A Lewis acid-promoted reduction of acylsilanes to α-hydroxysilanes by diethylzinc

Article abstract of DOI:10.1016/j.tetlet.2012.02.059

We report here the first example of the reduction of acylsilanes to α-hydroxysilanes, in which diethylzinc was used as a highly reactive agent in the presence of Ti(OiPr)₄ or other Lewis acids. The reduction typically proceeds to give synthetically useful α-hydroxysilanes in good yields.

Full text of DOI:10.1016/j.tetlet.2012.02.059

Tetrahedron Letters 53 (2012) 2164–2166
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A Lewis acid-promoted reduction of acylsilanes to
by diethylzinc
a-hydroxysilanes
Guang Gao a, Xing-Feng Bai a, Fei Li a, Long-Sheng Zheng a, Zhan-Jiang Zheng a, Guo-Qiao Lai a, Kezhi
Jiang a, Fuwei Li b, Li-Wen Xu a,
⇑
a Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University, Hangzhou 310012, China
b State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
We report here the first example of the reduction of acylsilanes to a-hydroxysilanes, in which diethylzinc
Received 26 October 2011
Revised 11 December 2011
Accepted 14 February 2012
Available online 26 February 2012
was used as a highly reactive agent in the presence of Ti(OiPr)4 or other Lewis acids. The reduction typ-
ically proceeds to give synthetically useful -hydroxysilanes in good yields.
Ó 2012 Elsevier Ltd. All rights reserved.
a
Keywords:
Organosilicon chemistry
Reduction
Diethylzinc
Silane
Lewis acid
Acylsilanes and corresponding a-hydroxysilanes are interesting
1.5 eq. Et2Zn
functional organometallic compounds exhibiting specific chemical
properties and reactivities beside the usual ones of carbonyl deriv-
atives, that allow for the generation of many synthetically and
pharmaceutically useful compounds.1,2 It is noteworthy that the
HO
H
1.0 eq. Ti(OiPr)4
CHO
BINMOL L1 (10 mol-%)
R
Et2O, 5 h, RT
R
96->99%ee
acylsilanes and
a-hydroxysilanes function similarly to carbonyl
HO
89-95% yield
and alcoholic compounds, but the inherent striking differences be-
tween carbon and silicon element allow for the chemistry of sili-
con’s own.3 Therefore, acylsilanes and their derivatives have
received increasing research interest in organosilicon chemistry
and organic synthesis, and have been recognized as important
synthons and valuable intermediates in the synthesis of complex
molecules via a number of synthetically useful transformations.4
During our investigation of a new family of diol ligands, the
Ar-BINMOLs, for the asymmetric 1,2-addition of diethylzinc to
aldehydes, we observed that the treatment of various aromatic
aldehydes afforded chiral secondary alcohols in excellent yields
and enantioselectivities (Scheme 1, up to >99.9% ee).5
Despite many methods reported for the transformations of car-
bonyl compounds, there are a few based upon bulky silicon-based
acylsilanes. In view of the great importance of acylsilanes in syn-
thetic organic chemistry, we are interested in testing the notion
that these chiral ligands could be employed for the asymmetric
1,2-addition to acylsilanes with diethylzinc and Grignard reagents
O
HO
H
OH
L1
Scheme 1. Asymmetric 1,2-addition of diethylzinc.
as well. Therefore, we first examined the 1,2-addition of diethyl-
zinc to acylsilane 1a (Scheme 2). When treated with 2 equiv of
diethylzinc in the presence of Ti(OiPr)4 and BINMOL in Et2O at
room temperature for 12 h, no desired adduct 3a but only reduc-
a-hydroxysilane 2a, was obtained with completed
conversion and in excellent yields (85% isolated yield).
tive product,
Although transfer hydrogenation and general reduction of acyl-
silanes are straightforward methods to produce a
-hydroxysilanes,6
there are very few examples on the reduction of acylsilanes via
hydride transfer from organometallic compounds.7 On the basis
of the above results, we envisioned that the use of diethylzinc as
the reducing agent would offer the effective process for the synthe-
⇑
Corresponding author. Tel.: +86 0571 28867756; fax: +86 0571 28865135.
E-mail addresses: licpxulw@yahoo.com, liwenxu@hznu.edu.cn (L.-W. Xu).
sis of a-hydroxysilanes. To the best of our knowledge, there are no
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.02.059

G. Gao et al. / Tetrahedron Letters 53 (2012) 2164–2166
2165
under the optimized conditions (Table 1). As shown in Table 1,
the evaluation of substrate scopes revealed that the reduction with
both electron-neutral and electron-rich aryl acyl silanes with TMS-,
TBS-, and TBDPS-groups proceeded equally well. Notably, the
reduction is excellent in completed conversion, simultaneously
with almost no by-product, and the somewhat lower yields arise
from purification with column chromatography, for example, there
are no obvious differences in the conversion of reduction with
para-methoxyl substituted aromatic acylsilane compared to ortho-
and meta-substituted analogues, however, the stability of the cor-
OH
Si
Ti(OiPr)4 (1.0 eq.)
2a
BINMOL L2 (10 mol-%)
O
Et2Zn (2.0 eq.)
85% yield
Si
1a
Et2O, 12 h, rt
OH
Si
responding a-hydroxysilane is different so that the isolated yields
H
HO
OH
were obtained from 35% to 69% (entries 12–14). The major by-
products are silanol and benzyl alcohol arising from silical gel-in-
duced desilylation.
3a
No observed
L2
Hence, on the basis of the above results, we envisioned that the
use of a chiral ligand or an auxiliary would offer the possibility of
enantioselective reduction. We first examined the enantioselective
reduction with diethylzinc with known BINOL and Ar-BINMOLs5
(1.0 equiv) using (tert-butyldimethylsilyl)(phenyl)methanone 1a
as the substrate. Unfortunately, although the reduction occurred
smoothly in high yields, no enantioselectivity was observed. Other
auxiliaries, such as cinchona alkaloids, also gave low levels of
enantioselectivity (up to 5% ee). In our screening experiments, only
L3 was found to give slight improvement to the promising levels of
asymmetric induction (21% ee) in the presence of large amount of
diethylzinc (Scheme 3).9
As Ti(OiPr)4 has been proved to be an efficient promoter or cat-
alyst for the reduction of acylsilane 1a in the presence of diethyl-
zinc, we choose a series of Lewis acids to catalyze the reduction
of the acylsilane. As shown in Table 2, experimental results showed
the reaction of acylsilane 1a with Et2Zn in the presence of these Le-
wis acids gave simply the reduction product 2a in different yields
(25–90%). When the reaction conducted in the presence of catalytic
Scheme 2. 1,2-Addition of diethylzinc to acylsilane.
reports in the literature about the diethylzinc-induced hydride
transfer reduction of acylsilanes. Therefore the development of
an efficient procedure for the selective hydride transfer reduction
of acylsilanes with new organometallic reagents is highly
desirable.
Preliminary studies were carried out with the model reaction of
(tert-butyldimethylsilyl)(phenyl)methanone 1a and diethylzinc or
Grignard reagent. After optimization of the solvent and tempera-
ture, this reaction was best carried out in Et2O as solvent at room
temperature, and the yield of
a-hydroxysilane reached an excel-
lent 86% isolated yield (Table 1, entry 1).8 Interestingly, the
Grignard reagent, i-PrMgCl, was also effective and gave 40% iso-
lated yield under the same reaction conditions (entry 2).6a Notably,
no addition of Ti(OiPr)4 to this reaction resulted in only moderate
yield (56% isolated yield, entry 3), thus the addition of Ti(OiPr)4
was beneficial to the improvement of the conversion (see Scheme
S2, Supplementary data).
Ti(OiPr)4 (0.1 eq.)
Have established a new method to reduce acylsilane to
hydroxysilane, the reaction of various acylsilanes was examined
a-
BINMOL L3 (2.0 eq.)
O
OH
∗
Et2Zn (6.0 eq.)
Si
1a
Si
Et2O, 12 h, rt
Table 1
2a
Ti-catalyzed reduction of acylsilanes in the presence of diethylzinca
53% yield
21%ee
O
OH
Ti(OiPr)4 (1.0 eq.)
Et2Zn (2.0 eq.)
H
HO
R1
R2
R1
R2
O
Si
Si
R3
R4
R4
R3
Et2O, 12 h, rt
1
2
R1
R2
R3
R4
Yieldb (%)
L3
Entry
1
2
3
4
5
6
7
8
Me
Me
Me
Me
Me
Et
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Et
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
t-Bu
t-Bu
t-Bu
Me
t-Bu
Et
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
H
H
H
H
m-F
H
o-F
m-F
p-F
m-Me
p-Me
o-OMe
m-OMe
p-OMe
2a: 86
2a: 40c
2a: 56d
2b: 78
2c: 75
2d: 54
2e: 77
2f: 71
Scheme 3. Asymmetric reduction of acylsilane 1a in the presence of Ar-BINMOL
derivatives (L3).
Table 2
Lewis acid-catalyzed reduction of acylsilanes in the presence of diethylzinca
Entry
Lewis acid
Time (h)
Yieldb (%)
9
2g: 59
2h: 67
2i: 59
1
2
3
4
5
6
7
8
9
YCl3
YbCl3
LaCl3
FeCl3
Ni(OAc)2
RhCl3
RhCl3(PPh3)2
RuCl3
24
24
24
24
24
24
24
24
10
90
25
72
67
83
29
51
45
90
10
11
12
13
14
2j: 61
2k: 69
2l: 35(80)e
Note:
a
Unless otherwise stated, reactions were conducted using 1.0 mmol of 1, diethyl
zinc (2.0 mmol), and Ti(Oi-Pr)4 (1.0 mmol), in Et2O (4 mL). And the reactions were
run for 12 h at room temperature unless otherwise noted.
Al(OiPr)3
b
Note:
Isolated yields.
i-PrMgCl was used as reductant instead of Et2Zn.
No addition of Ti(Oi-Pr)4.
GC yield in parenthesis.
a
c
Unless otherwise stated, reactions were conducted using 1.0 mmol of 1a, die-
d
thyl zinc (2.0 mmol), and Lewis acid (0.1 mmol, 10 mol %), in Et2O (4 mL).
b
e
Isolated yields.

2166
G. Gao et al. / Tetrahedron Letters 53 (2012) 2164–2166
Brigaud, T.; Lefebvre, O.; Plantier-Royon, R.; Portella, C. Chem. Eur. J. 2001, 7,
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O
M
Si
R
R
R
M = Zn, Ti, Mg
3. a) Allred, A. L.; Rochow, E. G. J. Inorg. Nucl. Chem. 1958, 5, 264; b) Brook, M. A.
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Figure 1. Proposed transition state in the reduction.
amount of YCl3, Ni(OAc)2, or Al(OiPr)3, the corresponding a-hydrox-
ysilane 2a was obtained in excellent isolated yields (entries 1, 5,
and 9). In the treatment of acylsilane 1a with Et2Zn in the presence
of YbCl3 and RhCl3, poor yields were observed. From these studies, it
was clear that some Lewis acids showed effective catalytic activity
in the hydride transfer reduction of acylsilane with diethylzinc.
Encouraged by these results, we examined the enantioselective
reduction of acylsilane (1a) was used as model substrate and cin-
chona alkaloids as chiral ligands. However, only Ni(OAc)2 gave only
6% ee10 in the presence of cinchonine (110 mol %).
Although the mechanism of the reduction with Et2Zn is unclear
at present, it could be interpreted probably as being the result of a
H-transfer process via a six-membered transition state (Fig. 1).7a
The current model for the reduction of acylsilane involves the coor-
dination of the carbonyl moiety in the molecule to metal center/
zinc and subsequent b-hydride shift and extrusion of ethylene.
In conclusion, we report here the first example of the reduction
4. Selected recent examples: (a) Sardina, F. J.; Rapoport, H. Chem. Rev. 1825, 1996,
96; (b) Takeda, K.; Tanaka, T. Synlett 1999, 705; (c) Obora, Y.; Ogawa, Y.; Imai,
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Synlett 2007, 177; (g) Shen, Z.; Dong, V. M. Angew. Chem., Int. Ed. 2009, 48, 784;
(h) Li, F. Q.; Zhong, S.; Lu, G.; Chan, A. S. C. Adv. Synth. Catal. 1955, 2009, 351; (i)
Lettan, R. B., II; Galliford, C. V.; Woodward, C. C.; Scheidt, K. A. J. Am. Chem. Soc.
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L. W. Eur. J. Org. Chem. 2011, 5039.
6. Selected examples of reduction of acylsilanes: (a) Biernbaum, M. S.; Mosher, H.
S. J. Org. Chem. 1971, 36, 3168; (b) Soderquist, J. A.; Anderson, C. L.; Miranda, E.
L.; Rivera, I.; Kabalka, G. W. Tetrahedron Lett. 1990, 31, 4677; (c) Linderman, R.
J.; Ghannam, A.; Badej, I. J. Org. Chem. 1991, 56, 5213; (d) Buynak, J. D.;
Strickland, J. B.; Lamb, G. W.; Khasnis, D.; Modi, S.; Williams, D.; Zhang, H. J.
Org. Chem. 1991, 56, 7076; (e) Cirillo, P. F.; Panek, J. S. Org. Prep. Proced. Int.
1992, 24, 553; (f) Cirillo, P. F.; Panek, J. S. J. Org. Chem. 1994, 59, 3055; (g)
of acylsilanes to
a-hydroxysilanes, in which diethylzinc was used
as a reducing agent in the presence of Ti(OiPr)4 or other Lewis
acids. The reduction typically proceeds in good yields. Further re-
search on the asymmetric reduction with organozinc compounds
is currently under way in our laboratory.
Sakaguchi,
; Mano, H.; Ohfune, Y. Tetrahedron Lett. 1998, 39, 4311; (h)
Patrocínio, A. F.; Corrêa; Mortan, P. J. S. J. Chem. Soc., Perkin Trans. 1 1999,
3133; (i) Huckins, J. R.; Rychnovsky, S. D. J. Org. Chem. 2003, 68, 10135; (j) Lou,
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Ed. 2008, 47, 1770; (l) Matsuo, J.-i.; Hattori, Y.; Ishibashi, H. Org. Lett. 2010, 12,
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Acknowledgments
7. a) Giacomelli, G.; Lardicci, L.; Santi, R. J. Org. Chem. 1974, 39, 2736; b) Takeda,
K.; Takeda, M.; Nakajima, A.; Yoshii, E. J. Am. Chem. Soc. 1995, 117, 6400; (c)
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Financial support by the National Natural Science Founder of
China (No. 20973051 and 21173064), Program for Excellent Young
Teachers in Hangzhou Normal University (HNUEYT), and Zhejiang
Provincial Natural Science Foundation of China (Y4090139) is
appreciated.
8. General procedure for reduction of acylsilane 1a to a-hydroxysilane 2a: Under
dry nitrogen atmosphere, Ti(OiPr)4 (1.0 mmol) and 2.0 mmol of Et2Zn (1.0 M
solution in hexane) were mixed in 4 mL of Et2O at room temperature. After
10 min, acylsilane 1a (1.0 mmol) was added and then the reaction was carried
out at room temperature for 12 h. The reaction was quenched with 1 N HCl. The
aqueous phase was extracted with ethyl acetate, dried over Na2SO4, filtered,
and concentrated. The product was known (e.g., see: Ref. 6k) and purified by
chromatography (86% isolated yield was obtained).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2012.02.059.
9. 4.0 or 2.0 equiv of Et2Zn resulted in poor conversion.
10. Enantiomeric excess was determined by chiral HPLC analysis (Chiralcel OD-H
References and notes
column). When 1 equiv of cinchonine (CN) was chiral auxiliary, 6% ee of
a-
hydroxysilane 2a was obtained. And other cinchona alkaloids (CD, QN, QD)
resulted in poorer enantioselectivities. When N-(2-amino-1,2-diphenylethyl)-
4-methylbenzenesulfonamide (Ts-DPEN) was used as a ligand, only 4% ee was
observed in this reaction.
1. Reviews: (a) Ricci, A.; Degl’Innocenti, A. Synthesis 1986, 647; (b) Page, P. C. B.;
Klair, S. S.; Rosenthal, S. Chem. Soc. Rev. 1990, 19, 147.
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D.; Brigaud, T.; Bouillon, J. P.; Portella, C. Synlett 1999, 705; c) Berber, H.;