Facile and efficient reduction of ketones in the presence of zinc catalysts modified by phenol ligands

Article abstract of DOI:10.1002/asia.201000317

In the present study, the zinc-catalyzed hydrosilylation of various ketones to give their corresponding alcohols has been examined in detail. Diethyl zinc that can be modified by easily accessible phenol ligands allows the efficient reduction of various aryl and alkyl ketones. By using a practical in situ catalyst, excellent turnover frequencies up to 1000 h^-1 and a broad functional group tolerance were achieved.

Full text of DOI:10.1002/asia.201000317

DOI: 10.1002/asia.201000317
Facile and Efficient Reduction of Ketones in the Presence of Zinc Catalysts
Modified by Phenol Ligands
Stephan Enthaler,* Bjçrn Eckhardt, Shigeyoshi Inoue, Elisabeth Irran, and
Matthias Driess[a]
Abstract: In the present study, the zinc-catalyzed hydrosilylation of various ke-
tones to give their corresponding alcohols has been examined in detail. Diethyl
zinc that can be modified by easily accessible phenol ligands allows the efficient
reduction of various aryl and alkyl ketones. By using a practical in situ catalyst, ex-
cellent turnover frequencies up to 1000 hÀ1 and a broad functional group tolerance
were achieved.
Keywords: catalysis
tion · ketones · phenol ligands · zinc
· hydrosilyla-
Introduction
only a few reports are available. Pioneering work in the
field was reported by Mimoun and co-workers.[6] Later on,
several research groups enhanced this method for increased
group tolerance, in situ deprotection of the silyl ether, the
application of PMHS (polymethylhydrosiloxane) as inexpen-
sive hydride source or incorporation of chirality.[7] However,
some catalyst systems display some drawbacks: the use of
catalyst loadings above 1.0 mol% and long reaction times.
Hence, the development of better methods is desired.
Herein, we report the successful application of a homogene-
ous hydrosilylation catalyst based on diethyl zinc modified
by phenol ligands; this catalyst has excellent performance
and is capable of reducing a variety of aromatic and aliphat-
ic ketones.
Alcohols have an extensive range of applications including,
for example, as building blocks and synthons for pharma-
ceuticals, agrochemicals, polymers, in the syntheses of natu-
ral compounds, auxiliaries, ligands and as key intermediates
in organic syntheses.[1] One key approach to their synthesis
is the reduction of ketones or aldehydes. Besides the reduc-
tion with metal hydrides (e.g., NaBH4, LiAlH4), the applica-
tion of transition metal catalysts offers efficient and versatile
strategies, such as the addition of organometallic compounds
to aldehydes, hydrosilylation, and hydrogenation of carbonyl
functionalities.[2] Catalytic hydrogenation or transfer hydro-
genation of C=O bonds are the most direct routes to alco-
hols. Nonetheless, catalytic hydrosilylation is an alternative
to (transfer) hydrogenation, because of mild reaction condi-
tions and simplicity.[3] Furthermore, the C=O bond is first re-
duced to a silyl ether (CH-OSiR3), which functions as a pro-
tecting group of the alcohol and allows sensitive additional
transformations. Up to now, manifold catalysts for the hy-
drosilylation of carbonyl compounds rely on precious
metals, such as rhodium, ruthenium, and iridium.[4] Less-ex-
pensive metals, such as titanium, zinc, tin, copper, and iron
have also been investigated.[5] In the case of zinc catalysts,
Results and Discussion
It was shown by Mimoun and co-workers that unmodified
ZnEt2 was not able to catalyze the hydrosilylation of car-
bonyl compounds. The addition of ligands to ZnEt2 was
found to significantly improve the outcome of the reaction.
Most ligands that have been used were based on diamine li-
gands. In addition, some groups demonstrated the usefulness
of zinc diamine catalysts in combination with alcohols.[7a,e,f]
We wanted to investigate whether one could apply catalysts
[a] Dr. S. Enthaler, B. Eckhardt, Dr. S. Inoue, Dr. E. Irran,
Prof. Dr. M. Driess
À
containing Zn O bonds in the absence of nitrogen-contain-
Technische Universitꢀt Berlin
Department of Chemistry
Cluster of Excellence “Unifying Concepts in Catalysis”
Straße des 17. Juni 135, 10623 Berlin (Germany)
Fax : (+49)3031429732
ing ligands, because the highly oxophilic character of the
zinc should improve the stability of the catalyst. Indeed,
À
DFT calculations showed a higher bond energy for the Zn
O bond in [MeOZnMe] (73.9 kcalmolÀ1) compared with the
À
E-mail: stephan.enthaler@tu-berlin.de
N Zn bond in the analogous [Me2NZnMe] (53.5 kcal
Chem. Asian J. 2010, 5, 2027 – 2035
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FULL PAPERS
molÀ1).[8] Based on this, we reacted dimethyl zinc with tert-
butanol in a 1:1 ratio to form a potential pre-catalyst with
the structural motif [MeZnOtBu]. The replacement of one
methyl group significantly increased the stability and ease of
handling of the compound with respect to the unmodified
dimethyl zinc. The well-defined structure contains four
[MeZnOtBu] units that form a hetero cubane structure in
the solid state.[9] Thus, the catalytic abilities of cubane 1
were investigated in the hydrosilylation of acetophenone (2;
Table 1). First, we dedicated to investigate the influence of
zinc catalyst composed of diethyl zinc and 2,4,6-tri-tert-butyl
phenol (4), a sterically more congested and less basic ligand.
First, the performance of several hydride sources was
studied at 608C for one hour. Excellent conversion of
>99% was found in the case of triethoxysilane as the hy-
dride source compared to the hetero cubane 1 (Table 2,
Table 2. Hydrosilylation of acetophenone (2) in the presence of a zinc-
phenol pre-catalyst.[a]
Table 1. Hydrosilylation of acetophenone (2) in the presence of zinc
cubane 1.[a]
Entry Catalyst [mol%] M/L
H Source
(EtO)3SiH
Me(EtO)2SiH
Ph3SiH
Ph2SiH2
PhSiH3
Me2PhSiH
Et3SiH
PMHS
T [8C] Yield [%]
1
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:0
0:0
1:1
1:1
1:1
1:3
1:5
1:10
G
60
60
60
60
60
60
60
60
60
60
25
90
60
25
25
25
99
57
<1
55
27
<1
1
2
3
4
5
6
7
ACHTUNGTRENNUNG
Entry
H Source
(EtO)3SiH
Me(EtO)2SiH
Ph3SiH
Ph2SiH2
PhSiH3
Yield [%] (Toluene)
Yield [%] (THF)
1
2
3
4
5
6
7
G
61
<1
<1
<1
21
54
23
<1
46
51
<1
<1
ACHTUNGTRENNUNG
8[b]
9[c]
10[d]
11
12
13
14
15
16
27
40
R
Me2PhSiH
Et3SiH
<1
<1
T
<1
58
>99
>99
51
1.0
1.0
0.1
1.0
1.0
1.0
ACHTUNGTRENNUNG
[a] Reactions were carried out with 0.024 mmol cubane 1, 2.4 mmol ace-
tophenone, 3.6 mmol silane, 985 mL THF/24 mL n-hexane for 1 hour. The
yield was determined by GC (30 m Rxi-5 ms column, 40–3008C; 1-phe-
nylethanol: 6.20 min, acetophenone: 6.28 min) with dodecane: 7.84 min
as the internal standard.
N
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
U
58
53
N
[a] Reactions were carried out with 0.024 mmol diethyl zinc (1.0m solu-
tion in n-hexane) and 0.024 mmol 4, 2.4 mmol acetophenone, 3.6 mmol
silane, 985 mL THF/24 mL n-hexane for 1 hour. The yield was determined
by GC (30 m Rxi-5 ms column, 40–3008C; 1-phenylethanol: 6.20 min,
acetophenone: 6.28 min) with dodecane: 7.84 min as the internal stan-
dard. [b] PMHS=polymethylhydrosiloxane. [c] Instead of the in situ cat-
alyst 0.024 mmol diethyl zinc (1.6m in n-hexane) without addition of
ligand were applied as catalyst precursor. [d] Without catalyst, 96% of
acetophenone was recovered.
solvent and the hydride source on the hydrosilylation reac-
tion. Various silanes were tested in tetrahydrofuran and tol-
uene at 608C. After one hour, the resultant silyl ether was
cleaved by a base to yield the corresponding alcohol. The
best results were obtained with (EtO)3SiH (61%) in tolu-
ene, whilst all other silanes gave low yields in toluene. In
tetrahydrofuran solvent, Ph2SiH2 (46%) and PhSiH3 (51%)
gave reasonable amounts of product next to (EtO)3SiH
(54%). To further improve the catalytic ability, we modified
the structure of the precursor to afford an in-situ-generated
entry 1). Moderate yields of 1-phenylethanol were produced
with diethoxymethylsilane and diphenylsilane (Table 2, en-
tries 2 and 4). In contrast, triphenylsilane, dimethylphenylsi-
lane, and triethylsilane showed no hydride transfer. Unfortu-
nately, the cheap and low toxic polymethylhydrosiloxane
(PMHS) gave only moderate yields of 3. However, for ongo-
ing studies, the highly active triethoxysilane was applied. To
clarify the influence of the ligand, diethyl zinc was used as
the precursor (Table 2, entry 9). Diethyl zinc did operate as
a pre-catalyst, but with somewhat lower conversion, whilst
in its absence, no reaction took place. Hence, the addition
of phenol is important for the acceleration of the reaction.
In addition, the zinc to ligand ratio was examined in the
range of 1:0.5 to 1:10 in more detail. Next, the reaction tem-
perature was decreased to room temperature. At ambient
conditions, a turnover number of 58 hÀ1 was feasible. In-
creasing the temperature to 908C resulted in full conversion
within one hour, even if a non-identified black precipitate
Abstract in German: Im Rahmen dieser Arbeit wird die
Zink-katalysierte Hydrosilylierung von Ketonen zu den ent-
ACHTUNGTRENNUNGsprechenden Silylethern mit anschließender Hydrolyse zu
deren Alkoholen vorgestellt. Wobei exzellente Ausbeuten
und Umsꢀtze durch die Modifikation des katalytisch einge-
setzten Diethylzink mit Phenolen erreicht werden konnten.
Nach genauer Untersuchung verschiedenster Reaktionspara-
meter konnten turnover frequencies (TOF) von ca. 1000 hÀ1
erzielt werden. Die hervorragenden Eigenschaften des Kata-
lysatorsystems konnte weiterhin in der Hydrosilylierung ver-
schiedenster Ketone erfolgreich gezeigt werden. Zum besse-
ren Verstꢀndnis der Reaktion wurden verschiedene mecha-
nistische Experimente durchgefꢂhrt.
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Zinc-Catalyzed Ketone Reduction
Table 3. Hydrosilylation of acetophenone (2): ligand variation.[a]
was formed after several minutes. Lowering the catalyst
loading to 0.1 mol% also revealed excellent activity at 608C
with a turnover frequency of >999 hÀ1.
After optimization of the reaction conditions, we investi-
gated the influence of the ligand structure in more detail.
Several phenols were tested in combination with diethyl
zinc in the hydrosilylation of acetophenone. First, the bulki-
ness of our model 2,4,6-tri-tert-butylphenol ligand was re-
duced (Table 3, entries 1–10). Interestingly, substitution in
the 2- and 6-postions was not necessary for obtaining good
yields (Table 3, entry 9). However, the result from the use of
unsubstituted phenol implies the necessity for alkyl groups
in the ligand moiety. Next, the influence of electron-donat-
ing as well as electron-withdrawing functional groups was
studied. First, the substitution pattern of a methoxy group
was investigated (Table 3, entries 11–13). Best results were
obtained with para-substitution, whilst the yield decreased
with meta- and ortho-substitution. In the case of trifluoro-
methyl- and chloro-substitution, no connectivity was ob-
served. Furthermore, additional donor atoms at the ligand
scaffold decreased the yield. The activity of the pre-catalyst
is probably reduced by its coordination to the metal
(Table 3, entries 20 and 21).
Entry
1
ligand
Yield [%]
58
4
5
6
7
2
3
4
50
53
61
Next, the scope and limitations of the zinc pre-catalyst,
synthesized from diethyl zinc and phenol 9 in a ratio of 1:1,
was studied. The reaction was carried out using 1.0 mol% of
the in-situ-generated catalyst at 608C for 1 hour. The pro-
duced silyl ether was hydrolyzed under basic conditions to
obtain the corresponding alcohol. The influence of substitu-
tion on the phenyl moiety of acetophenone was also investi-
gated (Table 4). Good to excellent yields were achieved
with electron-withdrawing as well as electron-donating sub-
stituents (Table 4, entries 2, 4–9). Extraordinary yields were
obtained with ketones 31 and 36, because full conversion
was observed after 30 minutes. However, an increase in the
steric congestion at the 2- and 6-positions gave no detecta-
ble product at all (Table 4, entry 3).[10] On the contrary, an
increase of the bulkiness of the alkyl chain had no negative
influence on the conversion (Table 4, entries 10–13). The hy-
drosilylation of a ketone containing a a-C=C bond yielded
the a-saturated ketone (Table 4, entry 16). In addition, sev-
eral dialkyl ketones were reduced with excellent conversions
by this zinc pre-catalyst (Table 4, 17–19).
5
6
8
9
46
64
7
10
30
8
9
11
12
43
64
10
11
13
14
27
51
Competitive hydrosilylation experiments of para/meta-
substituted acetophenones were also carried out. Equimolar
amounts of substituted ketone (2.4 mmol) and unsubstituted
acetophenone (2.4 mmol) were reacted with triethoxysilane
(2.4 mmol) in the presence of our in situ catalyst (ZnEt2/9).
The reaction mixture was hydrolyzed after one hour and
purified as described. The yields of both compounds were
determined by GC analysis and correlated with Hammett
s+ values.[11] The values were correlated according to log-
12
15
17
13
14
15
16
17
18
28
26
26
ACHTUNGTRENNUNG
(kX/kH)=1s+ (Figure 1). A linear regression led to a reac-
tion constant value of 1=À0.90. The negative Hammett
value indicated a partial positive charge in the transition
state in comparison with the starting substrates. Therefore,
electron-donating groups accelerate the rate of reaction by
16
19
34
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S. Enthaler et al.
FULL PAPERS
Table 3. (Continued)
Table 4. (Continued)
Entry
17
ligand
Yield [%]
27
Entry[a]
Substrate
Yield [%][b]
20
8
35
36
>99 (93)
18
19
21
22
35
50
9
>99[c] (87)
20
21
23
24
11
5
10
11
12
37
38
39
94[c] (90)
>99 (96)[c]
86 (81)[c]
22
23
25
26
29
47
13
14
40
41
99 (87)
[a] Reactions were carried out with 0.024 mmol diethyl zinc (1.0m solu-
tion in n-hexane) and 0.024 mmol phenol, 2.4 mmol acetophenone,
3.6 mmol silane, 985 mL THF/24 mL n-hexane for 1 hour. The yield was
determined by GC (30 m Rxi-5 ms column, 40–3008C; 1-phenylethanol:
6.20 min, acetophenone: 6.28 min) with dodecane: 7.84 min as the inter-
nal standard.
>99[c] (89)
15
16
17
42
43
44
37 (34)[c]
Table 4. Scope and limitations of the in situ system composed of ZnEt2
and ligand 9.
24[d]
>99 (93)
Entry[a]
1
Substrate
Yield [%][b]
18
19
45
46
>99 (83)
>99 (79)
2
>99 (96)
2
3
27
98 (84)
20
21
47
48
>99 (82)
28: R1 =H; R2 =Me
29: R1 =H, R2 =tBu
30: R1 =Me, R2 =Me
<1
<1
<1
87 (69)
[a] Reactions were carried out with 0.024 mmol 0.024 mmol ZnEt2 and
0.024 mmol 9, 2.4 mmol ketone, 3.6 mmol triethoxysilane, 1.0 mL THF
for 1 hour at 258C, The yield was determined by GC (30 m Rxi-5 ms
column, 40–3008C) and by 1H NMR. [b] In brackets the isolated yield is
stated. The analytical properties are in agreement with literature reports.
[c] Reaction time: 30 min. [d] 4-phenyl-butan-2-one.
4
5
31
32
>99 (94)[c]
89 (80)
resonance stabilization. The positive charge could be created
at the carbonyl carbon by the coordination of the oxygen to
zinc and the shift of electron density onto the zinc center.
In order to study the reaction in detail, several complexes
were synthesized and isolated by the reaction of equimolar
amounts of phenol (13) or substituted phenols (6, 7, and 9)
with dimethyl zinc in toluene (Scheme 1).[12] The corre-
sponding phenol was dissolved in toluene and cooled to
6
7
33
34
71[c] (68)
60 (51)
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Zinc-Catalyzed Ketone Reduction
Figure 2. Molecular structure of 49a. Hydrogen atoms are omitted. Ther-
mal ellipsoids are drawn at the 50% probability level.
Figure 1. Hammett correlation for the hydrosilylation of p-/m-substituted
acetophenone (logACHTUNGTRENNUNG
Figure 3. Molecular structure of 49b. Hydrogen atoms are omitted. Ther-
mal ellipsoids are drawn at the 50% probability level.
other and the square (Table 5). In consequence, the cube is
far off the ideal shape. On the other hand, performing the
reactions in tetrahydrofuran and crystallization in toluene
Scheme 1. Synthesis of catalyst precursors.
yielded a complex with a four-membered Zn2O2 ring bearing
[14,15]
À
two Zn Me subunits and two phenoxides (Figure 3).
À788C. A stock solution of dimethyl zinc (1.2m in toluene)
was added through a syringe. The clear solution was allowed
to reach room temperature. All volatiles were removed in
vacuum and the white residues were recrystallized from con-
centrated solutions.
In the case of ligand 7, the reaction was carried out with
dimethyl zinc as well as diethyl zinc. Suitable crystals for
single-crystal X-ray diffraction analysis were obtained in tol-
uene (49a, 51, 53) and n-hexane (52), while compound 49b
was obtained in tetrahydrofuran (reaction medium) and
later crystallized in toluene.[13] Unfortunately, compound 50
gave no crystals suitable for X-ray diffraction. The X-ray
crystal structures of 49a, 49b, 51, 52, and 53 are depicted in
Figure 2–6.
Furthermore, each zinc atom is stabilized by one solvent
molecule. The methyl groups attached to the zinc atoms are
out of plane and trans with respect to each other. Remarka-
bly, the spiro-zinc compound 51 crystallized out of toluene
solution by increasing the bulkiness of the phenol in 2,6-po-
sition with isopropyl groups (Figure 4). Here two four-mem-
Table 5. Selected bond distances (pm) and angles (deg) for 49a, 49b, 51,
52, and 53.
49a
49b
51
52
53
À
Zn1 O1
2.059(2) 1.988(2) 1.9465(2)
2.254(3) 2.003(2) 1.9456(19) 1.945(2) 1.9869(12)
2.144(3) 1.988(2) 1.9549(19) 1.958(2) 1.9720(12)
2.045(2) 2.003(2) 1.975(2)
1.928(4) 1.988(2) 1.929(3)
81.01(9) 99.75(8) 80.94(9)
1.968(2) 1.9720(12)
À
Zn1 O2
À
Zn2 O1
À
Zn2 O2
1.970(2) 1.9869(12)
1.931(4) 1.934(2)
99.01(10) 81.42(5)
In the case of phenol 13, we observed the formation of
two different types of structure depending on the solvent
(Figure 2 and 3). A hetero cubane motif (Zn4O4) was found
À
Zn1 Me/Et
À
À
Zn1 O1
Zn2
À
À
Zn1 O2
Zn2
84.04(10) 99.75(8) 80.46(8)
99.31(10) 81.42(5)
À
in the crystals that crystallized out of toluene. The Zn O
bond lengths and angles in the top square differ from each
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2031

S. Enthaler et al.
FULL PAPERS
Figure 6. Molecular structure of 53. Hydrogen atoms are omitted. Ther-
mal ellipsoids are drawn at the 50% probability level.
plexes with the [(RO)2Zn] moiety by reacting ZnMe2 with
an excess of phenols were unsuccessful. The [(RO)ZnMe]
unit was the only major product obtained.
Figure 4. Molecular structure of 51. Hydrogen atoms are omitted. Ther-
mal ellipsoids are drawn at the 50% probability level.
The isolated complexes were then subjected to the cata-
lytic hydrosilylation of acetophenone (2) under the reaction
conditions described in Table 3 (Scheme 2). Here, excellent
bered rings are connected through a bridging zinc atom in a
spiro-like fashion. Two different types of zinc atoms are ob-
served, two ZnMe subunits are bonded to two phenoxides,
while the second Zn type is surrounded by four phenoxide
ligands. Both four-membered rings are twisted with respect
to each other. The same structural motif was seen in the
case of ZnEt2 with 2,6-di-iso-propyl phenol (Figure 5). In
the early 90’s Power and co-workers reported the use of Zn-
ACHTUNGTRENNUNG
(CH2SiMe3)2 in combination with ligand 7.[16] Here, the cor-
responding dimer with the same structural motif was ob-
tained after crystallization from n-hexane.
Scheme 2. Application of catalyst precursors in the hydrosilylation of ace-
tophenone.
performance at room temperature was found using 1 mol%
catalyst with respect to zinc. In most cases a better catalyst
performance was observed. Comparing the results for com-
plexes 49a and 49b showed an extraordinary behavior for
the tetramer, while the dimer produced lower yields. This
fact indicated that the complexes are perhaps stable under
the reaction conditions and no decomposition to smaller
units (e.g., monomers) occurred.
Although the mechanism is still unknown, different
1H NMR experiments were carried out with the isolated
complexes 49–53, with the hope of identifying the primary
steps of substrate activation. Accordingly, [D8]THF solutions
containing complexes 49–53 and acetophenone (2) in molar
ratios of 1:1–1:10 were investigated. However, no significant
1H NMR spectroscopic changes were observed when com-
pared with the spectra of the pure components, even after
heating the mixtures to 808C for several hours. Only a mar-
ginal shift of 0.03–0.06 ppm was observed for the complexes,
which was probably caused by either solvation or coordina-
tion of acetophenone to the complexes. Likewise, stoichio-
metric mixtures of 49–53 and triethoxysilane showed no sig-
Figure 5. Molecular structure of 52. Hydrogen atoms are omitted. Ther-
mal ellipsoids are drawn at the 50% probability level. A disordered sol-
vent molecule (toluene) has also been omitted.
An increase in bulkiness using tert-butyl groups in the 2,6-
position resulted in a four-membered square planar system
À
spanned by alteration of Zn Me units and 2,6-di-tert-butyl-
phenoxides (Figure 6). In comparison to the simple phenol
ligand, all substituents are in-plane with the Zn2O2 moiety.
A similar structure with ethyl groups attached to the zinc
has already been reported.[17] Attempts to synthesize com-
1
nificant changes in the H NMR spectrum, even after heat-
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Zinc-Catalyzed Ketone Reduction
À
ing for several hours. Notably, no Zn H signals could be as-
signed. On the other hand, a mix of the three components,
namely, complexes 49–53, acetophenone, and triethoxysilane
at room temperature exhibited new signals in the aromatic
region and new multiplets for the ethoxysilyl groups, whilst
tion of a broad variety of substrates (aryl and alkyl ketones).
In addition, experiments were also carried out to give an
idea of the reaction mechanism.
À
the hydride (Si H) signals disappeared. In all cases, the
Experimental Section
À
signal for Zn CH3 changed from singlets into a set of mul-
General: All manipulations with oxygen- and moisture-sensitive com-
pounds were performed under dinitrogen using standard Schlenk tech-
niques. Toluene, n-hexane and THF were distilled in sodium/benzophe-
none ketyl under dinitrogen. Diethyl zinc solution (1.0m in n-hexane pur-
chased from Aldrich) and the phenols were used without further manipu-
lations. 1H and 13C NMR spectra were recorded on a Bruker AFM 200
spectrometer (1H: 200.13 MHz; 13C: 75.5 MHz) using the proton signals
of the deuterated solvents as reference. Single crystal X-ray diffraction
measurements were recorded on an Oxford Diffraction Xcalibur S Sa-
phire spectrometer. IR spectra were recorded either on a Nicolet Series
II Magna-IR-System 750 FTR-IR or on a Perkin–Elmer Spectrum 100
FT-IR spectrophotometer. Electron-impact mass spectra (EI-MS) were
recorded on a Finnigan MAT95S mass spectrometer. GC-MS measure-
ments were carried out on a Shimadzu GC-2010 gas chromatograph
(30 m Rxi-5 ms column) linked with a Shimadzu GCMA-QP 2010 Plus
mass spectrometer. Safety consideration: During our studies we used trie-
thoxysilane as a reducing reagent without any incident. However, Buch-
wald et al. reported difficulties with triethoxysilane.[18]
tiplets, but was still observed in the same region. This proba-
bly indicates that the aggregates (e.g., tetramer, dimer) are
still intact and cause the multiplicity of the signals. We
assume that the complexity arose because of the coordina-
tion of the product/substrate to the zinc complex, which
lead to the formation of diastereomers or by the formation
of higher aggregated zinc species. On the other hand, a se-
lective transfer of the hydride to the carbonyl carbon was
observed by labelling studies without any scrambling, which
means that the hydride was incorporated at the carbon of
the carbonyl functionality.
Based on the results we have proposed a catalytic mecha-
nism, which is illustrated in Scheme 3. In the initial step of
the catalytic cycle, the substrate coordinates to the zinc,
General procedure for the hydrosilylation reaction: A Schlenk tube was
charged with an appropriate amount of the corresponding phenol
(0.024 mmol, 1.0 mol%) and purged with nitrogen (nitrogen/vacuum
three cycles). The phenol was dissolved in anhydrous tetrahydrofuran
(850 mL), and diethyl zinc (240 mL 0.024 mmol) from a stock solution
(1.0 mL diethyl zinc, 1.0m in n-hexane, diluted with 9.0 mL THF) was
added and the mixture was stirred for 10 min at room temperature. To
the clear solution, acetophenone (2.4 mmol) and triethoxysilane
(3.6 mmol, 1.5 equiv) were added through a syringe. The reaction mixture
was stirred in a preheated oil bath at 608C for 60 min. The mixture was
cooled on an ice bath and was treated with dodecane (10 mL) as GC stan-
dard (for GC-analysis), methanol (1.0 mL), and aqueous sodium hydrox-
ide solution (1.0 mL) with vigorous stirring (Caution: The reaction mix-
ture bubbled vigorously upon the addition of the base). The reaction mix-
ture was stirred for 60 min at 08C and was then extracted with diethyl
ether (2x 10.0 mL). The combined organic layers were washed with brine,
dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The
yield was monitored by GC (30 m Rxi-5 ms column, 40–3008C; 1-phenyl-
ethanol: 6.20 min, acetophenone: 6.28 min).
Scheme 3. Potential reaction pathway of the hydrosilylation with zinc-cat-
alysts.
Procedure for the competitive hydrosilylation reaction: A pressure tube
was charged with 2,6-dimethylphenol (0.024 mmol, 1.0 mol%) and
purged with nitrogen (nitrogen/vacuum three cycles). The phenol was dis-
solved in anhydrous tetrahydrofuran (850 mL), and diethyl zinc (240 mL
0.024 mmol) from a stock solution (1.0 mL diethyl zinc, 1.0m in n-hexane,
diluted with 9.0 mL THF) was added and the mixture was stirred for
10 min at room temperature. To the mixture, acetophenone (2.4 mmol),
substituted acetophenone (2.4 mmol) and triethoxysilane (2.4 mmol)
were added with a syringe. The reaction mixture was stirred in a preheat-
ed oil bath at 608C for 60 min. The mixture was cooled on an ice bath
and was treated with dodecane (10 mL) as GC standard (for GC-analy-
sis), methanol (1.0 mL), and aqueous sodium hydroxide solution (1.0 mL)
with vigorous stirring (Caution: The reaction mixture bubbled vigorously
upon the addition of the base). The reaction mixture was stirred for
60 min at 08C and was then extracted with diethyl ether (2x 10.0 mL).
The combined organic layers were washed with brine, dried over anhy-
drous Na2SO4, and filtered. The yields were monitored by GC (30 m Rxi-
5 ms column, 40–3008C).
thereby activating the carbonyl carbon and increases the
À
electrophilic character, which allows its interaction with Si
H. Next, the hydride is transferred to the carbonyl carbon,
while the silyl group is transferred to the oxygen. In the
final step, the product is released and the starting complex
is regenerated.
Conclusions
We have demonstrated the successful application of a cata-
lyst concept based on zinc for the hydrosilylation of ketones.
The novel in situ system is easily prepared by mixing diethyl
zinc and a phenol ligand. The influence of different reaction
parameters were investigated and presented. Excellent turn-
over frequencies (up to 999 hÀ1) were obtained under opti-
mized conditions. The best catalyst was applied in the reduc-
General synthesis of methyl zinc phenoxides and ethyl zinc phenoxide: A
solution of the corresponding phenol (7.6 mmol) in toluene (10 mL) was
cooled to À788C under an atmosphere of dinitrogen. A solution of di-
methyl zinc (7.6 mmol, 1.2m in toluene) or diethyl zinc (7.6 mmol, 1.0m
in n-hexane) was added dropwise with a syringe. The solution was al-
lowed to warm to room temperature overnight. The volatiles were re-
Chem. Asian J. 2010, 5, 2027 – 2035
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
2033

S. Enthaler et al.
FULL PAPERS
moved in vacuum to yield a white powder. Colourless crystals were ob-
tained by crystallization from toluene.
1.240 mgmÀ3; m (MoKa)=1.339 mmÀ1; 24498 collected reflections; 9664
crystallographically independent reflections (Rint =0.0403); 9664 reflec-
tions with I>2s(l); qmax =25.008; R(Fo)=0.0428 (I>2s(l)); wRACHTUNGTRENNUNG
(F2o)=
49a: yield: 47% (colourless crystals obtained from toluene); IR (KBr):
n˜ =2958 (m), 1590 (s), 1485 (s), 1206 (s), 1169 (w), 1022 (w), 760 (m), 689
0.0794 (all data); 661 refined parameters.
1
(m) cmÀ1; H NMR (200 MHz, C6D6, 258C): d=6.70–7.12 (m, 5H, C6H5),
52: Orthorhombic; space group P212121; a=13.2039(5), b=16.9896(4),
c=25.3489(7) ꢃ; V=5686.4(3) ꢃ3; Z=4; 1calc =1.233 mgmÀ3; m (MoKa)=
1.297 mmÀ1; 22977 collected reflections; 9991 crystallographically inde-
À0.29 ppm (s, 3H, Zn-CH3); 13C NMR (75 MHz, C6D6, 258C): d=158.2
(C=O), 130.4, 122.5, 119.0, À14.2 ppm (Zn-CH3); MS MS (70 eV, EI): m/
z (%)=685 [M+-2H].
pendent reflections (Rint =0.0497); 9991 reflections with I>2s(l); qmax
=
25.008; R(Fo)=0.0398 (I>2s(l)); wRACTHNUTRGNEUNG
(F2o)=0.0533 (all data); 660 refined
49b: yield: 46% (reaction solvent: THF, colourless crystals from tolu-
ene); IR (KBr): n˜ =2957 (m), 1592 (s), 1487 (s), 1246 (s), 1169 (w), 1018
parameters.
(w), 824 (m), 760 (m), 692 (m) cmÀ1 1H NMR (200 MHz, C6D6, 258C):
;
53: Monoclinic; space group P21/n; a=10.1554(2), b=9.4553(2), c=
1calc
15.3500(4) ꢃ;
b=95.380(2)8;
V=1467.45(6) ꢃ3;
Z=2;
=
d=6.50–7.19 (br, Ar), 3.13 (br), 0.83 (br), À0.22 ppm (br); 13C NMR
(75 MHz, C6D6, 258C): d=158.7, 130.4 (br), 129.3 (br), 122.1 (br), 120.4
(br), 119.0 (br), 24.9 (br), À14.3 ppm; MS (70 eV, EI): m/z (%)=335,
285, 235, 169, 94 (Molpeak was not detectable).
1.293 mgmÀ3; m (MoKa)=1.657 mmÀ1; 6500 collected reflections; 2579
crystallograp,hically independent reflections (Rint =0.0214); 2579 reflec-
tions with I>2s(l); qmax =25.008; R(Fo)=0.0243 (I>2s(l)); wRACHTUNGTRENNUNG
(F2o)=
0.0553 (all data); 161 refined parameters.
51: yield: 44% (colorless crystals from toluene); IR (KBr): n˜ =2959(s),
2870 (w), 1463 (m), 1464 (m), 1439 (m), 1384 (w), 1259 (w), 1194 (m),
1045 (s), 1016 (s), 748 (w) cmÀ1; d=(broad signals were found, we
assume a dynamic process) 6.80–7.16 (m, br), 3.76 (br), 2.98 (br), 0.84–
1.62 (br), 0.41 (br), À0.61 ppm (Zn-CH3); 13C NMR (75 MHz, C6D6,
258C): d=153.7, 138.2 (br), 129.3, 125.6, 124.1, 122.2 14.3–31.9 (br),
À13.7 ppm (Zn-CH3); MS (70 eV, EI): m/z (%)=911, 565, 466, 440, 410
(Molpeak was not detectable).
Acknowledgements
This work was supported by the Cluster of Excellence “Unifying Con-
cepts in Catalysis” (sponsored by the Deutsche Forschungsgemeinschaft
and administered by the Technische Universitꢀt Berlin). The authors
thank Prof. M. Beller, Dr. K. Junge, Dipl. Chem. K. Schrçder, and Dipl.
Chem. T. Schulz (Leibniz-Institut fꢂr Katalyse e.V. an der Universitꢀt
Rostock) for general discussions, generous chemical gifts and technical
support.
52: yield: 63% (colourless crystals from toluene); IR (KBr): n˜ =2960 (s),
2868 (m), 1585 (w), 1552 (m), 1456 (m), 1435 (s), 1384 (w), 1362 (w),
1320 (m), 1187 (s), 1110 (w), 1043 (w), 933 (w), 885 (w), 837 (m), 798
1
(w), 756 (s), 681 (w), 550 (w) cmÀ1; H NMR (200 MHz, C6D6, 258C): d=
(broad signals were found, we assume a dynamic process) 6.80–7.17 (m,
br), 3.79 (br), 2.95 (br), 1.02–1.60 (br), 0.67–0.78 (br), 0.33–0.51 (br),
À0.21–0.36 ppm (br); 13C NMR (75 MHz, C6D6, 258C): d=154.1, 138.0
(br), 129.3, 125.6, 124.1 (br), 122.2 21.7–27.9 (br), 11.0, 1.2 ppm; MS
(70 eV, EI): m/z (%)=598, 549, 478, 463, 419, 302, 232, 161 (Molpeak
was not detectable).
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53: yield: 78%; (colourless crystals obtained from toluene); IR (KBr):
n˜ =2952 (s), 2871 (m), 1479 (s), 1426(m), 1385 (s), 1366 (m), 1267 (m),
1206 (s), 1093 (m), 1044 (s), 1016 (s), 761 (w) cmÀ1 1H NMR (200 MHz,
;
C6D6, 258C): d=7.33 (d, 2H, J=7.84 Hz, m-H C6H3), 6.87 (t, 1H, J=
7.84 Hz, p-H C6H3), 1.65 (s, 18H, tert-Bu), À0.53 ppm (s, 3H, Zn-CH3);
13C NMR (75 MHz, aceton-d6, 258C): d=159.4, 140.6, 126.0, 120.4, 35.5,
32.6, À13.0 ppm (Zn-CH3); MS MS (70 eV, EI): m/z (%)=566 (M+-2H),
284 ((6)ZnMe).
Single-crystal X-ray structure determination: Crystals were mounted on a
glass capillary in perfluorinated oil and measured in a cold N2 flow. The
data were collected using an Oxford Diffraction Xcalibur S Saphire at
150 K (MoKa radiation, l=0.71073 ꢃ). The structures were solved by
direct methods and refined on F2 with the SHELX-97[19] software pack-
age. The positions of the hydrogen atoms were calculated and considered
isotropically according to a riding model.
CCDC 76536 (49a), CCDC 765370 (49b), CCDC 773477 (51),
CCDC 765368 (52), CCDC 765369 (53) contain the supplementary crys-
tallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif
49a: Monoclinic; space group P21/c; a=20.0628(6), b=7.9081(2), c=
19.1543(5) ꢃ; b=108.142(3)8; V=2887.92 ꢃ3; Z=5; 1calc =1.596 mgmÀ3
;
m (MoKa)=3.312 mmÀ1; 24228 collected reflections; 9518 crystallographi-
cally independent reflections (Rint =0.0662); 9518 reflections with I>
2s(l); qmax =25.008; R(Fo)=0.0471 (I>2s(l)); wRACTHNUTRGNEUNG
(F2o)=0.0656 (all data);
329 refined parameters.
¯
49b: Triclinic; space group P1; a=8.9595(3), b=9.8203(4), c=
13.0239(5) ꢃ;
a=86.826(3),
b=88.262(3),
g=80.106(3)8;
V=
1126.88(7) ꢃ3; Z=2; 1calc =1.448 mgmÀ3; m (MoKa)=2.152 mmÀ1; 8924
collected reflections; 3968 crystallographically independent reflections
(Rint =0.0348); 3968 reflections with I>2s(l); qmax =25.008; R(Fo)=
0.0384 (I>2s(l)); wR
ACHTUNGTRENNUNG
(F2o)=0.0808 (all data); 255 refined parameters.
51: Monoclinic; space group P21/c; a=17.0669(4), b=12.9770(4), c=
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V=5502.6(2) ꢃ3;
Z=4;
1calc =
2034
www.chemasianj.org
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 2027 – 2035

Zinc-Catalyzed Ketone Reduction
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Received: April 30, 2010
Published online: July 15, 2010
Chem. Asian J. 2010, 5, 2027 – 2035
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
2035