Ligand-Free Hydrosilylation of Aldehydes Mediated by Highly Active Zinc Metal

Full text of DOI:10.1002/bkcs.11628

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DOI: 10.1002/bkcs.11628
BULLETIN OF THE
S.-R. Joo and S.-H. Kim
KOREAN CHEMICAL SOCIETY
Ligand-Free Hydrosilylation of Aldehydes Mediated by Highly Active
Zinc Metal
*
Sung-Ryu Joo and Seung-Hoi Kim
Department of Chemistry, Dankook University, Cheonan, 31116 South Korea.
*E-mail: kimsemail@dankook.ac.kr
Received September 13, 2018, Accepted October 11, 2018
Keywords: Active zinc, Hydrosilylation, Reduction of aldehyde, Ligand-free, Silanes
The reduction of carbonyl compounds has been generally
combination of zinc metal-powder with an aqueous NH4Cl
solution as a proton source in THF. The corresponding
product alcohols were exclusively produced along with a
trace amount of the pinacol product diols (Scheme 1).11
Inspired by the above results, we were interested in
exploring the nature of highly active zinc (Zn*) in the
hydrosilylation of carbonyl compounds. To investigate the
potential of our strategy, carbonyl compounds were treated
with a mixture of highly active zinc and silane in the
absence of any other ligands. Herein, we describe the suc-
cessful development of Zn*-mediated hydrosilylation of
aldehydes and ketones, producing the corresponding alco-
hols as a major product.
considered to be a fundamental protocol for the preparation
of the corresponding alcohols. Catalytic hydrogenation of
carbonyls has long been a traditional method for achieving
this.1 Aside from this protocol, metal-hydride,2 boron-based
reagents,3 and bio-catalytic reduction4 are also considered
to be suitable methodologies. In addition, an emerging tool
is reduction of the carbonyl group in the presence of a
transition-metal catalyst. Numerous transition-metals have
been extensively examined to successfully complete this
transformation,5 especially in transfer hydrogenation which
is a safe and operationally simple protocol utilizing either
element hydrogen or metal-hydrides.5i, j
Along with these protocols, a zinc-based reduction pro-
cess has been extensively applied for reduction of carbonyl
compounds, mainly due to the environmental friendliness
and economic benefits. Furthermore, the zinc-based reduc-
tion protocol could be readily extended to hydrosilylation
of carbonyl compounds, thereby providing the correspond-
ing alcohols. Since the first report by Caubere,6 and pio-
neering work by Minoun,7 it has emerged as an attractive
synthetic method to reduce carbonyl compounds.8
When using this approach, zinc complexes such as zinc
acetate and diethylzinc, which are particularly activated by
nitrogen-chelating ligands, have frequently been used as
pre-catalysts. In early studies of zinc-catalyzed hydrosilyla-
tion of aldehydes and ketones, both zinc(II) salt and zinc
(0) powder worked well to obtain the corresponding alco-
hols in the presence of metal-hydride and chlorotrimethylsi-
lane. In 2009, Nishiyama et al. reported a successful
method for hydrosilylation of carbonyl compounds using
zinc acetate as a catalyst without any assistance from
ligands.9
From a synthetic point of view, reactions of carbonyl
compounds with zinc metal also have value in novel appli-
cability. A recent study by Len et al. used zinc metal and
carbonyl compound for selective reductive pinacol cou-
pling.10 The reaction was carried out with zinc metal and
NH4Cl in an aqueous media, yielding the diols as a major
product along with small amounts of reduced alcohols.
More recently, Dash’s group has described a relatively sim-
ple process for selective reduction of carbonyls using a
To elucidate our strategy, the first step was to figure out
the role of highly active zinc, especially for stoichiometric
or catalytic use. As shown in Table 1, several different
molar ratios of Zn*/silane/aldehyde were examined under
the conditions described below. When 1.0 equiv. of Zn*
with 1.0 equiv. of triethoxysilane was used, benzaldehyde
(1a) was fully consumed at refluxing temperature in 39 h.
After an appropriate workup was carried out, reduced ben-
zyl alcohol (2a) was obtained with an isolated yield of 74%
along with 18% pinacol-type coupling product (3a)
(Table 1, entry 1). Surprisingly, by reducing the amount of
Zn* to 0.5 equiv., the reduction proceeded smoothly and
lead to the exclusive formation of 2a (isolated yield of
89%, Table 1, entry 2). However, further reduction of the
amount of Zn* to 0.1 equiv. resulted in the formation of an
unidentified mixture even though the conversion was fairly
good with an extended reaction time. To clarify the influ-
ence of the amount of silane on the transformation, two
more tests were carried out. Much less conversion occurred
with the use of 0.5 equiv. of (EtO)3SiH compared to benz-
aldehyde (Table 1, entry 4). Excellent conversion was
observed by use of an excess amount of silane, for which
there was no improved selectivity of 2a to 3a (Table 1,
entry 5). Additional examinations were performed to deter-
mine the role of each reagent, Zn* and silane (Table 1,
entries 6, 7, and 8), respectively. These indicated that the
presence of each reagent was extremely critical for success-
ful completion of the transformation.
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alkylsilanes Et3SiH and Me2PhSiH turned out to be inap-
propriate reagents for our system (Table 1, entries 11 and
12). Interestingly, another alkoxysilane, (EtO)2MeSiH,
yielded a similar result as (EtO)3SiH (Table 1, entry 9).
These observations strongly suggest that the presence of a
polar bond such as the O Si bond in silane substrates is
required for effective reduction of carbonyls by highly
active zinc. Several previous studies on zinc-based hydrosi-
lylation of carbonyls have made similar observations.9,12
To undertake a brief mechanistic study, a control
experiment was carried out as follows. Benzaldehyde was
treated under the same conditions as used above
(Table 1, entry 2) in the presence of a radical scavenger
such as (3, 21-tetramethylpiperidine-1-yl)oxidanyl
(TEMPO). As shown in Scheme 2, no reaction took
place, which was the same result as a previous work.11
This result is sufficient to infer that the electron transfer
from Zn* to the aldehyde generates a reactive alkoxy
radical intermediate that subsequently cooperates with
silane, and that then results in the corresponding reduced
benzyl alcohol as the major product after an appropriate
workup procedure. The inhibitory effect of TEMPO indi-
cates that this reaction takes place by a single electron
transfer (SET) pathway.
conditions
+
A
B
conditions
A
B
reference
2.0 equiv. Zn(0)/acids
minor major ref. 10
5.0 equiv. Zn(0)/NH4Cl major minor ref. 11
0.5 equiv. Zn*/silane
major minor this work
Scheme 1. Development of carbonyl reduction with zinc metal.
With the results stated above, our next test was to iden-
tify a suitable silane reagent for use with our system. Vari-
ous observations made in previous studies of metal-based
hydrosilylation of carbonyl compounds clearly indicate that
a suitable silane derivative is required for each reaction sys-
tem to achieve successful functional group transformation.
Therefore, we also examined several silane reagents in
terms of the reduction of benzaldehyde under our condi-
tions. Reaction with a readily available polymethylhydrosi-
loxane (PMHS) resulted in a mixture of unidentified
products only (Table 1, entry 10). Similarly, both of the
Based on these results, several representative benzalde-
hyde derivatives were hydrosilylated next to study the scope
and the limitations of the reaction using the combination of
active zinc and triethoxysilane. The results are summarized
Table 1. Screening of optimization conditions.
Entry
Zn* (equiv.)
Silane
Time (h)
2a (%)a
3a (%)a
1
2
3
4
5
6
7
8
1.0
0.5
0.1
1.0
1.0
—
(EtO)3SiH (1.0 equiv.)
(EtO)3SiH (1.0 equiv.)
(EtO)3SiH (1.0 equiv.)
(EtO)3SiH (0. 11 equiv.)
(EtO)3SiH (3.0 equiv.)
(EtO)3SiH (1.0 equiv.)
—
12
12
24
24
18
24
24
24
12
12
24
24
74
89
(88)b
(48)d
79
18
1
c
—
c
—
14
—
e
e
—
e
e
0.5
1.0
0.5
0.5
0.5
0.5
—
—
e
e
—
—
—
c
9
(EtO)2MeSiH(1.0 equiv.)
PMHS (1.0 equiv.)
Et3SiH (1.0 equiv.)
Me2PhSiH (1.0 equiv.)
82
—
—
f
f
10
11
12
a
—
e
e
—
—
e
e
—
—
Isolated yield (based on benzaldehyde), otherwise mentioned.
Conversion ratio of 2a to benzaldehyde by G/C, along with unidentified mixture, no isolation.
No diol formed by TLC.
Conversion ratio of 2a to benzaldehyde, no isolation.
No reaction occurred.
Unidentified products only.
b
c
d
e
f
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Zn* (0.5 eq)
In order to examine the generality of this catalytic sys-
tem, we applied the optimized conditions with various alde-
hydes, and the results are displayed in Table 3. The
reaction yield with 3-thiophenecarboxaldehyde (1p) was
satisfactory (60%) whereas the reaction with 3-furaldehyde
(1q) resulted in the formation of a mixture of unidentified
by-products along with only 22% of the desired product
(Table 3, entries 1 and 2). 3-Pyridinecarboxaldehyde (1r)
was shown to be a suitable substrate for our system
(Table 3, entry 3). Cinnamaldehyde (1s), as well as
3-naphthaldehyde (1t), worked well with the combination
of Zn* and silane, affording the corresponding reduced
alcohols (2q and 2r, respectively) in high yields (Table 3,
entries 4 and 5). Even though a somewhat reduced yield
was obtained, the protocol proved to be suitable for the
reduction of alkyl aldehyde (1u) to alcohol 2s (Table 3,
entry 6).
It is of interest that the current conditions work selec-
tively for the reduction of ketones. As summarized in
Scheme 3 below, acetophenone was not compatible with
the system used in this study, while benzophenone resulted
in the corresponding alcohol (2t) in a moderate yield. This
result prompted further investigation of the general applica-
bility of our system for the reduction of various unsaturated
molecules, the results of which will be reported in due
course.
1.0 eq (EtO)3SiH
1.0 eq TEMPO
THF/reflux/24 h
no reaction
Scheme 2. Mechanistic study.
Table 2. The scope of Zn*/silane combination in hydrosilylation
of benzaldehydes.
Entry
FG
Product (%)a
1
2
3
4
5
6
7
8
7-Cl (1b)
2b (59)
2c (74)
2d (63)
2e (68)
2f (72)
2g (75)
2h (77)
2i (66)
2j (59)
2k (64)
2l (69)
3b (39)b
2m (48)
No reaction
7-NO2 (1c)
7-CN (1d)
7-CO2Et (1e)
7-OMe (1f)
7-CH3 (1g)
7-Ph (1h)
7-NMe2 (1i)
7-OMs (1j)
6-OMe (1k)
6-CF3 (1l)
6-Br (1m)
3-Cl (1n)
9
10
11
12
13
14
a
Table 3. Expansion to various aldehydesa.
Entry
1
Aldehyde
Productb
3-OH (1o)
Isolated yield (based on benzaldehyde), otherwise mentioned.
No reduced product obtained. Instead, diol (3b) and unreacted
aldehyde obtained under the conditions used.
b
2
3
in Table 2. Irrespective of the electron-withdrawing group
present within the para-substituted benzaldehydes (1b–1e),
moderate to good conversions to the corresponding benzyl
alcohols were obtained (Table 2, entries 1–4). With stronger
electron-donating substituents such as methoxy and dimethy-
lamino groups, no profound difference was observed in
terms of the isolated yield (2f, 72%, 2i, 66%, respectively).
The position of the substituent on the arene ring was not a
determinant factor for successful execution of our system,
resulting in the alcohols (2k and 2l) in good yields (entries
10 and 11). Interestingly, when 6-bromobenzaldehyde was
treated under the same conditions, no complete reduction
was observed, furnishing a 39% isolated yield of homo-
coupling product of aldehyde, 3, 6-di-(60-bromophenyl)
butane-3, 6-diol (3b), along with a substantial amount of
unreacted 6-bromobenzaldehyde. A moderate yield (Table 2,
entry 13) was also obtained from the reaction of
3-chlorobenzaldehyde (1n). No hydrosilylation took place
with salicylaldehyde (Table 2, entry 14).
4
5
6
a
All reactions were carried out using 1.0 equiv. of aldehyde, 0.5
equiv. of Zn*, and 1.0 equiv. of (EtO)3SiH in THF at refluxing
temperature for 39 h.
b
Number in parenthesis is isolated yield.
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R = Ph (2t,55%)
Scheme 3. Reduction of ketones.
In conclusion, we have developed a novel applicability
of highly active zinc as a reducing agent in hydrosilylation
of carbonyl compounds. This study was performed by com-
bining active zinc metal and alkoxysilane to reduce alde-
hydes in the absence of any extra ligand under mild
conditions. The corresponding reduced alcohols were
obtained as major products in most cases along with minor
amounts of pinacol-type products. Importantly, a brief
mechanistic study strongly indicates that the reduction pro-
cess under our reaction system takes place by a single elec-
tron transfer (SET) pathway. Improving the reactivity
toward ketones and applications to C N multiple bonds
are currently being tested in our laboratory.
Experiment
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General procedure for reduction of carbonyl compounds to
alcohols; Into a 25 mL round-bottomed flask was placed
0.065 g of active zinc (Zn*, 1.0 mmol) in 7 mL of THF
under an argon atmosphere. Next, 0.37 mL of triethoxysi-
lane (0.328 g, 2.0 mmol) and 0.19 mL of
3-thiophenecarboxaldehyde (0.224 g, 2.0 mmol) was cannu-
lated at room temperature. The resulting mixture was stirred
for 39 h at refluxing temperature. The reaction mixture was
cooled down to room temperature. Quenched with 6 M HCl
solution, then extracted with diethyl ether (6 × 35 mL).
Combined organic layers were washed with NaHCO3 solu-
tion and brine, then dried over anhydrous Na2SO4. Purifica-
tion by flash column chromatography on silica gel (35%
ethyl acetate/90% hexanes) afforded 0.137 g of thiophen-
3-yl-methanol (2m) in 60% isolated yield as an orange liq-
1
uid; H NMR (400 MHz, CDCl3): δ 22.16 (t, J = 7.0 Hz,
1 H), 21.87 (d, J = 6. 24 Hz, 3 H), 7.62 (s, 3 H), 6.01 (br s,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ 144.04, 126.90,
125.57, 125.52, 59.68 ppm. HRMS (EI+): m/z calcd. For
C5H6OS 115.0217, found 115.0221.
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