Shortened synthesis of a silicon-stereogenic cyclic silane

Article abstract of DOI:10.1055/s-0030-1259989

The previous racemic synthesis of a six-membered ring silane from tert-butyltrichlorosilane required six steps (22% overall yield). A considerably shortened reaction sequence now allows for its preparation from rarely used tert-butylsilane in only two ste

Full text of DOI:10.1055/s-0030-1259989

2062
PRACTICAL SYNTHETIC PROCEDURES
Shortened Synthesis of a Silicon-Stereogenic Cyclic Silane
S
ilicon-Stereogen
.
ic
S
ilane David F. Königs, Martin Oestreich*
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstr. 40, 48149 Münster, Germany
Fax +49(251)8336501; E-mail: martin.oestreich@uni-muenster.de
Received 2 March 2011; revised 22 March 2011
Dedicated to Professor Dieter Hoppe on the occasion of his 70th birthday
PSP
No202
Abstract: The previous racemic synthesis of a six-membered ring silane from tert-butyltrichlorosilane required six steps (22% overall
yield). A considerably shortened reaction sequence now allows for its preparation from rarely used tert-butylsilane in only two steps (42%
overall yield). The new access also offers more facile purification of the intermediate(s) and the target compound.
Key words: cyclization, Grignard reaction, hydrosilylation, nucleophilic substitution, silicon
previous approach
6 steps
22%
with t-BuSiCl3
Br
♦ stereoselective silicon–oxygen coupling
♦ silicon-to-carbon chirality transfer
♦ stereochemical probe in reaction mechanisms
Si
Si
Br
H
t-Bu
H
t-Bu
(SiR)-2
1
rac-2
chiral silicon
reagent
new approach
with t-BuSiH3
2 steps
42%
Scheme 1 From six steps to only two: a shortened route to a tert-butyl-substituted six-membered-ring silane
week to prepare gram quantities of 2. We were, therefore,
particularly intrigued by a recent contribution by the
Introduction
Our laboratory had introduced a family of silicon-stereo- Urabe group,12 showing that such cyclic silanes are acces-
genic cyclic silanes bearing a tert-butyl or isopropyl group sible from phenylsilane by a one-pot nucleophilic silicon
at the silicon atom.1 The rigidity imparted by the cyclic substitution–intramolecular alkene hydrosilylation se-
skeleton and the steric demand around the silicon atom quence. In relation to our particular purposes, rarely used
rendered these silanes useful chiral reagents in palladi- tert-butylsilane13 would be the requisite silicon precursor.
um(II)-catalyzed alkene hydrosilylation2 (chirality trans- We describe herein the Urabe protocol applied to a scal-
fer from silicon to carbon) as well as copper(I)-3 and able synthesis of our silicon-stereogenic silane 2 in four
rhodium(I)-catalyzed4 silicon–oxygen couplings (kinetic steps fewer than the previous one.
resolution of alcohols). We were also able to employ these
silanes as stereochemical probes to give additional insight
into the mechanism of transition metal5 and Lewis acid6
Silane Syntheses
catalyses. This recent progress7 has brought a unique twist
to the neglected synthetic chemistry of chiral silicon com- Our previous synthesis of rac-2 (Scheme 2) starts with
pounds.8
benzyl bromide 1, prepared from 3 by conventional radi-
cal bromination. The homologation (1 → 5)10a is achieved
by Meyers’ two-carbon chain elongation14 (1 → 4) and a
sequence consisting of hydrolysis, carboxy reduction, and
alcohol bromination (4 → 5).
The tert-butyl-substituted six-membered-ring silane 2 had
emerged as privileged, producing high diastereo- and, if
applicable, enantioselectivities. Our routine approach
(Scheme 1) to access 29 and related silanes10 in racemic
form is based on a seminal route established by the Reaction of 5 (purified by distillation) and tert-butyl-
Gilman group.11 It requires six steps from commercially trichlorosilane under Barbier conditions affords a mixture
available tert-butyltrichlorosilane, usually taking almost a of cyclic chloro- and bromosilanes. Direct treatment with
excess lithium aluminum hydride then yields rac-2 (5 →
2).9 Purification by distillation is again favored over flash
chromatography on a multigram scale. The target com-
pound is isolated in 22% yield after six steps from 1.
SYNTHESIS 2011, No. 13, pp 2062–2065
Advanced online publication: 05.04.2011
DOI: 10.1055/s-0030-1259989; Art ID: T24111SS
x
x.
x
x
.
2
0
1
1
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Silicon-Stereogenic Silane
2063
O
MgBr (1.1 equiv)
CuI (10 mol%)
Br
N
2,2'-bipyridine (10 mol%)
Br
NBS
(1.0 equiv)
DBPO
Br
toluene
–78 °C
(1.0 equiv)
n-BuLi
O
Br
(1.0 mol%)
(1.2 equiv)
Br
N
Br
1
8: 66%
(1.2 equiv)
Br
CCl4
Δ
THF
–78 °C → r.t.
1)
YCl3 (28 mol%)
MeLi (18 mol%)
THF, r.t.
3
1: 82%
4
Mg
(10 equiv)
MgBr
Si
H
t-Bu
2) t-BuSiH3
(1.0 equiv)
THF, Δ
THF
r.t.
1) Mg, THF, Δ
2) t-BuSiCl3
(1.0 equiv)
THF, Δ
1) 3 M HCl, Δ
2) LiAlH4
(1.5 equiv)
Et2O, Δ
Br
Br
rac-2: 65% (4.2 mmol)
42% from 1 (2 steps)
rac-2: 56% (21 mmol)
37% from 1 (2 steps)
Si
H
3) PBr3
(0.75 equiv)
Δ
3) LiAlH4
(1.8 equiv)
THF, Δ
t-Bu
5
rac-2:
22% from 1
Scheme 4 New preparation of silane rac-2
(6 steps)
Cyclization precursor 8 nicely transformed into the
Grignard compound, and we were pleased to find that its
reaction with tert-butylsilane in the presence of sub-
stoichiometric amounts of yttrium(III) chloride and meth-
yllithium produced cyclic silane rac-2 in 65% (small
scale) and 56% (large scale) isolated yields, respectively
(Scheme 4). Only trace amounts (£ 5%) of the acyclic si-
lane 9 (cf. Scheme 5) with the unreacted double bond
were detected.
Scheme 2 Previous preparation of silane rac-2
As indicated above, the Urabe group reported a one-step
assembly of our cyclic silane motif.12 The preformed
Grignard compound of 6 and phenylsilane were heated at
reflux in the presence of an yttrium(III) chloride–methyl-
lithium combination to yield rac-7 (Scheme 3). A salt
metathesis liberates lithium chloride which, in turn, is as-
sumed to mediate the nucleophilic displacement at the sil-
icon atom (hydride as leaving group), followed by an
unusual yttrium(III)-catalyzed intramolecular hydro-
silylation15 with preferential endo regioselectivity.
The identification of 9 as a minor impurity prompted us to
briefly examine the order of bond-forming events
(Scheme 5). Urabe et al. had proposed that the nucleo-
philic substitution occurs prior to the intramolecular hy-
drosilylation.12 Part of the reasoning was the fact that
yttrium(III) chloride–methyllithium is not a good catalyt-
ic system for intermolecular hydrosilylation,15 and that
was indeed confirmed by us in a separate experiment with
tert-butylsilane and 8 (no reaction). We were able to inde-
pendently prepare a sample of 9 (8 → 9, Scheme 5), the
supposed intermediate of 8 → 2 (Scheme 4). That trans-
formation suggests that lithium chloride is not necessarily
required in the substitution step.17 We were then surprised
to see that 9 was inert, not undergoing the ring closure 9
→ 2 with the yttrium(III) chloride–methyllithium additive
(Scheme 5). It is now obvious that the one-pot addition–
cyclization is mechanistically more complex than initially
thought.12
1) Mg
2) YCl3 (30 mol%)
MeLi (18 mol%)
THF, r.t.
Br
Si
H
Ph
3) PhSiH3 (1.0 equiv)
THF, Δ
MeO
MeO
OMe
OMe
6
rac-7: 65%
Scheme 3 Urabe’s preparation of cyclic silane rac-7
This procedure would also provide an access to silane rac-
2 by using tert-butylsilane instead of phenylsilane. Steri-
cally hindered silanes were, however, not included in the
Urabe paper.12 Moreover, there are only few examples of
synthetic applications of tert-butylsilane in the literature,
presumably due to its low boiling point of 32 °C. Con-
versely, we found tert-butylsilane to be an easy-to-handle
liquid that could be stored as a solution in tetrahydrofuran
at –18 °C for several months. According to a protocol re-
ported by Märkl et al.,13 tert-butylsilane distilled from a
suspension of lithium aluminum hydride in high-boiling
bis(2-methoxymethyl) ether upon addition of tert-butyl-
trichlorosilane. The precursor of the Grignard compound
was prepared by copper(I)-catalyzed vinylation of the cor-
responding benzyl bromide (1 → 8, Scheme 4).16
YCl3
(30 mol%)
MeLi
(18 mol%)
1)
Mg
(6.0 equiv)
THF, r.t.
H
Br
Si
Si
H
t-Bu
H
2) t-BuSiH3
(1.0 equiv)
THF, Δ
t-Bu
THF
Δ
rac-2
8
9: 56%
Scheme 5 Investigation into the order of bond-forming events
Synthesis 2011, No. 13, 2062–2065 © Thieme Stuttgart · New York

2064
C. D. F. Königs, M. Oestreich
PRACTICAL SYNTHETIC PROCEDURES
rac-1-tert-Butyl-1-silatetralin (rac-2)
Summary
A 2-necked 250-mL flask equipped with a reflux condenser and a
pressure-equalizing dropping funnel was charged with Mg turnings
(9.00 g, 370 mmol, 10.0 equiv). Thermal activation by flame-drying
was followed by addition of THF (50 mL) and 1,2-dibromoethane
(0.1 mL). A soln of 1-allyl-2-bromobenzene (8, 7.27 g, 36.9 mmol)
in THF (15 mL) was then slowly added, maintaining a gentle reflux.
The thus-obtained Grignard reagent (0.48 M in THF) was stirred at
r.t. for a further 1 h. Under an inert atmosphere, a 250-mL Schlenk
flask was charged with YCl3 (1.17 g, 5.97 mmol, 28.3 mol%) in
THF (60 mL), and 1.6 M MeLi in Et2O (2.40 mL, 3.84 mmol, 18.2
mol%) was added to this suspension at r.t. The mixture was stirred
at this temperature for 20 min, and then the freshly prepared soln of
the Grignard of 8 (44.0 mL, 21.1 mmol) was added. Subsequently,
0.98 M t-BuSiH3 in THF (22.0 mL, 21.6 mmol, 1.02 equiv) was
added. The Schlenk flask was then equipped with a flame-dried re-
flux condenser, and the mixture was heated at reflux for 3.5 h. The
reaction was quenched after cooling to r.t. by addition of sat. aq
NH4Cl (50 mL) and filtered through a pad of Celite which was
washed with t-BuOMe. After extraction with t-BuOMe (3 × 20
mL), the combined organic layers were washed with brine (30 mL)
and dried (Na2SO4). Evaporation of the solvents under reduced
pressure and purification by flash chromatography (silica gel, cy-
clohexane) afforded the analytically pure product rac-2 (2.40 g,
11.7 mmol, 56%) as a colorless liquid; Rf = 0.69 (cyclohexane).
We showed that the Urabe protocol is applicable to the
synthesis of a tert-butyl-substituted cyclic silane. The use
of tert-butylsilane is neither problematic nor inconve-
nient. The new reaction sequence is four steps shorter than
the previous six-step route that our laboratory had used for
a number of years.1–6,9 With this simplified method at
hand, the chemistry of readily available silicon-stereogen-
ic silane 2 might become more attractive.
All reactions were performed in flame-dried glassware using
Schlenk techniques under a static pressure of argon. Liquids or so-
lutions were transferred either with syringes or cannulas. Solvents
were purified and dried following standard procedures [THF, tolu-
ene, bis(2-methoxymethyl) ether]. Technical grade solvents for ex-
traction or chromatography (cyclohexane, EtOAc, t-BuOMe) were
distilled before use. t-BuSiCl318 and 1-bromo-2-(bromomethyl)ben-
zene (1)10a were prepared according to reported procedures. Analyt-
ical TLC was performed on silica gel SIL G-25 glass plates from
Macherey-Nagel and flash chromatography on silica gel 60 (40–63
mm, 230–400 mesh, ASTM) by Merck using the indicated solvents.
1H, 13C, and 29Si NMR spectra were recorded in CDCl3 on Bruker
AV 300 and Bruker AV 400 instruments. IR spectra were recorded
on a Varian 3100 FT-IR spectrophotometer equipped with an ATR
unit. Mass spectral data as well as elemental analyses were obtained
from the Analytical Facility at the Organisch-Chemisches Institut of
the Westfälische Wilhelms-Universität Münster.
IR (ATR) = 3056 (w), 3000 (w), 2950 (w), 2926 (s), 2855 (s), 2103
(s), 1592 (w), 1470 (m), 1462 (m), 1437 (m), 1361 (m), 823 (s), 801
(s), 746 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 0.86–0.97 (m, 1 H), 1.03 (s, 9 H),
1.10–1.22 (m, 1 H), 1.79 (mc, 1 H), 1.99–2.20 (m, 1 H), 2.26–2.78
(m, 2 H), 4.19 (dd, J = 3.7, 3.7 Hz, 1 H, SiH), 7.14 (d, J = 7.5 Hz, 1
H), 7.21 (dd, J = 7.0, 7.0 Hz, 1 H), 7.28 (ddd, J = 7.4, 7.4, 1.6 Hz, 1
H), 7.56 (dd, J = 7.2, 1.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 6.6, 17.2, 23.1, 27.1, 35.5, 125.2,
128.8, 129.2, 130.3, 136.1, 149.9.
29Si NMR (60 MHz, CDCl3): d = –13.3.
tert-Butylsilane (1 M in THF)
LiAlH4 (5.10 g, 0.135 mol, 1.75 equiv) was suspended in bis(2-
methoxymethyl) ether (50 mL) in a 2-necked 100-mL flask con-
nected to a distillation apparatus and equipped with a pressure-
equalizing dropping funnel. A soln of t-BuSiCl3 (15.0 g, 77.0
mmol) in bis(2-methoxymethyl) ether (14 mL) was carefully added
to this suspension. Immediately formed t-BuSiH3 began to distill
over during the addition (bp 32 °C). The mixture was then warmed
to 50 °C until complete distillation of t-BuSiH3. The title compound
was obtained as a volatile colorless liquid (3.60 g, 40.8 mmol,
54%)13 and stored at –18 °C as a soln in THF (42 mL, 0.98 M).
Anal. Calcd for C13H20Si (204.39): C, 76.40; H, 9.86; Found: C,
76.02; H, 9.61.
(2-Allylphenyl)tert-butylsilane (9)
Mg turnings (0.75 g, 31 mmol, 5.9 equiv) were thermally and me-
chanically activated by flame-drying and vigorous stirring in a 2-
necked 50-mL flask equipped with a reflux condenser and a pres-
sure-equalizing dropping funnel. After further activation with 3
drops of 1,2-dibromoethane in THF (10 mL), a soln of 1-allyl-2-
bromobenzene (8, 1.0 g, 5.2 mmol) in THF (4 mL) was slowly add-
ed, maintaining a gentle reflux. The mixture was stirred for a further
1 h and then transferred into a sealed tube with a syringe. A 0.98 M
soln of t-BuSiH3 in THF (5.5 mL, 5.4 mmol, 1.0 equiv) was added
and the mixture was heated at 85 °C for 24 h. The reaction was
quenched after cooling to r.t. by addition of sat. aq NH4Cl (10 mL).
After extraction with t-BuOMe (3 × 15 mL), the combined organic
layers were washed with brine (10 mL) and dried (Na2SO4). Evap-
oration of the solvents under reduced pressure and purification by
flash chromatography (silica gel, cyclohexane) afforded 9 (0.60 g,
2.9 mmol, 56%) as a colorless liquid; Rf = 0.69 (cyclohexane).
1-Allyl-2-bromobenzene (8)
In a 250-mL Schlenk flask, 0.81 M vinylmagnesium bromide in
THF (29 mL, 23 mmol, 1.1 equiv) was added to a suspension of 1-
bromo-2-(bromomethyl)benzene (1, 5.3 g, 21 mmol), CuI (0.40 g,
2.1 mmol, 10 mol%), and 2,2¢-bipyridine (0.33 g, 2.1 mmol, 10
mol%) in toluene (50 mL) at –78 °C. The dark mixture was allowed
to slowly warm to r.t. and was then maintained at this temperature
overnight. The reaction was quenched with sat. aq NH4Cl (30 mL)
and extracted with t-BuOMe (3 × 30 mL). The combined organic
layers were washed with brine (20 mL) and dried (Na2SO4). After
removal of the solvents under reduced pressure, the residue was pu-
rified by flash chromatography (silica gel, cyclohexane–EtOAc,
100:1), affording 8 (2.7 g, 14 mmol, 66%) as a colorless liquid; Rf =
0.62 (cyclohexane).
1H NMR (400 MHz, CDCl3): d = 3.52 (ddd, J = 6.5, 1.4, 1.4 Hz, 2
H), 5.06–5.16 (m, 2 H), 5.98 (ddt, J = 16.7, 10.1, 6.5 Hz, 1 H), 7.03–
7.16 (m, 1 H), 7.17–7.35 (m, 2 H), 7.43–7.69 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 40.3, 116.6, 124.6, 127.6, 127.9,
130.5, 132.8, 135.6, 139.5.
IR (ATR) = 3059 (w), 3004 (w), 2950 (m), 2927 (m), 2856 (m),
2129 (s), 1638 (w), 1589 (w), 1470 (m), 1432 (m), 1362 (w), 1127
(w), 1010 (w), 992 (w), 940 (s), 914 (m), 842 (s), 822 (s), 752 (m),
735 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.03 (s, 9 H), 3.54 (br d, J = 6.5
Hz, 2 H), 4.24 (s, 2 H, SiH2), 5.00–5.10 (m, 2 H), 5.97 (ddt, J = 16.7,
10.1, 6.5 Hz, 1 H), 7.17–7.21 (m, 1 H), 7.23 (d, J = 7.8 Hz, 1 H),
7.36 (ddd, J = 7.6, 7.6, 1.5 Hz, 1 H), 7.53 (dd, J = 7.4, 1.2 Hz, 1 H).
HRMS (EI): m/z [M]+ calcd for C9H9Br: 197.9868; found:
197.9840.
Synthesis 2011, No. 13, 2062–2065 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Silicon-Stereogenic Silane
2065
13C NMR (75 MHz, CDCl3): d = 17.2, 28.0, 41.0, 116.1, 125.4,
129.1, 130.2, 131.4, 137.6, 137.8, 146.2.
(4) Klare, H. F. T.; Oestreich, M. Angew. Chem. Int. Ed. 2007,
46, 9335.
(5) Rendler, S.; Oestreich, M.; Butts, C. P.; Lloyd-Jones, G. C.
J. Am. Chem. Soc. 2007, 129, 502.
(6) Rendler, S.; Oestreich, M. Angew. Chem. Int. Ed. 2008, 47,
5997.
29Si NMR (60 MHz, CDCl3): d = –19.4.
HRMS (EI): m/z [M]+ calcd for C13H20Si: 204.1334; found:
204.1297.
(7) For a recent summary, see: Xu, L.-W.; Li, L.; Lai, G.-Q.;
Jiang, J.-X. Chem. Soc. Rev. 2011, 40, 1777.
(8) For authoritative summaries, see: (a) Sommer, L. H.
Stereochemistry, Mechanism and Silicon; McGraw-Hill:
New York, 1965. (b) Sommer, L. H. Intra-Sci. Chem. Rep.
1973, 7, 1. (c) Corriu, R. J. P.; Guerin, C. Adv. Organomet.
Chem. 1982, 20, 265. (d) Corriu, R. J. P.; Guerin, C.;
Moreau, J. J. E. Top. Stereochem. 1984, 15, 43.
(9) Rendler, S.; Auer, G.; Keller, M.; Oestreich, M. Adv. Synth.
Catal. 2006, 348, 1171.
Anal. Calcd for C13H20Si (204.39): C, 76.40; H, 9.86; Found: C,
76.02; H, 9.86.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
C.D.F.K. thanks the International Research Training Group
Münster–Nagoya (GRK 1143 of the Deutsche Forschungsgemein-
schaft) for a predoctoral fellowship (2011–2012).
(10) (a) Oestreich, M.; Schmid, U. K.; Auer, G.; Keller, M.
Synthesis 2003, 2725. (b) Oestreich, M.; Auer, G.; Keller,
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(11) (a) Gilman, H.; Marrs, O. L. J. Org. Chem. 1964, 29, 3175.
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(13) Märkl, G.; Höllriegel, H.; Schlosser, W. J. Organomet.
Chem. 1984, 260, 129.
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Synthesis 2011, No. 13, 2062–2065 © Thieme Stuttgart · New York