Room temperature hydroamination of alkynes with anilines catalyzed by anti-Bredt di(amino)carbene gold(i) complexes

Article abstract of DOI:10.1039/c6nj00980h

The room temperature hydroamination of alkynes with phenylhydrazine and anilines was achieved with an anti-Bredt di(amino) carbene gold(i) chloride as precatalyst, in the presence of KBArF as chloride scavenger. These reactions were highly regioselective and excellent conversions were obtained (up to 99%) for a series of alkynes and anilines.

Full text of DOI:10.1039/c6nj00980h

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Room temperature hydroamination of alkynes
with anilines catalyzed by anti-Bredt
di(amino)carbene gold(I) complexes†
Cite this:DOI: 10.1039/c6nj00980h
Received (in Montpellier, France)
29th March 2016,
Xingbang Hu,‡a David Martin*ab and Guy Bertrand*a
Accepted 10th May 2016
DOI: 10.1039/c6nj00980h
www.rsc.org/njc
The room temperature hydroamination of alkynes with phenyl- di(amino)carbenes, are significantly more p-accepting than
hydrazine and anilines was achieved with an anti-Bredt di(amino) classical cyclic di(amino)carbenes (often referred as N-heterocyclic
carbene gold(I) chloride as precatalyst, in the presence of KBArF as carbenes, or NHC), while retaining their strong s-donation to the
chloride scavenger. These reactions were highly regioselective and metal.11 Complexes 1 were found to be superior to their NHC
excellent conversions were obtained (up to 99%) for a series of counterparts as precatalysts for challenging hydroarylations of
alkynes and anilines.
alkenes9b and for hydrohydrazination of terminal alkynes under
mild conditions.9a Only a handful of catalysts are able to promote
The hydroamination of alkynes is a process, in which the N–H such hydrohydrazination of alkynes at room temperature.8l More
fragment of an amine is added to the C–C triple bond, with generally, only rare homogeneous catalysts can perform hydro-
cleavage of the N–H bond and formation of a new C–N bond. amination of alkynes without heating,8f,m,12 and herein, we
This reaction has attracted a considerable interest due to the explore the scope of precatalysts 1 for such hydroamination
central role of amino compounds in organic chemistry.1 The of terminal alkynes at room temperature (Scheme 1).
resulting imines or enamines are key synthons, including for
First, we checked that our catalytic system (1a and potassium
the synthesis of bioactive or naturally occurring products.2 The tetrakis(pentafluorophenyl)borate) was not limited to the parent
intermolecular variant allows for the atom-economic assembling hydrazine. Unsurprisingly, in presence of 5% of the catalyst,
of simple amines and alkynes and, therefore, is especially phenylhydrazine added cleanly to a set of arylacetylenes and
relevant for the chemical industry. A variety of Lewis acids metal 1-ethynylcyclohexene, to afford quantitatively hydrazones 2a–d at
complexes are known to catalyze this reaction, but they all face room temperature after 24 h (Scheme 2).
limitations. For instance, early transition metals complexes are
In such Au(I)-catalyzed hydroamination, it is well-accepted
very active, but they are generally highly moisture-sensitive and that the presence of a catalytic amount of chloride scavenger
suffer from low functional group tolerance.3 Among late transition (such as KBarF) is critical to generate a L–Au(I)+ cation. The latter
metal-based catalysts,1d,4 complexes of gold(I) with stable carbene is the active form of the catalyst, which binds to the acetylene.
ligands have led to remarkable achievements in terms of stability Then, the C–N is formed by attack of the nucleophilic amine
and activity,5–8,9a including the first example of the very challenging to the activated alkyne through an outer-sphere mechanism.5b
hydroamination of alkynes with ammonia.7b We recently reported N-nucleophiles can compete with the alkyne for binding the gold(I)
gold(I) complexes 1,9 which bear cyclic diaminocarbenes with a center and difficulties to perform the hydroamination are often
pyramidalized nitrogen atom.10 These ligands, so-called anti-Bredt paralleled with the ability of the amine to inhibit the catalyst by
either a competing coordination of the amine to the gold
center,7,9a,13 or in the case of terminal alkynes by a competing
a UCSD-CNRS Joint Research Laboratory (UMI 3555),
Department of Chemistry and Biochemistry, University of California,
San DiegoLa Jolla, California 92093-0343, USA. E-mail: guybertrand@ucsd.edu
b
´
´
UMR CNRS 5250, Departement de Chimie Moleculaire,
´
Universite Joseph Fourier B. P. 53, 38041 Cedex 9 Grenoble, France.
E-mail: david.martin@univ-grenoble-alpes.fr
† Electronic supplementary information (ESI) available: NMR and mass spectro-
metry data; NMR spectra. See DOI: 10.1039/c6nj00980h
‡ Present address: School of Chemistry and Chemical Engineering, Nanjing
University, Nanjing 210093, P. R. China.
Scheme 1 Carbene–gold(I) chloride precatalysts 1a–d.
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Table 1 Hydroamination of phenylacetylene with aniline
Entrya
Catalytic system
Time (h)
Conversionb (%)
1
2
3
4
5
6
7
8
1a + TosylAg
1a + AgSbF6
1a + KBArF
1a
3
3
3
35
44
75
3
0
1a + KBArF
1b + KBArF
1c + KBArF
1d + KBArF
24
24
24
24
499
499
499
499
Scheme 2 Hydroamination of terminal alkynes with phenyl hydrazine
(conversions after 24 h at room temperature).
formation of the corresponding gold acetylides.14 Conversely,
for the present study, it could be inferred that our system will
be active for hydroamination with anilines, which are less
nucleophilic than phenylhydrazine.
a
0.5 mmol phenylacetylene, 0.55 mmol aniline, 5 mol% catalyst,
b
0.6 ml C6D6, room temperature. Determined by NMR.
Thus, we examined the hydroamination of phenylacetylene
with aniline. A set of experiments showed that, as for the hydro-
hydrazination, KBarF was an optimal co-catalytic salt; the use of
a Ag(I) cation, which is an excellent chloride scavenger, appeared
to be detrimental (entries 1–3). Unsurprisingly, complex 1a alone
couldn’t catalyze the reaction (entries 4). Furthermore, the
reaction rate proved to be insensitive to the N-substituent of the
ligand. All complexes 1a–d resulted in identical kinetics, nearly full
conversion being reached after a day at room temperature (Fig. 1
and entries 5–8 in Table 1). We chose to use precatalyst 1a for the
rest of the study.
Next, we explored the scope of this catalytic system for the
reaction of aryl alkynes and 1-ethynylcyclohexene with various
anilines (Scheme 3). Nearly complete conversion was observed
after 24 hours at room temperature for 16 combinations, each
partner bearing electron-withdrawing substituents, or donating
groups as well. The regioselectivity was excellent, the formation
of the Markovnikov products 3a–d, 4a–d, 5a–d and 6a–d being
exclusively observed.
Importantly, the reactions had to be performed in the
absence of water because the products were sensitive to hydrolysis
in presence of the catalytic system. For instance, when the crude
reaction mixture of 3a was kept in air for 24 hours, the formation of
acetophenone and aniline was observed (see ESI†). Interestingly,
this confirms the absence of moisture in our series of experiments
and allows for ruling out the addition of water to the alkyne,
Scheme 3 Hydroamination of terminal alkynes with anilines (conversions
after 24 h).
followed by condensation of the amine with the resulting ketone.
Such two-step pathway could have been considered, especially for
Fig. 1 NMR monitoring of the reaction of phenylacetylene with aniline at
room temperature with catalysts 1a–d (5 mol%).
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K. Gooßen, H. Heydt and L. J. Gooßen, Chem. Rev., 2015,
115, 2596.
the formation of 2a–d, as hydrazines are known to add readily to
ketones to form hydrazones.
2 For representative examples, see: (a) P. L. McGrane and
In conclusion, the combination of anti-Bredt NHC gold
complex 1a and KBarF was found to be highly active for promoting
the hydroamination of aryl alkynes and 1-ethynylcyclohexene with
phenyl hydrazine and various anilines. This is one of the very rare
catalytic systems to allow for these transformations at room
temperature. As for the hydrohydrazination of alkynes, the high
activity and selectivity is likely the result of both the specific
electronic properties and low steric hindrance of the anti-Bredt
NHCs. Further ligand and catalyst optimizations are ongoing in
order to extend the scope to even more challenging room tem-
perature hydroaminations of multiple bonds.
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General considerations on experiments
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All reactions were performed under an atmosphere of argon.
Solvents were dried by standard methods and distilled under
argon. 1H and 13C NMR spectra were recorded on a Bruker Avance
300 spectrometer. NMR multiplicities are abbreviated as follows:
s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet,
br = broad signal. Mass spectroscopy (MS) measurements were
performed on an Agilent LCTOF spectrometer or a Thermo
Finnigan GC-MS. An Agilent 6890N GC system was used to
monitor the reaction conversion. Substrates were purchased
from commercial sources and used as it. Catalysts 1a–d were
synthesized according to our reported procedure.9b
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Hydroamination reactions
Under an argon atmosphere, 0.5 mmol alkyne, 0.55 mmol
amine, 5 mol% catalyst 1, 5 mol% KBArF, 0.6 ml C6D6 and
were loaded in a dried schlenk. The solution was stirred at
room temperature for 24 hours. Conversion were determined
by NMR. Residual signal of non-deuterated solvent was used as
standard. We found no measurable difference between conver-
sions (referred to substrates) and product yields, indicating that
very few by-product was formed. The structures of the product
were confirmed with NMR and mass spectrometry (see ESI†).
Acknowledgements
The authors gratefully acknowledge financial support from the
DOE (DE-FG02-13ER16370). Thanks are due to the National
Natural Science Foundation of China (No. 21176110) and
Jiangsu Province Natural Science Foundation (BK20141311)
for a Fellowship (X. H.).
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