Tungsten-Catalyzed Transamidation of Tertiary Alkyl Amides

Article abstract of DOI:10.1021/acscatal.1c01840

Transamidation has recently emerged as a straightforward and convenient means to diversify amides. However, the kinetically and thermodynamically demanding transamidation of notoriously robust, fully alkyl-substituted tertiary amides still remains a longstanding challenge. Here, we describe a method for the activation of tertiary alkyl amides to streamline transamidation using simple tungsten(VI) chloride as a catalyst and chlorotrimethylsilane as an additive. The highly electrophilic and oxophilic tungsten catalyst enables the selective scission of a C-N bond of tertiary alkyl amides to effect transamidation of a myriad of structurally and electronically diverse tertiary alkyl amides and amines. Mechanistic study implies that the synergistic effect of the catalyst and the additive could pronouncedly induce the nucleophilic acyl substitution of tertiary alkyl amide with amine to realize transamidation.

Full text of DOI:10.1021/acscatal.1c01840

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Tungsten-Catalyzed Transamidation of Tertiary Alkyl Amides
Fang-Fang Feng, Xuan-Yu Liu, Chi Wai Cheung,* and Jun-An Ma*
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ABSTRACT: Transamidation has recently emerged as a straight-
forward and convenient means to diversify amides. However, the
kinetically and thermodynamically demanding transamidation of
notoriously robust, fully alkyl-substituted tertiary amides still
remains a longstanding challenge. Here, we describe a method
for the activation of tertiary alkyl amides to streamline trans-
amidation using simple tungsten(VI) chloride as a catalyst and
chlorotrimethylsilane as an additive. The highly electrophilic and
oxophilic tungsten catalyst enables the selective scission of a C−N bond of tertiary alkyl amides to effect transamidation of a myriad
of structurally and electronically diverse tertiary alkyl amides and amines. Mechanistic study implies that the synergistic effect of the
catalyst and the additive could pronouncedly induce the nucleophilic acyl substitution of tertiary alkyl amide with amine to realize
transamidation.
KEYWORDS: transamidation, C−N activation, tertiary alkyl amide, amide, tungsten catalysis
transamidation of tertiary amides is most challenging owing to
their steric bulkiness around the C−N bond and the lack of an
activation site on the nitrogen atom.10 Current transamidation
strategies rely on the use of electronically or sterically biased
tertiary amides, including small-sized dimethylformamide and
dimethylacetamide11 (Scheme 1b-i), activated benzamides and
N-aryl amides10,12 (Scheme 1b-ii), and unconventional twisted
amides6h,13 (Scheme 1b-iii), which either reduce the activation
barriers or destabilize ground-state energies to enable trans-
amidation. Fully alkyl-substituted tertiary amide, however, is
deemed to be the most robust and chemically stable amide, as
dictated by its formally planar architecture, highest C(acyl)−N
rotation energy, and lowest carbonyl electrophilicity.14 The
electron-donating nature of the three alkyl moieties probably
further mitigate the reactivity of tertiary alkyl amides toward
oxidative addition or nucleophilic acyl substitution, the two
characteristic amide C−N cleavage patterns in transamidation.
Whereas Stahl, Gellman, and co-workers engaged Al-amido7c
and Zr-amido7d complexes to catalyze the transamidation of
tertiary alkyl amides (Scheme 1b-iv, top), the formation of an
equilibrium mixture of amides and limited substrate scope
remain unaddressed. Furthermore, transamidation of tertiary
alkyl amides with less nucleophilic aromatic amines is an uphill
reaction,5 further hampering the general utility of trans-
amidation of tertiary amides in organic synthesis.
1. INTRODUCTION
Amides,1 including fully alkyl-substituted tertiary amides (i.e.,
tertiary alkyl amides2 (Scheme 1a)), are prevalent chemical
feedstocks and omnipresent structural motifs in natural
products, pharmaceuticals, and agrochemicals. Notwithstand-
ing the exceeding robustness of an amide C−N bond,3−5
amides are attractive compounds for chemical transformations
owing to their abundance, versatility, and stability. Over the
past decade, the amide C−N bond cleavage has been efficiently
achieved by harnessing suitable catalysts and activation
protocols, offering a valuable synthetic disconnection for
chemical transformations.6 Among these, a transamidation
reaction has emerged as a reliable route for amide
diversification.4,6g,h Whereas amides are most commonly
accessed via the amidation of carboxylic acids, transamidation
could be a more striking synthetic alternative in chemical and
industrial settings: (1) transamidation is a more straightfor-
ward and telescoped strategy to diversify amides, obviating the
multistep practice via amide hydrolysis, activation, and
coupling steps that can be incompatible with sensitive
functional groups; (2) when amide feedstocks are achievable
or more economic than the acid counterparts, transamidation
is more expedient or cost effective for amide production; and
(3) transamidation represents a valuable synthetic handle to
upcycle the less potent or unused amides to other variety of
amides of interest in drug and agrochemical discoveries.
Transamidation has been inherently challenging owing to
the kinetically unfavorable and typically thermoneutral trans-
formation governed by the stability and robustness of an amide
C−N bond.3−5,7 While the general transamidation of primary8
and secondary9 amides could be driven by the formation of
ammonia gas or by preactivation of the amide C−N bonds, the
Received: April 22, 2021
Revised: May 18, 2021
Published: June 2, 2021
https://doi.org/10.1021/acscatal.1c01840
© 2021 American Chemical Society
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Scheme 1. Development of General Transamidation of Tertiary Alkyl Amides
Given the ubiquity of diversely functionalized tertiary alkyl
amides and amines in chemical feedstocks, biologically active
molecules, drugs, and agrochemicals, a unified transamidation
method based on these two functionalities would offer an
appealing and practical toolkit to expediently broaden the
spectrum of amides. As inspired by the remarkable electro-
philicity and oxophilicity of tungsten(VI) chloride (WCl6) that
is capable of facilely activating the carbonyl groups of
carboxylic acids and their derivatives for chemical trans-
formations,15−17 we hypothesized that such a W-mediated
activation strategy would be viable to activate the most robust
tertiary alkyl amides to trigger transamidation. Herein, we
describe the development of a modular transamidation method
based on abundant tungsten18 as a catalyst (Scheme 1b-iv),
bottom). A wide range of variegated tertiary alkyl amides and
amines, particularly aromatic amines, can be employed to offer
new amides. The utility of this protocol is showcased by the
shortened and upcycling routes to access existing or novel
drugs and agrochemicals.
2. RESULTS AND DISCUSSION
2.1. Reaction Optimization. To testify the hypothesis, we
employed N,N-diethyl 4-phenylbutanamide A1 and aniline B1
as model substrates to study the transamidation (Table 1).
Chlorotrimethylsilane (TMSCl) was utilized as a Lewis acid
additive to activate amides as well as for transformations.19
The use of 20 mol % WCl6 in association with a
phenanthroline ligand (L1) as a catalytic system and TMSCl
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Al, Fe, Zr) or alternative group VI metals (e.g., MoCl5) did not
catalyze this reaction (entries 2−5 and Table S1 in the
Supporting Information (SI)). Likewise, lower yields were
obtained when other nitrogen and phosphine ligands were
used (entry 6 and Table S2 in the SI). When WCl6 or L1 was
omitted, the product formations were negligible (entries 7 and
8), revealing that the L1-ligated W complex likely serves as a
catalyst. In the absence of TMSCl, the transamidated product
1a was formed in a 20% yield, suggesting that TMSCl is indeed
requisite for amide activation (entry 9). The optimal
transamidation conditions, upon meticulous screening, were
identified to give amide 1a in a 90% yield, involving the use of
1.5 equiv of aniline and TMSCl, 15 mol % WCl6, 30 mol % L1,
and reaction temperature of 140 °C (entry 10 and Table S3 in
the SI).
Table 1. Optimization of Catalytic Transamidation of
Tertiary Alkyl Amide
a
2.2. Scope of Transamidation. The transamidation
protocol proved to be general. A vast number of substituted
and functionalized primary aromatic and aliphatic amines
(B1−B35) could be employed to react with N,N-diethyl-4-
phenylbutanamide A1 to afford the corresponding amides 1a−
1ai (Scheme 2a), irrespective of the numbers, positions, and
electronic and steric properties of the substituents. It is worth
noting that anilines containing protic hydroxy (1i) and
carboxylic acid (1q) groups and other functional groups
prone to nucleophilic substitution or addition with amines
[fluoro (1j, 1k), chloro (1l), bromo (1m, 1n), keto (1o), ester
(1p), and nitrile (1t)] were all tolerated without noticeable
diminishment in yields. Naphthyl (1w, 1x) and heterocyclic
amines (1y−1ac) were also suitable reaction substrates.
Interestingly, the aniline moiety reacted solely without
engaging indolyl N−H (1aa), demonstrating the superior
a
Reaction conditions: A1 (0.2 mmol, 1 equiv), B1 (0.6 mmol, 3
equiv), WCl6 (0.04 mmol), L1 (0.048 mmol), TMSCl (0.6 mmol),
NMP (2 mL), an argon atmosphere, 130 °C, and 36 h. Isolated
yield. A1 (1 equiv), B1 (1.5 equiv), WCl6 (15 mol %), L1 (30 mol
b
c
%), TMSCl (1.5 equiv), and 140 °C.
as an additive was feasible, effecting the transamidation in a N-
methylpyrrolidone (NMP) solvent at 130 °C to give the
transamidated product 1a in a 68% yield (entry 1). Various
Lewis acid metals previously employed in transamidation (e.g.,
a b
,
Scheme 2. Scope of Amines in Transamidation of Tertiary Alkyl Amides
a
b
All reactions were conducted based on 0.5 mmol tertiary amide substrates A. Reaction based on 0.2 mmol A1.
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a
Scheme 3. Scope of Tertiary Alkyl Amides in Transamidation
a
All reactions were conducted based on 0.5 mmol tertiary amide substrates A.
chemoselectivity for transamidation. The results showcased the
unprecedented broad scope of aniline derivatives in trans-
amidation with tertiary alkyl amides. Additionally, acyclic and
cyclic primary aliphatic amines could also be employed for
transamidation to form the corresponding amides 1ad−1ai,
wherein the eminently bulky tert-butyl amine remained
reactive to afford the product 1ai in a 40% yield. The more
bulky secondary amine substrates, such as N-methyl anilines
and N,N-dialkyl amines (B36−B39, Scheme 2b), could
participate in the transamidation with N,N-dimethyl 4-
phenylbutanamide A2 as well to give the corresponding
amides 1aj−1am in 38−78% yields.
Next, we studied the scope of tertiary alkyl amides. When
the C-alkyl skeletons of amides (A3−A18, Scheme 3a) were
substituted with primary, secondary, and tertiary alkyl groups,
the transmidation proceeded smoothly to furnish amides 1an−
1bc in good to excellent yields. Likewise, the functional groups
on amides, such as chloro (A9), bromo (A10), alkene (A11),
and ester (A12), remained intact without reacting with amines.
It is worth noting that tertiary amide derived from
inflammatory drug indomethacin (A19) underwent the
transamidation chemoselectively to give 1bd without interfer-
ing with the more electron-deficient N-acyl indolyl amide
linkage. Cinnamide and benzamide, a class of activated amides,
were also suitable substrates in this manifold (A20 and A21).
Furthermore, the steric pattern of N-substitutions on tertiary
amides displayed an unmeasurable effect on transamidation
(Scheme 3b). Tertiary amides derived from symmetric or
unsymmetric N-methyl (A2), -propyl (A22), -butyl (A23),
-benzyl (A24), -isopropyl (A25), and -tert-butyl (A26) amines,
as well as pyrrolidine (A27) and piperidine (A28), collectively
reacted smoothly to afford the transamidated products in
generally high yields. As expected, the activated N-aryl tertiary
amide (A29) also transamidated equally well.
Taken together, this W-catalyzed transamidation protocol is
general, tolerates wide-ranging tertiary alkyl amides and
amines, and is insensitive to the electronics and sterics of the
reaction substrates to achieve amide diversification.
2.3. Synthetic Utility. Transamidation is still an under-
represented reaction in pharmaceutical and agrochemical
settings compared with the condensation reaction of carboxylic
acids with amines. Thus, we sought to explore the potential
utility of this transamidation for the synthesis of biologically
active molecules. Piperine-derived amides have shown
promising activities in medicinal chemistry, as exemplified by
the free radical scavenger and α-glucosidase inhibitor 2a20 as
well as the antianxiolysis agent 2b21 (Scheme 4a). Previously,
they were prepared via the hydrolysis of piperine to piperic
acid followed by the subsequent activation and coupling with
amine, or alternatively, by subjecting the commercially more
costly piperic acid to amidation. Our protocol directly
harnessed the inexpensive piperine for transamidation to
access 2a and 2b in 60% and 48% yields, respectively,
providing a step-economical and cost-efficient route for drug
synthesis.
Recently, Maulide and co-workers employed readily
available tertiary alkyl amide 3 to access a fluorinated variant
of an antidepressant drug citalopram22 (Scheme 4b). Likewise,
we were able to engage 3 in transamidation with various
anilines and alkylamines to afford the citalopram variants 4a−
4c. Zolpodem, a hypnotic drug, could also be transformed to
an aniline-derived variant 5 (Scheme 4c). These amide drug
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a b
,
Scheme 4. Synthetic Utility of Tungsten-Catalyzed Transamidation
a
b
All reactions were conducted based on 0.5 mmol tertiary amide substrates. WCl6 (20 mol %) and L1 (40 mol %) were used.
variants could be readily accessible for biological study. The
transamidation was also amenable for gram-scale synthesis of
4a in an 80% yield without remarkable erosion of the yield,
implicating the possible utility in process chemistry.
Furthermore, this transamidation could find use in the
agrochemical industry, offering a straightforward route to
convert the synthetic intermediate 9 to the herbicide 1024 in a
55% yield (Scheme 4e). Previously, 10 was obtained via
hydrolysis, chlorination, and amidation of 9. In transition-
metal-catalyzed reactions, 8-aminoquinoline has emerged as a
versatile ancillary to direct the chemo- and regioselective
transformations of carboxylic acids.25 This transamidation
protocol permitted the direct installation of an 8-amino-
quinolyl group into both tertiary alkyl (A1 and A2) and
aromatic (A21) amides to form 11a and 11b, respectively
(Scheme 4f), offering an alternative potential disconnection
strategy in oriented C−H functionalization. Such a dis-
connection approach also provided access to benzamide 12
based on N,N-dimethyl benzamide en route to the hyper-
lipidaemia drug bezafibrate26 (Scheme 4g).
In drug discovery, only several amides are eventually
employed as the most potent drugs upon screening a vast
number of structurally analogous amides. The one-step
upcycling of less potent amides to other novel amide
candidates would aid in speeding up the drug discovery
process and minimizing the chemical waste generation,
especially when the preparation of amide precursors is
nontrivial. For instance, N-methoxy-N-methyl-2-phenoxyace-
tamide 6 is a potent drug-like molecule for treatment of
hypnosis, whereas N,N-diethylacetamide 7 is a less potent
congener23 (Scheme 4d). Under our tranamidation protocol, 7
reacted with N-methyl-4-anisole to obtain an aryl amide
analogue 8a. Amine drugs, procaine and aminoglutethimide,
could also be incorporated into 7 to form the drug variants 8b
and 8c. The results demonstrated the potential utility of
transamidation in industrial upcycling.
2.4. Mechanistic Investigation. Oxophilic WCl6 could be
successively hydrolyzed in the presence of residual water in a
reaction system to form tungsten oxytetrachloride (WOCl4),
tungsten dichloride dioxide (WO2Cl2), and tungsten trioxide
(WO3);27 meanwhile, electron-deficient WCl6 can be reduced
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Scheme 5. Probing the Reactivity of Viable W Species for Transamidation
by amides,16,17,28 amines,29 and/or ligand L127 to form
tungsten(V) or tungsten(IV) species (Scheme 5a). To probe
the formation of the proposed W species, we studied the
stoichiometric reaction based on an equimolar ratio of WCl6
and L1 in dichloromethane under ambient conditions. In the
presence of an equivalent of aniline, a WVI(phen)(O)2Cl2
complex (C1) was formed (Figure S1 in the SI). In contrast,
when an equivalent of tertiary amide A1 was added, the W(VI)
center was further reduced to give a WV(phen)(O)Cl3 complex
(C2, Figure S2 in the SI). The formation of both C1 and C2
complexes were unambiguously identified by X-ray crystallo-
graphic analysis. The expected WVI(phen)Cl6 (C1′) and
WV(phen)Cl5 (C2′) were not observed, indicating the
propensity of W complexes toward hydrolysis.27 The observed
oxygenation and reduction of WCl6 suggested that both
hydrolysis and reduction WCl6 are feasible in the course of
transamidation.
(Scheme 5c). All W species were able to catalyze the
transmidation to give the desired product 1a in 52−90%
yields, again in line with the Lewis acidity of W species. It is
worth noting that the least reactive tungesten-oxo complexes
WO2Cl2 and WO3 saliently promoted the reaction yields to
over 50% in the presence of TMSCl. We surmised that one of
the crucial roles of TMSCl is to act as an oxo scavenger of
possibly formed tungsten-oxo complexes,30 regenerating the
more labile tungsten polychlorides to sustain the productive
transamidation (Scheme 5d). Given the observed reactivity
pattern of the W species, we speculated that WCl6 is likely the
predominant catalyst to mediate the transamidation, in
association with limited W(O)Cl4-, WCl5-, and WCl4-catalyzed
transmidation.
To identify whether the transamidation is driven by a radical
mechanism, an equivalent of butylated hydroxytoluene (BHT)
was added as a radical trap in the model reaction (Scheme 6a).
The product 1a was formed in a 70% yield without remarkable
diminishment of the yield, while no radical-trapped organic
species was detected. We speculated that radical organic
intermediates are not involved in transamidation. Subse-
quently, the pattern of C−N activation of tertiary amide was
evaluated. First, we proposed that amine initially reacts with
TMSCl to give N,N-bis(trimethylsilyl)amine, which would
react with WCl6 to give a W-imido or W-amido complex31 to
mediate the transamidation (Figure S4 in the SI). Only a trace
of 1a was formed when N,N-bis(trimethylsilyl)aniline 13 was
subjected to transamidation (Scheme 6b), revealing that N-
Next, we examined the reactivity of the proposed W species
based on their stoichiometric transamidation reaction with
tertiary amide A1 in the absence of TMSCl (Scheme 5b).
Hinging on the yields of transamidation as the indicator of
reactivity, the reactivity of transamidation is essentially
consistent with the Lewis acidity of W species (WCl6
>
W(O)Cl4 > WO2Cl2 > WO3; WCl6 > WCl5 > WCl4). A similar
reactivity pattern was displayed as well when 25 mol % WCl6,
W(O)Cl4, and WO2Cl2 was employed (Figure S3 in the SI).
Subsequently, the catalytic reactivity of the W species under
otherwise identical transamidation conditions was examined
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Scheme 6. Mechanistic Insights into Transamidation
silyl-substituted amine could not be involved in trans-
amidation. Second, we proposed the transamidation via the
W-mediated amide CO scission16 (Figure S5 in the SI),
wherein the Vilsmeier salt (Int-1) may also be involved as an
intermediate. This reaction pathway would afford the amino-
substituted iminium salt (Int-2), which, upon hydrolysis in
workup, furnishes the amide product. If this mechanism was
involved, 18O-enriched amide would be formed after hydrolysis
with 18O-water. A control experiment demonstrated that such
an 18O-labeled amide product (18O-1a) was not formed but
only unlabeled 1a (Scheme 6c, top), indicating that the amide
oxygen remains intact throughout transamidation. Further-
more, Vilsmeier salt 14 derived from A1 did not react with
aniline to give the amide product (Scheme 6c, bottom),
precluding its formation for transamidation. Finally, we
proposed the trimethylsiloxy-substituted iminium salt (Int-3)
as the reaction intermediate, which could be generated via the
O-trimethylsilylation of tertiary alkyl amide with TMSCl32
(Figure S6 in the SI). The trimethylsiloxy iminium salt 15,
which was formed in situ from A1 and trimethylsilyl
trifluoromethanesulfonate (TMSOTf),33 reacted with aniline
to give only a trace of product 1a, even when a WCl6 catalyst
was added (Scheme 6d). Transamidation via the intermediacy
of Int-3 is also unlikely.
tungsten catalyst activates the amide bond of tertiary alkyl
amide A to form a cationic O-bound W-iminium species Int-4,
wherein TMSCl could serve as a Lewis acid to expedite the
process. Int-4 is highly electron-deficient, thereby promoting
the nucleophilic addition of amine B to form the tetrahedral
intermediate Int-5. The proton is then shifted from B to the
nitrogen of A to give the intermediate Int-6, which is
particularly favorable when a more protic aromatic amine or
primary alkylamine undergoes transamidation. Subsequently,
TMSCl presumably aids in the elimination of more basic
dialkyl amine to form Int-8, in concert with the formation of
the W-iminium species Int-7. Eventually, Int-7 splits to give
the transamidated product and the W complex for a
subsequent catalytic cycle. To gain further mechanistic insight,
the competitive transamidation among tertiary (A1), secon-
dary (A30), and primary (A31) alkyl amides was studied,
indicating that tertiary amide underwent transamidation more
readily than secondary and primary amides (Scheme 7b). We
rationalized that the transamidation of tertiary amide involves
the putative formation of cationic Int-4 that strongly favors
amine addition; on the contrary, the transamidation of
secondary and primary amides presumably involves the neutral
imine Int-9 (Scheme 7a) that is less prone to amine attack. We
postulated that the synergistic effect of the tungsten catalyst
and TMSCl pronouncedly lowered the activation barrier of the
transamidation reaction. Furthermore, the use of slightly
excessive amine B (1.5 equiv) and the stronger dipole
interaction between TMSCl and dialkyl amine in form of
Based on experimental evidence, we proposed a plausible
transamidation mechanism (Scheme 7a). WCl6 coordinates
with L1 to form ligated tungsten catalysts, which could be
chlorinated W(VI), W(V), and W(IV)-based species. The
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Scheme 7. Plausible Mechanism of W-Catalyzed Transamidation
Int-834 probably drive the reaction. Consequently, the overall
reaction rate is promoted both kinetically and thermodynami-
cally to furnish the transamidated products in generally good
to high yields.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acscatal.1c01840.
■
sı
Experimental details, screening of catalyst and control
experiments; screening of ligands; formation of
WVI(phen)(O)2Cl2 (C1); formation of WV(phen)(O)-
Cl3 (C2); transamidation via the intermediacy of
trimethylsilyoxy imine species; competition experiments
among tertiary, secondary and primary amides; probing
the reactivity of viable W species; and spectral data of all
compounds (PDF)
3. CONCLUSIONS
In summary, we have demonstrated that the use of tungsten-
phenanthroline complexes and a chlorotrimethylsilane additive
enable the catalytic transamidation of intrinsically robust
tertiary alkyl amides, tolerating a diverse array of tertiary alkyl
amides and amines for amide diversification. Furthermore, this
method telescopes the access of amide drug and agrochemical
molecules, provides handles for upcycling of tertiary amide
drugs, and offers an alternative disconnection in chemical
elaborations. Amide is a privileged structure in a broad
spectrum of research fields. We anticipate that this trans-
amidation manifold would be applicable in speeding up amide
diversification for organic synthesis, particularly streamlining
the drug discovery processes.
AUTHOR INFORMATION
Corresponding Authors
■
Chi Wai Cheung − Department of Chemistry, Tianjin Key
Laboratory of Molecular Optoelectronic Sciences, Frontiers
Science Center for Synthetic Biology (Ministry of Education),
and Tianjin Collaborative Innovation Centre of Chemical
Science & Engineering, Tianjin University, Tianjin 300072,
P. R. China; Joint School of National University of Singapore
and Tianjin University, International Campus of Tianjin
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University, Fuzhou 350207, P. R. China; orcid.org/0000-
0003-4415-0767; Email: zhiwei.zhang@tju.edu.cn
Jun-An Ma − Department of Chemistry, Tianjin Key
Laboratory of Molecular Optoelectronic Sciences, Frontiers
Science Center for Synthetic Biology (Ministry of Education),
and Tianjin Collaborative Innovation Centre of Chemical
Science & Engineering, Tianjin University, Tianjin 300072,
P. R. China; Joint School of National University of Singapore
and Tianjin University, International Campus of Tianjin
University, Fuzhou 350207, P. R. China;
Email: majun_an68@tju.edu.cn
Authors
Fang-Fang Feng − Department of Chemistry, Tianjin Key
Laboratory of Molecular Optoelectronic Sciences, Frontiers
Science Center for Synthetic Biology (Ministry of Education),
and Tianjin Collaborative Innovation Centre of Chemical
Science & Engineering, Tianjin University, Tianjin 300072,
P. R. China
Xuan-Yu Liu − Department of Chemistry, Tianjin Key
Laboratory of Molecular Optoelectronic Sciences, Frontiers
Science Center for Synthetic Biology (Ministry of Education),
and Tianjin Collaborative Innovation Centre of Chemical
Science & Engineering, Tianjin University, Tianjin 300072,
P. R. China
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Complete contact information is available at:
https://pubs.acs.org/10.1021/acscatal.1c01840
Author Contributions
This manuscript was written through the contributions of all
authors.
Notes
The authors declare no competing financial interest.
́
́
(8) Markovic, M. K.; Markovic, D.; Laclef, S. Amide synthesis by
transamidation of primary carboxamides. Synthesis 2020, 52, 3231−
3242.
ACKNOWLEDGMENTS
■
The authors thank the National Key Research and Develop-
ment Program of China (No. 2019YFA0905100), the National
Natural Science Foundation of China (Nos. 21772142,
21971186, and 21961142015), the Tianjin Municipal Science
& Technology Commission (20JCYBJC00900), and TJU
(start-up grant) for financial support. They also thank Xue-
Qi Wang (TJU) and Zhe Feng (TJU) for assistance in the
preparation of reaction substrates and the study of the reaction
scope. They are also grateful to Professor Xinsheng Lei of
Fudan University for his gift of Zolpidem.
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