Balancing Bulkiness in Gold(I) Phosphino-triazole Catalysis

Article abstract of DOI:10.1002/ejoc.201900850

The syntheses of a series of 1-phenyl-5-phosphino 1,2,3-triazoles are disclosed, within which, the phosphorus atom (at the 5-position of a triazole) is appended by one, two or three triazole motifs, and the valency of the phosphorus(III) atom is completed by two, one or zero ancillary (phenyl or cyclohexyl) groups respectively. This series of phosphines was compared with tricyclohexylphosphine and triphenylphosphine to study the effect of increasing the number of triazoles appended to the central phosphorus atom from zero to three triazoles. Gold(I) chloride complexes of the synthesised ligands were prepared and analysed by techniques including single-crystal X-ray diffraction structure determination. Gold(I) complexes were also prepared from 1-(2,6-dimethoxy)-phenyl-5-dicyclohexyl-phosphino 1,2,3-triazole and 1-(2,6-dimethoxy)-phenyl-5-diphenyl-phosphino 1,2,3-triazole ligands. The crystal structures thus obtained were examined using the SambVca (2.0) web tool and percentage buried volumes determined. The effectiveness of these gold(I) chloride complexes to serve as precatalysts for alkyne hydration were assessed. Furthermore, the regioselectivity of hydration of but-1-yne-1,4-diyldibenzene was probed.

Full text of DOI:10.1002/ejoc.201900850

DOI: 10.1002/ejoc.201900850
Full Paper
Keytopic: Bulky Ligands
Balancing Bulkiness in Gold(I) Phosphino-triazole Catalysis
[
a]
[a]
[a]
[b]
Yiming Zhao, Matthew G. Wakeling, Fernanda Meloni, Tze Jing Sum,
[a]
[b]
[a]
[a]
Huy van Nguyen, Benjamin R. Buckley, Paul W. Davies, and John S. Fossey*
Abstract: The syntheses of a series of 1-phenyl-5-phosphino pared and analysed by techniques including single-crystal X-ray
,2,3-triazoles are disclosed, within which, the phosphorus atom diffraction structure determination. Gold(I) complexes were also
at the 5-position of a triazole) is appended by one, two or three prepared from 1-(2,6-dimethoxy)-phenyl-5-dicyclohexyl-phos-
1
(
triazole motifs, and the valency of the phosphorus(III) atom is phino 1,2,3-triazole and 1-(2,6-dimethoxy)-phenyl-5-diphenyl-
completed by two, one or zero ancillary (phenyl or cyclohexyl) phosphino 1,2,3-triazole ligands. The crystal structures thus ob-
groups respectively. This series of phosphines was compared tained were examined using the SambVca (2.0) web tool and
with tricyclohexylphosphine and triphenylphosphine to study percentage buried volumes determined. The effectiveness of
the effect of increasing the number of triazoles appended to these gold(I) chloride complexes to serve as precatalysts for alk-
the central phosphorus atom from zero to three triazoles. yne hydration were assessed. Furthermore, the regioselectivity
Gold(I) chloride complexes of the synthesised ligands were pre- of hydration of but-1-yne-1,4-diyldibenzene was probed.
Introduction
Bulky phosphines offer significant and well-documented advan-
tages as ligands in metal-catalysed reactions. The landmark
contributions of Buchwald and co-workers have led to a deeper
understanding of the synthetic chemistry enabled by such
bulky ligands, and ligands such as S-Phos and X-Phos are an
often-required component of the toolbox of today's synthetic
[
1]
chemists. There is emerging interest in the importance of cat-
[
2]
egorising and evaluating steric and electronic parameters of
[
3]
Figure 1. Selected examples of a previously reported 1-aryl-5-phosphino tri-
these types of bulky phosphines in order to correlate and
ultimately predict their suitability for use in metal-mediated ca-
azoles (left) (1a–b) and single-crystal X-ray diffraction structure of 1a (right),
[8]
as reported elsewhere, H-atoms omitted for clarity.
[
4]
talysis. The Tolman cone angle has been used to describe the
bulkiness of ligands,[ this descriptor has been complemented
by Nolan describing bulkiness in terms of a percentage buried
5]
[
6]
The 1-aryl-5-phosphino-triazole ligands, such as 1a, present
their 1-aryl fragment in the same orientation as the phosphorus
lone pair (of the free ligand) or in the direction of the metal (of
a phosphorus-metal complex thereof), thus significantly im-
volume (%Vbur). The %Vbur described by a ligand can be calcu-
lated by using Cavallo and co-workers' web tool SambVca
[
7]
(
2.0).
Some authors of this report previously detailed the synthesis,
[
8]
pacting the determined buried volume. Noting that ortho-
and application to palladium-catalysed Suzuki–Miyaura cross-
coupling reactions, of 1,2,3-triazole-containing phosphines in-
cluding analogues of the aforementioned Buchwald-type li-
aryl tris-phenylene phosphines (first reported, and somewhat
[
10]
overlooked, in 1940)
can impart favourable properties as li-
[
11]
gands in catalysis, it struck us that a bulky, and thus possibly
superior, version of the triazole phosphine ligand is possible if
the phosphorus atom were to be flanked by up to three, rather
than one, triazole. A series of ligands ranging from zero to three
triazoles, for comparison of the manifested bulk about the
phosphorus centre by 1,5-disubstituted-triazole motif(s), was
proposed. As such, a series of phosphines comprising of tri-
phenylphosphine (2a) and tricyclohexylphosphine (2b) along
with mono-triazole-appended phosphines 3a and 3b (available
from a previous study), and the previously unprepared bis-tri-
azoles 4a and 4b and 1-phenyl-5-phosphino-tris-triazole, 5 (Fig-
ure 2), was conceived.
[
8]
gands, such as 1a (Figure 1). Analysis of the steric parameters
[
6,9]
using the SambVca (2.0) web tool,[7] con-
(
buried volume)
firmed that the bulkier ligands of those tested were the most
[
8]
effective in said catalysis.
[
[
a] School of Chemistry, University of Birmingham,
Edgbaston, Birmingham, West Midlands, B15 2TT, UK
E-mail at j.s.fossey@bham.ac.uk
b] Department of Chemistry, Loughborough University,
Loughborough, Leicestershire, LE11 3TU, UK
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201900850.
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The same protocol for selective deprotonation of 6 at the 5-
[
12]
position,
was followed by addition of cyclohexyl- or phenyl-
phosphorus dichloride leading to the formation and subse-
quent isolation of 4a and 4b in 71% and 54% yield respectively
[Scheme 1 (iii)]. When a third of an equivalent of phosphorus
trichloride was added to deprotonated 6, the expected tris-1-
phenyl 5-phosphino triazole 5, resulted and was subsequently
isolated in 77% yield [Scheme 1 (iv)]. The proton and carbon
NMR spectrums of 5 (in [D]chloroform at ambient temperature)
displayed a single set of well-defined resonances, correspond-
ing to the three equivalent triazole arms of the 5, suggesting a
high degree of symmetry in solution on the NMR timescale.
Both 4a and 4b provided single crystals suitable for struc-
Figure 2. The series of phosphines conceived to probe the influence the num-
ber of 1-phenyl-5-phosphino triazole fragments about the phosphorus centre
upon their “bulkiness” as ligands.
Results and Discussion
The substituents attached to phosphorus and the triazole nitro- tural analysis by XRD (Figure 3a and Figure 3b, respectively, and
gen, could in principle be varied significantly. To provide a supplementary material). In both cases the 1-phenyl substitu-
benchmark in this initial investigation cyclohexyl (a) and phenyl ents of the triazole components point broadly in the same gen-
(
b) groups attached to phosphorus were selected and the sub- eral direction as the phosphorus lone pair, thus boding well for
stituent attached at the 1-N-position of the triazole was re- a systematic study of the effect of modulating the steric crowd-
stricted to phenyl in the first instance (Figure 2). As such two ing or bulkiness about a coordinated metal in a catalytically
series of aryl- and alkyl-substituted phosphines were planned.
relevant complex. For compound 5, a single crystal XRD struc-
ture was obtained (Figure 4), the solid-state conformation con-
tains two unique molecules in the unit cell, both of which show
the aryl arms of the triazole are directed along the same orien-
tation as the phosphorus lone pair, creating a bowl-shaped li-
gand.
Phosphine Synthesis
Dicylohexylphosphino- and 5-diphenylphosphino- 1-phenyl tri-
azoles, 3a and 3b respectively, were available from an earlier
study. Their synthesis required 6 [Scheme 1 (i)] to be deproto-
[
12]
nated with n-butyllithium
and reacted with dicyclohexyl- or
diphenyl- phosphorus chloride, Scheme 1 (ii) (see earlier re-
[
8,13]
ports, and citations therein
).
Figure 3. (a) A molecule of 4a determined by single-crystal X-ray diffraction
structure analysis. Ortep representation, ellipsoid probability 50% (rendered
in PovRay, H-atoms omitted for clarity) (lower) and a chemical drawing of 4a
(
upper). (b) A molecule of 4b determined by single-crystal X-ray diffraction
structure analysis. Ortep representation, ellipsoid probability 50% (rendered
in PovRay, H-atoms omitted for clarity) (lower) and a chemical drawing of 4b
(
upper).
Gold(I) Chloride Complex Synthesis and Structural Analysis
Complemented by commercially sourced tricyclohexylphos-
phine 2a and triphenylphosphine 2b, two ligand sets corre-
sponding to Figure 2 (R = Cy or Ph) were therefore available for
comparison in the complexation of a chosen metal. Owing to
[
14]
the importance of gold(I) phosphines in catalysis,
and that
Scheme 1. (i) The synthesis of triazole 6. Deprotonation of 6 and reaction
with: (ii) dicyclohexyl- or diphenyl-phosphorus chloride depicting the previ-
ously reported synthesis of 3a and 3b; (iii) cyclohexyl- or phenyl-phosphorus
dichloride for the synthesis of 4a and 4b by respectively; (iv) phosphorus
trichloride for the synthesis of tristriazole phosphine 5.
X-ray crystal structures of gold(I) chloride complexes 2a and 2b
[
15]
have been previously reported by others, the gold(I) chloride
complexes of the ligands in the series presented in Figure 2
were compared. Ligation of the triazole-phosphines (3–5) to
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Figure 4. A molecule of 5 determined by single-crystal X-ray diffraction struc-
ture analysis. Ortep representation, ellipsoid probability 50% (rendered in Pov-
Ray, H-atoms omitted for clarity) (lower) and a chemical drawing of 5 in
approximately the same orientation (upper).
gold(I), through phosphorus, was achieved by performing di-
methyl sulfide-phosphine exchange reactions on chloro(di-
methyl sulfide)gold(I) (Scheme 2). Isolated yields of the corre-
sponding gold(I) chloride complexes ranged from 58 to 91%.
Scheme 2. Synthesis of gold(I) chloride complexes (i) 8a–b; (ii) 9a–b; and (iii)
10.
Triphenylphosphine and tricyclohexylphosphine gold(I) chlor- and Figure 5b, (i) and (ii) respectively] and determine the per-
ide complexes (7a and 7b) were purchased from commercial centage buried volume using SambVca (2.0) [alternative repre-
suppliers.
sentations of the XRD structure and a steric map thus resulting
The single-crystal X-ray structures of gold(I) chloride com- are shown in part (iii) of the corresponding figures ]. Tricyclo-
plexes 7a and 7b [gold(I) chloride complexes of tricyclohexyl- hexylphosphine gold(I) chloride 7a has a 33.9%Vbur whereas the
phosphine and triphenylphosphine] have been previously re- triphenylphosphine gold(I) chloride complex 7b has
a
[
15]
ported in the literature.
The deposited PDB files were used 30.8%Vbur. The single-crystal X-ray diffraction structures of 8a
to render images [Ortep III for Windows and PovRay, Figure 5a (Figure 6a), 8b (Figure 6b), 9a (Figure 7a), 9b (Figure 7b) and
Figure 5. (a) Single-crystal X-ray diffraction structure of arising from literature deposited CIF file of 7a: (i) Ortep representation, ellipsoid probability 50%
(
(
rendered in PovRay, H-atoms omitted for clarity); (ii) Space-filling representation. (iii) Percentage buried volume determined from the crystal structure of 7a
[
15a]
33.9%) steric map of ligand depicted (right).
(b) Single-crystal X-ray diffraction structure of 7b arising from literature deposited CIF file: (i) Ortep representa-
tion, ellipsoid probability 50% (rendered in PovRay, H-atoms omitted for clarity). (ii) Space-filling representation. (iii) Percentage buried volume determined
from the crystal structure of 7b (30.8%) steric map of ligand depicted (right).[
15b]
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Figure 6. (a) Single-crystal X-ray diffraction structure of 8a: (i) Ortep representation, ellipsoid probability 50% (rendered in PovRay, H-atoms omitted for clarity).
(
ii) Space-filling representation. (iii) Percentage buried volume determined from the crystal structure of 8a (44.3%) steric map of ligand depicted (right). (b)
Single-crystal X-ray diffraction structure of 8b: (i) Ortep representation, ellipsoid probability 50% (rendered in PovRay, H-atoms omitted for clarity). (ii) Space
filing representation. (iii) Percentage buried volume determined from the crystal structure of 8b (40.3%) steric map of ligand depicted (right).
Figure 7. (a) Single-crystal X-ray diffraction structure of 9a: (i) Ortep representation, ellipsoid probability 50% (rendered in PovRay, H-atoms omitted for clarity).
(
ii) Space-filling representation. (iii) Percentage buried volume determined from the crystal structure of 9a (54.5%) steric map of ligand depicted (right); (b)
Single-crystal X-ray diffraction structure of 9b: (i) Ortep representation, ellipsoid probability 50% (rendered in PovRay, H-atoms omitted for clarity). (ii) Space-
filling representation. (iii) Percentage buried volume determined from the crystal structure of 9b (45.1%) steric map of ligand depicted (right).
1
0 (Figure 8) were obtained from the complexes synthesised chloride complexes thereof was also attempted. The gold(I)
herein, and similarly analysed to determine the corresponding chloride complex of 1a (11) was prepared by the aforemen-
buried volumes described by the ligands in their complexes tioned dimethyl sulfide ligand exchange reaction, in good yield
with gold(I) chloride (presented in Figure 9). The crystal struc- (95%, 0.25 mmol scale). A single crystal XRD structure of 11
tures of the gold-phosphorus bond lengths used in the buried was obtained (Figure 10a), and closely matched (by visual in-
volume determinations were those obtained crystallographi- spection) the structure of 9a, with a 46.0%Vbur. Attempts to
cally.
prepare a 1:1 complex of 1b and gold(I) chloride under the
Since previously prepared mono-triazole-containing phos- same conditions were inconclusive. However, a trigonal 2:1 li-
phines 1a and 1b were readily available to this programme of gand/gold(I) chloride complex 12 was identified by single-
study, and as 1a was shown previously to have been among the crystal X-ray diffraction crystal structure determination (Fig-
superior ligands of the mono-triazole set in earlier palladium- ure 10b) from a mixture of otherwise unidentified products. A
mediated Suzuki–Miyaura catalysis, the synthesis of gold(I) 76.6%Vbur (Figure 10b) was determined from the obtained crys-
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Figure 8. Single crystal X-ray diffraction structure of 10: (i) Ortep representa-
tion ellipsoid probability 50% (rendered in PovRay, H-atoms omitted for clar-
ity). (ii) Space-filling representation. (iii) Percentage buried volume deter-
mined from the crystal structure of 10 (60.8%) steric map of ligand depicted
(
right). The unit cell contains two molecules of the complex wherein the
phenyl ring centroid to gold distances are on average 3.58 Å (3.456 Å, 3.581 Å
and 3.634 Å in the one molecule and 3.351 Å, 3.692 Å and 3.759 Å in the
other). Between the two molecules of the unit cell a head to tail arrangement
is present and the closest intermolecular Au···Cl intermolecular distances are
7
.365 Å (see supplementary material for depictions).
Figure 9. Cyclohexyl and phenyl replacement by 1-phenyl triazole motif and
corresponding; triazole number vs. XRD-determined percentage buried vol-
ume [SambVca (2.0)].
tal structure. Attempts to prepare 12 by employing two equiva-
lents of ligand 1b gave inconclusive results. It is noteworthy
that this 2:1 trigonal gold(I) structure is similar to crystal struc-
Catalysis
(
I) [16]
(I)
[17]
tures reported for [(Ph P) Au Cl]
and [(Ph P) Au (SCN)].
With the set of gold chloride complexes of Figure 2 (7a–b, 8a–
3
2
3
2
Furthermore
a
linear cationic gold(I) chloride complex b, 9a–b and 10) along with complex 11 in hand, their effective-
+
–
[
(Ph P) Au ][Cl ] bearing two triphenyl phosphine ligands with ness as precatalysts for gold-catalysed alkyne hydration was
3
2
[
15b]
[19]
a fully dissociated chloride counterion also been reported.
probed (Table 1).
Catalytically active cationic gold(I) species
Therefore, the crystal structure of 12 is included for complete- may be generated by silver-mediated halide abstraction, and
ness. Attempts to prepare two and three 2,6-dimethoxyl phenyl choice of appropriate counter-anion has been shown to modu-
[
20]
triazole-containing variants of 4(a or b) and 5 failed to deliver late catalytic effects.
any desired products.
In this case, triflate was selected as a
[
18]
counter-anion across all cationic gold(I) catalytic systems stud-
Figure 10. (a) Single-crystal X-ray diffraction structure of 11: (i) Ortep representation, ellipsoid probability 50% (rendered in PovRay, H-atoms omitted for
clarity). (ii) Space-filling representation. (iii) Percentage buried volume determined from the crystal structure of 11 (46.0%) steric map of ligand depicted
(
right). Compound 11. (b) Single-crystal X-ray diffraction structure of 12: Molecular drawing and Ortep representation, ellipsoid probability 50% (rendered in
PovRay, H-atoms omitted for clarity) upper; space-filling representation and steric map [SambVca (2.0)] from which a 76.6% buried volume was determined.
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ied. Initially the gold-catalysed hydration of dec-1-yne (13a) was ide abstraction in the same manner from complex 11 gave
performed by in situ preactivation of 0.5 mol% of the corre- quantitative conversion of 13a to 14a (Table 1, entry 8).
sponding gold complex through silver triflate-mediated halide
Synthetic modification of phosphorus-containing ligands can
abstraction, using an excess of silver triflate in methanol (or as result in significant differences in the outcomes of reactions
explained below, dichloromethane in the case of 10), alkyne catalysed by their corresponding cationic gold(I) com-
1
3a was stirred in methanol to which the preactivated catalyst plexes.[4c,19a,21] The regioselectivity of hydration of unsymmetri-
solution was added. Since complex 10 was not well solubilised cal internal alkynes has been previously probed by Nolan and
in methanol a protocol of activation in dichloromethane and co-workers who identified anti-Markovnikov-selective gold(I)-
[
22]
dilution in methanol was deployed. To facilitate comparison in carbene complex-catalysed hydration. As such, a model reac-
the subsequent reactions with lower catalyst loadings (0.25 and tion, namely the hydration of unsymmetrical internal alkyne 15
0.05 mol% of gold complex), the dichloromethane activation was selected to probe selectivity that might arise from the
and methanol dilution protocol was used in those cases. Follow- structural modifications across the series of gold(I) complexes
ing the addition of water (2 equiv.) all reactions were heated at of phosphino-triazoles prepared in this study (Table 2). The re-
80 °C in a sealed tube for two hours and conversions to ketone action of water at the benzylic position (15-a) represents the
1
4a were determined by gas chromatography.
generally expected (Markovnikov) outcome, with selective reac-
tion at the alternate alkyne position (15-b, anti-Markovnikov)
being more challenging.
Table 1. Screening of ligands for gold-catalysed hydration of dec-1-yne (13a)
to 2-decanone (14a).
Table 2. Selectivity of the hydration of unsymmetrical alkyne 15 to give ket-
ones 16a and/or 16b.
Entry
L-
AuCl
R1
R2
Triazole
No. (n)
Conversion [%] (mmol%)
[
a]
[b]
[b]
0.50
0.25
0.05
Entry
L-AuCl
R1
R2
Triazole
No. (n)
Conv.
[%]
Ratio[a]
(16a/16b)
1
2
3
4
5
6
7
8
7a
8a
9a
10
9b
8b
7b
11
Cy
Cy
Cy
–
Ph
Ph
Ph
Cy
–
Ph
Ph
Ph
Ph
Ph
–
0
1
2
3
2
1
0
1
> 99
> 99
> 99
86
> 99
46
11
26
57
52
> 99
10
9
3
4
2
4
3
10
1
2
3
4
5
6
7
8
7a
8a
9a
10
9b
8b
7b
11
Cy
Cy
Cy
–
Ph
Ph
Ph
Cy
–
Ph
Ph
Ph
Ph
Ph
0
1
2
3
2
1
0
1
> 99
> 99
> 99
64
3.5:1
3.2:1
4.3:1
[
b]
32
[b]
> 99
> 99
> 99
> 99
[b]
3.8:1
3.3:1
4.2:1
4.0:1
2.3:1
> 99
> 99
> 99
[
c]
2,6-DMP
–
[
a] Methanol used as solvent, unless otherwise started. [b] Catalyst precursor
initially solubilised in dichloromethane and dispersed in methanol, such that
the resulting solvent composition was 10% CH Cl and 90% MeOH. [c] 2,6-
2,6-DMP[
d]
95
[c]
2
2
[
a] (a) Ratio determined by GC analysis of reaction mixture. [b] Ratio deter-
DMP = 2,6-dimethoxyphenyl. These conditions were deployed across all tests
experiments at 0.25 and 0.05 mol% gold(I) complex loading.
mined by analysis of the proton NMR spectrums of mixtures of 16a and 16b
obtained from the reactions. [c] Complete consumption of 16 was observed,
the product mixture contained 5% of a dimethyl acetal adduct as determined
by GC/GC–MS. [d] 2,6-DMP = 2,6-dimethoxyphenyl.
At the highest catalyst loading of 0.5 mol% only the bulkiest
complex (10) failed to give complete conversion to product 14a
(
Table 1, entry 10 vs. other entries in same table ). When lower
Compound 15 was added to a mixture of catalyst precursor
catalyst loadings were probed 0.05 mol% of gold(I) complexes (1 mol%) (which had undergone silver triflate (2 mol%)-medi-
proved to be too low to achieve satisfactory conversion within ated in situ halide abstraction) in a degassed methanol/water
[
23]
two hours (the maximum conversion observed across the set mixture.
Consumption of 15 and the ratio of products
1
was 10% under these conditions). Good gradation across the 16a:16b was determined by H NMR spectroscopy or gas chro-
test series was seen at a 0.25 mol% catalyst loading (Table 1) matography. That quantitative conversion was observed in all-
[
19a]
and confirmed the superior ligands, for this gold-catalysed but-one case (tris-triazole complex 10, Table 2 entry 4),
is in
transformation, to be those with one triazole substituent. The keeping with the results from the hydration of dec-1-yne 13a
dicyclohexylphosphine-containing complex 8a afforded quanti- (Table 1). All complexes showed a preference for Markovnikov
tative conversion to 14a (Table 1, entry 2). The corresponding addition at the benzylic position of the alkyne (position [a]).
mono-triazole-diphenylphosphine-containing complex 8b gave Whilst all cases gave product 16a in preference to 16b (ranging
the best conversion to 14a among the phenyl-appended phos- from 4.2:1 to 2.3:1 ratios of products 16a/16b), it is noteworthy
phine series of 57% (Table 1, entry 6). The three triazole conge- that use of complexes 8a and 11 as catalyst precursors (Table 2,
ner (10) (Table 1, entry 4) gave only 11% conversion under the entries 2 and 8 respectively) afforded a greater proportion of
same conditions. Pleasingly, however, catalysts derived by hal- the challenging anti-Markovnikov product 16b.
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Table 3. Substrate scope survey for triazole-appended phosphine ligate
gold(I) catalysed alkyne hydration.
Having established that, for gold(I)-mediated hydration of
alkynes, cationic gold(I) complexes bearing dicyclohexyl mono-
triazole ligands 1a and 3a (complexes 11 and 8a respectively)
were superior in terms of activity (Table 1); and the 1a derived
catalyst gave regioselectivity of <3:1 for 16a:16b (Table 2);
complex 11 was deployed in a brief substrate scope survey
(
Table 3).
Linear alkyl-alkynes 13a and 13f (Table 3, entries 1 and 6)
gave slightly higher yields than the cyclic alkane ethynylcyclo-
hexane 13b (Table 3, entry 2), 79 and 89% vs. 64% respectively.
1
-Ethynylcyclohex-1-ene 13c (Table 3, entry 3) gave a similar
yield (69%) to 13b. Phenylacetylene 13d (Table 3, entry 4) gave
8% yield, with the yield for the methylnaphthyl derivative 13e
5
being somewhat better (80% yield, Table 3, entry 5). The yield
for use of para-methoxy phenyl acetylene 13g was better than
for phenylacetylene (88 vs. 58% yield, Table 3, entries 7 & 4
respectively). Pleasingly an aryl boronic ester 13g was accom-
modated under the reaction conditions employed (81% yield,
Table 3, entry 8), as was thiophene derivative 13i, albeit in a
slightly lower isolated yield (61% yield, Table 3, entry 9). Quater-
nary oxindoles containing alkynes have been of interest to co-
authors of this report and their availability to this programme
allowed 13j–l to be probed as substrates for gold(I) catalysed
[
24]
hydration (Table 3, entries 10 to 12).
To obtain appreciable
conversion to isolable oxindole-containing products catalyst
loading had to be increased to 1 mol%. The N-H bearing sub-
strate 13j was converted to product 14j in relatively low con-
versions (27%, Table 3, entry 10). The N-benzyl analogue 13k
fared better giving 85% isolated yield (Table 3, entry 11). A
major side product arose from in situ removal of the Boc-group
upon reaction of 13l (Table 3, entry 12) giving rise to a mixture
of desired product 14l (in 30% isolated yield) and deprotected
product 14j (61% isolated yield). The reaction of 14m gave the
dimethyl acetal of overall reaction at the alkyne terminus in
9
4% isolated yield (14m′, Table 3, entry 13). Nitroarene 13n,
aryl ester 13o, aryl bromides 13p and 13q, pyridyl substrates
3r and 13s and tertiary butyl 13t appended alkynes all failed
1
to give any detectable hydration products under the conditions
employed (Table 3, combined entry 14). Further optimisation to
facilitate these transformations was not conducted.
Conclusions
1
,2,3-Triazoles bearing 1-aryl and 5-phosphino functionalities
were prepared, wherein the phosphorus atom was appended
to one, two or three such triazole motifs. In addition, the corre-
sponding gold(I) chloride coordination complexes bearing
phosphino triazoles [with ancillary cyclohexyl or phenyl groups
on phosphorus to complete the valence requirement of phos-
phorus(III) where required] were also prepared and their relative
bulkiness determined using the online tool SambVca (2.0). Two
more gold(I) chloride complexes were prepared from ligands
containing a phosphorus atom appended by one triazole of
the same general formula, where the 1-aryl substituent on the
triazole was 2,6-dimethoxy phenyl. These complexes, along
with complexes of tricyclohexyl phosphine and triphenyl phos-
phine were in situ converted into their corresponding cationic
[
a] 1 mol% L-AuCl and 2 mol% AgOTf. [b] Significant Boc-deprotection ob-
served, isolated yield of 14j given in parenthesis.
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gold(I) triflate phosphine ligated congeners and compared as J003220/1). JSF and HvN. are thankful for the support of the
alkyne hydration catalysts. Increasing the “triazole number” NEURAM H2020 FET Open project 712821. Dr Chi Tsang, Alex
about the phosphorus atom confirmed that, among the triazole S. Quy and Dr Peter Ashton are thanked for assistance with
appended phosphines investigated, the monotriazole-contain- mass spectrometry. Dr Cécile S. Le Duff is thanked for advice
ing phosphines were the most effective ligands for cationic on NMR spectroscopy. JSF and BRB acknowledge the support
gold(I)-catalysed hydration of alkynes.
of a Wellcome Trust ISSF award within the University of
In summary, the data derived from the above experimenta- Birmingham. A Royal Society Research Grant (2012/R1) under-
tion show triazole-phosphine ligand 1a to be the most promis- pinned initiation of this project.
ing of the ligands reported. The ease of synthesis and modifica-
tion of the triazole ligand framework should prove useful in
Keywords: Click chemistry · Gold · Homogeneous
future ligand design, screening and optimisation campaigns.
catalysis · Phosphane ligands · Triazoles
Supporting Information (see footnote on the first page of this
article): General and experimental procedures are available as sup-
porting information, which also includes a summary of the crystal-
lographic data collection and analysis, and further analysis of struc-
tural features of the crystal structures of the complexes discussed.
All crystal structures disclosed in this report have had the corre-
sponding data deposited at the CCDC with deposition numbers
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reactions, drafted a proportion of the ESI, offered critical sugges-
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Received: June 13, 2019
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Keytopic: Bulky Ligands
The synthesis of gold(I) complexes of
1
-phenyl-5-phosphino 1,2,3-triazoles
Y. Zhao, M. G. Wakeling, F. Meloni,
T. J. Sum, H. v. Nguyen, B. R. Buckley,
P. W. Davies, J. S. Fossey* ............. 1–10
with varying numbers of triazole units
appended to phosphorus are dis-
closed and compared to tricyclohexyl-
phosphine and triphenylphosphine.
The gold(I) chloride complexes synthe-
sised were analysed by techniques in-
cluding single-crystal X-ray diffraction
structure determination and percent-
age buried volumes thereof deter-
mined. These complexes were com-
pared as catalyst precursors for gold(I)-
mediated alkyne hydration and the
corresponding results surveyed with
respect to the bulkiness of the ligands
deployed.
Balancing Bulkiness in Gold(I) Phos-
phino-triazole Catalysis
DOI: 10.1002/ejoc.201900850
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