Ligand influence in the selective gold-mediated synthesis of allenes

Article abstract of DOI:10.1039/c0cc03071f

The use of [(IPr)AuOH] permits the generation of gold(i)-amine complexes by a silver-free protocol. These in situ or well-defined complexes are used in a straightforward synthetic route to substituted allenes from propargylic acetates. The catalytic activ

Full text of DOI:10.1039/c0cc03071f

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Ligand influence in the selective gold-mediated synthesis of allenesw
Pierrick Nun, Sylvain Gaillard, Alexandra M. Z. Slawin and Steven P. Nolan*
Received 5th August 2010, Accepted 20th September 2010
DOI: 10.1039/c0cc03071f
The use of [(IPr)AuOH] permits the generation of gold(I)–amine
complexes by a silver-free protocol. These in situ or well-defined
complexes are used in a straightforward synthetic route to
substituted allenes from propargylic acetates. The catalytic
activity can be modulated as a function of the nature of the
ligand bound to the gold–NHC moiety.
original and simple method to prepare these useful organic
compounds from readily available substrates. Allenes are
useful synthetic intermediates in organic chemistry as they
possess versatile reactive properties.5 Thus, it is not surprising
that many synthetic methods have been described to prepare
these compounds.6 Among them, their copper mediated
formation from alkynes has been reported by Crabbe and
´
co-workers.7 Other methods have made use of alternate
metals, chiral amines and microwaves activation.8 All these
reactions leading to allenes involve an alkyne activation step
promoted by a metal. Gagosz et al. have recently shown that
allenes could be prepared from propargyl benzyl ethers after a
gold(I)-catalyzed hydride transfer/fragmentation sequence.9
As part of ongoing studies focused on the synthesis and catalytic
applications of [Au(NHC)]+ complexes (NHC = N-heterocyclic
carbene), we reasoned that dampening the Lewis acid character of
the gold center might result in less active catalytic species and
permit the isolation of organic intermediates, such as the allene 3a
in Scheme 1. Indeed, when coordinating bases are present in the
reaction medium, for instance when [(IPr)Au(pyr)][BF4] (4)
(pyr = pyridine)2e,10 was used as catalyst, the allene 3a was
exclusively formed after 1 h at RT (eqn (1)).
Gold has progressively emerged in recent years as a very efficient
catalyst in many transformations, especially in activation of
propargylic compounds.1 In most of these transformations,
the active species is generated in situ via reaction between
phosphine or N-heterocyclic carbene gold(I) chloride complex
and a silver salt. It has been noticed that the presence of a ligand
coordinated to the cationic gold center could lead to air- and
moisture-stable complexes.2 Usually, this ligand is used as a
stabilizing agent, allows the preparation and storage of these
complexes and therefore eliminates the need for the use of silver
salts in the reaction. Nevertheless, silver salts are still required to
prepare these complexes. In our ongoing research on gold(I)
catalysis, we decided to investigate if the nature and the
electronic properties of this ligand could lead to variations in
reactivity displayed by the gold center. In previous work, we
have shown that the [(IPr)AuCl]/AgBF4 (IPr = N,N0-bis-
(2,6-diisopropylphenyl)-imidazol-2-ylidene), catalytic system,
could mediate the transformation of propargylic acetate 1a to
indene 2a (Scheme 1).3 This reaction proceeds via a [1,3] acyl-
shift of the propargylic acetate4 giving allene 3a, as a transient
intermediate that undergoes an intramolecular hydroarylation
to form indene 2a. Under these conditions, the hydroarylation
step is too rapid to permit the isolation of the allene.
ð1Þ
Under these conditions, the intramolecular hydroarylation can
occur to produce 2a but only after a further reaction time of
12 hours. The use of species such as 4 could therefore provide a
potentially attractive alternative to selectively prepare allenes 3
from propargylic acetates 1.
Our initial hypothesis was to dampen the reactivity of the
gold center in order to isolate the allene and to propose an
The synthesis of [(IPr)Au(OH)] (5) was recently reported11,12
and with its alkaline properties, an opportunity was identified
to easily generate 4 by a silver-free acid–base reaction involving
5 and pyridinium tetrafluoroborate. Propargylic acetate 1a
was subjected for 30 min at RT to a mixture of 5 (2 mol%)
and various ammonium salts (3 mol%) (Table 1). Taking
advantage of this user-friendly methodology, several ammonium
or pyridinium salts were tested to activate 5 and form
[(IPr)Au(L)][BF4] complexes (L = amine or pyridine). Results
of the catalyst generation protocol and subsequent transfor-
mation of 1a are summarized in Table 1. As expected, the use
of pyridinium tetrafluoroborate (Table 1, entries 1 and 2)
allows the reaction to proceed smoothly leading to allene 3a
without any trace of indene 2a. These results are comparable
with those previously obtained with 4 and suggested that 4 is
effectively formed in situ using this protocol. A range of
ligands was investigated, showing that substitutions on pyr-
idine can modulate the reactivity. Indeed, the presence of a
halide on the pyridine ortho position increased the conversion
Scheme 1 Synthesis of indenes from propargylic acetates via the
hydroarylation of allenes.
EaStCHEM, School of Chemistry, University of St Andrews,
North Haugh, KY16 9ST, St Andrews, UK.
E-mail: snolan@st-andrews.ac.uk
w Electronic supplementary information (ESI) available: Synthetic
details and complete analytical data, NMR spectra and crystallo-
graphic data. CCDC 759012 (4), 759010 (6). For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/
c0cc03071f
c
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 9113–9115 9113

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Table 1 Formation of allene 3a from alkyne 1a using an in situ
catalyst generation protocol
Entry Catalyst L
Solvent
T
Conversiona (%)
75b
1
2
5
5
Pyridine
Pyridine
CH2Cl2 RT
CH2Cl2 40 1C 100b
3
4
5
6
5
5
5
5
2-Chloropyridine CH2Cl2 RT
2-Bromopyridine CH2Cl2 RT
4-Cyanopyridine CH2Cl2 RT
2-Cyanopyridine CH2Cl2 RT
92b
95b
62b
50b
90b
68
Fig. 1 Ball and stick representation of [(IPr)Au(Pyr)][BF4] 4. H atoms
are omitted for clarity. Selected bond distances (A) and angles (1),
for 4: Au1–C1, 1.988(5); Au1–N31, 2.065(4); C1–Au1–N31, 177.2(18).
7
8
9
5
5
5
2,6-Lutidine
NEt3
NEt3
CH2Cl2 RT
CH2Cl2 RT
CH2Cl2 40 1C 100
10
11
12
13
14
5
5
NEt3
NEt3
NEt3
NEt3
None
THF
Toluene RT
DMF RT
CH2Cl2 RT
CH2Cl2 RT
RT
70
24
0
0
0
5
None
5
a
b
Conversions are the average of at least two runs. The presence of
o5% enone (PhCHQCHCOBu) was detected.13
(Table 1, entries 3 and 4) whereas cyano group in ortho or para
positions leads to lower yields (Table 1, entries 5 and 6).
2,6-Lutidine, featuring two electron-donating groups, also
leads to high conversion (Table 1, entry 7). The less expensive
triethylamine was also examined and led to a conversion of
68% at RT (Table 1, entry 8) and complete conversion at 40 1C
after only 30 min (Table 1, entry 9). Comparable results were
obtained in THF (Table 1, entry 10) but lower conversions
were observed in toluene and DMF (Table 1, entries 11 and 12).
No conversion was observed when reactions were conducted
in the absence of 5 or when no acid additive was used,
permitting us to exclude a simple acid activation and to
confirm that the formation of a cationic gold specie is essential
to the alkyne activation step. When NEt3 is used, no traces of
the parasitic enone13 PhCHQCHCOBu are observed. This
selective reactivity even after overnight reaction confirmed
that the in situ catalyst was not reactive enough to induce
the rearrangement leading to the indene. Noteworthy, the
same reaction carried out with [Au(IPr)(MeCN)][BF4]2e led
under these conditions to 2a exclusively.
Fig. 2 Ball and stick representation [(IPr)Au(Et3N)][BF4] 6. H atoms
are omitted for clarity. Selected bond distances (A) and angles (1) for
6: Au1–C1, 1.987(7); Au1–N21, 2.104(6); C1–Au1–N21, 176.2(3).
only to [(IPr)Au]+, a resonance at 159.0 ppm was recorded.
These results suggest that the Lewis acid character of these
three complexes can be expressed in an order: 6 o 4 o
[(IPr)Au]+.14 These observations are in line with our results
showing the lower reactivity of 4 and 6 compared to that obtained
using the [(NHC)Au]+ species. The scope of the methodology
was extended to tri- and tetra-substituted allenes. Results are
presented below (Table 2).
All propargylic acetates 1 were fully converted into allenes 3
in good yields. Three different reaction conditions had to be
used to perform the allene formation with all substrates 1a–k.
Compounds 1a–f were fully converted after 30 min at 40 1C
(conditions A; Table 2, entries 1–6) with in situ formed complex
6. Higher temperatures (80 1C) were required with acetates 1g–k
(conditions B; Table 2, entries 7–10). Finally, the use of pyridine
as ligand (conditions C; Table 2, entry 11) was necessary to
convert compound 1k in allene 3k. Under all conditions, the
formation of the indene product was never observed.
Reactions involving 5 and LꢀHBF4 were performed in order
to isolate the cationic gold complexes 4 and 6 (eqn (2)).
RT; 15 min
ƒƒƒƒƒƒ!
½ðIPrÞAuOHꢁ þ L ꢀ HBF4
½ðIPrÞAuðLÞꢁ½BF ꢁ þ H O
4
2
CH2Cl2
In conclusion, we have developed a silver-free method for
the synthesis of allenes catalyzed by cationic gold(I) complexes
generated in situ from an air and moisture stable precatalyst
[(IPr)AuOH] and ammonium or pyridinium salts. This study
illustrates that the Lewis acidity of a gold center can be
attenuated and modulated by coordinated nitrogen-based
ligand. This dampening of reactivity leads to the selective
catalytic formation of allenes in a previously reported reaction
leading to indenes with allenes as transient species. Ongoing
studies are aimed at capitalizing on this control feature in gold
catalysis.
L ¼ pyridine; NEt3
ð2Þ
Single crystals were grown by slow diffusion of pentane into
saturated dichloromethane solution and subjected to X-ray
diffraction. Ball-and-stick representations are presented in
Fig. 1 and 2 and confirm the identity of the cationic species.
As expected, the amine moiety is coordinated to the gold
center. The analysis of the 13C NMR spectra of each complex
can also afford a possible explanation concerning their different
reactivity observed towards propargylic acetates. Interestingly,
the carbenic carbon 13C chemical shift in 4 and 6 were
recorded at 169.2 and 167.1 ppm, respectively. When the same
acid activation was performed with HBF4 etherate leading
The ERC (FUNCAT) and the EPSRC are gratefully
acknowledged for support of this work. Umicore AG and
c
9114 Chem. Commun., 2010, 46, 9113–9115
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Table 2 Synthesis of allenes 3 from propargylic acetates 1 catalyzed
by cationic gold complexes
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1a
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3
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86
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11
C
3k
1k
a
Isolated yields are the average of two runs. Conditions A: 5 (2 mol%),
Et3NꢀHBF4 (3 mol%), CH2Cl2, 40 1C, 30 min; B: 5 (2 mol%), Et3Nꢀ
HBF4 (3 mol%), ClCH2CH2Cl, 80 1C, 60 min. C: 5 (2 mol%),
PyrꢀHBF4 (3 mol%), CH2Cl2, 40 1C, 30 min.
Johnson Matthey are thanked for their generous gifts of
materials. SPN is a Royal Society-Wolfson Research Merit
Award holder.
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c
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 9113–9115 9115