Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
1
Supporting Information for
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 A. Toutov
†
,
Yong
Liang
‡
,
Hendrik 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 Technology,
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 Unive
rsity, Stanford, California 94305 United States
♣
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037
United States
*houk@chem.ucla.edu
;
*stoltz@caltech.edu
#
These authors contributed equally to this work
Table of Contents
:
Materials and Methods
................................
................................
................................
...............................
S
3
Computational details
................................
................................
................................
................................
.
S
4
Calculated energies and free energy profiles for selected substrates
................................
.....................
S
5
1
H NMR concentration dependence of silylation product 2
................................
................................
..
S
10
General m
ethod for the screening of base catalysts and kinetic profile
................................
...............
S
11
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
2
Procedure for time course reaction monitoring by in situ
1
H NMR
................................
.....................
S
11
Procedure for time course rea
ction monitoring by GC analysis of reaction aliquots
.........................
S
13
Procedure for regioselectivity and reversibility of silylation experimentation
................................
...
S
1
4
General procedure of gas collection by eudiometry
................................
................................
...............
S
16
Procedure for silylation reaction in
the presence of TEMPO.
................................
..............................
S
17
Effect of additives on the silylation reaction
................................
................................
...........................
S
19
Procedure for reactions using chemical generation of
tert
-
butoxyl radical
................................
.........
S
20
Procedure for react
ion time course using ReactIR.
................................
................................
...............
S
21
General procedure of ATR
-
FTIR measurment
................................
................................
......................
S
22
Procedure for kinetic isotope effect
................................
................................
................................
.........
S
23
Procedure for the acquisition of electron paramagnetic resonance (EPR) spectra.
...........................
S
23
Procedure for reaction calorimetry
................................
................................
................................
.........
S
24
General procedure for KO
t
-
Bu
-
catalyzed silylation and cha
racterization data of new compounds.
S
27
EPR Spectrum
................................
................................
................................
................................
...........
S
52
1
H NMR and
13
C NMR Spectra
................................
................................
................................
................
S
53
Zero
-
point correction (ZPE), thermal correction to energy (
Δ
E), thermal correction to enthalpy (
Δ
H),
thermal correction to Gibbs free energy (
Δ
G), energies (E), enthalpies (H), and Gibbs free
energies
(G) (in Hartree) of the structures calculated at the M06
-
2X/6
-
311+G(d,p)
-
CPCM(THF)//B3LYP/6
-
31G(d) level of theory.
................................
................................
................................
...............................
S
75
Cartesian coordinates of the stru
ctures
................................
................................
................................
..
S
77
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
3
Materials and Methods
Unless otherwise stated, reactions were performed
in a nitrogen
-
filled glovebox or
in
flame
-
dried glassware under an argon or nitrogen atmosphere using dry, deoxygenated
solvents.
Solvents were
dried by passage through an activated alumina column und
er
argon.
1
Reaction progress was monitored by thin
-
layer chromatography (TLC)
, GC
or
Agil
ent 1290
UHPLC
-
MS
.
TLC was performed using E. Merck silica gel 60 F254
precoated glass plates (0.25 mm) and visualized by UV fluorescence quenching,
p
-
anisaldehyde, or KMnO
4
staining.
Silicycle Silia
Flash
®
P60 Academic Sili
ca gel
(particle size 40
–
63 nm)
was used for flash chromatography.
1
H NMR spectra were
recorded on
Varian Inova 500 MHz
or
B
r
uker
400
MHz
spectrometer
s
and are
reported
relative to residual CH
Cl
3
(
δ
7.26 ppm)
, C
6
H
6
(
δ
7.1
6 ppm
),
or THF (
δ
3.58, 1.72 ppm)
.
13
C NMR
spectra were
recorded on a Varian Inova 500 MHz spectrometer (125 MHz)
or
Bruker 400 MHz spectrometers (100 MHz) and
are reported relative to CH
Cl
3
(
δ
77.16
ppm
)
.
Data for
1
H NMR are report
ed as follows: chemical shift (
δ
ppm
) (multiplicity,
coupling constant (Hz), integration). Multiplicities are reported as follows: s = singlet, d
= doublet, t = triplet, q = quartet, p = pentet, sept = septuplet, m = multiplet, br s = broad
singlet, br d = broad doublet, app = apparent.
Da
ta for
13
C
NMR
are reporte
d in terms of
chemical shifts (
δ
ppm). IR spectra were obtained by use of a
Perkin Elmer Spectrum
BXII
spectrometer
or Nicolet 6700 FTIR
spectrometer
using thin films deposited on
NaCl plates and reported in frequency of absorpti
on (cm
–
1
).
GC
-
FID analyses were
obtained on an Agilent 68
50
N gas chromatograph equipped with a HP
-
1 100%
di
methylpolysiloxane capillary column (Agilent). GC
-
MS analyses were obtained on an
Agilent 6850 gas chromatograph equipped with a HP
-
5 (5%
-
phenyl)
-
m
ethylpolysiloxane
capillary column (Agilent).
High resolution mass sp
ectra (HRMS) were obtained from
Agilent 6200 Series TOF with an Agilent G1978A Multimode source in electrospray
ionization (ESI+), atmospheric pressure chemical ionization (APCI+), or mixed
ionization mode (MM: ESI
-
APCI+), or obtained from Caltech mass spectrometry
laboratory.
FT
-
ATR IR
measurements were carried out on a Thermo Scientific Nicolet
1
A. M. Pangborn, M. A. Gia
rdello, R. H. Grubbs, R. K. Rosen and F. J. Timmers,
Organometallics
,
1996
,
15
, 1518.
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
4
iS 5 FT
-
IR
spectrometer equipped with an
iD5 ATR accessory. ReactIR measurements
were carried out on a Mettler
-
Toledo ReactIR ic10 using a K4 conduit with a Sentinel
high
-
pressure probe and SIC
omp window. Electron paramagnetic resonance (EPR)
spectra were acquired on a X
-
band Bruker EMX spectrometer
.
An Omnical SuperCRC
or Insight CPR 220
reaction calorimeter
were
used to monitor heatflow.
Triethyl silane (99%,
Sure/Seal™)
and
KO
t
-
Bu
(
sublimed
grade, 99.99% trace
metals basis
)
were
purchased from Aldrich and used directly.
KOH was
pulverized
and
dried in a desiccator over P
2
O
5
under vacuum
for 24 h
prior to use.
Di
-
tert
-
butyl
h
yponitrite
was
synthesized
according to literature procedure
.
2
Other r
eagents were
purchased from Sigma
-
Aldrich, Acros Organics, Strem, or Alfa Aesar and used as
received unless otherwise stated.
Computational details
All the calculations were carried out with Gaussian 09.
3
Geometry optimization and
energy calculati
ons were performed with the B3LYP method
4
using the 6
-
31G(d)
basis
set
5
for all atom.
Frequency analysis verified that the stationary points were minima or
first
-
order saddle points. Single point energies were calculated at the M06
-
2X
6
/6
-
311+G(d,p) level w
ith solvent effects (solvent = THF) modeled using the CPCM
7
2
(a) Banks, J. T.; Scaiano, J. C.; Adam, W.; Oestrich, R.
S.
J. Am. Chem. Soc.
1993
, 115, 2473. (b)
Mendenhall, G. D.
Tetrahedron Lett
.
1983
,
24
, 451.
3
Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani,
G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.;
Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenb
erg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.;
Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J.
A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Starov
erov, V. N.;
Keith, T.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi,
J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stra
tmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski,
J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslo
wski, J.; Fox, D. J.
Gaussian
09, Rev. D.01
; Gaussian, Inc., Wallingford, CT, 2010.
4
(
a
) Lee, C.; Yang W.; Parr, R. G.
Phys. Rev. B
1988
,
37
, 785. (
b
) Becke, A. D.
J. Chem. Phys.
1993
,
98
,
1372. (c) Becke, A. D.
J. Chem. Phys.
1993
,
98
, 5648. (
d
) Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.;
Frisch, M. J.
J. Phys. Chem.
1994
,
98
, 1623.
5
(a) Ditchfield, R.; Hehre, W. J.; Pople, J. A.
J. Chem. Phys.
1971
,
54
, 724. (b) Hehre, W. J.; Ditchfield,
R.; Pople, J. A.
J. Chem. Phys.
1972
,
56
, 2257.
(c) Hariharan, P. C.; Pople, J. A.
Theor. Chim. Acta.
1973
,
28
, 213.
6
Zhao, Y.; Truhlar, D.
Theor. Chem. Acc.
2008
,
120
, 215.
7
(a) Barone, V.; Cossi, M.
J. Phys. Chem. A
1998
,
102
, 1995. (b) Cossi, M.; Rega, N.; Scalmani, G.;
Barone, V.
J. Comput. Chem.
2003
,
24
, 669. (c) Takano, Y.; Houk, K. N.
J. Chem. Theory Comput.
2005
,
1
, 70.
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
5
solvation model. Gibbs free energies in THF at 298.15 K were calculated by adding the
thermochemical quantities derived from the B3LYP frequency calculation to the M06
-
2X
solution
-
phase electronic
potential energy. Computed structures are illustrated using
CYLVIEW.
8
Calculated energies and free energy profiles for selected substrates
Figure S1
.
Calculated energetics of formation of pentacoordinate
silicates their IR spectra of Si
-
H
bonds. The distances of Si
-
H are shown in angstrom.
Figure S2.
Free energy profile for generation of silyl radical with oxygen.
8
Legault, C. Y. CYLView, 1.0b; Universite ́ de Sherbrooke, Canada,
2009
; http://www.cylview.org.
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
6
Figure S3.
Transition s
tructures of hydrogen abstraction by tetrameric
(KOt
-
Bu)
4
and (NaOt
-
Bu)
4
.
Figure S
4
.
Free energy profile for C
–
H silylation of 1
-
methylpyrrole at C2 and C3 positions.
Hydrogen atom is abstracted by tetrameric (KOt
-
Bu)
4
.
Gibbs free energies, including
THF solvation, are shown in kcal/mol.
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
7
0
.
0
T
S
-
1
4
1
3
.
6
Δ
G
T
H
F
(
2
9
8
K
)
i
n
k
c
a
l
/
m
o
l
M
e
3
S
i
+
O
O
S
i
M
e
3
H
O
S
i
M
e
3
T
S
-
1
5
O
S
i
M
e
3
H
1
7
.
6
-
7
.
1
2
.
1
0
.
9
1
.
2
C
-
1
9
C
-
1
8
1
4
.
2
2
2
.
8
T
S
-
1
6
T
S
-
1
7
C
-
1
7
T
S
-
1
4
C
-
2
0
C
-
2
1
C
-
2
0
+
H
2
M
e
3
S
i
+
M
e
3
S
i
H
O
S
i
M
e
3
H
O
K
O
K
K
O
K
O
t
-
B
u
t
-
B
u
t
-
B
u
t
-
B
u
(
K
O
t
-
B
u
)
4
(
K
O
t
-
B
u
)
4
T
S
-
1
6
5
.
4
5
.
7
H
O
K
O
K
K
O
K
O
t
-
B
u
t
-
B
u
t
-
B
u
t
-
B
u
+
C
-
9
Figure S
5
.
Free energy profile for C
–
H silylation of furan at C2 and C3 positions. Hydrogen atom is
abstracted by tetrameric (KOt
-
Bu)
4
. Gibbs free ene
rgies, including THF solvation, are
shown in kcal/mol.
Figure S
6
.
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
8
Free energy profile for C
–
H silylation of thiophene at C2 and C3 positions. Hydrogen
atom is abstracted by tetrameric (KOt
-
Bu)
4
. Gibbs free energies,
including THF solvation,
are shown in kcal/mol.
Figure S
7
.
Free energy profile for C
–
H silylation of 1
-
methylpyrrole at C2 and C3 positions.
Hydrogen atom is abstracted by pentacoordinate silicate anion. Gibbs free energi
es,
including THF solvation, are shown in kcal/mol.
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
9
Figure S
8
.
Free energy profile for C
–
H silylation of furan at C2 and C3 positions. Hydrogen atom is
abstracted by pentacoordinate
silicate anion. Gibbs free energies, including THF
solvation, are shown in kcal/mol.
Figure S
9
.
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
10
Free energy profile for C
–
H silylation of furan at C2 and C3 positions. Hydrogen atom is
abstracted by pentacoordinate silica
te anion. Gibbs free energies, including THF
solvation, are shown in kcal/mol.
1
H NMR concentration dependence of silylation product 2
in CDCl
3
.
Figure
S10
Isolated
1
-
Methyl
-
2
-
(triethylsilyl)
-
1
H
-
indole
was dissolved in CDCl
3
at the indicated
concentration
an
1
H NMR spectra were acquired,
as
shown in Fi
gure
S10
. This
demonstrated the anticipated variation for the product signal under reaction or analytical
conditions.
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
11
General
method for the screening of base catalysts
and kine
tic profile
:
Table 1
In a nitrogen
-
filled glove
box
,
1
-
methylindole (0.5 mmol, 1 equiv)
, triethylsilane (1.5
mmol, 3 equiv), the indicated base (0.1 mmol
, 20 mol%), and
THF (5 mL)
were added to
a 1 dram vial equipped with a magnetic stirring ba
r. At the
indicated time, aliquots were
removed using a glass capillary tube, diluted with Et
2
O, and analyzed using GC
-
FID to
determine regioselectivity and yield.
GC
c
onversion is reported as product
(C2
-
and C3
-
silylation)
divided by product and starting
material.
For further base screening, see
the
S
upporting
I
nformation
of our initial disclosure.
9
Procedure
for time course
reaction monitoring
by in situ
1
H NMR
In a nitrogen
-
filled glove box,
a stock solution containing KO
t
-
Bu (60.5 mg,
0.
539
mmol) and
1,2,5
-
trimethoxybenzene (
if used,
45.4mg,
0.
267 mmol) is prepared in THF
-
D
8
(2.7 ml)
.
C
ontinuing in the glove box, a J
-
Young gas
-
tight NMR tube is then charged
9
Toutov, A. A.; Liu, W.
-
B.; Betz, K. N.; Fedorov, A.; Stoltz, B. M.; Grubbs, R
. H.
Nature
2015
,
518
, 80
–
84
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
(%)
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
KC
8
KOH
Al(O
t
-Bu)
3
CsOH•
H
2
O
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
entry
1
4
5
2
3
6
7
8
9
10
11
12
13
14
15
16
KOAc
Supporting Information for Liu, Schuman,
Yang,
Toutov,
Liang,
Klare, Nesnas,
Oestreich
,
Blackmond,
Virgil,
Banerjee, Zare,
Grubbs
, Houk,
and Stoltz
S
12
with 1
-
methylindole (32.8 mg, 0.25 mmol, 1 equiv), Et
3
SiH (
0.75 mmol, 3 equiv), and
0.25 mL of
stock solution. The tube is tightly capped with the corresponding Teflon
plug, removed from the glove box, placed in the bore of the NMR, and heated to 45 ºC.
1
H NMR spectra were acquired in “array” mode, with a spectrum taken approximately
every 3 minut
es for the length of experiment.
The data was processed using
MestReNova
and peak integrations were normalized to 1,2,5
-
trimethoxybenzene
(if
used)
.
Data is displayed using the MestReNova “stack” function with the axis to the right
corresponding to NMR s
can number,
Scheme
3.
Figure S11
A study was conducted
following the procedure for time course reaction monitoring by
1
H NMR (using internal standard)
while
varying indole
[
1
]
, from 0.25
–
0.76 mmol (0.5
–
1.5 equiv
). We observed an initial burst phase of product formation,
unfortunately
due to
the induction period
we had difficulty assigning an initial rate for this phase but all trials
appear to have a similar rate during the burst phase. The length of the burst
phase (i.e.
product formed) appears to be related to indole [
1
]. Interestingly, after the burst phase
the slope of all 4 plots appear to be consistent, indicating the reaction may not depend on
[
1
]. This work helped us to understand the reaction occurred
in the following 3 regimes;
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0
500
1000
1500
2000
2500
3000
3500
4000
4500
product (M)
time (s)
Order%in%[indole]%revisited:
%
%
%
%
%
%
%
%
%
%%%%%
%
%
1.025%M
%
%
%
%
%
%
%
%
%
%
%
0.676%M
%
%
%
%
%
%
%
%
%
%
%
0.507%M
%
%
%
%
%
%
%
%
%
%
0.338%M
%
%
%
%
%
%
%
%
%
%
%
%
%
%
%
%
%
There%appears%to%be%two%separate%rate%regimes,%a%fast%initial%rate%that%lasts%longer%
at%higher%[indole],%followed%by%a%slower%plateau%
rate%that%is%independent%of%
[indole].
%
Which%is%more%important%for%mechanistic%understanding?
%
Certainly%“same%excess”%experiments%would%seem%to%be%important%to%understand%
whether%the%catalytic%cycle%is%operating%in%%a%robust%manner.
%
This%system%may%be%amena
ble%to%reaction%calorimetric%monitoring
,%which%would%
provide%rate%as%a%direct%measurement.
%