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Article
KOt-Bu-Catalyzed Dehydrogenative C–H Silylation of Heteroaromatics:
A Combined Experimental and Computational Mechanistic Study
Wen-Bo Liu, David P Schuman, Yun-Fang Yang, Anton Alexandrovich Toutov, Yong Liang,
Hendrik F. T. Klare, Nasri Nesnas, Martin Oestreich, Donna G Blackmond, Scott C Virgil,
Shibdas Banerjee, Richard N. Zare, Robert H. Grubbs, Kendall N. Houk, and Brian M. Stoltz
J. Am. Chem. Soc.
,
Just Accepted Manuscript
• DOI: 10.1021/jacs.6b13031
• Publication Date (Web): 12 Apr 2017
Downloaded from http://pubs.acs.org on April 13, 2017
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KO
t
-
Bu
-
Catalyzed
Dehydrog
en
ative
C
–
H
Silylation of He
t-
eroaromatics
: A Combined Experimental and Computational
Mechanistic
Study
Wen
-
Bo Liu
†
,
#
, David
P.
Schuman
†
,
#
,
Yun
-
Fang Yang
‡
,
#
,
Anton A. Toutov
†
,
Yong Liang
‡
,
Hendri
k
F.
T.
Klare
∫
,
Nasri Nesnas
§
,
Martin Oestreich
∫
,
Donna G. Blackmond
♣
,
Scott C. Virgil
†
,
Shibdas Banerjee
ǁ
,
Richard N. Zare
ǁ
,
Robert H. Grubbs
†
,
K. N. Houk
‡
,
*
,
and Brian M. Stoltz
†
,
*
†
Division of Chemistry and
Chemical Engineering, California Institute of Technol
ogy, Pasadena, California 91125
United States
‡
Department of Chemistry and Biochemistry, University of California
, Los Angeles, California 90095
United States
∫
Institut für Chemie, Technische
Universität Berlin, Strasse des 17. Juni 115, 10623 Berlin, Germany
§
Department of Chemistry, Florida Institute of Technology, 150 West University Boulevard, Melbourne, Florida 32901
United States
ǁ
Department of Chemistry, Stanford University, Stanford,
Ca
lifornia
94305
United States
♣
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037 United States
KEYWORDS: silylation, heteroaromatics,
cross
-
dehydrogenative
coupling
, transition
-
metal free, radical
chain process
,
mechanistic investigation, computational chemistry
.
ABSTRACT:
We recently reported a
new method
for the direct dehydrogenative C
–
H silylation of heteroaromatics utilizing Earth
-
abundant potassium
tert
-
butoxide
.
Herein
we
report a systematic
experimental a
nd computational
mechanistic investigation of
this
transformation
. Our experimental results are consistent with a radical chain mechanism
. A trialkylsilyl
radical
may be
initially ge
n-
erated by homolytic cleavage of a weakened Si
–
H bond
of a
hyper
coordinat
ed
silicon species
as detected by IR
, or by traces of
oxygen
which
can generate a reactive peroxide by reaction with (KO
t
-
Bu)
4
as indicated by density functional theory (DFT) calcul
a-
tions.
Radical clock and kinetic isotope experiments support a mechanism
in which the C
–
Si bond is formed th
r
ough silyl radical
addition to the heterocycle followed by subsequent
β
-
hydrogen scission.
DFT
calculations
reveal
a reasonable energy profile for a
radical mechanism and support the experimentally observed regioselectivity. The silylation reaction is shown to be reversibl
e, with
an
equilibrium favoring products due to the generation of H
2
gas. In situ NMR
experimen
ts
with deuterated substrates
show that
H
2
is
formed by a cross
-
dehydrogenative mechanism. The stereochemical course
at
the silicon center was investigated utilizing a
2
H
-
labeled silolane probe
;
complete
scrambling
at the silicon center
was observed
, cons
istent with a
number of possible
radical
inte
r-
mediates
or hypercoordinate silicates
.
Introduction
H
eteroarenes
are
important
components
of nat
u-
ral pr
oducts and bio
active molecules
,
and
considerable r
e-
search
has
focused
on
their
functionaliza
tion and deriva
tiz
a-
tion
.
1
D
irect functionalization of
unactivated C
–
H bonds
in
heteroarenes
is a powerful method
to access
heteroarylsilanes
and heteroarylboranes.
2
Th
ese intermediates provide
route
s
to
build complexity in
molecules
by
well
-
established
cross
-
coupling techniques.
3
Heteroarylsilanes
are
stab
le
and
find
widespread
use in
polymer synthesis, medical imaging appl
i-
ca
tions, and drug discovery
.
4
Given the diversity and abu
n-
dance of both heteroarenes and hydrosilanes, d
irect
C
–
H s
i-
lylation
between
heteroarenes and silanes
is
a powerful tool
for the selective construction of C
–
Si bonds
.
5
,
6
In
comparison
with traditional meth
ods
(i.e.,
metalation
/
nucleophile trapping
),
direct cross
-
dehydrogenative C
–
H silylation constitute
s
an
appealing alternative
without requiring
prefunctionaliz
a
tion of
the hetero
arene
, cryogenic conditions, or pyrophoric reagents
.
7
Significant advances in this field include the development of
Ir/Rh catalysts that efficiently enable
C
–
H silylation of he
t-
eroarenes
in the presence
of
super
-
stoichiometric
sacrificial
hydrogen acce
p
tors
(Scheme 1a)
and more recent examples of
catalytic
Friedel
-
Crafts silylation of arenes
.
6
,
8
,
9
Given the
state of the art in C
–
H silylation
, we
sought
a
practical,
su
s-
tainable
, and scalable silylation
method
achieving efficient
silylation of a broad scope of substrates
. We
have
demo
n-
strated
that
potassium
tert
-
butoxide
(KO
t
-
Bu)
alone
can cat
a-
lyze the direct cross
-
dehydrogenative coupling of heteroarenes
with hydrosilanes
(Scheme 1b
)
.
10
This method features mild
reaction conditions,
an
operationally sim
ple procedure,
good
functional group tolera
nce
, and environmental
ly
friendly
re
a-
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gents
.
However
,
the mechanism by which this rea
ction occurs
is not obvious and
has driven a
broad
collaborative study t
o-
ward gaining insight into the
reaction, described in both this
and
the acco
m
p
anying paper
.
11
Herein
w
e report
a collection
of evidence consistent with a
radical mechanism,
indicated
by
both
experimental and computational
mechanistic
investig
a-
tion
s
.
The companion publication describes an ionic and ne
u-
tral mechanism for this
reaction.
Scheme 1. Synthesis of Heteroarylsilanes by Catalytic D
i-
rect C
–
H Silylations
Computational details.
Calculations
were carried out with
Gaussian 09
.
12
Geometry optimization
s
and energy calcul
a-
tions were performed with the B3LYP
and UB3LYP (for
rad
i-
cal species)
method
.
13
The 6
-
31G (d) basis set
was used for all
atoms.
14
Frequency analysis verified the stationary points are
minima or saddle points.
Single point ener
gies were calcula
t-
ed at the M06
2X
(UM062X)
/6
-
311+G(d,p) level.
15
Solvent
effect
(solvent = THF) was calculated by using CPCM
solv
a-
tion model.
16
The radical species were calculated with the
Results and Discussion:
Effect of
C
atalyst
Identity
.
We have previously reported
that
the
combination of a bulky basic anion and a potassium
cation
is crucial for the C
–
H
silylation of 1
-
methylindole.
10
A d
e-
tailed study of the catalytic competency of a variety of alkali
,
alkaline
ea
rth
, and other
metal
derived bases has been co
n-
ducted
. As
shown in
Table 1,
alkoxide
s
and hydroxide
s
of
alkali metals
with larger radius
cations (
i.e.
radius
≥
K
+
)
, such
as K
+
, Rb
+
, and Cs
+
could provide the silylation product in
moderate to good
yields
(
Table 1,
entries 1
–
4
, 6, 9 and
10
).
A
mong all the catalysts examined
, KO
t
-
Bu was proven to be
the ideal
catalyst
,
afford
ing the
highest overall yield
.
Howe
v-
er, n
o
product was detect
ed when
KOAc or KH
was e
mployed
as
the
catalyst (entries 5 and
7).
Perhap
s surprisingly
, potass
i-
um
on g
raphite
(KC
8
) afforded
the desired product in good
yield (entry 8).
Alkali metal
bases with small cations (e.g.
LiO
t
-
Bu and NaO
t
-
Bu
)
demonstrated a
complete lack of rea
c-
tivity and
no product was observed
even
after
extended
rea
c-
tion time
(
entries
1
1 and
1
2)
.
A
lkoxides of
alkali
earth metals
or aluminum
were also investigated
as catalysts
and failed t
o
afford any product (entries 13
–
16
).
Table
1
.
Evaluation of Base Metal
C
atalyst
a
a
Reaction conditions:
1
(0.5 mmol)
,
Et
3
SiH (1.5 mmol)
, and
catalyst (0.1 mmol, 20 mol%) in THF (0.5 mL) at 45
º
C.
b
Dete
r-
mined by GC analyses.
c
Dried KOH, see Supporting Information
for details.
d
Potassium graphite.
e
The hydroxides may be co
n-
verted to silanolates, and subseque
ntly silicates, which serve as
the active catalysts under the reaction conditions.
17
Figure 1
.
A representative time course of the
silylation of
1
,
monitor
ed
by in situ
1
H NMR.
Reaction conditions:
1
(0.
2
5
mmol)
,
Et
3
SiH (0.75
mmol)
, and
KO
t
-
Bu (0.05
mmol, 20 mol%)
in THF
-
D
8
(0.
2
5 mL) at 45
º
C in a
sealed
NMR tube.
The kinetic behavior of the silylation reaction with KO
t
-
Bu
catalyst was studied
using in situ
1
H NMR
spectroscopy
.
As
depicted in Figure 1,
the silylation reaction was
found to take
place in three stages: an induction period
(
Figure 1,
0
-
3500 s
)
,
an active
peri
od with rapid formation
of product
(3500
-
4500
s)
,
18
and a final period
with
significantly reduced
reaction rate
(
>
4500 s
)
.
Our investigations were then expanded to include
each activ
e catalyst presented in Table 1 (Figure 2)
.
The
length of the
induction period was found to
depend
on the
nature of both metal and counter ion.
For anions, the indu
c-
tion period increase
d
in the o
rder of
KC
8
(shortest)
<
KOEt
<
H
Ar
cat.
[M]
[Si]
Ar
[Si]–H
cat.
KO
t
-Bu
[Si]–
H
+
H
H
(a)
Previous
Transition-Metal-Catalyzed
C–
H
Silylation
Work
(b)
KO
t
-Bu-Catalyzed
Cross-Dehydrogenative
C–
H
Silylation
Method
H
Het
[Si]
Het
M
=
Pt,
Ir,
Rh,
Ru
H
2
acceptors
N
Me
catalyst
(20
mol%)
THF,
45
°C
N
Me
SiEt
3
Et
3
SiH
(3
equiv)
N
Me
SiEt
3
+
1
2
3
catalyst
conv
(%)
b
11:1
88
53
0
55
35
0
52
64
38
73
12:1
–
9:1
9:1
11:1
–
8:1
10:1
8:1
0
0
0
0
–
–
–
–
2
:
3
b
KC
8
d
KOH
c,e
Al(O
t
-Bu)
3
CsOH•
H
2
O
e
Mg(O
t
-Bu)
2
Ca(O
i
-Pr)
2
Ba(O
t
-Bu)
2
KOTMS
KOEt
KH
KO
t
-Bu
KOMe
time
(h)
10
20
60
10
20
36
20
10
10
10
36
36
36
36
0
0
–
–
LiO
t
-Bu
NaO
t
-Bu
36
36
RbOH•
x
H
2
O
e
entry
1
4
5
2
3
6
7
8
9
10
11
12
13
14
15
16
KOAc
0"
0.05"
0.1"
0.15"
0.2"
0.25"
0.3"
500"
1500"
2500"
3500"
4500"
5500"
6500"
7500"
8500"
9500"
product({M}(
,me((s)(
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60
KO
t
-
Bu
<
KOH
(longest)
. A
n
increase
in induction period
was observed
with
decreasing
radius
of cations
, with
Cs
OH
(shortest) <
RbOH
<
K
OH
(longest)
.
19
It is worth
noting
that
t
he
induction periods vary
based on
catalyst loading,
solvents,
and reaction temperature.
Additives and moisture
could also
have a significant
impact on the induction period, generally
prolong
ing
the duration of
such period (
see S
upporting
I
nfo
r-
mation
).
Nevertheless
, the induction period
s
howed good
reproducibility for identical reactions setup at different times.
A
lthough
the induction
period
with KO
t
-
Bu
is
not the shortest
o
f
all catalysts tested (Figure 2
),
this
catalyst
provides
the
highest
post
-
initiation
turnover fr
equency and product
yield
.
Further discussion related to the c
ause of this induction period
is
explored
in
later
spectroscopic and com
putational
exper
i-
ments
.
Figure
2
.
A comparison of the
kinetic profiles of
multiple
base
catalysts
.
Data was acquired via GC analysis of
aliquots of crude
reaction mixture.
Regioselectivity and Reversibility.
Although
the
major
product of KO
t
-
Bu
-
catalyzed silylation is the incorporation of
a
triethylsilyl group at
the
C2
-
position
of 1
-
methylindole
(
2
),
C3
-
silylation product
3
is
also form
ed
.
Increase in rea
ction
time and temperature
tend
s
to shift the
major product
from C2
-
to C3
-
silylation. As illustrated in Table 2,
t
he reaction in THF
at 45
º
C affords
a
n
11:1
ratio
of C2
-
:C3
-
products (
2
:
3
)
after
10
h
,
but after 15 days under the same conditions
only C3
-
product
3
is
observed (i.e. 1:
>
20 C2
-
:C3
-
,
entries 1 and 2).
Similarly, when
the reaction is conducted at
100
º
C,
C3
-
silylation
predominates
with
a 1:9
ratio of products
2
:
3
(entry
3).
These
results are
consistent with
C2
-
silylation
as the
kine
t-
ic
product, while C3
-
silylation is
the
thermodynamic
product
.
Finally, solvent
selection
was
found to have a
dramatic impact
on the C2
-
and C3
-
selectivity
.
In
the
absence of solvent
,
the
C2
-
product
is
exclusively
observed
at 45
º
C and even at 100
ºC
C2
-
silylation is still the major
pathway
(entries 4 and 5).
Table
2
.
Regioselectivity as a Function of Reaction Cond
i-
tions
a
a
Reaction conditions:
1
(0.5 mmol),
Et
3
SiH (1.5 mmol)
, and
KO
t
-
Bu (0.1 mmol, 20 mo
l%)
in
THF
(
0.5
mL,
if
indicated)
.
b
Determined by GC analyses.
c
After 15 days.
Several experiments
were conducted to
probe the
reversibility
of the silylation reaction
(Scheme 2)
.
T
reatment of
C2
-
silylated compound
2
with KO
t
-
Bu
in THF
does not
result
in
conversion to
the C
3
-
silylated
3
(Scheme 2a)
,
showing that
catalyst alone is insufficient for reversibility
.
However,
trea
t-
ment
of
2
with
both
Et
3
SiH
and KO
t
-
Bu in THF
led to
the
conversion of
C2
-
silylated
product
2
to C3
-
silylated product
3
,
along with
approximately
5% of desilyla
ted product
1
(Scheme 2
b)
. Moreover,
a crossover experiment involving
compound
2
,
stoichiometric EtMe
2
SiH
, and
catalytic KO
t
-
Bu
provided
a mixture of starting material
2
, cross
-
silylation
product
4
, and desilylation product
1
(Scheme 2
c).
The
se
results indicate
that
the conversion of
C2
-
to C3
-
silylation
product
likely does
not
occur
through
intramolecular
silyl m
i-
gration.
In fact
,
the observation
of cross
-
silylation and des
i-
lyla
ti
on can be better
explai
ned by
a reversible
silylation
rea
c-
tion
under
these
conditions
.
Scheme 2. R
eversibility of the Silylation
Cross
-
dehydrogenative F
ormation of H
2
.
T
he process of H
2
formation
was
probed
by in situ NMR
using deuterium labeled
substrates
.
20
As
shown
in
Scheme 3a
,
a
trace amount
of
H
2
was
detected
during the induction period
.
This is followed by
rapid
H
2
evolution along with generation of the
silylation
product
2
.
Similarly, H
2
is
initially
slowly
generated
in the
case
of
the
2
-
deuterated
indole
[D]
-
1
,
Et
3
SiH
,
and KO
t
-
Bu
under identical conditions
, followed by the
cross
-
dehydrogenative formation of
HD
(1:1:1 triplet,
J
= 43 Hz)
after the
induction period
(Scheme 3b
).
Further experiment
a-
0"
10"
20"
30"
40"
50"
60"
70"
80"
90"
100"
0"
5"
10"
15"
20"
25"
30"
35"
40"
conversion (%)
time (h)
KOt-Bu
KOEt
KOMe
KOTMS
KOH
KC8
CsOH•H2O
RbOH•xH2O
N
Me
KO
t
-Bu
(20
mol%)
Et
3
SiH
(3
equiv)
N
Me
SiEt
3
solvent
N
Me
SiEt
3
+
1
2
3
temp
(ºC)
11:1
1:>20
1:9
2
:
3
b
45
45
100
time
(h)
10
15d
c
20
entry
1
2
3
solvent
THF
THF
THF
>20:1
45
48
4
neat
conv
(%)
b
88
>95
94
88
4:1
100
24
5
neat
>95
KO
t
-Bu
(20
mol%)
Et
3
SiH
(3
equiv)
THF,
100
°C,
21
h
N
Me
SiEt
3
N
Me
SiEt
3
+
2
3
KO
t
-Bu
(20
mol%)
THF,
100
°C,
21
h
(
2:3
=
36:1)
2
+
3
SM
recovered
(
2:3
=
36:1)
(a)
N
Me
SiEt
3
N
Me
SiEt
3
+
2
3
(
2:3
=
36:1)
2
+
3
SM
recovered
(
2:3
=
9:1)
(b)
+
N
Me
1
(~5%)
KO
t
-Bu
(20
mol%)
EtMe
2
SiH
(1
equiv)
THF,
45
°C,
16.5
h
N
Me
SiEt
3
2
2
+
(c)
+
N
Me
1
N
Me
SiMe
2
Et
4
2:4:1
=
2.4:2.2:1
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tion
with indole
1
and Et
3
SiD was also conducted under the
same conditions.
Small amounts of HD were
detected
at the
beginning
of the NMR
study
and
further HD
gas formation
was observed
with the formation of product
(Scheme 3c
)
.
These data demonstrate that H
2
is generated from th
e cross
-
dehydrogenative
pathway;
moreover, a very small percentage
of H
2
may be
produced from
the consumption of trace
amount
s
of water or the radical initiation pro
cess
.
21
Furthe
r-
more,
large
-
scale reaction
s were
performed and
gas evolution
was
monitored via
eudiometry
(Fig
ure
3
).
The results from
two identical runs
produced H
2
in 69
–
71% yields
,
consistent
with
yields of silylation product
2
based on
1
H
NMR
and the
plot of H
2
vs t
ime correlates well to a plot of silylation product
2
vs t
ime
(
Fig
ure
3
vs Figure 1)
.
Scheme 3. Hydrogen Gas Formation through Dehydr
o-
genative Coupling
Figure
3
.
Hydrogen gas evolution.
a
Reaction conditions:
1
(5
mmol), Et
3
SiH (15 mmol), and KO
t
-
Bu (1 mmol, 20 mol%) in
THF
(5 mL)
(
conducted in duplicate
).
b
Conversion, determined by
1
H NMR.
c
Yield bas
ed on
collected H
2
volume.
To probe the nature of the induction period, we p
er
formed a
series of experiments
using
TEMPO
as a radical inhibitor
. As
shown
in
Figure
4
,
although
the addition of 3 mol%
of
TEMPO
at
the beginning
of the reaction
essentially
doubles
the
delay in product formation (i
.
e. TEMPO inhibition plus
induction)
in
contrast to the reaction without TEMPO
(Figure
4
, Plot a
)
, the conversions are comparable after 8 h
(Plot b
)
.
Similar trends were observed when TEMPO was added after
the
initiation period
(i.e.,
at 3.33 h with 54
% conversion
,
Plot
c and d
)
;
the product formation
ceased
for a period
and
then
continue
d
. A larger
TEMPO
addition,
6
mol
%
compared to
3
mol%
,
prolon
gs
the resultant induction period
accordingly
.
Interestingly,
the addition of TEMPO to the initiated reaction
mixture leads to immediate bleaching (from dark purple to
light yellow)
,
with the dark purple color
returning over the
period of hours
.
Careful
a
nal
ysis of the reaction with stoich
i-
ometric TEMPO by GC
-
MS
dis
played
a sig
nal with m/z
that
matches
the expected mass of the
TEMPO
–
SiEt
3
adduct
form
ed
from the
capture of the
triethylsilyl
radical by
TEMPO
.
22
These
experiments
suggest that
by coupling
with
the
silyl radical,
TEMPO terminates
the radical chain process
and the reaction restarts only after the
substoichiometric
amount of
TEMPO has been fully consu
med.
23
Further
stu
d-
ies found that
the mixture of
KO
t
-
Bu and Et
3
SiH in THF at 45
ºC
is EPR
active
.
N
KO
t
-Bu
(20
mol%)
Et
3
Si
H
(3
equiv)
THF-D
8
,
45
°C
NMR
tube
N
SiEt
3
Me
Me
H
+
H
2
2
1
-
Trace
amount
of
H
2
initially
observed
-
Rapid
H
2
evolution
after
induction
period
(a)
(b)
N
KO
t
-Bu
(20
mol%)
Et
3
Si
H
(3
equiv)
THF-D
8
,
45
°C
NMR
tube
N
SiEt
3
Me
Me
D
H
–
D
+
+
H
2
2
[D]-1
N
KO
t
-Bu
(20
mol%)
Et
3
Si
D
(
3
equiv)
THF-D
8
,
45
°C
NMR
tube
Me
H
1
-
H
2
observed
initially
-
H
–
D
observed
after
induction
period
-
H
–
D
observed
initially
-
H
2
observed
after
induction
period,
along
with
increased
H
–
D
production
N
SiEt
3
Me
H
–
D
+
+
H
2
2
(c)
0"
10"
20"
30"
40"
50"
60"
70"
80"
90"
0"
50"
100"
150"
200"
250"
H2#volume#(mL)#
-me#(min)#
N
KO
t
-Bu
(20
mol%)
Et
3
SiH
(
3
equiv)
THF
,
45
°C
N
SiEt
3
Me
Me
H
2
1
5
mmol
2
72–73%
b
69–71%
c
(77–80
mL)
run
1
run
2
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Figure
4
.
Rea
c
tion
profiles with TEMPO
addition
.
a
Reaction
conditions:
1
(0.5 mmol), Et
3
SiH (1.5 mmol),
and
KO
t
-
Bu (0.1
mmol, 20 mol%)
in THF (0.5 mL) at 45 ºC
.
b
With 3 mol%
TEMPO added at the beginning of the reaction.
c
With
3 mol% of
TEMPO added during the reaction at t = 3.33 h.
d
With 6 mol% of
TEMPO added du
ring the reaction at t = 3.33 h
, product fo
r-
mation resumes at 11
h.
Conversion was determined by monito
r-
ing aliquots via GC.
Based on
these
results,
we postulate
that
a
si
lyl radical species
is
involved in this catalytic C
–
H silylation reaction.
Our e
f-
forts were focus
ed
on the understanding of radical initiation
under
the
standard reaction conditions. Although there are
a
considerable
number
of examples of silyl radical reactions
known in the literature, the means of generating
sil
yl
radicals
are rather limited.
24
In
our case,
the silylation reaction
results
in comparable yields when kept
in the dark as
exposed to
a
m-
bient light, which rule
s
o
ut t
he possibility of visible light
-
induced radical formation. Recently, Itami, Lei and others
reported that KO
t
-
Bu could mediate the cross
-
coupling of aryl
bromide and benzene without the use of
transition
-
metal
cata
l-
ysis.
25
Subsequent mechanistic studie
s revealed that in the
presence of
1,10
-
phenanthroline
a
radical species was genera
t-
ed.
26
This process is accelerated dramatically with
catalytic
amount
s
of organic electron transfer reagents, such as
N
-
methylpyrrolidone,
N
-
methlyglycine
, and glyci
ne,
as
demo
n-
strated by Murphy
.
27
However,
in our silylation reaction
the
addition of
any
of these
compounds
resulted
in a significant
decrease in reactivi
ty (Ta
ble 3
, entries 1
–
4).
Table
3
.
Effect
of A
dditives
a
a
Reaction conditions:
1
(0.5 mmol), Et
3
SiH (1.5
mmol), KO
t
-
Bu (0.1 mmol, 20 mol%), and additive
(5 mol%)
in THF (0.5 mL)
at 45 ºC.
b
Determined by GC analyses
.
A reported
method for
the
generation
of
s
il
ane based
radicals
is
the
abstraction of a hydrogen atom from hy
drosilanes using
organic radicals (
e.
g.
n
-
Bu
3
Sn•,
t
-
BuO•).
28
To test whether
this mechanism is involved in our reaction, w
e have
underta
k-
en
a
series
of experiments with
tert
-
butoxy radical
s
generated
in situ
.
No product was obtained with 2
0 mol% of
di
-
tert
-
butyl peroxide (
DTBP
)
at 135 ºC
(Table 4, entry 2
). Utilizing
stoichiometric
DTBP at 135 ºC led to
only small amounts of
desired product along with very complicated mixtures as ind
i-
cated by the GC
-
MS traces
(entry
3
).
Attempts to carry out
the silylation
reaction
u
nder milder conditions
with
1
0 mol%
of
di
-
tert
-
butyl hyponitrite (
TBHN
)
or
a
mixture of
TBHN and
NaO
t
-
B
u
failed to
furnish product
(entries 5
and 6).
A
ddition
of KO
t
-
Bu
with either DTBP or TBHN
furnished
the desired
silylation
product
,
albeit with decreased yields (entri
es 4 a
nd
7
).
Moreover, u
nder our standard reaction conditions
(i
.
e
.
e
ntry 1)
,
the
desired product was
always
accompanied by
t
-
BuOSiEt
3
(
5
)
.
T
he reactions with DTBP or TBHN did not
produce
t
-
BuOSiEt
3
,
which suggests that
t
-
BuOSiEt
3
may not
be
formed through
the reaction of
t
-
BuO• with silane or silyl
radical
, but through
a differing
pathway (
vide infra
).
Al
t-
hough the
involvement
of
a
t
-
butox
y
radical
can
not be exclu
d-
ed
based on these
experiments
, t
here
is
little evidence to
su
p-
port
the initiation of
a
triet
hylsilyl radical
via
hydrogen
atom
abstraction
from
Et
3
SiH by
t
-
butox
y
radical.
Table
4
.
Effect of
t
-
Butoxy Radical Precursors
a
a
Reaction conditions:
1
(0.5 mmol), Et
3
SiH (1.5 mmol), KO
t
-
Bu (0.1 mmol, 20 mol%
, if
used), and
radical initiator
in THF (0.5
mL) at 45
º
C.
b
Determined by GC analyses.
Investigation of
C
oordinate
d
Sil
ane
Species
by FTIR Stu
d-
ies
.
It has been well documented that the addition of strong
silicophilic Lewis bases (
e.g.
fluoride, alkoxide)
can
increase
the reactivity of
hydrosilanes in the hydrosilylation of C=O
bond
s
.
29
It is believed that strong
ly
reducing hy
percoordinate
silicate complexes
are formed by coordination of nucleophilic
anions during such process
es
, which typically weakens the Si
–
H bond and increases the hy
dridic
character
of t
his
bond.
30
,
31
S
tudies by
Corriu et al. revealed
that the direct reaction of
(RO)
3
SiH with
the
corresponding KOR (R = alkyl or aryl) in
THF at room temperature affords the anionic
,
five
-
coordinate
hydridosilicate [HSi(OR)
4
]K in good
yield.
32
Such species are
found to
be
very effective in
the reduction of
carbonyl co
m-
N
KO
t
-Bu
(20
mol%)
Et
3
SiH
(3
equiv)
THF,
45
°C
TEMPO
(x
mol%)
N
SiEt
3
Me
Me
1
2
0"
10"
20"
30"
40"
50"
60"
70"
80"
90"
0"
1"
2"
3"
4"
5"
6"
7"
8"
conversion (%)
time (h)
(A) control
(B) with 3 mol% TEMPO
(C) with 3 mol% TEMPO
(D) with 6 mol% TEMPO
a
b
c
d
3.33
h
TEMPO
added
for
runs
C
and
D
additive
conversion
(%)
b
>20:1
>20:1
52
79
7
67
10
54
0
50
>20:1
19:1
>20:1
>20:1
–
>20:1
2
:
3
b
N
-methylglycine
1,10-phenanthroline
N
-methylpyrrolidone
time
(h)
8
24
8
24
8
24
8
24
entry
1
4
2
3
glycine
N
Me
KO
t
-Bu
(20
mol%)
Et
3
SiH
(3
equiv)
N
Me
SiEt
3
THF,
45
°C
additive
(5
mol%)
N
Me
SiEt
3
+
1
2
3
93
>20:1
8
5
none
N
Me
conditions
Et
3
SiH
(3
equiv)
N
Me
SiEt
3
N
Me
SiEt
3
+
1
2
3
temp
(ºC)
135
135
45
time
(h)
14
14
14
entry
2
3
4
DTBP
DTBP
DTBP
+
KO
t
-Bu
conditions
45
45
45
10
24
10
24
10
24
5
6
7
TBHN
+
KO
t
-Bu
TBHN
TBHN
+
NaO
t
-Bu
conv
(%)
b
1
10
42
0
0
0
54
0
0
+
t
-BuOSiEt
3
5
detection
of
5
b
no
no
yes
no
no
no
yes
no
no
mol%
100
20
20,
20
10,
20
10
10,
20
THF
45
24
1
KO
t
-Bu
80
yes
20
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