Alkyne Trifunctionalization via Divergent Gold Catalysis: Combining π-Acid Activation, Vinyl-Gold Addition, and Redox Catalysis

Article abstract of DOI:10.1021/jacs.1c01811

Here we report the first example of alkyne trifunctionalization through simultaneous construction of C-C, C-O, and C-N bonds via gold catalysis. With the assistance of a γ-keto directing group, sequential gold-catalyzed alkyne hydration, vinyl-gold nucleophilic addition, and gold(III) reductive elimination were achieved in one pot. Diazonium salts were identified as both electrophiles (N source) and oxidants (C source). Vinyl-gold(III) intermediates were revealed as effective nucleophiles toward diazonium, facilitating nucleophilic addition and reductive elimination with high efficiency. The rather comprehensive reaction sequence was achieved with excellent yields (up to 95%) and broad scope (>50 examples) under mild conditions (room temperature or 40 °C).

Full text of DOI:10.1021/jacs.1c01811

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Article
Alkyne Trifunctionalization via Divergent Gold Catalysis: Combining
π‑Acid Activation, Vinyl−Gold Addition, and Redox Catalysis
Teng Yuan, Qi Tang, Chuan Shan, Xiaohan Ye, Jin Wang, Pengyi Zhao, Lukasz Wojtas, Nicholas Hadler,
Hao Chen, and Xiaodong Shi*
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ABSTRACT: Here we report the first example of alkyne trifunctionalization through simultaneous construction of C−C, C−O, and
C−N bonds via gold catalysis. With the assistance of a γ-keto directing group, sequential gold-catalyzed alkyne hydration, vinyl−gold
nucleophilic addition, and gold(III) reductive elimination were achieved in one pot. Diazonium salts were identified as both
electrophiles (N source) and oxidants (C source). Vinyl−gold(III) intermediates were revealed as effective nucleophiles toward
diazonium, facilitating nucleophilic addition and reductive elimination with high efficiency. The rather comprehensive reaction
sequence was achieved with excellent yields (up to 95%) and broad scope (>50 examples) under mild conditions (room temperature
or 40 °C).
chemistry has gained increasing attention for its unique
reactivity, arguably opening a new era of homogeneous gold
catalysis.23−28 The combination of π-activation and redox
chemistry will intrinsically initiate new strategies for efficient
and versatile transformations.
INTRODUCTION
■
Alkynes represent an important group of compounds in
chemical synthesis.1−6 Over the past decade, alkyne
functionalization has gained increasing attention for easy
access to complicated molecular scaffolds.3,7−10 Although
alkyne difunctionalization is more commonly reported, its
trifunctionalization has been rare.11 Among the reported
examples, rigorous degassing or harsh reaction conditions are
generally required, which limits the application of these
methods.12 Moreover, previous literature mainly focused on
C−O and C−X bond formation. Therefore, an efficient and
practically useful approach for alkyne trifunctionalization
involving C−C bond formation is highly desirable.
Throughout the first two decades of this century, gold
catalysis has enjoyed the spotlight of organometallic
chemistry, mainly due to its exceptional ability to activate
alkynes and allenes under mild conditions.13−17 The
nucleophilic addition toward an alkyne−gold π-complex
followed by protodeauration has been applied as an efficient
strategy in many important chemical transformations
(Scheme1A, paths A and B).1,18−22 Recently, with the joint
efforts from numerous groups around the world, gold redox
With the high oxidation potential between AuI and AuIII
(1.4 eV), strong oxidants are usually required in gold redox
chemistry, leading to incompatibility with many nucleophiles
for gold-activated alkynes.29−37 Moreover, protodeauration
has been a serious problem for any subsequent trans-
formations using intermediates containing C−Au bonds.38−41
Therefore, limited success was achieved combining gold π-
activation and redox catalysis.42−49 On the other hand, the
good electron-donating ability of gold cation toward CC
bond renders vinyl−gold a potentially good nucleophile,
Received: February 15, 2021
Published: March 4, 2021
https://dx.doi.org/10.1021/jacs.1c01811
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© 2021 American Chemical Society
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Scheme 1. Representative Reaction Paths in Gold Catalysis
Figure 1. Vinyl−gold reactivity toward different electrophiles.
(Figure 1B). Initially, the ligand-assisted aryl iodide oxidative
addition protocol, recently reported by Bourissou and
Patel,56−61 was tested. Unfortunately, the dominant hydration
product 3a was obtained with no vinyl gold addition product
or reductive elimination product observed. Then photo-
initiated diazonium activation was also performed, giving
similar results with 3a as the dominant product. Both results
highlighted the significance and necessity of preventing the
rapid protodeauration to access any valid vinyl−gold
reactivity. Interestingly, carefully monitoring the reaction
under photocatalytic conditions revealed the formation of a
new product 4a though in a very low yield. X-ray diffraction
identified the structure of this compound as a result of
potential vinyl−gold addition toward diazonium. Notably, the
aldehyde addition product 2a or 2aa was not obtained in all
cases with diazonium presented, suggesting that the
diazonium salt might be a more reactive electrophile over
aldehyde toward vinyl−gold.
provided that protodeauration could be prevented. Although
few examples have been reported so far, nucleophilic addition
of vinyl gold provides an interesting new reaction path that
further enriches the versatile reactivity of gold catalysis.50−55
Clearly, the possibility of integrating all three gold reaction
modes (π-activation, redox catalysis, and vinyl gold
nucleophilic addition) is not only mechanistically fascinating
but also practically appealing, featuring multiple functionaliza-
tions in one step. Herein, we report the concurrent
construction of C−O, C−N, and C−C bonds from
unactivated alkynes through the divergent gold catalysis. To
the best of our knowledge, this is the first example of a
transformation that successfully combines three gold reaction
modes in a single step. The alkyne trifunctionalization
products were obtained with high efficiency (up to 95%)
and broad substrate scope (>50 examples) under mild
conditions (Scheme 1B).
To prevent protodeauration, the Fe(acac)3 cocatalyst
strategy was applied to the reaction with diazonium salt.
Indeed, addition of 10% Fe(acac)3 raised the yield of 4a to
34%. Unfortunately, Fe(acac)3 quenched the photocatalytic
reactivity and gave almost no conversion over time,
suggesting its poor compatibility with photopromoted
diazonium activation (see the Supporting Information). Our
group has recently reported the base-assisted diazonium
activation as an alternative approach to achieve gold
oxidation.62−65 It is expected that conducting the reaction
under basic conditions will not only help diazonium
activation but also reduce the rate of protodeauration. As
expected, addition of Li2CO3 (1 equiv) further improved the
yield of 4a to 79% along with formation of 5a (reductive
elimination product) for the first time.
These exploratory studies were inspiring to us in the
following aspects: (A) diazonium is a valid electrophile for
vinyl−gold addition (new C−N bond formation strategy);
(B) the integration of gold redox catalysis is theoretically
feasible (formation of 5a). To develop this new reactivity, we
first focused our efforts on the vinyl−gold(I) diazonium
RESULTS AND DISCUSSION
■
Reaction Development. To achieve the integration of
multiple gold reactivities, the compatibility of vinyl−gold
nucleophilic addition (path C) is the most crucial factor.
Because of the competing protodeauration, successful vinyl−
gold nucleophilic addition examples are extremely rare in the
literature, especially in a catalytic fashion. Recently, with the
introduction of the γ-keto directing group (DG), our group
reported the first intermolecular crossed aldol reaction using
synergistic gold/iron catalysis (Figure 1A, room temperature,
open air, neutral solution).55 Fe(acac)3 was identified as the
critical cocatalyst to effectively prevent C−Au bond from
protodeauration. The γ-keto directing group is also crucial as
the reaction of phenylacetylene gave only hydration product
3a′ under identical conditions with no aldol product 2a′
observed.
Encouraged by this result, we set our goal to explore the
possibility of integrating vinyl−gold chemistry with gold
redox catalysis by conducting reactions of 1a and
benzaldehyde under various reported gold redox conditions
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addition. Reactions between 1a and the aryldiazonium salt
were screened under various conditions (see details in the
Supporting Information). The combination of (p-CF3−
C6H4)3PAuNTf2 catalyst (5%) and 10% Fe(acac)3 was
identified as the optimal condition, giving the desired
product 4a in 88% isolated yields (5% of 3a). The
performance of some alternative conditions is summarized
in Table 1.
A series of aryldiazonium salts were prepared as coupling
partners with alkyne 1a. In general, the reaction worked well
for electron-deficient aryldiazoniums, affording arylhydrazones
4a−4o in good to excellent yields. Electron-rich aryldiazo-
niums offered <30% yields (4p) due to reduced electro-
philicity. Remarkably, with Fe(acac)3 as cocatalyst, the
reaction even tolerated weakly acidic functional groups,
giving the desired addition product (4i) with little hydration
byproducts observed. Variations on γ-keto directing groups
have also been evaluated. Most aryl-substituted carbonyl
directing groups (DG) are tolerated, giving the desired
product in good to excellent yields (4aa−4ai, 4an). The
aliphatic carbonyl DG also worked though with slightly
reduced yields (4aj, 4ao). Impressively, a variety of substrates
containing functional groups, such as cyclopropyl, alkynyl,
and allyl groups, gave desired products in good yields (4ak−
4am). This result highlighted the mild condition and
excellent functional group tolerance of this method.
For many reported gold catalysis, activation of internal
alkynes remains a formidable task due to reduced reactivity,
especially under mild conditions. In our case, both aryl- and
alkyl-substituted internal alkynes provided good to excellent
yields (4ba−4bl, 5a). Notably, single regioisomers consistent
with the 5-exo-dig activation mechanism were obtained in all
cases (no 6-endo-dig products observed). The room
temperature activation of internal alkynes highlighted the
reactivity boosting effect upon our strategic application of the
γ-keto directing group. Similar to our previous observation,
extending the keto DG to the δ-position (one extra carbon)
led to dramatic reduction of coupling product yield
(dominant hydration, see the Supporting Information),
emphasizing the choice of the γ-keto directing group in
achieving vinyl−gold addition. Having applied the gold/iron
dual catalytic system effectively to vinyl−gold diazonium
addition, we moved on to the more challenging alkyne
trifunctionalization integrating redox catalysis.
a b
,
Table 1. Optimization of Reaction Conditions
entry
variations
4a (%)
3a (%) 5a (%)
c
1
2
3
4
5
6
7
8
none [L = P(p-CF3−C6H4)3]
L = PPh3
L = JohnPhos
L = IPr
L = P(ArO)3
93 (88)
83
35
0
0
85
90
34
<5
80
78
<50
<78
5
15
60
80
93
12
6
25
<5
12
20
>40
>8
n.d.
n.d.
trace
n.d.
n.d.
trace
n.d.
10
n.d.
n.d.
n.d.
<10
<15
L = PCy3
L = P(p-F−C6H4)3
Na2CO3 instead of Li2CO3
other bases
9
10
11
12
13
1.0 equiv of H2O
5.0 equiv of H2O
d
other solvents
40 °C or higher
a
Standard conditions: 5% (p-CF3C6H4)3PAuNTf2, 10% Fe(acac)3, 3
equiv of water, and 0.2 mmol of Li2CO3 were added to a THF
solution (0.5 mL) of alkyne 1a (0.2 mmol) and aryldiazonium salt
(0.4 mmol), and the reaction was kept stirring at room temperature
b
for 6 h. Conversion and yields were determined by 19F NMR and 1H
NMR spectroscopy by using trifluorobenzene and 1,3,5-trimethox-
c
d
ybenzene correspondingly as internal standard. Isolated yield. See
the Supporting Information.
As shown in Scheme 1A, the alkyne trifunctionalization can
be achieved from two slightly different reaction sequences:
(1) vinyl−AuI oxidation to [vinyl−AuIII−aryl] followed by
reductive elimination and (2) in situ formation of [Ar−AuIII]
π-acid for alkyne activation followed by reductive elimi-
nation.66 Although the former strategy is extremely attractive
for rapid, simultaneous bond construction, to the best of our
knowledge, no catalytic reaction through this path has been
realized yet, likely due to various competing side reactions.
The vinyl−gold addition to diazonium shown above provided
a good platform to explore this new transformation since
diazonium could serve as potential oxidant for gold redox
chemistry under proper conditions. Very recently, Hashmi’s
group reported an interesting example of vinyl−gold addition
to diazonium for the formation of the C−N bond, which
strongly supported this hypothesis.67 However, there are two
major mechanistic concerns: (A) protodeauration remains the
key challenge for any reaction sequence involving Au−C
bond, and (B) gold(III) reductive elimination is a fast
process due to its high redox potential. On the basis of this
analysis, we proposed that in situ formation of [Ar−AuIII] for
alkyne activation is preferred in a practical sense for alkyne
trifunctionalization. To testify this idea, L−AuI−Cl type
catalysts were used to react with diazonium salts with the
hope to generate active [AuIII−Ar] prior to alkyne activation.
After tuning several typical reaction parameters, the
trifunctionalization product 5a was obtained in excellent
As shown in Table 1, the primary ligand on gold plays a
pivotal role with P(p-CF3−C6H4)3AuNTf2 giving the best
yield, suggesting the balance of electron density on gold is
critical (entries 1−7). The [L−Au−L′]+ types of catalysts,
such as [LAu(TA)]+ and [LAu(CH3CN)]+, were also tested,
giving dominantly hydration product 3a (see the Supporting
Information). The choice of base was also proved to be vital.
While Li2CO3 was the optimal base, Na2CO3 gave
significantly reduced yield of 4a (entry 8), presumably due
to the reaction with [Fe] cocatalyst under stronger basic
conditions. Some alternative organic and inorganic bases were
also tested but gave poor performance (see the Supporting
Information). Because the reaction involved both alkyne
hydration and vinyl−gold nucleophilic addition, the amount
of water should be important to reach the ideal balance
between vinyl−gold addition and minimal protodeauration.
After screening, 3 equiv of water gave the best result with
THF as solvent. Notably, conducting the reaction at elevated
temperature (40 °C) gave arylhydrazone 5a as the minor
product, suggesting the feasibility of the proposed alternative
gold redox process (entry 13). With the optimal condition in
hand, the substrate scopes of alkynes and aryldiazonium salts
were evaluated. The results are summarized in Scheme 2.
An extensive survey of the reaction scope was presented
with three variations: diazonium, directing group, and alkyne.
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a b
,
Scheme 2. Reaction Scope of Difunctionalization
a
Standard conditions: 5% (p-CF3−C6H4)3PAuNTf2, 10% Fe(acac)3, 3 equiv of water, and 0.2 mmol of Li2CO3 were added to a THF solution (0.5
b
c
mL) of alkyne 1a (0.2 mmol) and aryldiazonium salt (0.4 mmol), and the reaction was running at room temperature for 6 h. Isolated yields. 40
°C.
yields (94% isolated yields) with Cy3PAuCl as catalyst and
3.0 equiv of diazonium salt under basic conditions (2 equiv
of Li2CO3) at 40 °C. Results from typical alternative
conditions are shown in Table 2 (see detailed screening
conditions in the Supporting Information).
First, the typical photocatalytic diazonium activation was
not suitable for this transformation (entry 2), forming
dominatly ketone 3a as the hydration product. Second, our
previously developed base-promoted conditions for thermal
activation of diazonium proved essential in this trans-
formation. While Cy3PAuCl appeared to be the optimal
catalyst (entries 3−7), the choice of solvent, base, and
amount of water also had huge impacts on the reaction
performance (see detailed screening in the Supporting
Information). Higher reaction temperature (>50 °C)
significantly raised the hydration rate. Nevertheless, under
the optimal condition, the trifunctionalization of alkyne was
successfully achieved with high efficiency. Based on this
optimal condition, the reaction scope was explored. The
results are summarized in Scheme 3.
The reaction scope was also evaluated through three
variations: diazonium salts, directing groups, and internal
alkynes. A variety of aryldiazonium salts were tested as
reaction partner with alkyne 1a. Compared to alkyne
difunctionalization, this reaction exhibited a broader scope
presumably owing to the higher reactivity of vinyl−gold(III)
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aforementioned “boosting effect”. On the other hand, the low
diastereoselectivity of product 5bp was likely an outcome of
α-carbon epimerization.
Table 2. Alkyne Trifunctionalization with Gold Redox
Catalysis
a b
,
Mechanistic Studies and Functional Group Con-
versions. Under photochemical (blue LED) or thermal
conditions, arylgold(III) species were formed by treating
aryldiazonium with the gold(I) chloride complex.66,68 To gain
more mechanistic insight, we monitored the reaction with
nESI-MS (Figure 2A). Diagnostic signals of [AuIII−Ar]
catalyst and key intermediates A and B were all successfully
captured, whereas their structure compositions confirmed by
CID (MS-MS, see details in the Supporting Information).
These HRMS results greatly supported the proposed reaction
sequence with formation of [AuIII−Ar] followed by alkyne π-
activation, vinyl−gold nucleophilic addition toward diazo-
nium salts, and finally AuIII reductive elimination.
Apart from its mechanistic novelty, the resulting 1,4-
diketone products contain versatile functional groups, which
make them interesting building blocks for complex molecular
skeleton construction. It is well-known that 1,4-diketone is a
good synthon for the synthesis of hetereocycles through
double condensation by reacting with amine or hydra-
zine.69,70 This approach was further confirmed by the
example shown in Figure 2B: treating 4a with Lawesson’s
reagent produces hydrozone-substituted thiophene 6a, a
corrector of a mutant cystic fibrosis transmembrane
conductance regulator (CFTR), in excellent yield.71 To
explore the synthetic applications of this new method, we put
our efforts into exploring new transformations that are
uniquely associated with the resulting products from the
following three perspectives: (1) selective carbonyl reduction
over hydrazone, (2) effective protocol for directing group
removal, and (3) selective hydrazone reduction to the N−N
bond.
For effective transformations of the resulting products, one
practical concern is the selective reduction of ketone (CO)
over CN and NN, or vice versa. After exploring multiple
typical reduction conditions, we are pleased to identify Pd/
C/H2 as an optimal condition for selective imine−ketone
reduction (5a to 6b, 90%). In addition, NaBH4 was identified
as the optimal reagent for ketone reduction over imine, giving
6c in 93% yields. Interestingly, the resulting diol 6c could be
readily coverted into substituted THF 6d, bearing an imine
moiety with no hydration. The result greatly enriched good
synthetic potential of this method by introducing multiple
functional groups in one simple step. Notably, the hydrazones
(6a−6d) were all assigned as E isomer based on X-ray single
crystals of starting material 5a. Although the γ-ketone
directing group is an useful synthetic handle as demonstrated
above, it could be more attractive if an effective directing
group removal strategy could be developed to further extend
the synthetic applications. After extensive condition screening,
aqueous HCl (3 N) was identified as the practical condition
for γ-ketone dissociation, giving hydrazones (7a−7c) in good
to excellent yields. Notably, this method not only gives an
effective approach to prepare hydrazones bearing more
reactive aldehyde (traditional condensation will not work)
but also allows the rapid construction formation of alkyl−aryl
hydrazone (7b, 7c), which could be readily converted into
the substituted cinnoline 8 by using reported conditions (two
steps, high yields). The hydrazones (7b, 7c) were assigned as
Z configuration based on the literature reported.72
entry
variation
5a (%)
3a (%)
1
2
3
4
5
6
7
8
none
95 (94)
0
90
trace
10
0
85
88
<89
30
<10
<67
2
48
7
35
50
0
12
8
>8
15
<15
>20
no Li2CO3, Ru(bpy)3PF6, blue LED
PPh3AuCl
JohnPhosAuCl
IPrAuCl
(ArO)3PAuCl
(4-CF3C6H4)3AuCl
3.0 equiv of H2O
c
9
10
11
other solvents
Na2CO3 instead of Li2CO3
c
other bases
12
50 °C or higher
a
Standard conditions: 5% Cy3PAuCl, 1 equiv of water, and 0.4 mmol
of Li2CO3 were added to a MeCN solution (0.6 mL) of alkyne 1a (0.2
mmol) and aryldiazonium salt (0.6 mmol), and reaction was running
b
at 40 °C for 3 h. Conversion and yields were determined by 19F
1
NMR and H NMR spectroscopy using trifluorobenzene and 1,3,5-
trimethoxybenzene correspondingly as internal standard. See the
Supporting Information.
c
intermediates. In general, the reaction worked well for both
electron-deficient and electron-rich aryldiazonium salts. The
reaction of electron-deficient diazonium salts afforded
arylhydrazones 5a−5i with good to excellent yields while
the electron-rich diazonium salt gave a moderate yield (5j).
Interestingly, ortho- and meta-substituted aryldiazonium salts,
which were unsatisfactory substrates in the base-promoted
gold-redox process, worked well in this transformation (5k−
5n). Disubstitued aryldiazonium salts also exhibit decent
reactivity (5o−5r). Furthermore, substrates with diverse γ-
carbonyl DG including both aryl (including heterocycles) and
aliphatic substituents displayed good to excellent yields
(5aa−5an). Notably, although Ar−AuIII is a superior π-acid
which can activate alkenes, great chemoselectivity was
observed with carbon−carbon double bond remaining intact
in this transformation (5al). Some other functional groups
such as cyclopropyl and alkynyl also survived under the
reaction condition, exemplifying mildness and robustness of
this transformation. Significantly, when treating internal
alkynes with aryldiazonium 1a, azo compounds containing a
quaternary carbon center were formed (5ba−5bq). The
electron-deficient aryl-substituted internal alkynes dominantly
went through 5-exo-dig cyclization, providing azo compounds
in good to excellent yields (5ba−5bg, 5bj−5bm). In contrast,
less electron-deficient aryl-substituted internal alkynes
afforded azo products in slightly reduced yields as 5:1 and
3.5:1 regioisomers (1,4-diketones from 5-exo addition vs 1,5-
diketones from 6-endo addition), respectively (5bh and 5bi).
The electron-rich aryl-substituted internal alkyne (5bo) gave
exclusively 1,5-diketone in a good yield. Impressively, internal
alkynes with cyclic ketone directing group reacted with
diazonium salts, giving the desired product 5bq in modest
yield but with good diastereoselectivity. This result featured
stereoselectivity improvement of vinyl gold nucleophilic
addition by the 5-exocyclization mechanism besides the
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a b
,
Scheme 3. Reaction Scope of Alkyne Trifunctionalization
a
Standard conditions: 5% Cy3PAuCl, 1 equiv of water, and 0.4 mmol of Li2CO3 were added to a MeCN solution (0.6 mL) of alkyne 1a (0.2 mmol)
b
and aryldiazonium (0.6 mmol), and the reaction was running at 40 °C for 3 h. Isolated yields.
Finally, while the reduction of N−N to NH2 is a well-
studied process with numerous conditions reported,73−75 it is
important to develop practical conditions for selective NN
hydrogenation to the N−N single bond with CO
presented. After exploring multiple typical reduction con-
ditions, we are pleased to discover that the azo compounds
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Experimental procedures, characterization data, and
crystallographic data (PDF)
Accession Codes
CCDC 2044472−2044479 contain the supplementary
crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_-
request/cif, or by emailing data_request@ccdc.cam.ac.uk, or
by contacting The Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223
336033.
AUTHOR INFORMATION
Corresponding Author
■
Xiaodong Shi − Department of Chemistry, University of
South Florida, Tampa, Florida 33620, United States;
orcid.org/0000-0002-3189-1315; Email: xmshi@
usf.edu
Authors
Teng Yuan − Department of Chemistry, University of South
Florida, Tampa, Florida 33620, United States
Qi Tang − Department of Chemistry, University of South
Florida, Tampa, Florida 33620, United States
Chuan Shan − Department of Chemistry, University of South
Florida, Tampa, Florida 33620, United States
Xiaohan Ye − Department of Chemistry, University of South
Florida, Tampa, Florida 33620, United States
Jin Wang − College of Chemistry, Chemical Engineering and
Material Science, Shandong Normal University, Jinan,
Shandong 250014, China
Pengyi Zhao − Department of Chemistry and Environmental
Science, New Jersey Institute of Technology, Newark, New
Jersey 07102, United States; orcid.org/0000-0002-7873-
1773
Lukasz Wojtas − Department of Chemistry, University of
South Florida, Tampa, Florida 33620, United States
Nicholas Hadler − Department of Chemistry, University of
South Florida, Tampa, Florida 33620, United States
Hao Chen − Department of Chemistry and Environmental
Science, New Jersey Institute of Technology, Newark, New
Jersey 07102, United States; orcid.org/0000-0001-8090-
8593
Figure 2. Derivatization and proposed mechanism.
bearing tertiary carbon (such as 5ba, prepared from internal
alkynes) could be readily reduced to the N−N single bond
product 7d without further reduction of CO (92%). This
example highlights the diverse substitution pattern (two
different aryl groups) of the reporting method and provides a
practical synthesis of substituted hydrazine and amine
derivatives.
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.1c01811
CONCLUSION
■
Notes
In summary, we disclosed herein a divergent gold catalysis for
alkyne trifunctionalization. The overall sequence combined
gold π-activation, vinyl gold nucleophilic addition, and
gold(III) reductive elimination. Aryldiazonium salts were
identified as the effective electrophile and oxidant. Besides
the ability to construct complex molecular motifs within
simple steps, this new method demonstrated a new strategy
to apply vinyl−AuIII as effective nucleophiles for the
construction of new bonds. This new design principle of
gold catalysis could certainly be applied to other gold-
promoted chemical transformations, which is currently under
investigation in our lab.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the NSF (CHE-1665122) and NIH
(1R01GM120240-01) for financial support. This work has
been supported in part by University of South Florida
Interdisciplinary NMR Facility and the Chemical Purification,
Analysis, and Screening (CPAS) Core Facility, The Depart-
ment of Chemistry and the College of Arts and Sciences,
Tampa, Florida. Dedicated to the 100th anniversary of
Chemistry at Nankai University.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.1c01811.
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■
■
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