Supporting Information
Kinetic and Spectroscopic Studies of Aerobic Copper(II)-Catalyzed
Methoxylation of Arylboronic Esters and Insights into Aryl
Transmetalation to Copper(II)
Amanda E. King, Bradford L. Ryland, Thomas C. Brunold, Shannon S. Stahl*
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue,
Madison, WI 53706
Table of Contents
1. Kinetic dependence on O2 in the presence of added acetic acid ...................................S2
2. Kinetic dependencies with a 1:1 CuII:OAc ratio .....................................................S2-S3
3. Gas-uptake experiments in the presence of sodium methoxide ....................................S3
4. Effect of added acetate and acetic acid on EPR spectra ..........................................S4-S5
5. Use of B(OMe)3 to generate spectrum of species A ................................................S5-S6
5. EPR spectroscopic time course with 1 equivalent of NaOAc .......................................S6
6. Full EPR spectra for figures in the manuscript .......................................................S7-S8
7. Additional experimental details .............................................................................S8-S11
8. Data tables for kinetics plots and EPR titration curves........................................S12-S15
9. Reference ...................................................................................................................S15
S1
1. Kinetic Dependence on O2 in the Presence of Added Acetic Acid
Figure S1. O2 uptake rate dependence on initial pressure of O2 with added acetic acid.
Conditions: (A) 7.5 mM Cu(OAc)2, 30 mM AcOH = 30 mM, 150 mM tolylboronic ester,
pO2(i) = 500-1000 torr, 27 °C.
2. Kinetic Dependencies with a 1:1 CuII:OAc Ratio
(a)
(b)
S2
(c)
Figure S2. Kinetic dependence on the reaction components with a 1:1 mixture of
Cu(ClO4)2 and NaOAc. Standard conditions: 7.5 mM Cu(ClO4)2, 150 mM tolylboronic
ester, 7.5 mM NaOAc, 600 torr pO2(i), 27 °C. (a) pO2(i) = 400 – 800 torr. (b)
[tolylboronic ester] = 37.5 – 350 mM. (c) [Cu(ClO4)2] = [NaOAc] = 0-7.5 mM.
3. Gas-uptake Experiments in the Presence of Sodium Methoxide
The activity of Cu(OTf)2 in the presence of 0, 0.5, 1, and 1.5 equiv NaOMe was
examined via manometric methods. A reaction catalyzed by a 1:2 ratio of
Cu(OTf)2:NaOAc was used as a control. All reactions performed in the presence of
NaOMe showed >95 % yield of and exhibited significantly faster rates than the mixture
with NaOAc. The results from this experiment are summarized in Table S1.
Table S1. Rates and Yields of Methoxylation of Tolylboronic Ester with
CuII/NaOMe.a
GC Yield
Catalyst
Me
a
c
OH
OMe
Total O2 consumed
(µmol)
Rate (mM/s)c
Me
Cu(OTf)2
12
34
78.5
0.00315
Cu(OTf)2 + 0.5 equiv NaOMe
53
47
347
0.163
Cu(OTf)2 + 1.0 equiv NaOMe
58
41
331
0.224
Cu(OTf)2 + 1.5 equiv NaOMe
46
48
317
0.1912
Cu(OTf)2 + 2 equiv NaOAc
67
21
315
0.0302
II
Conditions: 150 mM tolylboronic ester, 7.5 mM Cu source, 27 °C, pO2(i) = 600 torr, 6 h. b GC Yield.
Initial O2 uptake rate.
S3
4. Effect of added acetate and acetic acid on EPR spectra
Titrating sodium acetate into a solution of Cu(OTf)2 demonstrates that one equivalent of
acetate is needed in order to replicate the EPR spectra acquired under catalytic
conditions. With no acetate present (red trace), the spectrum is consistent with a
previously reported CuII alcohol solvent complex.1
0
-
0 equivalents AcO
-
0.25 equivalents AcO
-
0.5 equivalents AcO
-
1.0 equivalents AcO
-
2.0 equivalents equivalents AcO
-
4.0 equivalents equivalents AcO
-5
-10
2.60
2.6
2.59
2.58
2.57
2.56
2.55
2.4
2.54
2.2
2.0
1.8
g value
Figure S3. Effect of sodium acetate on Cu speciation by EPR. Conditions: [Cu(OTf)2] =
7.5 mM, [ArB(OMe)2]= 150 mM. Spectra at 77 K. At < 1:1 ratios of [NaOAc]:[Cu(OTf),
we observe species that are not observed under normal catalytic conditions.
S4
(a)
(b)
(c)
(d)
Figure S4. Lowest field EPR signal displaying the effects of sodium acetate (a-b) and
acetic acid (c-d) on EPR titration curves. (a) Lowest field EPR signal in the presence of
10 equivalents of sodium acetate. (b) Concentrations of species present upon fitting
spectra in a. (c) Lowest field EPR signal in the presence of 10 equivalents of acetic acid.
(d) Concentrations of species present upon fitting spectra in (c). Addition of boronic acid
increases the concentration of EPR-active CuII with the concentration of species 1 being
greater than the concentration of species 2. Conditions: [Cu(OAc)2·H2O] = 3.8 mM,
[acetic acid or sodium acetate] = 38 mM, [ArB(OMe)2] = 0-150 mM. Solutions made at
room temperature in methanol and flash frozen at 77 K.
5. Use of B(OMe)3 to Generate Spectrum of Species A
The addition of B(OMe)3 to either a solution of Cu(OTf)2 with two equivalents of NaOAc
or a solution of Cu(OAc)2 (data not shown) results in the formation of a species with EPR
parameters similar to those observed for species A (Figure S5)
S5
Figure S5. Comparison of the EPR spectra of Cu(OTf)2 + 2 equiv NaOAc + B(OMe)3
(green) and Cu(OAc)2 + tolylboronic ester under reaction conditions (red). Conditions:
7.5 mM CuII source, 150 mM boron species, 15 mM NaOAc (green trace only).
5. EPR Spectroscopic Time Course with 1 equiv NaOAc
In the presence of 1 equiv of NaOAc relative to Cu(OTf)2, a time course similar to that of
Figure 9 was observed (Figure S6). Under conditions with only one equivalent of acetate,
the initial concentration of B is diminished relative to the standard conditions. B
disappears as the reaction proceeds.
Figure S6. Relative concentrations of A and B during catalytic turnover as determined by
spectral simulation. Conditions: 7.5 mM Cu(ClO4)2, 150 mM tolylboronic ester, 7.5 mM
NaOAc, 1 atm O2, room temperature, spectra acquired at 77 K.
S6
6. Full EPR Spectra for Truncated Figures in Full Text
Full spectra for Figures 11a, 11c, and 12 are given in Figures S7, S8, and S9,
respectively.
Figure S7. Effect of acetic acid on the EPR signal of Cu(OAc)2 with 150 mM
tolylboronic ester. See Figure 11a.
Figure S8. Effect of sodium acetate on the EPR signal of Cu(OAc)2 with 150 mM
tolylboronic ester See Figure 11c.
S7
Figure S9. Comparison of Cu(OTf)2 in the presence of different additives. Only in the
presence of both acetate and boron can spectra be observed with the characteristic
parameters for species observed under normal catalytic conditions. See Figure 12.
7. Additional Experimental Details
Inhibition Effect of Acetic Acid and Acetate as Additives. A procedure similar to that
described for gas-uptake studies was employed (see Experimental section of manuscript),
with the following modifications. A stock solution of glacial acetic acid or
tetrabutylammonium acetate (or NaOAc) in methanol (567.7 mM) was made and known
amounts added to the reaction vessels prior to the equilibration period. The total volume
of reaction was adjusted to 5 mL. The final concentrations of the additives under catalytic
conditions ranged from 0 mM to 30.6 mM.
Overall Acetate Effect. A procedure similar to that described for earlier gas-uptake
studies was employed, with the following modifications. A stock solution of sodium
acetate in methanol (567.7 mM) was made and known amounts were added to the
S8
reaction vessels prior to the equilibration period. The final concentrations of sodium
acetate under catalytic conditions ranged from 0 mM to 30.6 mM. A tolylboronic ester
stock solution (250 mM in MeOH, 3 mL, 0.75 mmol) was added to the reaction vessel
via syringe through a septum, and the pressure was allowed to equilibrate at 27 °C. The
reaction was initiated by the addition of a Cu(ClO4)2 solution (37.5 mM in MeOH, 1 mL,
0.038mmol). The total volume of the final solution was adjusted to 5 mL.
Kinetic Dependencies with Constant Acetate Concentration. A procedure similar to that
described for gas-uptake studies was employed (see main text) with the following
modifications. 3 mL of a stock solution consisting of the 4-tolylboronic ester (250 mM in
MeOH, 0.75 mmol) and 1 mL of a stock solution sodium acetate (37.5 mM, 0.15 mmol)
in methanol was added to the reaction vessel via syringe through a septum, and the
pressure was allowed to equilibrate at 27 °C. Subsequently, the reaction was initiated by
adding 1 mL of a solution consisting of Cu(ClO4)2.
Kinetic Dependencies with Constant Acetic Acid Concentration. A procedure identical to
that described for gas-uptake studies with added sodium acetate was employed, replacing
the sodium acetate solution with AcOH.
Hammett Study. A procedure similar to that described for gas-uptake studies was
employed with the following modifications. The boronic anhydrides were weighed
directly into the reaction vessels (0.75 µmol ester equivalent) and placed on the gasuptake apparatus. After the reaction vessels were charged with O2 to a final pressure of
S9
500 torr, 3 mL of methanol was added. After equilibration at 27 °C, the reaction was
initiated by adding the Cu(OAc)2 solution (18.75 mM in methanol, 2 mL, 0.038 mmol)
via syringe through a septum.
Gas-uptake Experiments with Cu(OTf)2 and NaOMe. The standard gas-uptake procedure
was used, with the following modifications. The O2 pressure in the reaction wells
containing 4 mL of a methanol solution of Cu(OTf)2 (0.03 mmol, 9.38 mM) and NaOMe
(0-0.045 mmol, 0-1.5 equiv). Reactions were initiated by injecting 1 mL of a 750 mM
solution of tolylboronic ester in methanol. The final volume of CuII and tolylboronic ester
were 7.5 mM and 150 mM, respectively. An additional well containing 2 equiv NaOAc
(0.06 mM, 15 mM), instead of NaOMe served as a reference to normal catalytic
conditions. After the reaction was complete, the solutions were diluted with EtOAc and
purified through a silica plug, trimethoxy benzene was added as an external standard, and
samples were analyzed by GC.
Preparation of EPR Samples for Titration Experiments. A typical titration procedure was
conducted as follows. A stock solution of Cu(OAc)2 (7.5 mM, 25 mL) and a stock
solution of the titrant was made in methanol. 1 mL of the Cu(OAc)2 stock solution was
combined with known volumes of the titrant stock solution and methanol to give a final
volume of 2 mL (3.75 mM in Cu(OAc)2). Aliquots of the samples were analyzed as
described in the General Considerations section.
S10
EPR Spectra of Different Boron Lewis Acids. 0.1 mmol of boronic anhydrides (0.3 mmol
ester equivalent) were weighed directly into the reaction flask to which a 2 mL solution
of 7.5 mM Cu(OAc)2 (0.015 mmol) in MeOH was added under air. After the solution was
homogeneous, 0.5 mL were removed and rapidly frozen for EPR spectroscopic analysis.
33.4 µL B(OMe)3 (0.3 mmol, 150 mM) were injected into a flask for the spectrum with
that additive.
Standard Procedure Preparation of EPR Samples for Catalytic Time Course
Experiments. A typical catalytic time course was conducted as follows. The tolylboronic
ester stock solution in methanol (260 mM, 3 mL, 0.78 mmol) was added to a reaction
vessel under O2 at 25 °C. Subsequently, the reaction was initiated by adding 2 mL of a
Cu(OAc)2 solution in methanol (18.75 mM, 2 mL, 0.038 mmol) via syringe. At timerecorded intervals 0.5 mL aliquots were removed from the reaction mixture and analyzed
as previously described.
EPR Time Course with Cu(OTf)2 and 1 Equivalent of NaOMe. The standard procedure
was used with the following modifications. 10 µL of a stock solution of NaOMe (0.785
mmol, 7.3 mM), prepared as described under General Considerations, was added to a 5
mL solution of Cu(OTf)2 (0.0365 mmol, 7.3 mM) and tolylbornic ester (0.785 mmol) in
methanol under 1 atm O2 at room temperature. At time-recorded intervals 0.5 mL aliquots
were removed from the reaction mixture and analyzed as previously described.
S11
8. Data Tables for Kinetics Plots
Tables S2a-2c. Data for Figure 2a-2c
[Cu II ]
(mM)
0.152
0.304
0.376
0.457
0.609
0.751
0.761
0.939
1.502
1.878
2.253
3.004
3.755
3.755
7.510
Rate
(mM/s)
0.0024(1)
0.0073(4)
0.0099(6)
0.0081(5)
0.0089(5)
0.0105(6)
0.0095(5)
0.0114(7)
0.0124(7)
0.0128(7)
0.0144(9)
0.0163(10)
0.0201(12)
0.0192(11)
0.0274(16)
[ArB(OMe)2]
(mM)
26.3
34.6
51.2
77.0
92.1
105.0
145.4
203.2
280.7
341.5
Rate
(mM/s)
0.0097(6)
0.0128(8)
0.0164(10)
0.0209(13)
0.0217(13)
0.0228(14)
0.0259(16)
0.0277(17)
0.0302(18)
0.0310(19)
Initial O2
pressure
(torr)
400
500
600
700
800
Rate
(mM/s)
0.030(2)
0.030(2)
0.030(2)
0.030(2)
0.030(2)
Table S3. Data for Figure 3. Effect of Added Acetic Acid or Acetate.
[AcOH]
(mM)
0.0
8.0
11.4
15.3
30.7
Rate
(mM/s)
0.025(1)
0.0108(6)
0.0079(5)
0.0064(4)
0.0036(2)
[Bu4NOAc]
(mM)
0.0
16.5
27.0
63.7
Rate
(mM/s)
0.025(2)
0.0101(6)
0.0077(2)
0.0037(2)
Table S4. Data for Figure 4. Overall Effect of Acetate on the Reaction Rate.
[NaOAc]
(mM)
0.0
3.8
7.5
11.3
15.0
30.0
Rate
(mM/s)
0.0060(2)
0.0491(30)
0.0666(39)
0.0479(29)
0.0299(18)
0.0164(9)
S12
Tables S5a-S5d. Data for Figures 5a-5d. Kinetic Dependences in the presence of NaOAc
(Tables S5a,S5b) or AcOH (Tables S5c, S5d)
[Cu II ]
(mM)
0.8
1.9
3.8
5.6
7.5
Rate
(mM/s)
0.00026(2)
0.00061(4)
0.00121(7)
0.00187(11)
0.00236(14)
[ArB(OMe)2]
(mM)
23.6
37.0
77.5
103.5
150.8
176.4
220.4
287.4
309.9
340.6
Rate
(mM/s)
0.0008(1)
0.0010(1)
0.0017(1)
0.0020(1)
0.0022(2)
0.0027(2)
0.0026(2)
0.0034(2)
0.0035(2)
0.0032(2)
[Cu II ]
(mM)
0.8
1.9
3.8
5.6
7.5
Rate
(mM/s)
0.00160(1)
0.0031(2)
0.0075(4)
0.0108(6)
0.0144(8)
[ArB(OMe)2]
(mM)
24.4
40.1
77.7
104.9
124.8
198.2
229.7
150.5
291.7
252.0
Rate
(mM/s)
0.0091(5)
0.0120(7)
0.0156(9)
0.0158(9)
0.0161(9)
0.0170(10)
0.0171(10)
0.0179(11)
0.0183(11)
0.0186(11)
Table S6. Data for Figure 6. Hammett Plot.
X
OMe
t
Bu
Me
H
Cl
CF 3
NO 2
!p
-0.27
-0.2
-0.17
0
0.24
0.54
0.78
ln(kX /kH)
0.038
0.164
0.192
0.000
-0.178
-0.322
-0.264
S13
Tables S7a-S7d. Data for Figures 8a-8d. EPR Titration Curves.
[ArB(OMe)2]
[EPR(mM)
active Cu II ]
0
0.61(6)
0.375
0.84(8)
0.9375
0.73(7)
1.875
1.23(12)
3.75
1.95(19)
9.375
2.31(23)
37.5
3.57(36)
150
3.81(38)
[ArB(OMe)2]
[EPR(mM)
active Cu II ]
0
0.35(3)
1.8864
0.48(4)
3.93
0.59(6)
5.24
0.58(5)
7.8599
0.71(7)
10.075
0.52(5)
18.864
0.77(7)
20.15
0.82(8)
37.728
1.10(10)
78.599
2.00(19)
131
2.61(26)
[B(OMe) 3]
(mM)
0
0.375
0.9375
1.875
3.75
9.375
37.5
150
[EPRactive Cu II ]
0.44(4)
0.42(4)
0.79(7)
0.86(8)
1.16(11)
1.78(18)
3.13(31)
3.79(35)
[ArB(OMe)2]
[EPR(mM)
active Cu II ]
0
0.67(6)
0
0.64(6)
1.8864
0.61(6)
3.93
0.67(7)
7.8599
0.83(8)
18.864
1.22(12)
37.728
1.45(15)
78.599
2.18(22)
131
2.50(24)
139.93
2.25(22)
Table S8. Data for Figure S1. O2 Dependence in the Presence of Added Acetic Acid.
Initial
Pressure O2
(torr)
561
666
769
855
984
Rate
(mM/s)
0.0026(1)
0.0024(1)
0.0027(2)
0.0026(2)
0.0025(2)
S14
Tables S9a-S9c. Data for Figures S2a-S2c. Dependences in the Presence of 1 equiv
NaOAc.
Initial
Pressure O2
(torr)
400
500
600
600
700
800
Rate
(mM/s)
0.064(5)
0.070(4)
0.073(4)
0.068(4)
0.069(4)
0.068(4)
[ArB(OMe)2]
(mM)
26.058
48.775
58.964
75.334
98.552
135.8
155.68
206.96
259.08
335.91
Rate
(mM/s)
0.023(1)
0.036(2)
0.040(2)
0.048(3)
0.056(3)
0.066(4)
0.074(4)
0.084(5)
0.093(6)
0.106(6)
[Cu(ClO4 )2 ]
(mM)
0
0.75
0.9
1.875
2.775
3.75
4.65
5.625
6.525
7.5
7.5
Rate
(mM/s)
0.0000
0.025(1)
0.028(2)
0.034(2)
0.049(3)
0.058(3)
0.063(4)
0.065(4)
0.070(4)
0.070(4)
0.075(4)
References
1. Poupko, R.; Luz, Z. J. Chem. Phys. 1972, 57, 3311-3318.
S15