Hydrative syntheses of amides from alkynes catalyzed by an Au(I) complex containing pyridyl-functionalized NHC ligand

Article abstract of DOI:10.1016/j.jorganchem.2019.02.011

An Au(I)-NHC complex [L¹AuBr] (1) with appended pyridyl group on the ligand scaffold is synthesized and its catalytic efficacy for the direct synthesis of the amide from alkyne and sodium azide in acidic water is evaluated. Catalyst 1 readily converts a wide range of internal and terminal alkynes to the corresponding amides with low catalyst loading in TFA/DCE (2 mL, 1:1 v/v) at room temperature in short reaction time (2 h) and without the use of Ag(I) additive. A related catalyst that is devoid of the pyridyl fragment displays significantly lower activity illustrating the role of the promoter ligand for water activation. Mechanistic studies reveal an initial alkyne hydration to ketone followed by the Schmidt reaction to afford the amide.

Full text of DOI:10.1016/j.jorganchem.2019.02.011

Accepted Manuscript
Hydrative syntheses of amides from alkynes catalyzed by an Au(I) complex
containing pyridyl-functionalized NHC ligand
Kuldeep Singh, Nilay Kumar Pal, Chirajyoti Guha, Jitendra K. Bera
PII:
S0022-328X(18)31037-4
DOI:
https://doi.org/10.1016/j.jorganchem.2019.02.011
JOM 20713
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 24 December 2018
Revised Date: 12 February 2019
Accepted Date: 12 February 2019
Please cite this article as: K. Singh, N.K. Pal, C. Guha, J.K. Bera, Hydrative syntheses of amides
from alkynes catalyzed by an Au(I) complex containing pyridyl-functionalized NHC ligand, Journal of
Organometallic Chemistry (2019), doi: https://doi.org/10.1016/j.jorganchem.2019.02.011.
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Hydrative Syntheses of Amides from Alkynes Catalyzed
by an Au(I) Complex containing Pyridyl-Functionalized
NHC Ligand $
Kuldeep Singh, Nilay Kumar Pal, Chirajyoti Guha and Jitendra K. Bera*
Department of Chemistry and Center for Environmental Science and Engineering,
Indian Institute of Technology Kanpur, Kanpur 208016, India.
E‒mail: jbera@iitk.ac.in
* To whom correspondence should be addressed.
$ Special issue on “Main-group molecules to Materials” dedicated to Dr. Vadapalli
Chandrasekhar on the occasion of his 60th birthday

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Highlights
• Au(I) complex bearing a pyridyl-functionalized NHC ligand is synthesized
• Catalytic efficacy is evaluated for nitrogenation of alkynes to amides
• Catalyst featuring a pyridyl group on the ligand scaffold displays higher
activity
• A hydrative mechanism is proposed supported by experiments
TOC

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Abstract
An Au(I)-NHC complex [L1AuBr] (1) with appended pyridyl group on the ligand
scaffold is synthesized and its catalytic efficacy for the direct synthesis of the amide
from alkyne and sodium azide in acidic water is evaluated. Catalyst 1 readily
converts a wide range of internal and terminal alkynes to the corresponding amides
with low catalyst loading in TFA/DCE (2 mL, 1:1 v/v) at room temperature in short
reaction time (2 h) and without the use of Ag(I) additive. A related catalyst that is
devoid of the pyridyl fragment displays significantly lower activity illustrating the role
of the promoter ligand for water activation. Mechanistic studies reveal an initial
alkyne hydration to ketone followed by the Schmidt reaction to afford the amide.
Keywords
Au(I)–NHC Complex, Amide Synthesis, Alkyne Hydration, Water Reaction, C-C
Bond Functionalization

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Introduction
Amides have ubiquitous presence in chemical synthesis, natural products, and
biology.1 Traditional amide syntheses rely heavily on the reactions of activated
carboxylic acid derivatives with amines.2 Alternative methodologies are available but
many of these methods suffer from poor atom economy and demand harsh reaction
conditions.3 Metal-catalyzed hydrative amide synthesis utilizing alkyne, azide and
water is an attractive option that allows facile C-C bond functionalization through a
nitrogenation process (Scheme 1).4 Nitrile hydration provides a direct, convenient
and atom-economic route to amides.5 Cadeirno and co-workers have developed
several ruthenium/rhodium catalysts under homogeneous conditions which utilize a
pendant Brønsted basic unit on the ligand scaffold to accelerate hydration activity.6
H
[Au]/[Cu]
N
Ar
R
Ar
R
Azide, H2O
O
Scheme 1. Hydrative synthesis of amide.
We recently reported a NiII complex containing pyridyl-functionalized N-
heterocyclic carbene (NHC) ligands for selective nitrile hydration to amide under
base-free conditions. The hemilabile pyridyl unit is shown to promote nucleophilic
water attack to a metal-bound nitrile through hydrogen-bonding interaction (Scheme
2a).7 Exploiting the combined effects of metal and ligand in bifunctional catalysts,
hydration reactions of alkynes are realized.8 Grotjahn demonstrated that imidazole or
pyridyl containing phosphine ligand on a CpRu fragment dramatically accelerates the
rate and selectivity of anti-Markovnikov alkyne hydration (Scheme 2b).9 Recently,
Iwasawa has reported an Au(I)-functionalized cavitand featuring phosphite and
oxidized phosphite units for the catalytic hydration of alkynes. Synergic activation of

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alkyne and water at Au and P=O fragment respectively is proposed (Scheme 2c).10
As part of ongoing efforts to utilize a pyridyl-type fragment suitably placed on a metal
catalyst for water reactions, we have reported nitrile hydration,11 olefin oxygenation12
and oxidation of alcohol to acid.13 Hydration activity of Au-NHC compounds for both
terminal and internal alkynes is well recognized.14 We sought to incorporate a basic
group on the ligand scaffold and examine its role in promoting alkyne hydration and
related chemistry.15 Such complexes with basic groups have been investigated with
both NHC and phosphane ligands.16 Herein we report an Au(I)-NHC complex
featuring a pendant pyridyl on the ligand architecture and study its catalytic utility for
the hydrative syntheses of the amides from alkynes and sodium azide in acidic
water. A related catalyst lacking the pyridyl group affords only 37% conversion for
the phenylacetylene in comparison to >90% for the same precursor by the pyridyl-
bearing catalyst, illustrating the role of the promoter ligand for water reactions.
(a) Bera
Scheme 2. Strategies for water activation.
(b) Grotjahn
(c) Iwasawa
Result and Discussion
Syntheses and Structure
Syntheses of pyridyl- and benzyl-functionalized NHC ligand precursors [L1.H]Br and
[L2.H]Br were earlier reported from our group.7 The reaction of a THF solution of

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n
[L1.H]Br with BuLi (1.6 equivalent), followed by addition of (SMe2)AuCl in 1:1 ratio
with respect to the ligand afforded [L1AuBr] (1) as a yellow solid in 82% yield.
Following a similar procedure using [L2.H]Br afforded [L2AuBr] (2) in 77% yield
(Scheme 3). Both compounds are characterized spectroscopically and by X-ray
crystallography as well. 1H NMR spectra of the products show the disappearance of
imidazolium proton indicating metalation. The carbene carbon signals appear at δ =
191.77 and 181.98 ppm for 1 and 2, respectively. Molecular structures are
determined by single crystal X-ray crystallography (Fig. 1). For both complexes, the
Au center reveals linear coordination bound to NHC and Br. The Au1-C1 distance is
1.989(7) (Å) and the Au1-Br1 distance is 2.3954(8) (Å). The corresponding distances
in 2 are 1.986(5) and 2.3950(6) (Å), respectively. The C1-Au1-Br1 angles
179.34(19)° and 177.75(13)°, respectively for 1 and 2, reflect the linear geometry
around the metal. For 1, a long Au1…N3 separation (5.048 Å) and the disposition of
the pyridyl ring with respect to NHC (ϕ N1-C8-C9-N3 = 164.1(5)°) demonstrates the
absence of any interaction between the pyridyl nitrogen and the metal. The ESI–MS
signal at m/z = 544.0359 (z = 1) for 1 is assigned for [M+H]+ (Fig. S1). Interestingly,
the ESI-MS of 2 revealed a prominent signal at m/z = 729.2546 (z = 1) which is
assigned for [Au(L2)2]+. (Fig. S2).
1) nBuLi, THF, 0°C
2) [AuCl(SMe2)]
Br
X
O
N
N
N
N
reflux, 24h
Au
Br
O
X
X = N [L1.H]Br
X = CH [L2.H]Br
(1)
X = N
(2)
X = CH
Scheme 3. Syntheses of 1 and 2.

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1
2
Fig. 1. X-ray structure (40% probability thermal ellipsoids) of 1 (left) and 2
(right) with important atoms labelled. Hydrogen atoms are omitted for the
sake of clarity. Selected bond lengths (Å) and angles (°): For 1, Au1-C1
1.989(7), Au1-Br1 2.3954(8), N3-Au1 5.048; C1-Au1-Br1 179.34(19); for 2,
Au1-C1 1.986(5), Au1-Br1 2.3950(6); C1-Au1-Br1 177.75(13).
Catalytic Studies
Scheme 4. Synthesis of amide from alkyne catalyzed by 1.
The catalytic utility of 1 was investigated for the syntheses of secondary amides from
alkynes. Phenylacetylene (1 equiv.), catalyst 1 (2 mol%), NaN3 (2 equiv.) and H2O (2
equiv.) were reacted in 2 mL trifluoroacetic acid (TFA)/1,2-dichloroethane (DCE) (1:1
v/v) to obtain N-phenylacetamide in 91% isolated yield after 2 hours at room
temperature (25°C) (Scheme 4). The optimized condition was derived after a series
of experiments (Table S2). Initially, 10 mol% catalyst loading gave 96% amide
conversion (Table S2 entry 1). While decreasing the catalyst loading to 2 mol%, a
similar yield of 91% was obtained. When catalyst loading was further reduced to 1

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mol%, the formation of amide was drastically reduced to 52%. In absence of the
catalyst, trace amount of amide and 15% acetophenone was observed. Employing 2
mol% (SMe2)AuCl as the catalyst afforded 25% conversion of the desired amide.
Different solvent combinations were screened, among which TFA/DCE (1:1 v/v) gave
the best result. When the reaction was performed in absence of TFA, the desired
amide was not observed. The use of acetic acid instead of TFA failed to afford the
product. The conversion was very similar when TMSN3 was used as nitrogen source.
We pursued the reaction with cheaper, accessible and easy-to-handle NaN3.17 Two
equivalents of NaN3 were necessary to obtain the maximum conversion. A mixture of
acetophenone and acetamide was observed when one equivalent of azide was
employed. In the absence of the azide, acetophenone was observed exclusively in
94% yield.
The substrate scope was investigated using a variety of terminal and internal
alkynes. Catalyst 1 exhibited greater proficiency for terminal alkynes compared to
internal alkynes affording the corresponding secondary amides. Phenylacetylene
and its electron-rich derivatives gave excellent yields (90-95%) (Table 1, entries 1-4).
Yields are reduced for electron-deficient alkynes 4-bromophenylacetylene and 4-
fluorophenylacetylene (85% and 68% respectively) (entries 5, 6). Bulkier substrate 2-
ethynylnaphthalene was successfully converted to N-(naphthalen-2-yl)acetamide
albeit in a lower yield (71%) (entry 7). Heterocyclic alkynes such as 2-ethynylpyridine
and 2-ethynylthiophene gave analogous amides with moderate yields 72% and 75%
respectively (entries 8, 9). The substrate scope was further extended to long chain
aliphatic alkynes where conversions were relatively lower and starting materials were
found at the end of the reactions. Aliphatic alkynes 1-Hexyne, 1-heptyne and 1-
octyne led to the formation of corresponding amides in yields 75%, 70% and 70%

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respectively (entries 10-12). N-cyclohexylacetamide was prepared from related
alkynes with moderate yield (entry 13). A lower yield of 31% was observed for N-
cyclopropylacetamide (entry 14). Ethynyltrimethylsilane did not afford the amide
presumably due to decomposition under the reaction conditions as indicated by GC
(entry 15).
Table 1. Syntheses of secondary amides from terminal alkynes catalyzed by 1.a
2 mol% 1, NaN3 (2 equiv.),
H
H2O (2 equiv.)
N
TFA/DCE (2 mL, 1:1 v/v),
O
RT, 2h
R
R
1, 91%b
2, 95%b
5, 85%b
3, 94%b
6, 68%b
4, 90%b
7, 71%b,
8, 72%b
9, 75%b
10, 75%b
13, 62%b
11, 70%b
14, 31%c
12, 70%b
15, 0%c
a Reaction conditions: 0.5 mmol alkyne, 1 mmol NaN3, 1 mmol H2O, 2 mol% 1, 2 mL
TFA/DCE (1:1 v/v), room temperature, 2 h. bIsolated yields. cYields were determined
by GC–MS with dodecane as the internal standard.

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Further, internal alkynes were tested under optimized conditions (Table 2). The
yields were in general lower than terminal alkynes. The nitrogenation occurs
preferably at electron-rich side of the alkynes. Diphenylacetylene gave N,2-
diphenylacetamide in 62% yield. Regioselectivity was observed when asymmetric
alkynes were chosen for the synthesis of secondary amides. Alkynes 1,2-dimethyl-4-
(phenylethynyl)benzene, 1,3-dimethyl-5-(phenylethynyl)benzene, 1,2-dimethoxy-
4(phenylethynyl)benzen and 1-ethoxy-4-(phenylethynyl)benzene were converted to
their respective amides in the range of yields 61-68% (entries 2-5). For 1-fluoro-4-
(phenylethynyl)benzene,
2-(4-fluorophenyl)-N-m-tolylacetamide
was
formed
preferably in 47% yield illustrating the regioselectively of the reaction (entry 6). For
1,3,5-trimethyl-2-(phenylethynyl)benzene, only N-mesityl-2-phenylacetamide was
obtained with 55% yield (entry 7). The electronic factor appears to dominate over the
steric consideration.
Catalyst 1 thus readily affords the amides from alkynes and sodium azide in acidic
water with low catalyst loading and in short duration without needing Ag(I) salt as an
additive.

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Table 2. Syntheses of amides from internal alkynes catalyzed by 1.a
H
1
2 mol% , NaN3 (2 equiv.),
N
H2O (2 equiv.)
R
R
O
TFA/DCE (2 mL, 1:1 v/ v),
RT, 2h
R = Aryl group
1, 62%b
2, 61%b
6, 47%b
3, 63%b
4,66 %b
5, 68%b
7, 55%b
a Reaction conditions: 0.5 mmol alkyne, 1 mmol NaN3, 1 mmol H2O, 2 mol% 1, 2
mL TFA/DCE (1:1 v/v), room temperature, 2 h. bIsolated yields.
Mechanistic Investigation
Control Experiments
To gain insight into the reaction mechanism, several control experiments were
carried out. At first, catalyst 2 that is devoid of the appended pyridyl functionality was
evaluated for the same reaction. Under optimization conditions, catalyst 2 gave 37%
conversion of N-phenyl acetamide that is much lower than the 91% yield offered by 1
(Scheme 5a). This result clearly demonstrates the role of the basic unit to promote
the amide synthesis. In the absence of water under the optimized reaction
conditions, both catalysts failed to afford the amide product. When the reaction was
performed in the absence of NaN3 under the standard conditions, catalyst 1 afforded
94% conversion to acetophenone (Scheme 5b), suggesting that amide formation
likely proceeds through the intermediacy of the hydration product ketone. When
acetophenone was used as starting precursor under identical conditions, N-phenyl
acetamide was obtained in 93% and 76% yields for catalysts 1 and 2 respectively.

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(Scheme 5c). However, without the catalyst, only trace amount of amide was
observed (Scheme 5d).
H
N
Standard conditions
Catalyst
a)
Ph
Ph
O
Cat. 1 : 91%
2
Cat. : 37%
O
Standard conditions
Without NaN3
b)
c)
Ph
Ph
Ph
94%
O
O
H
N
Standard conditions
Catalyst
Ph
O
1
Cat. : 93%
Cat. 2 : 76%
H
N
d)
Standard conditions
Without catalyst
Ph
Ph
O
trace
Scheme 5. Control experiments
.
NMR Experiment
The progress of the reaction was monitored by 1H NMR spectroscopy.
Phenylacetylene, sodium azide, catalyst 1 and D2O were taken with TFA/CD2Cl2
inside a NMR tube (Figure 2). Within a minute, new signals at δ 5.24, 5.66 ppm and
at δ 2.75 ppm appear. These signals grow in intensity up to five minutes after which
the signals at δ 5.24, 5.66 ppm decrease and the signal at δ 2.75 ppm increases. We
assume at this stage that these protons correspond to the alkyne hydration products.
Two sets of protons at higher frequencies are attributed to olefinic protons of the enol
X, which is in equilibrium with ketone Y that exhibits methyl protons at δ 2.75 ppm.
Although ketone is the stable product, acid catalyzed enolization is evident here.18

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As the reaction progresses, the equilibrium is shifted towards ketone. The alkyne (δ
3.12 ppm) is gradually consumed with the advancement of the reaction. The amide
product, identified by the methyl signal at δ = 2.26 ppm, starts appearing after five
minutes and progressively grows in intensity. After 2 hours, only product signals are
observed with the trace amount of alkyne and no ketone.
1
2 mol% , NaN3 (2 equiv.),
O
OH
H
D2O (2 equiv.)
Ph
N
Ph
Ph
TFA/CD2Cl2
Ph
O
Y
X
Fig. 2. Monitoring the progress of reaction by 1H NMR spectroscopy. = alkynyl
proton, = olefin proton in X, = methyl proton in Y, = methyl proton in amide.
Reaction conditions: phenylacetylene (0.25 mmol), NaN3 (0.50 mmol), 1 (2
mol%), D2O (0.5 mmol) and CD2Cl2 (0.4 mL) were taken in NMR tube and TFA
(200 µL) was added.

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Plausible Mechanism
Two possible pathways could be proposed19 for the amide formation from alkyne - (i)
alkyne hydration14 to ketone and subsequent Schmidt reaction,20 referred as
‘hydrative’ pathway, and (ii) hydroazidation of alkyne followed by acid catalyzed
rearrangement.4 The pyridyl group in catalyst 1 accelerates the amide formation and
such effect is absent for catalyst 2 that lacks the promoter unit. Further,
acetophenone is readily converted to the amide under the catalytic reaction
conditions. These results led us to argue in favor of a water attack to alkyne over the
azide reaction. NMR experiments do show the formation of ketone at the initial stage
of the reaction which is subsequently consumed to the amide. Consistent with these
observations, a hydrative mechanism (Scheme 6) is thus proposed. Initially, alkyne
is coordinated to the metal (A) via removal of the bromide that is assisted by the
trans NHC ligand.21 It is followed by water attack to the metal-coordinated alkyne in
accordance with Markovnikov’s rule.22 The pyridyl unit enhances the nucleophilicity
of the catalytically relevant water molecule by hydrogen-bond interaction as shown in
B.7 It results in the formation of ketone via enol intermediate.18 Nucleophilic attack of
azide to carbonyl carbon, facilitated by the protons present in the reaction medium,
affords D. A well-established Schmidt reaction is likely to operate in the final step.
The aryl group preferably migrates to the nitrogen atom with the simultaneous
liberation of N2 leading to the release of E, which readily tautomerizes to the amide
product. The alkyne coordination to the metal completes the catalytic cycle.

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1
Ph
Br
H
N
Ph
O
N
O
N
N
Ph
Au
H2O
N2
Ph
N
Ph
OH
E
A
Ph
N
N
N
H
O
O
Au
H
Ph
H
N
Au
N
N
O
N
N
N
O
B
Ph
D
O
H+, N3
Au
N
N
N
O
C
Scheme 6. Proposed hydrative mechanism for the synthesis of amide.
Concluding Remarks
An Au(I) complex bearing pyridyl-functionalized NHC ligand is synthesized. It
catalyses the amide synthesis from alkyne, azide and acidic water in excellent yield.
This silver-free protocol is advantageous in terms of low catalyst loading, short
reaction time, and works well for both terminal and internal alkynes. A related
catalyst that lacks pyridyl fragment performs much inferior. The role of the pyridyl
fragment to accelerate the amide synthesis is established. Control experiments and
NMR data suggest a hydrative pathway. This work endorses the use of pyridyl
functionality appended on the catalyst to promote water reactions.

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Experimental Section
General procedures
All reactions with metal complexes were carried out under an atmosphere of purified
nitrogen using standard Schlenk–vessel and vacuum line techniques. NMR spectra
1
were obtained on JEOL JNM–LA 400 MHz and 500 MHz spectrometer. H NMR
chemical shifts were referenced to the residual hydrogen signal of the deuterated
solvents. Elemental analyses were performed on a Thermoquest EA1110 CHNS/O
analyzer. The crystallized compounds were powdered, washed several times with
dry diethyl ether, and dried in vacuum for at least 48 h prior to elemental analyses.
ESI–MS were recorded on a Waters Micromass Quattro Micro triple–quadrupole
mass spectrometer. The GC–MS experiments were performed by using an Agilent
7890A GC and 5975C MS. Conversions were determined (uncorrected GC areas)
with respect to the internal standard.
Materials
Solvents were dried by conventional methods, distilled under nitrogen and
deoxygenated prior to use. Gold powder was purchased from Arora Matthey, India.
nBuLi was bought from Acros Organics. All other chemicals were purchased from
Sigma–Aldrich. Chloro(dimethylsulfide)gold(I)23, internal alkynes24 and ligands7 were
synthesized following reported procedures.
Caution: Under the reaction conditions, NaN3 may be hydrolyzed to form toxic and
explosive HN3. Protective measures are essential during experiment.
X-Ray Data Collection and Refinements: Single-crystal X-ray studies were
performed on a CCD Bruker SMART APEX diffractometer equipped with an Oxford

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Instruments low–temperature attachment. All the data were collected at 100(2) K
using graphite–monochromated Mo–Kα radiation (λα = 0.71073 Å). The frames were
indexed, integrated, and scaled using the SMART and SAINT software packages,25
and the data were corrected for absorption using the SADABS program.26 The
structures were solved and refined with the SHELX suite of programs.27 All hydrogen
atoms were included in the final stages of the refinement and were refined with a
typical riding model. Pertinent crystallographic data for compounds 1, 2 are
summarized in (Table S1.) The crystallographic figures used in this manuscript have
been generated using Diamond 3.1e software.28 CCDC numbers 1877275, 1877276
contain the supplementary crystallographic data for compounds 1 and 2. This data
can be obtained free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
Synthesis of 1
A flame dried Schlenk flask was charged with [L1.H]Br (150 mg, 0.43 mmol). It was
then dissolved in 15 mL THF and kept for cooling to 0°C in ice bath. Dropwise nBuLi
(0.69 mmol, 1.6 M in hexanes, 1.6 equivalents) was added to the reaction mixture
followed by addition of (SMe2)AuCl (127 mg, 0.43 mmol, 1 equivalents). The reaction
was heated to reflux for 24 hrs. After completion of the reaction, the mixture was
allowed to cool and solvent was evaporated under reduced pressure. The resulted
crude solid was further redissolved in 15 mL dichloromethane and the mixture was
filtered through a small pad of celite. To induce precipitation, 15 mL diethyl ether was
added after concentrating the reaction mixture under reduced pressure. Discarding
the supernatant solution through cannula filtration, the precipitate was again washed

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with ether (3x10 mL). Finally, a yellow solid was obtained after drying the precipitate
under vacuum. Suitable crystals were grown for X-ray diffraction inside an 8 mm o.d.
vacuum−sealed glass tube after layering diethyl ether over a concentrated
dichloromethane solution. Yield: 192 mg (82%). Anal. Calcd. for Au1C16H17N3O1Br1:
C, 35.36; H, 3.16; N, 7.74. Found: C, 35.02; H, 3.06; N, 7.31. ESI–MS, m/z:
1
544.0359 (z = 1), [M+H]+. H NMR (400 MHz, CDCl3) δ = 8.55 (d, J = 4.56 Hz, 1H,
Py), 7.66-7.54 (m, 4H, BzIm), 7.43-7.31 (m, 3H, Py), 5.80 (s, 2H, CH2Py), 4.65 (t, J =
13
5.04 Hz, 2H, CH2), 3.89 (t, J = 5.04 Hz, 2H, CH2), 3.30 (s, 3H, CH3); C NMR (100
MHz, CDCl3): δ = 191.77, 154.85, 149.59, 137.53, 134.14, 133.52, 124.97, 124.74,
123.48, 122.32, 112.56, 112.24, 77.54, 59.23, 54.17, 49.50.
Synthesis of 2
Compound 2 was synthesized following a similar procedure as for 1 using [L2.H]Br
n
(150 mg, 0.43 mmol), BuLi (0.69 mmol, 1.6 M in hexanes) and (SMe2)AuCl (127
mg, 0.43 mmol). Yield: 180 mg (77%). Anal. Calcd. for Au1C17H18N2O1Br1: C, 37.64;
H, 3.35; N, 5.17. Found: C, 37.11; H, 3.12; N, 5.03. ESI–MS, m/z: 729.2546 (z = 1),
[2+L2-Br]+. 1H NMR (400 MHz, CDCl3) δ = 7.59 (d, J = 6.44 Hz, 1H, BzIm), 7.37-7.30
(m, 8H, all aromatic), 5.71 (s, 2H, CH2Ben), 4.66 (t, J = 5.48 Hz, 2H, CH2), 3.90 (t, J
13
= 5.48 Hz, 2H, CH2), 3.31 (s, 3H, CH3); C NMR (100 MHz, CDCl3): δ = 181.98,
134.57, 134.43, 132.76, 129.13, 128.62, 127.46, 124.65, 112.63, 111.94, 72.00,
59.25, 52.91, 48.86.
General procedure for catalysis
Alkynes (0.5mmol), NaN3 (1 mmol), H2O (1 mmol), catalyst 1 (2 mol%) and
TFA/DCE (2 mL, 1:1 v/v) were taken in a Schlenk tube inside a fume hood. The

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reaction mixture was allowed to stir for 2 hours at room temperature. Then 25 mL
water was added to it and the organics were extracted with ethyl acetate (3 x 10 mL).
The solvent was evaporated under reduced pressure. The residue was purified by
column chromatography on silica gel (petroleum ether/ethyl acetate) to give the
desired amide product. Yields were calculated based on isolated products. GC yields
were reported in presence of internal standard dodecane.
Acknowledgments
Financial supports from the Department of Atomic Energy (DAE) and Indo-French
Centre for the Promotion of Advanced Research (IFCPAR) are gratefully
appreciated. J.K.B. thanks the DAE India for an SRC-OI fellowship. K.S. and N.K.P.
thank the UGC India for fellowships. C. G. thanks the CSIR India for fellowships.
References
1
a) A. Greenberg, C.M. Breneman, J.F. Liebman (Eds.), The Amide Linkage: Selected Structural
Aspects in Chemistry, Biochemistry, and Materials Science, Wiley-Interscience, New York, (2000);
b) T. Wieland, M. Bodanszky, The World of Peptides: A Brief History of Peptide Chemistry, Springer,
(1991);
c) N. Sewald, H.-D. Jakubke, Peptides: Chemistry and Biology, Wiley-VCH, Weinheim, Germany,
(2002);
d) V.R. Pattabiraman, J.W. Bode, Nature 480 (2011) 471;
e) J. M. Humphrey, A. R. Chamberlin, Chem. Rev. 97 (1997) 2243;
f) B. Saha, G. Sengupta, A. Sarbajna, I. Dutta, J. K. Bera, J. Organomet. Chem. 771 (2014) 124.
2 a) R.C. Larock, Comprehensive Organic Transformations, Wiley-VCH, New York, (1999);
b) M.B. Smith, in: Compendium of Organic Synthetic Methods, vol. 9, Wiley, New York, (2001);
c) J. Clayden, N. Greeves, S. Warren, P. Wothers, Organic Chemistry, Oxford University Press,
(2001);
d) J. March, Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, third ed., Wiley,
New York, (1985);
e) E. Valeur, M. Bradley, Chem. Soc. Rev. 38 (2009) 606;
f) P. D. Bailey, I. D. Collier, K. M. Morgan, In ComprehensiVe Organic Functional Group
Transformations; A. R. Katritzky, O. Meth-Cohn, C. W. Rees, Eds.; Pergamon: Cambridge, 5 (1995)
Chapter 6.
3 a) B. L. Bray, Nat. Rev. 2 (2003) 587;
b) F. Albericio, Curr. Opin. Chem. Biol. 8 (2004) 211;
c) P.A.S. Smith, Org. React. 3 (1946);
d) R.E. Gawley, Org. React. 35 (1988);

ACCEPTED MANUSCRIPT
e) J.H. Boyer, J. Hamer, J. Am. Chem. Soc. 77 (1955) 951;
f) N.A. Owston, A.J. Parker, J.M.J. Williams, Org. Lett. 9 (2007) 3599;
g) S. Murahashi, T. Naota, E. Saito, J. Am. Chem. Soc. 108 (1986) 7846;
h) J.M. Lee, D.-S. Ahn, D.Y. Jung, J. Lee, Y. Do, S.K. Kim, S. Chang, J. Am. Chem. Soc. 128 (2006)
12954;
i) W.-J. Yoo, C.-J. Li, J. Am. Chem. Soc. 128 (2006) 13064;
j) W.-K. Chan, C.-M. Ho, M.-K. Wong, C.-M. Che, J. Am. Chem. Soc. 128 (2006) 14796;
k) C. Zhang, N. Jiao, J. Am. Chem. Soc. 132 (2010) 28;
l) N.D. Schley, G.E. Dobereiner, R.H. Crabtree, Organometallics 30 (2011) 4174;
m) H. Jiang, B. Liu, Y. Li, A. Wang, H. Huang, Org. Lett. 13 (2011) 1028;
n) J.Y. Kim, S.H. Park, J. Ryu, S.H. Cho, S.H. Kim, S. Chang, J. Am. Chem. Soc. 134 (2012) 9110;
o) R. Cadoni, A. Porcheddu, G. Giacomelli, L.D. Luca, Org. Lett. 14 (2012) 5014;
p) S.C. Ghosh, J.S.Y. Ngiam, A.M. Seayad, D.T. Tuan, C.L.L. Chai, A. Chen, J. Org. Chem. 77 (2012)
8007;
q) C. Zhang, X. Zong, L. Zhang, N. Jiao, Org. Lett. 14 (2012) 3280;
r) B. Zhou, Y. Yang, J. Shi, H. Feng, Y. Li, Chem. Eur. J. 19 (2013) 10511;
s) I. Kim, C. Lee, Angew. Chem. Int. Ed. 52 (2013) 10023.
4 a) S. H. Cho, E. J. Yoo, I. Bae, S. Chang, J. Am. Chem. Soc. 127 (2005) 16046;
b) S. H. Cho, S. Chang, Angew. Chem. Int. Ed. 46 (2007) 1897;
c) C. Qin, P. Feng, Y. Ou, T. Shen, T. Wang, N. Jiao, Angew. Chem. Int. Ed. 52 (2013) 7850;
d) Q. Nie, F. Yi, B. Huang, M. Cai, Adv. Synth. Catal. 359 (2017) 3968.
5 a) The Chemistry of Amides, J. Zabicky, Ed., Wiley-Interscience, New York, (1970);
b) The Amide Linkage: Structural Significance in Chemistry, Biochemistry and Materials Science, A.
Greenberg, C. M. Breneman, J. F. Liebman, Eds., John Wiley & Sons, New York,(2000);
c) T. J. Ahmed, S. M. M. Knapp, D. R. Tyler, Coord. Chem. Rev. 255 (2011) 949;
d) The Chemistry of Functional Groups, The Chemistry of Cyano Group, Z. Pappoport, S. Patai, Eds.,
Wiley, London, (1970);
e) V. R. Pattabiraman, J. W. Bode, Nature 480 (2011) 471.
f) X. Xing, C. Xu, B. Chen, C. Li, S. C. Virgil, R. H. Grubbs, J. Am. Chem. Soc. DOI:
10.1021/jacs.8b11667;
g) I. G. Molnár, P. Calleja, M. Ernst, A. S. K. Hashmi, T. Schaub, ChemCatChem 9 (2017) 4175.
6 a) R. García-Álvarez, J. Díez, P. Crochet, V. Cadierno, Organometallics 29 (2010) 3955;
b) R. García-Álvarez, M. Zablocka, P. Crochet, C. Duhayon, J.-P. Majoral, V. Cadierno, Green Chem.
15 (2013) 2447;
c) V. Cadierno, J. Francos, J. Gimeno, Chem.-Eur. J. 14 (2008) 6601;
d) V. Cadierno, J. Díez, J. Francos, J. Gimeno, Chem.-Eur. J. 16 (2010) 9808;
e) R. García-Álvarez, J. Francos, P. Crochet, V. Cadierno, Tetrahedron Lett. 52 (2011) 4218;
f) R. García-Álvarez, J. Díez, P. Crochet, V. Cadierno, Organometallics 30 (2011) 5442;
g) R. García-Álvarez, A. E. Díaz-Álvarez, P. Crochet, V. Cadierno, RSC Adv. 3 (2013) 5889;
h) E. Tomas-Mendivil, F. L. Suárez, J. Diez, V. ́ Cadierno, Chem. Commun. 50 (2014) 9661;
i) E. Tomás-Mendivil, R. García-Álvarez, C. Vidal, P. Crochet, V. Cadierno, ACS Catal. 4 (2014) 1901;
j) R. González‐Fernández, P. Crochet V. Cadierno, ChemistrySelect 3 (2018) 4324;'
k) R. González‐Fernández, P. Crochet, V. Cadierno, M. I. Menéndez, R. López, Chem.-Eur.J. 23
(2017) 15210.
7 K. Singh, A. Sarbajna, I. Dutta, P. Pandey, J. K. Bera, Chem.-Eur. J. 23 (2017) 7761.
8 a) F. Boeck, T. Kribber, L. Xiao, L. Hintermann, J. Am. Chem. Soc. 133 (2011) 8138;
b) D. B. Grotjahn, Chem.-Eur. J. 11 (2005) 7153;
c) A. Labonne, T. Kribber, L. Hintermann, Org. Lett., 8 (2006) 5854;
d) D. B. Grotjahn, E.J. Kragulj, C. D. Zeinalipour-Yazdi, V. Miranda-Soto, D. A. Lev, A. L. Cooksy, J.
Am. Chem. Soc. 130 (2008) 10860.
9 a) D. B. Grotjahn, C. D. Incarvito, A. L. Rheingold, Angew. Chem., Int. Ed. 40 (2001) 3884;

ACCEPTED MANUSCRIPT
b) D. B. Grotjahn, D. A. Lev, J. Am. Chem. Soc. 126 (2004) 12232.
10 M. Inoue, K. Ugawa, T. Maruyama, T. Iwasawa, Eur. J. Org. Chem. (2018) 5304.
11 P. Daw, A. Sinha, S.M.W. Rahaman, S. Dinda, J.K. Bera, Organometallics 31 (2012) 3790.
12 T. Ghatak, M. Sarkar, S. Dinda, I. Dutta, S.M.W. Rahaman, J.K. Bera, J. Am. Chem. Soc. 137
(2015) 6168.
13 A. Sarbajna, I. Dutta, P. Daw, S. Dinda, S.M.W. Rahaman, A. Sarkar, J.K. Bera, ACS Catal. 7
(2017) 2786.
14 a) S. Díez-González, N. Marion, S. P. Nolan, Chem. Rev. 109 (2009) 3612;
b) F. Li, N. Wang, L. Lu, G. Zhu, J. Org. Chem. 80 (2015) 3538;
c) R. Dorel, A. M. Echavarren, Chem. Rev. 115 (2015) 9028;
d) A. S. K. Hashmi, Chem. Rev. 107 (2007) 3180;
e) R. Casado, M. Contel, M. Laguna, P. Romero, S. Sanz, J. Am. Chem. Soc. 125 (2003) 11925;
f) A. Leyva, A. Corma, J. Org. Chem. 74 (2009) 2067;
g) E. Mizushima, K. Sato, T. Hayashi, M. Tanaka, Angew. Chem. Int. Ed. 41 (2002) 4563;
h) D. Pflästerer, A. S. K. Hashmi, Chem. Soc. Rev. 45 (2016) 1331;
i) A. M. Asiri, A. S. K. Hashmi, Chem. Soc. Rev. 45 (2016) 4471.
15 a) C. M. Krauter, A. S. K. Hashmi, M. Pernpointner, ChemCatChem 2 (2010) 1226;
b) M. Lein, M. Rudolph, A. S. K. Hashmi, P. Schwerdtfeger, Organometallics 29 (2010) 2206;
c) M. C. B. Jaimes, F. Rominger, M. M. Pereira, R. M. B. Carrilho, S. A. C. Carabineiro, A. S. K.
Hashmi, Chem. Commun. 50 (2014) 4937;
d) M. C. B. Jaimes, C. R. N. Böhling, J. M. Serrano-Becerra, A. S. K. Hashmi, Angew. Chem. Int. Ed.
52 (2013) 7963.
16 a) M. Pažický, A. Loos, M. J. Ferreira, D. Serra, N. Vinokurov, F. Rominger, C. Jäkel, A. S. K.
Hashmi, M. Limbach, Organometallics 29 (2010) 4448;
b) L. Huang, , F. Rominger, M. Rudolph, A. S. K. Hashmi, Chem. Commun. 52 (2016) 6435;
c) L. Huang, M. Rudolph, F. Rominger, A. S. K. Hashmi, Angew. Chem. Int. Ed. 55 (2016) 4808;
d) C. Khin, A. S. K. Hashmi, F. Rominger, Eur. J. Inorg. Chem. (2010) 1063.
17 a) W. Zhua, D. Ma, Chem. Commun. (2004) 888;
b) H. Sharghi, R. Khalifeh, M. M. Doroodmanda, Adv. Synth. Catal. 351 (2009) 207;
c) H. R. Sahoo, J. G. Kralj, K. F. Jensen, Angew. Chem. Int. Ed. 46 (2007) 5704;
d) M. Nasrollahzadeh, Y. Bayat, D. Habibi, S. Moshaee, Tetrahedron Lett. 41 (2000) 4193.
18 G. E. Lienhard, T.-C. Wang, J. Am. Chem. Soc. 91 (1969) 1146;
b) Y. Chiang,f A. J. Kresge,s,t J. A. Santaballa/1 and J. Wirz, J. Am. Chem. Soc. 110 (1988) 5506;
c) J. A. Keith, P. M. Henry, Angew. Chem. Int. Ed. 48 (2009) 9038.
19 A. S. K. Hashmi, Angew. Chem. Int. Ed. 49 (2010) 5232.
20 a) K. F. Z. Schmidt, Angew. Chem. 36 (1923) 511;
b) S. Lang, J. A.Murphy, Chem. Soc. Rev. 35 (2006)146.
21 H. Ibrahim, P. d. Frémont, P. Braunstein, V. Théry, L. Nauton, F. Cisnetti, A. Gautier, Adv. Synth.
Catal. 357 (2015) 3893.
22 a) W. Markownikoff, Eur. J. Org. Chem. (1870) 228;
b) F. Li, N. Wang, L. Lu, G. Zhu, J. Org. Chem. 80 (2015) 3538;
c) A. K. Das, S. Park, S. Muthaiah, S. H. Hong, Synlett. 26 (2015) 2517.
23 M.-C. Brandys, M. C. Jennings, R. J. Puddephatt, J. Chem. Soc., Dalton Trans. (2000) 4601.
24 a)K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 16 (1975) 4467;
b) J.-C. Hierso, A. Fihri, R. Amardeil, P. Meunier, Org. Lett. 6 (2004) 3473;
c) G. Adjabeng, T. Brenstrum, C. S. Frampton, A. J. Roberson, J. Hillhouse, J.McNulty, A. Capretta, J.
Org. Chem. 69 (2004) 5082
25 SAINT+ Software for CCD Diffractometers; Bruker AXS, Madison, WI, (2000).
26 G. M. Sheldrick, SADABS 2.0, (2000)
27 G. M. Sheldrick, SHELXL-2014: Program for Crystal Structure Refinement; University of Göttingen:
Göttingen, Germany, (2014).
28 K. Bradenburg, Diamond, version 3.1e; Crystal Impact GbR, Bonn, Germany, (2005).