Using alcohols as simple H2-equivalents for copper-catalysed transfer semihydrogenations of alkynes

Article abstract of DOI:10.1039/c9cc06637c

Copper(i)/N-heterocyclic carbene complexes enable a transfer semihydrogenation of alkynes employing simple and readily available alcohols such as isopropanol. The practical overall protocol circumvents the use of commonly employed high pressure equipment when using dihydrogen (H₂) on the one hand, and avoids the generation of stoichiometric silicon-based waste on the other hand, when hydrosilanes are used as terminal reductants.

Full text of DOI:10.1039/c9cc06637c

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Using alcohols as simple H2-equivalents for
copper-catalysed transfer semihydrogenations of
alkynes†
Cite this: Chem. Commun., 2019,
55, 13410
Received 26th August 2019,
Accepted 15th October 2019
Trinadh Kaicharla,
Johannes F. Teichert
Birte M. Zimmermann,
*
Martin Oestreich
and
DOI: 10.1039/c9cc06637c
rsc.li/chemcomm
Copper(I)/N-heterocyclic carbene complexes enable
a transfer copper hydride-based catalytic transformation, namely the semi-
semihydrogenation of alkynes employing simple and readily available reduction of internal alkynes to alkenes.10–12
alcohols such as isopropanol. The practical overall protocol circumvents
The alkyne semihydrogenation poses challenges in stereo-
the use of commonly employed high pressure equipment when using selectivity (E vs. Z) and chemoselectivity (overreduction of the
dihydrogen (H2) on the one hand, and avoids the generation of stoichio- formed alkene to the corresponding alkane, Scheme 1),10 and thus
metric silicon-based waste on the other hand, when hydrosilanes are serves as an ideal model reaction for catalyst development. To probe
used as terminal reductants.
a possible transfer of a hydrogen atom from the a-position of an
alcohol by means of a copper(I) catalyst, we investigated the transfer
Catalytic transfer hydrogenations (TH) are attractive for the semihydrogenation of internal alkyne 1, using a,a-dideuterated
reduction of a variety of functional groups, as they offer practical benzyl alcohol (2-d2, Scheme 1). Employing readily available [SIMes-
protocols circumventing the need for high pressure equipment.1 CuCl]13 in catalytic amounts (10 mol%) and NaOtBu as base, full
In general, for catalytic TH there is a need for easy-to-use and safe conversion either with microwave or conventional heating to the
dihydrogen (H2) sources, as these reactants are associated with the corresponding alkene 3 was found. Furthermore, significant
generation of one molecule of waste per turnover. Alcohols, 2H-incorporation (19–58%) in the b-position of the styrene moiety
such as the commonly employed isopropanol, fulfil the above- of 3 was observed, which suggested the envisaged presence of a
mentioned criteria.1
copper(I) hydride/deuteride intermediate.14–16
Copper-catalysed reductive transformations (so-called copper
No formation of the overreduced alkane was observed in this
hydride catalysis)2 pose formidable challenges with regard to initial experiment, which encouraged us to further develop the
transfer hydrogenations: On the one hand, copper hydride cata-
lysis almost exclusively relies on hydrosilanes as reducing agents,2
bringing forward a problem of atom economy due to silicon-based
waste generated. On the other hand, copper(I)-catalysed homo-
geneous hydrogenations (based on the atom economic H2) as
investigated by us and others3–5 generally require elevated H2
pressure, hampering their overall practicability. Finally, copper
is a readily available metal, which renders it highly attractive for
catalytic (transfer) hydrogenations.6 It comes to a surprise that
for homogeneous copper hydride catalysis, transfer hydrogena-
tions using alcohols as H2 equivalents have not been reported so
far, as this would manifest an atom economic and practical access
to copper hydride chemistry, addressing the abovementioned
limitations.7–9 Herein, we show that simple alcohols (such as
isopropanol) can be employed as H2 equivalents for a prototypical
Scheme 1 Deuterated alcohol as formal HD source in
a copper-
¨
¨
catalysed transfer hydrogenation. Reaction was carried out on a 0.2 mmol
scale. Conversion monitored by GC analysis. Deuterium incorporation
Institut fur Chemie, Technische Universitat Berlin, Strasse des 17. Juni 115,
10623 Berlin, Germany. E-mail: johannes.teichert@chem.tu-berlin.de
† Electronic supplementary information (ESI) available: Experimental procedures,
characterisation and NMR spectra. See DOI: 10.1039/c9cc06637c
a
determined by 1H/2H NMR spectroscopy. The Ha resonances could not
be resolved by 2H NMR spectroscopy.
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copper-catalysed transfer semihydrogenation of alkynes. There- under optimised conditions, the reaction could also be carried
fore, the viability of alcohols as H2 sources for copper hydride out with microwave heating to deliver the same results as
catalysis in a transfer hydrogenation setting was established.
To optimise the conditions of the catalytic protocol, we
conventional heating (Table 1, entry 11).
As the conduction of the reaction outside the microwave
opted for tolane (4) as model substrate (Table 1). We first leads to a simpler overall procedure, we investigated the sub-
demonstrated that 10 mol% of well-defined copper(I) com- strate scope of the copper(I)-catalysed transfer semihydrogenation
plexes of standard N-heterocyclic carbene (NHC) ligands17 with conventional heating next (Scheme 2). A variety of tolane
(SIMes, IMes and IPr, respectively)18 sufficed to achieve high derivatives gave the corresponding products 8a–c in very good
or full conversion in the catalytic transfer semihydrogenation of yields and Z-stereoselectivity (Z94%, Z/E Z 91 : 9). Both electron-
4 employing readily available isopropanol as H2 equivalent rich as well as electron-poor stilbene derivatives 8d to 8g were
(Table 1, entries 1–5). Along these lines, [SIMesCuCl] as catalyst obtained with similarly good results in terms of yield and
delivered the highest conversion and stereoselectivity to give Z/E-selectivity, albeit that trifluoro-substituted stilbene 8g was
stilbene Z-5 (100%, Z/E = 92 : 8, Table 1, entry 2). Notably, none of isolated with a somewhat lower yield of 66%. Moving on to aryl
the NHC/copper(I) complexes investigated gave any overreduction alkyl-substituted alkynes as substrates, we were able to isolate
to 1,2-diphenylethane (6). Other primary and/or secondary benzyl-protected hexenol-derivative 8h with Z/E = 82 : 18 and in
alcohols such as benzyl alcohol (2), glycerol or ethanol also gave 90% yield. This result is noteworthy, as no benzyl ether depro-
detectable conversion, however, these H2 equivalents could not tection was detected, albeit the overall reducing conditions of
compete with isopropanol in terms of either conversion or Z/E the overall process.19 The sterically more demanding cyclohexyl
selectivity (Table 1, entries 6–8). The change in stereoselectivity derivative 8i was the only compound studied which was accom-
is an indication that the alcohol employed alters the structure panied by a negligible amount of the corresponding alkane
and/or reactivity of the active catalyst. Indeed, when other (4%). The clean isolation of cyclopropyl styrene 8j with very good
secondary alcohols (2-pentanol and 2-hexanol) were tested, also, results (84%, Z/E = 97 : 3), and no evidence for a ring-opening
unselective reactions in terms of stereo- and chemoselectivity gives an important indication that no radical intermediates are
were observed (see the ESI,† Section S2). The omission of NHC involved in the overall process.20 Finally, the fully stereoselective
ligands led to diminished or complete loss of chemoselectivity, production of Z-6-dodecene (Z-8k) in acceptable yields shows
as with CuCl itself either 6% (with NaOtBu as base) or complete that isopropanol can also be used as H2 equivalent with dialkyl
conversion to undesired alkane 6 (using LiOtBu) was detected alkynes as substrates, which are relatively unreactive in copper-
(Table 1, entries 9 and 10). These results indicate the presence based semihydrogenations.3
of heterogeneous copper catalysts when no ligand is employed
It should be noted that generally, no overreduction to the
(see also Scheme 3 for more details). Finally, we established that corresponding alkane was observed, underscoring the ability of
Table 1 Copper-catalysed transfer semihydrogenation, optimisationa
Entry
Catalyst, loading
Base
Alcohol/solventb
Conv. [%]
Z/E-5
6 [%]
1
2
3
4
5
6
7
8
[SIMesCuCl], 5 mol%
[SIMesCuCl], 10 mol%
[IPrCuCl], 10 mol%
[IMesCuCl], 10 mol%
[SIMesCuCl], 10 mol%
[SIMesCuCl], 10 mol%
[SIMesCuCl], 10 mol%
[SIMesCuCl], 10 mol%
CuCl, 20 mol%
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBuc
NaOtBu
NaOtBu
NaOtBu
NaOtBu
LiOtBu
iPrOH
iPrOH
iPrOH
iPrOH
49
100
90
100
100
100
69
90 : 10
92 : 8
92 : 8
o1
o1
o1
o1
o1
o1
o1
o1
6
90 : 10
84 : 16
70 : 30
93 : 7
86 : 14
80 : 20
41%
95 : 5
iPrOH
BnOH/1,4-dioxaned
Glycerol/1,4-dioxanee
EtOH
29
9
iPrOH
iPrOH
iPrOH
100
100
100
10
CuCl, 20 mol%
[SIMesCuCl], 10 mol%
499
o1
11f
NaOtBu
a
b
Reactions were carried out on a 0.2 mmol scale. Conversion and selectivity determined by GC and 1H NMR analysis. If not noted otherwise,
c
d
1 mL of the corresponding alcohol was employed as solvent. 50 mol% NaOtBu was employed. 2.0 equiv. BnOH in 1 mL 1,4-dioxane was used.
e
f
1 mL of a glycerol/1,4-dioxane mixture (1 : 10 v/v) was employed. Reaction was performed with microwave heating at 120 1C for 16 h.
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the NHC ligand to control chemoselectivity in the transfer
hydrogenation. This feature is in stark contrast to related
transfer hydrogenations employing catalytic amounts of copper
nanoparticles which cleanly deliver the corresponding alkanes
from alkyne starting materials.7a The present protocol thus
achieves hitherto unreached chemoselectivity for copper-catalysed
transfer semihydrogenations, which can be related back to the key
influence of NHC ligands. The high Z selectivity reached for most
alkynes deserves some more comments: When following the
reaction with 8h, a relatively fast aforegoing alkyne semihydro-
genation takes place (100% conversion reached after 4h),
followed by a period in which no alkane was formed but the
Z/E ratio diminished, indicating a secondary isomerisation
process (see the ESI† for details). These results show that close
optimization of the reaction time for an alkyne of interest can
lead to even higher Z/E ratios.
Scheme 3 Influence of the NHC ligand on chemoselectivity.
To underscore the significant presence of the SIMes ligand
on the selectivity of the transfer semihydrogenation, we have
re-investigated chlorotolane 7f as substrate. In the presence of
SIMesCuCl under standard conditions, clean and stereo-
selective formation of the corresponding chlorostilbene 8f
was observed (91%, Z/E = 93 : 7, see Scheme 2). Under identical
reaction conditions but employing only copper(I) chloride as
catalyst, no alkene formation was observed, instead high con-
version to the corresponding dechlorinated and chlorinated
overreduced alkane 9 and 10 was detected (9/10 = 66 : 34). The
amount of dechlorination also depended on the counterion
of the base employed: with lithium tert-butoxide, a higher
percentage of the dechlorinated alkane 9 was found. (9/10 =
66 : 34 vs. 9/10 = 20 : 80 with NaOtBu) This result serves as
additional evidence for the fact that the active catalyst present
in the transfer semihydrogenations comprises an NHC ligand
which is vital for high selectivities.21
To address the need for readily available and cheap H2
equivalents for transfer hydrogenations, we have demonstrated
that simple alcohols can be employed in copper-catalysed
transfer hydrogenations. The results show that in the realm
of copper hydride catalysis both, high pressure equipment
(when using H2) as well as waste-generating hydrosilanes can
be circumvented, offering a cheap access to copper hydrides
and a practical overall protocol. The use of NHCs as key ligands
leads to high chemoselectivity (little or no overreduction to the
corresponding alkanes) and stereoselectivity (very high Z/E
ratios observed). The present first entry way to copper hydride
catalysis in a transfer hydrogenation setting from alcohols thus
has implications for a potential broader application in reductive
copper-catalysed transformations. The extension of this methodology
to other common copper hydride-based transformations is
currently ongoing.
This work was supported by the German Research Council
(DFG, Emmy Noether Fellowship for J. F. T., TE1101/2-1; funding
for T. K. through the cluster of excellence Unifying Concepts in
Catalysis).
Conflicts of interest
There are no conflicts to declare.
Notes and references
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Scheme 2 Copper-catalysed transfer semihydrogenation, substrate scope.
13412 | Chem. Commun., 2019, 55, 13410--13413
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