Anti-Bredt N-heterocyclic carbene: An efficient ligand for the gold(i)-catalyzed hydroamination of terminal alkynes with parent hydrazine

Article abstract of DOI:10.1039/c3cc41279b

An anti-Bredt N-heterocyclic carbene gold(i) chloride complex was synthesized by taking advantage of the reversible insertion of the free carbene into the NH bond of hexamethyldisilazane. This precatalyst promotes the parent hydrazine hydroamination of te

Full text of DOI:10.1039/c3cc41279b

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Anti-Bredt N-heterocyclic carbene: an efficient ligand
for the gold(I)-catalyzed hydroamination of terminal
alkynes with parent hydrazine†
Cite this: DOI: 10.1039/c3cc41279b
Received 19th February 2013,
Accepted 22nd March 2013
´
´
Mar´ıa J. Lopez-Gomez, David Martin and Guy Bertrand*
DOI: 10.1039/c3cc41279b
www.rsc.org/chemcomm
An anti-Bredt N-heterocyclic carbene gold(I) chloride complex was
synthesized by taking advantage of the reversible insertion of the
free carbene into the NH bond of hexamethyldisilazane. This
precatalyst promotes the parent hydrazine hydroamination of
terminal alkynes at room temperature.
Chart 1
Over 2 ꢀ 105 tonnes of hydrazine (H2NNH2) are produced
annually and processed worldwide for pharmaceutical, agro-
chemical, polymer and aeronautic industries.1 Despite its
industrial importance, and the central role of carbon–nitrogen
bond formation in organic synthesis, this cheap N-containing
building block has rarely been used as a substrate in homo-
geneous organometallic catalysis. Several issues hamper its use
with transition metal catalysts. Its strong reducing properties
can lead to inactive metal(0) particles2 or undesired side-reactions
on organic co-substrates.3 Like ammonia,4 hydrazine also gives
rise to Werner-type complexes, which are usually inert.5,6 There
are only two reports of successful metal catalyzed function-
alizations of hydrazine. In 2010, Lundgren and Stradiotto7
demonstrated that the use of an electron rich bulky P-ligand
(Mor-DalPhos) allowed for the Pd-catalyzed cross-coupling of
hydrazine with aryl chlorides and tosylates. A year later our
group reported that cationic gold(I) complexes,8 bearing a cyclic
(alkyl)(amino)carbene (CAAC)9 A ligand (Chart 1) promoted
the hydroamination10 of alkynes and allenes with parent
hydrazine;11 however, elevated temperatures, typically 90–110 1C,
were required. Here we report the preparation of a new gold(I)
complex, which allows for the room temperature hydroamination
of terminal alkynes with hydrazine.
Of particular importance, because of the presence of only one
nitrogen p-donor substituent, CAACs A are considerably more
p-accepting12 than classical N-heterocyclic carbenes (NHCs) B.13–15
Recently, we reported the preparation of NHCs of type C in
which one of the two nitrogen atoms of classical NHCs is
placed in a strained bridgehead position, thus being restricted
from donating its lone pair.16 Compared to classical NHCs A,
this topological feature considerably increases the p-accepting
character of the carbene, without diminishing its s-donor
properties. As a result, these so-called ‘‘anti-Bredt NHCs’’
C resemble CAACs A more than NHCs B, and thus are
potential ligands for efficient gold-catalyzed intermolecular
hydroaminations.
In an attempt to synthesize the (carbene)gold chloride
1ꢁAuCl, imidazolium salt 1ꢁH+ was reacted with potassium
hexamethyldisilazide (KHMDS) in THF at ꢂ78 1C, and sub-
sequent addition of one equivalent of chloro(tetrahydro-
thiophene) gold(I)17 yielded a black-red slurry (Scheme 1). After
workup, mass spectroscopy showed a molecular peak at m/z =
765.41 indicating the formation of the bis(carbene)Au(I) complex 2,
The peculiar electronic properties of CAACs A clearly
account both for the robustness of cationic gold complexes
and the reactivity of the corresponding Werner complexes.
UCSD-CNRS Joint Research Laboratory (UMI 3555), Department of Chemistry and
Biochemistry, University of California, San Diego, La Jolla, CA 92093-0343, USA.
E-mail: guybertrand@ucsd.edu; Tel: +1 858 534 5412
† Electronic supplementary information (ESI) available: Synthetic procedures and
analytical data; CIF files for single crystal X-ray structural analysis. CCDC 924514
and 924515. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c3cc41279b
Scheme 1 Synthesis of gold complexes 2 and 1ꢁAuCl.
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Table 1 Catalytic hydroamination of 1-hexyne with hydrazine
Fig. 1 X-ray structure of 2 (left) and 1ꢁAuCl (right) with thermal ellipsoids drawn
at 50% probability level. Triflate anion of 2, hydrogen atoms and solvent
molecules are omitted for clarity.
Entry
L
Solvent
Temp.
Time (h)
Conversiona (%)
1
2
3
4
5
6
7
1
1
1
1
5
6
7
CDCl3
CD2Cl2
THF-d8
C6D6
C6D6
C6D6
rt
rt
rt
rt
rt
rt
rt
3
3
3
3
4
16
16
42
56
68
91
22
10
o5
instead of the desired complex 1ꢁAuCl. Under the same experi-
mental conditions, but using two equivalents of carbene 1,
complex 2 was isolated in good yield (85%) and fully charac-
terized. In the 13C NMR spectrum, both carbene ligands gave a
single set of signals, including a singlet at 223 ppm, in the
range expected18 for a carbene carbon coordinated to gold,
C6D6
a
Determined by 1H NMR with 1,4-di-tertbutylbenzene as an internal
standard.
indicating the diastereoselective formation of the bis(carbene)gold stable for weeks in solution and in the solid state. No evidence
complex 2. An X-ray diffraction study showed that it was the of disproportionation into 2 was observed.
meso isomer (Fig. 1).
In marked contrast with CAAC–gold complexes, which typi-
Bis(carbene) gold(I) complexes19 are known to be cata- cally require a temperature higher than the standard boiling
F
lytically inactive, and therefore we looked for an alternative point of the solvent, a mixture of 1ꢁAuCl (5 mol%) and KBAr 4
synthetic route to access complex 1ꢁAuCl. We reported that (5 mol%) promoted the hydrazine hydroamination of 1-hexyne
metal free carbene 1 could only be isolated if separated from at room temperature. A brief screening of solvents (Table 1,
hexamethyldisilazane (HMDS) at ꢂ78 1C, otherwise the carbene entries 1–4) showed that benzene gave the best results; a 91%
inserts into the NH bond of HMDS upon warming to ꢂ20 1C, conversion was reached after 3 hours (entry 4). Under the same
giving adduct 3.16 However, careful examination of the experimental conditions, only a 20% conversion was observed
13C NMR spectrum of the crude reaction mixture of 1ꢁH+ with after 4 hours with the C-adamantyl substituted CAAC 5 as
KHMDS revealed that, in addition to 3, small amounts (approx. ligand, and 10% conversion after 16 h in the case of CAAC 6,
5%) of unreacted carbene 1 and free HMDS, were present even which features a more bulky menthyl group (entries 5 and 6);
at room temperature. Importantly, the corresponding NMR the six-membered classical NHC 7 proved to be even less
signals persisted despite two succesive crystalizations of 3 efficient (entry 7).
(Fig. 2). These results demonstrate that the insertion of carbene
As shown in Table 2, for alkyl substituted terminal alkynes,
1 into the N–H bond of HMDS is reversible and that this the efficiency of the catalyst decreases when the steric
unprecedented equilibrium is not completely shifted towards hindrance of the substrates increases (entries 1–5). Note that
adduct 3.20
for the extreme case of tert-butyl acetylene, only a 29% con-
We wondered whether the slow release of carbene 1 in the version was observed after 1.5 day at room temperature, com-
presence of a gold(I) precursor could prevent the formation of pletion of the reaction required heating at 90 1C for 6 h.
bis(carbene) gold complex 2 and favor the selective formation The activation of electron-poor alkynes is of course more
of the mono(carbene) gold(I) chloride complex 1ꢁAuCl. Indeed, challenging. Phenyl-, anisyl- and 1-cyclohexenyl-acetylenes,
addition of freshly prepared 3 to a slight excess of (tetrahydro weakly react at room temperature. However, the corresponding
thiophene)gold(I) chloride yielded, after stirring overnight at hydrazones were obtained in good to excellent yields after
room temperature, the desired 1ꢁAuCl, which was isolated in heating at 75–90 1C for few hours (entries 6–9). The hydro-
57% yield, and comprehensively characterized including a single hydrazination of diphenylacetylene occurs with complete conver-
crystal X-ray diffraction study (Fig. 1). Importantly, 1ꢁAuCl is sion in chloroform within 6 hours but only at 110 1C (entry 10).
Fig. 2 13C NMR spectra of purified 3 ( ) after a night at room temperature in C6D6, featuring signals of free carbene 1 ( ) and HN(SiMe3)2
( ).
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Table 2 Catalytic hydroamination of alkynes with hydrazine
3166–3169; (g) X. Zeng, R. Kinjo, B. Donnadieu and G. Bertrand,
Angew. Chem., Int. Ed., 2010, 49, 942.
9 (a) V. Lavallo, Y. Canac, C. Prasang, B. Donnadieu and G. Bertrand,
Angew. Chem., Int. Ed., 2005, 44, 5705; (b) V. Lavallo, Y. Canac,
A. DeHope, B. Donnadieu and G. Bertrand, Angew. Chem., Int. Ed.,
2005, 44, 7236; (c) R. Jazzar, R. D. Dewhurst, J.-B. Bourg,
B. Donnadieu, Y. Canac and G. Bertrand, Angew. Chem., Int. Ed.,
2007, 46, 2899; (d) R. Jazzar, J.-B. Bourg, R. D. Dewhurst,
B. Donnadieu and G. Bertrand, J. Org. Chem., 2007, 72, 3492.
10 For recent reviews on gold-catalyzed hydroamination, see:
(a) A. S. K. Hashmi, D. Riedel, M. Rudolph, F. Rominger and
T. Oeser, Chem.–Eur. J., 2012, 18, 3827; (b) A. S. K. Hashmi,
Entry R, R0
Temp. Time (h) Conversionb (%) Yield (%)
1
2
3
4
5
6
7
8
9
nButyl, H
Cyclohexyl, H
Benzyl, H
tertButyl, H
tertButyl, H
Phenyl, H
rt
rt
rt
rt
3
18
4
36
6
12
3
4
91
78
87
29
88
o5
100
100
100
100
83
71
83
—
79
—
87
95
77
82
¨
90 1C
rt
90 1C
C. Lothschu¨tz, K. Graf, T. Haffner, A. Schuster and F. Rominger,
´
Adv. Synth. Catal., 2011, 354, 1407; (c) C. Bartolome, Z. Ramiro,
´
´
´
Phenyl, H
4-Methoxyphenyl, H 90 1C
D. Garcıa-Cuadrado, P. Perez-Galan, M. Raducan, C. Bour,
A. M. Echavarren and P. Espinet, Organometallics, 2010, 29, 951;
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Synth. Catal., 2010, 352, 1315; (e) A. S. K. Hashmi, C. Lothschu¨tz,
1-Cyclohexenyl, H
75 1C
110 1C
6
6
10a Ph, Ph
¨
C. Bohling, T. Hengst, C. Hubbert and F. Rominger, Adv. Synth.
a
b
1
CDCl3 was used as the solvent. Determined by H NMR with 1,4-di-
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tert butylbenzene as an internal standard.
The last result indicates that the high efficiency of 1ꢁAuCl may
be limited to terminal alkynes.
To summarize, the anti-Bredt NHC gold(I) complex 1ꢁAuCl
promotes the addition of hydrazine to terminal alkynes under
unprecedented mild conditions. Since the electronic properties
(strong s-donor and p-acceptor) of anti-Bredt NHCs are similar
to those of CAACs, the superior catalytic activity of 1ꢁAuCl can
be attributed to steric factors. In contrast to the CAAC series,
the non-hindered mono(anti-Bredt)NHCs gold complex 1ꢁAuCl
does not undergo a dismutation into a catalytically inactive
bis(carbene) gold(I) complex.
11 R. Kinjo, B. Donnadieu and G. Bertrand, Angew. Chem., Int. Ed.,
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This work was supported by DOE (DE-FG02-09ER16069).
M.J.L.-G. thanks the university of Oviedo, the FICYT and the
Principado de Asturias for a postdoctoral Cların Research
´
Fellowship.
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