Catalytic Hydrogenations with Cationic Heteroleptic Copper(I)/N-Heterocyclic Carbene Complexes

Article abstract of DOI:10.1055/s-0037-1612302

A new heteroleptic cationic copper(I) complex bearing two N-heterocyclic carbene (NHC) ligands has been prepared. In situ, a Cu-O bond can be generated which enables the complex to catalytically activate H ₂. The resulting complex shows activit

Full text of DOI:10.1055/s-0037-1612302

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© Georg Thieme Verlag Stuttgart · New York
2019, 30, A–D
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N. O. Thiel et al.
Letter
Synlett
Catalytic Hydrogenations with Cationic Heteroleptic Copper(I)/N-
Heterocyclic Carbene Complexes
Niklas O. Thiel1
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cationic Cu(I)
catalyst
Lea T. Brechmann
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Johannes F. Teichert*
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Institut für Chemie, Technische Universität Berlin,
Straße des 17. Juni 115, 10623 Berlin, Germany
johannes.teichert@chem.tu-berlin.de
iPr
iPr
Cu
H
O
O
N
N
OH
R
R'
R
R'
H
base, H2
Received: 15.01.2019
Accepted after revision: 08.02.2019
Published online: 06.03.2019
tive manner and are characterized by their negligible ten-
dency for overreduction to the corresponding alkanes. For a
systematic optimization, however, both catalysts pose par-
ticular challenges: Complexes of the type 1 with a tethered
ligand have so far not been isolated due to their tendency to
oxidize to the corresponding (inactive) copper(II) counter-
parts.6a In addition, this catalyst requires high H2 pressure
(generally 50–100 bar), which impedes the practicability of
the overall catalytic hydrogenation. However, this catalyst
type is modular and can easily be varied both structurally
as well as electronically through a variety of substituents.6c
While the second type of catalyst (2) is air-stable and can
therefore be operated without special precautions, it shares
the limitation of being active only at elevated H2 pres-
sure.6b,d In addition, with the exception of one closely relat-
ed complex,10 copper(I) hydroxide/NHC complexes based
on other NHC ligands are highly unstable, which hampers
their use and systematic optimization.
DOI: 10.1055/s-0037-1612302; Art ID: st-2019-k0025-l
Abstract A new heteroleptic cationic copper(I) complex bearing two
N-heterocyclic carbene (NHC) ligands has been prepared. In situ, a
Cu–O bond can be generated which enables the complex to catalytical-
ly activate H2. The resulting complex shows activity in catalytic chemo-
and stereoselective alkyne semihydrogenations as well as conjugate re-
ductions of enones.
Key words copper, NHC ligands, hydrogenation, homogeneous catal-
ysis, alkynes, enones
Well-defined copper(I) complexes bearing N-heterocy-
clic carbene (NHC) ligands have emerged as powerful cata-
lysts for a variety of transformations.2 While the vast ma-
jority of the complexes reported bear one NHC ligand (lead-
ing to Cu(NHC)X complexes, where X is an additional
anionic ligand), also the corresponding cationic complexes
of the general formula Cu(NHC)2+ have been investigated as
catalysts, albeit to a much lesser extent.3,4 Our group and
others have identified copper(I)/NHC complexes bearing a
Cu–O bond as useful catalysts for the activation of H2 and
subsequent hydrogenations or other reductive transforma-
tions.5–7 For catalytic chemo- and stereoselective alkyne
semihydrogenations, two general types of complexes have
been disclosed: i) copper(I) complexes such as 1 based on
bidentate (‘tethered’) NHC ligands bearing additional het-
eroatom tethers6a,e,8 that were generated in situ from the
corresponding imidazol(in)ium salts and a suitable cop-
per(I) precursor (Scheme 1, bottom left); ii) the simple and
preactivated copper(I) hydroxide complex [IPrCuOH]9 (2,
Scheme 1, bottom right).6b,d Both catalysts lead to a variety
of Z-alkenes from internal alkynes in a highly stereoselec-
cat. [Cu]
H2
(Z)
H
H
R
R
R'
chemo- and stereoselective
alkyne semihydrogenation
R'
reported catalysts:
iPr
iPr
N
N
N
R
N
iPr
iPr
Cu
OH
1
2
Cu
O
· modular setup
· air-stable
· facile structural variatons
· preactivated towards H2
· requires high pressure
· complex air-sensitive
· requires high pressure
· ligand cannot be varied
(has to be generated in situ)
Scheme 1 Reported copper(I)/NHC catalysts for alkyne semihydroge-
nations
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–D

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N. O. Thiel et al.
Letter
Synlett
We therefore decided to investigate cationic cop-
per(I)/NHC complexes 3 (Figure 1), with the aim to take ad-
vantage of a possible air stability while maintaining viable
pathways for derivatizations. Such a setup, with two differ-
ent NHC ligands coordinated to one copper(I) atom (hetero-
leptic complex), could serve as ideal platform for rapid and
systematic optimization of catalysts for a catalytic transfor-
mation of choice. At the same time, at least one of the NHC
moieties would have to be bidentate, with an additional
alkoxide moiety available for the generation of a Cu–O bond
required for H2 activation.
Figure 2 X-ray crystal structure of complex 5 (hydrogen atoms omit-
ted for clarity)
N
N
N
N
R
R
R
active to be isolated (Scheme 3). When polymethylhydrosi-
loxane (PMHS) was added to the reaction mixture at room
temperature, a fast appearance of a yellow color, indicative
for a possible (most probably dimeric)14 copper(I) hydride
complex 7, could be observed.15 Copper(I) hydrides are
known to be formed from complexes bearing a Cu–O bond
in the presence of hydrosilanes.16 At present, the structure
and bonding situation of the intermediately formed com-
plex 6 are unknown. The unknown intermediate 6 could
possess a Cu–O bond in a possible T-shape or trigonal coor-
dination mode.17
HO
Cu
3
Figure 1 Envisaged heteroleptic cationic copper(I)/(NHC)2complexes
We decided to take advantage of the high basicity9a of
the [IPrCuOH] complex (2) for the preparation of the envis-
aged cationic copper(I) complexes, and therefore anticipat-
ed that 2 could itself deprotonate an imidazolinium salt
such as 411 to generate the desired complex 5 (Scheme 2).
Indeed, when [IPrCuOH] (2) and imidazolinium salt 4 were
reacted in THF at room temperature, we were able to isolate
the new heteroleptic cationic copper(I) complex 5 in 52%
yield. We did not detect any copper(I) alkoxide complex
which could form through direct deprotonation of the alco-
hol moiety of ligand precursor 4.12 Heteroleptic cationic
copper(I) complex 5 was susceptible to X-ray crystal-struc-
ture analysis (Figure 2).13 The C–Cu–C angle was found to be
175°, and no interaction between the copper and the oxy-
gen atom was found. The new cationic copper(I) complex
was found to be bench-stable under air for months.
iPr
N
iPr
N
iPr
nBuLi (1 equiv)
iPr
Cu
O
5
THF, 21 °C,
5 min
colorless
N
N
6 (unstable - not isolated)
colorless
excess PMHS
THF, 21 °C
1 min
7
bright yellow
–
PF6
N+
Scheme 3 Attempted isolation of copper(I)/alkoxide complex 6 and evi-
dence for copper(I) hydride formation (PMHS = polymethylhydrosiloxane)
O
N
Mes
+
H
–
iPr
iPr
PF6
H
N
N
4
(1.0 equiv)
iPr
iPr
To assess the catalytic activity of the new cationic com-
plex 5, we decided to activate it in situ to generate the puta-
tive active complex 6 and then directly carry out an alkyne
semihydrogenation with tolane (8) and pentynol derivative
10 as representative internal alkynes. With 100 bar H2 pres-
sure at 60 °C, we found that tolane (8) showed 85% conver-
sion to Z-stilbene (9) with excellent stereoselectivity (E/Z
>95:5, Scheme 4), and no overreduction to the correspond-
ing alkane (not shown) detected. Without the addition of n-
butyllithium, no catalytic alkyne semihydrogenation was
observed. Full conversion of 8 was reached after 39 hours
reaction time. Under these conditions, alkyne 10 was also
fully converted with similar stereoselectivity, albeit in this
Cu
2
THF, 21 °C, 5 h
N
N
OH
5
52%
Scheme 2 Synthesis of cationic heteroleptic copper(I)/NHC complex 5
For catalytic activity with H2, the formation of a Cu–O
bond emanating from complex 5 was necessary. We there-
fore decided to deprotonate 5 with n-butyllithium as in our
earlier protocol.6a,e While full conversion of 5 was detected
after 5 minutes, the new complex 6 turned out to be too re-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–D

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N. O. Thiel et al.
Letter
Synlett
case with 3% alkane detected in the reaction mixture. Cat-
ionic complex 5 therefore shows the known characteristics
of a copper(I)/NHC complex in catalytic alkyne semihydro-
genations (high chemo- and stereoselectivity). When com-
paring the present catalyst 5 with the parent complex 2 un-
der similar conditions, two features of 5 become clear: i)
complex 5 is comparatively less reactive than 2 (as evident
from the significantly higher conversion of 8 under all con-
ditions). ii) complex 5 becomes active after a substantial
initiation period (of at least 8 hours). One reasonable expla-
nation for these results could be that one of the NHC ligands
on the cationic complex 5 acts as a ‘sacrificial’ ligand, which
is lost prior to the actual catalysis, leading to an active cata-
lyst. The observed induction period supports such an expla-
nation.18
5 (5 mol%)
nBuLi (5 mol%)
H
O
O
H2 (100 bar)
Ph
Ph
Ph
Ph
THF, 60 °C, 39 h
87% conv.
H
13
12
5 (5 mol%)
nBuLi (5 mol%)
O
Me
O
Me
Ph
H
H2 (100 bar)
OEt
Ph
OEt
THF, 60 °C, 16 h
<5% conv.
H
15
14
Scheme 5 Catalytic conjugate reductions with cationic complex 5
In summary, we have demonstrated that cationic, hetero-
leptic copper(I) complexes bearing two NHC ligands can be
employed as catalysts for H2 activation and alkyne semihy-
drogenations as well as conjugate reductions. The new com-
plex presented herein serves as an ideal platform for further
systematic development of well-defined copper(I)/NHC cat-
alysts, as it offers several advantages: The catalyst precursor
is air-stable and does not require special handling and addi-
tionally bears a multitude of sites for systematic variation
of electronic and steric parameters of the resulting cata-
lysts. This variation could stem from different NHC back-
bones, N-substituents, and/or the alkoxide tether.
5 (5 mol%)
nBuLi (5 mol%)
H
Ph
H2 (100 bar)
H
Ph
Ph
THF, 60 °C, 16 h
85% conv.
(>99% conv. after 39 h)
Ph
Z-9
8
Z/E >95:5
direct comparison of 2 and 5a at 100 bar H2, 60 °C:
2 (5 mol%), 8 h, 84% conversion of 8
5 (5 mol%), 8 h, <1% conversion of 8
2 (1 mol%), 16 h, 46% conversion of 8
5 (1 mol%), 16 h, no conversion of 8
5 (5 mol%)
nBuLi (5 mol%)
Funding Information
Ph
H2 (100 bar)
H
This work was supported by the German Research Council (DFG,
THF, 60 °C, 39 h
>99% conv.
Ph
BnO
10
H
Emmy Noether Fellowship for J. F. T., TE1101/2-1).
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e
F
orsc
h
u
n
gsg
e
m
e
i
nsc
h
aft(T
E
1
1
0
1/2-1)
BnO
Z-11
Z/E >95:5
3% alkane
Acknowledgment
Scheme 4 Alkyne semihydrogenations catalyzed by cationic copper(I)
complex 5. a An equimolar amount of nBuLi was added for activation of
the catalyst.
Dr. Elisabeth Irran is thanked for elucidation of the crystal structure.
Prof. Dr. Martin Oestreich (all TU Berlin) is kindly thanked for gener-
ous support.
One of the hallmark reactions of the so-called ‘copper
hydride catalysis’ is the conjugate reduction of ,-unsatu-
rated carbonyl or carboxyl derivatives.15 We therefore de-
cided to test the new cationic complex for these transfor-
mations as well. Chalcone (12) and cinnamic ester 14 were
chosen as model substrates. Under similar reaction condi-
tions as before (100 bar H2, 60 °C, THF), chalcone (12) could
be reduced to ketone 13 with 87% conversion, while no 1,2-
reduction of the ketone was observed (Scheme 5). The less
reactive and sterically more demanding enoate 14 showed
negligible conversion, displaying that the activity of the cat-
ionic complex 5 is limited at present in comparison to relat-
ed neutral copper(I)/NHC complexes.6f Nevertheless, the
observed reactivity of the new catalyst with enone 12 gives
an important indication that copper(I) hydride complexes
are indeed present after H2 activation.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1612302.
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References and Notes
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Letter
Synlett
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–D