Rhodium(III)-catalyzed [4+2] annulation via C-H activation: Synthesis of multi-substituted naphthalenone sulfoxonium ylides

Article abstract of DOI:10.3390/molecules24101884

A convenient Rh(III)-catalyzed C-H activation and cascade [4+2] annulation for the synthesis of naphthalenone sulfoxonium ylides has been developed. This method features perfect regioselectivity, mild and redox-neutral reaction conditions, and broad substrate tolerance with good to excellent yields. Preliminary mechanistic experiments were conducted and a plausible reaction mechanism was proposed. The new type naphthalenone sulfoxonium ylides could be further transformed into multi-substituted naphthols, which demonstrates the practical utility of this methodology.

Full text of DOI:10.3390/molecules24101884

molecules
Article
Rhodium(III)-Catalyzed [4+2] Annulation via C-H
Activation: Synthesis of Multi-Substituted
Naphthalenone Sulfoxonium Ylides
Xiaohan Song 1,2, Xu Han 1,2, Rui Zhang 1,2, Hong Liu 1,2,* and Jiang Wang 1,2,
*
1
State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research, Shanghai Institute of
Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; xiaohanpharm@163.com (X.S.);
dtchx_cbdml@hotmail.com (X.H.); ruipharmacy@163.com (R.Z.)
University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China
Correspondence: hliu@simm.ac.cn (H.L.); jwang@simm.ac.cn (J.W.); Tel.: +86-50807042 (H.L.)
2
*
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
Academic Editor: Il Kim
Received: 28 April 2019; Accepted: 14 May 2019; Published: 16 May 2019
ꢀꢁꢂꢃꢄꢅꢆ
Abstract: A convenient Rh(III)-catalyzed C-H activation and cascade [4+2] annulation for the
synthesis of naphthalenone sulfoxonium ylides has been developed. This method features perfect
regioselectivity, mild and redox-neutral reaction conditions, and broad substrate tolerance with
good to excellent yields. Preliminary mechanistic experiments were conducted and a plausible
reaction mechanism was proposed. The new type naphthalenone sulfoxonium ylides could be
further transformed into multi-substituted naphthols, which demonstrates the practical utility of
this methodology.
Keywords: rhodium(III); sulfoxonium ylides; naphthols
1. Introduction
Substituted naphthols have been characterized as crucial organic motifs and are embedded in
various pharmaceuticals and natural products such as rifampicin [
A [ ], propranolol [10 13], and naftopidil [14 16] (Figure 1). As a result, the development of efficient
methods to synthesize multi-substituted naphthols is important [17 20]. Over the past few years,
transition-metal-catalyzed C–H activation has been demonstrated to be a convenient strategy to
establish aromatic and heteroaromatic skeletons [21 24]. Nevertheless, the synthetic approach for
multi-substituted naphthols is scarcely reported [25 29]. For example, it can be synthesized by the
Rh(III)-catalyzed cross-coupling of benzoylates with diphenylacetylene (Scheme 1a) [25 27]. Recently,
1–3], gossypol [4–6], dioncophylline
7–
9
–
–
–
–
–
–
Li and co-workers have demonstrated a strategy using phosphonium ylides and diazo compounds
to access naphthol derivatives [29]. Thus, development of an efficient, straightforward route to the
naphthol framework is highly desired.
Molecules 2019, 24, 1884; doi:10.3390/molecules24101884
www.mdpi.com/journal/molecules

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Figure 1. Representative compounds with a 1-naphthol moiety.
Scheme 1.
(a) Reports of approaches to substituted naphthol; (b) Recent advances in the synthesis of
bis-substituted sulfoxonium ylide.

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Recently, sulfoxonium ylides have been identified as a precursor of carbenoid in the
transition-metal-catalyzed reactions [30 32]. Being successfully applied to the multi-kilogram
synthesis of drug intermediates via Ir(I)-catalyzed reactions in industry [33 34] sulfoxonium ylides
have also been widely investigated in the Rh(III)- [35 44], Co(III)- [45], or Ru(II)-catalyzed [46,47]
–
,
–
C-H bond functionalization. However, the application of sulfoxonium ylides is severely limited by
its substrate scope because the C1 position substitution in the ylide center is only H. To overcome
such limitations, Bayer and co-workers reported the synthesis of bis-substituted sulfoxonium ylides
via rhodium-catalyzed coupling of iodonium ylides with sulfoxides (Scheme 1b) [48]. Burtoloso et al.
described another strategy to access
Aïssa et al. developed a palladium-catalyzed C
aryl halide to afford the (hetero)aryl-substituted sulfoxonium ylides, which expanded the scope of the
substitution in the ylide center [50]. However, the synthetic approach for cyclic sulfoxonium ylides
remains unexplored.
α
-aryl-
β
-keto sulfoxonium ylides using aryne [49]. Furthermore,
H cross-coupling of -ester sulfoxonium ylides with
−
α
A seminal work reported by Li and co-workers revealed that sulfoxonium ylides could serve as
weak directing-groups to participate in C-H activation [27,51]. Inspired by the previous work, we report
a Rh(III)-catalyzed C-H activation and [4+2] annulation to afford the naphthalenone sulfoxonium ylides
and its synthetic utility is further demonstrated through simple reactions to access multi-substituted
naphthols. It is worth mentioning that, during our submission, Fan’s group also reported a very similar
approach to the synthesis of naphthalenone sulfoxoniums [52].
2. Results and Discussion
We initiated our studies with model substrates sulfoxonium ylide 1a and diazo compound 2a
to investigate the optimal reaction conditions (Table 1). Initially, transition-metal catalysts (Ru(II),
Co(III), Ir(III), and Rh(III)), which could potentially trigger the cross-coupling of 1a with 2a, were
screened to demonstrate the feasibility of this method (entries 1–4). To our delight, the target molecule
naphthalenone sulfoxonium ylide 3aa could be obtained in a moderate yield of 65% in the presence of
[Cp*RhCl2]2 and AgSbF6 under air condition at r.t. for 12 h. Several typical additives, including PivOH,
CsOAc, Zn(OTf)2, Cu(OAc)2, and Zn(OAc)2, were subsequently explored (entries 5–9), and Zn(OAc)2
exhibited the best additive for this annulation, because a more powerful catalyst Cp*Rh(OAc) could be
formed after adding Zn(OAc)2 [42], while CsOAc and Zn(OTf)2 could not afford compound 3aa at all.
Subsequent Ag salt screening revealed that replacement of AgSbF6 by AgNTf2 decreased the yield
(entry 10). Encouraged by these results, we further screened the solvent and found that TFE, MeOH,
and MeCN reduced the reaction conversion (entries 11–13). The optimal results could be achieved
when sulfoxonium ylide (1a, 0.2 mmol) and diazo compounds (2a, 0.44 mmol) were treated with the
catalytic system of [Cp*RhCl2]2 (5 mol%), AgSbF6 (30 mol%), and Zn(OAc)2 (30 mol%) in DCE at room
temperature for 12 h.

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Table 1. Optimization of the reaction conditions a.
Yield b
Entry
Catalyst
Additive
Ag Salt
Solvent
DCE d
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
N.R. f
N.R.
N.R.
65%
77%
N.R.
N.R.
65%
1
2
3
4
5
6
7
8
9
10
11
12
13
[RuCl2(p-cymene)]2
Cp*C◦COI2c
[Cp*IrCl2]2
-
-
-
-
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
PivOH
CsOAc
Zn(OTf)2
Cu(OAc)2
Zn(OAc)2
Zn(OAc)2
Zn(OAc)2
Zn(OAc)2
Zn(OAc)2
95% (90% g)
48%
DCE
TFE e
MeOH
MeCN
85%
14%
trace
a
Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), catalyst (5 mol%), Ag salt (20 mol%), additive (30
b
c
mol%), in solvent (3 mL), tube for 12 h at room temperature.
1,2,3,4,5-pentamethylcyclopenta-1,3-diene.
reaction. Yield of the isolated product.
Yield determined by 1H NMR. Cp* =
d
e
f
DCE = dichloroethane.
TFE = trifluoroethanol. N.R. = No
g
With the optimal reaction conditions in hand, we started to explore the generality and scope of
sulfoxonium ylides (1a 1j) by performing the annulation with diazo compound 2a (Scheme 2).
–
It was found that this reaction could tolerate various substrates with both electron-donating
and electron-withdrawing substituents in the sulfoxonium ylides system, and afforded the
corresponding naphthalenone sulfoxonium ylides in good to excellent yields (3aa–3da, 44–96%).
Generally, sulfoxonium ylides with electron-donating substituents gave higher yields compared
with electron-withdrawing substituents. To further investigate the effect of substituted group of the
sulfoxonium yield, several moieties were independently introduced at the para-position of the phenyl
ring while the ortho-position was blocked by chlorine. As a result, the naphthalenone sulfoxonium
ylides were obtained in good to excellent yields (3ea
the meta-position resulted in excellent yields (3ja 3la, 84–94%). It is worth noting that using
1p) with 2a, the dialkylated product could be
–3ia, 78–96%). Introducing substituents at
–
ortho-non-substituted benzoyl sulfoxonium ylides (1m
–
obtained in good yields (3ma–3pa, 59–76%).

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O
O
S
[Cp*RhCl2]2 5 mol%
AgSbF6 20 mol%
O
O
S
O
O
R1
+
Ph
OEt
R1
Ph
Zn(OAc)2 30 mol%
DCE r.t. 12 h
N2
2a
COOEt
1
3aa-3ja
O
O
S
Cl
O
O
S
Br
O
O
S
CF3
O
O
S
Ph
Ph
COOEt
Ph
Ph
COOEt
COOEt
COOEt
3aa
, 90%
3ca
3da
, 44%
, 96%
3ba
, 91%
Cl
O
O
S
Cl
O
O
S
Cl
O
O
S
Cl
O
O
S
Ph
F
Ph
COOEt
Cl
Ph
MeO
Ph
COOEt
COOEt
COOEt
3ea
, 96%
3ga
Cl
, 96%
3ha
Cl
, 87%
3fa
, 98%
Cl
O
O
O
O
S
O
O
Cl
O
O
S
S
S
Br
F3C
Ph
Ph
Ph
Ph
COOEt
COOEt
OMe COOEt
COOEt
3ia
, 78%
3ka
, 85%
3la
3ja
, 94%
, 84%
O
O
O
O
COOEt
O
COOEt
O
COOEt
COOEt
O
Ph
O
S
Ph
O
S
Ph
O
O
S
Ph
Br
O
S
Ph
Ph
tBu
Ph
Ph
COOEt
COOEt
COOEt
COOEt
c
c
c
c
3ma
, 76%
3na
, 72%
3oa
3pa
, 74%
, 59%
a, b
a
Scheme 2. Scope of sulfoxonium ylides
.
Reaction conditions: 1 (0.2 mmol), 2a (0.22 mmol),
[Cp*RhCl2]2 (5 mol%), AgSbF6 (20 mol%), and Zn(OAc)2 (30 mol%) in DCE (2 mL) at r.t. for 12 h under
b
c
air condition. Yield of the isolated product. Reaction conditions: sulfoxonium ylide 1 (0.2 mmol),
diazo compound 2a (0.44 mmol), [Cp*RhCl2]2 (5 mol%), AgSbF6 (20 mol%), and Zn(OAc)2 (30 mol%)
in DCE (2 mL) at 60 ◦C for 4 h under air condition.
Next, in order to expand the utility of this reaction, we investigated the scope and generality
of the diazo compounds (Scheme 3). Diazo compounds with the electron-donating and halogen
groups at the para-position of its phenyl ring (R2) resulted in good to excellent yields of corresponding
products (3ab–3ad and 3af, 79–95%), while electron-withdrawing group led to poor yield (3ae, 53%).
The structure of product 3ac was confirmed by X-ray crystallography (CCDC 1899265). It should be
mentioned that the substituents of diazo compounds at the different positions of its phenyl ring (R2)
did not alter the reaction efficiency, provided the desired products in high yields (3ag
Moreover, when R2 was replaced by methyl or cyclopropyl the yields are 91% and 72%, respectively
3ak and 3al), which indicated that increasing of the steric hindrance of R2 group decreased the yield
–3aj, 77%–84%).
(

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of this reaction. At the same time, R3 groups with the large steric hindrance were well tolerated in this
reaction (3am and 3an, 89% and 61%).
a
Scheme 3. Scope of diazo compounds a,b
.
Reaction conditions: sulfoxonium ylide 1a (0.2 mmol),
diazo compounds 2 (0.22 mmol), [Cp*RhCl2]2 (5 mol%), AgSbF6 (20 mol%), and Zn(OAc)2 (30 mol%)
b
c
in DCE (2 mL) at r.t. for 12 h under air condition. Yield of the isolated product. Determined by
single X-ray crystal structure analysis.
To further assess synthetic utility of the reaction, a gram-scale reaction between 1a and 2a has
been performed, and the product 3aa was isolated with a 79% yield (Scheme 4a). Moreover, as a
versatile structural motif, the synthetic application of the naphthalenone sulfoxonium ylides has
been investigated. Naphthalenone sulfoxonium ylide 3ak was transformed to the tetra-substituted
α
-naphthol 5ak, of which the skeleton was embedded in rifampicin [1–3], via Ir(II)-catalyzed amination
in a moderate yield of 45% (Scheme 4b) [49]. In addition, compound 3ak was reduced to sulfoxide 6ak
in a good yield of 65%, which could be used to synthesize the FabH inhibitor [51,53], (Scheme 4c).

Molecules 2019, 24, 1884
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Scheme 4. (a) Gram-scale synthesis of compound 3aa; (b) Synthetic applications of 3ak.
To obtain more insight into the mechanism of this annulation, a series of experiments were
performed (Scheme 5). First, a hydrogen deuterium exchange experiment of 1a was carried out using
CD3OD under the standard conditions (Scheme 5a). Compound 1a underwent slight H/D exchange
in the presence of the Rh(III) catalyst, indicating the reversibility of the C(aryl) H bond cleavage.
−
−
To further probe the C-H activation process, the kinetic isotopic effect (KIE) studies with separate kinetic
experiments were performed to gain insights into the rate-determining step for this cross-coupling
reaction (Scheme 5b). The KIE was determined by performing intermolecular competition experiments
using an equimolar mixture of 1a and 1a-d7 in the couplings with 2k under standard conditions.
The KIE value was 2.8, which was observed on the basis of the 1H NMR analysis (see supplementary
materials), indicating that the C–H activation was involved in the turnover-limiting step.
Scheme 5. (a) H/D exchange experiment of 1a; (b) KIE experiment.

Molecules 2019, 24, 1884
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Based on these preliminary mechanistic investigations, a plausible reaction mechanism for
the formation of naphthalenone sulfoxonium ylide 3aa is proposed in Scheme 6. Initially, oxygen
coordination of 1a is followed by cyclometalation to deliver a five-membered rhodacyclic intermediate
A
. Then, the nucleophilic C(aryl)
carbene species with the loss of N2. The resulting species
insertion to furnish another six-membered rhodacyclic intermediate
by HX releases the key intermediate with the regeneration of the active Rh(III) catalyst. Finally,
−
Rh species further attacks the diazo compound 2a to generate Rh(III)
further undergoes carbene migratory
. Protonolysis of the Rh C bond
B
B
C
−
D
intermediate D undergoes a sequential aldol condensation to form the desired product 3aa.
Scheme 6. Proposed reaction mechanism.
3. Materials and Methods
3.1. General Information
The reagents (chemicals) were purchased from commercial sources, and used without further
purification. Analytical thin layer chromatography (TLC) was HSGF 254 (0.15–0.2 mm thickness).
All products were characterized by their NMR and MS spectra. The 1H- (500 MHz) and 13C-NMR
(125 MHz) spectra were recorded in deuterochloroform (CDCl3) on Bruker Avance III spectrometer
(Billerica, MA, USA). Chemical shifts were reported in parts per million (ppm, δ) downfield from
tetramethylsilane. Proton coupling patterns are described as singlet (s), doublet (d), triplet (t), quartet
(q), or multiplet (m). Low-resolution mass spectra (LRMS) were measured on Agilent 1260 Infinity II
(Palo Alto, CA, USA). High-resolution mass spectra (HRMS) were measured on Agilent 1290-6545
UHPLC-QTOF respectively (Palo Alto, CA, USA).
3.2. Experimental Part Method
3.2.1. General Procedure for the Preparation of Sulfoxonium Ylides 1a–1p
Sulfoxonium ylides 1a–1p were prepared according to the reported procedures [28]. To a stirred
solution of potassiumtert-butoxide (3.3 equiv.) in THF was added trimethylsulfoxonium iodide
(3.0 equiv.) at room temperature. The resulting mixture is refluxed for 2 h. Then reaction mixture
was cooled to 0 ◦C, followed by the addition of acyl chlorides (1.0 equiv.) in THF. The reaction was

Molecules 2019, 24, 1884
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allowed to reach room temperature and stirred for 3 h. Next, the solvent was evaporated, and water
and ethylacetate were added to the resulting slurry. The layers were separated and the aqueous layer
was washed with ethyl acetate and the organic layers were combined. The organic solution was dried
over anhydrous sodium sulphate (Na2SO4), filtered over a sintered funnel, and evaporated to dryness.
The crude product was purified by flash chromatography over silica gel using DCM/MeOH (95:5) to
afford the corresponding sulfoxonium ylides 1a–1p.
3.2.2. General Procedure for the Preparation of α-Diazocarbonyl Compounds 2a–2n
The
α
-diazocarbonyl compounds 2a
–
2n were prepared according to the reported procedures [29].
To a solution of
β
-ketoester or
β
-diketone (1.0 equiv.) and N-(4-azidosulfonylphenyl)acetamide
◦
(1.2 equiv.) in CH3CN at 0 C was added DBU (1.2 equiv.). The resulting solution was stirred at
0 ◦C for 3 h and slowly brought to room temperature. Upon completion, as indicated by thin layer
chromatography (TLC), the reaction was quenched with water, extracted with ethyl acetate, and dried
over anhydrous Na2SO4. The reaction mixture was concentrated under reduced pressure, and the crude
product was purified by column chromatography using n-hexane/EtOAc (92:8) to afford corresponding
α-diazocarbonyl compounds 2a–2n.
3.2.3. General Procedures for the Products 3aa–3la, 3ab–3an (Compound 3aa as the Example)
A tube was charged with [Cp*RhCl2] 2 (6.0 mg, 5 mol%), AgSbF6 (14 mg, 20 mol%), Zn(OAc)2
(14 mg, 30 mol%), sulfoxonium ylide (1a, 0.2 mmol), α-diazocarbonyl compound (2a, 0.24 mmol),
and DCE (3 mL). The reaction mixture was stirred at room temperature for 12 h under air condition.
After that, the solvent was removed under reduced pressure and the residue was purified by silica gel
chromatography using DCM/MeOH (98:2) to afford the product 3aa as a light yellow solid.
3.2.4. General Procedures for the Products 3ma–3pa (Compound 3ma as the Example)
A tube was charged with [Cp*RhCl2] 2 (6.0 mg, 5 mol%), AgSbF6 (14 mg, 20 mol%), Zn(OAc)2
(14 mg, 30 mol%), sulfoxonium ylide (1m, 0.2 mmol), α-diazocarbonyl compound (2a, 0.44 mmol), and
DCE (3 mL). The reaction mixture was stirred at 60 ◦C for 4 h under air condition. After that, the solvent
was removed under reduced pressure and the residue was purified by silica gel chromatography using
DCM/MeOH (98:2) to afford the product 3ma as a light yellow solid.
3.2.5. Gram-Scale Synthesis of Compound 3aa
A round bottomed flask was charged with [Cp*RhCl2]2 (147 mg, 238
µmol), AgSbF6 (327 mg,
951
µmol), Zn(OAc)2 (262 mg, 1.43 mmol), sulfoxonium ylide (1a, 4.76 mmol), α
-diazocarbonyl
compound (2a, 1.25 g, 5.71 mmol). Dichloroethane (35 mL) was then added to the reaction mixture
and stirring was turned on. The reaction mixture was stirred at r.t. for 12 h under air condition. After
that, the solvent was removed under reduced pressure and the residue was purified by silica gel
chromatography using DCM/MeOH (99:1) to afford the product 3aa (1.45 g, 79%, light yellow solid).
3.2.6. Synthesis of Compound 5ak
To a 15 mL microwave glass tube containing a magnetic stirrer and fitted with a Teflon cap,
sulfoxonium ylide 3ak (64 mg, 1.0 equiv.), p-methoxyaniline 4 (24 mg, 2.0 equiv.), [Ir(COD)Cl]2 (3 mg,
2.5 mol%), and toluene (1 mL) were added. The mixture was stirred for 1 h at 150 ◦C under microwave
irradiation. Then, the organic solvent was removed in a rotary evaporator and the crude product
purified by flash chromatography (petroleum ether: ethyl acetate = 10:1).
3.2.7. Synthesis of Compound 6ak
A mixture of 3ak (64 mg, 1 equiv.) and NaH (60%, dispersion in paraffin liquid) (28 mg, 0.7 mmol,
3.5 equiv.) was added to a Schlenk tube equipped with a stir bar. Dry THF (1.0 mL) was added and the

Molecules 2019, 24, 1884
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mixture was stirred at 80 ◦C for 24 h under Ar atmosphere. Then, the organic solvent was removed in
a rotary evaporator and the crude product was purified by flash chromatography (petroleum ether:
ethyl acetate = 10:1).
3.2.8. Mechanistic Studies
A tube was charged with [Cp*RhCl2] 2 (6.0 mg, 5 mol%), AgSbF6 (14 mg, 20 mol%), Zn(OAc)2
(14 mg, 30 mol%), sulfoxonium ylide (1a, 0.2 mmol), CD3OD (72 mg, 10 equiv.), and DCE (3 mL).
The reaction mixture was stirred at r.t. for 12 h under air condition. After that, the solvent was removed
under reduced pressure and the residue was purified by silica gel chromatography using DCM/MeOH
1
(96:4) to afford the product, which was characterized by 1H NMR spectroscopy. H NMR analysis of
1a revealed 47% deuteration at the 6-position of phenyl ring and 8% deuteration at the α-position of
the carbonyl.
Two tubes were charged with [Cp*RhCl2]2 (6.0 mg, 5 mol%), AgSbF6 (14 mg, 20 mol%), Zn(OAc)2
(14 mg, 30 mol%), sulfoxonium ylide (1a or 1a–d7, 0.2 mmol), -diazocarbonyl compounds (2k
α
,
0.24 mmol) and DCE (3 mL). The reaction mixture was stirred at r.t. for 2 h under air condition.
After that, the solvent was removed under reduced pressure and the residue was purified by silica gel
chromatography using DCM/MeOH (99:1) to afford the product. The KIE value was determined to be
kH/kD = 2.8 on the basis of 1H NMR analysis.
3.3. Product Characterization
Ethyl 3-(dimethyl(oxo)-λ6-sulfanylidene)-5-methyl-4-oxo-2-phenyl-3,4-dihydronaphthalene-1-
carboxylate (3aa): light yellow solid; m.p.:182–184 ◦C; 1H NMR (400 MHz, Chloroform-d)
δ
7.51 (d,
J = 8.3 Hz, 1H), 7.43 (dd, J = 8.3, 7.1 Hz, 1H), 7.38–7.31 (m, 5H), 7.17 (d, J = 7.1, 1H), 3.92 (q, J = 7.1
Hz, 2H), 3.77 (s, 6H), 2.99 (s, 3H), 0.90 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
176.1,
169.3, 139.5, 137.3, 136.9, 135.9, 130.2, 129.2, 128.8, 128.6, 127.4, 127.2, 123.1, 118.4, 98.3, 60.8, 44.2, 24.4,
δ
13.7. LRMS (ESI): 381.4 [M
381.1177.
−
H]+. HRMS (ESI) calculated for C21H20O4S [M
−
H]+: 381.1166; found:
Ethyl 5-chloro-3-(dimethyl(oxo)-
3ba): light yellow solid; m.p.: 225–226 C; H NMR (500 MHz, Chloroform-d)
3.1 Hz, 1H), 7.41–7.37 (m, 3H), 7.35–7.31 (m, 3H), 7.31–7.26 (m, 2H), 3.90 (q, J = 7.1 Hz, 2H), 3.79 (s, 6H),
0.88 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
172.7, 168.3, 138.1, 136.7, 135.7, 132.6,
λ
6-sulfanylidene)-4-oxo-2-phenyl-3,4-dihydronaphthalene-1-carboxylate
◦
1
(
δ 7.57 (dd, J = 6.4,
δ
129.9, 128.6, 128.2, 127.2, 126.8, 125.6, 123.7, 117.4, 99.1, 60.5, 43.9, 13.1. LRMS (ESI): 403.3 [M
−
H]+.
HRMS (ESI) calculated for C21H19ClO4S [M − H]+: 403.0765; found: 403.0774.
Ethyl5-bromo-3-(dimethyl(oxo)-
3ca): light yellow solid; m.p.: 203-204 ◦C; 1H NMR (400 MHz, Chloroform-d)
7.62 (d, J = 8.3 Hz, 1H), 7.42–7.23 (m, 6H), 3.89 (q, J = 7.1 Hz, 2H), 3.76 (s, 6H), 0.87 (t, J = 7.1 Hz, 3H).
13C NMR (125 MHz, Chloroform-d)
172.9, 168.7, 138.5, 137.1, 136.3, 132.5, 130.6, 129.1, 127.6, 127.2,
λ
6-sulfanylidene)-4-oxo-2-phenyl-3,4-dihydronaphthalene-1-carboxylate
(
δ 7.66 (d, J = 7.6 Hz, 1H),
δ
126.6, 124.8, 120.2, 117.7, 99.2, 61.0, 44.2, 13.6. LRMS (ESI): 447.2 [M
−
H]+. HRMS (ESI) calculated for
C21H19BrO4S [M − H]+: 447.0260; found: 447.0254.
Ethyl 3-(dimethyl(oxo)-
1-carboxylate (3da): light yellow solid; m.p.: 228-230 ◦C; 1H NMR (400 MHz, Chloroform-d)
J = 8.4 Hz, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.41–7.30 (m, 5H), 3.98–3.85 (q, J = 7.2
Hz, 2H), 3.79 (s, 6H), 0.89 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, Chloroform-d)
172.0, 168.8, 139.2,
136.4, 136.2, 129.6, 129.3, 129.0, 127.7 (q, JC–F = 31.0 Hz), 127.7, 127.3, 125.2 (q, JC–F = 8.2 Hz), 124.5 (JC–F
λ
6-sulfanylidene)-4-oxo-2-phenyl-5-(trifluoromethyl)-3,4-dihydronaphthalene-
δ
7.91 (d,
δ
= 271.0 Hz), 117.4, 100.2, 61.0, 43.8, 13.6. 19F NMR (470 MHz, Chloroform-d)
δ -56.9. LRMS (ESI): 459.2
[M − H]+. HRMS (ESI) calculated for C22H19F3O4S [M + Na]+: 459.0848; found: 459.0857.
Ethyl 5-chloro-3-(dimethyl(oxo)-
λ
6-sulfanylidene)-7-methyl-4-oxo-2-phenyl-3,4-dihydronaphthalene-1
-carboxylate (3ea): light yellow solid; m.p.: 212–214 ◦C; 1H NMR (400 MHz, Chloroform-d)
δ
7.42–7.27

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(m, 6H),
δ
7.24 (d, J = 1.6 Hz, 1H). 3.89 (q, J = 7.1 Hz, 2H), 3.75 (s, 6H), 2.40 (s, 3H), 0.86 (t, J = 7.1 Hz,
173.0, 168.9, 141.0, 138.6, 137.1, 136.4, 132.8, 130.2, 129.1,
3H). 13C NMR (125 MHz, Chloroform-d)
δ
127.6, 127.2, 124.0, 123.7, 117.6, 99.0, 61.0, 44.4, 21.5, 13.6. LRMS (ESI): 417.4 [M
calculated for C22H21ClO4S [M − H]+: 417.0922; found: 417.0927.
−
H]+. HRMS (ESI)
Ethyl 5-chloro-3-(dimethyl(oxo)-
carboxylate (3fa): light yellow solid; m.p.: 208–210 ◦C; 1H NMR (500 MHz, Chloroform-d)
(m, 3H), 7.30–7.24 (m, 3H), 7.17 (dd, J = 8.3, 2.5 Hz, 1H), 3.87 (q, J = 7.1 Hz, 2H), 3.77 (s, 6H), 0.86 (t,
J = 7.2 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
172.2, 167.9, 161.8 (d, JC–F = 251.6 Hz), 139.8, 137.9
(d, JC–F = 10.4 Hz), 135.6, 134.7 (d, JC–F = 11.8 Hz), 128.4, 127.3, 126.8, 122.6, 117.0 (d, C–F = 26.3 Hz),
116.8 (d, JC–F = 3.7 Hz), 108.5 (d, JC–F = 22.2 Hz), 99.3, 60.7, 43.9, 13.1. 19F NMR (470 MHz, Chloroform-d)
λ6-sulfanylidene)-7-fluoro-4-oxo-2-phenyl-3,4-dihydronaphthalene-1-
δ
7.37–7.32
δ
J
δ −108.2. LRMS (ESI): 421.2 [M
−
H]+. HRMS (ESI) calculated for C21H18FClO4S [M
−
H]+: 421.0676;
found: 421.0671.
Ethyl 5,7-dichloro-3-(dimethyl(oxo)-λ6-sulfanylidene)◦-4-oxo-2-phenyl-3,4-dihydronaphthalene-1-
1
carboxylate (3ga): light yellow solid; m.p.: 215–217 C; H NMR (400 MHz, Chloroform-d)
δ
7.55
(d, J = 1.9 Hz, 1H), 7.37–7.31 (m, 4H), 7.29–7.25 (m, 3H), 3.87 (q, J = 7.1 Hz, 2H), 3.75 (s, 6H), 0.85 (t,
J = 7.1 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
δ
172.6, 168.3, 140.2, 137.7, 136.0, 135.9, 134.3, 129.0,
128.4, 127.8, 127.3, 124.4, 123.3, 116.8, 100.4, 61.2, 44.2, 13.6. LRMS (ESI): 437.2 [M
−
H]+. HRMS (ESI)
calculated for C21H18Cl2O4S [M − H]+: 437.0382; found: 437.0376.
Ethyl 5-chloro-3-(dimethyl(oxo)-
1-carboxylate (3ha): light yellow solid; m.p.: 217–218 C; H NMR (400 MHz, Chloroform-d)
7.35–7.25 (m, 5H), 7.03 (d, J = 2.5 Hz, 1H), 6.96 (d, J = 2.5 Hz, 1H), 3.86 (q, J = 7.1 Hz, 2H), 3.83(s, 3H),
3.72 (s, 6H), 0.85 (t, J = 7.1 Hz, 3H). 13C NMR (150 MHz, Chloroform-d)
172.7, 168.8, 160.1, 139.5,
λ
6-sulfanylidene)-7-methoxy-4-oxo-2-phenyl-3,4-dihydronaphthalene-
◦
1
δ
δ
138.3, 136.4, 134.3, 128.9, 127.5, 127.1, 120.5, 118.1, 117.1, 105.1, 98.4, 60.8, 55.4, 44.3, 13.5. LRMS (ESI):
433.3 [M − H]+. HRMS (ESI) calculated for C22H21ClO5S [M − H]+: 433.0871; found: 433.0874.
Ethyl 5-chloro-3-(dimethyl(oxo)-λ6-sulfanylidene)-4-oxo-2-phenyl-7-(trifluoro-methyl)-3,4-
dihydronaphthalene-1-carboxylate (3ia): light yellow solid; m.p.: 212–214 ◦C; 1H NMR (400 MHz,
Chloroform-d)
(m, 2H), 3.91 (q, J = 7.0 Hz, 2H), 3.79 (s, 6H), 0.88 (d, J = 7.0 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
172.4, 168.1, 140.5, 136.9, 135.7, 134.4, 131.8 (q, J = 33.1 Hz), 128.9, 128.2 (q, J = 274.7 Hz) 127.9,
127.6, 127.3, 124.1 (q, J = 3.3 Hz), 121.3 (q, J = 4.3 Hz), 117.5, 101.7, 61.3, 44.1, 13.5. 19F NMR (470
δ 7.85 (d, J = 1.8 Hz, 1H), 7.57 (d, J = 1.8 Hz, 1H), 7.37 (dd, J = 4.9, 2.3 Hz, 3H), 7.32–7.25
δ
MHz, Chloroform-d) δ −63.1. LRMS (ESI): 471.3 [M
−
H]+. HRMS (ESI) calculated for C22H18ClF3O4S
[M − H]+: 471.0639; found: 471.0644.
Ethyl 6-bromo-5-chloro-3-(dimethyl(oxo)-
-carboxylate (3ja): light yellow solid; m.p.: 232–234 ◦C; 1H NMR (400 MHz, Chloroform-d)
J = 8.9 Hz, 1H), 7.46 (d, J = 8.9 Hz, 1H), 7.38–7.34 (m, 3H), 7.32–7.29 (m, 2H), 3.89 (q, J = 7.1 Hz, 2H),
λ
6-sulfanylidene)-4-oxo-2-phenyl-3,4-dihydronaphthalene-1
7.74 (d,
δ
3.79 (s, 6H), 0.87 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
δ 172.3, 168.4, 139.4, 136.0, 134.7,
132.5, 129.0, 127.8, 127.6, 127.3, 124.8, 122.7, 117.4, 100.7, 61.1, 44.3, 13.6. LRMS (ESI): 480.8 [M − H]+
.
HRMS (ESI) calculated for C21H19BrClO4S [M − H]+: 480.9870; found: 48 0.9866.
Ethyl 5-chloro-3-(dimethyl(oxo)-
-carboxylate (3ka): light yellow solid; m.p.: 230–232 ◦C; 1H NMR (400 MHz, Chloroform-d)
J = 8.4 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.38–7.29 (m, 5H), 3.93–3.87 (q, J = 7.1 Hz 2H), 3.79 (s, 6H), 2.52
(s, 3H), 0.88 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
173.3, 168.9, 137.7, 136.4, 135.4,
λ
6-sulfanylidene)-6-methyl-4-oxo-2-phenyl-3,4-dihydronaphthalene-1
δ
7.50 (d,
δ
135.1, 133.0, 132.3, 129.1, 127.5, 127.2, 126.3, 123.3, 117.7, 99.7, 60.9, 44.5, 21.1, 13.6. LRMS (ESI): 416.9
[M − H]+.HRMS (ESI) calculated for C22H22ClO4S [M − H]+: 417.0922; found: 417.0922.
Ethyl 5-chloro-3-(dimethyl(oxo)-
-1-carboxylate (3la): light yellow solid; m.p.: 225–227 ◦C; 1H NMR (400 MHz, Chloroform-d)
(m, 6H), 6.90 (d, J = 8.5 Hz, 1H), 3.82 (q, 2H), 3.81 (s, 3H), 3.73 (s, 6H), 0.96 (t, J = 7.1 Hz, 3H). 13
λ
6-sulfanylidene)-8-methoxy-4-oxo-2-phenyl-3,4-dihydronaphthalene
δ
7.35–7.26
C

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NMR (150 MHz, Chloroform-d)
δ
172.4, 169.3, 153.7, 138.1, 135.3, 129.8, 128.5, 128.2, 127.5, 127.1, 126.9,
124.6, 114.6, 111.7, 100.5, 60.5, 56.7, 44.0, 13.9. LRMS (ESI): 432.9 [M
−
H]+. HRMS (ESI) calculated for
C22H22ClO5S [M − H]+: 433.0871; found: 433.0882.
Ethyl 3-(dimethyl(oxo)-
3,4-dihydronaphthalene-1-carboxylate (3ma): light yellow solid; m.p.: 88–90 ◦C; 1H NMR (400 MHz,
Chloroform-d) 8.08–8.00 (m, 2H), 7.95 (s, 1H), 7.64 (d, J = 8.3 Hz, 1H), 7.55–7.30 (m, 9H), 7.17 (d,
J = 7.3 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.91 (q, J = 7.2 Hz, 2H), 3.66 (s, 3H), 3.65 (s, 3H), 1.27 (t,
J = 7.1 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
195.4, 175.0, 170.4, 169.0,
137.6, 136.7, 136.6, 136.1, 133.8, 132.9, 130.2, 129.3, 129.2, 129.0, 128.5, 127.6, 127.2, 126.9, 125.3, 118.4,
λ
6-sulfanylidene)-5-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-4-oxo-2-phenyl-
δ
δ
99.5, 61.2, 60.9, 58.5, 44.0, 43.9, 14.2, 13.7. LRMS (ESI): 559.3 [M
−
H]+, HRMS (ESI) calculated for
C32H31O7S [M − H]+: 559.1785; found: 559.1793.
Ethyl 3-(dimethyl(oxo)-
-2-phenyl-3,4-dihydronaphthalene-1-carboxylate (3na): light yellow solid; m.p.: 95–97 ◦C; 1H NMR
(400 MHz, Chloroform-d) 8.03 (d, J = 7.4 Hz, 2H), 7.92 (s, 1H), 7.55–7.48 (m, 1H), 7.45–7.31 (m, 7H),
λ
6-sulfanylidene)-5-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-7-methoxy-4-oxo
δ
7.02 (d, J = 2.5 Hz, 1H), 6.80 (d, J = 2.4 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.89 (q, J = 7.1 Hz, 2H), 3.80
(s, 3H), 3.67 (s, 3H), 3.66 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H), 0.88 (t, J = 7.1 Hz, 3H). 13C NMR (150 MHz,
Chloroform-d)
δ 195.2, 174.7, 170.2, 169.2, 160.4, 138.6, 138.0, 136.8, 136.6, 135.8, 132.9, 129.2, 129.1,
129.0, 128.5, 127.6, 127.3, 121.5, 118.0, 117.9, 105.6, 98.2, 61.3, 60.9, 58.4, 55.2, 44.4, 44.2, 14.3, 13.7. LRMS
(ESI): 589.0 [M − H]+. HRMS (ESI) calculated for C33H33O8S [M − H]+: 589.1891; found: 589.1870.
Ethyl 7-(tert-butyl)-3-(dimethyl(oxo)-l6-sulfanylidene)-5-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-4-
oxo-2-phenyl-3,4-dihydronaphthalene-1-carboxylate (3oa): light yellow solid; m.p.: 110–112 ◦C; 1H
NMR (400 MHz, Chloroform-d)
δ 8.05–7.98 (m, 2H), 7.93 (s, 1H), 7.56 (d, J = 1.8 Hz, 1H), 7.50
(t, J = 7.5 Hz, 1H), 7.42-7.30 (m, 7H), 7.20 (d, J = 1.8 Hz, 1H), 4.28 (qd, J = 7.1, 3.3 Hz, 1H), 3.95
(q, J = 7.1 Hz, 2H), 3.70 (s, 3H), 3.69 (s, 2H), 1.29 (t, J = 7.1 Hz, 3H), 1.24 (s, 9H), 0.96 (t, J = 7.1 Hz, 3H).
13C NMR (125 MHz, Chloroform-d)
δ
195.8, 174.9, 170.4, 169.1, 152.9, 137.4, 136.9, 136.7, 135.9, 133.3,
132.6, 129.3, 129.2, 129.0, 128.4, 127.6, 127.3, 126.8, 120.9, 118.7, 98.7, 61.1, 60.8, 58.7, 44.3, 44.1, 35.0, 30.8,
14.3, 13.8. LRMS (ESI): 615.0 [M
found: 615.2396.
−
H]+. HRMS (ESI) calculated for C36H39O7S [M
−
H]+: 615.2411;
Ethyl 7-bromo-3-(dimethyl(oxo)-l6-sulfanylidene)-5-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-4-oxo-2
-phenyl-3,4-dihydronaphthalene-1-carboxylate (3pa): light yellow solid; m.p.: 113–115 ◦C; 1H NMR
(400 MHz, Chloroform-d)
(t, J = 7.6 Hz, 3H), 7.41–7.30 (m, 5H), 4.28 (q, J = 7.1 Hz, 2H), 3.91 (q, J = 7.2 Hz, 2H), 3.70 (s, 3H), 3.66
(s, 3H), 1.27 (t, J = 7.1 Hz, 3H), 0.88 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
194.5,
174.6, 169.8, 168.5, 139.0, 137.3, 136.7, 136.2, 135.8, 133.0, 130.3, 129.2, 129.1, 128.9, 128.6, 127.8, 127.7,
δ 8.03 (d, J = 7.7 Hz, 2H), 7.88–7.77 (m, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.44
δ
127.3, 125.5, 125.1. 117.5. 100.0, 61.5, 61.1, 58.1, 44.1, 14.2, 13.6. LRMS (ESI): 636.8 [M
−
H]+. HRMS
(ESI) calculated for C32H30BrO7S [M − H]+: 637.0890; found: 637.0903.
Ethyl 3-(dimethyl(oxo)-
λ
6-sulfanylidene)-2-(4-fluorophenyl)-5-methyl-4-oxo-3,4-dihydronaphthalene-1
-carboxylate (3ab): light yellow solid; m.p.: 217–218 ◦C; 1H NMR (500 MHz, Chloroform-d)
δ
7.47
(dd, J = 8.5, 1H), 7.42 (dd, J = 8.3, 7.1 Hz, 1H), 7.31-7.26 (m, 2H), 7.16 (d, J = 7.0, 1H), 7.07–7.01 (m,
1H), 3.95 (q, J = 7.1 Hz, 2H), 3.75 (s, 6H), 2.97 (s, 3H), 0.96 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz,
Chloroform-d)
δ 175.6, 168.7, 161.8 (d, J C–F = 246.3 Hz), 139.1, 135.6, 135.3, 132.1 (d, J C–F = 3.5 Hz),
130.4 (d, J C–F = 8.0 Hz), 129.8, 128.4, 128.3, 122.6, 118.4, 113.7 (J C–F = 21.5 Hz), 97.6, 60.4, 43.9, 23.9, 13.3.
19F NMR (470 MHz, Chloroform-d) δ −144.6. LRMS (ESI): 401.2 [M
−
H]+. HRMS (ESI) calculated for
C22H21FO4S [M − H]+: 401.1223; found: 401.1226.
Ethyl 2-(4-chlorophenyl)-3-(dimethyl(oxo)-
λ
6-sulfanylidene)-5-methyl-4-oxo-3,4-dihydronaphthalene-1
1
-carboxylate (3ac): light yellow solid; m.p.: 199–201◦C; H NMR (400 MHz, Chloroform-d)
δ 7.45
(d, J = 8.2 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.2 Hz, 2H), 7.14
(d, J = 7.0 Hz, 1H), 3.93 (q, J = 7.1 Hz, 2H), 3.69 (s, 6H), 2.94 (s, 3H), 0.93 (t, J = 7.1 Hz, 3H). 13C NMR

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(125 MHz, Chloroform-d)
δ
176.0, 169.1, 139.6, 135.9, 135.8, 135.3, 133.4, 130.6, 130.3, 128.8, 127.4, 123.1,
118.7, 98.0, 60.9, 44.2, 24.3, 13.7. LRMS (ESI): 417.2 [M
[M − H]+: 417.0922; found: 417.0927.
−
H]+. HRMS (ESI) calculated for C22H21ClO4S
Ethyl 2-(4-bromophenyl)-3-(dimethyl(oxo)-
1-carboxylate (3ad): light yellow solid, 88 mg, yield: 95%. m.p.: 217–219 C; H NMR (400 MHz,
Chloroform-d) 7.49–7.44 (m, 3H), 7.39 (t, J = 7.6 Hz, 1H), 7.19–7.08 (m, 3H), 3.92 (q, J = 7.1 Hz, 2H),
3.67 (s, 6H), 2.94 (s, 3H), 0.93 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
175.9, 169.0,
λ
6-sulfanylidene)-5-methyl-4-oxo-3,4-dihydronaphthalene-
◦
1
δ
δ
139.6, 135.9, 135.8, 135.8, 130.9, 130.3, 128.9, 123.1, 121.6, 118.5, 98.0, 60.9, 44.2, 24.4, 13.7. LRMS (ESI):
459.2 [M − H]+. HRMS (ESI) calculated for C22H21BrO4S [M − H]+: 459.0271; found: 459.0263.
Ethyl 3-(dimethyl(oxo)-λ6-sulfanylidene)-5-methyl-4-oxo-2-(4-(trifluoromethyl)ph-enyl)-3,4-
dihydronaphthalene-1-carboxylate (3ae): light yellow solid; m.p.: 202–204 ◦C; 1H NMR (400 MHz,
Chloroform-d)
J = 7.0 Hz, 1H), 3.91 (q, J = 7.1 Hz, 2H), 3.75 (s, 6H), 2.98 (s, 3H), 0.87 (t, J = 7.1 Hz, 3H). 13C NMR
(125 MHz, Chloroform-d) 176.1, 168.9, 140.8, 139.7, 135.8, 135.7, 130.4, 129.7, 129.3 (q, JC–F = 92.4 Hz),
129.0, 124.2 (q, JC–F = 270.3 Hz), 124.0 (q, JC-F = 8.2 Hz), 123.2, 118.6, 97.6, 60.9, 44.2, 24.4, 13.5. 19F
δ 7.61 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.2 Hz, 1H), 7.45 (d, J = 7.8 Hz, 3H), 7.19 (d,
δ
NMR (470 MHz, Chloroform-d) δ −62.4. LRMS (ESI): 451.2 [M
−
H]+. HRMS (ESI) calculated for
C23H21F3O4S [M − H]+: 451.1185; found: 451.1184.
Ethyl 3-(dimethyl(oxo)-
λ
6-sulfanylidene)-2-(4-methoxyphenyl)-5-methyl-4-oxo◦-3,4-dihydronaphthalene
1
-1-carboxylate (3af): light yellow solid, 78 mg, yield: 95%. m.p.: 152–154 C; H NMR (400 MHz,
Chloroform-d)
1.0 Hz, 1H), 6.90 (d, J = 8.6 Hz, 2H), 3.96 (q, J = 7.1 Hz, 2H), 3.84 (s, 3H), 3.76 (s, 6H), 2.98 (s, 3H), 0.97
(t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, Chloroform-d)
176.1, 169.4, 158.9, 139.5, 136.9, 135.8, 130.2,
δ 7.50–7.46 (m, 1H), 7.42 (dd, J = 8.3, 7.1 Hz, 1H), 7.25 (d, J = 8.6 Hz, 2H), 7.15 (dt, J = 7.1,
δ
130.1, 128.9, 128.7, 128.5, 122.9, 118.8, 112.6, 98.3, 60.8, 55.2, 44.3, 24.4, 13.8. LRMS (ESI): 413.3 [M
−
H]+,
HRMS (ESI) calculated for C23H24O5S [M − H]+: 413.1417; found: 413.1420.
Ethyl 3-(dimethyl(oxo)-
λ
6-sulfanylidene)-2-(3-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydronaphthalene
-1-carboxylate (3ag): light yellow solid; m.p.: 80–82 ◦C; 1H NMR (400 MHz, Chloroform-d)
δ
7.49 (d,
J = 8.2 Hz, 1H), 7.41 (dd, J = 8.3, 7.1 Hz, 1H), 7.30–7.21 (m, 1H), 7.14 (d, J = 7.1 Hz, 1H), 6.94–6.85 (m,
3H), 3.95 (q, J = 7.1 Hz, 2H), 3.80 (s, 3H), 3.70 (d, J = 2.6 Hz, 6H), 2.97 (s, 3H), 0.93 (t, J = 7.2 Hz, 3H).
13C NMR (125 MHz, Chloroform-d)
δ 176.1, 169.3, 158.6, 139.5, 138.2, 137.0, 135.8, 130.2, 128.8, 128.1,
123.0, 122.0, 118.1, 115.3, 112.8, 98.3, 60.8, 55.2, 44.2, 24.4, 13.7. LRMS (ESI): 413.3 [M
−
H]+, HRMS (ESI)
calculated for C19H24O4S [M − H]+: 413.1417; found: 413.1427.
Ethyl 2-(3-bromophenyl)-3-(dimethyl(oxo)-
1-carboxylate (3ah) light yellow solid; m.p.: 90–92 ◦C; 1H NMR (400 MHz, Chloroform-d)
(m, 3H), 7.43–7.37 (m, 1H), 7.25–7.16 (m, 1H), 7.16–7.11 (m, 1H), 3.94 (q, J = 7.1 Hz, 2H), 3.70 (s, 3H),
3.69 (s, 3H), 2.94 (s, 3H), 0.94 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
175.5, 168.5,
λ
6-sulfanylidene)-5-methyl-4-oxo-3,4-dihydronaphthalene-
7.49–7.43
δ
δ
139.1, 138.4, 135.3, 135.1, 131.7, 129.9, 129.8, 128.5, 128.2, 127.6, 122.7, 120.7, 118.1, 97.4, 60.5, 43.8, 43.7,
23.9, 13.3. HRMS (ESI) calculated for C22H21BrO4S [M − H]+: 461.0417; found: 461.0427.
Ethyl 2-(2-chlorophenyl)-3-(dimethyl(oxo)-
1-carboxylate (3ai): light yellow solid; m.p.: 86–88 ◦C; 1H NMR (500 MHz, Chloroform-d)
J = 8.1 Hz, 1H), 7.44–7.34 (m, 2H), 7.32–7.21 (m, 3H), 7.15 (d, J = 7.2 Hz, 1H), 3.96–3.82 (m, 2H), 3.81 (s,
3H), 3.71 (s, 3H), 2.97 (s, 3H), 0.90 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
175.2, 168.4,
λ
6-sulfanylidene)-5-methyl-4-oxo-3,4-dihydronaphthalene-
δ
7.54 (d,
δ
139.1, 135.7, 135.4, 134.0, 133.9, 130.2, 129.6, 128.7, 128.5, 127.8, 125.5, 123.0, 117.5, 96.7, 60.3, 43.5, 41.6,
24.0, 13.2. HRMS (ESI) calculated for C22H21BrO4S [M − H]+: 417.0922; found: 417.0931.
Ethyl 3-(dimethyl(oxo)-
λ
6-sulfanylidene)-2-(2-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydronaphthalene
-1-carboxylate (3aj): light yellow solid; m.p.: 210–212 ◦C; 1H NMR (500 MHz, Chloroform-d)
δ
7.59–7.54
(m, 1H), 7.38 (dd, J = 8.3, 7.2 Hz, 1H), 7.33 (td, J = 7.9, 1.8 Hz, 1H), 7.21 (dd, J = 7.4, 1.7 Hz, 1H), 7.13 (dt,
J = 7.2, 1.1 Hz, 1H), 6.96 (td, J = 7.4, 1.1 Hz, 1H), 6.87 (dd, J = 8.3, 1.0 Hz, 1H), 3.97–3.83 (m, 2H), 3.81 (s,

Molecules 2019, 24, 1884
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3H), 3.74 (s, 3H), 3.73 (s, 3H), 2.98 (s, 3H), 0.89 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
174.8, 168.9, 157.0, 138.9, 135.8, 133.8, 129.3, 129.3, 128.7, 128.4, 128.0, 125.9, 122.7, 119.8, 117.5, 109.4,
δ
97.9, 60.1, 55.2, 43.4, 41.3, 24.0, 13.2. LRMS (ESI): 413.3 [M
−
H]+. HRMS (ESI) calculated for C23H24O5S
[M − H]+: 413.1417; found: 413.1421.
Ethyl 3-(dimethyl(oxo)-
3ak): light yellow solid; m.p.: 146–148 ◦C; 1H NMR (500 MHz, Chloroform-d)
7.28 (d, J = 6.2 Hz, 1H), 7.06 (d, J = 7.1 Hz, 1H), 4.43 (q, J = 7.1 Hz, 2H), 3.80 (s, 6H), 2.90 (s, 3H), 2.43 (s,
3H), 1.40 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
175.6, 170.1, 138.8, 135.8, 132.6, 129.4,
λ
6-sulfanylidene)-2,5-dimethyl-4-oxo-3,4-dihydronaphthalene-1-carboxylate
7.37–7.32 (m, 1H),
(
δ
δ
127.6, 127.5, 117.4, 98.1, 60.7, 44.2, 23.8, 16.3, 13.8. LRMS (ESI): 321.2 [M
−
H]+. HRMS (ESI) calculated
for C17H20O4S [M − H]+: 321.1155; found: 321.1157.
Ethyl 2-cyclopropyl-3-(dimethyl(oxo)-λ6-sulfanylidene)-5-methyl-4-oxo-3,4-dihy-dronaphthalene-1-
carboxylate (3al): light yellow solid; m.p.: 180–182 ◦C; 1H NMR (500 MHz, Chloroform-d)
δ 7.47 (d,
J = 8.3 Hz, 1H), 7.35 (dd, J = 8.4, 7.2 Hz, 1H), 7.07 (dt, J = 7.1, 1.2 Hz, 1H), 4.42 (q, J = 7.2 Hz, 2H), 3.81
(d, J = 2.4 Hz, 6H), 2.89 (s, 3H), 2.25 (tt, J = 8.6, 5.9 Hz, 1H), 1.41 (t, J = 7.2 Hz, 2H), 0.93 (dd, J = 8.4,
1.7 Hz, 2H), 0.64 (dd, J = 5.9, 1.7 Hz, 2H). 13C NMR (125 MHz, Chloroform-d)
δ 175.6, 170.0, 139.2,
138.7, 135.7, 129.2, 128.1, 127.9, 122.1, 118.2, 99.7, 60.6, 44.0, 23.9, 13.86, 13.72, 8.3. LRMS (ESI): 331.4 [M
− H]+. HRMS (ESI) calculated for C19H24O4S [M − H]+: 331.1010; found: 331.1011.
Isopropyl 3-(dimethyl(oxo)-
3am): light yellow solid; m.p.: 148–150 ◦C; 1H NMR (400 MHz, Chloroform-d)
1H), 7.29 (d, J = 7.4 Hz, 1H), 7.05 (d, J = 7.0 Hz, 1H), 5.35 (hept, J = 5.7 Hz, 1H), 3.79 (s, 6H), 2.89 (s, 3H),
2.44 (s, 3H), 1.40 (d, J = 6.3 Hz, 6H). 13C NMR (125 MHz, Chloroform-d)
176.3, 170.1, 139.3, 136.3,
λ
6-sulfanylidene)-2,5-dimethyl-4-oxo-3,4-dihydronaphthalene-1-carboxylate
(
δ 7.35 (t, J = 7.6 Hz,
δ
132.8, 129.8, 128.2, 127.9, 122.3, 118.0, 98.3, 68.7, 44.6, 24.3, 21.9, 16.6. LRMS (ESI): 335.3 [M
−
H]+.
HRMS (ESI) calculated for C18H22O4S [M − H]+: 335.1312; found: 335.1308.
Tert-butyl 3-(dimethyl(oxo)-
3an): light yellow solid; m.p.: 152–154 ◦C; 1H NMR (400 MHz, Chloroform-d)
2H), 7.05 (s, 1H), 3.80 (s, 6H), 2.88 (s, 3H), 2.45 (s, 3H), 1.63 (s, 9H). 13C NMR (125 MHz, Chloroform-d)
176.0, 169.9, 139.3, 136.4, 132.1, 129.8, 128.1, 127.9, 122.3, 119.4, 98.2, 81.7, 44.7, 28.3, 24.3, 16.5. LRMS
(ESI): 349.3 [M
H]+. LRMS (ESI): 349.4 [M H]+, HRMS (ESI) calculated for C19H24O4S [M H]+:
349.1468; found: 349.1472.
λ
6-sulfanylidene)-2,5-dimethyl-4-oxo-3,4-dihydronaphthalene-1-carboxylate
(
δ 7.35 (d, J = 4.1 Hz,
δ
−
−
−
Ethyl 4-hydroxy-3-((4-methoxyphenyl)amino)-2,5-dimethyl-1-naphthoate (5ak): green oil, 33 mg, yield:
1
35%. H NMR (400 MHz, DMSO-d6)
δ
9.15 (s, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.34 (dd, J = 8.6, 6.9 Hz, 1H),
7.19 (d, J = 6.9 Hz, 1H), 6.96 (s, 1H), 6.74 (d, J = 8.9 Hz, 2H), 6.45 (d, J = 8.9 Hz, 2H), 4.39 (q, J = 7.1 Hz,
2H), 3.63 (s, 3H), 2.88 (s, 3H), 2.11 (s, 3H), 1.32 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, DMSO-d6)
169.8, 154.0, 152.3, 141.6, 135.7, 133.3, 130.6, 127.8, 126.9, 123.7, 123.4, 122.6, 122.3, 115.0, 114.9, 61.3,
δ
55.7, 25.2, 16.0, 14.5. LRMS (ESI): 364.4 [M
364.1154; found: 364.1157.
−
H]+, HRMS (ESI) calculated for C22H23NO4 [M – H]+:
Ethyl 4-hydroxy-2,5-dimethyl-3-(methylsulfinyl)-1-naphthoate (6ak): white solid, 40 mg, yield: 65%.
m.p.: 128–130 ◦C. 1H NMR (500 MHz, Chloroform-d)
12.33 (s, 1H), 7.53–7.48 (m, 1H), 7.43 (dd, J = 8.5,
7.0 Hz, 1H), 7.23 (dt, J = 7.0, 1.1 Hz, 1H), 4.51 (q, J = 7.2 Hz, 2H), 3.05 (s, 3H), 2.96 (s, 3H), 2.37 (s, 3H),
1.45 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz, Chloroform-d)
169.5, 162.9, 137.5, 133.9, 129.0, 129.0,
δ
δ
128.0, 124.5, 124.2, 114.5, 61.6, 39.4, 25.1, 16.0, 14.3. LRMS (ESI): 306.5 [M
for C16H18O4S [M − H]+: 308.0853; found: 308.0854.
−
H]+, HRMS (ESI) calculated
4. Conclusions
In summary, we developed a novel method to access naphthalenone sulfoxonium ylides via
Rh(III)-catalyzed C-H activation and [4+2] annulation of sulfoxonium ylides with diazo compounds.
High regioselectivity, mild and redox-neutral reaction conditions, and wide substrate tolerance

Molecules 2019, 24, 1884
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make this protocol efficient to prepare various naphthalenone sulfoxonium ylides. Moreover, the
new type of naphthalenone sulfoxonium ylides could be further transformed into multi-substituted
naphthols smoothly, which may find important applications in the synthesis of natural products and
biologically-active molecules.
Supplementary Materials: The Supplementary Materials are available online.
Author Contributions: Conceptualization: X.S.; experiments and analyses: X.S., X.H., and R.Z; writing—original
draft preparation: X.S.; writing—review and editing: J.W. and H.L.
Accession Codes: CCDC 1899265 contains the supplementary crystallographic data for this paper. These data can
be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk,
or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
Funding: This research was funded by the National Natural Science Foundation of China (nos. 21632008, 21672231,
21877118, and 81620108027) and the Strategic Priority Research Program of the Chinese Academy of Sciences
(XDA12040107 and XDA12040201) for financial support.
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Not available.
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2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
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