Synthesis of a highly enantiomerically enriched silyllithium compound

Article abstract of DOI:10.1039/b111687h

The highly enantiomerically enriched silyllithium compound lithiomethylphenyl(1-piperidinylmethyl)silane (4) reacts stereospecifically with chlorosilanes, but over a period of several hours slow racemization in solution at room temperature occurs, which c

Full text of DOI:10.1039/b111687h

Synthesis of a highly enantiomerically enriched silyllithium compound
Carsten Strohmann,* Jan Hörnig and Dominik Auer
Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany.
E-mail: c.strohmann@mail.uni-wuerzburg.de
Received (in Cambridge, UK) 2nd January 2002, Accepted 19th February 2002
First published as an Advance Article on the web 12th March 2002
The highly enantiomerically enriched silyllithium com-
pound lithiomethylphenyl(1-piperidinylmethyl)silane (4) re-
acts stereospecifically with chlorosilanes, but over a period
of several hours slow racemization in solution at room
temperature occurs, which can be supressed by a trans-
metalation reaction with MgBr2(thf)4.
equivalents of (R)-mandelic acid resulting in the separation of
the resonance signals of the methyl groups and the SiCH2N
group (AB-system). The ee-values of 5 were determined
analogously. Evaluation of the absolute configuration at the
silicon centre of (R)-2 was performed by single crystal structure
analysis of the diastereomeric salt (R)-2·(R)-mandelic acid,
which crystallizes in the monoclinic crystal system (space group
P21) with one equivalent of H2O.‡
Silyllithium compounds are useful reagents for the introduction
of silylgroups in organic and organometallic systems1a,b and for
the synthesis of complex polysilanes.2 The preparation of
lithiosilanes starting from chlorosilanes or disilanes is a well
established method.3a,b Sommer et al. described the first
synthesis of an optically active silyllithium compound by the
cleavage of an enantiomerically enriched disilane4 with lithium
metal.5 Corriu and coworkers also succeeded in the preparation
of an optically active silyllithium system via a cobalt–lithium
exchange reaction.6a,b The stability of configuration of the
metallated silicon centre was estimated by NMR experiments7
to be at least 100 kJ mol21. On the basis of these studies the
configuration is expected to be stable at room temperature and
the mechanism of racemization has been described in review
articles3a,8,9 and textbooks10,11 as the inversion of a free silyl
anion. A recent work by Kawakami and coworkers reports the
synthesis of an enantiomerically enriched silyllithium system
starting from enantiomerically enriched stannosilanes.12 Here
the authors report, for the first time, the racemization of a
silyllithium compound but key intermediates and products have
not been not characterized sufficiently. To our knowledge no
preparation of a highly enantiomerically enriched silyllithium
system (ee > 98%) starting from enantiomerically pure
disilanes or chlorosilanes has been reported so far.
In this work we present an easy synthetic access to a highly
enantiomerically enriched silyllithium compound. During our
studies we discovered that this system racemizes in solution at
room temperature. Closer observation shows an increase in
stability by transmetalation reactions.
The starting material for our studies is the enantiomerically
pure disilane (R)-2. From 1-(chloromethyl)-1,2-dimethyl-
1,2,2-triphenyldisilane13 (1) we were able to obtain 1,2-dime-
thyl-1,2,2-triphenyl-1-(1-piperidinylmethyl)disilane (2) in a
yield of 75 % (Scheme 1).†
Scheme 2
In the experiments described below (Scheme 2), the enantio-
merically pure disilane (R)-2 was cleaved with lithium metal in
THF at a temperature of 270 °C. The completeness of the
1
cleavage reaction was established by GC-MS and H NMR
spectroscopy after the trapping reaction with Me3SiCl. The
resulting disilane 5 could be isolated with ee > 98%. Isolated
solutions of lithiomethylphenyl(1-piperidinylmethyl)silane14
(4) racemize within a few hours at temperatures between 0 and
20 °C, but a very slow decomposition of 4 was also observed.
Due to this decomposition no exact determination of the
reaction rate law was possible.
Solutions of 4 left at room temperature for 2 h show reduced
ee-values of 53% after trapping with Me3SiCl. In order to
determine stabilizing effects on the configuration at the silicon
centre we performed
a transmetalation reaction with
MgBr2(thf)4 at 270 °C. After 2 h at room temperature no
significant racemization of the resulting metallated silane could
be observed (ee > 98%).
This increase of stability caused by the change of the metal is
in contrast to the proposed mechanism of racemization for
metalated silanes. Since the rate determining step of the
racemization process is discussed in the literature3a,8–11 as the
inversion of the free silyl anion system no drastic effect by
transmetalation should be expected. We are presently in-
vestigating the racemization process more closely by selective
variation of the solvent, the metal and the concentration of the
involved lithium compounds.
The results of cleavage of (R)-2 to give 4, followed by the
trapping reaction with Ph2MeSiCl to give (R)-2 (ee > 98%),
show that overall the configuration of the stereogenic silicon
centre is retained (see Scheme 2), although it is not clear
whether this is due to retention of the configuration at each step
or through double inversion during the course of the reaction.
Retention of configuration can also be observed if a trans-
metallation step with MgBr2(thf)4 is included in the reaction.
In summary, we were able to prove that it is possible to
synthesize the highly enantiomerically enriched silyllithium
Scheme 1
Separation of the enantiomers was carried out using (R)-
mandelic acid. The resulting enantiomerically pure disilane (R)-
2 could be isolated in a yield of 47% (yield relative to the
amount of (R)-2 in the diastereomeric salt). The ee-values were
1
determined by H NMR spectroscopy of 2 by addition of 3
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CHEM. COMMUN., 2002, 766–767
This journal is © The Royal Society of Chemistry 2002

0.36 mol l21) from the synthesis of 5 was warmed to room temperature (T
= 293 K). To another portion (360 mmol) of 4 450 mg (952 mmol)
MgBr2(thf)4 were added at 270 °C and the suspension warmed to room
temperature. After 2 h the samples were trapped, as described in the
synthesis of 5, with Me3SiCl and the ee-values were determined.
The reaction of 4 with Ph2MeSiCl (220 mg, 945 mmol) was performed
analogously to the method described for 5 resulted in (R)-2 (78 mg, 188
mmol, 52%; ee > 98%).
compound 4 (ee > 98 %) in large amounts and to perform
stereospecific reactions with chlorosilanes. Due to the observed
racemization of 4 in solution, we believe that a thorough
reassessment of previous work concerning optically active
silyllithium species is in order.
We gratefully acknowledge the Deutsche Forschungsge-
meinschaft DFG, the Sonderforschungsbereich (SFB) 347, and
the Fonds der Chemischen Industrie (FCI) for financial
support.
‡ Crystal structure determination of (R)-2·(R)-mandelic acid·H2O (colour-
less crystals from Et2O, 0.40 3 0.40 3 0.20 mm): C34H43NO4Si2, M =
585.89, monoclinic, space group P21 (no. 4), a = 9.886(2), b = 12.973(3),
c = 13.140(3) Å, b = 107.83(3)°, U = 1604.2(6) Å3, Z = 2, Dc = 1.213
Notes and references
Mg m23, Mo-Ka radiation, l
= 0.71073 Å, m = .
0.148 mm21
†
All preparations were performed using standard Schlenk techniques in
Measurements: Stoe IPDS diffractometer, T = 173 K. The structure was
solved using direct and Fourier methods. 18908 reflections measured with
q in the range 2.26–25.99°, 6102 unique reflections; 5693 with I > 2s(I);
refinement by full-matrix least-squares methods (based on Fo2, SHELXL-
93); anisotropic thermal parameters for all non-H atoms in the final cycles;
H atoms were refined on a riding model in their ideal geometric positions;
Flack parameter (20,03(11)); R = 0.0524 [I > 2s(I)], wR(Fo2) = 0.1416
(all data). SHELXS-8615 and SHELXL-9316 computer programs were used.
CCDC reference number 162970. See http://www.rsc.org/suppdata/cc/b1/
b111687h/ for crystallographic data in CIF or other electronic format.
an argon atmosphere.
2: A solution of 45.8 g (125 mmol) 1-(chloromethyl)-1,2-dimethyl-
1,2,2-triphenyldisilane (1) and 24.4 g (287 mmol) piperidine were heated
under reflux in toluene (150 ml) for 18 h. After separation of salts and
removing the solvent in vacuo the remaining product was purified by
Kugelrohr distillation (T = 225 °C; p = 1022 mbar) giving 39.2 g (94.3
mmol, 75%) of 2. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 0.49 (s, 3H;
NCSiCH3), 0.66 (s, 3H; NCSiSiCH3), 1.25–1.40 (m, 2H; NCCCH2),
1.40–1.50 (m, 4H; NCCH2), 2.15–2.30 (m, 4H; NCH2C), 2.22, 2.36 (AB-
system, JAB 14.7 Hz, 2H; SiCH2N), 7.20–7.55 (m, 15H; arom. H); 13C{1H}
NMR (100 MHz, CDCl3, 25 °C, CDCl3): d 24.8, 24.2 (NCSiCH3,
NCSiSiCH3), 23.8 (NCCCH2), 26.2 (2C; NCCH2), 49.2 (SiCH2N), 58.6
(2C; NCH2C), 127.67, 127.72, 127.74 (6C; C-m), 128.6, 128.7, 128.8 (C-p),
134.5, 135.18, 135.23 (6C; C-o), 136.8, 137.1, 137.8 (C-i); 29Si{1H} NMR
(59.6 MHz, CDCl3, 25 °C, TMS): d –23.3, –22.1; MS (EI, 70 eV): m/z (%):
218 (35) {[M 2 SiCH3(C6H5)2]+}, 197 (11) [SiCH3(C6H5)2+], 98 (100)
[(H2CNNC5H10)+].
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8 R. J. P. Corriu, C. Guerin and J. J. E. Moreau, in The Chemistry of
Organic Silicon Compounds, Part I, ed. S. Patai and Z. Rappoport,
Wiley, Chichester, 1989, pp. 305–370.
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Compounds, Part II, ed. S. Patai and Z. Rappoport, Wiley, Chichester,
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14 The exact molecular formula of 4 is unknown, but in solution THF
adducts are expected. Therefore all printed formulae of 4 simply
represent the reactivity of this compound.
(R)-2: (R)-2·(R)-mandelic acid·H2O was crystallized from diethyl ether
solutions of 2 with (R)-mandelic acid. Yield relative to the amount of (R)-2
in the diastereomeric salt: 47%, m/z (%): 416 (100) [(M + H)+]; mp 121 °C
(decomp.). Disilane (R)-2 was isolated using 2 M NaOH as a colourless
liquid and purified by Kugelrohr distillation (T = 225 °C; p = 1022 mbar).
The enantiomeric purity was verified by 1H NMR spectroscopy by addition
25
of 3 equiv. of (R)-mandelic acid. [a]D = 27.3 (c = 0.22, Et2O).
5 (ee > 98%): 750 mg (1.80 mmol) (R)-2 were added to a suspension of
37.5 mg (5.40 mmol) lithium in THF (5.0 ml) at 0 °C. At the first change of
colour the solution was immediately cooled to 270 °C and stirred for 5 h at
this temperature. The brown solution of 4 was divided into five equal
portions [five reactions were performed with one single portion (360 mmol)
each]. One portion of 4 was added at 280 °C to a solution of 100 mg (920
mmol) Me3SiCl in THF. Warming to room temperature and removing the
solvent in vacuo lead to an oily residue, which was treated with 2 ml 2 M
HCl. The byproducts were extracted with Et2O. After neutralization to pH
12 the product 5 was extracted with Et2O (70 mg, 240 mmol, 67%; ee >
98%). 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 0.08 (s, 9H;
NCSiSiCH3), 0.39 (s, 3H; NCSiCH3), 1.25–1.40 (m, 2H; NCCCH2),
1.45–1.55 (m, 4H; NCCH2), 2.2022.40 (m, 4H; NCH2C), 2.22, 2.32 (AB-
system, JAB 14.6 Hz, 2H; SiCH2N), 7.25–7.40 (m, 3H; arom. H), 7.45–7.55
(m, 2H; arom. H); 13C{1H} NMR (100 MHz, CDCl3, 25 °C, CDCl3): d 25.6
(NCSiCH3), 21.8 (3C; NCSiSiCH3), 23.8 (NCCCH2), 26.3 (2C; NCCH2),
49.1 (SiCH2N), 58.5 (2C; NCH2C), 127.7 (2C; C-m), 128.3 (C-p), 134.1
(2C; C-o), 138.7 (C-i); 29Si{1H} NMR (59.6 MHz, CDCl3, 25 °C, TMS): d
223.3, 218.6; MS (EI, 70 eV): m/z (%): 276 (1) [(M – CH3)+], 218 (12)
{[M 2 Si(CH3)3]+}, 98 (100) (H2CNNC5H10+).
The enantiomeric purity was determined by 1H NMR spectroscopy of 5
25
by addition of 3 equivalents of (R)-mandelic acid. [a]D = 25.1 (c = 0.22,
15 G. M. Sheldrick, SHELXS-86, Program for Crystal Structure Solution,
University of Göttingen, Germany, 1986.
Et2O).
Trapping reactions to determine the stability of the configuration of 4 in
solution: one of the remaining portions of the silyllithium solution 4 (c =
16 G. M. Sheldrick, SHELXL-93, Program for Crystal Structure Refine-
ment, University of Göttingen, Germany, 1993.
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