An efficient metal-free reduction using diphenylsilane with (tris-perfluorophenyl)borane as catalyst

Article abstract of DOI:10.1016/j.tetlet.2009.06.066

An efficient metal-free reduction of various C{double bond, long}X (X = O, N, C) bonds into their corresponding amines or hydrocarbons using the Ph₂SiH₂/B(C₆F₅)₃ catalytic system is demonstrated. This protocol reduces enamines, enol esters, carbonyls, amides, and isocyanates.

Full text of DOI:10.1016/j.tetlet.2009.06.066

Tetrahedron Letters 50 (2009) 4912–4915
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Tetrahedron Letters
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An efficient metal-free reduction using diphenylsilane
with (tris–perfluorophenyl)borane as catalyst
MeiXuan Tan, Yugen Zhang *
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient metal-free reduction of various C@X (X = O, N, C) bonds into their corresponding amines or
Received 29 April 2009
Revised 27 May 2009
Accepted 12 June 2009
Available online 16 June 2009
hydrocarbons using the Ph
ines, enol esters, carbonyls, amides, and isocyanates.
2 2 6 5 3
SiH /B(C F ) catalytic system is demonstrated. This protocol reduces enam-
Ó 2009 Elsevier Ltd. All rights reserved.
Reductions of unsaturated organic compounds by hydrogena-
tion, hydroboration, and hydrosilylation are well-known protocols
in organic synthesis. Among various methods, the widely used
have rarely been used in this protocol. Herein, we report a power-
ful B(C F ) -catalyzed hydrogenation protocol utilizing phenylhy-
6 5 3
drosilanes for the reduction of various groups, such as enamines
(indoles), enol esters, carbonyls, amides, and isocyanates (Scheme
1). Hydrogenation products were obtained instead of hydrosilyla-
1
transition metal-catalyzed reductions play a key role in these
transformations. However, the use of transition metal catalysts
has several shortcomings, such as metal leaching, expensive cata-
2
lysts, and difficulty in catalyst recycling. Other protocols also suf-
fer from various challenges. Main group hydride reagents such as
Previous work
4 4
NaBH and LiAlH provide stoichiometric reductions that are pla-
O
gued by high costs, tedious procedures, and toxic chemical
R1
R2
PMHS
R1
R2
wastes.3 Recently, metal-free catalytic systems for unsaturated
or Et SiH
bond reduction have attracted considerable attention. Organocata-
lysts have been developed for the hydrogenation of enones and
imines with dihydropyridine as the hydrogen source.4–6 The
groups of Stephan and Rieger reported ‘frustrated Lewis pairs’ con-
O
3
R1
R1
or n-ButylSiH3
OH
R1 OH
B(C F )
6
5 3
R1
H
6 5 3
sisting of a bulky Lewis acid B(C F ) and a base (amine, phosphine,
or N-heterocyclic carbene), which demonstrated significant poten-
1 O
R2
R
R1
H
tial in dihydrogen activation and metal-free catalytic hydrogena-
7
–11
tion of imines.
In this context, B(C
6
F
5
)
3
2
has also been shown
1
to catalyze the hydrosilylation of imines, reduction of alcohols
with silane, and hydrogenation of imines. In these protocols,
Lewis acidic B(C was critical for the formation of a hydridob-
1
3
14
This work
6 5 3
F )
orate counterion with different hydride sources, and further served
as a reductant in various reduction reactions. This concept opened
a new method for metal-free catalytic hydrogenation reactions.
However, it has been limited to imine and nitrile substrates.
NR2
R1
NR2
R1
O
R1
R1
OR2
It is known that B(C
6 5 3
F ) can extract a hydride from hydrosilane
2–14
to form a [R Si–H—B(C
3
6
F
5
)] ion pair.1
We are interested in
Ph2SiH2
B(C F )
H
R1 NCO
R1
N
extending the borane-based Lewis acid catalyst concept to exam-
ine different hydrosilane reagents for the reduction of a broader
range of functional groups. Previous studies were focused on using
6
5 3
OR2
R1
R1
1
5
alkyl silanes R4ÀnSiH
n
[polymethylhydrosiloxane (PMHS), Et3-
1
2,16
17
18
SiH,
and n-butylSiH
3
]. However, more active phenylsilanes
H
H
R2
N
R2
N
R1
R1
O
*
Corresponding author.
E-mail address: ygzhang@ibn.a-star.edu.sg (Y. Zhang).
Scheme 1.
0
040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.066

M.X. Tan, Y.G. Zhang / Tetrahedron Letters 50 (2009) 4912–4915
4913
tion products using our system. The B(C
6
F
5
)
3
-catalyzed reduction
Table 2
6 5 3
B(C F )
-catalyzed reduction of various functional groups with diphenylsilanea
protocol would be a particularly attractive process due to its mild
reaction conditions, broad applicability to different substrates, and
easy-to-handle silane reducing agent, as compared to the use of
stoichiometric hydride reagents for reduction and other conven-
tional catalytic systems.
Indole was chosen as the substrate to test this catalytic system.
It was reduced quantitatively to indoline at 75 °C with 2 equiv of
Entry
Substrate
Product
Yieldb (%)
H
N
H
N
1
99
6 5 3
diphenylsilane in the presence of 2 mol % of B(C F ) in toluene
for 16 h. The hydrogenation product, indoline was confirmed by
gas chromatography–mass spectrometry (GC–MS) and NMR spec-
troscopy. An NMR tube-scale reaction (Fig. 1) also clearly showed
that indole was fully consumed, and indoline was formed as the
only product. Different hydrosilanes were screened under the same
reaction conditions (see Table 1). The very bulky triphenylsilane
and less active triethylsilane did not promote any conversion.
Phenylsilane and diphenylsilane gave quantitative yields of the
reduction product, while phenyldimethylsilane and diphenylmeth-
ylsilane gave only 72–80% yields, probably due to steric hindrance
effects. Diphenylsilane was selected as the reducing agent in sub-
sequent studies. It was found that the solvent effect played a very
significant role in the reaction. The less active N-methylindole was
used for solvent screening (see Supplementary data). Generally,
this reaction proceeded well in polar solvents. Dichloromethane
N
N
2
3
4
5
6
7
8
9
75
85
N
N
N
N
99
H
N
H
N
(80)
(80)
(80)
99
O
N
N
O
H
N
H
O
N
OH
O
99
OH
1
0
1
99
Figure 1. 1H NMR spectra of the NMR tube-scale reaction of indole, diphenylsilane,
O
and B(C
6 5 3 3
F ) catalyst (5 mol %) in CDCl : (a) before reaction, and (b) after heating at
7
5 °C overnight.
1
N C
O
N
CH3
99 (92)
H
Table 1
B(C
F
5
)
3
-catalyzed indole reduction with various hydrosilanesa
6
H
H
N
O
N
silane, 2 mol% B(C F )
99c
6
5 3
12
toluene, 80 oC, 16 h
a
Reaction conditions: 1 mmol of substrate, 0.02 mmol of B(C
diphenylsilane, 2 ml of CH Cl , 75 °C, 16 h.
Yield was determined by GC or NMR integrations; isolated yield given in the
parentheses.
6
F
5
)
3
, 2–6 mmol of
Entry
Silane
Yieldb (%)
2
2
b
1
2
3
4
5
6
Ph(Me)
PhSiH
2
SiH
80
99
99
0
0
72
3
c
Ph
Ph
2
SiH
SiH
2
Reaction was performed at room temperature.
3
Et
Ph
3
SiH
(Me)SiH
2
and 1,1,2,2-tetrachloroethane gave better conversions (72–75%)
than solvents such as acetonitrile (60%) and toluene (35%). How-
ever, the use of oxygen-containing solvents, such as N,N-dimethyl-
formamide and THF resulted in none of the desired products. In
a
Reaction conditions: 0.2 mmol of indole, 0.004 mmol of borane, 0.4 mmol of
silane, 2 ml of toluene, 75 °C, 16 h.
b
Yield was determined by GC and GC–MS.

4
914
M.X. Tan, Y.G. Zhang / Tetrahedron Letters 50 (2009) 4912–4915
Ph2SiH2
B(C6F5)3
N
H
R
Ph2HSi--H--B(C6F5)3
B(C6F5)3
O
+
N
H
R
Ph2HSiOSiHPh2
SiHPh2
HB(C6F5)3
O
N
H
R
Ph HSi--H--B(C F )
6 5 3
2
HO SiHPh2
R
SiHPh2
N
O
N
R
HB(C6F5)3
H
SiPh2H
O
B(C6F5)3
N
R
H
2 2 6 5 3
Scheme 2. Suggested mechanism for amide reduction using the Ph SiH /B(C F ) system.
addition, 2 mol % of borane catalyst was sufficient for this reaction,
achieving a similar yield as 5 mol % of catalyst. Other compounds
such as enamines were reduced to tertiary amines in 85–99%
such as amides, alcohols, and ethers could be rationalized with the
formation of siloxane by-products, the reduction of activated C@C
double bonds (enamine or enol) would require a more in-depth
study of the quenching of silylium ions after the reaction. A sug-
gested mechanism for enamine reduction is provided in the Supple-
mentary data, however, it requires confirmation.
1
yields, as observed by H NMR (Table 2, entries 3 and 4).
6 5 3 3
The B(C F ) /R SiH system has been applied for the reduction of
1
3
13
15
16
alcohols, esters, carbonyls, and carboxylic acids under dif-
ferent conditions. Herein, the B(C /(Ph) SiH protocol was ex-
tended to reduce broader range of oxygen-containing
6
F
5
)
3
2
2
In conclusion, we have demonstrated an efficient metal-free
system for reducing various C@X (X = O, N, C) bonds to their cor-
a
compounds (see Table 2). 1-Phenylethanol and propiophenone
were reduced quantitatively to ethylbenzene and propylbenzene
under standard reaction conditions (Table 2, entries 8 and 9). Inter-
responding amines or hydrocarbons using the Ph
2 2 6 5 3
SiH /B(C F )
catalytic system. This B(C -catalyzed reduction system has a
6 5 3
F )
potential in organic synthesis due to the mild reaction conditions,
broad applicability to different substrates, and easy-to-handle si-
lane reducing agent, as compared to reduction by stoichiometric
hydride reagents or other conventional catalytic systems. Further
work is underway to investigate the reaction mechanism in
detail.
estingly, an
within the same substrate) were reduced to a saturated hydrocar-
bon (Table 2, entry 10). For the ,b-unsaturated methoxy-contain-
a,b-unsaturated aldehyde and a carboxy acid group
(
a
ing substrate, b-methoxy-b-methylstyrene (Table 2, entry 12), two
reduction products, propylbenzene and (1-phenylpropan-2-
yloxy)-diphenylhydrosilane were observed at reaction tempera-
tures of 40 °C and 80 °C. However, when the reaction was per-
Acknowledgments
2 2
formed at room temperature in CH Cl , propylbenzene was
obtained as the only product.
Remarkably, the reduction system was also applicable to the
reduction of amides. Various N-phenylamides (Table 2, entries 5–
We thank Professor Robert Grubbs of CALTECH for helpful dis-
cussions. This work was supported by the Institute of Bioengineer-
ing and Nanotechnology (Biomedical Research Council, Agency for
Science, Technology and Research, Singapore).
7
) were successfully reduced under standard conditions, yielding
the corresponding amines in good yields of ꢀ80%. On the other
hand, benzamide did not undergo any reduction under the reaction
conditions, even when heated at a higher temperature of 120 °C.
This was likely due to the carbonyl group being conjugated to
the phenyl ring, thus requiring greater activation, which cannot
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.06.066.
6 5 3
be achieved with the hydrosilane/B(C F ) catalytic system. How-
ever, an arylisocyanate was reduced to the corresponding amine
in quantitative yield under the standard conditions (entry 11).
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HSi–H—B(C
6
F
5
)
3
], formed
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