Tandem intermolecular-intramolecular carbolithiation: Application to the synthesis of silacyclopentanes

Article abstract of DOI:10.1016/S0040-4039(03)01843-4

Silacyclopentanes have been prepared from vinyl(homoallyl)silanes or vinyl(homopropargyl)silanes and organolithium reagents by a tandem intermolecular-intramolecular sequence involving a 5-exo cyclisation process. The unexpected stereochemical outcome of the sequence involving a 5-exo-dig cyclisation is rationalised.

Full text of DOI:10.1016/S0040-4039(03)01843-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7143–7146
Tandem intermolecular–intramolecular carbolithiation:
application to the synthesis of silacyclopentanes
Xudong Wei*,† and Richard J. K. Taylor*
Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
Received 9 June 2003; accepted 25 July 2003
Abstract—Silacyclopentanes have been prepared from vinyl(homoallyl)silanes or vinyl(homopropargyl)silanes and organolithium
reagents by a tandem intermolecular–intramolecular sequence involving a 5-exo cyclisation process. The unexpected stereochem-
ical outcome of the sequence involving a 5-exo-dig cyclisation is rationalised.
© 2003 Elsevier Ltd. All rights reserved.
Organosilicon compounds have received much interest
in view of their versatility in organic transformations
and their unique physical properties.1 Silacyclic com-
pounds, in which a silicon atom is embedded in a ring
system, are useful synthetic building blocks as well as
being interesting materials in their own right. Syntheses
and reactions of five- and six-membered siliconꢀcarbon
heterocycles have been comprehensively reviewed.2 We
have recently studied organolithium addition reactions
to styrenes and other activated alkenes including vinyl
silanes.3 As part of this programme we studied tandem
processes such as the tandem intermolecular–
Scheme 2.
intramolecular carbolithiation route to tetralins involv-
ing a 6-exo-cyclisation (Scheme 1).3b
Substrates 1a–d (Scheme 3) were designed to facilitate
the planned tandem intermolecular–intramolecular car-
bolithiation sequence in that:
(i) vinylsilanes are known to be good substrates for
intermolecular organolithium addition5 giving
anionic adducts stabilised by an adjacent silicon
group,6
We now report that similar tandem intermolecular–
intramolecular organolithium methodology can be
utilised to convert vinyl silanes 1 into silacyclopentanes
4 as outlined in Scheme 2; in this sequence, the key
intramolecular cyclisation (2“3) is of the well-
precedented3b,4 5-exo-type.
Scheme 1.
* Corresponding authors. E-mail: rjkt1@york.ac.uk
† Present address: Boehringer-Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01843-4

7144
X. Wei, R. J. K. Taylor / Tetrahedron Letters 44 (2003) 7143–7146
Scheme 3.
(ii) the presence of terminal phenyl or trimethylsilyl
t-butyllithium. Interestingly, COSY and NOE studies
indicated that these products derived from 5-exo-dig
cyclisation were formed predominantly as the Z-iso-
mers (entries iii–vi). Given the fast isomerisation of
phenyl- and trimethylsilyl-stabilised vinyl anions10 we
speculate that the ether-coordinated lithium atom may
have a greater steric demand than the trimethylsilyl
or phenyl groups. The variation of Z:E ratio over 4c,
4ct, 4d and 4dt certainly gives credence to this pro-
posal as going from the relatively sterically unde-
manding n-butyl/phenyl combination of substituents
through t-butyl/phenyl and n-butyl/trimethylsilyl to
the challenging t-butyl/trimethylsilyl arrangement, the
Z:E ratios increase from 3:1 to 10:1 to 19:1 to 24:1.
This process is illustrated in Scheme 4. Possibly due
to the steric hindrance between the t-butyl and
trimethylsilyl groups, the exocyclic vinyl compound
4dt slowly isomerised to the more stable silacyclopen-
tene 6 on standing at room temperature for 24 h
(Scheme 4).
substitutents on the pendant alkene/alkyne unit
should facilitate anionic cyclisation because of their
known anion stabilising ability.3e
The starting vinyl silanes 1a–e were successfully pre-
pared in moderate yields by the addition of commer-
cially available chloro(diphenyl)vinylsilane to a freshly
prepared solution of homoallyl- or homopropargyl-
lithium reagents 5a–e in diethyl ether at −78°C and
slowly warming the reaction mixture to room temper-
ature (rt) as shown in Scheme 3.7 The organolithium
reagents 5 were prepared from the corresponding
organo-iodides by lithium–halogen exchange at −78°C
using the Negishi/Bailey method.8
The reactions of the above vinylsilanes 1a–d with
organolithium reagents were explored at different
temperatures. Although reactions at temperatures
lower than 0°C were very sluggish, the desired
tandem reactions went smoothly (20–60 min) in
diethyl ether at room temperature giving the desired
silacyclopentanes 4 in good to excellent yields (62–
81%) as shown in Table 1.7,9
Finally, we established the importance of having an
activated receptor group containing an anion-stabilis-
ing substituent (Table, entry vii). When the ethyl sub-
stituted alkyne 1e was treated with n-butyllithium in
diethyl ether, no cyclisation to give a silacyclopentane
was observed and the major isolated product was the
simple n-butyllithium adduct 7.
It is noteworthy that the intermolecular organolithium
addition step is regioselective for the vinylsilane
group: addition of butyllithium to the remote disub-
stituted alkene or alkyne group was not observed in
any of the examples.
In summary, we have shown that organolithium addi-
tion to vinylsilanes can be coupled with a subsequent
intramolecular 5-exo-cyclisation to generate silacy-
clopentanes in good yields. In the case of the 5-exo-
dig cyclisation of homopropargyl silanes, the products
were obtained mainly as the Z-isomers which are
difficult to obtain by other procedures. The method-
ology is versatile in that by varying the structure of
the organolithium reagents, the vinylsilanes and the
quenching electrophiles, a wide range of substituted
silacyclopentanes should be available.
For reactions of the homoallyl vinylsilanes 1a,b, sila-
cyclopentanes 4a,b were obtained in good yield with
both phenyl and trimethylsilyl substituted starting
materials (entries i and ii). In each case, as expected,
the trans-isomeric products predominated based on
NOE experiments.
Reactions of the activated homopropargyl vinylsilanes
1c,d were equally effective, giving the expected prod-
ucts 4c,d (entries iii–vi) with both n-butyllithium and

X. Wei, R. J. K. Taylor / Tetrahedron Letters 44 (2003) 7143–7146
Table 1. Tandem intermolecular–intramolecular carbolithiation of 1a–ea
7145
Scheme 4.

7146
X. Wei, R. J. K. Taylor / Tetrahedron Letters 44 (2003) 7143–7146
5404–5406; (b) Negishi, E.-i.; Swanson, D. R.; Rousset,
References
C. J. J. Org. Chem. 1990, 55, 5406–5409.
1. For a thematic issue on silicon chemistry, see: Chem. Rev.
1995, 95, 1135–1673.
2. (a) Hermanns, J.; Schmidt, B. J. Chem. Soc., Perkin
Trans. 1 1998, 2209–2230; (b) Hermanns, J.; Schmidt, B.
J. Chem. Soc., Perkin Trans. 1 1999, 81–102.
3. (a) Wei, X.; Taylor, R. J. K. Chem. Commun. 1996,
187–188; (b) Wei, X.; Taylor, R. J. K. Tetrahedron Lett.
1997, 38, 6467–6470; (c) Wei, X.; Taylor, R. J. K. Tetra-
hedron: Asymmetry 1997, 8, 665–668; (d) Wei, X.; John-
son, P.; Taylor, R. J. K. J. Chem. Soc., Perkin Trans. 1
2000, 1109–1116; (e) Wei, X.; Taylor, R. J. K. Angew.
Chem., Int. Ed. 2000, 39, 409–412.
4. (a) Bailey, W. F.; Carson, M. W. J. Org. Chem. 1998, 63,
9960–9967; (b) Bailey, W. F.; Daskapan, T.; Rampali, S.
J. Org. Chem. 2003, 68, 1334–1338 and references cited
therein.
5. (a) Soderquist, J. A.; Rivera, I.; Negron, A. J. Org.
Chem. 1989, 54, 4051–4055; (b) Cerveau, G.; Chuit, C.;
Corriu, R. J. P.; Nayyar, A. K.; Reye, C. J. Organomet.
Chem. 1990, 389, 159–168 and references cited therein.
6. (a) Fleming, I. Chem. Soc. Rev. 1981, 10, 83–111; (b) van
Staden, L. F.; Gravestock, D.; Ager, D. J. Chem. Soc.
Rev. 2002, 31, 195–200.
7. All novel compounds were fully characterised (including
by high field 1H and 13C NMR spectroscopy and high-
resolution mass spectrometry).
9. General procedure for the synthesis of silacyclopentanes 4:
n-Butyllithium (0.14 mL, 1.6 M solution in hexanes,
0.225 mmol) was added to a solution of vinylsilane 1
(0.15 mmol) in dry diethyl ether (8 mL) at rt over 5 min.
The reaction mixture was stirred for 20 min and then
quenched with water (5 mL). The organic layer was
washed with water (8 mL) and dried over sodium sul-
phate. After removal of solvent in vacuo the residue was
purified by column chromatography on silica gel
(petroleum ether–dichloromethane, 20:1). Data for 4d:
obtained as a colourless oil (Z:E=19:1 by NMR spec-
troscopy), 81%, Rf 0.40 (petroleum ether–CH2Cl2, 10:1),
IR (neat): 3068, 2953, 1606, 1598, 1428, 1247, 1112, 837,
699 cm−1; lH (300 MHz, CDCl3) Z-isomer: 0.08 (9H, s,
Me3Si), 0.74 (3H, t, J=6.5 Hz, CH3), 0.85–1.54 (10H, m,
4×CH2 and CH2Si), 2.27 (1H, t, J=6.5 Hz, CH), 2.44–
2.57 (1H, m, CHaHbCꢁCH), 2.70–2.85 (1H, m,
CHaHbCꢁCH), 5.31 (1H, s, ꢁCHSi), 7.31–7.44 (6H, m,
Ph), 7.54–7.61 (4H, m, Ph); lC (75 MHz, CDCl3) Z-iso-
mer: 0.5, 9.5, 13.9, 22.3, 29.2, 31.9, 32.0, 33.4, 37.1, 121.9,
127.7, 127.8, 129.3, 129.5, 134.2, 134.9, 135.5, 136.3,
165.8; MS (EI): 392 (M+, 22%), 377 (7), 318 (8), 242 (65),
185 (65), 73 (100); HRMS (EI): 392.2354. Calcd for
C25H36Si2, 392.2356 (0.4 ppm error).
10. Bailey, W. F.; Ovaska, T. V. J. Am. Chem. Soc. 1993,
115, 3080–3090.
8. (a) Bailey, W. F.; Punzalan, E. R. J. Org. Chem. 1990, 55,