Expedient access to branched allylic silanes by copper-catalysed allylic substitution of linear allylic halides

Article abstract of DOI:10.1039/b920793g

An unprecedented copper-catalysed allylic transposition enables the regioselective synthesis of branched allylic silanes from linear allylic halides through direct C-Si bond formation.

Full text of DOI:10.1039/b920793g

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Expedient access to branched allylic silanes by copper-catalysed allylic
substitution of linear allylic halidesw
Devendra J. Vyas and Martin Oestreich*
Received (in Cambridge, UK) 7th October 2009, Accepted 25th November 2009
First published as an Advance Article on the web 11th December 2009
DOI: 10.1039/b920793g
An unprecedented copper-catalysed allylic transposition enables
the regioselective synthesis of branched allylic silanes from
linear allylic halides through direct C–Si bond formation.
us to test our catalytically generated ‘‘Me2PhSiCu’’ reagent
in branched-selective allylic transpositions. In this communi-
cation, we disclose an expedient route to branched allylic
silanes from linear precursors.
Our investigation commenced with a systematic screening of
leaving groups in the cinnamic system (1 - 2, Table 1).18 In
agreement with previous results using CuI,2 both acetate and
benzoate as well as carbamate and also carbonate reacted
with flawless a-selectivity in THF (1a–d - a-2, Table 1,
entries 1–4); in turn, 1a–c were inert and 1d reacted sluggishly
in Et2O (THF, introduced as part of the preparation
of (Me2PhSi)2Zn, was evaporated under reduced pressurew).
As anticipated based on the work of Gorzynski
Smith et al.,14a,16a phosphate and halides favoured the
formation of the g-isomer in both solvents (1e–g - g-2,
Table 1, entries 5–7); the poor regioselectivity for 1g in
Et2O is not understood, and there is a subtle temperature
dependence of the g : a ratio (vide infra).
Reactions of allylic halides 1f (rs = 83 : 17) and 1g
(rs = 90 : 10) with (Me2PhSi)2Zn–CuCN (5 mol%) were
promising in THF at 0 1C (Table 2, entries 1 and 4),
and we therefore compared these numbers with those
obtained in reactions with established silicon-based cuprates.
Me2PhSiCuÁLiCN, which might be regarded as the
stoichiometric variant of our reagent, produced g : a ratios
in the same order of magnitude within the experimental
Copper-catalysed allylic alkylation of linear allylic precursors
using magnesium and zinc reagents as nucleophilic reaction
partners is without question a fundamental C–C bond-
forming reaction.1 A central aspect in that process is to shift
the regioselectivity in favour of the branched rather than the
linear isomer by deliberate choice of the allylic leaving group
as well as the ligands coordinated to copper. The decisive
control of the branched-to-linear ratio is however an unsolved
challenge in the related allylic C–Si bond formation,2
and direct preparation of branched allylic silanes3,4 from
linear allylic precursors employing silicon nucleophiles is not
known.5,6
We had discovered
a while ago that stoichiometric
silicon-based cuprate chemistry7 might now be superseded
by copper-catalysed protocols.8 Our catalytic system is
composed of a bis(triorganosilyl) zinc reagent9 and a copper
salt, the former serving as a reservoir of nucleophilic silicon.
For example, (Me2PhSi)2Zn9 and CuX are assumed to
form ‘‘Me2PhSiCu’’, as experimentally supported by
a
reactivity pattern similar to that of Me2PhSiCuÁLiX
(X = I or CN).10
The (Me2PhSi)2Zn–CuI (5 mol%) combination performed
well in the diastereospecific formation of linear allylic
silanes from linear precursors having an oxygen-containing
leaving group, OC(O)R and OC(O)NHR.2,11 Our results
were nevertheless in accordance with the data obtained
by Fleming et al. with (Me2PhSi)2CuLiÁLiCN.12 It is clear
from these findings that the above-mentioned leaving
groups will typically bring about linear allylic silanes,2,12 yet
there is a noteworthy exception.13 Conversely, predominant
formation of the less stable branched isomer is seen in
error (Table 2, entries
2 and 5). In stark contrast,
(Me2PhSi)2CuLiÁLiCN was completely unselective (Table 2,
entries 3 and 6), a conceivable reason why its reported
chemistry is limited to acetates and carbamates
as substrates.12 These observations lend further support
to the notion that (Me2PhSi)2Zn–CuX transmetalates
to ‘‘Me2PhSiCu’’.10
We exemplarily verified the influence of the double bond
geometry on the reaction outcome (1f - 2, Scheme 1). The
alkene configuration is retained in the minor isomer, the linear
allylic silane a-2: Z - Z (Scheme 1) and E - E (Table 1,
entry 6). The g : a ratio is however slightly better for the
E (rs = 83 : 17) than for the Z isomer (rs = 73 : 27).
allylic displacements with Br14 and Cl14,15 as well as
16
OP(O)(OR)2
and OMs17 as leaving groups. All these
protocols trace back to the seminal work of Gorzynski
Smith et al.,14a,16a in which the use of Me3SiCuSMe2ÁLiI
in Et2O–HMPA at low temperature had emerged as
crucial for high levels of regiocontrol.14–17 The pivotal
role of the 1 : 1 stoichiometry of silicon and copper prompted
Encouraged by the solvent-independent regioselectivity
seen for the allylic bromide (1f - g-2, Table 1, entry 6),
we decided to further examine differently substituted allylic
bromides 3f–10f in Et2O at 0 1C (Table 3, left columns).
Difficulties in the preparation of aryl-substituted 3f–7f
were somewhat unexpected. The chemical lability of 3f–7f
might account for their so far limited use in allylic alkylation.1
This issue was overcome by subjecting 3f–7f (prepared from
the corresponding allylic alcoholsw) to the allylic substi-
Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat,
¨ ¨
Corrensstrasse 40, D-48149 Munster, Germany.
¨
E-mail: martin.oestreich@uni-muenster.de;
Fax: +49 (0)251 83-36501; Tel: +49 (0)251 83-33271
w Electronic supplementary information (ESI) available: Preparation
and characterisation data as well as 1H and 13C NMR spectra of all
new compounds. See DOI: 10.1039/b920793g
tution protocol immediately after purification over
a
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Table 1 Leaving group dependence of the regiochemical outcome in the copper-catalysed allylic substitution of linear precursors
CuCN (5 mol%) in THFa
CuCN (1 mol%) in Et2Oa
rsb,c (g : a)
Yieldd (%)
rsb,c (g : a)
Yieldd (%)
Entry
Allylic precursorb
Leaving group (LG)
e
12
2
1a
1b
1c
1d
1e
1f
OC(O)Me
OC(O)Ph
OC(O)NHPh
OC(O)OEt
OP(O)(OEt)2
Br
o1 : 99
o1 : 99
o1 : 99
o1 : 99
72 : 28
68
77
62
60
88
82
66
—
—
—
66 : 34
74 : 26
90 : 10
60 : 40
—
—
e
e
—
32
4
28
86
80
70
5
6
7
83 : 17
90 : 10
1g
Cl
a
Allylic substitution in THF required CuCN (5 mol%) for full conversion while considerable conversion was seen with CuCN (1 mol%) in
c
Et2O. E,Z ratio of linear compounds determined by GLC analysis and 1H NMR spectroscopy. Ratio of regioisomers determined by 1H NMR
d
analysis prior to purification. Combined yield of analytically pure regioisomers, isolated by flash chromatography on silica gel. No reaction.
b
e
Table 2 Comparative survey of cuprate reagentsa
Entry
Allylic precursor
Leaving group
Cuprate reagent
rsc (g : a)
Yieldd (%)
1
2
3
4
5
6
1f
1f
1f
1g
1g
1g
Br
Br
Br
Cl
Cl
Cl
(Me2PhSi)2Zn–CuCNb
Me2PhSiCuÁLiCN
83 : 17
77 : 23
50 : 50
90 : 10
88 : 12
50 : 50
82
79
88
80
92
90
(Me2PhSi)2CuLiÁLiCN
(Me2PhSi)2Zn–CuCNb
Me2PhSiCuÁLiCN
(Me2PhSi)2CuLiÁLiCN
a
b
All reactions were conducted using the indicated cuprate reagent (B1 equiv.) in THF at 0 1C. The zinc reagent is contaminated with Et2O as a
result of the lithium-to-zinc transmetalation step; CuCN (5 mol%). Ratio of regioisomers determined by 1H NMR analysis. Combined yield of
pure regioisomers, isolated by flash chromatography on silica gel.
c
d
93 : 7 at À78 1C in THF and in Et2O, respectively. These
branched-to-linear ratios were now synthetically useful, and
we therefore set out to repeat our substrate screening
with allylic chlorides 3g–10g in THF at À78 1C (Table 3,
right columns). Both aryl- and alkyl-substituted 3g–7g and
8g–9g underwent the allylic displacement in good chemical
yields and regioselectivities as high as >99 : 1 (Table 3,
Scheme 1 Retention of the double bond geometry.
entries 1–8). Again, silyl-substituted 10g was not suitable
(Table 3, entry 9).
Finally, we would like to note that these copper-catalysed
short pad of silica gel. The g : a ratios obtained ranged from
79 : 21 to 90 : 10 (Table 3, entries 1–6), and alkyl-substituted
8f–9f also produced similar regioselectivities of 88 : 12
and 91 : 9 (Table 3, entries 7 and 8). Regiocontrol only
collapsed with a terminal Me3Si group as in 10f (Table 3,
entry 9).
allylic substitutions were extremely fast without exception.
Allylic bromides required less than a minute at 0 1C for
full conversion (Table 3, left columns) and allylic chlorides
reacted within a quarter of an hour at À78 1C (Table 3,
right columns).
To recap, we accomplished a copper-catalysed, highly
branched-selective allylic substitution of linear aryl- and
alkyl-substituted allylic halides. We learned that several
reaction parameters govern the level of regiocontrol, Et2O
at 0 1C for allylic bromides (rs = 79 : 21 to 91 : 9) and THF
at À78 1C for allylic chlorides (rs = 93 : 7 to >99 : 1).
This novel copper catalysis might finally pave the way for
an asymmetric allylic silylation to directly access a-chiral
Aware of the pronounced influence of the temperature on
such transformations,14a we continued to study that effect
for both protocols. A temperature of 0 1C in Et2O was
already optimal for allylic bromide 1f (rs = 90 : 10), and the
regioselectivity declined dramatically at À78 1C (rs = 60 : 40).
On the other hand, we were delighted to find that
allylic chloride 1g afforded excellent g : a ratios of 96 : 4 and
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Table 3 Copper-catalysed, branched-selective allylic silylation of linear allylic bromides and chloridesa
Allylic bromide (LG = Br): CuCN
(1 mol%) in Et2O at 0 1C
Allylic chloride (LG = Cl): CuCN
(5 mol%) in THF at À78 1C
rsb (g : a)
Yieldc (%)
rsb (g : a)
Yieldc (%)
Entry
Allylic precursor
Substituent R
Allylic silanes
1
2
3
4
5
6
7
8
9
1f or 1g
Ph
g-2 and a-2
90 : 10
81 : 19
89 : 11
87 : 13
79 : 21
81 : 19
88 : 12
91 : 9
80
96 : 4
94 : 6
95 : 5
94 : 6
93 : 7
96 : 4
>99 : 1
98 : 2
76 : 24
85
69e
82
44e
91
84
84
86
89
3fd or 3gd
4fd or 4g
5fd or 5gd
6fd or 6g
7fd or 7g
8fg or 8gg
9fh or 9gh
10f or 10g
4-MeOC6H4
3-MeOC6H4
2-MeOC6H4
4-F3CC6H4
4-BrC6H4
Cy
g-11 and a-11
g-12 and a-12
g-13 and a-13
g-14 and a-14
g-15 and a-15
g-16 and a-16
g-17 and a-17
g-18 and a-18
60e
46e
49e
64e
f
—
88
83
85
iPr
Me3Si
58 : 42
a
b
All reactions were conducted using (Me2PhSi)2Zn (B1.0 equiv.) and a catalytic amount of CuCN in Et2O at 0 1C or THF at À78 1C. Ratio of
regioisomers determined either by GLC or by 1H NMR analysis prior to purification. Combined yield of analytically pure regioisomers, isolated
c
d
by flash chromatography on silica gel. Allylic bromides and chlorides were prepared from the corresponding allylic alcohols (E,Z > 99 : 1) and
e
used without further purification. Isolated yield based on allylic alcohol (two steps). Poor chemical yield. E,Z = 93 : 7. E,Z = 95 : 5.
f
g
h
allylic silanes,5,6,11,19,20 and future research will be directed
towards this challenge.
Tetrahedron Lett., 1984, 25, 1163–1166; (b) for the successful use of
(Me2PhSi)2Zn as a silicon source in cuprate chemistry, see:
M. Oestreich and B. Weiner, Synlett, 2004, 2139–2142.
10 G. Auer and M. Oestreich, Chem. Commun., 2006, 311–313.
11 For enantiospecific allylic substitutions using either (Me2PhSi)2Zn–
CuI or (Bu3Sn)2Zn–CuCN, see: (a) E. S. Schmidtmann
and M. Oestreich, Chem. Commun., 2006, 3643–3645;
(b) E. S. Schmidtmann and M. Oestreich, Angew. Chem., Int.
Ed., 2009, 48, 4634–4638.
D.J.V. thanks the NRW Graduate School of Chemistry for
a predoctoral fellowship (2008–2011).
Notes and references
1 (a) C. A. Falciola and A. Alexakis, Eur. J. Org. Chem., 2008,
3765–3780; (b) H. Yorimitsu and K. Oshima, Angew. Chem., Int.
Ed., 2005, 44, 4435–4439.
12 I. Fleming, D. Higgins, N. J. Lawrence and A. P. Thomas,
J. Chem. Soc., Perkin Trans. 1, 1992, 3331–3349.
2 M. Oestreich and G. Auer, Adv. Synth. Catal., 2005, 347, 637–640.
3 For a recent review on the chemistry of allylic silanes, see: L. Chabaud,
P. James and Y. Landais, Eur. J. Org. Chem., 2004, 3173–3199.
4 For the preparation of allylic silanes, see: T. K. Sarkar, in Science
of Synthesis, ed. I. Fleming and S. V. Ley, Thieme, Stuttgart, 2002,
vol. 4, pp. 837–925.
5 Hoveyda et al. elaborated an indirect synthesis of branched allylic
silanes by copper-catalysed allylic substitution of allylic
phosphates using zinc reagents: M. A. Kacprzynski, T. L. May,
S. A. Kazane and A. H. Hoveyda, Angew. Chem., Int. Ed., 2007,
46, 4554–4558.
6 For alternative methods of allylic silane synthesis through C–Si
bond formation, see: (a) palladium-catalysed hydrosilylation of
cyclic 1,3-dienes with MeCl2SiH: T. Hayashi, K. Kabeta,
T. Yamamoto, K. Tamao and M. Kumada, Tetrahedron Lett.,
1983, 24, 5661–5664; (b) palladium-catalysed allylic substitution of
allylic chlorides with Cl2PhSi–SiMe3: Y. Matsumoto, A. Ohno and
T. Hayashi, Organometallics, 1993, 12, 4051–4055; (c) palladium-
catalysed intramolecular bissilylation of alkenes using
Me2PhSi–SiPh2OR: M. Suginome, T. Iwanami, Y. Ohmori,
A. Matsumoto and Y. Ito, Chem.–Eur. J., 2005, 11, 2954–2965;
(d) palladium-catalysed silaboration of allenes with Me2PhSi–
Bpin: T. Ohmura, H. Taniguchi and M. Suginome, J. Am. Chem.
Soc., 2006, 128, 13682–13683.
13 H. Nakamura, T. Oya and A. Murai, Bull. Chem. Soc. Jpn., 1992,
65, 929–931.
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E. M. Rice, B. S. Taylor and M. Viswanathan, J. Org. Chem., 1984,
49, 4112–4120; (b) for its use in total synthesis, see: E. J. Corey and
R. M. Burk, Tetrahedron Lett., 1987, 28, 6413–6416.
15 For the use of hetereoatom-substituted (Et2N)Ph2SiCuÁLiCN in
total synthesis, see: I. R. Baldwin and R. J. Whitby, Chem.
Commun., 2003, 2786–2787.
16 (a) J. Gorzynski Smith, S. L. Henke, E. M. Mohler, L. Morgan and
N. I. Rajan, Synth. Commun., 1991, 21, 1999–2006; (b) for its use in
total synthesis, see: D. R. Williams and R. W. Heidebrecht, Jr.,
J. Am. Chem. Soc., 2003, 125, 1843–1850.
17 For the use of modified Me3SiCuP(OMe)3ÁLiI in complex molecule
synthesis, see: B. Radetich and E. J. Corey, J. Am. Chem. Soc.,
2002, 124, 2430–2431.
18 The branched-to-linear ratio was largely independent of the copper
source [CuI, CuCN, CuBr, CuBrÁSMe2, CuCl and Cu(OTf)2]. An
extensive screening of solvents showed that THF, Et2O and
benzene were superior to other common polar and non-polar
solvents.
19 C–C bond formation: (a) palladium-catalysed cross-coupling of
vinylic bromides and Grignard reagents: T. Hayashi, M. Konishi,
H. Ito and M. Kumada, J. Am. Chem. Soc., 1982, 104, 4962–4963;
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12650–12651.
7 R. K. Dieter, in Modern Organocopper Chemistry, ed. N. Krause,
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8 For
a comprehensive summary, see: A. Weickgenannt and
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9 (a) Prior to our investigations, (Me2PhSi)2Zn was considered
only once: Y. Morizawa, H. Oda, K. Oshima and H. Nozaki,
20 C–H bond formation: palladium-catalysed allylic substitution of
allylic carbonates with formic acid: T. Hayashi, H. Iwamura and
Y. Uozumi, Tetrahedron Lett., 1994, 35, 4813–4816.
ꢀc
This journal is The Royal Society of Chemistry 2010
570 | Chem. Commun., 2010, 46, 568–570