FeCl3-Catalyzed Regio-Divergent Carbosulfenylation of Unactivated Alkenes: Construction of a Medium-Sized Ring

Article abstract of DOI:10.1021/acs.joc.8b01621

A FeCl₃-catalyzed regio-divergent carbosulfenylation of unactivated alkenes with electrophilic N-sulfenophthalimides has been developed. This protocol provides a straightforward and efficient access to various medium-sized rings, especially strained 7- and 8-membered carborings with a sulfur atom attached. The endo/exo selectivity in the reaction depends on the atom number of the chain between arene and alkene. Broad substrate scope, high yields, and gram-scale synthesis exemplified the utility and practicability of this protocol. In addition, this methodology can be extended to the carboselenylation of isolated alkenes.

Full text of DOI:10.1021/acs.joc.8b01621

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Article
FeCl3-Catalyzed Regio-Divergent Carbosulfenylation of
Unactivated Alkenes: Construction of Medium-Sized Ring
Leiyang Lv, and Zhiping Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01621 • Publication Date (Web): 16 Aug 2018
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FeCl3-Catalyzed Regio-Divergent Carbosulfenylation of Unactivated Alkenes:
Construction of Medium-Sized Ring
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Leiyang Lv*†,‡ and Zhiping Li*‡
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†The State Key Laboratory of Applied Organic Chemistry, Lanzhou University 222 Tianshui Road, Lanzhou, Gansu 730000, China
‡Department of Chemistry, Renmin University of China, Beijing 100872, China
lvleiyang2008@ruc.edu.cn; zhipingli@ruc.edu.cn
Abstract: A FeCl3-catalyzed regio-divergent carbosulfenylation of unactivated alkenes with electrophilic
N-sulfenophthalimides has been developed. This protocol provides a straightforward and efficient access to various
medium-sized rings, especially strained 7-and 8-membered carborings with sulfur atom attached. The endo/exo
selectivity in the reaction depends on the atom number of the chain between arene and alkene. Broad substrate
scope, high yields and gram-scale synthesis exemplified the utility and practicability of this protocol. In addition,
this methodology can be extended to the carboselenylation of isolated alkenes.
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INTRODUCTION
Organosulfur plays a vital role in many significant biological activities, such as regulating hormone release,
improving immune resistance and maintaining human’s healthy metabolism. Sulfur-containing motifs also widely
exists in numerous natural products,1 pharmaceuticals and agricultures,2 as well as functional materials3. Therefore,
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C−S bond formation has gained much attention in the past decades and encouraged the chemists to develop new
and efficient synthetic strategies.4 Among various reported transformations, the difunctionalization of olefins has
been proved to be one of the most efficient and powerful methods to incorporate sulfur-containing functional
groups into target molecules.5 In this context, the thiyl radical addition to the activated alkenes has emerged as a
convenient route, and a variety of synthetically useful β-functionalized sulfides were prepared selectively and
efficiently (Scheme 1A).6-8 Notably, a breakthrough has been made by Denmark and his coworkers in 2011. They
first reported stoichiometric Brönsted acid catalyzed asymmetric carbo-sulfenylation of electron-rich olefinic aryls
with an electrophilic thiolating reagent by using a chiral Lewis base (Scheme 1B)9 In addition, they also extended
their protocol to realize enantioselective polyene cyclization, as well as efficient oxy-and amino-sulfenylation of
double bonds.10 Of particular note, Shaw and his coworkers reported an artistically Sc(OTf)3-catalyzed alkene
cyclizations for the stereoselective synthesis of complex “terpenoid-like” heterocycles with phenyl selenium/sulfur
chlorides.11 Control experiments revealed that Sc(OTf)3 served as a precatalyst, and the active catalyst was protic
acid produced by adventitious moisture. However, to the best of our knowledge, an efficient approach regarding
sulfeno-functionalization of alkenes to build strained 7-and 8-membered carbo-rings has not been explored.
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Scheme 1. Strategies for Sulfeno-Functionalization of Alkenes
Iron is notably attractive element in the life and synthetic chemistry due to its natural abundance, low cost,
versatile oxidation state and environmentally benign character.12 It also displayed Lewis acid interactions with a
variety of functional groups. To demonstrate the powerful flexibility of iron catalyst in the construction of C-S
bond, herein, we wish to report a FeCl3-catalyzed regio-divergent carbosulfenylation of unactivated alkenes with
electrophilic N-sulfenophthalimide (Scheme 1C). With this method, various medium-sized rings, especially
strained 7-and 8-membered carborings with sulfur atom attached, were constructed selectively and efficiently. The
endo/exo selectivity in the reaction depends on the atom number of the chain between arene and alkene. Broad
substrate scope, high yields, gram-scale synthesis and application to the carboselenylations exemplified the utility
and practicability of this protocol.
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RESULTS AND DISCUSSION
We commenced the studies by exploring the reactions of but-3-en-1-ylbenzene 1a with N-phenylsulfenylimide
2a for reaction condition optimization (Table 1). Catalytic amount (10 mol%) of Brönsted acid, such as
p-toluenesulfonic acid (PTSA) and methanesulfonic acid (MsOH), does not work well for this reaction (entries 1
and 2). The 6-endo-trig cyclization product 3aa was not observed in the presence of AlCl3, InCl3 and ZnCl2 (entries
3-5). In these cases, the competitive sulfenylation-chlorination product (ca. 10-20%) was obtained and more than
60% of 1a was remained. To our delight, 3aa was obtained exclusively13 in 95% yield when FeCl3 as the catalyst
(entry 6), and FeCl2 gave a slightly decreased yield (entry 7). Other iron catalysts, such as Fe(OTf)2 and Fe(acac)3,
were totally inactive with most starting meterial 1a (>85%) remianed, yet without dectection of any
sulfenylation-chlorination byproduct (entries 8 and 9). Although other Lewis acids, such as SnCl4, TMSOTf and
BF3•OEt2, also facilitated the 6-endo-trig cyclization (entries 10-12), they were less effective in the latter
construction of strained 7-and 8-memered rings. These results indicated that FeCl3 presented unique Lewis acid
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character, which was beneficial for the catalytic feasibility of this intramolecular carbosulfenylation. The survey of
solvents showed that other halogenated solvents, such as CHCl3, CCl4 and PhCl, were also effective for this
transformation (entries 13-15). However, the formation of 3aa was completely inhibited in non-halogenated
solvents due to the decomposation of N-sulfenylating agent 2a to disulfide (entries 16-20). The striking effect of
halogenated solvents on reaction efficiency might be attributed to its halogen bond interactions with 2a, which
greatly suppressed the undesired disulfide formation.14 The efficiency of this reaction was not affected when 20
mol% of NaHCO3 was added (entry 21). In addition, when HCl was utilized instead of iron catalyst, 3aa was not
detected with most alkene 1a remained (entry 22). These control experiments demonstrated that FeCl3 played the
role of Lewis acid, rather than the precursor of protic acid produced by adventitious moisture. The desired product
3aa was obtained in 76% yield alone with some uncharacterized by-products when the reaction was performed at
50 oC (entry 23). Furthermore, 3aa was not detected when the reaction was carried out at room temperature with 1a
recovered quantitatively (entry 24). These results indicated that the nucleophilic annulation step was most likely the
rate-determinating step of the transformation, and higher temperature was necessary to overcome the energy barrier.
It is noteworthy that the carbosulfenylation reaction did not occur in the absence of FeCl3 catalyst (entry 25).
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Table 1. Optimization of the Reaction Conditionsa
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entry
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catalyst
PTSA•H2O
MsOH
AlCl3
solvent
DCE
3aa (%)b
N.D.
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2
DCE
3
DCE
N.D.
N.D.
N.D.
95 (91)
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InCl3
DCE
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ZnCl2
FeCl3
DCE
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DCE
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FeCl2
DCE
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Fe(OTf)2
Fe(acac)3
SnCl4
TMSOTf
BF3•OEt2
FeCl3
DCE
N.D.
N.D.
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DCE
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DCE
DCE
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DCE
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CHCl3
CCl4
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FeCl3
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FeCl3
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FeCl3
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MeCN
THF
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FeCl3
FeCl3
1,4-dioxane
DMF
DCE
FeCl3
FeCl3
HCl
DCE
N.D.
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FeCl3
DCE
FeCl3
DCE
N.D.
N.D.
-
DCE
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a
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Reaction conditions: 1a (0.1 mmol), 2 (0.12 mmol), catalyst (10 mol%), solvent (1.0 mL), 100 C, 12 h, under N2
b
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unless otherwise noted. Reported yields were based on 1a and determined by H NMR using mesitylene as an
internal standard (isolated yield in parenthesis). cNaHCO3 (20 mol%) was added. dThe reaction was performed at 50
oC. eThe reaction was performed at room temperature. N. D.= not detected.
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With the optimal reaction conditions established, we turned our attention to investigate the scope of
N-sulfenylating agents (Table 2). In general, N-phenylsulfenyl phthalimides bearing both electron-donating and
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–withdrawing substituents on the aromatic ring were all suitable for this transformation, and the 6-exo-trig
cyclization products 3ba-ha were produced in 86-95% yields. The halogen groups, such as F, Cl, and Br, were all
well tolerated, thus allowing further manipulation of these structures. Additionally, N-sulfenylphthalimides derived
from both α-and β-naphthalenethiol served as suitable reaction partners to react with 1b, giving the sulfenylated
products 3ia and 3ja in good yields. To our delight, the S-alkyl thiophthalimide 2k was also applicable with 1a in
this sulfenylation-cyclization reaction, delivering the endo cyclized product 3ka in 95% yield.
Table 2. Scope of N-Sulfenylphthalimidesa
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Reaction conditions: 1a or 1b (0.1 mmol), 2 (0.12 mmol), FeCl3 (10 mol %), DCE (1.0 mL), 100 C, 12 h, under
N2; Reported yields were isolated ones based on 1a or 1b.
Next, the substrate scope of unactivated alkenes was explored (Table 3). The alkenes with electron-donating
groups, such as Me, OMe, SMe, i-Pr and t-Bu, attached to the aromatic ring reacted smoothly with 2a under the
optimized conditions, giving the corresponding products 3ab-af in excellent yields. Besides, the sterically hindered
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product 3ag could also be obtained in 95% yield. When electron-withdrawing groups, such as Br and NO2, attached
to the aryl moiety of alkene were tested, 3ah was obtained in moderate yield, while 3ai was not detected, possibly
due to the strong electron-withdrawing character of -NO2 decreased the nucleophilic property of phenyl ring.
Moreover, the desired 3aj and 3ak were obtained in good yields with the ester groups untouched. To our delight,
heterocyclic skeletons, such as chromane, cyclopenta[b]-thiophene, tetrahydroquinoline, were efficiently
constructed when O-or N-tethered alkenes applied under the optimized conditions (3al-aq). The coordination of
iron catalyst with substrate 1r, which was derived from 8-hydroxyquinoline, resulted in no formation of 3ar. It is
worth noting that double sulfeno-functionalization product 3as was obtained in 56% yield, accompanied by
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aryl-sulfenylated 3as´when electron-rich carbazole derived substrate was applied.
Table 3. Scope of Unactivated Alkenesa
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Reaction conditions: 1 (0.1 mmol), 2a (0.12 mmol), FeCl3 (10 mol %), DCE (1.0 mL), 100 C, 12 h, under N2;
Reported yields were isolated yields and based on 1.
Given the success of the carbosulfenylation to construct 6-memered ring, we turned our attention to the synthesis
of more challenging medium-sized ring (Table 4).15 To our delight, the 7-membered benzocarbo-rings, which are
hard to access due to its constrained configuration, were efficiently constructed with loading of 40 mol% FeCl3
(4a-f). Besides, tetrahydrobenzo[b]oxepine skeletons were also constructed with this method in excellent yields
(4g-h). Furthermore, even 8-memered benzo-ring 4i was accessed in 36% yield under this condition.
Table 4. Synthesis of 7-and 8-Membered Ring a
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Reaction conditions:1 (0.1 mmol), 2 (0.12 mmol), FeCl3 (40 mol %), DCE (1.0 mL), 100 C, 12 h, under N2;
Reported yields were isolated ones based on 1.
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In addition, other commonly used sulfenylating reagents, such as thiol, disulfides and sulfonothioate, were also
tested with 1a under the standard conditions (Scheme 2). Gratifyingly, benzenesulfenyl chloride 8 was also
identified as an efficient sulfenylating reagent, delivering the desired product 3aa in 93% yield. .
Scheme 2. Testing Other Sulfenylating Reagents.
Gram-scale experiment was then performed for the model reaction, and the desired product 3aa was obtained in
86% yield, which showed practicability of this reaction (Scheme 3).
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Scheme 3. Gram-Scale Synthesis.
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Organoselenium compounds have manifested potential applications in organic chemistry.16,17 As early as 1986,
Livinghouse reported the stoichiometric Lewis acid mediated selenylative carboannulations of electron-rich olefinic
arenes with N-(phenylseleno) succinimide.18 To further explore the potential of our catalytic methodology, the
reaction of substrate 1a with N-(phenylseleno)phthalimide (N-PSP) 9 was tested under the optimal conditions
(Table 5). Satisfyingly, the selenylated product 10a was obtained in 94% yield via endo-trig cyclization. When the
alkenes with one more atom added on the alkyl chain were applied, the 6-exo-trig carboselenylations underwent
smoothly to give the desired products 10b-i in excellent yields, which demonstrated the general and powerful
features of this FeCl3-catalyzed transformation.
Table 5. Carboselenylation of Unactivated Alkenes a
a
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Reaction conditions:1 (0.1 mmol), 9 (0.12 mmol), FeCl3 (10 mol %), DCE (1.0 mL), 100 C, 12 h, under N2;
Reported yields were isolated ones based on 1.
In order to gain the mechanism of this transformation, several control experiments were carried out (Scheme 4).
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Obvious kinetic isotope effect (kH/D = 2.8) was observed from inter-molecular competition (Scheme 4a). However,
two parallel reactions displayed no kinetic isotope effect (kH/D = 1.04) (Scheme 4b and 4c). These results indicated
that the cleavage of aromatic C-H bond may be not involved in the rate-determining step.19 Besides，the reaction
was almost unaffected in the presence of radical inhibitor butylated hydroxytoluene (BHT), which suggested that a
radical pathway might be excluded in this process. In addition, combined with the obvious electronic effects on the
phenyl ring of alkenes observed in the experiment (Table 3, 3ah and 3ai), we speculated that the reaction may
proceed through a Friedel–Crafts pathway, and nucleophilic attack of aryl ring to the thiiranium ion may be the key
step.9,10
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Scheme 4. Control Experiments
Based on the above investigations and reported literature,9-12 a plausible reaction mechanism was proposed in
Scheme 5. Activation of sulfenylating reagent 2a with FeCl3 gives the intermediate A, subsequent addition of C=C
bond of 1 to the sulfenyl group forms anion B and thiiranium ion species C, which undergoes ring-opening by the
intramolecular nucleophilic attack of the aryl group to give dearomatic cation D. The endo/exo selectivity of the
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ring-opening depends on the atom number of the chain between arene and alkene. The need of higher iron catalyst
loading in the formation of strained 7-and 8-membered ring suggested that FeCl3 played vital role in the
intermolecular nucleophilic capture process.12,20 Finally, deprotonation of intermediate D by anion B gives the
desired product 3 with release of FeCl3. The similar process is engaged in the carboselenylation reactions.
Scheme 5. Proposed Mechanism for Intramolecular Carbosulfenylation of Unactivated Alkenes.
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CONCLUSION
In summary, we have demonstrated a FeCl3-catalyzed regio-divergent carbosulfenylation of unactivated alkenes
with electrophilic N-sulfenophthalimides. With this method, a variety of medium-sized rings, especially strained
7-and 8-membered carborings with sulfur atom attached were constructed selectively and efficiently. The endo/exo
selectivity in the reaction depends on the atom number of the chain between arene and alkene. Preliminary
mechanistic studies suggested that a Friedel-Crafts pathway was involved in this transformation. Broad substrate
scope, high yields and gram-scale experiment exemplified the utility and practicability of this protocol. In addition,
this methodology could also be extended to the carboselenylation of isolated alkenes.
Experimental Section
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General Information. H NMR spectra were recorded on 500 MHz spectrometer and the chemical shifts were
reported in parts per million (δ) relative to internal solvent signal (7.28 ppm in CDCl3). The peak patterns are
indicated as follows: s, singlet; d, doublet; dd, doublet of doublet; t, triplet; q, quartet; m, multiplet. The coupling
constants, J, are reported in Hertz (Hz). 13C NMR spectra were obtained at 125 MHz and referenced to the internal
solvent signal (central peak is 77.0 ppm in CDCl3). CDCl3 was used as the NMR solvent. Flash column
chromatography was performed over silica gel 200-300. All reagents were weighed and handled in air at room
temperature. All reagents were purchased from commercial source and used without further purification. The
HRMS measurements were recorded on a TOF analyzer using an ESI or APCI source in the positive mode. The
substrate 1 was synthesized according to the reported literatures21.
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General procedure and characterization data for products 3 and 4. To a mixture of alkene 1 (0.1 mmol),
N-sulfenylimide 2 (0.12 mmol) and FeCl3 (1.6 mg, 10 mol %), 1,2-dichloroethane (1.0 mL) was added under
nitrogen at room temperature. Then the resulting mixture was sealed and stirred at 100 °C for 12 h. After the
mixture was cooled to room temperature, the resulting solution was directly filtered through a pad of celite by
dichloromethane. The solvent was evaporated in vacuo to give the crude product. The residue was purified by
preparative chromatography on silica gel (ethyl acetate/hexane) to give the pure product 3. In the case of synthesis
of 7-and 8-membered product 4, FeCl3 (6.4 mg, 40 mol %) was added instead.
Phenyl(1,2,3,4-tetrahydronaphthalen-2-yl)sulfane (3aa). (22 mg, 91%). Isolated by flash column
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chromatography (ethyl acetate/hexane = 1:100, Rf = 0.8); H NMR (500 MHz, CDCl3) δ 7.52-7.50 (m, 2H),
7.38-7.35 (m, 2H), 7.32-7.28 (m, 1H), 7.17-7.12 (m, 3H), 7.09-7.07 (m, 1H), 3.63-3.57 (m, 1H), 3.22-3.17 (m, 1H),
3.04-2.98 (m, 1H), 2.92-2.86 (m, 2H), 2.30-2.24 (m, 1H), 1.92-1.84 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 135.6,
135.1, 134.6, 132.1, 129.0, 128.9, 128.8, 127.0, 126.1, 125.9, 43.2, 36.1, 29.5, 28.6; HRMS (ESI) calcd for
C16H16NaS [M + Na+], 263.0865; found: 263.0871.
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Phenyl((1,2,3,4-tetrahydronaphthalen-1-yl)methyl)sulfane (3ba). (24 mg, 95%). Isolated by flash column
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2.14-2.08 (m, 1H), 1.96-1.90 (m, 1H), 1.89-1.83 (m, 1H), 1.82-1.75 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 139.1,
137.3, 136.9, 129.3, 129.0, 128.9, 126.2, 125.9, 125.8, 40.8, 37.1, 29.6, 26.5, 19.1; HRMS (ESI) calcd for
C17H18NaS [M + Na+], 277.1021; found: 277.1019.
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((1,2,3,4-Tetrahydronaphthalen-1-yl)methyl)(p-tolyl)sulfane (3ca). (25 mg, 92%). Isolated by flash column
chromatography (ethyl acetate/hexane = 1:100, Rf = 0.8); 1H NMR (500 MHz, CDCl3) δ 7.36 (d, J = 8.2 Hz, 2H),
7.17-7.10 (m, 6H), 3.34-3.32 (m, 1H), 3.08-3.00 (m, 2H), 2.86-2.74 (m, 2H), 2.37 (s, 3H), 2.15-2.10 (m, 1H),
1.96-1.88 (m, 1H), 1.87-1.76 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 139.2, 137.3, 136.1, 133.1, 130.1, 129.8,
129.3, 128.9, 126.1, 125.8, 41.5, 37.1, 29.6, 26.4, 21.0, 19.1; HRMS (APCI) calcd for C18H19S [M - H+], 267.1202;
found: 267.1190.
(4-(Tert-butyl)phenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)methyl)sulfane (3da). (29 mg, 95%). Isolated by
flash column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.7); 1H NMR (500 MHz, CDCl3) δ 7.39-7.35 (m,
4H), 7.21-7.18 (m, 1H), 7.17-7.14 (m, 2H), 7.13-7.10 (m, 1H), 3.39-3.33 (m, 1H), 3.10-3.03 (m, 2H), 2.86-2.75 (m,
2H), 2.15-2.10 (m, 1H), 1.97-1.91 (m, 1H), 1.90-1.83 (m, 1H), 1.81-1.75 (m, 1H), 1.35 (s, 9H); 13C NMR (125
MHz, CDCl3) δ 149.3, 139.2, 137.3, 133.3, 129.4, 129.3, 128.9, 126.1, 126.0, 125.8, 41.2, 37.2, 34.5, 31.3, 29.6,
26.5, 19.2; HRMS (ESI) calcd for C21H26NaS [M + Na+ ], 333.1647; found: 333.1643.
(3-Methoxyphenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)methyl)sulfane (3ea). (26 mg, 93%). Isolated by
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flash column chromatography (ethyl acetate/hexane = 1:50, Rf = 0.5); H NMR (500 MHz, CDCl3) δ 7.26 (t, J =
8.0 Hz, 1H), 7.24-7.21 (m, 1H), 7.20-7.15 (m, 2H), 7.14-7.11 (m, 1H), 7.03-7.01 (m, 1H), 6.98 (t, J = 2.0 Hz, 1H),
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6.77 (dd, J = 8.2, 2.0 Hz, 1H), 3.85 (s, 3H), 3.41-3.36 (m, 1H), 3.14-3.07 (m, 2H), 2.87-2.76 (m, 2H), 2.14-2.10 (m,
1H), 1.98-1.92 (m, 1H), 1.90-1.76 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 159.9, 139.1, 138.3, 137.3, 129.8, 129.3,
128.9, 126.3, 125.8, 121.2, 114.5, 111.6, 55.3, 40.5, 37.1, 29.6, 26.6, 19.2; HRMS (APCI) calcd for C18H21OS [M +
H+], 285.1308; found: 285.1294.
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(4-Fluorophenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)methyl)sulfane (3fa). (24 mg, 65%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.7); 1H NMR (500 MHz, CDCl3) δ 7.44-7.42 (m, 2H),
7.16-7.10 (m, 4H), 7.07-7.03 (m, 2H), 3.29 (dd, J = 12.2, 3.0 Hz, 1H), 3.08-2.98 (m, 2H), 2.86-2.74 (m, 2H),
2.13-2.08 (m, 1H), 1.96-1.89 (m, 1H), 1.88-1.76 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 161.7 (d, JC-F = 246.1 Hz),
138.9, 137.3, 132.3 (d, JC-F = 7.8 Hz), 131.7 (d, JC-F = 3.3 Hz), 129.3, 128.8, 126.2, 125.8, 116.1 (d, JC-F = 22.0 Hz),
42.3, 37.2, 29.6, 26.4, 19.1; 19F NMR (470 MHz, CDCl3) δ -115.7; HRMS (ESI) calcd for C17H17FNaS [M + Na+],
295.0927; found: 295.0913.
(4-Chlorophenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)methyl)sulfane (3ga). (26 mg, 92%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.7); 1H NMR (500 MHz, CDCl3) δ 7.36-7.34 (m, 2H),
7.31-7.29 (m, 2H), 7.18-7.15 (m, 3H), 7.13-7.11 (m, 1H), 3.34-3.31 (m, 1H), 3.11-3.02 (m, 2H), 2.86-2.75 (m, 2H),
2.11-2.06 (m, 1H), 1.96-1.90 (m, 1H), 1.89-1.76 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 138.8, 137.3, 135.5,
131.9, 130.6, 129.3, 129.1, 128.8, 126.3, 125.8, 41.1, 37.1, 29.6, 26.5, 19.1; HRMS (APCI) calcd for C17H16ClS [M
- H+], 287.0656; found: 287.0645.
(4-Bromophenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)methyl)sulfane (3ha). (28 mg, 86%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.7); 1H NMR (500 MHz, CDCl3) δ 7.46-7.43 (m, 2H),
7.29-7.27 (m, 2H), 7.17-7.15 (m, 3H), 7.12-7.10 (m, 1H); 3.34-3.31 (m, 1H), 3.11-3.02 (m, 2H), 2.86-2.75 (m, 2H),
2.11-2.05 (m, 1H), 1.96-1.90 (m, 1H), 1.89-1.76 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 138.8, 137.3, 136.2,
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132.0, 130.8, 129.3, 128.8, 126.3, 125.8, 119.7, 40.9, 37.1, 29.6, 26.5, 19.1; HRMS (APCI) calcd for C17H16BrS [M
- H+], 331.0151; found: 331.0137.
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Naphthalen-1-yl((1,2,3,4-tetrahydronaphthalen-1-yl)methyl)sulfane (3ia). (27 mg, 90%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.7); 1H NMR (500 MHz, CDCl3) δ 8.49 (d, J = 8.4 Hz,
1H), 7.89 (dd, J = 8.4, 1.0 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.68 (dd, J = 7.2, 1.0 Hz, 1H), 7.61 (td, J = 7.6, 1.4 Hz,
1H), 7.56 (td, J = 7.6, 1.4 Hz, 1H), 7.48-7.44 (m, 1H), 7.16-7.10 (m, 4H), 3.41 (dd, J = 12.6, 3.6 Hz, 1H), 3.21-3.17
(m, 1H), 3.12-3.07 (m, 1H), 2.87-2.75 (m, 2H), 2.24-2.19 (m, 1H), 2.01-1.95 (m, 1H), 1.93-1.85 (m, 1H), 1.84-1.77
(m, 1H); 13C NMR (125 MHz, CDCl3) δ 139.1, 137.3, 134.2, 134.0, 133.0, 129.3, 128.9, 128.6, 128.1, 127.2, 126.4,
126.3, 126.2, 125.8, 125.6, 125.1, 41.5, 37.3, 29.6, 26.7, 19.2; HRMS (ESI) calcd for C21H20NaS [M + Na+],
327.1178; found: 327.1178.
Naphthalen-2-yl((1,2,3,4-tetrahydronaphthalen-1-yl)methyl)sulfane (3ja). (26 mg, 86%). Isolated by flash
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column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.7); H NMR (500 MHz, CDCl3) δ 7.83 (s, 1H),
7.82-7,79 (m, 2H), 7.78-7.76 (m, 1H), 7.52-7.48 (m, 2H), 7.47-7.44 (m, 1H), 7.24-7.22 (m, 1H), 7.19-7.14 (m, 2H),
7.13-7.11 (m, 1H), 3.47 (dd, J = 12.6, 3.6 Hz, 1H), 3.22-3.17 (m, 1H), 3.14-3.09 (m, 1H), 2.87-2.75 (m, 2H),
2.17-2.12 (m, 1H), 1.99-1.92 (m, 1H), 1.91-1.85 (m, 1H), 1.84-1.76 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 139.1,
137.3, 134.5, 133.8, 131.7, 129.3, 128.9, 128.4, 127.7, 127.4, 127.0 126.8, 126.6, 126.2, 125.8, 125.6, 40.6, 37.1,
29.6, 26.6, 19.1; HRMS (ESI) calcd for C21H20NaS [M + Na+], 327.1178; found: 327.1178.
(1,2,3,4-Tetrahydronaphthalen-2-yl)(undecyl)sulfane (3ka). (30 mg, 95%). Isolated by flash column
chromatography (hexane, Rf = 0.8); 1H NMR (500 MHz, CDCl3) δ 7.15-7.08 (m, 4H), 3.18-3.14 (m, 1H), 3.12-3.06
(m, 1H), 3.00-2.95 (m, 1H), 2.90-2.79 (m, 2H), 2.65 (t, J = 7.5 Hz, 2H), 2.26-2.20 (m, 1H), 1.84-1.76 (m, 1H),
1.68-1.62 (m, 2H), 1.44-1.40 (m, 2H), 1.34-1.29 (m, 14H), 0.91 (t, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3)
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δ 135.8, 135.4, 128.9, 128.8, 126.0, 125.8, 40.1, 36.7, 31.9, 30.4, 30.0, 29.9, 29.6, 29.5, 29.4, 29.3, 29.1, 28.8, 22.7,
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((7-Methyl-1,2,3,4-tetrahydronaphthalen-1-yl)methyl)(phenyl)sulfane (3ab). (24 mg, 91%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.8); 1H NMR (500 MHz, CDCl3) δ 7.44-7.42 (m, 2H),
7.35-7.32 (m, 2H), 7.24-7.21 (m, 1H), 7.02-6.97 (m, 3H), 3.39-3.35 (m, 1H), 3.12-3.07 (m, 1H), 3.06-3.01 (m, 1H),
2.82-2.70 (m, 2H), 2.33 (s, 3H), 2.12-2.07 (m, 1H), 1.95-1.89 (m, 1H), 1.88-1.80 (m, 1H), 1.80-1.73 (m, 1H); 13
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NMR (125 MHz, CDCl3) δ 138.9, 137.1, 135.2, 134.2, 129.4, 129.2, 129.1, 128.9, 127.1, 125.9, 40.8, 37.1, 29.2,
26.6, 21.1, 19.2; HRMS (APCI) calcd for C18H21S [M +H+], 269.1358; found: 269.1355.
((7-Methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl)(phenyl)sulfane (3ac). (27 mg, 95%). Isolated by
flash column chromatography (ethyl acetate/hexane = 1:40, Rf = 0.6); 1H NMR (500 MHz, CDCl3) δ 7.44-7.42 (m,
2H), 7.35-7.32 (m, 2H), 7.24-7.20 (m, 1H), 7.03 (d, J = 8.8 Hz, 1H), 7.75-6.73 (m, 2H), 3.80 (s, 3H), 3.38-3.35 (m,
1H), 3.13-3.08 (m, 1H), 3.05-3.00 (m, 1H), 2.79-2.68 (m, 2H), 2.08-2.05 (m, 1H), 1.95-1.88 (m, 1H), 1.87-1.81 (m,
1H), 1.80-1.73 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 157.6, 140.2, 136.9, 130.1, 129.4, 129.3, 129.0, 126.0,
113.9, 112.2, 55.3, 40.8, 37.5, 28.8, 26.6, 19.4; HRMS (APCI) calcd for C18H19OS [M - H+], 283.1151; found:
283.1147.
Methyl(8-((phenylthio)methyl)-5,6,7,8-tetrahydronaphthalen-2-yl)sulfane (3ad). (27 mg, 90%). Isolated by
flash column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.5); 1H NMR (500 MHz, CDCl3) δ 7.44-7.42 (m,
2H), 7.35-7.32 (m, 2H), 7.24-7.21 (m, 1H), 7.10-7.07 (m, 2H), 7.05-7.03 (m, 1H), 3.35-3.32 (m, 1H), 3.11-3.06 (m,
1H), 3.04-2.99 (m, 1H), 2.81-2.69 (m, 2H), 2.48 (s, 3H), 2.12-2.07 (m, 1H), 1.93-1.87 (m, 1H), 1.86-1.75 (m, 2H);
13C NMR (125 MHz, CDCl3) δ 139.8, 136.8, 135.0, 134.6, 129.8, 129.4, 129.0, 127.7, 126.1, 125.3, 40.8, 37.2,
29.1, 26.5, 19.1, 16.5; HRMS (ESI) calcd for C18H20NaS2 [M + Na+], 323.0899; found: 323.0887.
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((7-Isopropyl-1,2,3,4-tetrahydronaphthalen-1-yl)methyl)(phenyl)sulfane (3ae). (26 mg, 88%). Isolated by
flash column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.7); 1H NMR (500 MHz, CDCl3) δ 7.45-7.43 (m,
2H), 7.35-7.33 (m, 2H), 7.24-7.21 (m, 1H), 7.07-7.03 (m, 3H), 3.39-3.36 (m, 1H), 3.14-3.10 (m, 1H), 3.07-3.03 (m,
1H), 2.92-2.86 (m, 1H), 2.83-2.72 (m, 2H), 2.13-2.08 (m, 1H), 1.95-1.88 (m, 1H), 1.87-1.74 (m, 2H), 1.27 (d, J =
7.0 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ 146.4, 138.9, 137.1, 134.6, 129.2, 128.9, 126.9, 125.9, 124.4, 40.8,
37.3, 33.8, 29.2, 26.6, 24.2, 24.1, 19.2; HRMS (ESI) calcd for C20H24NaS [M + Na+], 319.1491; found: 319.1489.
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((7-(Tert-butyl)-1,2,3,4-tetrahydronaphthalen-1-yl)methyl)(phenyl)sulfane (3af). (28 mg, 89%). Isolated by
flash column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.7); 1H NMR (500 MHz, CDCl3) δ 7.44-7.42 (m,
2H), 7.35-7.32 (m, 2H), 7.24-7.20 (m, 3H), 7.07-7.05 (m, 1H), 3.37-3.34 (m, 1H), 3.15-3.10 (m, 1H), 3.07-3.03 (m,
1H), 2.83-2.71 (m, 2H), 2.13-2.08 (m, 1H), 1.95-1.88 (m, 1H), 1.87-1.75 (m, 2H), 1.33 (s, 9H); 13C NMR (125
MHz, CDCl3) δ 148.6, 138.5, 137.2, 134.2, 129.2, 129.0, 128.9, 125.9, 125.7, 123.4, 41.0, 37.5, 34.4, 31.4, 29.1,
26.6, 19.1; HRMS (ESI) calcd for C21H26NaS [M + Na+], 333.1647; found: 333.1644.
((5,8-Dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)methyl)(phenyl)sulfane (3ag). (26 mg, 93%). Isolated by
flash column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.5); 1H NMR (500 MHz, CDCl3) δ 7.47-7.45 (m,
2H), 7.34-7.31 (m, 2H), 7.25-7.22 (m, 1H), 6.98 (d, J = 7.6 Hz, 1H), 6.94 (d, J = 7.6 Hz, 1H), 3.15-3.11 (m, 2H),
3.03-2.98 (m, 1H), 2.80-2.76 (m, 1H), 2.60-2.53 (m, 1H), 2.41-2.38 (m, 1H), 2.21 (s, 3H), 2.18 (s, 3H), 1.93-1.85
(m, 2H), 1.71-1.64 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 137.7, 136.6, 135.1, 134.4, 133.6, 130.4, 128.9, 127.7,
126.3, 37.8, 34.5, 26.7, 24.2, 19.7, 18.7, 17.1; HRMS (ESI) calcd for C19H22NaS [M + Na+], 305.1334; found:
305.1334.
((7-Bromo-1,2,3,4-tetrahydronaphthalen-1-yl)methyl)(phenyl)sulfane (3ah). (16 mg, 51%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.5); 1H NMR (500 MHz, CDCl3) δ 7.44-7.41 (m, 2H),
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7.36-7.33 (m, 2H), 7.30-7.29 (m, 1H), 7.26-7.22 (m, 2H), 6.97 (d, J = 8.2 Hz, 1H), 3.33-3.30 (m, 1H), 3.09-3.04 (m,
1H), 3.03-2.98 (m, 1H), 2.79-2.66 (m, 2H), 2.11-2.06 (m, 1H), 1.92-1.86 (m, 1H), 1.85-1.73 (m, 2H); 13C NMR
(125 MHz, CDCl3) δ 141.3, 136.5, 136.2, 131.6, 130.9, 129.6, 129.2, 129.0, 126.2, 119.2, 40.8, 37.1, 29.1, 26.2,
18.9; HRMS (APCI) calcd for C17H16BrS [M - H+], 331.0151; found: 331.0134.
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Dimethyl 4-((phenylthio)methyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (3aj). (29 mg, 78%).
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Isolated by flash column chromatography (ethyl acetate/hexane = 1:10, Rf = 0.4); H NMR (500 MHz, CDCl3) δ
7.43-7.41 (m, 2H), 7.33-7.30 (m, 2H), 7.25-7.22 (m, 2H), 7.20-7.15 (m, 3H), 3.78 (s, 3H), 3.61 (s, 3H), 3.54 (dd, J
= 12.8, 3.8 Hz, 1H), 3.36 (dd, J = 16.0, 1.6 Hz, 1H), 3.27-3.22 (m, 2H), 3.08 (dd, J = 12.8, 9.2 Hz, 1H), 2.93-2.88
(m, 1H), 2.13 (dd, J = 12.8, 9.2 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 172.2, 171.0, 136.7, 136.4, 134.0, 130.0,
129.1, 129.0, 127.1, 126.7, 126.6, 126.3, 53.9, 52.9, 52.6, 41.3, 35.4, 35.0, 34.1; HRMS (ESI) calcd for
C21H22NaO4S [M + Na+], 393.1131; found: 393.1128.
Diethyl 4-methyl-4-((phenylthio)methyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (3ak). (29 mg,
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71%). Isolated by flash column chromatography (ethyl acetate/hexane = 1:10, Rf = 0.5); H NMR (500 MHz,
CDCl3) δ 7.31-7.28 (m, 2H), 7.27-7.23 (m, 3H), 7.20-7.15 (m, 4H), 4.25-4.09 (m, 4H), 3.30 (d, J = 16.0 Hz, 1H),
3.24 (d, J = 16.0 Hz, 1H), 3.22 (d, J = 15.6 Hz, 1H), 3.20 (d, J = 15.6 Hz, 1H), 2.80 (d, J = 14.4 Hz, 1H), 2.39 (dd,
J = 14.4, 1.2 Hz, 1H), 1.41 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H), 1.21 (t, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3)
δ 171.7, 171.4, 140.7, 137.8, 133.7, 129.5, 128.9, 128.8, 126.8, 126.6, 126.2, 125.9, 61.6, 61.4, 52.7, 49.1, 38.9,
38.4, 35.5, 29.9, 14.0, 13.9; HRMS (ESI) calcd for C24H28NaO4S [M + Na+], 435.1601; found: 435.1591.
4-((Phenylthio)methyl)chromane (3al). (24 mg, 92%). Isolated by flash column chromatography (ethyl
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acetate/hexane = 1:50, Rf = 0.6); H NMR (500 MHz, CDCl3) δ 7.46-7.43 (m, 2H), 7.37-7.33 (m, 2H), 7.27-7.22
(m, 1H), 7.17-7.12 (m, 2H), 6.90 (td, J = 7.6, 1.2 Hz, 1H), 6.84 (dd, J = 8.4, 1.2 Hz, 1H), 4.26-4.13 (m, 2H),
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3.50-3.43 (m, 1H), 3.07-3.00 (m, 2H), 2.24-2.12 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 154.6, 136.2, 129.6,
129.2, 129.1, 128.0, 126.3, 124.5, 120.4, 117.1, 62.9, 40.3, 33.1, 25.7; HRMS (ESI) calcd for C16H16NaOS [M +
Na+], 279.0814; found: 279.0815.
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6-Phenyl-4-((phenylthio)methyl)chromane (3am). (29 mg, 87%). Isolated by flash column chromatography
(ethyl acetate/hexane = 1:50, Rf = 0.6); 1H NMR (500 MHz, CDCl3) δ 7.56-7.54 (m, 2H), 7.47-7.44 (m, 4H), 7.40
(dd, J = 8.4, 2.4 Hz, 1H), 7.38-7.32 (m, 4H), 7.27-7.24 (tt, J = 7.4, 1.2 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H), 4.30-4.26
(m, 1H), 4.24-4.19 (m, 1H), 3.56-3.50 (m, 1H), 3.14-3.08 (m, 2H), 2.27-2.18 (m, 2H); 13C NMR (125 MHz, CDCl3)
δ 154.2, 140.9, 136.1, 133.6, 129.7, 129.1, 128.8, 127.9, 126.9, 126.8, 126.7, 126.4, 124.7, 117.4, 63.0, 40.4, 33.3,
25.8; HRMS (ESI) calcd for C22H20NaOS [M + Na+], 355.1127; found: 355.1120.
6-Chloro-8-methoxy-4-((phenylthio)methyl)chromane (3an). (27 mg, 85%). Isolated by flash column
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chromatography (ethyl acetate/hexane = 1:50, Rf = 0.6); H NMR (500 MHz, CDCl3) δ 7.44-7.42 (m, 2H),
7.36-7.33 (m, 2H), 7.27-7.23 (m, 1H), 6.72 (s, 2H), 4.34-4.30 (m, 1H), 4.22-4.17 (m, 1H), 3.87 (s, 3H), 3.44-3.38
(m, 1H), 3.00-2.93 (m, 2H), 2.24-2.19 (m, 1H), 2.16-2.09 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 149.1, 142.8,
135.7, 130.0, 129.2, 126.6, 126.0, 124.6, 120.4, 110.3, 63.4, 56.1, 40.2, 33.0, 25.2; HRMS (ESI) calcd for
C17H17ClNaO2S [M + Na+], 343.0530; found: 343.0532.
5-methoxy-1-((phenylthio)methyl)-2,3-dihydro-1H-benzo[f]chromene (3ao). (25 mg, 82%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:50, Rf = 0.6); 1H NMR (500 MHz, CDCl3) δ 7.68 (d, J = 7.8 Hz,
1H), 7.57-7.55 (m, 2H), 7.41-7.38 (m, 2H), 7.36-7.33 (m, 2H), 7.32-7.29 (m, 1H), 7.26-7.22 (m, 1H), 7.05 (s, 1H),
4.58-4.55 (m, 1H), 4.33-4.28 (m, 1H), 4.00 (s, 3H), 3.57 (d, J = 13.6 Hz, 1H), 3.52-3.49 (m, 1H), 3.03-2.98 (m, 1H),
2.54 (dq, J = 14.2, 2.0 Hz, 1H), 2.20-2.13 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 148.8, 144.0, 135.5, 131.7,
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129.1, 129.0, 127.4, 127.2, 124.4, 123.8, 121.1, 116.7, 105.6, 62.1, 55.8, 39.3, 29.8, 23.4; HRMS (ESI) calcd for
C21H21O2S [M + H+], 337.1257; found: 337.1262.
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5-(Phenylthio)-4,5,6,7-tetrahydrobenzo[b]thiophene (3ap). (10 mg, 42%). Isolated by flash column
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chromatography (ethyl acetate/hexane = 1:100, Rf = 0.6); H NMR (500 MHz, CDCl3) δ 7.49-7.47 (m, 2H),
7.36-7.32 (m, 2H), 7.30-7.28 (m, 1H), 7.09 (d, J = 5.0 Hz, 1H), 6.74 (d, J = 5.0 Hz, 1H), 3.60-3.55 (m, 1H), 3.08
(dd, J = 15.6, 4.8 Hz, 1H), 2.99 (dt, J = 16.4, 4.8 Hz, 1H), 2.87-2.81 (m, 1H), 2.72-2.67 (m, 1H), 2.30-2.25 (m, 1H),
1.96-1.88 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 134.5, 134.4, 132.2, 128.9, 127.2, 127.1, 122.6, 43.2, 32.5, 30.0,
24.3; HRMS (APCI) calcd for C14H13S2 [M - H+], 245.0453; found: 245.0444.
4-((Phenylthio)methyl)-1-tosyl-1,2,3,4-tetrahydroquinoline (3aq). (31 mg, 76%). Isolated by flash column
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chromatography (ethyl acetate/hexane = 1:10, Rf = 0.5); H NMR (500 MHz, CDCl3) δ 7.90 (dd, J = 8.4, 1.0 Hz,
1H), 7.50 (d, J = 8.4 Hz, 2H), 7.33-7.28 (m, 4H), 7.27-7.22 (m, 2H), 7.19 (d, J = 8.4 Hz, 2H), 7.13 (td, J = 7.6, 1.2
Hz, 1H), 7.09 (dd, J = 7.6, 1.6 Hz, 1H), 3.89-3.84 (m, 1H), 3.81-3.75 (m, 1H), 3.04 (dd, J = 13.0, 4.4 Hz, 1H),
2.82-2.77 (m, 1H), 2.40-2.37 (m, 1H), 2.35 (s, 3H), 1.88-1.75 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 143.8, 136.6,
136.4, 135.9, 132.1, 129.6, 129.5, 129.0, 128.8, 127.3, 127.2, 126.4, 125.0, 124.8, 44.0, 40.0, 35.1, 25.3, 21.5;
HRMS (ESI) calcd for C23H23NNaO2S2 [M + Na+], 432.1062; found: 432.1054.
7-Methyl-8-(phenylthio)-4-((phenylthio)methyl)-2,3,4,7-tetrahydropyrano[3,2-c]carbazole (3as). (26 mg,
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56%). Isolated by flash column chromatography (ethyl acetate/hexane = 1:10, Rf = 0.4); H NMR (500 MHz,
CDCl3) δ 8.56 (d, J = 1.6 Hz, 1H), 7.61 (dd, J = 8.4, 1.8 Hz, 1H), 7.48-7.46 (m, 2H), 7.39 (d, J = 8.4 Hz, 1H), 7.36
(t, J = 8.0 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 7.22 (t, J = 8.0 Hz, 2H), 7.16-7.14 (m, 2H), 7.12-7.09 (m, 1H), 6.98 (d,
J = 8.4 Hz, 1H), 4.51-4.47 (m, 1H), 4.37 (td, J = 10.6, 3.0 Hz, 1H), 3.85 (s, 3H), 3.52 (dd, J = 12.8, 3.4 Hz, 1H),
3.21-3.16 (m, 1H), 3.13-3.09 (m, 1H), 2.36-2.24 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 150.9, 141.7, 140.6,
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140.5, 136.4, 131.7, 130.1, 129.6, 129.1, 128.8, 127.5, 126.9, 126.3, 125.0, 123.1, 121.1, 114.6, 111.0, 109.0, 101.1,
63.0, 40.7, 32.8, 29.4, 25.7; HRMS (ESI) calcd for C29H25NNaOS2 [M + Na+], 490.1270; found: 490.1263.
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4-(But-3-en-1-yloxy)-9-methyl-1-(phenylthio)-9H-carbazole (3as’). (9 mg, 25%). Isolated by flash column
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chromatography (ethyl acetate/hexane = 1:10, Rf = 0.5); H NMR (500 MHz, CDCl3) δ 8.55 (d, J = 1.5 Hz, 1H),
7.61 (dd, J = 8.4, 1.8 Hz, 1H), 7.43 (t, J = 8.1 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.26-7.20 (m, 4H), 7.15-7.12 (m,
1H), 7.05 (d, J = 8.1 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.01-5.93 (m, 1H), 5.25 (dq, J = 17.2, 1.6 Hz, 1H),
5.11-5.08 (m, 1H), 4.29 (t, J = 6.4 Hz, 2H), 3.87 (s, 3H), 2.73-2.69 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 155.5,
142.8, 140.2, 140.0, 134.6, 131.1, 129.7, 128.8, 127.6, 127.1, 125.2, 123.3, 121.9, 117.3, 111.6, 108.8, 101.5, 101.2,
67.3, 34.0, 29.5; HRMS (ESI) calcd for C23H22NOS [M + H+], 360.1417; found: 360.1426.
Phenyl((6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)methyl)sulfane (4a). (20 mg, 76%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:120, Rf = 0.8); 1H NMR (500 MHz, CDCl3) δ 7.39-7.37 (m, 2H),
7.33-7.30 (m, 2H), 7.23-7.19 (m, 1H), 7.18-7.11 (m, 4H), 3.45 (dd, J = 12.6, 6.2 Hz, 1H), 3.30 (dd, J = 12.6, 9.2 Hz,
1H), 3.17-3.12 (m, 1H), 2.88-2.80 (m, 2H), 1.99-1.87 (m, 2H), 1.81-1.74 (br, 2H), 1.73-1.64 (br, 2H); 13C NMR
(125 MHz, CDCl3) δ 143.8, 142.5, 136.8, 130.0, 129.3, 128.9, 126.4, 126.1, 125.9, 44.0, 37.4, 36.2, 32.0, 28.3, 27.9;
HRMS (ESI) calcd for C18H21S [M + H+], 269.1358; found: 269.1346.
((6,7,8,9-Tetrahydro-5H-benzo[7]annulen-5-yl)methyl)(p-tolyl)sulfane (4b). (23 mg, 81%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:120, Rf = 0.5); 1H NMR (500 MHz, CDCl3) δ 7.31-7.28 (m, 2H),
7.18-7.10 (m, 6H), 3.42-3.38 (m, 1H), 3.27-3.23 (m, 1H), 3.13-3.09 (m, 1H), 2.88-2.79 (m, 2H), 2.35 (s, 3H),
1.99-1.89 (m, 2H), 1.81-1,73 (br, 2H), 1.70-1.62 (br, 2H); 13C NMR (125 MHz, CDCl3) δ 143.9, 142.5, 136.1,
132.9, 130.2, 129.9, 129.7, 126.4, 126.1, 43.9, 38.1, 36.2, 31.9, 28.4, 27.9, 21.0; HRMS (ESI) calcd for C19H23S [M
+ H+], 283.1515; found:283.1501.
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(4-(Tert-butyl)phenyl)((6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)methyl)sulfane (4c). (27 mg, 85%).
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Isolated by flash column chromatography (ethyl acetate/hexane = 1:120, Rf = 0.5); H NMR (500 MHz, CDCl3) δ
7.36-7.32 (m, 4H), 7.19-7.11 (m, 4H), 3.42 (dd, J = 12.4, 6.0 Hz, 1H), 3.27 (dd, J = 12.4, 9.2 Hz, 1H), 3.17-3.12 (m,
1H), 2.89-2.80 (m, 2H), 2.00-1.91 (m, 2H), 1.82-1.73 (br, 2H), 1.72-1.64 (br, 2H), 1.34 (s, 9H); 13C NMR (125
MHz, CDCl3) δ 149.3, 144.0, 142.5, 133.1, 129.9, 129.6, 126.4, 126.1, 126.0, 44.0, 37.9, 36.2, 34.5, 32.0, 31.3,
28.4, 27.9; HRMS (ESI) calcd for C22H28NaS [M + Na+], 347.1804; found: 347.1800.
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(4-Fluorophenyl)((6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)methyl)sulfane (4d). (23 mg, 80%). Isolated
by flash column chromatography (ethyl acetate/hexane = 1:120, Rf = 0.5); 1H NMR (500 MHz, CDCl3) δ 7.39-7.36
(m, 2H), 7.18-7.14 (m, 2H), 7.13-7.10 (m, 2H), 7.04-7.00 (m, 2H), 3.40-3.36 (m, 1H), 3.26-3.22 (m, 1H), 3.10-3.06
(m, 1H), 2.88-2.78 (m, 2H), 1.98-1.89 (m, 2H), 1.81-1.74 (br, 2H), 1.71-1.64 (m, 2H); 13C NMR (125 MHz, CDCl3)
δ 161.8 (d, JC-F = 246.2 Hz), 143.6, 142.5, 132.4 (d, JC-F = 7.8 Hz), 131.5 (d, JC-F = 3.4 Hz), 130.0, 126.5, 126.1,
116.0 (d, JC-F = 21.8 Hz), 44.0, 38.8, 36.1, 31.9, 28.3, 27.9; 19F NMR (470 MHz, CDCl3) δ -115.7; HRMS (ESI)
calcd for C18H20FS [M + H+], 287.1264; found: 287.1260.
(4-Chlorophenyl)((6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)methyl)sulfane (4e). (25 mg, 65%). Isolated
by flash column chromatography (ethyl acetate/hexane = 1:120, Rf = 0.5); 1H NMR (500 MHz, CDCl3) δ 7.30-7.26
(m, 4H), 7.19-7.11 (m, 4H), 3.43-3.39 (m, 1H), 3.29-3.25 (m, 1H), 3.14-3.10 (m, 1H), 2.89-2.79 (m, 2H), 1.97-1.89
(m, 2H), 1.81-1.74 (br, 2H), 1.71-1.64 (br, 2H); 13C NMR (125 MHz, CDCl3) δ 143.5, 142.4, 135.3, 131.9, 130.6,
130.0, 129.0, 126.5, 126.2, 44.0, 37.6, 36.2, 32.0, 28.2, 27.8; HRMS (ESI) calcd for C18H20ClS [M + H+], 303.0969;
found: 303.0974.
(4-Bromophenyl)((6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)methyl)sulfane (4f). (26 mg, 76%). Isolated
by flash column chromatography (ethyl acetate/hexane = 1:120, Rf = 0.5); 1H NMR (500 MHz, CDCl3) δ 7.43-7.40
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(m, 2H), 7.24-7.21 (m, 2H), 7.17-7.13 (m, 2H), 7.13-7.11 (m, 2H), 3.43-3.39 (m, 1H), 3.29-3.24 (m, 1H), 3.14-3.10
(m, 1H), 2.89-2.79 (m, 2H), 1.97-1.87 (br, 2H), 1.83-1.74 (br, 2H), 1.72-1.63 (br, 2H); 13C NMR (125 MHz, CDCl3)
δ 143.5, 142.4, 136.0, 131.9, 130.7, 130.0, 126.5, 126.2, 119.7, 44.0, 37.4, 36.2, 32.0, 28.3, 27.8; HRMS (ESI)
calcd for C18H19BrNaS [M + Na+], 369.0283; found: 369.0273.
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5-((Phenylthio)methyl)-2,3,4,5-tetrahydrobenzo[b]oxepine (4g). (24 mg, 90%). Isolated by flash column
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chromatography (ethyl acetate/hexane = 1:50, Rf = 0.5); H NMR (500 MHz, CDCl3) δ 7.37-7.35 (m, 2H),
7.32-7.29 (m, 2H), 7.22-7.17 (m, 2H), 7.12 (dd, J = 7.4, 1.6 Hz, 1H), 7.05-7.01 (m, 2H), 4.38-4.34 (m, 1H), 3.69
(td, J = 11.8, 1.8 Hz, 1H), 3.46-3.41 (m, 1H), 3.38-3.34 (m, 1H), 3.13-3.08 (m, 1H), 2.30-2.16 (m, 2H), 1.86-1.79
(m, 2H); 13C NMR (125 MHz, CDCl3) δ 159.7, 136.9, 130.2, 129.2, 128.9, 128.1, 125.9, 123.8, 122.2, 73.7, 43.7,
36.0, 28.9, 27.1; HRMS (ESI) calcd for C17H18NaOS [M + Na+], 293.0971; found: 293.0961.
5-(((4-Chlorophenyl)thio)methyl)-7-isopropyl-2,3,4,5-tetrahydrobenzo[b]oxepine (4h). (29 mg, 84%).
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Isolated by flash column chromatography (ethyl acetate/hexane = 1:50, Rf = 0.5); H NMR (500 MHz, CDCl3) δ
7.28-7.24 (m, 4H), 7.04-7.01 (m, 1H), 6.92-6.90 (m, 2H), 4.36-4.32 (m, 1H), 3.64 (td, J = 12.0, 1.8 Hz, 1H),
3.43-3.38 (m, 1H), 3.35-3.30 (m, 1H), 3.07-2.99 (m, 1H), 2.90-2.81 (m, 1H), 2.28-2.11 (m, 2H), 1.84-1.76 (m, 2H),
1.25 (s, 3H), 1,23 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 157.6, 144.2, 136.2, 135.2, 131.7, 130.5, 128.9, 128.3,
125.8, 121.8, 73.5, 44.1, 36.2, 33.4, 29.0, 27.0, 24.2, 24.1; HRMS (APCI) calcd for C20H24OClS [M + H+],
347.1231; found: 347.1215.
((5,6,7,8,9,10-Hexahydrobenzo[8]annulen-5-yl)methyl)(phenyl)sulfane (4i). (10 mg, 36%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:150, Rf = 0.7); 1H NMR (500 MHz, CDCl3) δ 7.32-7.29 (m, 2H),
7.22-7.18 (m, 3H), 7.13-7.11 (m, 1H), 7.09-7.06 (m, 1H), 7.04-7.01 (m, 1H), 7.01-6.98 (m, 1H), 3.19-3.14 (m, 1H),
2.94-2.90 (m, 1H), 2.85-2.80 (m, 1H), 2.66-2.63 (m, 2H), 2.19-2.14 (m, 1H), 2.00-1.94 (m, 1H), 1.71-1.38 (m, 6H);
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General procedure and characterization data for product 10. To a mixture of alkene 1 (0.1 mmol),
N-(phenylseleno)phthalimide (N-PSP) 9 (0.12 mmol) and FeCl3 (1.6 mg, 10 mol %), 1,2-dichloroethane (1.0 mL)
was added under nitrogen at room temperature. Then the resulting mixture was sealed and stirred at 100 °C for 12 h.
After the mixture was cooled to room temperature, the resulting solution was directly filtered through a pad of
celite by dichloromethane. The solvent was evaporated in vacuo to give the crude product. The residue was purified
by preparative chromatography on silica gel (ethyl acetate/hexane) to give the pure product 10.
Phenyl(1,2,3,4-tetrahydronaphthalen-2-yl)selane (10a). (27 mg, 94%). Isolated by flash column
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chromatography (ethyl acetate/hexane = 1:100, Rf = 0.8); H NMR (500 MHz, CDCl3) δ 7.64-7.62 (m, 2H),
7.35-7.30 (m, 3H), 7.16-7.09 (m, 3H), 7.05-7.03 (m, 1H), 3.70-3.64 (m, 1H), 3.24 (dd, J = 16.6, 5.0 Hz, 1H),
3.02-2.94 (m, 2H), 2.90-2.84 (m, 1H), 2.32-2.27 (m, 1H), 2.00-1.92 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 135.6,
135.5, 134.9, 129.0, 128.9, 128.8, 128.7, 127.6, 126.0, 125.8, 39.0, 36.9, 30.3, 29.2; HRMS (ESI) calcd for
C16H17Se [M + H+], 289.0490; found: 289.0479.
Phenyl((1,2,3,4-tetrahydronaphthalen-1-yl)methyl)selane (10b). (26 mg, 85%). Isolated by flash column
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chromatography (ethyl acetate/hexane = 1:100, Rf = 0.8); H NMR (500 MHz, CDCl3) δ 7.58-7.56 (m, 2H),
7.32-7.26 (m, 3H), 7.15-7.10 (m, 4H), 3.35 (dd, J = 11.8, 3.2 Hz, 1H), 3.17-3.13 (m, 1H), 3.11-3.06 (m, 1H),
2.84-2.73 (m, 2H), 2.08-2.03 (m, 1H), 1.98-1.91 (m, 1H), 1.88-1.81 (m, 1H), 1.79-1.72 (m, 1H); 13C NMR (125
MHz, CDCl3) δ 139.5, 137.2, 132.7, 130.9, 129.2, 129.1, 128.8, 126.8, 126.1, 125.8, 37.9, 35.6, 29.7, 27.4, 19.2;
HRMS (ESI) calcd for C17H18NaSe [M + Na+], 325.0466; found: 325.0453.
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((7-Methyl-1,2,3,4-tetrahydronaphthalen-1-yl)methyl)(phenyl)selane (10c). (27 mg, 85%). Isolated by flash
column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.8); 1H NMR (500 MHz, CDCl3) δ 7.59-7.57 (m, 2H),
7.33-7.26 (m, 3H), 7.01-7.00 (m, 1H), 6.98-6.95 (m, 2H), 3.36 (dd, J = 11.8, 3.3 Hz, 1H), 3.18-3.13 (m, 1H),
3.09-3.04 (m, 1H), 2.81-2.69 (m, 2H), 2.31 (s, 3H), 2.07-2.02 (m, 1H), 1.97-1.91 (m, 1H), 1.88-1.80 (m, 1H),
1.78-1.71 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 139.3, 135.2, 134.1, 132.7, 131.0, 129.4, 129.1, 129.0, 127.1,
126.8, 38.0, 35.6, 29.3, 27.5, 21.1, 19.4; HRMS (APCI) calcd for C18H19Se [M - H+], 315.0647; found: 315.0631.
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((7-Methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl)(phenyl)selane (10d). (28 mg, 65%). Isolated by
flash column chromatography (ethyl acetate/hexane = 1:40, Rf = 0.6); 1H NMR (500 MHz, CDCl3) δ 7.58-7.56 (m,
2H), 7.32-7.27 (m, 3H), 7.02 (d, J = 8.4 Hz, 1H), 6.73 (dd, J = 8.4, 2.6 Hz, 1H), 6.68 (d, J = 2.6 Hz, 1H), 3.78 (s,
3H), 3.35 (dd, J = 12.0, 3.6 Hz, 1H), 3.17-3.13 (m, 1H), 3.08-3.03 (m, 1H), 2.78-2.66 (m, 2H), 2.05-2.00 (m, 1H),
1.96-1.90 (m, 1H), 1.87-1.79 (m, 1H), 1.77-1.70 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 157.6, 140.5, 132.7,
130.9, 130.1, 129.3, 129.1, 126.9, 113.9, 112.2, 55.3, 38.3, 35.6, 28.9, 27.5, 19.5; HRMS (APCI) calcd for
C18H19OSe [M - H+], 331.0596; found: 331.0582.
((7-Isopropyl-1,2,3,4-tetrahydronaphthalen-1-yl)methyl)(phenyl)selane (10e). (30 mg, 88%). Isolated by
flash column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.7); 1H NMR (500 MHz, CDCl3) δ 7.59-7.57 (m,
2H), 7.33-7.26 (m, 3H), 7.05-7.01 (m, 2H), 7.00 (s, 1H), 3.36 (dd, J = 12.0, 3.6 Hz, 1H), 3.19-3.14 (m, 1H),
3.10-3.05 (m, 1H), 2.89-2.83 (m, 1H), 2.81-2.69 (m, 2H), 2.07-2.02 (m, 1H), 1.97-1.90 (m, 1H), 1.87-1.79 (m, 1H),
1.78-1.71 (m, 1H), 1.26 (s, 3H), 1.24 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 146.4, 139.3, 134.5, 132.6, 131.0,
129.2, 129.1, 126.9, 126.8, 124.3, 38.1, 35.7, 33.8, 29.3, 27.5, 24.1, 24.0, 19.3; HRMS (ESI) calcd for C20H24NaSe
[M + Na+], 367.0935; found: 367.0925.
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((5,8-Dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)methyl)(phenyl)selane (10f). (30 mg, 92%). Isolated by
flash column chromatography (ethyl acetate/hexane = 1:100, Rf = 0.7); 1H NMR (500 MHz, CDCl3) δ 7.64-7.62 (m,
2H), 7.33-7.29 (m, 3H), 6.97 (d, J = 7.6 Hz, 1H), 6.92 (d, J = 7.6 Hz, 1H), 3.17-3.12 (m, 2H), 3.05-3.00 (m, 1H),
2.78-2.73 (m, 1H), 2.59-2.51 (m, 1H), 2.38-2.35 (m, 1H), 2.21 (s, 3H), 2.12 (s, 3H), 1.91-1.81 (m, 2H), 1.74-1.67
(m, 1H); 13C NMR (125 MHz, CDCl3) δ 138.1, 135.0, 134.4, 133.8, 133.6, 130.3, 129.0, 127.8, 127.7, 127.2, 35.2,
32.4, 26.8, 25.0, 19.7, 18.6, 17.0; HRMS (APCI) calcd for C19H21Se [M - H+], 329.0803; found: 329.0787.
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Dimethyl 4-((phenylselanyl)methyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (10g). (32 mg, 78%).
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Isolated by flash column chromatography (ethyl acetate/hexane = 1:10, Rf = 0.5); H NMR (500 MHz, CDCl3) δ
7.56-7.54 (m, 2H), 7.33-7.24 (m, 3H), 7.21-7.15 (m, 4H), 3.79 (s, 3H), 3.62 (s, 3H), 3.48 (dd, J = 12.0, 3.4 Hz, 1H),
3.37 (dd, J = 16.0, 2.1 Hz, 1H), 3.32-3.26 (m, 2H), 3.20-3.16 (m, 1H), 2.91-2.86 (m, 1H), 2.15-2.10 (m, 1H); 13C
NMR (125 MHz, CDCl3) δ 172.1, 171.0, 137.0, 133.9, 133.1, 130.3, 129.0, 128.9, 127.1, 127.0, 126.6, 126.5, 53.9,
52.8, 52.6, 35.6, 35.5, 35.4, 34.7; HRMS (ESI) calcd for C21H22NaO4Se [M + Na+], 441.0576; found: 441.0581.
4-((Phenylselanyl)methyl)chromane (10h). (29 mg, 95%). Isolated by flash column chromatography (ethyl
acetate/hexane = 1:60, Rf = 0.5); 1H NMR (500 MHz, CDCl3) δ 7.60-7.58 (m, 2H), 7.35-7.28 (m, 3H), 7.14 (td, J =
15.4, 1.6 Hz, 1H), 7.11 (dd, J = 7.6, 1.6 Hz, 1H), 6.89 (td, J = 7.6, 1.2 Hz, 1H), 6.85 (dd, J = 8.2, 1.2 Hz, 1H),
4.24-4.20 (m, 1H), 4.17-4.13 (m, 1H), 3.48-3.42 (m, 1H), 3.11-3.02 (m, 2H), 2.19-2.16 (m, 2H); 13C NMR (125
MHz, CDCl3) δ 154.5, 132.9, 130.2, 129.3, 129.2, 128.0, 125.0, 120.4, 117.0, 62.9, 34.7, 33.9, 26.5; HRMS (ESI)
calcd for C16H16NaOSe [M + Na+], 327.0259; found: 327.0268.
6-Phenyl-4-((phenylselanyl)methyl)chromane (10i). (33 mg, 87%). Isolated by flash column chromatography
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(ethyl acetate/hexane = 1:60, Rf = 0.5); H NMR (500 MHz, CDCl3) δ 7.61-7.59 (m, 2H), 7.55-7.53 (m, 2H),
7.46-7.43 (m, 2H), 7.39 (dd, J = 8.4, 2.2 Hz, 1H), 7.35-7.30 (m, 5H), 6.92 (d, J = 8.4 Hz, 1H), 4.28-4.24 (m, 1H),
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4.22-4.17 (m, 1H), 3.53-3.48 (m ,1H), 3.16-3.10 (m, 2H), 2.25-2.17 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 154.1,
140.9, 133.6, 133.0, 130.2, 129.3, 128.7, 127.9, 127.2, 126.8, 126.7, 126.6, 125.2, 117.4, 63.1, 34.7, 34.1, 26.7;
HRMS (ESI) calcd for C22H20NaOSe [M + Na+], 403.0572; found: 403.0570.
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Kinetic isotope effect experiment. Intermolecular competition: To a mixture of alkene 1a (0.05 mmol) and
1a-D7 (0.05 mmol) in the same tube, N-phenylsulfenylimide 2a (0.12 mmol), FeCl3 (1.6 mg, 10 mol %) and
1,2-dichloroethane (1.0 mL) was added sequentially under nitrogen at room temperature. Then the resulting
mixture was sealed and stirred at 50 °C for 0.5 h. Then the mixture was immediately cooled to 0 oC with ice-water.
The 1H NMR was carried out to determine the yields of 3aa and 3aa-D6 using mesitylene as an internal standard.
Two parallel reactions: To a mixture of alkene 1a (0.1 mmol), N-phenylsulfenylimide 2a (0.12 mmol), FeCl3 (1.6
mg, 10 mol %) and 1,2-dichloroethane (1.0 mL) was added sequentially under nitrogen at room temperature. In
another tube, 1a-D7 (0.1 mmol) was added, and the other conditions are the same. Then the two tubes were sealed
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and simultaneously stirred at 50 °C for 0.5 h. Then the mixtures were immediately cooled to 0 C with ice-water.
The 1H NMR was separately carried out to determine the yields of 3aa and 3aa-D6 using mesitylene as an internal
standard. 1-(But-3-en-1-yl-1,1-d2)benzene-2,3,4,5,6-d5 (1a-D7). 1H NMR (500 MHz, CDCl3) δ 5.94-5.85 (m, 1H),
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5.07 (dq, J = 17.2, 1.6 Hz, 1H), 5.02-5.00 (m, 1H), 2.40 (d, J = 6.6 Hz, 1H); EI-MS (m/z) = 139.1. 3aa-D6. H
NMR (500 MHz, CDCl3) δ 7.49-7.47 (m, 2H), 7.35-7.33 (m, 2H), 7.29-7.26 (m, 1H), 3.60-3.54 (m, 1H), 3.19-3.15
(m, 1H), 3.89-2.84 (m, 1H), 2.24-2.22 (m, 1H), 1.86-1.81 (m, 1H); EI-MS (m/z) = 246.4.
ASSOCIATED CONTENT
Supporting Information
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Copies of H and 13C NMR spectra of all new compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
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* lvleiyang2008@ ruc.edu.cn; zhipingli@ruc.edu.cn
ORCID
Leiyang Lv: 0000-0002-2850-8952
Zhiping Li: 0000-0001-7987-279X
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Financial support from the National Science Foundation of China is acknowledged (21672259). Dr. L. Lv is
grateful for the support from National Postdoctoral Program for Innovative Talents (No. BX201700110) and China
Postdoctoral Science Foundation Funded Project (No. 2017M623270).
REFERENCES
(1) (a) Wang, J.-M.; Ding, G.-Z.; Fang, L.; Dai, J.-G.; Yu, S.-S.; Wang, Y.-H.; Chen, X.-G.; Ma, S.-G.; Qu, J.; Xu, S.;
Du, D. Thiodiketopiperazines Produced by the Endophytic Fungus Epicoccum nigrum. J. Nat. Prod. 2010, 73,
1240-1249. (b) Guo, H.; Sun, B.; Gao, H.; Chen, X.; Liu, S.; Yao, X.; Liu, X.; Che, Y. Diketopiperazines from the
Cordyceps-Colonizing Fungus Epicoccum nigrum. J. Nat. Prod. 2009, 72, 2115-2119.
(2) (a) Feng, M.; Tang, B.; Liang, S. H.; Jiang, X. Sulfur Containing Scaffolds in Drugs: Synthesis and Application
in Medicinal Chemistry. Curr. Top. Med. Chem. 2016, 16, 1200-1216; (b) Ilardi, E. A.; Vitaku, E.; Njardarson, J. T.
Data-Mining for Sulfur and Fluorine: An Evaluation of Pharmaceuticals To Reveal Opportunities for Drug Design
and Discovery. J. Med. Chem. 2014, 57, 2832-2842. (c) Wilson, A. J.; Kerns, J. K.; Callahan, J. F.; Moody, C. J.
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