Silylzincation of carbon-carbon multiple bonds revisited

Article abstract of DOI:10.1039/b513528a

The first investigation of the copper-catalyzed silylzincation of alkynes as well as a diene and styrene using bis(triorganosilyl) zinc reagents led to the development of an efficient procedure and the disclosure of an unexpected bissilylation and unfores

Full text of DOI:10.1039/b513528a

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Silylzincation of carbon–carbon multiple bonds revisited
Gertrud Auer and Martin Oestreich*
Received (in Cambridge, UK) 23rd September 2005, Accepted 28th October 2005
First published as an Advance Article on the web 22nd November 2005
DOI: 10.1039/b513528a
of terminal triple bonds and, importantly, a regioselective
The first investigation of the copper-catalyzed silylzincation of
alkynes as well as a diene and styrene using bis(triorganosilyl)
zinc reagents led to the development of an efficient procedure
and the disclosure of an unexpected bissilylation and unfore-
seen regioselectivity.
silylzincation of non-symmetric triple bonds. Moreover, installa-
tion of a heteroatom-substituted silyl group serves as a linchpin for
subsequent cross-coupling reactions, thereby enabling the synthesis
of trisubstituted alkenes with defined double bond geometry.
Our investigation commenced with the silylzincation of
symmetric internal alkynes using (Me2PhSi)2Zn (3a)9,10 in the
presence of catalytic amounts of CuI (Scheme 2). Both bisarylated
4 and bisalkylated 5 performed equally well affording 7a and 8a,
respectively in high yield whereas the bissilylated alkyne 6 emerged
as inert not forming 9a under these standard reaction conditions.
A control experiment proved that 3a alone does not effect
silylzincation of internal alkynes. We routinely used 5.0 mol% of
the copper catalyst but 1.0 mol% was also sufficient. It must be
noted that, unless otherwise indicated, all reactions were conducted
with equimolar amounts of alkyne and zinc reagent.
Regiocontrolled addition of a silicon–metal bond across a carbon–
carbon triple bond is a prevalent method for the preparation of
stereodefined vinylic silanes.1 In this regard, stoichiometric
silylcupration [(R3Si)2CuLi?LiCN] of terminal as well as symmetric
internal alkynes has already been investigated by Fleming et al. to
considerable extent.2–4 Interestingly, a competitive silylmagnesa-
tion catalytic in copper [R3SiMgMe with CuI (5.0 mol%)] was
subsequently elaborated by Oshima et al., yet attracted somewhat
less attention.5,6 Almost simultaneously,
a copper-catalyzed
silylzincation of alkynes using (mixed) zincates [R3SiZnR2Li or
(R3Si)3ZnLi with CuCN (1.0 mol%)] originated from the same
laboratories.7 In all these transformations, regioselective silylme-
talation of terminal and internal non-symmetric triple bonds was
mostly realized for specific substrates often employing sterically
hindered reagents. This issue has recently been successfully
addressed by Uchiyama et al. in the silylzincation of terminal
alkynes using dianion-type zincates [R3SiZnR(OR)2Mg2Cl] in the
absence of any transition metal catalyst.8
Based on a report by Oshima et al.,9 we have established the
copper-catalyzed chemistry of bis(triorganosilyl) zincs as moder-
ately nucleophilic silicon sources [(R3Si)2Zn with CuI (5.0 mol%)].10
These reagents are conveniently accessed by reductive lithiation of
silyl chlorides (1 A 2)11 followed by transmetalation (2 A 3)9,10
(Scheme 1).{In this communication, we report the extension of this
reagent–copper catalyst combination to the silylzincation of
carbon–carbon multiple bonds with particular focus on alkynes.
Within our study, we have disclosed an unexpected bissilylation
We then examined the silylcupration of terminal alkynes 10–13
(Table 1). Using (Me2PhSi)2Zn (3a), phenylacetylene (10) gave the
expected linear regioisomer 14a (Table 1, Entry 1) while, under
identical reaction conditions, 1-hexyne (11) produced a mixture of
linear and branched 15a with opposite regioselectivity (Table 1,
Entry 2). Remarkably, this result provides a rough picture of
the catalytically active copper intermediate: In a related situation
using pre-formed cuprates, Fleming et al. showed that
(Me2PhSi)2CuLi?LiCN selectively favours the linear isomer (rs =
100 : 0) while Me2PhSiCu?LiCN favours the branched isomer with
moderate selectivity (rs = 25 : 75).2a,b We believe that these
observations imply the intermediacy of
a monosilylcopper
compound such as Me2PhSiCu?ZnX2 (X = Me2PhSi ,Cl, and/or
I). The strong influence of reaction temperature on yield and
regioselectivity, partially due to competing deprotonation, still
remains unclear (Table 1, Entries 3–5).2
The regioselectivity of the silylcupration of terminal alkynes
might be steered towards the linear isomer by employing
silylmetals bearing the sterically demanding t-BuPh2Si group.3b
Accordingly, (t-BuPh2Si)2Zn (3b) and catalytic amounts of CuI
facilitated the silylzincation of 10–13 with good to excellent
regioselectivities (Table 1, Entries 6–9). Conversely, functionalized
[(Et2N)Ph2Si]2Zn (3c) failed to undergo the silylzincation with
reasonable regiocontrol and useful yields (35–50%).12
Scheme 1 Preparation of bis(triorganosilyl) zinc reagents.
Institut fu¨r Organische Chemie und Biochemie,
Albert-Ludwigs-Universita¨t, Albertstrasse 21, D-79104 Freiburg im
Breisgau, Germany.
E-mail: martin.oestreich@orgmail.chemie.uni-freiburg.de;
Fax: +49 (0)761 203-6100; Tel: +49 (0)761 203-6020
Scheme 2 Copper-catalyzed silylzincation of symmetric internal alkynes.
Chem. Commun., 2006, 311–313 | 311
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Table 1 Copper-catalyzed silylzincation of terminal alkynes
Alkyne
Entry 10–13
Zinc
Product
Yield
(%)b
R
reagent T/uC 14–17
rsa
1
2
3
4
5
6
7
8
9
a
10
11
11
11
11
10
11
12
13
Ph
Bu
Bu
Bu
Bu
Ph
Bu
3a
3a
3a
3a
3a
3b
3b
0
0
14a
15a
.98 : 2 95
25 : 75 50
78 : 22 85
22 : 78 65
10 : 90 70
.98 : 2 90
250 15a
278 15a
2100 15a
0
0
0
0
14b
15b
16b
17b
95 : 5
86 : 14 95
94 : 6 95
85
CH2OH 3b
CH2OBn 3b
Ratio of regioisomers was determined from the 1H NMR spectra
by integration of baseline-separated resonance signals prior to
purification. Averaged yield (two or more runs) of product after
b
Scheme 5 Unforeseen regiocontrol for non-symmetric internal alkynes.
purification by flash chromatography and/or Kugelrohr distillation
in order to remove traces of R3Si–H and R3Si–SiR.
silylzincation of silicon-substituted internal alkynes (22 A (E)-19a,
Scheme 4) complement each other nicely.
Finally, we targeted the demanding silylzincation of non-
symmetric internal alkynes. These silylmetalations normally
proceed without any regiocontrol15,16 and, therefore, these
substrates have been almost invariably omitted in previous
studies.2–4 Not unexpectedly, 25 and 26 reacted unselectively with
(Me2PhSi)2Zn (3a) at 278 uC and 0 uC and (t-BuPh2Si)2Zn (3b)
was too unreactive (Scheme 5).
To our surprise, when performing the silylcupration of 10 and
11 at ambient temperature, we isolated the bissilylated alkenes (Z)-
18a and (Z)-19a in minor quantities (Scheme 3). Increasing the
amount of (Me2PhSi)2Zn (3a) to 2.5–3.0 equiv. led to smooth
bissilylation accompanied by formation of elementary zinc. Initial
silylmetalation followed by reductive elimination with carbon–
silicon coupling is well-precedented for manganese-based silicon
reagents [(R3Si)3MnMgMe].13,14
To our great delight, zinc reagent 3c incorporating an amino-
substituted silyl group cleanly added across the internal triple bond
(25 A 27c and 26 A 28c). After treatment with dry ethanol and
solid NH4Cl,12 the alkoxy-substituted vinylic silanes 27d and 28d,
respectively were obtained with substantial regioselectivity (rs =
92 : 8) and in excellent yield.{
We were pleased to find that copper-catalyzed silylzincation of
silicon-substituted non-symmetric alkynes 20–22 proceeded highly
regioselectively with the less hindered (Me2PhSi)2Zn (3a)
(Scheme 4). As demonstrated for one pair of alkene diastereomers,
bissilylation of a terminal alkyne (11 A (Z)-19a, Scheme 3) and
Heteroatom-functionalized silicon moieties are predestined for
palladium-catalyzed cross-coupling reactions.17 Thus, 27d and 28d
were subjected to a standard Hiyama coupling protocol reported
by Tamao et al. (Scheme 6).18 Under these reaction conditions,
iodobenzene as well as 1-bromonaphthalene afforded the trisub-
stituted alkenes 29–32 as single diastereomers (E : Z . 99 : 1).
Based on recent reports by Liepins and Ba¨ckvall on the
stoichiometric silylcupration with Me2PhSiCu?LiCN of 1,3-
dienes19 and even styrenes,20 we tested our method for these
acceptors. Treatment of isoprene (33) with 3a under copper
Scheme 3 Copper-catalyzed bissilylation of terminal alkynes.
Scheme 4 Copper-catalyzed silylzincation of silicon-substituted non-
Scheme 6 Hiyama cross-coupling reaction of alkenyl alkoxysilanes.
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symmetric internal alkynes.
312 | Chem. Commun., 2006, 311–313

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t-butyl methyl ether (10 mL). The aqueous phase was separated and
extracted with t-butyl methyl ether (3 6 10 mL). The combined organic
phases were extracted with brine (10 mL) and dried over Na2SO4. The
solvents were evaporated under reduced pressure and the crude product
was purified by flash chromatography on silica gel initially using
cyclohexane and then cyclohexane : t-butyl methyl ether = 9 : 1 as eluent.
The title compound 27d along with its regioisomer (321 mg, rs = 92 : 8,
90%) was isolated as a pale yellow oil. Depending on conversion in the
reductive metalation step, trace amounts of [(EtO)Ph2Si]2 needed to be
removed by Kugelrohr distillation to obtain an analytically pure sample.
Scheme 7 Copper-catalyzed silylzincation of 1,3-dienes.
1 (a) A. Barbero and F. J. Pulido, Acc. Chem. Res., 2004, 37, 817–825; (b)
R. K. Dieter, in Modern Organocopper Chemistry, ed. N. Krause, Wiley-
VCH, Weinheim, 2002, pp. 79–144.
2 (a) I. Fleming and F. Roessler, J. Chem. Soc., Chem. Commun., 1980,
276–277; (b) I. Fleming, T. W. Newton and F. Roessler, J. Chem. Soc.,
Perkin Trans. 1, 1981, 2527–2532; (c) I. Fleming and E. Mart´ınez de
Marigorta, J. Chem. Soc., Perkin Trans. 1, 1999, 889–900.
3 For studies probing the steric demand at silicon, see: (a) H.-M. Chen
and J. P. Oliver, J. Organomet. Chem., 1986, 316, 255–260; (b)
A. Barbero, P. Cuadrado, I. Fleming, A. M. Gonza´lez, F. J. Pulido and
A. Sa´nchez, J. Chem. Soc., Perkin Trans. 1, 1995, 1525–1532.
4 For the silylcupration of functionalized alkynes, see: (a) L. Capella,
A. Degl’Innocenti, G. Reginato, A. Ricci and M. Taddei, J. Org. Chem.,
1989, 54, 1473–1476; (b) A. Casarini, B. Jousseaume, D. Lazzari,
E. Porciatti, G. Reginato, A. Ricci and G. Seconi, Synlett, 1992,
981–983; (c) L. Capella, A. Capperucci, G. Curotto, D. Lazzari,
P. Dembech, G. Reginato and A. Ricci, Tetrahedron Lett., 1993, 34,
3311–3314; (d) G. Reginato, A. Mordini, M. Valacchi and E. Grandini,
J. Org. Chem., 1999, 64, 9211–9216.
5 (a) H. Hayami, M. Sato, S. Kanemoto, Y. Morizawa, K. Oshima and
H. Nozaki, J. Am. Chem. Soc., 1983, 105, 4491–4492; (b) Y. Okuda,
Y. Morizawa, K. Oshima and H. Nozaki, Tetrahedron Lett., 1984, 25,
2483–2486.
6 V. Liepins, A. S. E. Karlstro¨m and J.-E. Ba¨ckvall, J. Org. Chem., 2002,
67, 2136–2143.
7 (a) Y. Okuda, K. Wakamatsu, W. Tu¨ckmantel, K. Oshima and
H. Nozaki, Tetrahedron Lett., 1985, 26, 4629–4632; (b) K. Wakamatsu,
T. Nonaka, Y. Okuda, W. Tu¨ckmantel, K. Oshima, K. Utimoto and
H. Nozaki, Tetrahedron, 1986, 42, 4427–4436.
8 S. Nakamura, M. Uchiyama and T. Ohwada, J. Am. Chem. Soc., 2004,
126, 11146–11147.
Scheme 8 Copper-catalyzed silylzincation of styrene.
catalysis formed the isomers 34a and 35a in a ratio of 85 : 15 and
in high yield (Scheme 7) which compares well with reported data.19
Similarly, copper-catalyzed silylzincation of styrene (36) gave
desired silane 37a with perfect regioselectivity (Scheme 8).
This experiment once more supports our previous hypothesis
(vide supra) that Me2PhSiCu?ZnX2 is the actual silyl transfer
reagent since, according to Liepins and Ba¨ckvall,20
(Me2PhSi)2CuLi?LiCN polymerizes the starting material 36.
In summary, we have presented a novel transition metal-
catalyzed silylmetalation of carbon–carbon multiple bonds. The
catalyst system (R3Si)2Zn (3) and catalytic amounts of CuI enables
smooth silylzincation not only of alkynes but also of 1,3-dienes
and styrenes; experimental evidence suggests the in-situ formation
of a R3SiCu species. Increasing the amount of zinc reagent 3 from
1.0 to 3.0 equiv. allows for the stereoselective bissilylation of
terminal alkynes. For the first time, we have successfully utilized
functionalized [(Et2N)Ph2Si]2Zn (3c) in silylmetalation chemistry
which added regioselectively across non-symmetric internal triple
bonds. Extension of this noteworthy feature to the stereoselective
synthesis of tetrasubstituted alkenes is under investigation.
M. O. is indebted to the Deutsche Forschungsgemeinschaft for
an Emmy Noether fellowship (2001–2006) and to Professor
Reinhard Bru¨ckner for his continuous encouragement. The
authors thank the Dr Otto Ro¨hm Geda¨chtnisstiftung for
additional financial support.
9 Y. Morizawa, H. Oda, K. Oshima and H. Nozaki, Tetrahedron Lett.,
1984, 25, 1163–1166.
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11 A. Kawachi and K. Tamao, Bull. Chem. Soc. Jpn., 1997, 70, 945–955.
12 In a single example, 1-octyne was subjected to silylcupration using
(Et2N)Ph2SiMgMe and CuI (50 mol%). Treatment with ethanol and
NH4Cl provided the linear product in 56% yield which matches the
regioselectivity seen for (Me2PhSi)2CuLi?LiCN2a,b: K. Tamao,
A. Kawachi, Y. Tanaka, H. Ohtani and Y. Ito, Tetrahedron, 1996,
52, 5765–5772.
13 (a) J.-i. Hibino, S. Nakatsukasa, K. Fugami, S. Matsubara, K. Oshima
and H. Nozaki, J. Am. Chem. Soc., 1985, 107, 6416–6417; (b)
K. Fugami, J.-i. Hibino, S. Nakatsukasa, S. Matsubara, K. Oshima,
K. Utimoto and H. Nozaki, Tetrahedron, 1988, 44, 4277–4292.
14 For a palladium-catalyzed bissilylation of alkynes, see: Y. Ito,
M. Suginome and M. Murakami, J. Org. Chem., 1991, 56, 1948–1951.
15 J.-F. Betzer and A. Pancrazi, Synlett, 1998, 1129–1131.
16 (a) A. Zakarian, A. Batch and R. A. Holton, J. Am. Chem. Soc., 2003,
125, 7822–7824; (b) B. Shi, N. A. Hawryluk and B. B. Snider, J. Org.
Chem., 2003, 68, 1030–1042; (c) S. C. Archibald, D. J. Barden, J. F.
Y. Bazin, I. Fleming, C. F. Foster, A. K. Mandal, A. K. Mandal,
D. Parker, K. Takaki, A. C. Ware, A. R. B. Williams and A. B. Zwicky,
Org. Biomol. Chem., 2004, 2, 1051–1064.
17 (a) S. E. Denmark and R. F. Sweis, in Metal-catalyzed Cross-coupling
Reactions, ed. A. de Meijere and F. Diederich, Wiley-VCH, Weinheim,
2004, vol. 1, pp. 163–216; (b) S. Rendler and M. Oestreich, Synthesis,
2005, 1727–1747.
18 K. Tamao, K. Kobayashi and Y. Ito, Tetrahedron Lett., 1989, 30,
6051–6054.
Notes and references
{ Representative experimental procedures. Bis[(diethylamino)diphenylsilyl]
zinc (3c): (diethylamino)diphenylsilyl chloride (1c) (725 mg, 2.50 mmol,
2.50 equiv.) was maintained with freshly cut lithium wire (large excess and
pre-treated with Me3SiCl) in dry THF (4.00 mL) at 0 uC for 12 h under
argon atmosphere. The resulting dark green solution of (diethylamino)di-
phenylsilyl lithium (2c) (2.00 mmol, 80% average conversion) and THF was
separated from unreacted lithium metal by transfer via a double-ended
cannula into a separate flask. Addition of ZnCl2 (1.00 mL, 1.00 equiv., 1 M
in Et2O) at 0 uC was accompanied by a color change from dark green to
greenish yellow and afforded ready-to-use zinc reagent 3c.
(E)-2-[(Ethoxy)diphenylsilyl]-1-phenyl-1-butene (27d): a suspension of
CuI (9.6 mg, 0.050 mmol, 5.0 mol%) and THF (1.00 mL) was pre-cooled to
278 uC and 3c (1.00 mmol, 1.00 equiv.) was added via syringe. The dark
brown reaction mixture was allowed to warm to 0 uC and maintained at
this temperature for 0.5 h. Addition of 1-phenyl-1-butyne (25) (130 mg,
1.00 mmol, 1.00 equiv.) in THF (1.00 mL) was followed by stirring at 0 uC
for 1.0 h. The reaction mixture was then treated with dry ethanol (2.50 mL)
and solid NH4Cl (100 mg) at 0 uC and was maintained at room
temperature for several hours. Upon completion of the reaction, the
mixture was poured into water (10 mL) and the flask was rinsed with
19 (a) V. Liepins and J.-E. Ba¨ckvall, Org. Lett., 2001, 3, 1861–1864; (b)
V. Liepins and J.-E. Ba¨ckvall, Eur. J. Org. Chem., 2002, 3527–3535.
20 V. Liepins and J.-E. Ba¨ckvall, Chem. Commun., 2001, 265–266.
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