Chiral modular n-butyllithium aggregates: nBuLi complexes with anisyl fencholates

Article abstract of DOI:10.1002/1521-3765(20011015)7:20<4456::AID-CHEM4456>3.0.CO;2-S

Chiral, enantiopure aggregates are formed spontaneously by mixing solutions of n-butyllithium with anisyl fenchols. X-ray crystal analyses reveal the structures of these aggregates with different ortho substituents in the anisyl moieties (X), X=H (1-H), S

Full text of DOI:10.1002/1521-3765(20011015)7:20<4456::AID-CHEM4456>3.0.CO;2-S

FULL PAPER
Chiral Modular n-Butyllithium Aggregates:
nBuLi Complexes with Anisyl Fencholates
Bernd Goldfuss,* Melanie Steigelmann, Frank Rominger, and Heiko Urtel[a]
Dedicated to Professor Dieter Hoppe on the occasion of his 60th birthday
Abstract: Chiral, enantiopure aggre-
gates are formed spontaneously by mix-
ing solutions of n-butyllithium with
anisyl fenchols. X-ray crystal analyses
reveal the structures of these aggregates
with different ortho substituents in the
anisyl moieties (X), X ˆ H (1-H), SiMe3
(2-H), tBu (3-H) SiMe2(tBu) (4-H) and
Me (5-H). While the complex of 1-BuLi
shows a 3:1 composition, 2-BuLi, 3-BuLi
and 4-BuLi yield 2:2 stoichiometries.
The aggregate 5-BuLi crystallizes with a
2:4 composition and hence is a deriva-
tive of hexameric n-butyllithium, in
which two trans-situated nBuLi mole-
cules are substituted by lithium fencho-
late moieties. The variety in the synthe-
sized chiral nBuLi aggregates demon-
strates the high propensity of anisyl
fencholates to chirally modify nBuLi.
Variations in the modular ligand struc-
tures by alterations of the ortho-sub-
stituents (X) enable tunings of compo-
sitions and also of enantioselectivities in
nBuLi additions to benzaldehyde.
Keywords: carbanions ´ chirality ´
enantioselectivity ´ lithium ´ struc-
ture elucidation
lates (e.g. 1-Li, 2-Li) exhibit a high propensity to form chiral
aggregates with n-butyllithium.[12, 13]
Introduction
n-Butyllithium (nBuLi) is among the most frequently em-
ployed organometallic reagents, and chiral modifications of
nBuLi offer enormous potential in enantioselective synthe-
ses.[1, 2] Suitable mediators are necessary for efficiently tuning
reactivity and (enantio)selectivity of organolithium com-
pounds.[3, 4] Structural investigations in solution[5] and in the
solide state[1a, g, h, 6] yield precious information about the
nature of chiral organolithium compounds[7] and hence
provide the basis for a rational design of new reagents.[8]
Although quite a few X-ray crystal analyses of achiral nBuLi
complexes are known,[9] there is relatively little structural
information on chirally modified nBuLi species. Williard et al.
reported X-ray crystal structures of n-, sec- and tert-butyl-
lithium complexes with lithium N-isopropyl-O-methylvalino-
late.[6b] Additionally, the group of van Koten characterized a
chiral, but racemic (nBuLi)2 aggregate with lithiated 1-(di-
methylamino)ethyl benzene.[6c] Organozinc fencholates[10] are
efficient catalysts in diethylzinc additions to benzaldehyde
and their modular structures help to explore origins of
reactivities and enantioselectivities.[11] Lithium anisyl fencho-
Especially remarkable is the possibility to tune the binding
modes, the stoichiometries and the enantioselectivities of
these nBuLi aggregates through variation of ortho substitu-
ents (e.g. X ˆ H (1-H), SiMe3 (2-H)) in the anisyl moieties.[12]
The unsubstituted anisyl fenchol system 1-H (Scheme 1)
Scheme 1. Anisyl fenchols and lithium fencholates.
reacts with n-butyllithium to form the aggregate 1-BuLi
(Figure 1), which exhibits a nBuLi:fencholate ratio of 1:3. In
contrast to 1-H, the SiMe3-substituted anisyl fenchol 2-H
(Scheme 1) generates complex 2-BuLi (Figure 2) with a 2:2
stoichiometry, agostic Li-CH2(b) interactions and increased
enantioselectivity in butylation reactions with benzaldehyde
(80% ee for 2-BuLi, 46% ee for 1-BuLi; Scheme 2).[12]
We demonstrate here that, in addition to 1-H (X ˆ H) and
2-H (Xˆ SiMe3), lithium derivatives of the anisyl fenchols 3-H
(X ˆ tBu), 4-H (X ˆ SitBuMe2), and 5-H (X ˆ Me) are able to
aggregate and chirally modify n-butyllithium over a broad
[a] Dr. B. Goldfuss, Dipl. Chem. M. Steigelmann, Dr. F. Rominger,[‡]
Dipl. Chem. H. Urtel[‡‡]
Organisch-chemisches Institut der Universität Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
Fax : (‡49)6221-54-4205
E-mail: bernd.goldfuss@urz.uni-hd.de
‡
[ ] X-ray analyses.
‡‡
[
] NMR spectroscopy.
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4456±4464
ure 1) or 2-BuLi (Figure 2).[12b] Analogously, the fenchols 3-H,
4-H, and 5-H form colorless precipitates in mixtures of n-
butyllithium solutions in hexanes. Again, the pure lithium
fencholates (3-Li, 4-Li, 5-Li) are not formed, but the lithium
alcoholates generated in situ aggregate with nBuLi and form
crystalline solids. Single crystal analyses yield the X-ray
structures of the n-butyllithium lithium anisyl fencholate
complexes 3-BuLi (Figure 3), 4-BuLi (Figure 4), and 5-BuLi
(Figure 5).
Figure 1. X-ray crystal structure of 1-BuLi (X ˆ H). Hydrogen atoms are
omitted for clarity, the probability of the thermal elipsoids is 50%.
Figure 3. X-ray crystal structure of 3-BuLi (X ˆ tBu). Hydrogen atoms are
omitted for clarity, the probability of the thermal elipsoids is 50%.
Figure 2. X-ray crystal structure of 2-BuLi (X ˆ SiMe3). Hydrogen atoms
are omitted for clarity, the probability of the thermal elipsoids is 50%.
range of ortho substituents (X). X-ray crystal analyses of the
nBuLi anisyl fencholate aggregates show 2:2 ratios for 3-BuLi
and 4-BuLi and, for 4-BuLi, a hitherto unprecedented 2:4
composition (Scheme 2).
Figure 4. X-ray crystal structure of 4-BuLi (X ˆ SitBuMe2). Hydrogen
atoms are omitted for clarity, the probability of the thermal elipsoids is
50%.
Results and Discussion
Reactions of the fenchols 1-H or 2-H with n-butyllithium in
hexanes yield the n-butyllithium complex 1-BuLi[12a] (Fig-
In 3-BuLi, two nBuLi molecules and two lithium fencholate
units (3-Li) form a distorted Li4C2O2 cube (Figure 3). The
structure of 3-BuLi with a tBu
substituent (X) is similar to that
of 2-BuLi (Figure 2) with a
SiMe3 ortho substituent.[12b]
However, the orientations of
the n-butylide groups differ in
2-BuLi and 3-BuLi: In 2-BuLi,
nBu-bridged C ± Li edges are
situated directly over lithium
and oxygen atoms, which orig-
Scheme 2. n-Butyllithium anisyl fencholate aggregates.
inate from the same lithium
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B. Goldfuss et al.
FULL PAPER
and the lithium alkoxide units (mean values: 2-BuLi: 2.45 Š;
3-BuLi: 2.45 Š; 4-BuLi 2.38 Š, Table 1). Much more uniform
Li C(a) distances are apparent in the cubic Li4O3C core of
1-BuLi (Table 1). Slightly longer Li C(a) distances are found
in 5-BuLi for contacts connecting the two stacked six-
membered Li3OC2 rings (mean value: 2.26 Š) than for
Li C(a) contacts within the Li3OC2 rings (mean values:
2.19 Š and 2.21 Š).[16]
No agostic[17] Li-b-CH2 interactions are possible in 1-BuLi,
because lithium ions neighbored to the butylide group are
fourfold coordinated by contacts to the anisyl methoxy groups
(Figure 1). In 2-BuLi, threefold coordinated lithium ions are
able to form agostic interactions with the butylide moieties
(Figure 2). This is apparent from short distances between the
lithium centers and b-CH2 units (Li C(b): 2.36 and 2.38 Š,
Table 1).[12b] Despite the similar structure of 3-BuLi, analo-
gous Li C(b) interactions are less pronounced (Li C(b): 2.71
and 2.65 Š, Figure 3).[18] In 4-BuLi, however, agostic inter-
actions are again clearly apparent from short Li C distances
(Li C(b): 2.36 Š and 2.37 Š). The hetero-hexameric struc-
ture of 5-BuLi exhibits no such short Li C(b) contacts
(2.59 Š, 2.82 Š, Table 1, Figure 5).
The intrinsic steric influence of the ortho substituents (X)
on the geometries of the ligand systems is apparent from two
geometrical distortions: the bending of the methoxy groups
out of the plane of the benzene rings (MeO ± Ar dihedral
angle, Scheme 3) and the torsion angles of the aryl moieties
relative to the fenchane fragment (Fen ± Ar dihedral angle,
Scheme 3).
Figure 5. X-ray crystal structure of 5-BuLi (X ˆ Me). Hydrogen atoms are
omitted for clarity, the probability of the thermal elipsoids is 50%.
fencholate fragment (2-Li). In contrast, analogous nBu-
bridged Li ± C edges in 3-BuLi are aligned over Li and O
atoms, which belong to different lithium fencholate units
(3-Li; Scheme 2).
Aggregate 4-BuLi (Figure 4) also composes of two nBuLi
molecules and two lithium fencholates 4-Li. The orientations
of the n-butylide groups in 4-BuLi are very similar to those in
2-BuLi. The tBu moieties at the silicon atoms in 4-Bu point
away from the (nBuLi)2 unit, while the SiMe2 groups generate
a similar environment at the C2O2Li4 core as the SiMe3 groups
in 2-BuLi (Figure 2).
In the X-ray crystal structure of 5-BuLi, four nBuLi
molecules and two lithium fencholate units (5-Li) form a
Li6C4O2 core, which assembles from two stacked Li3C2O rings
(Figure 5).[14] Hence, 5-BuLi can be regarded as a ªhetero-
analogousº derivative of hexameric n-butyllithium, (nBu-
Li)6:[15] in the (nBuLi)6 aggregate two trans-situated nBuLi
units are replaced by lithium fencholate moieties (5-Li) to
form 5-BuLi (Figure 5).
Scheme 3. Methoxy ± aryl (MeO-Ar) and fenchyl ± aryl (Fen-Ar) dihedral
angles; steric repulsions ($) between X, OMe, and endo-Me are shown.
The appearance of (nBuLi)2 subunits in the 2:2 aggregates
of 2-BuLi, 3-BuLi, and 4-BuLi corresponds to the relatively
frequent formation of (nBuLi)2 moieties in nBuLi complex-
es.[6c, 9a±c] The Li C(a) distances in these (nBuLi)2 lithium
fencholates show a clear geometrical differentiation of
(nBuLi)2 subunits relative to the rest of the cubic Li4O2C2
cores: the Li C(a) distances are significantly shorter within
the (nBuLi)2 moieties (mean values: 2-BuLi: 2.17 Š; 3-BuLi:
2.20 Š; 4-BuLi: 2.18 Š) than in contacts between (nBuLi)2
These intrinsic steric effects of X are clearly apparent in
X-ray crystal structures of fenchols 1 to 5. With increasing
steric demand of the substituents X, the bending of the
methoxy groups out of the aryl planes (MeO ± Ar dihedral
angle) increases in the order X ˆ H ( 3.08) < Me ( 60.88) <
SiMe3
( ( 93.58)
72.48) < tBu ( 82.68)[19] < SitBuMe2
(Table 1). The out-of-benzene-ring-plane bending of the
Table 1. Distances [Š] and angles [8] in the X-ray crystal structures of nBuLi lithium fencholate complexes and (in parentheses) of the parent fenchols.
1-BuLi (1-H)
2-BuLi (2-H)
3-BuLi (3-H)
4-BuLi (4-H)
5-BuLi [a] (5-H)
Li C(a)
2.195, 2.221, 2.225
2.173, 2.192, 2.450
2.157, 2.172, 2.446
2.359, 2.381
1.974, 1.947
63.4, 63.7
2.181, 2.207, 2.478,
2.129, 2.280, 2.430
2.653, 2.705
1.929, 1.955
76.1, 75.1
2.175, 2.180, 2.365,
2.157, 2.193, 2.396
2.356, 2.371
2.200, 2.210, 2.291,
2.189, 2.211, 2.227
2.593, 2.820
1.933
62.8
( 60.8)
Li C(b)
Li O(Me)
MeO ± Ar angle[b]
±
1.982, 1.987, 2.025
19.4, 19.7, 32.6
1.950, 1.945
70.2, 67.2
(
3.0)[c]
(
72.4)
(
82.6)
(
93.5)[d]
Fen ± Ar angle[b]
51.2, 49.5, 46.6
(47.2)[c]
40.3, 43.6
(33.4)
36.2, 40.5
(30.3)
38.7, 39.2
(12.1)[d]
42.9
(42.4)
[a] Crystallographic C2 symmetry. [b] Methoxy ± aryl (MeO-Ar) and fenchyl ± aryl (Fen-Ar) dihedral angles (Scheme 3). [c] Mean value of four independent
molecules. [d] Disordered.
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n-Butyllithium Aggregates
4456±4464
1
Table 2. Total (a. u.‡ ZPE)[a] and relative [kcalmol
]
[b] B3LYP/6±31‡ G*
anisyl methoxy groups leads to repulsive interactions between
methoxy and endo-methyl groups of the fenchane moieties
(Scheme 3). Minimization of this repulsion gives rise to
rotation around the fenchyl-aryl bond (Fen-Ar). Indeed, the
Fen ± Ar dihedral angle decreases as the MeO ± Ar dihedral
angle increases: X ˆ H (47.28) > Me (42.48) > SiMe3 (33.48)
> tBu (30.38)[19] > SitBuMe2 (12.18) (Table 1). Hence, the
steric demand of X indirectly determines the geometry of the
energies of Li4OnCm aggregates (n ˆ 0, 1, 2, 3, 4, m ˆ 4 n) (Scheme 4).
6
7
8
9
10
total
relative
189.67513
0.0
225.69679
14.7
261.71801
29.1
297.73723
42.3
333.75580
55.0
[a] All equilibrium structures were optimized in C1 symmetry, unscaled
zero point energies are included. [b] The relative energies consider LiOH
(a. u. ‡ ZPE: 83.36976) and LiMe (a. u. ‡ ZPE: 47.37150), according
to Scheme 4.
_
chelating O O unit of the anisyl fenchols and, for bulky
substituents X, forces an increasingly coplanar arrangement
_
of the O O moiety (Scheme 3). In the nBuLi complexes, a
The replacement of organolithium groups (i.e. LiMe) by
LiOH units (as a model for lithium alkoxides) is favored for
all cubic Li4OnCm aggregates (n ˆ 0, 1, 2, 3, 4; m ˆ 4 n). The
high degree of oxido moieties in the aggregates is supported
electrostatically,[20] and cubic Li4O4 clusters are therefore
intrinsically the most favorable (Scheme 4).
similar increase in the mean value of the MeO ± Aryl dihedral
angles and a decrease in the mean Fen ± Ar angles, respec-
tively, is apparent from the order 1-BuLi (23.98, 50.48), 5-BuLi
(62.88, 42.98), 2-BuLi (63.68, 43.58), 4-BuLi (68.78, 39.08),
3-BuLi (75.68, 38.48) (Table 1).
The intrinsic driving force for the incorporation of LiOR
moieties in Li4C4 clusters and the formation of mixed-anionic
aggregates, like the lithium butylide fencholates, is evaluated
computationally from the equations in Scheme 4 (Table 2).
Inter-ligand repulsions between SiMe3 groups and endo-
methyl groups of the fenchane moieties were found to be
responsible for the instability of a hypothetical 3:1 aggregate
for X ˆ SiMe3, which preferentially forms the 2:2 complex (2-
BuLi, Figure 2).[12b] The 3:1 composition, however, is more
suitable for X ˆ H in 1-BuLi (Figure 1).[12a] This suggests that
the steric demand of the bulky anisyl fenchane moiety prevents
the formation of pure lithium fencholates, which should be favor-
able according to the equations in Scheme 4,[21] and stimulates
instead the incorporation of the smaller nBuLi fragments to
form the mixed nBuLi lithium fencholate aggregates.
The relative stabilities of mixed lithium fencholate nBuLi
aggregates with 3:1 and 2:2 compositions are evaluated
computationally by the aggregate formation energies for
different ortho substituents X in Schemes 5 and 6 (Table 3).
According to the higher intrinsic stability of the cubic
Li4O3C core (Scheme 4) and due to the small steric demand of
X ˆ H, lithium fencholate 1-Li and nBuLi preferentially form
the 3:1 aggregate 1-BuLi-cmp, cmp ˆ denotes computed to
1
differentiate from X-ray structures with 173 kcalmol
(Scheme 5), as the complex stabilization energy for the 2:2
1
species 1-(2:2) is smaller (169 kcalmol , Scheme 6).[22] This
explains the experimental composition of the X-ray crystal
structure 1-BuLi (Figure 1), which corresponds to the com-
puted 1-BuLi-cmp structure.
In contrast to X ˆ H, the bulky ortho substituents (X) tBu,
SiMe3, or SitBuMe2 favor the formation of 2:2 aggregates
(Scheme 6) over the 3:1 compositions (Scheme 5). Steric
effects of the ligands obviously overcompensate the higher
stability of the cubic Li4O3C cores versus the Li4O2C2
arrangements (Scheme 4). While only two ligands surround
the Li4O2C2 core in 2:2 aggregates, three bulky fencholates
Scheme 4. LiMe/LiOH replacement energies for cubic Li4OnCm (n ˆ 0, 1,
2, 3, 4; m ˆ 4 n) aggregates (Table 2).
1
[b]
Table 3. Total (a. u. ‡ ZPE)[a] and relative [kcalmol
]
B3LYP/6 ± 31G*//ONIOM(B3LYP(6 ± 31 ‡ G*): UFF energies for aggregate formation
(Scheme 3 and 4).
1
1
Li fencholate
a. u.
819.60607
1228.27372
976.83801
1346.19695
858.91680
nBuLi aggregates 3:1
a. u./stability [kcalmol
]
nBuLi aggregates 2:2
a. u./stability [kcalmol ]
1-Li
2-Li
3-Li
4-Li
5-Li
1-BuLi-cmp
2-(3:1)
3-(3:1)
4-(3:1)
5-(3:1)
2624.42572/ 172.7
3850.37232/ 137.4
3096.06385/ 136.5
4204.16198/ 149.9
2742.33259/ 156.8
1-(2:2)
197.14538/ 168.6
2787.45500/ 152.5
2284.57385/ 146.4
3023.30591/ 155.3
2048.74765/ 156.4
2-BuLi-cmp
3-BuLi-cmp
4-BuLi-cmp
5-(2:2)
[a] All equilibrium structures were optimized in C1 symmetry and characterized as minima by frequency computations (ONIOM), zero point energies are not
considered for the B3LYP/6 ± 31G* single-point energies. [b] Evaluated with n-butyllithium, a. u.: 165.33228.
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Scheme 5. Formation and stabilities of mixed lithium fencholate nBuLi
aggregates with 3:1 compositions (B3LYP/6 ± 31G*//ONIOM(B3LYP/6 ±
31 ‡ G*:UFF, Table 3). The favored structure, relative to 2:2 aggregates
(see Scheme 6), is highlighted ( ).
Figure 7. ONIOM (B3LYP/6 ± 31 ‡ G*:UFF)-optimized structure of 3-
(3:1) (X ˆ tBu). Hydrogen atoms are omitted for clarity. The shortest
inter-ligand C C distances are shown.
Scheme 6. Formation of mixed nBuLi lithium fencholate aggregates with
2:2 compositions (B3LYP/6 ± 31G*//ONIOM(B3LYP/6 ± 31 ‡ G*:UFF, Ta-
ble 3). The favored structures, relative to 3:1 aggregates (see Scheme 5),
are highlighted ( ).
have to be arranged at the Li4O3C cubes in 3:1 complexes. The
computed structures 2-(3:1) (Figure 6), 3-(3:1) (Figure 7), and
4-(3:1) (Figure 8) exhibit analogous geometries to 1-BuLi
Figure 8. ONIOM (B3LYP/6 ± 31 ‡ G*:UFF)-optimized structure of 4-
(3:1) (X ˆ SitBuMe2). Hydrogen atoms are omitted for clarity. The shortest
inter-ligand C C distances are shown.
(Figure 1), but close inter-ligand distances appear between X
substituents and endo-methyl groups of the fenchane moi-
eties. This may account for the decreased stabilities of 3:1
arrangements relative to the 2:2 aggregates (Scheme 5) and
agrees with the experimental formation of the structures 2-
BuLi, 3-BuLi, and 4-BuLi.[23]
For X ˆ Me, very similar complex formation energies of 3:1
and 2:2 aggregates (Scheme 5 and Scheme 6) show that both
developments are possible. Surprisingly, neither of them is
formed experimentally but the 2:4 composition is observed
instead in the X-ray crystal structure of aggregate 5-BuLi.[14]
Figure 6. ONIOM (B3LYP/6 ± 31 ‡ G*:UFF)-optimized structure of 2-
(3:1) (X ˆ SiMe3). Hydrogen atoms are omitted for clarity. The shortest
inter-ligand C C distances are shown.
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n-Butyllithium Aggregates
4456±4464
Enantioselective additions of n-butyllithium to benzalde-
hyde can be achieved with mixtures of nBuLi and the lithium
fencholates 1-Li to 5-Li (Scheme 7), which form in situ after
mixing an excess of nBuLi with the fenchols 1-H to 5-H.[24]
that the formations of mixed aggregates with cubic cores
originate from two competing effects: a) the tendency to form
aggregates with high degrees of alkoxido units in the cubic
cores, and b) inter-ligand repulsions, which prevent the
incorporation of too many bulky alkoxido moieties. To
complete the cubic core structures, smaller n-butyllithium
units are incorporated, yielding the mixed aggregates. Effects
like methoxy group coordination or solvation phenomena
might also be crucial for the origin of the aggregates: a fenchol
with CH2NMe2 instead of the OMe donor group yields no
nBuLi complex[26] and the anisyl fenchol with X ˆ Me yields a
4:2 aggregate. Enantioselectivities in nBuLi additions to
benzaldehyde show that the chiral modular lithium fencho-
lates are suitable mediators for enantioselective C C bond
formations. This points to further applications of these
enantiopure mixed-anionic organolithium aggregates in or-
ganic syntheses.
Scheme 7. Enantioselective nBuLi additions to benzaldehyde, mediated
by lithium fencholates, yielding (R)-1-phenyl-1-pentanol as the major
enantiomer (Table 4).
Increased ratios of lithium fencholates (i.e. 3:1 vs. 1:1) in
mixtures with nBuLi give rise to increased enantioselectivities
in reactions with benzaldehyde for the fencholates 1-Li to 4-
Li. (Table 4). This suggests that higher enantioselectivities can
be achieved with suppressed amounts of ªfreeº nBuLi.[24] For
both 3:1 and 1:1 ratios of lithium fencholates : nBuLi,
enantioselectivities increase with the bulkiness of the sub-
stituent X in the order H < Me < tBu < SiMe3, but are lower
again for SitBuMe2, indicating the best auxiliary structure for
2-Li amongst the studied fencholates (Table 4).
Experimental Section
General: The reactions were carried out under an argon atmosphere
(Schlenk and needle-septum techniques) with dried and degassed solvents.
X-ray crystal analyses were performed on a Bruker Smart CCD diffrac-
tometer with Moka radiation. NMR spectra were recorded on a Bruker
AC300 and DRX500 (1H, 13C chemical shifts referenced to [D8]toluene, 7Li
to LiBr), IR spectra on a Bruker Equinox 55 FT-IR spectrometer, and
optical rotations on a Perkin Elmer P241 machine. GC analyses were
carried out on a Chrompack (CP9001).
Table 4. n-Butyllithium additions to benzaldehyde with lithium fenchola-
te:nBuLi ratios of 1:1 and 3:1 (Scheme 7).[a]
1:1 ratio
X
% ee[b] Yield[c] 3:1 ratio X
% ee[b] Yield[c]
1-Li
2-Li
3-Li
4-Li
5-Li
H
SiMe3
tBu
SitBuMe2 51
Me 24
8
66
55
73
86
81
84
76
1-Li
2-Li
3-Li
4-Li
5-Li
H
SiMe3
tBu
SitBuMe2 56
Me 28
14
76
62
30
99
99
99
92
Crystallographic data (excluding structure factors) for the structures
reported in this paper have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication nos. CCDC-148412 (3-
H), CCDC-159905 (4-H), CCDC-148411 (5-H), CCDC-148414 (3-BuLi),
CCDC-159906 (4-BuLi), and CCDC-148413 (5-BuLi). Copies of the data
can be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB21EZ, UK (fax: (‡44)1223-336-033; e-mail: deposit@ccdc.
cam.ac.uk).
[a] All reactions were performed by mixing fenchols and nBuLi in hexane
solution, yielding the given lithium fencholate:nBuLi ratios. Benzaldehyde
was added at 788C, see Experimental Section. [b] Enantioselectivities
were determined by HPLC analyses, DAICEL OB-H, iso-
propanol:hexane ˆ 0.8:99.2. [c] Yields were obtained by GC with hexade-
cane as internal standard.
Enantioselective reactions - general procedure: A solution of n-butyllithi-
um (4 or 2 mmol for 3:1 or 1:1 ratios, respectively) in hexane (1.60 m) was
added at room temperature to fenchol (3 (3:1 ratio) or 1 (1:1 ratio) mmol).
After stirring the mixture for 20 min at 788C, benzaldehyde (1 mmol)
was added. The reaction mixture was kept for 30 min at 788C and then
warmed to room temperature (over 2 h). Hydrolytic workup, separation of
the layers, drying over Na2SO4, and column chromatographic purification
(silica gel, petroleum ether:ethylacetate (9:1)) yielded (R)-1-phenyl-1-
pentanol as the major product (Table 4). Enantioselectivities were
determined by HPLC analyses, DAICEL OB-H, isopropanol:hexane
0.8:99.2. Yields were obtained from GC with hexadecane as the internal
standard.
7Li NMR studies in [D8]toluene show two different lithium
ion environments for each of the lithium fencholate n-
butyllithium aggregates 1-BuLi, 2-BuLi, 3-BuLi, 4-BuLi and
5-BuLi. H ± 7Li COSY experiments reveal that one of the
1
chemically different lithium ions is coordinated by methoxy
groups, whilst the other lithium center exhibits no OMe
coordination. This suggests that in nonpolar hydrocarbon
solvents (e.g. toluene) similar structures to those in the solid
state exist (Figures 1 ± 5) and might also be involved in the
enantioselective nBuLi transfer reactions.[25]
Synthesis and characterization of 3-H: 2-tert-Butylanisol[27] (12.4 g,
0.076 mol) was added at 08C to a mixture of n-butyllithium (50.3 mL,
0.08 mol, 1.60 m solution in hexane) and TMEDA (12.1 mL, 0.08 mol). A
colorless precipitate formed after 12 h stirring at room temperature. ( )-
Fenchone (12.2 mL, 0.076 mol) was slowly added at 08C to this suspension,
and the mixture was stirred for two days at room temperature. Hydrolytic
workup, drying and concentration of the organic layer and recrystallization
from pentane yielded colorless 3-H (10.78 g, 0.034 mol, 45%): m.p. 768C;
elemental analysis (%): calcd: C 79.70, H 10.19, O 10.11; found C 79.64, H
Conclusion
1
10.22, O 10.14. H NMR (300 MHz, CDCl3, RT); d ˆ 0.54 (s, 3H), 1.06 (s,
3H), 1.10 (m, 1H), 1.13 (s, 3H), 1.28 (m, 1H), 1.39 (s, 9H), 1.47 (m, 1H),
1.74 (m, 2H), 2.28 (m, 1H), 2.40 (m, 1H), 3.75 (s, 3H), 6.01 (s, 1H), 6.95
(ªtº, J ˆ 7.9 Hz, 1H) 7.22 (d, J ˆ 7.8 Hz, 1H), 7.39 (d, J ˆ 8.0 Hz, 1H);
13C NMR (75.5 MHz, CDCl3, RT) d ˆ 17.9, 21.8, 23.6, 29.4, 31.9, 33.5, 35.6,
41.8, 46.5, 49.4, 54.3, 65.3, 86.7, 121.7, 126.6, 128.7, 136.3, 142.9, 158.9;
Anisyl fencholates with different substituents (X) in ortho-
positions of aryl groups all form mixed aggregates with n-
butyllithium in nonpolar solvents (i.e. hexanes, toluene).
X-ray crystal structures of the lithium fencholate nBuLi
complexes reveal 3:1 (X ˆ H), 2:2 (X ˆ tBu, SiMe3, SitBuMe2)
and 4:2 (X ˆ Me) compositions. Computational studies show
‡
‡
‡
MS(EI): m/z: 316.0 [M ], 233.0 [M
C6H11], 191.0 [M
C9H17]; IR
(KBr): nÄ ˆ 3457 (OH, s), 3074 ± 3002 (aryl, w), 2967 ± 2925 (alkyl, m), 1383,
1
21
1362 cm (tBu, m); [a]
(hexane) ˆ 99.6; X-ray analysis of 3-H:
Na
Chem. Eur. J. 2001, 7, No. 20
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0720-4461 $ 17.50+.50/0
4461

B. Goldfuss et al.
FULL PAPER
SHELXTL V5.10, C21H32O2, Mr ˆ 316.47, Tˆ 200(2) K, l ˆ 0.71073 Š,
monoclinic crystal system, space group: P21, Z ˆ 2, a ˆ 7.6760(2), b ˆ
3.68 (s, 9H; 3OCH3), 6.70 (d, J ˆ 8.1 Hz, 3H; 3H-ortho), 6.80 (ªtº, J ˆ
7.6 Hz, 3H; 3H-diortho), 6.95 (ªtº, J ˆ 7.7 Hz, 3H; 3H-diortho), 7.53 (d, J ˆ
8.1 Hz, 3H; 3H-ortho); 13C NMR (125 MHz, [D8]toluene, 108C): d ˆ 10.0
(Ca-BuLi), 14.3 (CH3-BuLi), 23.1 (CH3), 23.8 (CH3), 25.4 (CH2), 30.8
(CH3), 32.0 (CH2-BuLi), 34.8 (CH2-BuLi), 35.4 (CH2), 41.3 (CH2), 44.5
(Cq), 50.9 (CH), 53.0 (Cq), 56.6 (OCH3), 89.1 (Cq), 114.2 (CAr), 120.8 (CAr),
126.0 (CAr), 129.8 (CAr), 140.2 (CAr), 158.5 (CAr); 7Li NMR (194 MHz,
[D8]toluene, 108C): d ˆ 1.06 (coordinated by OCH3), 1.39.
Characterization of 2-BuLi: For the synthesis, see reference [12b].
Compound 2-BuLi for NMR experiments was obtained after washing an
amorphous precipitate with cold hexane (6 Â 0.2 mL) in 29% yield.
Evolution of gas and decomposition was observed at 100 ± 1608C.
1H NMR (500 MHz, [D8]toluene, 108C): d ˆ 0.97 (m, 2H; CaH2,
BuLi), 0.33 (m, 1H; CbHH, BuLi), 0.49 (s, 9H; Si(CH3)3), 0.76 (s, 3H; 10-
CH3), 0.80 (t, J ˆ 7.3 Hz, 3H; CH3, BuLi), 0.99 (m, 1H; CbHH, BuLi), 1.18
(m, 1H; CgHH, BuLi), 1.23 (m, 2H; H6-exo, H7-anti), 1.25 (s, 3H; 9-CH3),
1.28 (s, 3H; 8-CH3), 1.36 (m, 1H; CgHH, BuLi), 1.53 (m, 1H; H5-exo), 1.76
(m, 1H; H5-endo), 1.82 (s, 1H; 4-CH), 2.25 (m, 1H; H6-endo), 2.39 (d, J ˆ
10.0 Hz, 1H; H7-syn), 3.86 (s, 3H; OCH3), 6.89 (ªtº, J ˆ 7.4 Hz, 1H;
H-diortho) 7.30 (d, J ˆ 7.2 Hz, 1H; H-ortho), 7.53 (d, J ˆ 7.6 Hz, 1H;
H-ortho); 13C NMR (125 MHz, [D8]toluene, 108C): d ˆ 1.30 (Si(CH3)3),
10.7 (Ca-BuLi), 14.4 (CH3-BuLi), 19.2 (CH3), 23.5 (CH3), 24.4 (CH2), 31.3
(CH3), 32.9 (CH2-BuLi), 33.0 (CH2-BuLi), 35.8 (CH2), 41.5 (CH2), 44.0
(Cq), 51.0 (CH), 54.8 (Cq), 64.4 (OCH3), 88.1 (Cq), 121.9 (CAr), 131.1 (CAr),
132.1 (CAr), 134.5 (CAr), 142.0 (CAr), 164.7 (CAr); 7Li NMR (194 MHz,
[D8]toluene, 108C): d ˆ 1.08 (coordinated by OCH3), 2.06.
10.9920(3), c ˆ 10.8986(3) Š, b ˆ 97.778(1), Vˆ 911.10(4) Š3, 1calcd
ˆ
1.154 gcm 3, collected reflections: 9426, independent reflections: 4147,
1
observed reflections: 2650 (I > 2s(I)), absorption coefficient m: 0.072mm
,
Flack parameter: 0.5(16), R values (I > 2s(I)): R1 ˆ 0.054, wR2 ˆ 0.101,
largest difference peak and hole: 0.14, 0.19 eŠ 3; goodness-of-fit: 1.03.
Synthesis and characterization of 4-H: Anisol (10.8 g, 0.10 mol) was added
at 08C to a mixture of n-butyllithium (68.8 mL, 0.11 mol, 1.60 m solution in
hexane) and TMEDA (16.6 mL, 0.11 mol). A colorless precipitate of
2-lithioanisol formed after stirring for a few minutes. After 3 h, tert-
butyldimethylsilyl chloride (15.1 g, 0.10 mol) in hexane (10 mL) was added
at 08C. After the mixture had been stirred for 12 h followed by aqueous
workup, the layers were separated and the organic layer was dried and
concentrated. Distillation yielded o-(tert-butyldimethylsilyl)anisol (9.4 g,
0.042 mol; 42% yield; b.p. 898C at 8.2 Â 10 2 mbar).
o-(tert-Butyldimethylsilyl)anisol (9.4 g, 0.042 mol) was added at 08C to a
mixture of n-butyllithium (28.8 mL, 0.046 mol of a 1.60 m solution in
hexane) and TMEDA (6.9 mL, 0.046 mol). After the reaction mixture had
been stirred for 6 h, ( )-fenchone (6.8 mL, 0.042 mol) was added at 08C
and the mixture was stirred for 12 h. Hydrolytic workup and recrystalliza-
tion from pentane yielded 4-H (7.7 g, 0.021 mol, 50%): m.p. 938C;
elemental analysis (%) calcd: C 73.74, H 10.22; found: C 73.97, H 10.22.
1H NMR (300 MHz, CDCl3, RT): d ˆ 0.36 (s, 3H), 0.39 (s, 3H), 0.51 (s, 3H),
0.81 (s, 9H), 1.11 (m, 1H), 1.12 (s, 3H), 1.14 (s, 3H), 1.31 (m, 1H), 1.43 (m,
1H), 1.76 (m, 2H), 2.29 (m, 1H), 2.43 (m, 1H) 3.74 (s, 3H), 5.89 (s, 1H), 7.07
(ªtº, J ˆ 7.5 Hz, 1H), 7.32 (d, J ˆ 7.2 Hz, 1H), 7.59 (d, J ˆ 8.1 Hz, 1H);
13C NMR (75.5 MHz, CDCl3, RT): d ˆ -3.5, 18.0, 21.8, 23.8, 27.1, 29.6, 33.7,
37.4, 42.0, 46.7, 49.4, 54.0, 66.0, 86.4, 122.1, 130.7, 132.1, 135.1, 135.4, 164.8;
Synthesis and characterization of 3-BuLi: Compound 3-H (0.158 g,
0.5 mmol) was added at RT to nBuLi (0.63 mL, 1.0 mmol of a 1.60 m
solution in hexane). Slow evaporation of the hexane under reduced
pressure yielded 3-BuLi as colorless crystals. Compound 3-BuLi for NMR
experiments was obtained after washing an amorphous precipitate with
‡
‡
‡
MS(EI): m/z 374.3 [M ], 317.2, [M
C4H9], 249.1 [M
C9H17]; IR (KBr):
nÄ ˆ 3467, 3406 (OH, s), 3059 ± 3000 (aryl, w), 2996 ± 2876 (alkyl, s),
1
21
1
1362 cm (tBu, m); [a] (n-hexane) ˆ 53.5; X-ray analysis of 4-H:
Na
cold hexane (6 Â 0.2 mL) in 12% yield: m.p. 1228C; H NMR (500 MHz,
SHELXTL V5.10, C23H38O2Si, Mr ˆ 374.62, Tˆ 200(2) K, l ˆ 0.71073 Š,
triclinic crystal system, space group: P1, Z ˆ 2, a ˆ 7.7546(2), b ˆ 11.897, c ˆ
13.1300(3) Š, Vˆ 1123.28(4) Š3, 1calcd ˆ 1.11 gcm 3, reflections collected:
11605, independent reflections: 9538, observed reflections: 5945 (I >
2s(I)), absorption coefficient m: 0.12mm 1, Flack parameter: 0.1(12), R
values (I > 2s(I)): R1 ˆ 0.056, wR2 ˆ 0.097, largest difference peak and
hole: 0.18, 0.25 eŠ 3; goodness-of-fit: 0.98.
[D8]toluene, 108C): d ˆ 0.85 (t, J ˆ 12.6 Hz, 1H; CaHH, BuLi), 0.74
(t, 12.9, 1H; CaHH, BuLi), 0.71 (m, 1H; CbHH, BuLi), 0.85 (s, 3H; 10-
CH3), 0.89 (t, J ˆ 7.2 Hz, 3H; CH3, BuLi), 1.06 (m, 1H; CbHH, BuLi), 1.19
(m, 2H; H6-exo, H7-anti), 1.24 (s, 3H; 9-CH3), 1.25 (s, 3H; 8-CH3), 1.41 (m,
2H; CgH2, BuLi), 1.51 (m, 1H; H5-exo), 1.56 (s, 9H; C(CH3)3), 1.73 (m,
1H; H5-endo), 1.83 (s, 1H; 4-CH), 2.36 (m, 1H; H6-endo), 2.46 (d, J ˆ
10.1 Hz, 1H; H7-syn), 3.71 (s, 3H; OCH3), 6.85 (ªtº, J ˆ 7.8 Hz, 1H;
H-diortho), 7.17 (d, J ˆ 7.6 Hz, 1 H ; H-ortho), 7.38 (d, J ˆ 7.7 Hz, 1H;
H-ortho); 13C NMR (125 MHz, [D8]toluene, 108C): d ˆ 11.2 (Ca-BuLi),
14.4 (CH3-BuLi), 19.4 (CH3), 23.0 (CH3), 24.1 (CH2), 31.1 (CH3), 32.7 (CH2-
BuLi), 33.0 (C(CH3)3), 33.3 (CH2-BuLi), 35.7 (C(CH3)3), 36.4 (CH2), 42.1
(CH2), 44.4 (Cq), 51.1 (CH), 55.8 (Cq), 65.9 (OCH3), 89.3 (Cq), 122.2 (CAr),
126.6 (CAr), 128.3 (CAr), 142.5 (CAr), 144.0 (CAr), 158.3 (CAr); 7Li NMR
(194 MHz, [D8]toluene, 108C): d ˆ 1.05 (coordinated by OCH3), 2.17;
X-ray crystal analysis of 3-BuLi: SHELXTL V5.10, C50H80Li4O4, Mr ˆ
772.90, Tˆ 200(2) K, l ˆ 0.71073 Š, orthorhombic crystal system, space
group: P212121, Z ˆ 4, a ˆ 13.0685(2), b ˆ 13.8204(3), c ˆ 26.1159(6) Š, Vˆ
4716.84(17) Š3, 1calcd ˆ 1.314 gcm 3, reflections collected: 48849, indepen-
dent reflections: 10772, observed reflections: 4613 (I > 2s(I)), absorption
Synthesis and characterization of 5-H: 2-Methylanisol (12.2 g, 0.10 mol)
was added at 08C to a mixture of n-butyllithium (68.8 mL, 0.11 mol, 1.60 m
solution in hexane) and TMEDA (16.6 mL, 0.11 mol).
A colorless
precipitate formed after stirring for 12 h. )-Fenchone (16.1 mL,
(
0.10 mol) was slowly added at 08C to this suspension, and stirred for two
days at room temperature. Hydrolytic workup, drying, concentration of the
organic layer, and removal of residual fenchone in vacuo yielded a
yellowish substance. After recrystallization with pentane, colorless crystals
of 5-H were obtained (15.48 g, 0.056 mol, 56%): m.p. 818C; elemental
analysis (%) calcd: C 78.79, H 9.55, O 11.66; found: C 78.76, H 9.53, O 11.71;
1H NMR (300 MHz, CDCl3, RT): d ˆ 0.48 (s, 3H), 1.10 (m, 1H), 1.11 (s,
3H), 1.19 (s, 3H), 1.28 (m, 1H), 1.39 (m, 1H), 1.74 (m, 2H), 2.27 (m, 1H),
2.30 (s, 3H), 2.42 (m, 1H), 3.85 (s, 3H), 5.55 (s, 1H), 6.91 (ªtº, J ˆ 7.6 Hz,
1H), 7.00 (d, J ˆ 7.3 Hz, 1H), 7.36 (d, J ˆ 8.0 Hz, 1H); 13C NMR (75.5 MHz,
CDCl3, RT): d ˆ 17.6, 18.1, 21.7, 24.2, 29.7, 33.5, 41.4, 45.5, 49.6, 53.4, 61.4,
coefficient m: 0.092mm 1, Flack parameter: 1(2), R values (I > 2s(I)): R1 ˆ
3
0.082, wR2 ˆ 0.196, largest difference peak and hole: 0.65, 0.29 eŠ
;
goodness-of-fit: 1.00.
‡
85.9, 122.0, 122.6, 129.8, 130.3, 135.9, 157.8; MS(EI): m/z: 274.1 [M ], 191.0
Synthesis and characterization of 4-BuLi: Compound 4 (0.158 g, 0.5 mmol)
was added at RT to nBuLi (0.63 mL, 1.0 mmol of a 1.60 m solution in
hexane), and the mixture was stirred at 258C for 5 min. After freezing the
solution to 808C, the precipitate formed was dissolved in hot hexane.
Slowly cooling to room temperature yielded 4-BuLi as colorless crystals.
Compound 4-BuLi for NMR experiments was obtained after washing an
amorphous precipitate with cold hexane (6 Â 0.2 mL) in 57% yield.
Evolution of gas and decomposition was observed at 1718C. 1H NMR
(500 MHz, [D8]toluene, 108C): d ˆ 0.93 (m, 2H; CaH2, BuLi), 0.40 (s,
3H; SiCH3), 0.63 (m, 1H; CbHH, BuLi), 0.71 (s, 3H; SiCH3), 0.80 (s, 3H;
10-CH3), 0.87 (t, J ˆ 7.3 Hz, 3H; CH3, BuLi), 0.92 (m, 1H; CbHH, BuLi),
1.05 (s, 9H; SiC(CH3)3), 1.26 (m, 2H; H6-exo, H7-anti), 1.29 (s, 6H; 9-CH3,
8-CH3), 1.35 (m, 2H; CgH2, BuLi), 1.57 (m, 1H; H5-exo), 1.83 (m, 2H; H5-
endo, 4-CH), 2.32 (m, 1H; H6-endo), 2.41 (d, J ˆ 10.1 Hz, 1H; H7-syn),
3.96 (s, 3H; OCH3), 6.88 (ªtº, J ˆ 7.6 Hz, 1H; H-diortho) 7.36 (d, J ˆ 7.3 Hz,
1H; H-ortho), 7.54 (d, J ˆ 6.9 Hz, 1H; H-ortho); 13C NMR (125 MHz,
[D8]toluene, 108C): d ˆ 3.0 (SiCH3), 0.7 (SiCH3), 10.7 (Ca-BuLi), 14.4
‡
‡
[M
C6H11], 149.0 [M
C9H17]; IR (KBr): nÄ ˆ 3479 (OH, s), 3113 ± 3060
1 21
(aryl, w), 2996 ± 2876 cm (alkyl, s); [a] (n-hexane) ˆ 92.7; X-ray
Na
analysis of 5-H: SHELXTL V5.10, C18H26O2, Mr ˆ 274.39, Tˆ 200(2) K,
l ˆ 0.71073 Š, orthorhombic crystal system, space group: P212121, Z ˆ 4,
a ˆ 7.6043(1), bˆ 10.1176(1), c ˆ 19.9781(1) Š, Vˆ 1537.060(17) Š3, 1calcd
ˆ
1.186 g cm 3, reflections collected: 15694, independent reflections: 3528,
1
observed reflections: 3087 (I > 2s(I)), absorption coefficient m: 0.075mm
,
Flack parameter: 0.1(12), R values (I > 2s(I)): R1 ˆ 0.040, wR2 ˆ 0.095,
largest difference peak and hole: 0.20, 0.19 eŠ 3; goodness-of-fit: 1.07.
Characterization of 1-BuLi: For the synthesis, see reference [12a].
Compound 1-BuLi for NMR experiments was obtained after washing an
amorphous precipitate with cold hexane (6 Â 0.2 mL) in 31% yield.
1
Decomposition was observed at 2048C. H NMR (500 MHz, [D8]toluene,
108C): d ˆ 0.63 (t, J ˆ 12.4 Hz, 1H; Ca HH, BuLi), 0.39 (t, J ˆ
13.3 Hz, 1H; CaHH, BuLi), 0.49 (s, 9H; 3CH3), 0.97 (s, 9H; 3CH3), 1.27
(s, 9H; 3CH3), 0.26 ± 2.40 (m, 18H; CH2, ligand; m, 7H; CH2, CH3, BuLi),
4462
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0720-4462 $ 17.50+.50/0
Chem. Eur. J. 2001, 7, No. 20

n-Butyllithium Aggregates
4456±4464
(CH3-BuLi), 18.8 (CH3), 24.4 (CH3), 24.6 (CH2), 28.4 (SiC(CH3)3), 31.2
(CH3), 32.3 (CH2-BuLi), 33.2 (CH2-BuLi), 36.2 (CH2), 37.2 (SiC(CH3)3),
42.0 (CH2), 44.4 (Cq), 51.2 (CH), 55.3 (Cq), 65.1 (OCH3), 88.9 (Cq), 121.6
(CAr), 131.4 (CAr), 134.0 (CAr), 134.5 (CAr), 136.4 (CAr), 164.9 (CAr); 7Li
NMR (194 MHz, [D8]toluene, 108C): d ˆ 1.11 (coordinated by OCH3),
2.08; X-ray crystal analysis of 4-BuLi: SHELXTL V5.10, C54H92Li4O4Si2,
Mr ˆ 889.22, Tˆ 200(2) K, l ˆ 0.71073 Š, monoclinic crystal system, space
Acknowledgements
We are grateful for support from the Fonds der Chemischen Industrie
(Sachbeihilfe and Liebig-Stipendium for B.G.), the Deutsche Forschungs-
gemeinschaft (GO 930/1 ± 1, GO 930/3 ± 1 and Habilitationsstipendium GO
930/2 ± 1 for B.G.), the Forschungspool of the University of Heidelberg, the
Degussa AG, and the BASF AG. B.G. thanks Prof. Dr. P. Hofmann for
generous support at Heidelberg.
group: C2/c, Z ˆ 8, a ˆ 36.9230(6), b ˆ 13.5888(1), c ˆ 22.4589(3) Š, b ˆ
3
101.248, Vˆ 11052.2(2) Š3, 1calcd ˆ 1.07 gcm
,
reflections collected:
32985, independent reflections: 4403, observed reflections: 3460 (I >
2s(I)), absorption coefficient m: 0.10mm 1, Flack parameter: 1(2), R
values (I > 2s(I)): R1 ˆ 0.082, wR2 ˆ 0.195, largest difference peak and
hole: 0.61, 0.39 eŠ 3; goodness-of-fit: 1.13.
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[4] For a series of recent studies on chiral organometallic reagents see:
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Eur. J. 2000, 6, 3359 ± 3365; c) R. W. Hoffmann, B. Holzer, O. Knopff,
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Hoffmann, P. G. Nell, Angew. Chem. Int. Ed. 1999, 38, 338 ± 340.
[5] a) F. Xu, R. A. Reamer, R. Tillyer, J. M. Cummins, E. J. J. Grabowski,
P. J. Reider, D. B. Collum, J. C. Huffman, J. Am. Chem. Soc. 2000, 122,
11212 ± 11218; b) P. I. Arvidsson, P. Ahlberg, G. Hilmersson, Chem.
Eur. J. 1999, 5, 1348 ± 1354; c) A. Thompson, E. G. Corley, M. F.
Huntington, E. J. J. Grabowski, J. F. Remenar, D. B. Collum, J. Am.
Chem. Soc. 1998, 120, 2028 ± 2038; d) D. Hoffmann, D. B. Collum, J.
Am. Chem. Soc. 1998, 120, 5810. For studies on n-butyllithium
aggregates by means of diffusion-ordered NMR spectroscopy
(DOSY) see: e) I. Keresztes, P. G. Williard, J. Am. Chem. Soc. 2000,
122, 10228 ± 10229. For NMR studies on Williardꢁs nBuLi ± valinolate
complex see: f) G. Hilmersson, B. Malmros, Chem. Eur. J. 2001, 7,
337 ± 341.
Synthesis and characterization of 5-BuLi: Compound 5-H (0.137 g,
0.5 mmol) was added at RT to nBuLi (0.94 mL, 1.5 mmol 1.60 m solution
in hexane). Isothermal diffusion yielded 5-BuLi as colorless crystals.
Compound 5-BuLi for NMR experiments was obtained after washing an
amorphous precipitate with cold hexane (6 Â 0.2 mL) in 73% yield.
1
Decomposition was observed at 1608C. H NMR (500 MHz, [D8]toluene,
108C): d ˆ 0.84 (m, 4H; 2CaH2, BuLi), 0.15 (m, 1H; CbHH, BuLi), 0.58
(m, 1H; CbHH, BuLi), 0.66 (s, 3H; 10-CH3), 0.85 (m, 1H; CbHH, BuLi),
0.93 (t, J ˆ 7.2 Hz, 3H; CH3, BuLi), 1.00 (m, 3H; CH3, BuLi), 1.09 (m, 1H;
CbHH, BuLi), 1.15 (s, 3H; 9-CH3), 1.17 (m, 2H; H6-exo, H7-anti), 1.19 (s,
3H; 8-CH3), 1.42 (m, 5H; 2 CgH2, BuLi, H5-exo), 1.64 (m, 1H; H5-endo),
1.71 (s, 1H; 4-CH), 2.03 (m, 1H; H6-endo), 2.18 (s, 3H; CH3) 2.35 (d, J ˆ
9.2 Hz, 1H; H7-syn), 3.70 (s, 3H; OCH3), 6.77 (ªtº, J ˆ 7.6 Hz, 1 H ;
H-diortho) 6.81 (d, J ˆ 7.2 Hz, 1H; H-ortho), 7.34 (d, J ˆ 8.0 Hz, 1H;
H-ortho); 13C NMR (125 MHz, [D8]toluene, 108C): d ˆ 10.0 (Ca-BuLi),
13.8 (CH3), 14.1 (CH3-BuLi), 19.1 (CH3), 23.5 (CH3), 25.1 (CH2), 31.2
(CH3Ar), 32.8 (CH2-BuLi), 32.9 (CH2-BuLi), 35.1 (CH2), 41.2 (CH2), 44.1
(Cq), 50.9 (CH), 54.7 (Cq), 62.1 (OCH3), 88.8 (Cq), 122.1 (CAr), 127.5 (CAr),
129.8 (CAr), 130.3 (CAr), 142.6 (CAr), 158.2 (CAr); 7Li NMR (194 MHz,
[D8]toluene, 108C): d ˆ 1.02 (coordinated by OCH3), 2.23; X-ray analysis
of 5-BuLi: SHELXTL V5.10, C52H86Li6O4, Mr ˆ 816.85, Tˆ 200(2) K, l ˆ
0.71073 Š, tetragonal crystal system, space group: P43212, Z ˆ 4, a ˆ
13.5798(1), b ˆ 13.5798(1), c ˆ 27.2532(4) Š, Vˆ 5025.79(9) Š3, 1calcd
:
1.080 gcm 3, reflections collected: 35175, independent reflections: 3499,
observed reflections: 2383 (I > 2s(I)), absorption coefficient: m:
0.063mm 1, Flack parameter: 2(3), R values (I > 2s(I)): R1 ˆ 0.077,
3
wR2 ˆ 0.209, largest difference peak and hole: 0.29 and 0.17 eŠ
;
goodness-of-fit: 1.03.
Computational section: All computed structures were fully optimized by
using the program package GAUSSIAN 98.[28] For the ONIOM[29]
computations, hydrogen atoms were used as linkers between the two
layers. The ªUniversal Force Fieldº (UFF)[30] was employed for alkyl and
aryl moieties and the hybrid density functional method B3LYP/6 ± 31 ‡
G*[31] was used for the polar Li4O3(CH2) and Li4O2(CH2)2 cubic cores
(Scheme 8). All structures were analyzed by frequency computations and
showed no imaginary frequencies. Single point energies of the structures
were computed using the B3LYP/6 ± 31G* method.
[6] a) I. Hoppe, M. Marsch, K. Harms, G. Boche, D. Hoppe, Angew.
Chem. 1995, 107, 2328 ± 2330; Angew. Chem. Int. Ed. Engl. 1995, 34,
2158 ± 2160; b) P. G. Williard, C. Sun, J. Am. Chem. Soc. 1997, 119,
11693 ± 11694; c) J. G. Donkervoort, J. L. Vicario, E. Rijnberg,
J. T. B. H. Jastrzebski, H. Kooijman, A. L. Spek, G. v. Koten, J.
Organomet. Chem. 1998, 550, 463 ± 467; d) D. J. Pippel, G. A. Weisen-
burger, S. R. Wilson, P. Beak, Angew. Chem. 1998, 110, 2600 ± 2602;
Angew. Chem. Int. Ed. Engl. 1998, 37, 2522 ± 2524.
[7] Reviews on organolithiums: a) Lithium Chemistry (Eds.: A.-M. Sapse,
P. von R. Schleyer), Wiley, New York, 1995; b) C. Lambert, P. von R.
Schleyer, Angew. Chem. 1994, 106, 1187 ± 1199; Angew. Chem. Int. Ed.
Engl. 1994, 33, 1129 ± 1140; c) C. Lambert, P. von R. Schleyer,
Methoden Org. Chem. (Houben Weyl), 4th Ed.; 1952-, Vol. E19d,
Thieme, Stuttgart, 1993, 1; d) W. Bauer, P. von R. Schleyer in
Advances in Carbanion Chemistry, Vol. 1 (Ed.: V. Snieckus), Jai Press,
Greenwich, CT, 1992.
Scheme 8. Layers of ONIOM (B3LYP/6 ± 31 ‡ G* (bold):UFF) geometry
optimizations.
Chem. Eur. J. 2001, 7, No. 20
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0947-6539/01/0720-4463 $ 17.50+.50/0
4463

B. Goldfuss et al.
FULL PAPER
[8] P. I. Arvidsson, G. Hilmersson, Ö. Davidsson, Chem. Eur. J. 1999, 5,
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[9] A lithiated silylamine ´ (nBuLi)2: a) C. Strohmann, B. C. Abele,
Organometallics 2000, 19, 4173 ± 4175; lithiated aluminum tert-butyl-
amide ´ (nBuLi)2: b) J. K. Brask, T. Chivers, G. P. A. Yap, Chem.
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c) R. D. Davies, P. R. Raithby, R. Snaith, Angew. Chem. 1997, 109,
1261 ± 1263; Angew. Chem. Int. Ed. Engl. 1997, 36, 1215 ± 1217;
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Soc. 1993, 115, 1568 ± 1572; e) N. D. R. Barnett, R. E. Mulvey, J. Am.
Chem. Soc. 1993, 115, 1573 ± 1574; [nBuLi ´ LiOtBu]4 is the first
structurally characterized mixed lithium alkyl alcoholate: f) M.
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102, 334 ± 336; Angew. Chem. Int. Ed. Engl. 1990, 29, 308 ± 310.
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Philipova, V. Dimitrov, S. Simova, Tetrahedron: Asymmetry 1999, 10,
1381 ± 1391; c) M. Genov, K. Kostova, V. Dimitrov, Tetrahedron:
Asymmetry 1997, 8, 1869 ± 1876; d) V. Dimitrov, S. Simova, K.
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1891 ± 1894. For phosphorus derivatives of fenchol see: g) B. Goldfuss,
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[11] a) B. Goldfuss, M. Steigelmann, F. Rominger, Eur. J. Org. Chem. 2000,
65, 1785 ± 1792; b) B. Goldfuss, M. Steigelmann, S. I. Khan, K. N.
Houk, J. Org. Chem. 2000, 65, 77 ± 82; c) B. Goldfuss, M. Steigelmann,
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[19] The tBu group is smaller than SiMe3, but is closer to the benzene ring
due to the shorter CAr C(Me3) bond as compared to CAr Si(Me3).
[20] The more suitable arrangement of Li O contacts relative to Li C
bonds is due to shorter contacts and hence stronger electrostatic
interactions for the oxido ligands. Also, three lone pairs at O are more
‡
suitable for Li coordination than one lone pair at the carbanionic
unit, cf. ref. [7].
[21] Mixed anionic aggregates should also be favored entropically.
[22] The computed complex formation energies provide only crude
assessments of aggregate stabilities because other, unconsidered
species might also be involved in the complex development.
[23] The Si(tBu)Me2 group exhibits through the SiMe2 moiety a similar
steric demand to SiMe3.
[24] To ensure identical conditions, mixtures of fencholates and nBuLi
were used for the comparative alkylations. Higher enantioselectivities
can be obtained with isolated complexes, for example, 46% ee for 1-
BuLi or 80% ee for 2-BuLi.[12b]
[25] For recent mechanistic studies on 1,2-additions of organolithium
compounds to carbonyl substrates see: a) F. Haeffner, C. Sun, P. G.
Williard, J. Am. Chem. Soc. 2000, 122, 12542 ± 12546; b) C. Fressigne,
J. Maddaluno, A. Marquez, C. Giessner-Prettre, J. Org. Chem. 2000,
65, 8899 ± 8907 and reference [5a].
[26] NMe2 coordination to lithium ions apparently prevents larger
aggregates than dimers.[13]
[27] I. I. Schuster, M. Parvez, A. J. Freyer, J. Org. Chem. 1988, 53, 5819 ±
5825.
[12] a) B. Goldfuss, S. I. Khan, K. N. Houk, Organometallics 1999, 16,
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4136 ± 4139.
[13] In contrast to fencholates with anisyl groups, no aggregate formation
of nBuLi is observed with N,N-dimethylbenzylamino fenchol, which
yields the corresponding dimeric lithium fencholate: B. Goldfuss, F.
Eisenträger, Aust. J. Chem. 2000, 53, 209 ± 212.
[28] Gaussian 98, Revision A.7, M. J. Frisch, G. W. Trucks, H. B. Schlegel,
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[14] Complex 5-BuLi with 2:4 composition is also obtained with different
starting ratios of nBuLi and 5-H.
[15] a) T. Kottke, D. Stalke, Angew. Chem. 1993, 105, 619 ± 621; Angew.
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Â
[30] A. K. Rappe, C. J. Casewit, K. S. Colwell, W. A. Goddard III, W. M.
[16] Strong differentiation of Li C(a) distances is apparent in a hexameric
lithium acetylide: B. Goldfuss, P. von R. Schleyer, F. Hampel, J. Am.
Chem. Soc. 1997, 119, 1072 ± 1080.
Skiff, J. Am. Chem. Soc. 1992, 114, 10024 ± 10035.
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[18] Agostic interactions in organolithium compounds can increase the
tendency towards b-hydride elimination: K. N. Houk, N. G. Roudan,
Received: March 13, 2001 [F3129]
4464
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