Solvent-driven C(sp3)-H thiocarbonylation of benzylamine derivatives under catalyst-free conditions

Article abstract of DOI:10.1039/d0gc03832f

Due to the particularity of the thiocarbonyl group (C S bond), only limited C(sp³)-H thiocarbonylation methods, especially efficient and convenient methods, have been developed for the synthesis of thioamides. Inspired by the “solvent-specifici

Full text of DOI:10.1039/d0gc03832f

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Solvent-driven C(sp3)–H thiocarbonylation of
benzylamine derivatives under catalyst-free
Cite this: Green Chem., 2021, 23, 767
conditions†
Received 12th November 2020,
Accepted 4th January 2021
Jingwei Zhou, *a Songping Wang,a Yaoming Lu,b Lamei Li,a Wentao Duan,a
Qi Wang,a Hong Wang*a and Wentao Wei
*
a
DOI: 10.1039/d0gc03832f
rsc.li/greenchem
Due to the particularity of the thiocarbonyl group (CvS bond), hydroxymethyl thiolactam cyclothialidine.3 Thus, the develop-
only limited C(sp3)–H thiocarbonylation methods, especially ment of an efficient and convenient thioamide synthesis
efficient and convenient methods, have been developed for the method is of great methodological and pharmaceutical inter-
synthesis of thioamides. Inspired by the “solvent-specificity-based” est.4 In the past three decades, various thioamide synthesis
design strategy, we discovered a simple, practical and environmen- systems have been investigated, such as sulfur–phosphorus-
tally friendly C(sp3)–H thiocarbonylation of benzylamine sub- type,5 Friedel–Crafts-type,6 Willgerodt–Kindler-type7 and three-
strates for facile thioamide synthesis under catalyst-free con- component-type8 thioamide synthesis. Although very success-
ditions. A diverse array of benzylamine derivatives were tolerated ful, all these methods started from carboxylic acids, nitriles,
by this catalyst-free thiocarbonylation. Furthermore, the (QM) isothiocyanates, aryl aldehydes or aryl ketones, and avoided
computations and well-designed experiments on the reaction direct C(sp3)–H thiocarbonylation. So, limited C(sp3)–H thio-
mechanism revealed that this thiocarbonylation depends on the carbonylation methods have been developed so far. One con-
specific solvent that initially drives this reaction through the inter- ventional C(sp3)–H thiocarbonylation method is the Lawesson
molecular hydrogen atom transfer (HAT). And the following single reagent-dependent thiocarbonylation of amine derivatives9 in
electron transfer (SET) induces the electron-catalyzed C–S bond which the amine was first oxidized to amide and the Lawesson
formation and intramolecular HAT realizing the final establishment reagent or its analogues subsequently transformed the amide
of the CvS bond.
to thioamide (Scheme 1a). However, because it scarcely avoids
One class of non-negligible sulfur-containing groups is the
thiocarbonyl motif (CvS bond) of thioamides, which is attract-
ing increased research attention on account of its excellent
chemical functions in organic chemistry and distinctive bio-
logical activities in medicinal chemistry.1 For chemical func-
tions, the potential in the formation of the C–C bond and
CvC bond, such as the synthesis of jerantinine compound,
has recently been shown convincingly.2 For biological activi-
ties, the distinct positive effect has been shown continuously
in many preclinical and clinical drugs, such as the clinically
applied antineoplastic drug mercaptopurine and hypnotic
drug quazepam, as well as the potential DNA gyrase inhibitor
aInstitute of Clinical Pharmacology, Science and Technology Innovation Center,
Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China.
E-mail: wentao@gzucm.edu.cn, zhoujw@gzucm.edu.cn, zyjw@gzucm.edu.cn
bThe Second Affiliated Hospital of Chinese Medicine, Guangzhou University of
Chinese Medicine, Guangzhou 510405, Guangdong, China
Scheme 1 (a) Conventional Lawesson reagent-dependent C(sp3)–H
thiocarbonylation of amine derivatives. (b) State-of-the-art photometal-
lic-catalyst-mediated C(sp3)–H thiocarbonylation of N-heterocyclic
skeleton. (c) Proposed solvent-driven C(sp3)–H thiocarbonylation of
benzylamine derivatives under catalyst-free conditions.
†Electronic supplementary information (ESI) available: Experimental pro-
cedures, computational methods, Fig. S1 and S2, characterization data, refer-
ences, NMR spectra, molecular coordinates and free energies. See DOI: 10.1039/
d0gc03832f
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the high temperature and produces by-products that are based” design strategy for solvent-driven C(sp3)–H thiocarbo-
difficult to separate, as well as requires the non-economical nylation under catalyst-free conditions (Scheme 1c). In this
oxidants and Lawesson reagent, this method is accompanied strategy, we hypothesized that the DMF solvent could firstly
by the disadvantage of low environmental friendliness.9b Thus, react with the inorganic sulfide to produce the DMF•− species
•−
it is highly desirable to develop an efficient and economical and S3 species (Fig. 1a), and then through HAT and SET the
C(sp3)–H thiocarbonylation method for thioamide synthesis.10
DMF•− species could transform the amine substrate to the
The trisulfur radical anion (S3•−) has been studied for half a necessary iminium ion (Fig. 1d), which subsequently could
•−
century and can be very easily obtained from the inorganic couple with the S3 species to finally form the thioamide
sulfide or elemental sulfur in DMF solvent at room tempera- (Fig. 1b). Since all steps have been available under environ-
•−
ture (Fig. 1a).11 In recent years, some applications of S3
mentally friendly conditions except for the transformation step
species for C–S bond formation have been reported, such as between the amine substrate and iminium ion, our research
the sulfur insertion reactions, providing a brand new perspec- focus in this work was whether or how the DMF•− species
tive to explore the C(sp3)–H thiocarbonylation method for could transform the amine substrate to the iminium ion
thioamide synthesis.12 And indeed, through continuous without
a metal catalyst under environmentally friendly
•−
studies of S3 species, in 2019 Jiang’s group found that the conditions.
•−
iminium ion (B state) readily interacted with the S3 species
To examine the feasibility of our hypothesis, an amine sub-
to form the thioamide under environmentally friendly con- strate of 2-phenyl-1,2,3,4-tetrahydroisoquinoline (1a) was
ditions (Fig. 1b).10e Based on this result, they reported the selected to react with the inorganic sulfide (K2S) in the specific
photometallic-catalyst-mediated C(sp3)–H thiocarbonylation of DMF solvent under very mild conditions (nitrogen atmo-
the N-heterocyclic skeleton (Scheme 1b) in which the photo- sphere, room temperature and 12
h
reaction time).
metallic catalyst of Ru(bpy)3Cl2·6H2O was introduced to trans- Unfortunately, even after the introduction of light (425 nm
form the N-heterocycle to the α-aminoalkyl radical (A state), LED or sunlight), the expected C(sp3)–H thiocarbonylation
which subsequently could undergo single electron transfer reaction did not occur (entries 1–3 in Table 1). This indicated
(SET) affording the necessary iminium ion (B state) to couple that unless some necessary conditions were adopted, the
with the S3•− species (Fig. 1c), and thus realized the thioamide DMF•−
species
seemed
difficult
to
replace
the
synthesis via C(sp3)–H thiocarbonylation.10e Considering that Ru(bpy)3Cl2·6H2O catalyst to transform 1a to the expected
the metal catalyst is usually costly and non-environmentally iminium ion (B state). Our QM calculation15 of HAT between
friendly, a more efficient transformation method from amine the DMF•− species and 1a found that through a 30.93 kcal
to iminium ion without a metal catalyst is highly desirable. In mol−1 energy barrier in kinetics and a −5.72 kcal mol−1 feas-
2016, Ji’s group found that in addition to converting the in- ible energy in thermodynamics (Fig. 1e), the DMF•− species
•−
organic sulfide/sulfur into the S3 species (Fig. 1a), DMF could transform 1a to the α-aminoalkyl radical (A state), which
solvent has another specificity that the produced DMF radical could be further transformed to the iminium ion (B state) via
anion (DMF•−) during the formation of S3 species has the
•−
ability to undergo the hydrogen atom transfer (HAT) in the
sulfur insertion reaction.13 Herein, guided by the above two
Table 1 Reaction optimizationa for our C(sp3)–H thiocarbonylation of
1a
specificities of the DMF solvent and our previous studies of
the amine substrate,14 we developed a “solvent-specificity-
Entry
Sulfur reagent (equiv.)
Temp.
Yieldb
1
2
3
4
5
6
7
8
K2S (2.0)
K2S (2.0)
K2S (2.0)
K2S (2.0)
S (1.0)
S (2.0)
S (3.0)
S (2.0)
S (2.0)
S (2.0)
r.t.
—
—
—
425 nm LED
Sunlight
50 °C
50 °C
50 °C
50 °C
80 °C
90 °C
120 °C
90 °C
47%
32%
58%
56%
71%
75%
70%
—
9
10
11c
12d
13e
S (2.0), O2
S (2.0), BHT
S (2.0), DPPH
90 °C
90 °C
20%
15%
a Reactions were conducted with 1a (0.2 mmol), DMF (2 mL), 12 h,
under a nitrogen atmosphere. b Isolated yield. c Reaction was carried
out under an oxygen atmosphere. d BHT (0.2 mmol) was added.
e DPPH (0.2 mmol) was added.
Fig. 1 (a)–(e) Proposed “solvent-specificity-based” design strategy for
the solvent-driven C(sp3)–H thiocarbonylation.
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SET. We considered that the higher energy barrier of HAT bonylation, our thiocarbonylation could still be effectively
limited the reaction ability of the DMF•− species, and thus, a maintained but with
lower yield of thiocarbonylation
a
50 °C heating step was added (entry 4 in Table 1). Fortunately, product (17% and 31% for acetone and CH3CN, respectively).
a 47% yield of the anticipated product 2-phenyl-3,4-dihydroiso- This indicated that as long as the solvent replacing the DMF
quinoline-1(2H)-thione (2a) was obtained. Based on this suc- solvent has similar specificities with the DMF solvent, our
cessful case, the type and equivalent of sulfur reagent, as well thiocarbonylation can occur. More interestingly, our thiocarbo-
as reaction temperature, oxygen atmosphere and reaction time nylation reaction also showed that the yield of thiocarbonyla-
for our C(sp3)–H thiocarbonylation were optimized (entries tion product (2a) in DMF-like solvents, such as DMA and
4–11 in Table 1). After optimization, the following reaction DMPU, was almost comparable to that in DMF solvent (72%,
conditions were employed: 2.0 equivalents of elemental sulfur, 76% and 70% for DMA, DMPU and DMF, respectively), indicat-
90 °C, nitrogen atmosphere and 12 h reaction time. Overall, ing that our thiocarbonylation was specific to DMF-like sol-
our proposed C(sp3)–H thiocarbonylation reaction could not vents. Meanwhile, compared to previously reported C(sp3)–H
only produce excellent yield (75%), but also is simple, practi- thiocarbonylations,9,10e which usually need the toxic DMF
cal, environmentally friendly and noteworthy in that it does solvent or non-environmentally friendly Lawesson reagent, our
not require any catalysts. Meanwhile, we also investigated the thiocarbonylation to some extent not only included
influence of radical scavengers (BHT and DPPH) on our solvent (DMA), but also adapted to more environmentally
C(sp3)–H thiocarbonylation (entries 12 and 13 in Table 1). It friendly solvent (DMPU), although in the classification of
was revealed that our reaction could be inhibited by radical green solvents16 the toxicity of DMA is as dangerous as that of
scavengers, implicating some radical intermediates formed DMF and the greener DMPU remains problematic in scaling
during thiocarbonylation.
up of applications. To sum up, we can see it indeed was the
Some control experiments were carried out for the verifica- specific DMF-like solvents (DMF, DMPU and DMA) that drove
tion of the solvent dependence (solvent specificity) proposed the C(sp3)–H thiocarbonylation under catalyst-free conditions.
in our hypothesis. As shown in Table 2, taking 1a as an
With the optimal reaction conditions in hand, we then
example, once the DMF solvent was changed to the solvent further explored our C(sp3)–H thiocarbonylation with different
that cannot react with the elemental sulfur to form the solvent types of amine substrates (Scheme 2). For cyclic benzylamines,
radical anion to drive the thiocarbonylation, no yields besides the above-mentioned tetrahydroisoquinoline (1a), iso-
(dioxane, CH3OH, NMP, EtOAc, THF, DCM, HMPA and indoline (1b) also exhibited good reactivity, furnishing the
CH2ClCH2Cl) or only unmeasurable trace yields (toluene and thiocarbonylation product (2b) in 70% and 72% yields in DMF
DMSO) of the expected thiocarbonylation product (2a) were and DMPU solvents, respectively. The non-cyclic benzylamines
detected, suggesting that our thiocarbonylation cannot occur were also considered. For example N,N-dimethyl-1-phenyl-
in the absence of solvent actuation under the optimized reac- methanamine (1c) produced the thiocarbonylation product
tion conditions. Intriguingly, if DMF was replaced by acetone (2c) in a relatively low but acceptable yield (53% in DMF and
or CH3CN which can be similar to DMF as solvent to react 52% in DMPU). For naphthenic amines of piperidine (1d) and
with the elemental sulfur to form the solvent radical anion pyrrolidine (1e), the yields of thiocarbonylation products (2d–
(acetone•− species and CH3CN•− species) to drive the thiocar- 2e) in DMF and DMPU solvents further decreased to trace
amounts. Obviously, the higher the conjugation of the amine
substrate, the more it is tolerated by our C(sp3)–H
thiocarbonylation.
Table 2 Solvent dependence (solvent specificity) of our C(sp3)–H thio-
carbonylation. Isolated yield
We next turned our attention to the substituents in the
benzene rings of 1a to expand the scope of the best tolerated
cyclic benzylamine substrate (Scheme 3). For example, elec-
tron-donating group substitution of 2-methyl (1aa), 3-methyl
(1ab), 4-methyl (1ac), 3,5-dimethyl (1ad) and 4-methoxyl (1ae)
Entry
Solvent (2 mL)
Yield
1
2
3
4
DMF
70%
—
—
Dioxane
CH3OH
NMP
—
5
6
EtOAc
THF
—
—
7
8
9
10
11
12
13
14
15
DCM
—
—
—
Trace
Trace
17%
31%
72%
76%
HMPA
CH2ClCH2Cl
Toluene
DMSO
Acetone
CH3CN
DMA
Scheme 2 C(sp3)–H thiocarbonylation of different types of amine sub-
strates (1a–1e). Only benzylamine derivatives (1a–1c) were tolerated by
our thiocarbonylation. Data: (DMF; DMPU). Isolated yield.
DMPU
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Unfortunately, the electron-donating group substitution of
4-hydroxyl (1ar) and electron-withdrawing group substitution
of 4-nitro (1as) only afforded unmeasurable trace yields of thio-
carbonylation products (2ar–2as), and most of them were not
reacted. In fact, this non-reactivity of hydroxyl and nitro
groups has been reported for many radical reactions.17 We
considered that the hydroxyl and nitro groups may play a role
in scavenging free radicals, thereby inhibiting the occurrence
of our thiocarbonylation. The electron-donating group substi-
tution of methoxyl (1at–1au) and electron-withdrawing group
substitution of bromine (1av–1aw) in the benzene ring of tetra-
hydroisoquinoline in DMPU solvent also afforded the thiocar-
bonylation products (2at–2aw) in comparable yields of 71%,
70%, 75% and 75%, respectively. And similar degree of yields
were also obtained in DMF solvent. Thus, so to speak, most
electron-donating and electron-withdrawing groups main-
tained, even improved, the yield of our thiocarbonylation. In
addition, we also considered the heterocyclic substitution of
the cyclic benzylamine substrate. Similar to N-substituted pyri-
dine (1ax) and 1,6-naphthyridine (1ay), they also provided their
thiocarbonylation products (2ax–2ay) in good yields of 72%
and 65% in DMPU solvent, respectively (corresponding to 72%
and 68% in DMF solvent). Overall, although our thiocarbonyla-
tion reaction is affected by the type of amine substrate, it is
hardly restricted by various substituents for the appropriate
type of amine substrate.
Scheme 3 Substrate scope with respect to the benzylamine derivatives
(1aa–1ay). Both electron-donating and electron-withdrawing groups
were tolerated by our C(sp3)–H thiocarbonylation. Data: (DMF; DMPU).
Isolated yield.
The gram scale reaction was also employed to test the
utility of our C(sp3)–H thiocarbonylation. As shown in
Scheme 4, when substrate 1a was expanded to 5 mmol, a 71%
yield of desired thiocarbonylation product (2a) was isolated,
which was almost as good as the 76% yield of the small
sample experiment. This indicated the potential applications
of our C(sp3)–H thiocarbonylation reaction.
in an N-substituted benzene ring, as well as electron-withdraw-
ing group substitution of 3-chlorine (1af), 4-chlorine (1ag),
3-bromine (1ah), 4-bromine (1ai), 4-nitrile (1aj), 4-acetyl (1ak),
4-benzoyl (1al), 4-methoxycarbonyl (1am) and 4-methylsulfonyl
(1an) in an N-substituted benzene ring, in DMPU solvent they
all afforded the thiocarbonylation products (2aa–2an) in com-
parable yields of 70%–85%. And in DMF solvent their yields of
thiocarbonylation products (2aa–2an) were almost equal to
those in DMPU solvent. The electron-withdrawing group sub-
stitution of 4-carboxyl (1ao) in an N-substituted benzene ring
was also tolerated by our thiocarbonylation but only with 28%
and 47% yields of the thiocarbonylation product (2ao) in DMF
and DMPU solvents, respectively. The electron-withdrawing
group substitution of 4-formyl (1ap) in an N-substituted
benzene ring could directly afford the expected C(sp3)–H thio-
carbonylation product (2ap) in an acceptable yield of 62% in
DMPU solvent. Surprisingly, in DMF solvent the 1ap was not
converted to the desired 2ap, but to another two products,
N,N-dimethylthioamide (1aq, 65% yield) and its thiocarbonyla-
tion product (2aq, 20% yield). We guess that in DMF solvent
the 1ap was first converted to 1aq, and then converted to the
C(sp3)–H thiocarbonylation product (2aq) of 1aq. Further veri-
fication confirmed our guess and found that the 1aq indeed
could afford its thiocarbonylation product (2aq) in yields of
65% and 70% in DMF and DMPU solvents, respectively.
Considering the above experimental results, the first key
question is why the DMF-like solvents could drive our C(sp3)–
H thiocarbonylation under catalyst-free conditions. Based on
the reaction mechanism proposed in Fig. 1, we calculated the
whole reaction free energy profiles15 for the different types of
amine substrates in Scheme 2 (1a–1e) in DMPU solvent. As
shown in Fig. 2, we can see that under the condition that
elemental sulfur and DMPU solvent have reacted to form the
•−
DMPU•− species and S3 species, the DMPU•− species could
react with the substrate (1 state) through the intermolecular
HAT with a high energy barrier (28.63, 30.88, 31.88, 39.89 and
41.09 kcal mol−1 for 1a–1e, respectively) to generate the
α-aminoalkyl radical (A state) and DMPU_H− species. Then,
Scheme 4 5 mmol (1045 mg) scale reaction of our C(sp3)–H thiocar-
bonylation for substrate 1a. After the reaction, DMPU was recycled
through vacuum distillation at 145 °C in 60 mbar, and the crude product
was purified with flash chromatography.
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state) to form the iminium ion (B state), accomplishing the
cycle from the α-aminoalkyl radical (A state) to the thiocarbo-
nylation product (2 state); (2) the simultaneously formed
DMF_H2 species to some extent could improve the inter-
molecular HAT between the substrate (1 state) and DMF•−
species by promoting the right shift of reaction equilibrium,
which could lead more α-aminoalkyl radical (A state) to join in
the above cycle reaction and more DMF_H− species to react
with the HS•2 species produced by the above cycle reaction to
•−
generate the S2 species and DMF_H2 species again to con-
tinue to repeat the above two processes. Thus, our thiocarbo-
nylation process could partition into two stages (Fig. 1): one
was the activation stage in which the DMF•− species activated
the substrate through intermolecular HAT (from 1 state to A
state), and the other was the cycle stage driven by the DMF_H−
species (from A state to 2 state). Obviously, the higher the
thermodynamic feasibility of the activation stage, the easier
Fig. 2 Reaction profiles of 1a–1e in DMPU solvent based on the reac-
tion mechanism in Fig. 1 (mechanistic studies 1).
the obtained α-aminoalkyl radical (A state) would be willing to the occurrence of the subsequent cycle stage, and correspond-
undergo a low endothermic energy (12.43, 11.40, 11.27, 1.77 ingly, the more completely our thiocarbonylation will be
and 2.90 kcal mol−1 for 1a–1e, respectively) to facilely realize carried out. As shown in Fig. 2, from benzylamines (1a–1c) to
the SET and form the expected iminium ion (B state). Finally, naphthenic amines (1d–1e), the thermodynamic energy of the
through the C–S bond formation reaction and following S–S activation stage in DMPU solvent gradually changed from
bond homolysis reaction (induced by the intramolecular HAT) exothermic to endothermic (−8.66, −5.99, −4.27, 6.20 and
also with a high total reaction barrier (25.25, 25.46, 25.39, 6.62 kcal mol−1 for 1a–1e, respectively), accompanied by a
28.59 and 26.90 kcal mol−1 for 1a–1e, respectively), previously gradual decrease in yield of the thiocarbonylation product. A
•−
generated S3 species could interact with the iminium ion (B similar tendency was also found in DMF solvent (−5.72, −2.14,
state) to establish the CvS bond and form the final thiocarbo- 1.74, 8.06 and 8.49 kcal mol−1 for 1a–1e, respectively) as
nylation product (2 state) and HS•2 species whose proton could shown in Fig. S1.† Thus we considered that it was the thermo-
further be transferred to the previously generated DMPU_H− dynamic property of the activation stage that determined the
•−
species, producing the DMPU_H2 species and S2 species specificity of our thiocarbonylation to the benzylamine sub-
with the release of much energy and leading free energy lower strates (1a–1c). A similar explanation could also explain why
than the initial reactant (−28.91, −30.74, −28.20, −27.33 and our thiocarbonylation was specific to the DMF-like solvents
−28.99 kcal mol−1 for 1a–1e, respectively). Clearly, the driving (DMPU, DMF and DMA), as shown in Fig. 3. In addition, our
property of DMPU solvent was mainly reflected in three calculation15 also found that the stability of the C state in the
aspects: (1) DMPU solvent and elemental sulfur reacted to cycle stage may also have an influence on our thiocarbonyla-
•−
form the DMPU•− species and S3 species; (2) under heating tion (Fig. 4 and Fig. S2†). We considered that a stable C state
condition, DMPU•− species and S3•− species overcame the high may cause some side reactions to quench our thiocarbonyla-
energy barrier in kinetics to activate the double C(sp3)–H tion. This was confirmed by 1d and 1e since they have both
bonds through the intermolecular HAT and intramolecular
HAT, respectively; and (3) formed DMPU_H− species during
intermolecular HAT accepted the proton of final produced HS2•
species to push the whole thiocarbonylation reaction to be
exothermic. The above driving property was also reflected in
the DMF solvent based on the free energy profile calculations
for substrates 1a–1e in DMF solvent (Fig. S1†). Thus, due to
the kinetic feasibility that can be achieved by heating and the
thermodynamic feasibility, the DMF-like solvents could drive
the C(sp3)–H thiocarbonylation through simple heating under
catalyst-free conditions.
The next key question is why our C(sp3)–H thiocarbonyla-
tion was specific to the benzylamine substrates (1a–1c) and
DMF-like solvents. By further analysis on the final step of our
thiocarbonylation (the reaction between DMF_H− species and
HS•2 species in Fig. 1) we can deduce two processes: (1) the
Fig. 3 Reaction profiles of 1a in different solvents (DMPU, DMF, DMA,
•−
formed S2 species to some extent could prefer to act as an
acetone and CH3CN) based on the reaction mechanism in Fig.
1
oxidant to participate in the SET of α-aminoalkyl radical (A (mechanistic studies 2).
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Fig. 4 Influence of the C state on our C(sp3)–H thiocarbonylation
(mechanistic studies 3).
the computational stable C state and some experimental by-
products.
Conclusions
In summary, based on the “solvent-specificity-based” design
strategy, we have developed a solvent-driven C(sp3)–H thiocar-
bonylation of benzylamine derivatives, which proceeded
efficiently for thioamide synthesis under catalyst-free, opera-
tionally simple and environmentally friendly conditions. A
wide variety of substituents on the benzylamine substrates
were tolerated by our thiocarbonylation with excellent yields.
Our methodology is worth noting in that it cleverly utilized the
specificities of solvent instead of the property of the previously
reported metal catalyst to drive the C(sp3)–H thiocarbonylation
and got a good result. Given this, further studies on the appli-
cation of solvent specificities are ongoing in our laboratories.
In addition, our thiocarbonylation may play a role in the site-
directed thiocarbonylation since it focuses on the benzylamine
substrate and is almost unaffected by the substituents on the
benzylamine substrate, such as achieving the site-directed
thiocarbonylation of some compounds containing multiple
thiocarbonylation sites.
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Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
This work was supported by the National Science Foundation
of China (81803436 and 21702236) And Guangzhou Science
Technology and Innovation Commission Technology Research
Projects
(201805010005).
We
thank
the
National
Supercomputing Center in Guangzhou for providing the com-
putational resources. We also thank Prof. Ruibo Wu at SYSU
for his help in mechanism analysis.
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