Thioesters as Bifunctional Reagents for 2-Naphthylamine Sulfuracylation

Article abstract of DOI:10.1002/adsc.201900301

An efficient and convenient strategy for the preparation of diaryl sulfides via a Fe-promoted direct sulfuracylation of 2-naphthylamine using thioesters as bifunctional reagents is described. This synthetic strategy features high chemoselectivity, good substrate scope and functional group tolerance. (Figure presented.).

Full text of DOI:10.1002/adsc.201900301

Title: Thioesters as Bifunctional Reagents for 2-Naphthylamine
Sulfuracylation
Authors: Fuhong Xiao, Shanshan Yuan, Dahan Wang, Saiwen Liu,
Huawen Huang, and Guojun Deng
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201900301
Link to VoR: http://dx.doi.org/10.1002/adsc.201900301

10.1002/adsc.201900301
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Thioesters as Bifunctional Reagents for 2-Naphthylamine Sulfuracylation
Fuhong Xiao,a* Shanshan Yuan,a Dahan Wang,a Saiwen Liu,b* Huawen Huang,a Guo-
Jun Denga
aKey Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally
Friendly Chemistry and Application of Ministry of Education, College of Chemistry, XiangtanUniversity, Xiangtan
411105, China. E-mail: fhxiao@xtu.edu.cn.
bCollege of Materials and Chemical Engineering, Hunan City University, Yiyang, Hunan 413000, China.
liusaiwen7@163.com
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
and photoredox catalysis reactions. For example, in
preparation of diaryl sulfides via a Fe-promoted direct 2000, Liebeskind and Srogl reported Pd-catalyzed,
Abstract: An efficient and convenient strategy for the
sulfuracylation of 2-naphthylamine using thioesters as
bifunctional reagents is described. This synthetic strategy
features high chemoselectivity, good substrate scope and
functional group tolerance.
Cu-mediated cross-coupling of thiolesters with
boronic acids to get ketone products (so-called
"Liebeskind-Srogl cross coupling").[9] Since then,
employing thioesters as coupling partner to
synthesize ketones, thioethers or amides has
attracted considerable attention.[10] With the
development of green chemistry, more and more
attention has been paid to efficient atom-economic
reactions. Thioester as a bifunctional reagent could
better embody the characteristic of atomic economy
in green chemistry. In 2008, Kambe reported the
Pt-catalyzed decarbonylative fragmentation of
thioesters with internal alkynes to provide vinyl
sulfides.[11] Miura and Wang reported Rh-catalyzed
Keywords: Thioesters; bifunctional; sulfuracylation; diaryl
sulfides.
Sulfur-containing functional groups are widely
presented in numerous natural products and
bioactive compounds.[1] In particular, organosulfur
compounds have been more and more important in
organic synthesis since they can be used as the
efficient coupling partners or building blocks.
Hence, highly selective activation, cleavage, and
transformation of C-S bonds are a more attractive
and challenging area in organic chemistry.[2] Over
the past few decades, numerous synthetic strategies
have been developed for C–S bond transformations
with transition-metal-catalysis including cross-
couplings of thioethers,[3] thioesters,[4] ketene
dithioacetals,[5] sulfonyl chlorides,[6] and other
diverse organosulfur compounds.[7] However, most
methodologies use only one of the fragments from
C-S bond cleavage for coupling reaction. As a
consequence, the discovery of new fragment
assembling strategy for selective activation and
functionalization of the C–S bond deserves to be
explored.
Thioesters
are
extremely
important
in
pharmaceuticals and bioactive products, such as
thioesters of coenzyme A (CoA), polyketide
synthases (PKSs) and nonribosomal polypeptide
synthetases (NRPKs).[8] Furthermore, thioesters are
versatile synthetic building blocks in cross-
couplings, reductions, decarbonylation, cleavage
Scheme 1 New strategy for synthesis of diaryl sulfides.
1
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10.1002/adsc.201900301
Advanced Synthesis & Catalysis
Table 2. Scope of S-phenyl benzothioate.[a]
C–S/C–N coupling reaction of diazos with
thioester.[12] Recently, Gu and co-workers
developed Pd/Cu-catalyzed ortho C−H acylation
and ipso thiolation of aryl halides with thioesters.[13]
Despite of significant advances, these protocols
largely rely on precious 4d transition metals. In
sharp contrast, the use of less toxic 3d transition
metals as catalyst for C-S bond cleavage and
recombination is rare.[14] Inspired by these elegant
works and as our interest in C−H sulfuration,
herein, we supposed a simple and efficient
functionalization approach of 2-naphthylamine
using thioesters as bifunctional reagents. The
advantages of this reaction system include the first
iron catalysis, high chemoselectivity and good
substrate scope.
Table 1. Optimization of reaction conditions.[a]
Entry
Catalyst
FeCl3
Oxidant
NIS
Solvent
PhCl
PhCl
PhCl
PhCl
PhCl
Yield[b]
50
[a]
1
2
3
4
5
Conditions : 1a (0.2 mmol), 2a (0.4 mmol), Fe2O3 (5
mol%,≥ 99.9%), NIS (2 equiv), PhCl (1 mL), 130 °C, 12 h,
air. [b] 6 mmol.
Fe
NIS
47
Fe(acac)3
Ferrocene
Fe2(SO4)3
NIS
29
NIS
18
Our initial investigation began with 2-
naphthylamine (1a) and S-phenyl benzothioate (2a)
in the presence of FeCl3 and N-iodosuccinimide
(NIS) in chlorobenzene. To our delight, the desired
product 3aa was obtained in 50% yield (Table 1,
entry 1). Encouraged by this result, we screened
various other iron catalysts including iron powder,
Fe(acac)3, ferrocene, Fe2(SO4)3, and Fe2O3 (entries
2-6). Among them, Fe2O3 was proved to be the
most effective catalyst for the coupling reaction,
giving the desired product in 82% yield (entry 6),
whereas ferrocene gave a lower yield (entry 4). The
desired product was not observed when other
oxidants such as tert-butyl hydroperoxide (TBHP),
K2S2O8, NCS, and NBS were used (entries 7-10).
The use of PhI(OAc)2, ICl and molecular iodine did
not show better efficiency, in contast lower yields
were obtained (entries 11-13). Further investigation
of solvents revealed that PhCl demonstrated the
best performance, while DMSO, p-xylene, 1,2-
dichlorobenzene (o-DCB), toluene and 1,4-dioxane
were proved to be unsuitable reaction media
(entries 14-18). As a control experiments, no
reaction was occurred in the absence of any iodide-
containing additives (entry 19). The product 3aa
was obtained in only 20% yield when the reaction
was carried out without iron catalyst (entry 20). We
speculated that the addition of catalytic amount of
Fe2O3 would facilitate the C-S bond cleavage of
NIS
56
6
7
8
Fe2O3
Fe2O3
Fe2O3
NIS
PhCl
PhCl
PhCl
82
0
TBHP
K2S2O8
0
9
Fe2O3
Fe2O3
Fe2O3
NCS
NBS
PhCl
PhCl
PhCl
0
0
10
11
PhI(OAc)2
35
12
13
14
Fe2O3
Fe2O3
Fe2O3
ICl
I2 (1 eq.)
NIS
PhCl
PhCl
40
48
DMSO
trace
15
Fe2O3
Fe2O3
Fe2O3
Fe2O3
Fe2O3
NIS
NIS
NIS
NIS
p-xylene
o-DCB
PhCH3
1,4-dioxane
PhCl
68
57
35
26
0
16
17
18
19
20
NIS
NIS
NIS
PhCl
20
58
60
21[c]
22[d]
Fe2O3
Fe2O3
PhCl
PhCl
[a] Conditions : 1a (0.2 mmol), 2a (0.4 mmol), catalyst (5
mol%), oxidant (2 equiv), solvent (1 mL), 130 °C, 12 h, air.
[b] GC yield.
[c] NIS (1 equiv).
[d] 120 °C.
2
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10.1002/adsc.201900301
Advanced Synthesis & Catalysis
thioesters. Decreasing the amount of NIS or the
Furthermore, to further expand the scope of this
reaction temperature both led to decrease the methodology, the acyl component was also
product yields (entries 21-22). examined (Table 3). The results show that the
With this concurrent functionalization procedure desired product yields were significantly affected
in hand, the substrate scope toward this novel 2- by the alkyl chain length of acyl. Good yields were
naphthylamine sulfuration was then investigated, achieved when the length of acyl chain contains 3
and the results are listed in Table 1. First, we to 5 carbons (5aa-5ac). And the yields were
examined the influence of substituent on the phenyl decreased with the increasing of chain length (5ad-
sulfide ring. The desired product 3aa was isolated 5ah). Moderate to good yields of the target
in 74% yield when the model reaction of 1a and 2a products were generally obtained when other acyl
was carried out under established conditions. substrates with branched chains were used (5ai-
Substrates with electron-donating groups (-CH3, 5ao). Phenyl acetyl substrates produced the
and -OCH3) at the para position of the phenyl corresponding products (5ap and 5aq) with a big
sulfide ring (3ab–3ad) had similar yields except for gap in the yields. In addition, crotonoyl and
3ac in lower yield. Halogen substituents on the benzoyl thioesters can also work with 1a to afford
phenyl sulfide ring were also amenable for this the corresponding products 5ar and 5as in 31% and
sulfuracylation (3ae–3ag). Interestingly, the steric 35% yield, respectively.
hindrance effect of the substituent was not
apparent, whether the substituents were at ortho or substituted anilines such as 3,4-dimethoxyaniline
meta position. For example, when the methoxy was (6a), 2,4-dimethoxyaniline (6b), and 3-
Apart from 2-naphthylamine (1a), other methoxy
located in para (2d), ortho (2k) or meta (2q) methoxyaniline (6c) could also be applied in this
position on the phenyl sulfide ring, the reaction system to provide the corresponding products
corresponding products 3ad, 3ak and 3aq were in moderate yields. It is noteworthy that the
obtained in 77%, 70% and 71% yields, disulfuracylation product 7c was obtained when using
respectively. However, the yield was dramatically 3-methoxyaniline (6c) as the substrate (Table 4).
decreased when the chloro was located at both
Table 4. Scope of anilines.[a]
ortho and meta position (3ah). When S-
(naphthalen-2-yl) ethanethioate (2o) was used, the
desired product 3ao was observed albeit in 40%
yield. Unfortunately, no corresponding product was
obtained when the thioester was changed from S-
aryl ethanethioate to S-alkyl ethanethioate.
Table 3. Scope of the thioester.[a]
[a]
Conditions : 6 (0.2 mmol), 2a (0.4 mmol), Fe2O3 (5
mol%, ≥ 99.9%), NIS (2 equiv), PhCl (1 mL), 130 °C, 12 h,
air.
Further examples of the synthetic applications of
this method are shown in scheme 2. When 3aa was
o
treated with m-CPBA in dichloromethane at 0 C, the
oxidation product sulfoxide 8 was obtained in 60%
yield (Scheme 2, a). Furthermore, the sulfone product
[a]
Conditions : 1a (0.2 mmol), 4 (0.4 mmol), Fe2O3 (5
9 can be obtained in 80% when the temperature was
mol%, ≥ 99.9%), NIS (2 equiv), PhCl (1 mL), 130 °C, 12 h,
o
raised to 50 C (Scheme 2, b). Cyclization of the
air. [b] 30 mol% of Fe2O3 was used.
diaryl
sulfides
were
exemplified
using
paraformaldehyde as the carbon source promoted by
BF3·Et2O, which afforded the seven-membered ring
3
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10.1002/adsc.201900301
Advanced Synthesis & Catalysis
products in good yields (Scheme 2, c). The product N-(naphthalen-2-yl)acetamide 1a' (detected by GC-
10a was obtained in 62% yield when 3aa was used MS) with 1,2-diphenyldisulfane 2aa did not produce
as substrate. The yields of cyclization products 10b the corresponding product (Scheme 3, a). While 4-
and 10c were slightly increased when 3ab and 5ac methylbenzenethiol can react with N-(naphthalen-2-
were used as substrates. When N-(4,5-dimethoxy-2- yl)acetamide 1a' to produce the corresponding
(phenylthio)phenyl)acetamide (7a) was used, the product 3ab in 65% yield. The similar yield of 3ab
seven-membered ring product 10d was observed in was obtained without Fe2O3. But no desired product
72% yield. This reaction was initiated by the was obtained in absence of NIS (Scheme 3, b). The 1-
formation of an imide ion and then electrophilic (p-tolylthio)naphthalen-2-amine 3ab' (detected by
addition with the benzene ring to form a 7-membered GC-MS) can be acylated by 1-acetylpyrrolidine-2,5-
ring (Pictet–Spengler Reaction).[15]
dione to form corresponding amides 3ab in 78% yield.
And this reaction can be carried out smoothly without
iron or NIS (Scheme 3, c). Trace yield of desired
product 3aa was obtained when 1-iodonaphthalen-2-
amine 2aa' was used as a substrate with S-phenyl
ethanethioate under standard conditions (Scheme 3, d).
This result indicates the products are not generated
via sequential transformation involving ortho-
iodination, acylation with the thioesters. The time-
dependent change of the contained products (3aa,
3aa' and 1a') during the reaction has been analyzed
(see SI, Table S1). These results indicate this reaction
probably involves two pathways. In the first way,
naphthylamine is thioetherified to form 2-aminodiaryl
sulfide,[16] which can be acylated to synthesize the
corresponding products (Scheme 4, path a). In the
second way, naphthylamine was acylated to form
amides and then sulfided to synthesize the
corresponding products (Scheme 4, path b).
Unfortunately, the exact reaction mechanism of
Fe2O3 facilitate the C-S bond cleavage of thioesters
is still not clear at this stage.
Scheme 2. Application of products.
Scheme 4. Plausible mechanism.
In summary, we have reported an efficient
sulfuracylation reaction of 2-naphthylamine with
thioesters. In this strategy, thioesters were used as
bifunctional reagents, and C-S/C-N bonds were
formed with high chemoselectivity. Moreover, the
broad functional group tolerance makes this method
Scheme 3. Control experiments.
In order to elucidate the reaction mechanism, more
control experiments were carried out. The reaction of
4
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10.1002/adsc.201900301
Advanced Synthesis & Catalysis
2018, 20, 44; d) C. Liu, M. Szostak, Chem.
Commun. 2018, 54, 2130.
attractive for the synthesis of highly functionalized
diaryl sulfides.
[5] For selected examples, see: a) K. Murakami, H.
Yorimitsu, A. Osuka, Angew. Chem. Int. Ed. 2014
,
53, 7510; b) Q. Wang, X. Yang, P. Wu, Z. Yu, Org.
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Experimental Section
General procedure
[6] For selected examples, see: a) S. R. Dubbaka, P.
Vogel, J. Am. Chem. Soc. 2003, 125, 15292; b) C.
A 10 mL oven-dried reaction vessel was charged with
Fe2O3 (1.6 mg, 0.01 mmol), NIS (90 mg, 0.4 mmol),
2-naphthylamine (1a, 28.6 mg, 0.2 mmol), S-phenyl
ethanethioate (2a, 54 μL, 0.4 mmol), and PhCl (1 mL)
under air. The sealed reaction vessel was stirred at
M. R. Volla, P. Vogel, Angew. Chem. Int. Ed. 2008
,
47, 1305; c) G.-B. Deng, Z.-Q. Wang, J.-D. Xia, P.-
C. Qian, R.-J. Song, M. Hu, L-B. Gong, J.-H. Li,
Angew. Chem. Int. Ed. 2013, 52, 1535; d) S. K.
Pagire, A. Hossain, O. Reiser, Org. Lett. 2018, 20,
648.
o
130 C for 12 h. After cooling to room temperature,
[7] For selected examples, see: a) X. Zhou, J. Luo, J.
Liu, S. Peng, G. J. Deng, Org. Lett. 2011, 13, 1432;
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c) F.-L. Yang, X.-T. Ma, S.-K. Tian, Chem. Eur. J.
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the reaction was diluted with ethyl acetate (5 mL).
The residue was purified by column chromatography
on silica gel (petroleum ether/ethyl acetate = 10:1) to
yield the desired product 3aa as white solid (43.3 mg,
74% yield), mp = 129-131 °C. Rf = 0.45 (10:1 =
petroleum ether/EtOAc).
Acknowledgements
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Supported by the National Natural Science Foundation of China
(21502160, 21871226 and 21572194), the Collaborative
Innovation Center of New Chemical Technologies for
Environmental Benignity and Efficient Resource Utilization.
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5
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10.1002/adsc.201900301
Advanced Synthesis & Catalysis
COMMUNICATION
Thioesters as Bifunctional Reagents for 2-
Naphthylamine Sulfuracylation
Adv. Synth. Catal. Year, Volume, Page – Page
Fuhong Xiao,a* Shanshan Yuan,a Dahan Wang,a
Saiwen Liu,b* Huawen Huang,a Guo-Jun Denga
6
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