Stereoselective synthesis of allylsilanes bearing tetrasubstituted olefin via 2,2-Diborylethylsilane

Article abstract of DOI:10.1246/cl.2011.1440

The regio-and stereoselective synthesis of allylsilane derivatives bearing a tetrasubstituted olefin was achieved using 2,2-diborylethylsilane as a key intermediate. The regioselective deprotonation of a 2,2-diborylethylsilane with LTMP and the subsequent nucleophilic addition to ketones gave corresponding allylsilanes in good to excellent yield with excellent stereoselectivity.

Full text of DOI:10.1246/cl.2011.1440

doi:10.1246/cl.2011.1440
1440
Published on the web December 5, 2011
Stereoselective Synthesis of Allylsilanes Bearing Tetrasubstituted
Olefin via 2,2-Diborylethylsilane
Kohei Endo,*1,2 Akira Sakamoto,3 Takahiro Ohkubo,3 and Takanori Shibata*3
1Waseda Institute for Advanced Study, Shinjuku-ku, Tokyo 169-8050
2PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012
3Department of Chemistry and Biochemistry, School of Advanced Science and Engineering,
Waseda University, Shinjuku-ku, Tokyo 169-8555
(Received September 9, 2011; CL-110752; E-mail: kendo@aoni.waseda.jp, tshibata@waseda.jp)
Me
The regio- and stereoselective synthesis of allylsilane
derivatives bearing a tetrasubstituted olefin was achieved using
2,2-diborylethylsilane as a key intermediate. The regioselective
deprotonation of a 2,2-diborylethylsilane with LTMP and the
subsequent nucleophilic addition to ketones gave corresponding
allylsilanes in good to excellent yield with excellent stereo-
selectivity.
Me3Si
Me3Si
Ph
Bpin
(E)-3a
base (1.5 equiv)
THF, 0 °C, 5 min
Bpin
Bpin
1 (1.5 equiv)
Me3Si
+
then acetophenone (2a)
Ph
Me
Bpin
(Z)-3a
Allylation intermediates are important synthons for the
synthesis of various functionalized molecules. There have been
many efforts to synthesize easily available allylation reagents,
such as allylboranes and allylsilanes.1 Despite their attractive
features as an allylic intermediate, there are not many examples
to synthesize an allylborane or an allylsilane bearing a
tetrasubstituted olefin.2 We previously reported the highly
stereoselective synthesis of tetrasubstituted alkenylboronates
via the deprotonation/nucleophilic addition of 1,1-diboryl-
alkanes3 to ketones.4 DFT calculations can support the stereo-
selective syn-elimination after nucleophilic addition of 1,1-
diborylalkanes to ketones. As a part of our studies, we are
interested in the stereoselective synthesis of an allylborane or an
allylsilane bearing a tetrasubstituted alkenylboronate moiety. We
describe here the stereoselective synthesis of allylsilanes bearing
a tetrasubstituted olefin via the nucleophilic addition of a 2,2-
diborylethylsilane to ketones, which could not be obtained via
other conventional approaches.
The deprotonation of 2,2-diborylethylsilane 1 using a base
and the subsequent nucleophilic addition to acetophenone (2a)
was carried out (Scheme 1). To our delight, the regioselective
deprotonation of 2,2-diborylethylsilane 1 using lithium 2,2,6,6-
tetramethylpiperazide (LTMP) and the following nucleophilic
addition to acetophenone (2a) occurred to give the correspond-
ing product (E)-3a in 81% yield.5 In contrast, the use of
lithium diisopropylamide (LDA) as a base did not give the
desired product 3a at all. The geometry of 3a was confirmed
by NOESY experiment. We carefully checked the crude
products, but the stereoisomer (Z)-3a could not be detected.
The tentative reaction using ethane-1,1,2-triboronate 1B and
benzophenone mediated by LDA gave the corresponding
product 3B in moderate yield; the use of LTMP gave a lower
yield (Scheme 2). Furthermore, the reaction of unsymmetrical
ketones mediated by LDA or LTMP gave products in low
yields as a mixture of stereoisomers along with unidentified
by-products; the examination of reaction conditions did not
improve the yields and stereoselectivities. Thus, we focus on
the reaction of 2,2-diborylethylsilane 1 and ketones using
LTMP.
base = LTMP
base = LDA
81%, E/Z = >99/1
Not detected
Scheme 1. Addition of 2,2-diborylethylsilane.
R2
LDA or LTMP (1.5 equiv)
Bpin
Bpin
1B (1.5 equiv)
THF, 0 °C, 5 min
pinB
R1
pinB
then ketone
O
Bpin
3B
R1 = R2 = Ph, 64%
R1 R2
R1 ≠ R2, low yield, E/Z mixture
Scheme 2. Addition of ethane-1,1,2-triboronate.
The optimized conditions using 1 (2 equiv) and LTMP
(2 equiv) achieved good to excellent yields of allylsilanes using
aryl ketones (Table 1).6 The reaction using phenyl ketones 2a-2f
realized excellent stereoselectivities (Entries 1-6). The electron-
withdrawing group or -donating group could be compatible to
give the corresponding products 3g and 3h in moderate to high
yields, respectively (Entries 7 and 8). Although the reaction
using a 1,1-diborylalkane and an aliphatic ketone gave a desired
product as shown in our previous report,3 the reaction using 2,2-
diborylethylsilane 1 and aliphatic ketones, such as 2i and 2j gave
unidentified by-products in each case (Entries 9 and 10). The
symmetric ketone, benzophenone (2k), gave the desired product
3k in excellent yield (Entry 11).
We tested the Suzuki-Miyaura cross-coupling reaction of
the product 3c in the presence of Pd-catalyst (Scheme 3). The
coupling reaction with 4-iodoanisole in the presence of
[Pd(PPh3)4] (5 mol %) and KOH (2.2 equiv) at 60 °C gave the
desired product 4 in 55% isolated yield. The trimethylsilyl
moiety was intact under the present reaction conditions. The
present demonstration represents the synthetic utility for further
transformations.
A DFT computation study was performed at the B3LYP/6-
31G* level of theory to identify the stereoselectivity (Figure 1).7
Typical models for lithium alkoxide intermediates, Int-1 and
Int-2, are described after the nucleophilic addition to acetophe-
Chem. Lett. 2011, 40, 1440-1442
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1441
Bn
Ph
Table 1. Scope of ketones
I
[Pd(PPh3)4] (5 mol %)
KOH (2.2 equiv)
R2
LTMP (2 equiv)
Me3Si
Bn
Bpin
Bpin
THF, 0 °C, 5 min
Me3Si
R1
+
Me3Si
Me3Si
Ph
then ketone 2a–k
H2O/dioxane
60 °C, 24 h
Bpin
3a–k
time, rt
Bpin
3c (1.1 equiv)
1 (2 equiv)
Ketone
Me
OMe
4, 55%
OMe
(65% NMR)
Entry
1
Time/h
Product
Yield/%a,b
Me
Scheme 3. Suzuki-Miyaura cross-coupling of 3c.
Me3Si
Ph
98
1
1
O
O
O
O
Ph
Ph
Ph
Ph
Li
Li
Bpin
2a
O
B1
O
O
O
O
B2
O
B2
(E)-3a
B1
O
O
O
O
Et
Et
path (A)
path (B)
path (A)
path (B)
Me3Si
Ph
Ph
Me3Si
Me
Ph
Me3Si
Me
2
3
4
5
6
96
92
98
74
71
Bpin
2b
(E)-3bc
Int-1
Int-2
Bn
Bn
path (A)
path (A)
Me3Si
Ph
Ph
17
1
Li
Li
Bpin
2c
O
B1
O
O
B2
O
B2
(E)-3c
O
O
B1
O
O
O
Ph
O
i-Pr
i-Pr
Ph
Me3Si
Me3Si
Me3Si
Me
Me
Bpin
2d
Me3Si
Me3Si
(E)-3d
OG-2
+0.1 kcal/mol
OG-1
0 kcal/mol
c-Hex
c-Hex
Ph
Ph
B1–O
B1–O
elimination
1.5
O
B2–O
elimination
B2–O
elimination
Bpin
elimination
2e
(E)-3e
t-Bu
t-Bu
Ph
Me
Ph
Me
Me
Ph
1
O
Ph
Bpin
Me3Si
Me Me3Si
Ph
Me3Si
Me3Si
Ph
2f
(E)-3f
Bpin
Bpin
Bpin
Bpin
Me
Me
(Z)-3a
(E)-3a
(Z)-3a
(E)-3a
O
Me3Si
Bpin
Figure 1. DFT calculations of syn-elimination for 2,2-dibo-
rylethylsilane (B3LYP/6-31G*).
X
X
2g, X = CF3
(E)-3g
(E)-3h
87
52
7
8
5
6
X = OMe
2h,
(E)-3a. In contrast, DFT calculations of optimized geometries
derived from ethane-1,1,2-triboronate 1B showed that the
reaction leads to a mixture of stereoisomers (see the Supporting
Information8). Further examination of the optimization of four-
membered borate intermediates before syn-elimination were
performed (Figure 2).9 As a result, the relative energy of syn-E
Me
C. M.b
C. M.b
98
9
10
11
9
9
1
O
c-Hex
2i
Me
¹1
was 1.8 kcal mol higher than that of syn-Z, and the relative
O
t-Bu
¹1
energy of (E)-3a was 0.6 kcal mol higher than that of (Z)-3a.
2j
Thus, (Z)-3a should be obtained as a major isomer because of
the thermodynamic stability of borate intermediate syn-Z and
product (Z)-3a. In this context, the stereoselectivity could be
determined at the chelation intermediates OG-1 and OG-2 due
to its predominant stability.
Ph
Ph
Me3Si
Ph
O
Ph
Bpin
2k
3k
In conclusion, we have demonstrated the stereoselective
synthesis of allylsilanes bearing a tetrasubstituted olefinic
moiety derived from 2,2-diborylethylsilane. The use of aromatic
ketones gave the desired products with excellent stereoselectiv-
ity. In contrast, the reaction of ethane-1,1,2-triboronate gave
poor results in yield and stereoselectivity. DFT calculations
support their stereoselectivities, although the influence of the
silyl moiety in 2,2-diborylethylsilane 1 and boron moiety
in ethane-1,1,2-triboronate 1B was not fully elucidated. We
demonstrated the Suzuki-Miyaura cross-coupling reaction of the
aIsolated yields. The geometries were confirmed by NOESY
analysis. Complex mixture.
b
none (2a). The intramolecular coordination of the oxygen atom
in the pinacolboryl group to the lithium atom is feasible; the
optimized geometries gave OG-1 and OG-2, respectively.
Therefore, the rotation to path (A) should be predominant and
realized the syn-elimination through LiO-C-C-B2 to give
Chem. Lett. 2011, 40, 1440-1442
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1442
–
–
2
For recent examples of tetrasubstituted allylboranes: a) J.
Marco-Martínez, E. Buñuel, R. Muñoz-Rodríguez, D. J.
Cárdenas, Org. Lett. 2008, 10, 3619. b) P. V. Ramachandran,
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k) Y. Fujii, J. Terao, H. Kuniyasu, N. Kambe, J. Organomet.
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3115.
O
O
O
O
O
O
B
B
O
Me
B
B
O
O
O
Ph
Ph
Me3Si
Me
Me3Si
syn-E; +1.8 kcalmol−1
syn-Z; 0 kcalmol−1
Ph
Me
Me3Si
Me
Ph
Me3Si
Bpin
Bpin
(Z )-3a; 0 kcalmol−1
(E)-3a; +0.6 kcalmol−1
Figure 2. DFT calculations of borate intermediates and
products (B3LYP/6-31G*).
allylsilane and the silyl moiety was intact in the coupling
product. The further development of products as synthetic
intermediates are underway in our laboratory.
3
a) K. Endo, M. Hirokami, T. Shibata, Synlett 2009, 1331. b)
K. Endo, T. Ohkubo, M. Hirokami, T. Shibata, J. Am. Chem.
Soc. 2010, 132, 11033. c) K. Endo, T. Ohkubo, T. Shibata,
Org. Lett. 2011, 13, 3368.
This work was supported by JST PRESTO program and
Grant-in-Aid for Young Scientists (B) from the Japan Society for
the Promotion of Science.
4
5
K. Endo, M. Hirokami, T. Shibata, J. Org. Chem. 2010, 75,
3469.
A few examples were reported for the synthesis of allyl-
silane bearing tetrasubstituted alkenylboronate moiety, see:
a) K. K. Wang, K. E. Yang, Tetrahedron Lett. 1987, 28,
1003. b) T. Honda, M. Mori, Organometallics 1996, 15,
5464. c) S.-y. Onozawa, Y. Hatanaka, M. Tanaka, Chem.
Commun. 1999, 1863.
This paper is in celebration of the 2010 Nobel Prize
awarded to Professors Richard F. Heck, Akira Suzuki, and
Ei-ichi Negishi.
References and Notes
6
7
The reaction of benzaldehyde gave a mixture of stereo-
isomers in 59% yield, ca. 2/1 ratio of major and minor
isomers.
The DFT computational calculations were performed using
the Spartan’08 suite for Mac (Wave function, Inc.). Zero-
point vibrational energies (ZPEs) were calculated for all
structures, and the geometry was verified as true minima
using frequency analysis.
Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
The DFT calculations at the B3LYP/6-31+G* level of
theory gave similar results, indicating that syn-Z should be
more stable than syn-E.
1
For recent reviews of allylboration: a) W. R. Roush, in
Comprehensive Organic Synthesis, ed. by B. M. Trost,
I. Fleming, Pergamon Press, Oxford, 1991, Vol. 2,
p. 1. doi:10.1016/B978-0-08-052349-1.00023-8. b) S. E.
Denmark, N. G. Almstead, in Modern Carbonyl Chemistry,
ed. by J. Otera, Wiley-VCH, Weinheim, 2000, p. 299. c)
S. R. Chemler, W. R. Roush, in Modern Carbonyl
Chemistry, ed. by J. Otera, Wiley-VCH, Weinheim, 2000,
p. 403. Allylsilylation. d) M. A. Brook, Silicon in Organic,
Organometallic, and Polymer Chemistry, Wiley, Chichester,
2000. e) S. E. Denmark, R. A. Stavenger, Acc. Chem. Res.
2000, 33, 432. f) S. E. Denmark, J. Fu, Chem. Rev. 2003,
103, 2763.
8
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Chem. Lett. 2011, 40, 1440-1442
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/