of 30
S
1
Supporting Information for
Transition Metal Mediated Nucleophilic Aromatic Substitution with Acids
Matthew E. O’Reilly,
Samantha Johnson,
Robert J. Nielsen,
William A.
Goddard III*,
and T. Brent Gunnoe
*
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904
-
4319, United
States
Materials Process and Simulation Center, MC (139
-
74), California Institute of Technology,
Pasadena, California 91125, United States
Index
Page
Experimental
General Considerations
S
2
Synthesis of
Q
2
FB
(
2
)
S
2
Synthesis of
(Q
2
FB)Rh(TFA)(COE)
(
3
)
S
2
-
S
3
Synthesis of
(Q
2
FB)Rh(TFA)
3
(
1
)
S
3
General procedure for catalytic S
N
Ar in HTFA
S
3
NMR spectra
Table of NMR chemical shifts
S4
NMR spectra of
2
S5
-
S6
NMR spectra of
3
S6
-
S10
NMR spectra of
1
S10
-
S13
19
F NMR spectra of CF
3
C(O)F
S13
19
F NMR spectra of CH
3
C(O)F
S14
NMR spectra of intermediate
4
S14
-
S16
NMR spectra of proposed
5a
and
5b
S17
-
S18
NMR spectra of catalytic defluorination
S19
Kinetics
Defluorination of
1
S20
-
S21
References
S2
2
DFT
Calculations
S23
-
S
30
S
2
Experimental
General Considerations.
Unless otherwise noted, all synthetic procedures were performed under
anaerobic conditions in a nitrogen filled glovebox or by using standard Schlenk techniques. Glovebox
purity was maintained by periodic nitrogen purges and was monitored by an oxygen ana
lyzer (O
2
< 15
ppm for all reactions). Tetrahydrofuran
, pentane and diethyl ether were
dried by distillation from
sodium/benzophenone. Benzene, hexanes, and methylene chloride were purified by passage through a
column of activated alumina. Benzene
-
d
6
, chlo
roform
-
d
1
,
and
tetrahydrofuran
-
d
8
were stored over 4Å
molecular sieves in a nitrogen atmosphere.
1
H NMR spectra were recorded on a Varian Mercury Plus 300
MHz or a Varian Inova 500 MHz spectrometer, and the
13
C NMR spectra were recorded on a Varian
Inova 5
00 MHz spectrometer (operating frequency 126 MHz). All
1
H and
13
C NMR spectra are referenced
against residual proton signals (
1
H NMR) or the
13
C resonances of the deuterated solvent (
13
C NMR).
{(COE)
2
Rh(
μ
TFA
)}
2
was
prepared according to published literatu
re procedures.
2
All other reagents
were used as purchased from commercial sources.
Synthesis of
8,8'
-
(4,5
-
difluorobenzene
)diquinoline
(Q
2
FB)
(
2
).
Q
uinolin
-
8
-
ylboronic acid
(1.50 g,
8.
67
x10
-
3
mol, 2.
4
equiv.), 1,2
-
dibromo
-
4,5
-
difluorobenzene (0.985 g, 3.62
x10
-
3
mol, 1 equiv.),
Pd(PPh
3
)
4
(0.418 g,
3.62
x10
-
4
mol, 0.
10
equivalents), and K
3
PO
4
(17.0 g, 8.01 x10
-
2
mol, 22 equiv.) were
combined into the 250 mL Schlenk flask. Under an inert atmosphere, degassed dimethylformaldehyde (60
mL) and degassed DI water (60 mL
) were added to the Schlenk flask, and the flask was fitted with a glass
stopper and sealed. The glass stopper was secured to the Schlenk flask with several rubber bands, and
then the reaction mixture was heated in an oil bath at 110 °C with stirring for 1
4 h. Afterwards, the
reaction mixture was allowed to cool to room temperature, during which the aqueous and organic layers
separated. The lower aqueous phase was separated from the organic phase by separatory funnel and
discarded. The organic layer was col
lected, and a copious amount of DI water (500 mL) was added to
precipitate a yellow oily solid. The solid was collected by filtration
and then
dissolved in Et
2
O (30 mL)
and filtered. The filtrate was collected and reduced under mild pressure to an oil. The
product was
purified by column chromatography (silica). The mono
-
coupled product was removed as the first fraction
using a solvent 1:10 (v/v) ethyl acetate:hexanes mixture
,
then the product was collected using ethyl
acetate as an
eluent
. Evaporating the solvent in vacuo of the second fraction affords a yellow oily solid.
The product was dried under vacuum for 2 days, triturated in pentane, and then filter
ed
to obtain a white
analytically pure
1
(0.229 g, Yield = 17%).
1
H NMR (CD
Cl
3
, 6
00
MHz):
δ
=
8.81
(
br
, 2H, Ar
H
),
8.00
(
br
, 2H, Ar
H
), 7.5
4
(
d
, 2H, Ar
H
,
3
J
HH
= 8 Hz
),
7.43 (t
, 2H,
Ar
H
,
3
J
HH
= 9 Hz
),
7.28 (br
,
4
H,
Ar
H
),
and 7.11 (br,
2
H,
Ar
H
)
ppm.
19
F NMR
(CD
Cl
3
, 6
00 MHz):
δ
=
-
140.6 (br, 2F) ppm.
13
C{
1
H} NMR
(
CD
Cl
3
, 15
0 MHz):
δ
=
150.2
(s, Ar
C
),
149.2
(s, Ar
C
,
1
J
CF
= 249 Hz,
2
J
CF
= 14 Hz
),
146.5
(s, Ar
C
),
139.2
(s, Ar
C
),
136.3
(s, Ar
C
),
136.0
(s, Ar
C
),
131.2
(s, Ar
C
),
128.2
(s, Ar
C
),
127.5
(s, Ar
C
),
125.6
(s, Ar
C
),
120.9
(s, Ar
C
),
and 120.6
(s, Ar
C
,
2
J
CF
= 13 Hz,
3
J
CF
= 6 Hz
) ppm. Anal. Calcd. for
C
2
4
H
14
F
2
N
2
(
368.39
g/mol): C:
78.25
%; H:
3.83
%; N:
7.70
%, Found; C:
78.12
%; H:
4.13
5
%; N:
7.81
%.
Synthesis of
(Q
2
FB)Rh(TFA)(COE)
(
3
).
A THF solution (5 mL) of ligand
2
(0.103 g, 2.80 x10
-
4
mol)
was added to a THF solution (5 mL) of {Rh(
μ
TFA)(COE)
2
}
2
(0.266 g, 6.1 x10
-
4
mol) dropwise and
stirred for 0.5 h.
The reaction mixture was dried under vacuum and t
he solid residue was washed with
pentane (2
5 mL)
. The solid was dissolved in minimal TH
F (2 mL)
and pentane (20 mL)
was added
to the
solution to precipitate an orange powder
.
The solid was collected by filtration, washed with
Et
2
O
(
3x
5
mL
), and dried under vacuum to afford the analytically pure
2
(0.
135 g, yield = 69
%).
1
H NMR (
d
8
-
THF,
6
00 MHz):
δ
=
10.53
-
10.58
(s, 1H, Ar
H
), 8.2
8
(s, 1H, Ar
H
), 8.1
5
(
br
, 1H, Ar
H
)
, 7.9
2
-
8.03
(
br
,
2
H,
Ar
H
), 7.
76
-
7.81
(s, 1H, Ar
H
), 7.
60
(br,
3
H, Ar
H
), 7.
49
(d, 1H, Ar
H
,
3
J
HH
= 8 Hz),
6.88
-
7.01
(br, 3H,
Ar
H
),
6.75
(
br
, 1H, Ar
H
),
5.51
-
5.59 (s, 1H, COE =
C
H
),
3.01
-
3.81 (br, 3
H, COE
-
H
),
and 0.89
-
2.42
(m
, COE
-
H
) ppm.
19
F NMR (
d
8
-
THF,
600
MHz):
δ
=
-
75.
2
(
br
, TFA, minor isomer
-
30
%) and
-
7
4
.
4
(
d
,
TFA,
J
= 6 Hz
major isomer
-
7
0
%)
,
-
139.1 (m, Ar
F
, minor isomer
-
30%),
-
139.2 (m, Ar
F
, major
isomer
-
70%),
-
140.0 (m, Ar
F
, major isomer
-
70%), and
-
140.3 (m, Ar
F
, major isomer
-
70%)
ppm.
S
3
13
C{
1
H} NMR (
d
8
-
THF, 150 HMz):
δ
= 157.
7
(s, Ar
C
), 15
7
.
5
(s, Ar
C
), 15
6
.5 (s, Ar
C
), 15
2
.
2
(s, Ar
C
), 1
50
.
5
(s, Ar
C
),
140
.
5
(s, Ar
C
), 13
9
.
6
(s, Ar
C
),
137.1
(s, Ar
C
),
136.
4
(s, Ar
C
), 134.5 (s, Ar
C
),
13
3
.
8
(s, Ar
C
), 13
2
.
1
(s, Ar
C
),
130
.
8
(s, Ar
C
), 1
29
.
7
(s, Ar
C
),
129
.
4
(s, Ar
C
),
129
.
1
(s, Ar
C
),
128.4
(s, Ar
C
)
,
128.3
(s, Ar
C
),
128.1
(s, Ar
C
),
126.5
(s, Ar
C
),
126.4
(s, Ar
C
), 12
2
.
6
(s, Ar
C
),
12
2
.
4
(s, Ar
C
), 1
22
.
3
(s, Ar
C
), 12
1
.
6
(s, Ar
C
), 12
1
.
4
(s, Ar
C
),
121.
3
(s, Ar
C
),
1
18
.
7
(s, Ar
C
),
1
18
.
6
(s, Ar
C
),
68.4
(s, COE
-
C
),
68.2
(s, COE
-
C
),
68.1
(s, COE
-
C
),
61.3
(s, COE
-
C
),
61.1
(s, COE
-
C
),
56.8
(s, COE
-
C
),
56.7
(s, COE
-
C
),
51.3
(s, COE
-
C
),
51.2
(s, COE
-
C
),
35.2
(s, COE
-
C
), 3
1
.
1
(s, COE
-
C
),
30.
8
(s, COE
-
C
),
30.2
(s, COE
-
C
),
30.0
(s, COE
-
C
),
2
9
.
3
(s, COE
-
C
),
28.6
(s, COE
-
C
), 2
7.8
(s, COE
-
C
),
2
7
.
6
(s, COE
-
C
), 2
7
.
5
(s, COE
-
C
),
27.4
(s, COE
-
C
),
27.2
(s, COE
-
C
),
26.6
(s, COE
-
C
),
26.4
(s, COE
-
C
),
26.2
(s, COE
-
C
),
26.0
(s, COE
-
C
),
23.4
(s, COE
-
C
),
and 14.5
(s, COE
-
C
)
ppm.
Anal. Calcd. for
C
34
H
28
F
5
N
2
O
2
Rh (
694
.
51
g/mol): C:
58.80
%; H:
4.06%; N: 4.03
%,
Found; C:
58.62
%; H:
3.97
%; N:
3.81
%.
Synthesis of
(Q
2
FB)Rh(TFA)
3
(
1
).
Complex
3
(0.046 g, 6.62 x10
-
5
mol) was dissolved
in
THF (10
mL) and Ag(TFA) (0.031 g, 1.40 x10
-
4
mol) was added. The reaction mixture was stirred for 0.5 h turning
from red to brown
-
yellow and depositing Ag(0). The reaction mixture was filtered, and the filtrate was
reduced to a solid
. The residue was washed with pentane before dissolving
in
minimal THF (1 mL) and
precipitating the complex as a yellow
-
brown powder upon the addition of Et
2
O (15 mL). Analytically
pure
3
was isolated by filtration and dried under vacuum (0.026 g, 54%).
1
H
NMR
(
d
-
THF, 6
00 MHz):
δ
= 9.
23
(
d
, 2
H,
Ar
H
,
3
J
HH
=
5
Hz
),
8.46
(
d
,
2
H, Ar
H
,
3
J
HH
=
8
Hz
),
7.86
(
d
, 2H, Ar
H
,
3
J
HH
=
8
Hz
),
7.74
(
t
, 2H, Ar
H
,
3
J
H
F
=
9
Hz
),
7.69
(
t
, 2H, Ar
H
,
3
J
H
H
=
6
Hz
),
7.54
(
t
, 2H, Ar
H
,
3
J
H
H
=
8
Hz
),
and 7.43
(
d
,
2H, Ar
H
,
3
J
H
H
=
8
Hz
) ppm.
19
F NMR
(
d
-
THF, 6
00 MHz):
δ
=
-
73.4 (s, 3F, TFA),
-
73.6 (s, 6F, TFA),
and
-
124.9 (t, 2F,
3
J
FH
=
9
Hz
) ppm.
13
C{
1
H} NMR (CDCl
3
, 1
50
MHz):
δ
=
163.1 (q, O
C
(O)CF
3
,
1
J
CF
=
33
Hz
), 160.9 (q, O
C
(O)CF
3
,
1
J
CF
=
40
Hz
),
156.0 (dd,
Ar
C
,
1
J
CF
= 249 Hz,
2
J
CF
= 16 Hz
),
15
5
.
5
(s, Ar
C
),
152.8
(s, Ar
C
), 14
1
.
7
(s, Ar
C
),
134.9
(s, Ar
C
),
134.5
(s, Ar
C
),
128.8
(s, Ar
C
),
1
27.0 (d
d
, Ar
C
,
2
J
CF
=
13 Hz,
3
J
CF
=
6 Hz
),
12
3
.
6
(s, Ar
C
) and
123.0
(s, Ar
C
) ppm.
Anal. Calcd. for C
30
H
14
F
11
N
2
O
6
Rh
(
810.34
g/mol): C: 44
.
47
%; H:
1.74%; N: 3.46
%,
Found; C:
44.46
%; H:
1.90
%; N:
3.41
%.
Catalytic Defluorination.
In a
typical
experiment, a
J
. Y
oung tube was
filled with
10
μ
L of
fluoroarene,
5 mg of [Cp
*
Rh(C
6
H
6
)][BF
4
]
2
or 5 mg of Ru(C
6
H
6
)Cl
2
/15 mg AgTFA, and 0.3 mL of
H
TFA.
The contents were heated in an oil bath at 180 °C for 20 h prior to analysis by
1
H and
19
F NMR
spectroscopy.