G. Hilmersson et al.
6
1
The lithium atom in a nonsolvated dimer only interacts with
two anions with some degree of covalent character in the
NÀLi bond. The fraction of covalency in the NÀLi bond
bath. For experimental details regarding the Li, H-HOESY experiments,
[
24]
see previous studies.
NMR spectroscopy instrumentation: The NMR studies were conducted
by using a Varian Unity 500 spectrometer equipped with 5 mm
C, Li, H triple-resonance probe head manufactured by the Nalorac
Company. Measuring frequencies were 500 ( H), 125 ( C) and 73 MHz
( Li). The H and C NMR spectra were referenced to the solvent
a
should be expected to decrease upon coordination of a
Lewis base to the atom. Although this dependency does not
rely on a theoretical basis, it serves as a rough guide in the
13
6
1
1
13
6
1
13
1
6
15
1
À
13
À
2 3 2
[D10]Et Osignals at d=1.06 ( H, CH ) and d=65.5 ppm ( C, CH ),
analysis of the observed
J( Li, N) coupling constants.
A
H
R
U
G
1
13
the [D
and the [D
8
]THF signals at d=1.72 ( H, ÀCH
3
) and d=67.6 ppm ( C, ÀCH
2
)
Based on our findings, it is possible to estimate the number
of ether molecules actually coordinating to a lithium nu-
cleus. Such information is crucial for the understanding of
the reactivity of, for example, chiral lithium amides in ethe-
real solvents.
1
13
]toluene signals at d=2.09 ( H, ÀCH
3
) and d=20.4 ppm ( C,
8
6
6
ÀCH ). The Li NMR spectra were referenced to external 0.3m LiCl in
3
[D ]methanol (d=0.0 ppm). Probe temperatures were measured after
1
more than 1 h of temperature equilibrium by using both a calibrated
methanol–freon NMR spectroscopy thermometer and the standard meth-
anol thermometer supplied by Varian Instruments.
Experimental Section
Synthesis of the amines
1
5
The chiral
[
N-labelled amines 1–4 were prepared from (S)-
Acknowledgements
1
5
[5]
N]phenylalanine according to previously published methods.
R)-2-Isopropylamino-1-phenylpropane ((R)-5): (S)-2-[(tert-Butoxycar-
bonyl)amino]-1-iodo-3-phenylpropane
was dissolved in a solution of SmI (270 mL, 0.11m, 29.8 mmol, 2.5 equiv)
in THF under nitrogen atmosphere. Triethylamine (6.02 g, 8.25 mL,
9.5 mmol, 5.0 equiv) followed by water (1.61 mL, 89.3 mmol, 7.5 equiv)
were added by using gas-tight syringes and the mixture was stirred at RT
for 20 min. The septum was removed and air was allowed to react with
2
the excess SmI until the solution was decolourised. The mixture was fil-
Financial support from The Swedish Research Council and the Knut and
Alice Wallenberg Foundation is gratefully acknowledged.
(
[
21]
A
C
H
T
R
E
U
N
G
(4.30 g, 11.9 mmol, 1.0 equiv)
2
5
[1] For reviews, see: a) A. Magnus, S. K. Bertilsson, P. G. Andersson,
Chem. Soc. Rev. 2002, 31, 223–229; J. Eames, Eur. J. Org. Chem.
2002, 393–401; b) P. OꢀBrien, J. Chem. Soc. Perkin Trans. 1, 1998,
1439–1457; c) D. M. Hodgson, A. R. Gibbs, G. P. Lee, Tetrahedron
1996, 52, 14361–14384; d) P. J. Cox, N. S. Simpkins, Tetrahedron:
Asymmetry 1991, 2, 1–26.
tered and the precipitate was extracted with THF (325 mL). The com-
bined filtrates were concentrated under reduced pressure and the result-
ing solid was dissolved in Et
Na SO and again concentrated under reduced pressure, resulting in a
white solid (2.69 g, 96%), (R)-2-[(tert-butoxycarbonyl)amino]-phenylpro-
2
O, washed with brine (50 mL), dried over
[2] M. Asami, T. Ishizaki, S. Inoue, Tetrahedron: Asymmetry 1994, 5,
793–796.
[3] D. Pettersen, M. Amedjkouh, P. Ahlberg, Tetrahedron 2002, 58,
4669–4773.
2
4
[
21]
pane (spectral data consistent with literature ).
[
4] M. Amedjkouh, D. Pettersen, S. O. Nilsson Lill, Ö. Davidsson, P.
Ahlberg, Chem. Eur. J. 2001, 7, 4368–4377.
5] a) J. Granander, R. Sott, G. Hilmersson, Tetrahedron: Asymmetry
The amide (2.69 g, 11.4 mmol, 1.0 equiv) was dissolved in dichlorome-
thane (100 mL) and trifluoroacetic acid (7.80 g, 5.08 mL, 68.4 mmol,
[
6
.0 equiv) was added to the solution. The resulting mixture was stirred
2
003, 14, 439–447; b) J. Granander, R. Sott, G. Hilmersson, Tetrahe-
overnight at RT before a NaOH solution (100 mL, 2.0m) was added. The
phases were separated and the aqueous phase was extracted with di-
chloromethane (325 mL). The combined organic extracts were washed
dron 2002, 58, 4717–4725.
[
[
6] a) P. I. Arvidsson, Ö. Davidsson, G. Hilmersson, Tetrahedron: Asym-
metry 1999, 10, 527–534; b) A. Corruble, J.-Y. Valnot, J. Maddaluno,
P. Duhamel, J. Org. Chem. 1998, 63, 8266–8275; c) A. Corruble, J.-
Y. Valnot, J. Maddaluno, P. Duhamel, Tetrahedron: Asymmetry
with brine (100 mL), dried over Na
2 4
SO and concentrated under reduced
pressure yielding a clear yellow oil (1.54 g, quantitative yield), (R)-2-
[
22]
amino-1-phenylpropane (spectral data consistent with literature ).
1
997, 8, 1519–1523; d) M. B. Eleveld, H. Hogeveen, Tetrahedron
The amine (1.54 g, 11.4 mmol. 1.0 equiv) and acetone (2.65 g, 3.35 mL,
Lett. 1984, 25, 5187–5190.
7] a) Y. Yuan, S. Desjardins, A. Harrison-Marchand, H. Oulyadi, C.
FressignØ, C. Giessner-Prettre, J. Maddaluno, Tetrahedron 2005, 61,
4
5.6 mmol, 4.0 equiv) were dissolved in benzene (50 mL) and refluxed by
using a Dean–Stark trap for 6 h. The mixture was allowed to cool to RT
and the solvent and excess acetone were removed under reduced pres-
3
2
325–3334; b) R. Sott, J. Granander, G. Hilmersson, Chem. Eur. J.
002, 8, 2081–2087; c) P. I. Arvidsson, G. Hilmersson, Ö. Davidsson,
sure. The residue was dissolved in dry ethanol (50 mL), NaBH
4
(0.86 g,
2
2.8 mmol, 2.0 equiv) was added and the mixture was stirred overnight at
Chem. Eur. J. 1999, 5, 2348–2355.
RT. Water (50 mL) was added and the ethanol was removed under re-
duced pressure. The residue was extracted with dichloromethane (3
[
[
8] A. Corruble, D. Davoust, S. Desjardins, C. FressignØ, C. Giessner-
Prettre, A. Harrison-Marchand, H. Houte, M.-C. Lasne, J. Maddalu-
no, H. Oulyadi, J.-Y. Valnot, J. Am. Chem. Soc. 2002, 124, 15267–
5
0 mL) and the combined organic extracts were washed with brine
(
50 mL), dried over Na SO and concentrated under reduced pressure
2
4
1
5279.
yielding a clear yellow oil. The crude product was purified by column
chromatography (aluminium oxide, ethyl acetate/hexane 1:4) yielding the
desired product as a clear colourless oil (1.01 g, 50%, spectral data con-
9] a) G. Hilmersson, B. Malmros, Chem. Eur. J. 2001, 7, 337–341; b) C.
Sun, P. G. Williard, J. Am. Chem. Soc. 2000, 122, 7829–7830; c) P. I.
Arvidsson, P. Ahlberg, G. Hilmersson, Chem. Eur. J. 1999, 5, 1348–
[
23]
sistent with literature ).
1
1
354; d) P. G. Williard, C. Sun, J. Am. Chem. Soc. 1997, 119, 11693–
1694; e) A. Corruble, J.-Y. Valnot, J. Maddaluno, Y. Prigent, D.
1
5
15
The chiral N-labelled amine (R)-[ N]5 was prepared from (S)-
1
5
[
N]phenylalanine by following the same procedure as the preparation
Davoust, P. Duhamel, J. Am. Chem. Soc. 1997, 119, 10042–10048;
f) G. Hilmersson, Ö. Davidsson, J. Organomet. Chem. 1995, 489,
175–179.
of (R)-5 above.
NMR spectroscopy studies: The chiral lithium amides and their mixed
complexes with nBuLi were generated in situ in septum-sealed NMR
tubes by the careful addition of the respective amine and nBuLi through
gas-tight syringes to the deuterated solvent. During this procedure, the
solutions were kept cooled to À788C over an acetone/dry-ice cooling
[10] R. Sott, J. Granander, G. Hilmersson, J. Am. Chem. Soc. 2004, 126,
6798–6805.
[11] R. Sott, J. Granander, G. Hilmersson, Tetrahedron: Asymmetry
2004, 15, 267–274.
4196
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 4191 – 4197