An ambiphilic phosphine/H-bond donor ligand and its application to the gold mediated cyclization of propargylamides

Article abstract of DOI:10.1039/c7cc06065c

We describe the synthesis of an ambiphilic phosphine/H-bond donor ligand featuring a trifluoroacetamide functionality, its coordination to gold(i) chloride, and its application as a self-activating catalyst for the cyclization of propargylamides.

Full text of DOI:10.1039/c7cc06065c

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An ambiphilic phosphine/H-bond donor ligand and its application
to the gold mediated cyclization of propargylamides
Received 00th January 20xx,
c
Srobona Sen and François P. Gabbaï
We describe the synthesis of an ambiphilic phosphine/H-bond donor ligand featuring a trifluoroacetamide functionality, its
coordination to gold(I) chloride, and its application as a self-activating catalyst for the cyclization of propargylamides.
Access to electrophilic transition metal catalysts is typically The structure of 1 was also confirmed by X-ray analysis which
achieved through the use of a Lewis acid that activates the revealed that the N-H hydrogen atom is not interacting with
1
metal centre by abstraction of an anionic ligand. This strategy the phosphorus atom.
has been applied to diverse areas including olefin
polymerization catalysis where the role of the Lewis acids is
usually fulfilled by strongly Lewis acidic fluorinated boranes.
O
Li
X-ray
1
-2
N
Li
The same principles apply to electrophilic late transition metal
catalysts which are typically activated by abstraction of a
halide anion using a silver salt. While the exposed nature of
F3C
3
a, b
the resulting cationic transition metal center is usually desired
for high catalytic activity, it can also be a source of instability
and a conduit for catalyst decomposition, especially in the case
O
H
N
PPh2
4
of late transition metals that are prone to reduction. For this
reason, alternative activation methods are being actively
F3C
1
5
pursued, for example with the use of milder Lewis acids. It
Scheme 1. Left: Synthesis of 1. (a) 1. nBuLi, 2. 2 eqv. tBuLi., 3.Ph
Et O) in THF at -78° C. Right: Crystal structure of 1.
2
PCl, (b) HCl (1M in
has also been argued that improved catalyst stability could
derive from the presence of an ancillary Lewis acidic site
2
6
positioned within the ligand architecture.
combined with recent advances in the field of anion-pairing
This idea,
Reaction of
1 with one equivalent of (tht)AuCl (tht =
7
organocatalysis using hydrogen-bond donor systems, has led
us to question whether an intramolecular hydrogen-bond
tetrahydrothiophene) in THF at room temperature afforded
3
as a light-sensitive white solid. A peak at 22.2 ppm in the
2
1
P
donor functionality could also be used to activate an NMR spectrum, downfield to the peak corresponding to the
organometallic catalyst via interaction with a metal-bound free ligand, confirmed the formation of the gold(I) complex.
1
The H NMR resonance corresponding to the N-H is observed
anionic ligand.
To explore this possibility, we decided to first synthesize an
ambiphilic ligand in which the role of the acidic functionality is
fulfilled by a hydrogen bond donor group. Reaction of o-
as a broad singlet at 8.54 ppm. The structure of
2
indicates
Cl
lithiotrifluoroacetanilide with Ph
up produced o-(diphenylphosphino)trifluoroacetanilide (
2
PCl followed by acidic work
) as a
O
H
N
O
H
N
Au
1
) was characterized by H,
Ph
Ph
1
19
PPh2
P
pale yellow solid. The ligand (
and P NMR spectroscopy and also by ESI /MS. Salient
1
F
31
-
F3C
1 eqv. (tht)AuCl
THF, rt
F3C
1
spectroscopic features include a H NMR resonance at 8.81
3
1
ppm corresponding to the the amide hydrogen atom and a
NMR resonance at -21.9 ppm. The trifluoroacetamide
P
1
2
1
functionality also gives rise to a F NMR signal at -76.1 ppm.
9
O
F3C
O
0.5 eqv.
tht)AuCl
CF3
(
NH
HN
THF, rt
Cl
Department of Chemistry, Texas A&M University, College Station, Texas 77843,
USA.
Au
P
P
E-mail: francois@tamu.edu
†
Ph
Ph
2
2
Electronic Supplementary Information (ESI) available: General experimental
details and characterization data for all the reported complexes are included in the
ESI. CCDC 1566425- 1566427 contain the supplementary crystallographic data for
this paper. These data can be obtained from the Cambridge Crystallographic Data
Center.
3
Scheme 2. Synthesis of 2 and 3.
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+
-
that the complex exists as a dimer held by an aurophilic equilibrium involving the formation of [L
2
Au] [AuCl
interaction of 2.997(7) Å. The dimer also benefits from two (See SI). Finally, VT P NMR spectroscopy shows that the
hydrogen-bonds connecting the N-H proton of one molecule to chemical shift of (12 mM) in CD Cl shows only a downfield
2
] as a salt
8
31
2
2
2
the chlorine atom of the other one. The presence of these shift of 0.8 ppm upon elevation of the temperature from -30°C
hydrogen bonds is supported by N-H•••Cl hydrogen bonds as to 50°C. We interpret these last results as an indication that
3
confirmed by the Cl1-N1 and Cl1-N1 separations of 3.199(8) Å the nuclearity of the complex has little impact on the P NMR
1
9
and 3.164(8) Å which fall in the expected range. The structure chemical shift.
of
2
shows no evidence for a hydrogen-bonding interaction
1
involving the gold atom.
We also tested the 2:1 reaction of
1 and (tht)AuCl. This
0
reaction affords the corresponding bis(phosphine) complex
3
3
Scheme 2). Complex 3 gives rise to a broad P NMR
1
(
1
resonance at 35.78 ppm. In the H NMR spectrum, the N-H
proton resonates at 10.55 ppm, indicating its involvement in a
hydrogen-bonding interaction. The solid state structure of
3
confirms the formation of the expected complex. The gold
center adopts a trigonal planar geometry. The short contact
between the amide nitrogen atoms and the gold-bound
chlorine atom (Cl2-N1 = 3.224(5) Å and Cl1-N2 = 3.197(5) Å)
are consistent with the presence of N-H•••Cl interactions. A
further evidence for the presence of this interaction comes
from the Au-Cl bond distance of 2.6614(14) Å which is
1
3
significantly longer than that in (PPh ) AuCl (2.526(10) Å). It
2
3
is also interesting to note that, as a result of this hydrogen
bonding motif, the P1-Au-P2 angle in (144.95(5)°) is
significantly wider than that in (PPh ) AuCl (136.4(3)°).
3
1
3
3
2
Figure 1. Crystal structure of 2. Displacement ellipsoids are scaled to the 50% Complex
3 did not show any luminescence at room
probability level. All the hydrogen atoms except the amide hydrogens are omitted for
temperature or at 77 K when irradiated with a hand-held UV
lamp.
clarity. Selected bond lengths (Å) and angles (deg) for 2: Au1-Au2 2.9976(7), Au1-Cl1
.314(2), Au2-Cl2 2.316(2), N1-H1A 0.8800, N2-H2A 0.8800, H1A---Cl2 2.3802(22), H2A-
2
-
-Cl1 2.4050(24); P1-Au-Cl1 171.93(8), P2-Au2-Cl2 172.94(7).
Next, we decided to investigate the molecularity of
2 in
solution using the pulse gradient spin-echo (PGSE) NMR
method, which has proved to be well adapted for
1
1
organometallic compound molecular size determination.
PGSE measurements were carried out using a solution of in
CD Cl and its diffusion was compared to that obtained with
2
2
2
1
,3,5-tri-tert-butylbenzene (
internal standard. This molecule was chosen because of its
apolar nature and inertness toward . Its molecular size (VX-
) = 454 Å ) is also close to that of monomeric (VX-ray ) =
04 Å ). A quantitative treatment of the diffusion data
obtained with a 36 mM solution of in CD Cl afforded a
A), a molecule that we used as an
2
3
12
ray(
A
2
(2
3
5
2
2
2
3
molecular volume of VPGSE
(
2
, 36 mM) = 865 Å . This value, Figure 2. Crystal structure of 3. Displacement ellipsoids are scaled to the 50%
3
) = 504 Å but smaller
probability level. All the hydrogen atoms except the amide hydrogens are omitted for
which is higher than the value of VX-ray(
3
than that of the dimer (1008 Å ) was taken as an indication
that the gold complex undergoes monomer-dimer
2
clarity. Selected bond lengths (Å) and angles (deg) for 2: Au1-Cl1 2.6614(14), N1-H1A
0
1
.8800, N2-H2A 0.8800, P1-Au-P2 144.90(5), Cl1-A12-P2 108.32(5), Cl1-A12-P2
06.74(5).
a
equilibrium in solution. To confirm this hypothesis, the same
PGSE measurement was repeated after a three-fold and nine-
fold dilution of the sample. These measurements afforded
3
3
V
PGSE
(
2
, 12 mM) = 747 Å and VPGSE
(
2
, 4 mM) = 648 Å . The
Given the demonstrated ability of the trifluoroacetamide
observed volume decrease is consistent with increasing functionality to form a hydrogen bond with a gold-bound
dissociation of the dimer upon dilution, thus supporting the chloride anion, we questioned whether such an interaction
hypothesis that
The PGSE data could also be fitted to this monomer-dimer complexes catalytically active. With this in mind, we decided to
equilibrium, affording an association constant K of 1020(±100) investigate the catalytic activity of and in the
in cycloisomerization of propargylamides, without addition of a
2
is indeed in a monomer-dimer equilibrium. would be sufficiently strong to render the gold center of these
2
3
-
1
M
(see SI). We also found that solutions of compound
Cl
2
CH
2
2
are non-conducting, thus ruling out the possibility of an silver activating agent. Initially , both complexes were tested at
2
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room temperature in CDCl
3
using N-(prop-2-yn-1-yl)benzamide hydroamination of phenylacetylene with p-toluidine or in the
was cyclization of dimethyl 2-allyl-2-(2-propynyl)malonate.
employed as a catalyst, H NMR and gas chromatography In summary, we describe a phosphine gold chloride
monitoring showed smooth conversion when was added to complex which acts as a self-activating catalyst for the
as a substrate. While no cyclisation was observed when
3
1
2
the reaction. In all cases, the reactions were accompanied by cyclization of propargylamide. Although the activity of the
the slow production of purple gold particles, raising doubt catalyst is low, our results provide proof-of-concept evidence
about the nature of the catalytically active species. For this that the self-activating nature of the catalyst originates from
reason, we decided to use a different solvent. We found that
2
the presence of a hydrogen bond donor group which activates
is stable in dichloromethane, with no sign of decomposition the gold atom, presumably by interaction with the chloride
after 24h as confirmed by visual inspection of the solution and anion. While the results are compelling, we have not yet been
3
1
P NMR spectroscopy. The catalysis in dichloromethane was able to ascertain the nuclearity of the catalyst which we
monitored by GC and the results are compiled in Table 1. presume could be either monomeric or dimeric as suggested
Formation of only one isomer of the cyclized oxazole was by the solid state structure and the PGSE studies. We are
observed consistent with the presence of a reactive gold(I) currently working on clarifying this point through mechanistic
1
4
catalytic center. A comparison of the percentage conversion and kinetic analyses.
of the different starting materials after 24 h, revealed that the
reaction occurs faster in the case of electron rich N-(prop-2-yn-
Acknowledgements
1-yl)-4-methoxybenzamide in line with the amide functionality
acting as the nucleophile toward the activated alkyne. In the
case of N-(prop-2-yn-1-yl)-2-methylbenzamide, the relatively
slow progress of the reaction can be attributed to the steric
hindrance resulting from the o-Me group.
This work was supported by the National Science Foundation
CHE-1566474), the Welch Foundation (A-1423), and Texas
(
A&M University (Arthur E. Martell Chair of Chemistry). We
thank Ms. Chia-Hsiu Chen for her assistance with the PGSE
measurements. We are grateful to Prof. Christian Hilty for his
invaluable suggestions and for allowing us to use his NMR
facilities.
Scheme 3. Catalytic cyclization of propargylic amides by 2.
Notes and references
Table 1. Catalytic conversion of the propargylic amides by 2 (5 mol%) in CH
monitored by GC
2 2
Cl
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2
2
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