Gas-liquid segmented flow microfluidics for screening copper/tempo-catalyzed aerobic oxidation of primary alcohols

Article abstract of DOI:10.1002/adsc.201400925

Aerobic oxidation using a combination of copper salts and 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) represent useful tools for organic synthesis and several closely related catalyst systems have been reported. To gain further insights, these catalytic systems were evaluated in a gas-liquid segmented flow device. The improvement of oxygen mass transfer has a significant influence on the turnover-limiting step. Hence, an improved catalytic system using copper(II) as copper source was implemented in a microreactor for the safe and efficient oxidation of primary alcohol.

Full text of DOI:10.1002/adsc.201400925

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DOI: 10.1002/adsc.201400925
Gas–Liquid Segmented Flow Microfluidics for Screening
Copper/TEMPO-Catalyzed Aerobic Oxidation of Primary
Alcohols
a
a
a
Laurent Vanoye, Mertxe Pablos, Claude de Bellefon,
a,b,
and Alain Favre-Rꢀguillon *
Laboratoire de Gꢀnie des Procꢀdꢀs Catalytiques, CPE Lyon, 43 Boulevard du 11 novembre 1918, 69100 Villeurbanne,
a
France
E-mail: afr@lgpc.cpe.fr
Conservatoire National des Arts et Mꢀtiers, CASER-SITI, 2 rue Contꢀ, 75003 Paris, France
b
Received: September 22, 2014; Revised: November 21, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400925.
[
5]
Abstract: Aerobic oxidation using a combination of
copper salts and 2,2,6,6-tetramethylpiperidine N-
oxyl (TEMPO) represent useful tools for organic
synthesis and several closely related catalyst sys-
tems have been reported. To gain further insights,
these catalytic systems were evaluated in a gas–
liquid segmented flow device. The improvement of
oxygen mass transfer has a significant influence on
the turnover-limiting step. Hence, an improved cat-
alytic system using copper(II) as copper source was
implemented in a microreactor for the safe and effi-
cient oxidation of primary alcohol.
used Cu(I)/TEMPO in DMF. Sheldon et al. found
the accelerating effect of 2,2’-bipyridine (bpy) ligands
on the Cu(II) catalytic system, Koskinen et al. opti-
mized the type and amount of base with Cu(II), and
Stahl et al. performed scope and limitation studies as
well as kinetic and mechanistic investigations demon-
strating the importance of Cu(I) salts and N-methyl-
[
6]
[7]
[
8–11]
A
H
U
G
E
N
N
The applicability of the
[
12]
dehydes or alcohols using aqueous ammonia or to
and amino alcohols
and amino carbonyl compounds, respectively.
[
13]
[14]
oxidize amine
into imines
Increasing reaction efficiency is fundamental to
chemistry. It was reported by Stahl et al. that the reac-
tion rate is limited by aerobic oxidation of Cu(I).
Keywords: aerobic oxidation; alcohols; copper;
flow chemistry; 2,2,6,6-tetramethylpiperidine N-
oxyl (TEMPO)
[11]
One way this issue can be addressed is to operate at
a higher oxygen pressure and this was recently report-
[15]
ed by Stahl et al. in a continuous flow reactor.
However, even if near quantitative formation of ben-
zaldehyde from benzyl alcohol was obtained with
Green chemistry and green engineering practices a residence time of 5 min with 35 bar of diluted
have to be integrated into the development of new re- oxygen source (9% O in N ) at 1008C, these experi-
2
2
action conditions for fine chemistry. This is particular- mental conditions (diluted O and elevated tempera-
2
ly true for the oxidation of alcohol where many pro- ture) might not be optimum for the following reasons.
cedures using stoichiometric metal oxides, activated
DMSO, or hypervalent iodine oxidants continue to cess is essential since fuel, oxidant and energy are
Firstly, for aerobic oxidation, the safety of the pro-
[
1]
find widespread use. Over the past decade, major present at the same time in the reactor. One possibili-
advances have been made in the development of cata- ty is to operate outside the flammability limits of the
[
2]
[15]
lytic methods for the oxidation of alcohols and ex- solvent/reactants or to use the safety advantages of
tensive efforts have focused on the development of flow chemistry already demonstrated for highly reac-
[
16,17]
catalytic methods that use oxygen as the stoichiomet- tive chemical processes.
While the composition
[
3]
ric oxidant. Among them, persistent nitroxide and and temperature of the gas phase in microreactors are
Cu/nitroxide homogenous catalytic systems are some generally far above the flammability limits, the small
of most versatile catalysts for the aerobic oxidation of dimensions of the channels prevent explosion as dem-
[
4]
[18]
alcohol to aldehydes using oxygen. For the latter onstrated for the H /O reaction. The assumption of
2
2
system, numerous improvements have been reported inherent safety was recently mitigated by investiga-
since the pioneering work of Semmelhack et al. that tions showing that an explosion could propagate
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Recently, we have shown that aerobic aldehyde oxi-
dations are frequently limited by oxygen mass trans-
[
23]
fer resistance.
flask) the chemical performances of aerobic oxidation
chemical rate, selectivity, …) can be falsified by
Under lab scale conditions (stirred
(
oxygen starvation in the liquid. Microreactors and
continuous flow technology in general represent an
important opportunity towards greener chemical pro-
[
17]
duction. One of the main advantages of continuous
flow processing is the enhanced heat and mass trans-
fer characteristics in particular for biphasic reactions.
Gas–liquid reactions have been dramatically im-
proved using gas–liquid segmented flows (Taylor flow
pattern) owing to an enhanced mass transfer of gas-
eous reactants into the liquid phase due to of the re-
[
24]
circulation within the liquid slugs. As such, the use
of microreactors to study aerobic oxidation comprises
[
25]
an important and growing area of research. Using
microreactor technology, we have recently shown that
aldehydes could be safely and efficiently oxidized into
Scheme 1. Simplified catalytic cycle for the Cu-catalysed
the corresponding carboxylic acid using 5 bar of O at
2
aerobic oxidation of primary alcohols (adapted from
[
26]
[10,11]
room temperature. This prompted us to re-investi-
gate the continuous-flow aerobic oxidation of primary
refs.
).
alcohols with pure O using the Cu/TEMPO catalytic
2
[
19]
through the microreactor.
However, it should be system. The continuous-flow reactor already used for
[
26]
noticed that the small size of the microreactors leads aldehyde oxidation was slightly modified. A sample
to a small reactor inventory of hazardous chemicals loop was added (Figure 1) which allowed a rapid
and thus continuous flow methods provide a means to scanning of different catalysts, ligands, bases and co-
address safety issues associated with aerobic oxida- catalyst ratios.
tion.
The initial study was carried out using benzyl alco-
Secondly, small activation energies (Ea) for dioxy- hol in CH CN as the model substrate using the exper-
3
À1
gen binding (about 4–12 kJ·mol ) have been found imental conditions previously studied by Stahl et al.
[
20]
[9,10,27]
for copper and cobalt complexes.
Thus if aerobic [Cu(I)/bpy/NMI/TEMPO].
High conversion
[
11]
oxidation is the turnover-limiting step, the increase (70%) of benzyl alcohol was obtained in 5 min at
in temperature will have a limited effect on the rate room temperature using 5 bar of oxygen. The conver-
of the oxidation. It should also be noticed that a small sion as a function of residence time was then studied
Ea has also been calculated for the Cu(II)/nitroxyl- (Figure 2).
mediated oxidation of the alcohol to aldehyde via the
Residence times can be adjusted by varying the
H abstraction (steps C of the catalytic cycle in total flow rate of the feed or the PFA tubing length
[21,22]
Scheme 1).
(Figure 2). Within the accuracy of the measurement
Figure 1. Experimental set-up for the aerobic oxidation of alcohol by the Cu/TEMPO catalytic system.
2
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Figure 3. Top view of the PFA tubing layout and visualisa-
tion of the colour of the liquid slug during the aerobic oxi-
dation of benzyl alcohol with the Cu(I)/bpy/NMI/TEMPO
catalyst system. Reaction conditions: 6 mmol benzyl alcohol
in CH CN (0.4M), 5 bar O , room temperature, PFA tubing
3
2
i.d.: 1.6 mm; 0.3 mmol of Cu(CH CN) (OTf) (5 mol%),
3
4
0
0
.3 mmol of bpy (5 mol%), 0.6 mmol of NMI (10 mol%),
.03 mmol of TEMPO (0.5 mol%). Residence time: 10 min
Figure 2. Conversion as the function of residence time for
Taylor flow aerobic oxidation of benzyl alcohol with the
Cu(I)/bpy/NMI/TEMPO catalyst system. Reaction condi-
tions: 6 mM benzyl alcohol in CH CN (0.4M), 5 bar O ,
(see the Supporting Information for a colour figure).
a benzyl alcohol conversion close to 50% under these
conditions. From this point, benzyl alcohol oxidation
Cu(CH CN) (OTf) (5 mol%), 0.3 mmol of bpy (5 mol), proceeds with copper species present in solution pre-
3
2
room temperature, PFA tubing i.d.: 1.6 mm; 0.3 mmol of
3
4
0
.6 mmol of NMI (10 mol%), 0.3 mmol of TEMPO dominantly in the form of Cu(II). With these results
(
5 mol%). The line in the Figure is only a guide for the eye. in mind, we turned our attention to a previously pub-
Insert: Arrhenius plots for Taylor flow aerobic oxidation of
lished catalytic mechanism (Scheme 1). The colour
change highlights the benefit of using Taylor flow pat-
tern for aerobic oxidation of alcohol with the Cu(I)/
bpy/NMI/TEMPO catalyst system. This behaviour is
benzyl alcohol.
(
about 2 and 5% absolute and relative conversion, re- in accordance with the proposed mechanism where
spectively), both possibilities lead to the same de- the aerobic oxidation of Cu(I) is rate-controlling
[9,10]
pendency between conversion and residence time. (steps A in Scheme 1) in a classical stirred flask.
Indeed it has been checked that the total flow rate The improvement of oxygen mass transfer changes
has no influence on conversion (see the Supporting the turnover-limiting step of the catalytic system
Information). Benzyl alcohol was totally and selec- (Scheme 1) and we can speculate that under Taylor
tively converted to benzaldehyde (>98%) at room flow conditions, the rate of aerobic oxidation of Cu(I)
temperature for residence times above 12 min. The (steps A) became slightly faster than steps B and C
apparent activation energy, Ea, is determined from corresponding to the formation of Cu-alkoxide spe-
the Arrhenius plots in the temperature range of 293– cies and oxidation of the alcohol to the aldehyde via
3
53 K (Figure 2, insert). The least-squares analysis hydrogen transfer to TEMPO consistent with the re-
À1
yields an Ea value below 10 kJ·mol which emphasiz- duction of Cu(II) to Cu(I).
es the use of room temperature for Cu/TEMPO oxi-
Scheme 1 highlights the pivotal role of Cu(II) spe-
dation unlike aerobic oxidation using Au or Ru/ cies and in particular Cu(II)OH and Cu(II)-alkoxide.
TEMPO catalytic systems which have higher Ea So, the reactivity of the Cu(II) species towards the
À1 [21,28]
values (from 20 to 60 kJ·mol ).
It should be no- aerobic oxidation of alcohol was re-evaluated using
ticed that to the best of our knowledge Ea for benzyl our microreactor device. The Cu(I) and Cu(II) cata-
alcohol oxidation was only estimated to be lytic systems were compared: the Cu source, ligand,
À1 [11]
<
60 kJ·mol .
base and cocatalyst ratio were varied while the use of
During the aerobic oxidation of benzyl alcohol room temperature, 5 bar of oxygen, 0.4M of benzyl
using Cu(I)OTf we noticed a progressive colour alcohol in CH CN and residence time of 5 or 10 min
3
change at the mid point of the transparent PFA tube were retained throughout (Table 1).
(
Figure 3 and Supporting Information).
Starting from beige, the colour of the liquid slug cohol could be selectively oxidized into benzaldehyde
With a residence time of 5 min or 10 min, benzyl al-
changes blue indicating a change in the oxidation with a conversion of 70% and 98%, respectively
degree of the majority of the copper species, i.e., (Table 1, entry 1) using Cu(I). As expected from the
[
8–10]
from Cu(I) to Cu(II) (see the Supporting (Informa- work of Stahl et al.,
modification of Cu(I)/bpy/
tion for colour figures). As calculated from the resi- NMI ratio and concentration only decreases conver-
dence time, this colour change was observed for sion. As anticipated by the apparent zero order de-
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[a]
Table 1. Copper-TEMPO aerobic oxidation of benzyl alcohol to benzaldehyde.
[b]
Entry
Cu salt (5 mol%)
Ligand (mol%)
Base (mol%)
Co-catalyst (mol%)
Conversion [%]
[
c]
[d]
1
2
3
4
5
6
7
8
9
Cu(I)OTf
Cu(I)OTf
Cu(II)(OTf)2
Cu(II)Br2
[(bpy)Cu(II)(OH)] (OTf)
[(bpy)Cu(II)(OH)] (OTf)
[(bpy)Cu(II)(OH)] (OTf)
[(bpy)Cu(II)(OH)] (OTf)
[(bpy)Cu(II)(OH)] (OTf)
bpy (5)
bpy (5)
bpy (5)
bpy (5)
–
NMI (10)
NMI (10)
NMI (10)
NMI (10)
–
NMI (10)
–
NMI (5)
NMI (5)
TEMPO (5)
TEMPO (0.5)
TEMPO (5)
TEMPO (5)
TEMPO (5)
TEMPO (5)
TEMPO (5)
TEMPO (5)
TEMPO (0.5)
70 , >98
[d]
>95
[
c]
c]
c]
c]
<2[
<2[
<2[
<2
2
2
2
2
2
2
–
2
[c]
bpy (10)
bpy (5)
bpy (5)
55
2
[c]
>98
> 98
2
[c]
2
[a]
[b]
[c]
[d]
Reaction conditions: 0.4M benzyl alcohol in CH CN, 5 bar O , room temperature, PFA tubing: 2.6 m, i.d.: 1.6 mm.
3
2
On-line GC yield. Post-run GC-MS analysis was used to confirm conversion and selectivity.
À1
À1
Residence time 5 min; O flow rate 4 NmL·min and liquid flow rate 0.16 mL·min .
2
À1
À1
Residence time 10 min: O flow rate 2 NmL·min and liquid flow rate 0.08 mL·min . bpy=2,2’-bipyridine, NMI=N-
2
methylimidazole, OTf=trifluoromethanesulfonate, TEMPO=2,2,6,6-tetramethyl-piperidine N-oxyl.
[
9]
pendency on TEMPO concentration, a conversion ing quantitative conversion and high selectivity
95% could be obtained with a concentration of (Table 1, entry 9). The conversion as the function of
TEMPO down to 0.5 mol% for a residence time of residence time for [(bpy)Cu(/II)(OH)] (OTf) com-
>
2
2
1
0 min (Table 1, entry 2). In our work, Cu(II) salts plex was then studied (Figure 4).
[8]
and particularly CuBr2 were found to be an ineffec-
The presence of an excess of bpy improves the cat-
tive copper source (Table 1, entries 3 and 4). Experi- alytic properties of the new catalytic system using
mental data suggests that Cu(II)OH species are key [(bpy)Cu(II)(OH)] (OTf) as the copper source.
2
2
[
11]
intermediates of the catalytic cycle (Scheme 1).
Indeed, [(bpy)Cu(II)(OH)] (OTf) complex could be
2
2
considered as an interesting Cu(II)OH source. This
[
29]
complex is readily synthesized from Cu(OTf)2 but
shows no activity (residence time of 5 min) in the
presence of 5 mol% of TEMPO (Table 1, entry 5).
When 10 mol% of NMI and 5 mol% of TEMPO were
added, a Cu/bpy/NMI/TEMPO ratio of 1/1/2/1 compa-
rable with the optimized catalytic system was ob-
[9]
tained. However, under our conditions (residence
time of 5 min) no conversion could be detected
(
Table 1, entry 6). It should be noticed that such a cat-
alytic system has been already evaluated by Stahl
et al. and was found to have similar rate to that with
Cu(I) after an induction period.
[
9]
A more positive result was obtained by the substi-
tution of NMI by bpy, which gave a 55% conversion
(
Table 1, entry 7), and the use of 5 mol% of bpy and
Figure 4. Conversion as the function of residence time for
Taylor flow aerobic oxidation of benzyl alcohol with the
Cu(II)/bpy/NMI/TEMPO catalyst system. Reaction condi-
tions: 6 mmol benzyl alcohol in CH CN (0.4M), 5 bar O ,
NMI with the [(bpy)Cu)(II)(OH)] (OTf) complex,
leading to a Cu/bpy/NMI/TEMPO ratio of 1/2/1/1,
gave a complete conversion (Table 1, entry 8) in
2
2
3
2
5
min. Thus, we could hypothesise that an excess of
room temperature, PFA tubing i.d.: 1.6 mm; 0.15 mmol of
bpy can lead to the formation of stabilised Cu(II)OH
species from the di-m-hydroxo-Cu(II) complexes.
[
(bpy)Cu(II)(OH)] (OTf) (5 mol%), 0.3 mmol of bpy
2 2
(
10 mol% taking into account of bpy present in the Cu com-
Under those conditions, the concentration of TEMPO plex), 0.3 mmol of NMI (5 mol%), 0.3 mmol of TEMPO
could be decreased to as low as 0.5 mol% while keep- (5 mol%). The line in the Figure is only a guide for the eye.
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Figure 5. Dependence of [bpyCu(OH)] (OTf) /bpy/NMI/TEMPO benzyl alcohol oxidation on (A) initial bpy concentration;
2
2
(
B) initial NMI concentration; (C) initial TEMPO concentration; (D) oxygen pressure; (E) initial benzyl alcohol concentra-
tion; (F) initial [(bpy)Cu(OH)] (OTf) concentration. Standard reaction conditions: 6 mmol benzyl alcohol in CH CN
2
2
3
(
0.4M), 5 bar O , molar ratio O /ROH=8; residence time=12 s, room temperature, tube length 0.25 m, id 1.6 mm;
2 2
0
.15 mmol of [(bpy)Cu(II)(OH)] (OTf) (5 mol%), 0.3 mmol of bpy (10 mol% taking into account of bpy present in the Cu
2 2
complex), 0.3 mmol of NMI (5 mol%), 0.03 mmol of TEMPO (0.5 mol%).
Under the same conditions, Cu(II) (Figure 4) shows a Cu(I) solution (without alcohol and TEMPO) was
a better reaction rate than Cu(I) (Figure 2). Quantita- evaluated after being kept on the shelf for more than
tive conversion of benzyl alcohol is obtained in 5 and 4 h, lower conversions were obtained. On the other
10 min, for Cu(II) and Cu(I) catalytic systems, respec- hand, when the Cu(II) solution (without alcohol and
tively, at room temperature using 5 bar of oxygen. It TEMPO) was evaluated after a night standing on the
should be noticed that, as expected, the Cu(I) catalyt- shelf at room temperature, the same conversions were
ic system was found to be sensitive to aging. When obtained. These results show that the Cu speciation
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has a strong impact on the catalytic efficiency. This Table 2. Cu(II)/TEMPO-catalysed aerobic oxidation of alco-
[a]
[
7]
hols to aldehydes.
was noticed previously and the influence of the
major components of the [(bpy)Cu(II)(OH)] (OTf)
2
2
[b]
Entry Product
Initial rates
(
Conversion
[c]
catalytic system, i.e., TEMPO, bpy, NMI, O pressure
À1
À1
2
mol·L ·min ) at 5 min
and benzyl alcohol concentration, were then investi-
gated independently to understand their role using
standard experimental conditions. The kinetic data of
the oxidation were easily obtained using our micro-
flow reactors (Figure 5).
The dependence on TEMPO concentration was
first evaluated using the standard reaction conditions.
A saturation dependence on TEMPO concentration
was observed under those conditions (Figure 5A), and
an optimum ratio of TEMPO/Cu of 1/10 could be
1
2
0.82
0.36
>99%
99%
3
4
5
0.22
0.16
0.05
96%
90%
50%
found.
A
concentration of TEMPO of 2 mM
(
0.5 mol%) was then used throughout the optimisa-
tion. A first-order dependence on Cu was obtained,
indicating that the reaction is not transfer limited
under our conditions (Figure 5B and see also the Sup-
porting Information). However, this increase stalled
progressively above 20 mM. This may be explained by
the formation of inactive intermediate Cu species due
to a non-optimum amount of NMI and bpy. As ex-
pected, the chemical speciation of the Cu and accord-
ingly the kinetics of the reaction can be tuned by
changing the concentrations of bpy and NMI (Fig-
ure 5C and 5D). An optimum ratio between Cu, bpy
and NMI of 2/3/2 taking into account the bpy already
present in the di-m-hydroxo-Cu(II) complex can be
found. A more detailed investigation on Cu(II) speci-
ation by EPR will be done in due course. At the pres-
ent time, we can only speculate that excess bpy and
NMI could dissociate the initial di-m-hydroxo-Cu(II)
complex and stabilise the Cu(II)OH species
6
7
0.03
0.02
39%
28%
[a]
Reaction conditions: 6 mmol alcohol in CH CN (0.4M),
, room temperature, 0.15 mmol of [(bpy)Cu(II)-
(OH)] (OTf) (5 mol%), 0.3 mmol of bpy (10 mol%
3
5 bar O
2
A
H
U
G
R
N
U
G
2
2
taking into account amount of bpy present in the Cu
complex), 0.3 mmol of NMI (5 mol%), 0.03 mmol of
TEMPO (0.5 mol%).
b]
[
Calculated for various residence times for a conversion
below 20%.
PFA tubing: 2.6 m, i.d.: 1.6 mm, O2 flow rate
NmL·min and liquid flow rate 0.16 mL·min . On-line
GC yield. Post-run GC-MS analysis was used to confirm
conversion and selectivity.
[c]
À1
À1
4
[
8–11]
[7]
(
Scheme 1). A first order reaction was observed for chemical rates.
As expected, no by-products
O pressure (Figure 5E), clearly demonstrating the could be detected during the oxidation of an unsatu-
2
usefulness of working with pressurised pure oxygen rated alcohol (Table 2, entries 4–6). For aliphatic alco-
and accordingly justifying the advantages of using hols (Table 2, entries 5 and 7) and propargylic alcohol
a micro-flow reactor. A first order reaction was also (Table 2, entry 6), the chemical rates were lower. Con-
observed for benzyl alcohol up to a concentration of versions below 50% for these alcohols, were obtained
0.5M where an inhibition was noticed that could be with a residence time of 5 min. However, higher con-
attributed to a solvent effect (Figure 5F). The fact version could be obtained at higher residence time
that both O and the reactant have positive orders im- (i.e., increasing the length of the PFA tubing or de-
2
plies that both steps A and B (Scheme 1) have com- creasing the total flow rate of the feed).
parable rates under those conditions (steps Bꢀsteps
In conclusion, we have demonstrated that the direct
A). This is in accordance with the colour change ob- aerobic oxidation of primary alcohols to the corre-
served during the course of the experiment using sponding aldehydes can be dramatically enhanced by
Cu(I) as copper source and lack of colour change using continuous-flow methodology with
a Cu/
using Cu(II) as copper source. TEMPO catalytic system and pressurised molecular
The oxidation of a small series of alcohols was then oxygen at room temperature. We have found that the
examined under the optimised conditions for benzyl speciation of the Cu species in solution has a signifi-
alcohol oxidation (Table 2). As expected, both benzyl- cant effect of the kinetics profile of the Cu/TEMPO
ic and allylic alcohols were efficiently converted to catalytic system. Stabilisation of Cu(II)OH using
the corresponding aldehydes at room temperature excess of bpy and NMI is essential for the catalytic
using pressurised molecular oxygen.
activity. Cu(II) salts could be used instead of Cu(I)
The chemical rate was a function of the alcohol and the reaction times could be significantly reduced
structure, allylic and benzylic ones having the higher from hours to minutes when the oxygen partial pres-
6
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sure is safely increased by using pressurised molecular
oxygen and microreactor technology.
b) B. L. Ryland, S. S. Stahl, Angew. Chem. 2014, 126,
968–8983; Angew. Chem. Int. Ed. 2014, 53, 8824–8838.
5] M. F. Semmelhack, C. R. Schmid, D. A. Cortes, C. S.
8
[
Chou, J. Am. Chem. Soc. 1984, 106, 3374–3376.
[
6] a) P. Gamez, I. W. C. E. Arends, J. Reedijk, R. A. Shel-
don, Chem. Commun. 2003, 2414–2415; b) P. Gamez,
I. W. C. E. Arends, R. A. Sheldon, J. Reedijk, Adv.
Synth. Catal. 2004, 346, 805–811.
Experimental Section
Typical Reaction Conditions with Cu(I)
[
7] E. T. T. Kumpulainen, A. M. P. Koskinen, Chem. Eur. J.
[
5
Cu(I)(CH CN) ]OTf (189 mg, 5 mol%), bpy (47 mg,
mol%) and NMI (50 mg, 10 mol%) were dissolved in
3 4
2
009, 15, 10901–10911.
CH CN (15 mL, 11.79 g). Then, TEMPO (47 mg, 5 mol%)
and benzyl alcohol (0.65 g, 0.4M) were added to the solu-
tion that should be used promptly.
[8] J. M. Hoover, S. S. Stahl, J. Am. Chem. Soc. 2011, 133,
16901–16910.
[9] J. M. Hoover, B. L. Ryland, S. S. Stahl, ACS Catal.
3
2
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[
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