angew. Chem., Int. Ed. Engl. 1994, 33, 2281. (c)
Hughes, C. C.; Scham, D.; Mulzer, J.; Trauner, D. Org. Lett. 2002, 4, 4109.
(d) Steiner, A.; Stalke, D. Angew. Chem., Int. Ed. Engl. 1995, 34, 1752.
(e) Rabe, G. W.; Zhang-Preâe, M.; Yap, G. P. A. Acta Crystallogr. 2002,
E58, m434. (f) Jastrzebski, J. T. B. H.; van Koten, G.; Konijn, M.; Stam.
C. H. J. Am. Chem. Soc. 1982, 104, 5490. (g) Jastrzebski, J. T. B. H.; van
Koten, G.; Goubitz, K.; Arlen, C.; Pfeffer, M. J. Organomet. Chem. 1983,
246, C75. (h) Wehman, E.; Jastrzebski, J. T. B. H.; Ernsting, J.-M.; Grove,
D. M.; van Koten, G. J. Organomet. Chem. 1988, 353, 145. (i) Donkervoort,
J. G.; Vicario, J. L.; Rijnberg, E.; Jastrzebski, J. T. B. H.; Kooijman, H.;
Spek, A. L.; van Koten, G. J. Organomet. Chem. 1998, 550, 463.
(20) (a) Bauer, W.; Winchester, W. R.; Schleyer, P. v. R. Organometallics 1987,
6, 2371. (b) Bauer, W.; Seebach, D. HelV. Chim. Acta 1984, 67, 1972. (c)
Wehman, E.; Jastrzebski, J. T. B. H.; Ernsting, J.-M.; Grove, D. M.; van
Koten, G. J. Organomet. Chem. 1988, 353, 133. (d) Reich, H. J.; Green,
D. P.; Medina, M. A.; Goldenberg, W. S.; Gudmundsson, B. O¨ .; Dykstra,
R. R.; Phillips, N. H. J. Am. Chem. Soc. 1998, 120, 7201.
(21) Schu¨mann, U.; Hopf, J.; Weiss, E. Angew. Chem., Int. Ed. Engl. 1985, 24,
215.
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Self-Assembly of Chiral Diamine-Chelated Aryllithiums
A R T I C L E S
Figure 3.
Figure 4. Different stereochemical possibilities of C∧N∧N′-type aryllithium monomeric units.
DA)]2.11 (In fact these compounds may be regarded as PhLi
containing an intramolecularly connected ortho-ethylenediamine
unit.) A difference is the orientation of the aryl ring with respect
to the Cipso-Li-Cipso-Li plane. In [LiPh(TMEDA)]2 the aryl
rings are oriented perpendicular to this plane.11 In 1b,6 2b, and
(R)-3b, the dihedral angles are 63.3(5)°/66.4(5)°, 53.53(7)° and
50.27(15)°/55.51(15)° (molecule A), 49.66(17)°/58.62(16)°
(molecule B), respectively, which is not unexpected because
they are a consequence of ortho-chelation.
Before discussing the observed data in detail, the various
implications of the stereochemical aspects of this type of
compounds will be outlined.
Elegant studies by Reich et al. have shown that 2-[(dialkyl-
amino)methyl]phenyllithium compounds exist in polar, coor-
dinating solvents such as THF as an equilibrium mixture of three
geometrically different dimeric aggregates, A, B, and C, in each
of which the dialkylamino substituent is coordinated to lithium;
see Figure 3.5b-e
at nitrogen is blocked and the nitrogen atoms become rigid chiral
centers (labeled (R)N or (S)N).
The dimers A, B and C may serve as models for the
compounds discussed here, in which R ) Me or Et and R′ is a
CH2CH2NR2 group. The structures of 1b and 2b in the solid
state and their NMR data (vide supra) show that the terminal
nitrogen atoms of the 2-(dialkylamino)ethyl substituents are
involved in Li-N coordination and thus have replaced the
coordinated THF molecules present in structures A, B, and C.
Previous modeling studies6 have shown that in a type A structure
the terminal nitrogen atom of the 2-(dialkylamino)ethyl sub-
stituent can never reach the second lithium atom. Therefore,
such a structure can be a priori excluded, and only B and C
type aggregates have to be considered as possible structures.
For a better understanding of the stereochemical aspects that
may play a role in the formation of such aggregates, it is useful
to discuss these aspects for a hypothetical monomeric unit. First,
it should be noted that the bridging Cipso atom is a stereogenic
In the A type aggregate both dialkylamino substituents are
coordinated to the same lithium atom, while they are positioned
at opposite sites of the Cipso-Li-Cipso-Li plane. Coordination
saturation of the second lithium atom is reached by coordination
of two THF molecules. In the B and C type aggregates each
lithium atom is coordinated to only one dialkylamino substituent
and one THF molecule. The difference between B and C is the
orientation of the dialkylamino substituents with respect to the
Cipso-Li-Cipso-Li plane. In B these amino substituents lie on
opposite sides of this plane, while in C both substituents lie on
the same side. The ratio of A, B, and C in solution depends on
the nature of R and R′. (For example, for R ) R′ ) Me in a
THF/Me2O/Et2O mixture this ratio is 54:38:8, and for R ) R′
) Et the major isomer is B.)5c,d An important feature of the
present (LiC∧N∧N′)2 structures is that when R and R′ are
different and Li-N coordination is rigid, pyramidal inversion
center in the rotation conformers (aryl rotation around C4-Cipso
)
shown in A-C (Figure 3, labeled (R)C(i) or (S)C(i)).22 Because
a monomeric unit contains two chiral centers there are four
different possibilities, (R)C(i)(R)N, (S)C(i)(S)N (an enantiomeric
pair), (R)C(i)(S)N, and (S)C(i)(R)N (also an enantiomeric pair, but
diastereoisomers with respect to the previous pair). In Figure 4
these four different stereochemical possibilities I, II, III, and
IV are schematically shown, together with a Newman projection
along the Cipso-Li axis.
As a consequence of the different orientations in space of
the two substituents at the benzylic nitrogen atoms, only in two
(22) (a) The configuration of the bridging Cipso center in the rotamer having the
aryl plane perpendicular to the Li-Li vector is determined by the priority
of the atoms connected to Cipso in the C,N-chelate ring, viewing in the
direction of the second lithium atom. (b) van Koten, G.; Noltes, J. G. J.
Am. Chem. Soc. 1979, 101, 6593.
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A R T I C L E S
Arink et al.
Figure 5. Possible combinations of two C∧N∧N′-type aryllithium monomeric units.
combinations of the two chiral centers, i.e., (R)C(i)(R)N and
(S)C(i)(S)N, the 2-(dialkylamino)ethyl substituent is oriented so
that the terminal nitrogen atom can coordinate with the lithium
atom (I and II in Figure 4). Therefore, in resting-state structures,
i.e., when both nitrogen atoms are coordinated and the Li-N
coordination-decoordination process is slow or blocked, only
two structures (I and II) have to be considered.
There are two ways in which a dimeric molecule can be
assembled from two monomeric units; see Figure 5. The first
involves the combination of either two I-type or two II-type
monomers, affording (R)C(i)(R)N/(R)C(i)(R)N and (S)C(i)(S)N/
(S)C(i)(S)N overall stereochemistries (enantiomeric pairs). These
are by definition dimers of the C-type; i.e., both benzylic
nitrogen atoms lie at the same side of the Cipso-Li-Cipso-Li
plane.
atom (labeled (R)C(b) in (R)-3b), three different aggregated
dimers should be considered. These will have (R)C(i)(R)C(b)(R)N/
(S)C(i)(R)C(b)(S)N (B-type), (R)C(i)(R)C(b)(R)N/(R)C(i)(R)C(b)(R)N, and
(S)C(i)(R)C(b)(S)N/(S)C(i)(R)C(b)(S)N (both C-type) stereochemistries,
respectively, as shown in Figure 6. The latter two dimers are
not enantiomers but diastereoisomers. It should be noted that
the first aggregate (B-type) lacks a symmetry element, and
therefore the two halves of the dimer are inequivalent. In both
C-type aggregates the two halves of the dimer are symmetry
related. Consequently, this would give rise to the observation
of only one resonance pattern in the 1H and 13C NMR spectra.
It is this B-type structure that is found for (R)-3b by an X-ray
crystal structure determination (vide supra). The dissymmetry
of this structure in the solid state was furthermore confirmed
by its 13C CP-MAS spectrum, showing two different resonance
patterns (vide supra).
The second possibility is a combination of a I-type and II-
type monomer, affording a B-type dimer, having (R)C(i)(R)N/
(S)C(i)(S)N stereochemistry. In this case the benzylic nitrogen
atoms lie on opposite sides of the Cipso-Li-Cipso-Li plane.
This dimer is a meso compound and a diastereoisomer of the
previous two.
1
The solution H and 13C NMR spectra of (R)-3b also show
two resonance patterns in a 1:1 intensity ratio indicating that
this dissymmetric B-type structure is also present in solution.
1
A variable temperature H and 13C NMR study of (R)-3b in
toluene solution points to the occurrence of two different
processes. The coalescence of the diastereotopic NMe2 methyl
resonances at 25 °C points to a process involving N-Li
coordination-decoordination that becomes fast on the NMR
time scale above this temperature. At this temperature still two
different resonance patterns are observed for the two diastereo-
isomeric halves of the dimer. This indicates that the configu-
ration of the stereogenic benzylic nitrogen atom is still rigid on
the NMR time scale. However, at 100 °C coalescence of these
two resonance patterns occurs to a single resonance pattern. The
only explanation for this observation is a process involving
Li-N coordination-decoordination of the benzylic nitrogen atom
that becomes fast on the NMR time-scale. Such a process allows
pyramidal inversion of configuration of this benzylic nitrogen
atom and thus would render the two diastereoisomeric parts in
the dimer homotopic.
The X-ray crystal structure determination of 2b reveals a
B-type structure with (R)C(i)(R)N/(S)C(i)(S)N stereochemistry. This
is in contrast with the observed structure for 1b, for which a
C-type was established by an X-ray crystal structure determi-
nation.6 For this latter compound both enantiomers, i.e.,
(R)C(i)(R)N/(R)C(i)(R)N and (S)C(i)(S)N/(S)C(i)(S)N, are present in
the crystal lattice. That 2b exists as one diastereoisomer in the
solid state became evident from its 13C CP-MAS spectrum. In
apolar solvents, however, the 1H and 13C NMR spectra of both
1b and 2b show in each case the presence of two resonance
patterns for each compound (vide supra), indicating the existence
of an equilibrium between a B-type and a C-type aggregate in
solution. The NMR intensity ratios between the different
aggregates, 6:1 and 2:1 for 1b and 2b, respectively, point to a
relatively small difference in thermodynamic stability between
a B-type and a C-type aggregate. Which aggregate finally
crystallizes from solution is controlled by solubility differences
and packing effects in the crystal lattice.
For (rac)-3b, apart from the three different diastereoisomers
(and their corresponding enantiomers) obtained from a combina-
tion of two hypothetical monomers having the same stereo-
chemistry at the benzylic carbon center (vide supra), also the
Based on the same arguments, outlined above, when a third
rigid chiral center is introduced, i.e., the chiral benzylic carbon
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Self-Assembly of Chiral Diamine-Chelated Aryllithiums
A R T I C L E S
Figure 6. Possible combinations of two C∧N∧N′-type aryllithium monomeric units with a (R)-chiral benzylic carbon atom.
Figure 7. Possible combinations of two C∧N∧N′-type aryllithium monomeric units with one (R)- and one (S)-benzylic carbon atom.
formation of aggregated dimers in which the chiral benzylic
carbon atoms have opposite stereochemistry must be considered;
see Figure 7.
Based on the above-described arguments, for the racemic
material six different diastereoisomeric dimers (three B-types
and three C-types) and their corresponding enantiomers might
be formed. Interestingly, the observation of relatively simple
1H and 13C NMR spectra in solution and 13C CP-MAS spectrum
in the solid state (vide supra) indicates that (rac)-3b exists in
solution and in the solid state as a single diastereoisomer.
Because single resonance patterns are observed in the NMR
The various combinations afford four possible structures
having (R)C(i)(R)C(b)(R)N/(R)C(i)(S)C(b)(R)N, (S)C(i)(R)C(b)(S)N/
(S)C(i)(S)C(b)(S)N (both C-type), (R)C(i)(R)C(b)(R)N/(S)C(i)(S)C(b)(S)N,
and (R)C(i)(S)C(b)(R)N/(S)C(i)(R)C(b)(S)N (both B-type) stereochem-
istries, respectively. The first two are enantiomers, but due to
lack of a symmetry element, the dimers consists of two
diastereoisomeric parts. In the latter two compounds, the two
halves of the dimers are symmetry-related by a center of
symmetry and therefore these dimers are meso compounds.
spectra, it is either the one with (R)C(i)(R)C(b)(R)N/(S)C(i)(S)C(b)
-
(S)N or the one with (R)C(i)(S)C(b)(R)N/(S)C(i)(R)C(b)(S)N (both
B-type) stereochemistry. It is obvious that in the first one the
steric congestion between the various substituents present in
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A R T I C L E S
Arink et al.
the molecule is more enhanced compared to that in the latter
dimer. Therefore the latter proposed structure seems to be more
likely. The low intensity resonance pattern (<5%) observed in
pieces of 2b combine; in this case only the meso form (R),(S)-
[Li2(CNN)2] is observed.
Attempts to direct or modify the diasteromeric ratio of these
dimers was addressed in a classical sense by the addition of a
second fixed chiral center (one moiety of the (R)-3b dimer) and
then comparing the self-assembly properties of this species with
that of complex 1b. In this case, secondary chirality at the
benzylic position does not lead to modified diastereoselectivity
((R)-3b is “meso” with respect to chirality at Li when compared
to 2b). Thus, the overall stereochemical outcome at Li is
identical to the purely steric (not enantiomeric) modifications
of bulkier alkyl groups displayed by 2b. That is to say that
exchange of methyl groups on the N atoms of 1b by ethyl groups
(2b) has the identical stereochemical influence at Li in the
resulting dimeric aggregate as does the introduction of an
auxiliary chiral center ((R)-3b). Thus, steric effects (not auxiliary
chirality) appear to be a primary gateway to controlling the
diastereoisomeric ratios in these aggregates. This is further
exemplified by our examination of (rac)-3b, where chiral (at
Li) [Li(CNN)] fragments selectively self-assemble only with
the fragments having opposite (at Li) chiral centers. Such
unusual stereoselective self-assembly has been observed previ-
ously by us in the selective self-aggregation of [(R),(R),(R),(R)-
{Li2(NCN*)2}] (NCN* ) 1,3-[Me2NCH(Me)]2C6H3) isolated
from mixtures of 1:1 rac/meso 1,3-bis[1-(dimethylamino)-
ethyl]-2-lithio-benzene.13i Again, steric effects are likely playing
a vital role. These experiments have further demonstrated the
complex nature of organolithium aggregation phenomena in the
solid state and in apolar solVents. In the latter situation, the
formation of monomeric or other Li aggregates is excluded by
the addition of a secondary (tertiary) N-donor group held in
close proximity to the lithium nuclei. This additional binding
fragment leads to kinetically and thermodynamically stable
dimeric species [Li2(CNN)2]. Future work will entail attempts
to control such aggregation properties in mixed aryl/alkyl
organolithium and related species.
1
the H NMR spectrum of (rac)-3b is superimposed with that
of (R)-3b. It is obvious that in solution an equilibrium exists
between all possible diastereoisomers, but only one, most
probably with (R)C(i)(S)C(b)(R)N/(S)C(i)(R)C(b)(S)N stereochemistry,
is the thermodynamically favored one, while a small amount
of (R)-3b and its enantiomer (S)-3b is observable.
It can be concluded that, although for both (R)-3b and (rac)-
3b a variety of diastereoisomeric dimers is possible, in both
cases only one specific dimer is formed in excess, both in the
solid state and in solution. This indicates that the aggregation
process of two monomeric aryllithium units to one dimer is
highly monomer-dimer diastereoselective.
Concluding Remarks
In previous work, Reich et al. have made extensive use of
6Li and 13C (VT) NMR spectroscopy to examine the solution
properties of [RLi] species in polar solvents such as THF.5b-d
This work effectively quantified (in solution) the relative ratios
of monomers, dimers, and higher order aggregates with and
without the addition of donor solvent molecules (e.g., HMPA).
These studies have detailed the complex solution chemistry of
many [RLi] species and include those compounds that contain
a tertiary amine functionality that is capable of coordination to
the Li atom(s).
The work herein entails an investigation of [RLi] compounds
that are known to exist only as dimers in the solid state (X-ray)
and in solution (NMR, cryoscopy) in exclusively nonpolar
solvent environments. The central theme is concerned with the
structural effect(s) (in both solid-state and solution) on ortho-
lithiated aromatic benzylamines that contain a further tethered
amine group. This group can be envisioned as representing a
single donor “solvent” molecule that is kept in close proximity
to the Li metal center(s). The advantage here is that these
dimeric species do not undergo any observable secondary
equilibrium processes resulting in the formation of monomeric,
dimeric, or higher order aggregates. We therefore have the
unique opportunity to study the structural ramifications of
induced and/or predetermined chirality on the diastereomeric
[RLi]2 aggregation properties. The observations discussed above
have been centered on providing information which is key to
the understanding of the structural aspects which lead to
selective formation of diastereomeric and enantiomeric [Li(CNN)]2
species. That is, bonded pairs of organolithiums in which
chirality has been rigorously defined by a secondary chiral center
((R)-3b) and/or induced chirality at Li and N (1b, 2b, rac-3b).
These chiral properties are shown to influence both the solution
and solid-state formation of various possible diastereomers of
the [RLi]2 aggregates.
Experimental Section
All experiments were carried out under a dry, oxygen-free nitrogen
atmosphere using standard Schlenk techniques. Solvents were dried
and distilled prior to use. All standard chemicals were purchased from
ACROS and Aldrich Chemical Co. and used as received. Reactions
involving organolithium syntheses were carried out in flame-dried
Schlenk flasks. The starting material (S)-(-)-2-bromo-R-methylbenzyl
alcohol with an optical purity of 99% was obtained from Aldrich
Chemical Co.. The starting materials C6H4Br(CH2N(Et)CH2CH2NEt2)-
26 and (rac)-2-bromo-R-methylbenzyl-alcohol9,23 were prepared ac-
1
6
cording to a literature procedure. H, 13C, and Li NMR spectra were
recorded on a 300 MHz spectrometer at ambient temperature unless
otherwise stated. Chemical shifts (δ) are given in ppm relative to SiMe4
as an internal standard (1H and 13C) or to LiCl in D2O (1 M) as an
external standard. Coupling constants are in Hz.
13C CP-MAS NMR spectra were recorded at 75 MHz on a Varian
Inity Inova spectrometer equipped with a 7 mm VT CP-MAS probe.
Samples were spun at 7000 Hz in silicon nitride rotors. Cross
polarization contact times ranged from 1 to 3.5 ms. Spectra were
averaged from 900 to 3000 FIDS. A line broadening factor of 10 Hz
was applied. Chemical shifts are relative to SiMe4. External adamantane
(δ 29.2 and 38.3 ppm) was used as secondary chemical shift reference.
Elemental analyses were obtained from Kolbe Mikroanalytisches
Laboratorium, Mu¨lheim a.d. Ruhr, Germany. Cryoscopic measurements
Let us now conclude and consider a brief summary of the
effects of induced chirality at Li (and N) on the formation of
the various complexes described herein. The self-assembly of
two [Li(CNN)] fragments which comprise 1b gives exclusively
only the racemic mixture (1:1) of (R),(R)-[Li2(CNN)2] and
(S),(S)-[Li2(CNN)2] (chirality in this case being defined only at
the Li centers). The meso form of 1b (i.e., (R),(S)-[Li2(CNN)2])
is not a thermodynamic aggregate. Steric effects appear to be
responsible for the opposite result when the two [Li(CNN)]
(23) Reynolds, K. A.; Finn, M. G. J. Org. Chem. 1997, 62, 2574.
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Self-Assembly of Chiral Diamine-Chelated Aryllithiums
A R T I C L E S
were carried out using a S2541 thermolyzer and a metal-mantled
Pt-100 sensor.24 For calibration, naphthalene was used to determine
(NCH2CH3 (A)), 10.20 (N(CH2CH3)2 (A, B)), 10.71 (NCH2CH3 (B)),
45.8 (N(CH2CH3)2 (A, B)), 46.3 (NCH2CH2N (A)), 48.4 (NCH2CH2N
(B)), 49.7 (NCH2CH3 (A)), 50.2 (NCH2CH3 (B)), 52.0 (NCH2CH2N
(B)), 52.3 (NCH2CH2N (A)), 67.4 (ArCH2N (A)), 68.6 (ArCH2N (B)),
124.5, 124.6 (Ar(3) and Ar(4) (A, B)), 126.2 (Ar(5) (B)), 126.4 (Ar(5)
(A)), 143.4 (Ar(6) (A)), 144.1 (Ar(6) (B)), 151.3 (Ar(2) (A)), 152.1
(Ar(2) (B)), 187.5 (Ar(1), 1J(7Li-13C) ) 18 Hz (A) and (B). 6Li NMR
(44.165 MHz, toluene-d8): δ (in ppm) 0.36 (B), 0.46 (A). 13C
CP-MAS NMR: δ (in ppm) 4.7 and 6.1 (N(CH2CH3)2), 13.5 (NCH2CH3),
42.4, 43.7, 47.5, 48.2 and 52.7 (NCH2 5 ×), 65.7 (ArCH2N), 123.0,
123.7 and 126.6 (Ar(3,4,5)), 142.7 (Ar(6)), 150.8 (Ar(2)), 188.5 (Ar(1)).
Due to its extreme sensitivity no reliable elemental analysis could be
abtained. Molecular weight determination by cryoscopy (0.21 g in 16.32
g C6H6). Calcd. for monomer: 240.3. Found: 436.
(R)-[LiC6H4(CH(Me)N(Me)CH2CH2NMe2)-2]2 ((R)-3b). Prepared
according to a published procedure,6 (R)-3b was started from (R)-
[1-BrC6H4(CH(Me)N(Me)CH2CH2NMe2)-2] ((R)-3a) (2.31 g; 8.10
mmol) and n-BuLi (5.2 mL of a 1.6 M solution in hexane, 8.20 mmol)
in pentane (10 mL), yielding 1.57 g (87%). Crystals suitable for an
X-ray analysis were obtained from a saturated solution of (R)-3b in
Et2O at -30 °C.
the cryoscopic constant Kf ) 5.54 K kg mol-1
.
(R)-[BrC6H4(CH(Me)N(Me)CH2CH2NMe2)-2] ((R)-3a). (S)-(-)-
2-Bromo-R-methyl-benzyl alcohol (5.03 g; 25.05 mmol) and triethyl-
amine (7 mL; 50.03 mmol) were dissolved in CH2Cl2 (70 mL) and
cooled to -78 °C. Methanesulfonyl chloride (2.15 mL; 27.52 mmol)
was added dropwise within 30 min, and the mixture was stirred at low
temperature for another 30 min. N,N,N′-Trimethylethylenediamine (3.5
mL; 27.52 mmol) was added in portions of 1 mL to the suspension.
This mixture was stirred for an additional 2 h at low temperature and
then left overnight to warm to room temperature slowly. The suspension
formed was quenched with an aqueous HCl solution (2 M; 100 mL;
until pH < 2) and separated from the organic layer. The aqueous layer
was washed with Et2O and subsequently made alkaline with solid KOH
to pH > 12. The product was extracted with pentane (80 mL, 3×).
The combined organic layers were washed with brine and dried over
Na2SO4, and the solvent was removed in vacuo to yield (R)-3a as an
almost colorless oil. Purification via Kugelrohr distillation yielded 2.34
g (33%) of (R)-3a as a colorless oil. The ee (98%) was determined by
HPLC analysis: eluent 2% propan-2-ol in hexane; flow rate 1.0 mL
min-1; retention time 252 s for the (S)-enantiomer and 285 s for the
(R)-enantiomer.
1H NMR (toluene-d8, 300.105 MHz, 233 K): δ (in ppm) Two ligand
patterns are observed in a 1:1 ratio, labeled A and B. 1.02 (s, 3H, NMe2
(A)), 1.10-1.60 (m, 4H, NCH2CH2N (A, B)), 1.30 (d, 3H, CH(Me)
(B)), 1.44 (s, 3H, NMe2 (B)), 1.46 (s, 3H, NMe2 (A)), 1.57 (s, 3H,
NMe2 (B)), 1.59 (d, 3H, CH(Me) (A)), 2.04 (m, 3H, NCH2CH2N (A,
B)), 2.30 (s, 3H, N(Me) (B)), 2.49 (s, 3H, N(Me) (A)), 2.92 (m, 1H,
NCH2CH2N (A or B)), 3.16 (q, 1H, ArCH (B)), 4.08 (q, 1H, ArCH
(A)), 7.08-7.35 (ArH(3,4,5) (A, B)), 8.16 (d, 1H, ArH(6) (A)), 8.33
(d, 1H, ArH(6) (B)). 13C NMR (toluene-d8, 75.469 MHz, 233 K): δ
(in ppm) 8.89 (CH(Me) (A)), 24.6 (CH(Me) (B)), 39.6, 41.5 (NCH2CH2N
(A and B)), 42.8, 44.7 (NMe2 (A, B)), 45.2 (NCH2CH2N (A)), 47.9
(NMe2 (A, B)), 52.8 (NCH2CH2N (B)), 56.9, 57.3 (N(Me) (A, B)), 68.6
(ArCH (A)), 72.0 (ArCH (B)), 142.3, 143.1 (Ar(2) (A, B)), 154.0, 157.4
3
1H NMR (C6D6, 300.105 MHz, 298 K): δ 1.15 (d, 3H, J ) 6.6
Hz, CH(Me)), 2.01 (s, 6H, NMe2), 2.14 (s, 3H, N(Me)), 2.29, 2.51 (2
3
× m, 2H, NCH2CH2N), 3.99 (q, 1H, J ) 6.6 Hz, CH(Me)), 6.67 (t,
1H, ArH(4)), 6.98 (t, 1H, ArH(5)), 7.37 (d, 1H, ArH(3)), 7.57 (d, 1H,
ArH(6)). 13C NMR (C6D6, 75.469 MHz, 298 K): δ (in ppm) 19.9
(CH(Me)), 39.4 (N(Me)), 45.8 (NMe2), 53.2, 58.0 (NCH2CH2N), 63.0
(CH(Me)), 124.3, 127.6, 128.1, 129.0, 132.9 (Ar(2,3,4,5,6), 145.1
(ArCipso). [R]20 ) +19.9° (c ) 1 (MeOH)). Anal. Calcd for
D
C13H21N2Br: C, 54.74; H, 7.42; N, 9.82. Found: C, 54.70; H, 7.34; N,
9.68.
(rac)-[BrC6H4(CH(Me)N(Me)CH2CH2NMe2)-2] ((rac)-3a). The
synthetic route is identical to that described for the chiral compound
(R)-3a, starting from (rac)-2-bromo-R-methylbenzyl alcohol (6.78 g;
33.72 mmol) and N,N,N′-trimethylethylenediamine (4.5 mL; 35.42
mmol), yielding 3.99 g (42%).
1H and 13C NMR spectra are identical to that of (R)-3a. Anal. Calcd
for C13H21N2Br: C, 54.74; H, 7.42; N, 9.82. Found: C, 54.82; H, 7.52;
N, 9.76.
6
(Ar(6) (A, B)), 183.0, 190.0 (ArCipso (A, B)). Li NMR (toluene-d8,
44.165 MHz, 298 K): δ (in ppm) 0.87 and 0.60. 13C CP-MAS NMR:
see Figure 2 in the Results section. Due to its extreme sensitivity, no
reliable elemental analysis could be obtained. Molecular weight
determination by cryoscopy (0.29 g in 10.58 g C6H6), calcd for
monomer: 212.3. Found: 430.
(rac)-[LiC6H4(CH(Me)N(Me)CH2CH2NMe2)-2]2 ((rac)-3b). Pre-
pared according to the procedure for ((R)-3b), (rac)-3b was started
from (rac)-[1-BrC6H4(CH(Me)N(Me)CH2CH2NMe2)-2] ((rac)-3a) (3.39
g; 11.89 mmol) and n-BuLi (7.5 mL of a 1.6 M solution in hexane,
12.00 mmol), yielding 2.50 g (99%).
[LiC6H4(CH2N(Et)CH2CH2NEt2)-2]2 (2b). To a solution of
BrC6H4(CH2N(Et)CH2CH2NEt2)-2 (2.67 g; 8.5 mmol) in pentane (30
mL) was added slowly n-butyllithium (6.8 mL of a 1.5 M solution in
pentane; 10.2 mmol) in 45 min at -78 °C. The mixture was stirred for
45 min at -78 °C and was allowed to warm to room temperature in
1.5 h. The resulting suspension was centrifuged, and the supernatant
was removed by decantation. The solid obtained was washed with
pentane (2 × 10 mL) and then dried in vacuo to afford 2 as a white
powder (1.90 g, 70% yield). Crystals suitable for an X-ray analysis
were obtained from a saturated solution of 2b in Et2O at -30 °C.
1H NMR (toluene-d8, 300.105 MHz, 308 K): δ (in ppm) 1.10-
1.60 (m, 2H, NCH2CH2N), 1.45 (br, 6H, NMe2, 1.55 (d, 3H, CH(Me)),
2.20 (m, 1H, NCH2CH2N), 2.40 (s, 3H, NMe), 2.98 (m, 1H, NCH2CH2N),
3.20 (q, 1H, ArCH), 7.08-7.35 (ArH(3,4,5)), 8.20 (d, 1H, ArH(6)).
13C NMR (toluene-d8, 75.469 MHz, 233 K): δ (in ppm) 25.4 (CH(Me),
40.5 (NCH2CH2N), 45.0 and 48.2 (NMe2), 54.0 (NCH2CH2N), 58.7
(N(Me)), 72.6 (ArCH), 124.0, 124.3 and 125.3 (Ar(3,4,5), 143.4 (Ar(2)),
157.8 (Ar(6)), 184.0 (Ar(1)). 6Li NMR (toluene-d8, 44.165 MHz,
298K): δ (in ppm) 0.64. 13C CP-MAS NMR: see also Figure 2 in the
Results section. δ (in ppm) 25.1 (CH(Me)), 39.6, 47.0, 48.8 (NMe 3×),
52.3, 64.9 (NCH2CH2N), 72.0 (ArCH), 124.5, (Ar(3,4,5), 142.4 (Ar(2)),
157.6 (Ar(6)), 183.5 (Ar(1)). Due to its extreme sensitivity no reliable
elemental analysis could be obtained. Molecular weight determination
by cryoscopy (0.21 g in 10.73 g C6H6). Calcd for monomer: 212.3.
Found: 440.
1
The H and 13C NMR data of a solution of 2b showed that two
different species are present in a ∼2:1 ratio (labeled A and B). 1H NMR
(300.105 MHz, toluene-d8, 298 K): δ (in ppm) 0.59 (br s, 2 × 3H,
3
N(CH2CH3)2 (A)), 0.77 (t, 3H, NCH2CH3 (B), J ) 6.9 Hz), 0.90 (br
3
s, 2 × 3H, N(CH2CH3)2 (B)), 1.08 (t, 3H, NCH2CH3 (A), J ) 7.0
Hz), 1.44-2.86 (m, 4 × 2H, NCH2CH2N (A, B) and N(CH2CH3)2 (A,
B)), 2.39 (m, 1H, NCH2CH3 (B)), 2.51 (m, 1H, NCH2CH3 (B)), 3.02
(m, 1H, NCH2CH3 (A)), 3.17 (m, 1H, NCH2CH3 (A)), 3.23/4.29 (AB,
2H, CH2N (B), JAB ) 12 Hz), 3.45/4.21 (AB, 2H, CH2N (A), JAB
)
11.7 Hz), 7.10 (m, 1H, ArH (A, B)), 7.20 (m, 2H, ArH (A, B)), 8.21
(br d, 1H, ArH (B), 3J ) 4.8 Hz), 8.27 (d, 1H, ArH (A), 3J ) 6.0 Hz).
13C NMR (75.469 MHz, toluene-d8, 298 K): δ (in ppm) 8.77
Structure Determinations and Refinement of 2b and (R)-3b.
Compound 2b: C30H50Li2N2, Fw ) 480.62, colorless block, 0.36 ×
0.33 × 0.21 mm3, T ) 110(2) K, monoclinic, P21/c (no. 14), a )
9.9986(1) Å, b ) 11.8266(1) Å, c ) 13.6183(2) Å, â ) 113.4371(5)°,
(24) (a) Bauer, W.; Seebach, D. HelV. Chim. Acta, 1984, 67, 1972. (b) Gerold,
A.; Jastrzebski, J. T. B. H.; Kronenburg, C. M. P.; Spek, A. L.; van Koten,
G. J. Am. Chem. Soc. 1998, 120, 9688.
V ) 1477.50(3) Å3, Z ) 2, F(000) ) 528, Dcalcd ) 1.080 g cm-3
,
22 188 reflections were measured on a Nonius KappaCCD diffracto-
9
J. AM. CHEM. SOC. VOL. 126, NO. 49, 2004 16257

A R T I C L E S
Arink et al.
meter with rotating anode (λ ) 0.710 73 Å). The data were merged
using the program SortAV,25 resulting in 3378 unique reflections (Rint
) 0.036). An absorption correction was not considered necessary. The
structure was solved with direct methods (SHELXS-97)26 and refined
against F2 of all reflections (SHELXL-97).27 199 refined parameters,
no restraints. R [I > 2σ(I)]: R1 ) 0.0364, wR2 ) 0.0902. R [all data]:
R1 ) 0.0524, wR2 ) 0.0993. S ) 0.955. Residual electron density
(min/max) ) -0.21/0.21 e/Å3. Structure calculations, drawings, and
checking for higher symmetry were performed with the PLATON
package.28 An earlier structure determination of this compound is
available from the Cambridge Structural Database.29
28 269 reflections were measured on a Nonius KappaCCD diffracto-
meter with rotating anode (λ ) 0.710 73 Å). The data were merged
using the program SortAV,25 resulting in 4556 unique reflections (Rint
) 0.073). An absorption correction was not considered necessary. The
structure was solved with direct methods (SHELXS-97)26 and refined
against F2 of all reflections (SHELXL-97).27 593 refined parameters,
1 restraint. The absolute structure could not be determined reliably and
was assigned according to the synthesis. R [I > 2σ(I)]: R1 ) 0.0365,
wR2 ) 0.0855. R [all data]: R1 ) 0.0438, wR2 ) 0.0904, S ) 1.041.
Residual electron density (min/max) ) -0.14/0.12 e/Å3. Structure
calculations, drawings, and checking for higher symmetry were
performed with the PLATON package.28
Compound (R)-3b: C26H42Li2N2, Fw ) 424.52, colorless block, 0.40
× 0.40 × 0.30 mm3, T ) 150(2) K, monoclinic, P21 (no. 4), a )
9.6895(1) Å, b ) 17.2620(2) Å, c ) 16.2017(2) Å, â ) 94.7843(5)°,
Acknowledgment. This work was supported in part (A.M.A.,
M.L., A.L.S.) by the Council for Chemical Sciences of The
Netherlands Organization for Scientific Research (CW-NWO).
Dr. J. Boersma is kindly thanked for critical reading of this
manuscript.
V ) 2700.46(5) Å3, Z ) 4, F(000) ) 928, Dcalcd ) 1.044 g cm-3
,
(25) Blessing, R. H. J. Appl. Crystallogr. 1997, 30, 421.
(26) Sheldrick, G. M. SHELXS-97. Program for crystal structure solution.
University of Go¨ttingen: Germany, 1997.
Supporting Information Available: X-ray crystallographic
data of 2b and (R)-3b (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
(27) Sheldrick, G. M. SHELXL-97. Program for crystal structure refinement.
University of Go¨ttingen: Germany, 1997.
(28) Spek, A. L. J. Appl. Crystallogr. 2003, 36, 7.
(29) Spek, A. L.; Veldman, N. Private communication to the Cambridge
Structural Database (deposit@ccdc.cam.ac.uk), reference code HIGQOD
(CCDC-113983), 1999.
JA045914Q
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16258 J. AM. CHEM. SOC. VOL. 126, NO. 49, 2004