Expeditious Access to Spiro-Fused 2,5-Cyclohexadienones via Thio(seleno)cyanative ipso-Cyclization

Article abstract of DOI:10.1021/acs.joc.0c02270

A facile oxidative dearomatization of N-(p-methoxyaryl)propiolamides has been established for the synthesis of spiro-fused 2,5-cyclohexadienone frameworks via thio(seleno)cyanative ipso-cyclization in the presence of ceric ammonium nitrate (CAN) as the oxidant. The present method, involving the formation of C-S and C-C bonds, was also extended to (p-methoxyaryl)propiolates for thiocyanative ipso-cyclization. Furthermore, the obtained chalcogeno-spirocyclohexadienones were transformed into uniquely functionalized spirocyclohexadienone derivatives.

Full text of DOI:10.1021/acs.joc.0c02270

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Expeditious Access to Spiro-Fused 2,5-Cyclohexadienones via
Thio(seleno)cyanative ipso-Cyclization
Chada Raji Reddy,* Uprety Ajaykumar, and Dattahari H. Kolgave
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ABSTRACT: A facile oxidative dearomatization of N-(p-
methoxyaryl)propiolamides has been established for the synthesis
of spiro-fused 2,5-cyclohexadienone frameworks via thio(seleno)-
cyanative ipso-cyclization in the presence of ceric ammonium
nitrate (CAN) as the oxidant. The present method, involving the
formation of C−S and C−C bonds, was also extended to (p-
methoxyaryl)propiolates for thiocyanative ipso-cyclization. Fur-
thermore, the obtained chalcogeno-spirocyclohexadienones were
transformed into uniquely functionalized spirocyclohexadienone
derivatives.
sponding reagents for the addition reaction with the alkyne to
initiate the domino process.15 In this context, only two
approaches were disclosed to access thiocyanato-containing
spirocyclohexadienone N-(aryl)propiolamides. In 2008, Li and
co-workers briefly studied the electrophilic ipso-cyclization
involving an electrophile-exchange process, wherein only three
substrates were studied using CuSCN in the presence of an
electrophilic fluoride reagent, N-Fluoro-N′-(chloromethyl)-
triethylenediamine bis(tetrafluoro-borate), in acetonitrile at
90 °C (Scheme 1a).16a Very recently, He and coworkers
reported a visible-light-mediated thiocyanate radical addition/
ipso-cyclization/oxidation cascade reaction of N-phenylpropa-
namides using ammonium thiocyanate in the presence of
acridinium perchlorate as an organic photocatalyst in
acetonitrile under irradiation of a 23 W compact fluorescent
lamp (Scheme 1b).16b Despite the merits, these methods also
suffer from either low yield of the products or a longer reaction
time and may be inconvenient for large-scale reactions. Thus,
the development of novel and efficient domino thiocyanation/
ipso-cyclization under mild reaction conditions is still needed
and a favorable alternative to make diverse SCN-containing
spirocyclohexadienones is required. Recently, we developed a
domino Ag-catalyzed oxidative ipso-cyclization of N-arylpro-
piolamides with α-keto acids/alkyl carboxylic acids to access 3-
acyl/alkyl-spiro[4,5]-trienones via decarboxylative acylation/
alkylation (Scheme 1c).17a In continuation of our work on
INTRODUCTION
■
Carbon−sulfur bond construction symbolizes one of the most
prevailing approaches for the production of organosulfur
compounds, which have found extensive applications in
pharmaceuticals, agrochemicals, and materials science.1
Among the organosulfur compounds, thiocyanates are
ubiquitous motifs in bioactive compounds due to their stability
and promising physiochemical properties.2 They also serve as
valuable intermediates in the synthesis of diverse organosulfur
compounds such as thioethers,3 thiols,4 thiotetrazoles,5
trifluoromethyl sulfides,6 disulfides,7 thiocarbamates,8 alkynyl
thioethers,9 sulfonyl chlorides,10 etc. Hence, numerous
methods have been developed for the synthesis of alkyl, aryl,
and vinyl thiocyanates.11 Nevertheless, the construction of
thiocyanated-cyclic compounds via a domino thiocyanation/
annulation of unsaturated carbon−carbon bonds, in particular
alkynes, is still underexplored.12 Given the significant reactivity
of alkynes in synthetic chemistry through difunctionalization,13
the development of further conversions of alkynes is necessary
to intensify their utility, precisely in domino reactions to make
diversely functionalized annulated products.
Spirocyclohexadienones are found as a valuable motif of
pharmaceutical chemistry in various natural products showing
notable biological activities and serve as convenient fore-
runners toward the synthesis of natural products.14 Hence,
these scaffolds have drawn growing attention of synthetic
organic chemists. In recent years, a common concise approach
for the assembly of spirocyclohexanedienones from dearoma-
tization of N-(p-methoxyaryl)propiolamides by a domino
electrophilic or radical addition/ipso-spirocyclization method
has attracted great attention. To accomplish this trans-
formation by installing the number of functional groups,
several efforts have been made using carbon-centered or
heteroatom-centered electrophiles/radicals from their corre-
Received: September 21, 2020
https://dx.doi.org/10.1021/acs.joc.0c02270
© XXXX American Chemical Society
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A

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a
Scheme 1. Spirocyclohexadienones via
Table 1. Optimization of Conditions
Thio(seleno)cyanative or Oxidative ipso-Cyclization
e
entry
oxidant
thiocyanate
solvent
time (h) yield (%)
b
1
K2S2O8
K2S2O8
K2S2O8
CAN
CAN
CAN
CAN
CAN
CAN
NH4SCN
NH4SCN
AgSCN
AgSCN
AgSCN
AgSCN
AgSCN
NH4SCN
KSCN
AgSCN
AgSCN
AgSCN
AgSCN
CH3CN
DMSO
DMSO
DMSO
DMSO
CH3CN
DCE
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
12
8
4
0.5
5
8
10
24
55
92
65
36
25
17
32
2
3
b
4
c
5
6
7
8
9
10
11
5
10
10
12
12
4
d
TBHP
Oxone
Phl(OAc)2
d
12
13
14
12
a
ipso-cyclization reactions,17 herein, we disclose a facile
synthesis of diversely substituted thiocyanato-spirocyclohex-
adienones from the domino thiocyanation/ipso-cyclization of
N-(p-methoxyaryl)propiolamides in the presence of ceric
ammonium nitrate (CAN) as the oxidant. The method is
extended to an unprecedented domino selenocyanate radical
addition/ipso-cyclization of N-(p-methoxyaryl)-propiolamides.
Further, transformations of the thiocyanated-spirocyclohex-
adienones to their corresponding derivatives with unique
structural motifs are established for the first time (Scheme 1d).
Unless otherwise noted, the reactions were carried out with 1a (0.3
mmol), thiocyanate (0.6 mmol), and oxidant (0.9 mmol) in 2 mL of
the solvent for the specified time at 60 °C. No progress in the
reaction at room temperature. Oxidant used in 2 equiv. No product
b
c
d
e
formation was observed. Isolated yield.
substitutions on the alkyne of N-(p-methoxyphenyl)-propiola-
mides. The reactions of propiolamides bearing electron-
donating groups, such as methyl and methoxyl, on the para-
position of the phenyl ring attached to alkyne produced the
desired spiro-compounds 2b and 2c in 88 and 85% yields,
respectively. It was found that halide substituents, fluoro and
chloro groups, were endured well under the CAN-mediated
domino thiocyanation/ipso-cyclization to deliver the corre-
sponding halo-spirocyclohexadienones 2d (89%) and 2e
(86%), giving the opportunity for further structural elabo-
ration. To our delight, the propiolamides with electron-
withdrawing groups, such as nitro, cyano, and acyl groups,
could also take part in this one-pot reaction to give the
matching thiocyano-dearomative spiro-cyclized compounds 2f
(NO2), 2g (CN), and 2h (COMe) in high yield. The
applicability of this cascade reaction was also shown by varying
the aryl as well as heteroaryl substituents on the alkyne,
affording 3-thiocyanato-1-azaspiro-cyclohexadienones 2i (3,5-
dimethyl-phenyl), 2j (3-trifluoromethylphenyl), 2k (2-naph-
thyl), and 2l (2-thiophenyl) in good yield. Notably, alkyl-
propiolamides were also amenable to thiocyanative ipso-
cyclization to provide the expected spiro-products 2m (methyl,
81%) and 2n (ethyl, 83%). Moreover, the replacement of
methyl substitution (R1) on the nitrogen of N-(p-methox-
yphenyl)-propiolamides with benzyl (2o), 2-iodo-benzyl (2p),
and 3-CF3-benzyl (2q) groups was also feasible to give
azaspirocyclohexadienones in decent yield. Likewise, the
introduction of supplementary R2 substituents such as 2-
methyl, 3-methyl, and 3-fluoro on the N-(4-methoxyphenyl)
group offered the required products 2q to 2u in high yields.
To further widen the substrate choice, we tested the
reactivity of N-(alkynoyl)-6-methoxytetrahydroquinolines with
AgSCN in the presence of CAN to get pyrrolo-[2,1-j]-
quinolone, an inspiring structural motif found in tricyclic
marine alkaloids.18 Gratifyingly, the domino thiocyanative ipso-
RESULTS AND DISCUSSION
■
To identify the optimal conditions, the reactions were carried
out with N-(p-methoxyphenyl)-3-phenylpropiolamide (1a) as
the model substrate, and the results are presented in Table 1.
Primarily, the envisaged conversion was attempted using
NH4SCN as a thiocyanating agent in the presence of K2S2O8
as an oxidant in acetonitrile and no progress was found in the
reaction at room temperature. However, the formation of
azaspirocyclohexadienone 2a was observed at 60 °C after 12 h
(entry 1, Table 1). When, the same reaction was carried out in
dimethyl sulfoxide (DMSO), the yield of the product 2a
slightly improved to 24% (entry 2, Table 1). The replacement
of the thiocyanating agent with AgSCN gave the product 2a in
55% yield (entry 3). To our delight, the reaction of 1a with
AgSCN using a different oxidizing agent, CAN, in DMSO at 60
°C proceeded well and provided 2a in 92% yield (entry 4,
Table 1). The use of CAN in 2 equiv lowered the yield to 65%
(entry 5). Later, the experiment was carried out in other
solvents such as CH3CN and DCE using CAN/AgSCN, and
the results revealed that DMSO was the best solvent (entries 6
and 7). However, the results are inferior when NH4SCN or
KSCN was used in the presence of either 3 or 5 equiv of CAN
(entry 8 and 9). Further studies using diverse oxidants such as
TBHP and oxone were unsuccessful (entries 10 and 11), while
PhI(OAc)2 offered 14% of 2a (entry 12, Table 1). As
anticipated, no reaction progress was observed in the absence
of CAN (entry 13, Table 1).
With the optimized conditions for the thiocyanative ipso-
cyclization established, we then examined the substrate scope
as presented in Scheme 2. First, we explored the choice of the
B
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Scheme 2. Scope of N-(p-Methoxyaryl)propiolamides
Scheme 4. Synthesis of 3-Thiocyanato-1-oxaspirocycles
6d (86%) and 6e (78%). Likewise, the reaction effectively
progressed with 4-methoxyphenyl propiolates having the
heteroaryl group, 2-thiophenyl, delivering the product 6f in
65% yield.
In the next part of this study, we turned our attention to
verify the feasibility of this domino selenocyanation/ipso-
cyclization, hitherto unknown transformation (Scheme 5).
Scheme 5. Domino Selenocyanation/ipso-Cyclization of N-
(p-Methoxyphenyl)-propiolamides
cyclization of 3 progressed well, giving the thiocyanato-
pyrrolo-[2,1-j]-quinolone 4 in 80% yield (Scheme 3).
Scheme 3. Synthesis of Thiocyanato-pyrrolo-[2,1-
j]quinolone 4
Pleasantly, the selenocyanative cyclization of 1a ensued cleanly
to offer the selenocyanato azaspirocyclohexadienone 7a (72%)
in 12 h. The slower reactivity of a SeCN radical compared to a
SCN radical might be due to the difference in redox potentials
and sizes of these two chalcogen radicals.20 The reaction
tolerates the 4-fluoro-phenyl (7b) and 2-thiophenyl (7c)
groups on the alkyne of propiolamides. Interestingly, other N-
(p-methoxyphenyl)propiolamides having a methyl group on
aryl and a benzyl group on nitrogen also underwent the ipso-
cyclization successfully, furnishing the products 7d and 7e in
74 and 61% yields, respectively. Regrettably, selenocyanative
ipso-cyclization of N-(p-methoxyphenyl)-propiolate 5a was
futile.
The scalability of the reaction was explored with 1.18 g
(4.5mmol) of phenylpropiolamide 1a under optimal con-
ditions that provided the required product 2a (1.2 g) in 92%
yield (Scheme 6). In addition, the possible synthetic efficacies
of thiocyanato-azaspirocyclohexadienones 2a were also studied
by the conversion of thiocyanate (SCN) into a wide variety of
sulfur-containing useful frameworks (Scheme 6). For example,
the SCN group of 2a was efficiently transformed into
We next extended the scope of this thiocyanative ipso-
cyclization to 4-methoxyphenyl propiolates (Scheme 4) and to
the best of our knowledge, only one such example is known in
the literature using the combination of bis(iodoarene) and
mCPBA/p-TsOH.19 Various 4-methoxyphenyl 3-aryl/hetero-
arylpropiolates gave the corresponding thiocyanated products
in good yield, regardless of the effect of a substituent on alkyne
functionality. Substrates with electronically different substitu-
ents such as phenyl, 4-Cl-phenyl, and 4-COMe-phenyl gave
the resultant products 6a, 6b, and 6c in 82, 78, and 72% yields,
respectively. 3,5-Dimethyl phenyl and 1-naphthyl groups on
the alkyne were also compatible in this thiocyanative ipso-
cyclization to give 3-thiocyanato-1-oxaspirocyclohexadienones
C
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a
Scheme 6. Diversification of Thiocyanate 2a
Scheme 8. Outcome of the Control Experiment
Scheme 9. Possible Reaction Mechanism
a
(a) CsF (1 equiv), TMSSCF3 (2 equiv), CH3CN, rt, 2 h; (b) NaN3
(1.2 equiv), ZnCl2 (1 equiv), iPrOH, 50 °C, 1.5 h; (c) phenlacetylene
(1.5 equiv), Cul (0.2 equiv), Cs2CO3 (1 equiv), CH3CN, 2 h rt; (d)
n-BuLi (2 equiv), Et2NH (3 equiv), THF, 0 °C-rt, 3 h.
trifluoromethylthiolate (SCF3, ubiquitous lipophilic group),
using TMSSCF3 and CsF to obtain 8 in 80% yield (Scheme
6a).12c The click reaction of 2a with NaN3 in the presence of
ZnCl2 provided the corresponding thiotetrazole (metabolically
stable substitute for the carboxyl) 9 in 84% yield.5b
Interestingly, the thio-alkynylation of 2a with phenylacetylene
using CuI (20 mol %) and Cs2CO3 in CH3CN at room
temperature offered the alkynyl sulfide 10 in 90% yield.9a
Pleasingly, the treatment of 2a with nBuLi in the presence of
Et2NH in THF afforded the disulfide 11, albeit in low yield
(40%).12c
CONCLUSIONS
■
In summary, earlier to this work, thiocyanative ipso-cyclizations
were studied in the presence of either an electrophilic fluoride
reagent or an acridinium perchlorate photocatalyst with limited
substrates. In this paper, we successfully established a CAN
mediated domino thiocyanation/ipso-cyclization/dearomatiza-
tion of N-(p-methoxyphenyl)-propiolamides, leading to
numerous spiro-fused 2,5-cyclohexadienones in good to
excellent yields. The method was also extended to 4-
methoxyphenyl propiolates. Another unprecedented trans-
formation, selenocyanative ipso-cyclization of propiolamides,
has also been demonstrated. Moreover, the resulting
chalcogenocyanates were smoothly converted into unique
azaspirocyclohexadienones bearing diverse frameworks for the
first time. This method can be projected to find inclusive
synthetic applications due to the mild reaction conditions, easy
operation, high efficiency, and good yields.
Further, the conversion of SeCN in 7a into alkynyl selenide
12 with phenylacetylene using CuI (20 mol %) and Cs2CO3 in
CH3CN was also successful through seleno-alkynylation
(Scheme 7).
Scheme 7. Seleno-alkynylation of Selenide 7a
EXPERIMENTAL SECTION
■
General Information. All of the reactions were performed in
oven-dried glass apparatus. Reactions requiring anhydrous conditions
were performed under a nitrogen atmosphere using freshly distilled
anhydrous solvents. Commercially available reagents were used as
received. All reactions were monitored by thin-layer chromatography
(TLC) carried out on silica plates using UV light and anisaldehyde for
visualization. Column chromatography was performed on silica gel
(100−200 meshes) using hexane and ethyl acetate or methanol and
dichloromethane as eluents. NMR spectra were reported in parts per
million (δ) relative to tetramethylsilane (0.00 ppm) for protons and
To gain mechanistic perception, we next executed a radical
trap experiment. The treatment of 1a using standard reaction
conditions in the presence of radical scavenger 2,2,6,6-
tetramethylpiperidine 1-oxyl (TEMPO) does not lead to
formation of 2a (Scheme 8), suggesting that the reaction
pathway involves free radical intermediates.
According to the experimental outcomes and literature
reports,12a a possible reaction mechanism for the CAN-
mediated domino thiocyanation/ipso-cyclization/dearomatiza-
tion is proposed (Scheme 9). Initially, CAN oxidizes AgSCN
to generate a SCN radical, which attacks propiolamide 1a
regioselectively to produce radical A. Next, an ipso-carbacyc-
lization of A affords intermediate B, which subsequently
oxidizes to oxonium ion C. Finally, hydrolytic demethylation of
C eventually delivers the desired azaspirocyclohexadienone 2a.
1
carbon. Coupling constants (J) are reported in hertz (Hz). H NMR
spectra were recorded in CDCl3 or CD3OD at 500, 400, and 300
MHz, and 13C NMR spectra were recorded at 125, 100, and 75 MHz.
1
δ 7.26 and δ 77.2 correspond to CDCl3 in H NMR and 13C NMR,
respectively.
All of the starting materials (1a−1e, 1g−1p, 1r−1t),17a (1f, 2b,
2f),21a and (2a, 2c−2e)21b were prepared based on the literature
reports, and spectral data was compared.
D
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N-(4-Methoxy-3-methylphenyl)-3-phenyl-N-(2-(trifluoromethyl)-
benzyl)propiolamide (1q).
completion of the reaction (monitored by TLC), water was added to
the mixture, and the mixture was extracted with ethyl acetate (3 × 10
mL). The combined organic layers were dried over Na2SO4 and
concentrated to get the crude product, which was purified by column
chromatography on silica gel using ethyl acetate and hexane as an
eluent to afford the corresponding 3-thiocyanato[4,5] spirotrienones.
1-Methyl-4-phenyl-3-thiocyanato-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (2a). Following the general procedure, N-(4-
methoxyphenyl)propiolamide 1a (80 mg, 0.3 mmol), AgSCN (112
mg, 0.6 mmol), and CAN (493 mg, 0.9 mmol) were reacted in
DMSO (3 mL). After the workup, column chromatography
purification gave 2a as a white solid (85 mg, 92% yield). Mp: 150−
To a stirred solution of phenylpropiolic acid (285 mg, 1.1 equiv) in
CH2Cl2 under a nitrogen atmosphere at 0 °C was added 2-(1H-
benzotriazole-1-yl)-1,1,3,3-tetramethylaminium hexafluorophosphate
(HBTU, 877 mg, 1.5 equiv). After 30 min, 4-methoxy-3-methyl-N-
(2-(trifluoromethyl)benzyl)aniline (500 mg, 1 equiv) and N,N-
diisopropylethylamine (DIPEA, 0.9 ml, 3 equiv) were added drop
wise for a period of 5 min. The reaction mixture was allowed to stir
for 12 h at room temperature and quenched with water. The aqueous
solution was extracted with dichloromethane (DCM, 3 × 50 mL), and
the combined organic layers were washed with brine (50 mL) and
dried with Na2SO4. The solvent was removed under reduced pressure
to get the crude product, which was purified by column
chromatography on silica gel (100−200 meshes) using hexane and
ethyl acetate as an eluent to obtain 1q (as an equimolar ratio of
rotamers) as a brown color oil (527 mg, 70% yield). Rf = 0.4
1
152 °C; Rf = 0.3 (hexane:ethyl acetate = 7:3); H NMR (400 MHz,
CDCl3): δ 7.50−7.40 (m, 3H), 7.28−7.25 (m, 2H), 6.55−6.49 (m,
4H), 2.95 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 183.3,
164.9, 157.0, 143.1, 134, 131.1, 129.1, 128.9, 127.8, 122.4, 106.3, 68.4,
26.6; IR (KBr): νmax = 2925, 2162, 1709, 1629, 1268, 754 cm−1;
HRMS (ESI/Q-TOF): m/z calcd for C17H13N2O2S (M + H)+
309.0698, found 309.0696.
1-Methyl-3-thiocyanato-4-(p-tolyl)-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (2b). Following the general procedure, N-(4-
methoxyphenyl)-N-methyl-3-(p-tolyl)propiolamide 1b (85 mg, 0.3
mmol), AgSCN (103 mg, 0.6 mmol), and CAN (497 mg, 0.9 mmol)
were reacted in DMSO (3 mL). After the workup, column
chromatography purification gave 2b as a brown solid (85 mg, 88%
1
1
(hexane:ethyl acetate = 7:3); H NMR (400 MHz, CDCl3) δ 7.57−
yield). Mp: 125−127 °C; Rf = 0.3 (hexane:ethyl acetate = 6:4); H
7.38 (m, 5H), 7.36−7.29 (m, 1H), 7.25−7.20 (m, 1H), 7.17−7.12
(m, 2H), 6.96−6.88 (m, 2H), 6.76 (d, J = 8.5 Hz, 1H), 4.99 (s, 2H),
3.84 (s, 3H), 2.19 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ
157.5, 154.9, 137.9, 133.6, 132.5, 132.2, 130.4, 129.9, 129.0, 128.3,
127.6, 126.9, 125.6, 124.5, 124.4, 120.5, 109.9, 91.8, 82.5, 55.6, 52.1,
16.2; 19F NMR (377 MHz, CDCl3) δ −62.61; IR (neat): νmax = 2218,
1638, 1328, 764 cm−1; HRMS (ESI/Q-TOF): m/z calcd for
C25H21F3NO2 (M + H)+ 424.1524, found 424.1513.
NMR (400 MHz, CDCl3): δ 7.24−7.15 (m, 4H), 6.55−6.47 (m, 4H),
2.94 (s, 3H), 2.38 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ
183.4, 165.1, 157.3, 143.3, 141.8, 133.8, 129.8, 127.6, 126.0, 121.5,
106.4, 68.3, 26.5, 21.5; IR (KBr): νmax = 2924, 2163, 1709, 1671,
1379, 758 cm−1; HRMS (ESI/Q-TOF): m/z calcd for C18H15N2O2S
(M + H)+ 323.0854, found 323.0856.
4-(4-Methoxyphenyl)-1-methyl-3-thiocyanato-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (2c). Following the general procedure,
N-3-bis(4-methoxyphenyl)-N-methylpropiolamide 1c (90 mg, 0.3
mmol), AgSCN (101 mg, 0.6 mmol), and CAN (491 mg, 0.9 mmol)
were reacted in DMSO (3 mL). After the workup, column
chromatographic purification gave 2c as a white solid (86 mg, 85%
N-(2-Iodobenzyl)-N-(4-methoxy-3-methylphenyl)-3-phenylpro-
piolamide (1u).
1
yield). Mp: 132−134 °C; Rf = 0.3 (hexane:ethyl acetate = 7:3); H
NMR (400 MHz, CDCl3) δ 7.33−7.28 (m, 2H), 6.95−6.90 (m, 2H),
6.57−6.47 (m, 4H), 3.83 (s, 3H), 2.93 (s, 3H); 13C{1H} NMR (101
MHz, CDCl3): δ 183.4, 165.3, 161.8, 157.0, 143.6, 133.7, 129.5,
121.1, 120.3, 114.6, 106.7, 68.1, 55.4, 26.4; IR (KBr): νmax = 2927,
2163, 1706, 1671, 1258, 759 cm−1; HRMS (ESI/Q-TOF): m/z calcd
for C18H15N2O3S (M + H)+ 339.0803, found 339.0805.
To a stirred solution of phenylpropiolic acid (237 mg, 1.1 equiv) in
DCM under a nitrogen atmosphere at 0 °C, HBTU (763 mg, 1.5
equiv) was added. After 30 min, N-(2-iodobenzyl)-4-methoxy-3-
methylaniline (500 mg, 1 equiv) and DIPEA (0.8 ml, 3 equiv) were
added dropwise for a period of 5 min at 0 °C. The reaction mixture
was allowed to stir for 12 h at room temperature and quenched with
water. The aqueous solution was extracted with DCM (3 × 50 mL),
and the combined organic layers were washed with brine (50 mL) and
dried with Na2SO4. The solvent was removed under reduced pressure
to get the crude product, which was purified by column
chromatography on silica gel (100−200 meshes) using hexane and
ethyl acetate as an eluent to obtain 1u (as an equimolar ratio of
rotamers) as a red liquid (452 mg, 64% yield). Rf = 0.5 (hexane:ethyl
4-(4-Fluorophenyl)-1-methyl-3-thiocyanato-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (2d). Following the general procedure, 3-
(4-fluorophenyl)-N-(4-methoxyphenyl)-N-methylpropiolamide 1d
(85 mg, 0.3 mmol), AgSCN (101 mg, 0.6 mmol), and CAN (491
mg, 0.9 mmol) were reacted in DMSO (3 mL). Column
chromatography purification gave 2d as a brown solid (87 mg, 89%
1
yield). Mp: 109−111 °C; Rf = 0.4 (hexane:ethyl acetate = 6:4); H
NMR (500 MHz, CDCl3): δ 7.32−7.27 (m, 2H), 7.16−7.11 (m, 2H),
6.56−6.53 (m, 2H), 6.51−6.47 (m, 2H), 2.95 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3): δ 183.1, 165.3, 164.8, 162.7, 155.6, 142.9, 134.1,
130.1, 130.0, 124.8, 122.7, 116.7, 116.5, 106.1, 68.4, 26.6; 19F NMR
(377 MHz, CDCl3): δ −107.20; IR (KBr): νmax = 2924, 2164, 1705,
1668, 1232, 753 cm−1; HRMS (ESI/Q-TOF): m/z calcd for
C17H12FN2O2S (M + H)+ 327.0604, found 327.0602.
1
acetate = 7:3); H NMR (500 MHz, CDCl3): δ 7.79−7.76 (m, 1H),
7.43−7.38 (m, 1H), 7.35−7.30 (m, 2H), 7.27−7.23 (m, 2H), 7.19−
7.16 (m, 2H), 7.06−7.00 (m, 2H), 6.96−6.92 (m, 1H), 6.74 (d, J =
8.5Hz, 1H), 5.04 (s, 2H), 3.82 (s, 3H), 2.18 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3): δ 157.4, 154.9, 139.5, 138.7, 133.7, 132.5, 130.4,
129.9, 129.3, 129.1, 128.5, 128.4, 127.3, 126.7, 120.6, 109.8, 99.0,
91.7, 82.7, 56.9, 55.6, 16.2; IR (neat): νmax = 2951, 2217, 1638, 1437,
1134, 759 cm−1; HRMS (ESI/Q-TOF): m/z calcd for C24H21INO2
(M + H)+ 482.0617, found 482.0615.
4-(4-Chlorophenyl)-1-methyl-3-thiocyanato-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (2e). Following the general procedure, 3-
(4-chlorophenyl)-N-(4-methoxyphenyl)-N-methylpropiolamide 1e
(91 mg, 0.3 mmol), AgSCN (103 mg, 0.6 mmol), and CAN (496
mg, 0.9 mmol) were reacted in DMSO (3 mL). After the workup,
column chromatography purification gave 2e as a brown solid (90 mg,
86% yield). Mp: 167−169 °C; Rf = 0.3 (hexane:ethyl acetate = 6:4);
1H NMR (400 MHz, CDCl3): δ 7.44−7.39 (m, 2H), 7.25−7.21 (m,
General Procedure for Synthesis of 3-Thiocyanato [4,5]
Spirotrienones (2). N-(4-Methoxyaryl)-propiolamide 1 (0.3 mmol),
silver thiocyanate (0.6 mmol), and CAN (0.9 mmol) were taken in a
reaction vessel, and DMSO (3 mL) was added. The reaction mixture
was stirred at 60 °C (oil bath temperature) for 30 min. After
2H), 6.57−6.53 (m, 2H), 6.51−6.47 (m, 2H), 2.95 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3): δ 183.1, 164.7, 155.4, 142.9, 137.6, 134.2,
129.6, 129.2, 127.2, 123.0, 105.9, 68.4, 26.6; IR (KBr): νmax = 3023,
E
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Article
2163, 1707, 1672, 1215, 745 cm−1; HRMS (ESI/Q-TOF): m/z calcd
for C17H12N2O2SCl (M + H)+ 343.0308, found 343.0308.
TOF): m/z calcd for C18H12F3N2O2S (M + H)+ 377.0572, found
377.0569.
1-Methyl-4-(naphthalen-1-yl)-3-thiocyanato-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (2k). Following the general procedure,
N-(4-methoxyphenyl)-N-methyl-3-(naphthalen-1-yl)propiolamide 1k
(95 mg, 0.3 mmol), AgSCN (102 mg, 0.6 mmol), and CAN (493 mg,
0.9 mmol) were reacted in DMSO (3 mL). Column chromatography
purification gave 2k as a yellow solid (92 mg, 85% yield). Mp: 179−
1-Methyl-4-(4-nitrophenyl)-3-thiocyanato-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (2f). Following the general procedure, N-(4-
methoxyphenyl)-N-methyl-3-(4-nitrophenyl)propiolamide 1f (94 mg,
0.3 mmol), AgSCN (103 mg, 0.6 mmol), and CAN (495 mg, 0.9
mmol) were reacted in DMSO (3 mL). Column chromatography
purification gave 2f as a white solid (97 mg, 90% yield). Mp 160−162
°C; Rf = 0.4 (hexane:ethyl acetate = 5:5); 1H NMR (400 MHz,
CDCl3): δ 8.34−8.28 (m, 2H), 7.49−7.44 (m, 2H), 6.58−6.49 (m,
4H), 2.98 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 182.7,
164.3, 153.1, 149.1, 142.2, 134.7, 134.6, 129.3, 125.3, 124.3, 105.3,
68.6, 26.8; IR (KBr): νmax = 2922, 2854, 2164, 1709, 1669, 1350
cm−1; HRMS (ESI/Q-TOF): m/z calcd for C17H12N3O4S (M + H)+
354.0549, found 354.0543.
1
181 °C; Rf = 0.3 (hexane:ethyl acetate = 6:4); H NMR (500 MHz,
CDCl3): δ 7.97−7.91 (m, 2H), 7.61−7.54 (m, 2H), 7.51−7.42 (m,
2H), 7.25−7.22 (m, 1H), 6.72 (dd, J = 10.0, 3.0 Hz, 1H), 6.64 (dd, J
= 10.0, 1.7 Hz, 1H), 6.52 (dd, J = 10.1, 3.0 Hz, 1H), 6.16 (dd, J =
10.1, 1.7 Hz, 1H), 3.04 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3):
δ 183.1, 164.8, 154.5, 142.6, 142.5, 134.7, 133.7, 133.4, 131.3, 129.9,
129.6, 127.9, 126.9, 126.8, 125.8, 125.1, 124.6, 123.4, 105.4, 69.9,
27.1; IR (KBr): νmax = 2924, 2164, 1708, 1671, 759 cm−1; HRMS
(ESI/Q-TOF): m/z calcd for C21H15N2O2S (M + H)+ 359.0854,
found 359.0854.
4-(1-Methyl-2,8-dioxo-3-thiocyanato-1-azaspiro[4.5]deca-3,6,9-
trien-4-yl)benzonitrile (2g). Following the general procedure, 3-(4-
cyanophenyl)-N-(4-methoxyphenyl)-N-methylpropiolamide 1g (88
mg, 0.3 mmol), AgSCN (102 mg, 0.6 mmol), and CAN (496 mg,
0.9 mmol) were reacted in DMSO (3 mL). After the workup, column
chromatography purification gave 2g as a pale-yellow solid (89 mg,
88% yield). Mp: 173−175 °C; Rf = 0.4 (hexane:ethyl acetate = 5:5);
1H NMR (400 MHz, CDCl3): δ 7.77−7.72 (m, 2H), 7.43−7.38 (m,
1-Methyl-3-thiocyanato-4-(thiophen-2-yl)-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (2l). Following the general procedure, N-(4-
methoxyphenyl)-N-methyl-3-(thiophen-2-yl)propiolamide 1l (82 mg,
0.3 mmol), AgSCN (102 mg, 0.6 mmol), and CAN (494 mg, 0.9
mmol) were reacted in DMSO (3 mL). Column chromatography
purification gave 2l as a yellow solid (75 mg, 79% yield). Mp: 143−
2H), 6.58−6.49 (m, 4H), 2.97 (s, 3H); 13C{1H} NMR (101 MHz,
CDCl3): δ 182.8, 164.4, 153.7, 142.3, 134.5, 133.1, 132.8, 128.8,
124.7, 117.5, 114.9, 105.5, 68.5, 26.7; IR (KBr): νmax = 2925, 2164,
1709, 1671, 1379, 1217, 751 cm−1; HRMS (ESI/Q-TOF): m/z calcd
for C18H12N3O2S (M + H)+ 334.0650, found 334.0653.
1
145 °C; Rf1= 0.3 (hexane:ethyl acetate = 5:5); H NMR (500 MHz,
CDCl3) δ H NMR (500 MHz, CDCl3): δ 7.66 (dd, J = 5.1, 1.0 Hz,
1H), 7.53 (dd, J = 3.9, 1.0 Hz, 1H), 7.15 (dd, J = 5.1, 3.9 Hz, 1H),
6.67−6.63 (m, 2H), 6.55−6.52 (m, 2H), 2.92 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3): δ 183.5, 165.2, 150.8, 144.1, 133.8, 132.4, 131.7,
130.6, 128.3, 116.4, 106.4, 66.8, 26.1; IR (KBr): νmax = 2924, 2160,
1702, 1630, 1374, 1269, 754 cm−1; HRMS (ESI/Q-TOF): m/z calcd
for C15H11N2O2S2 (M + H)+ 315.0262, found 315.0259.
4-(4-Acetylphenyl)-1-methyl-3-thiocyanato-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (2h). Following the general procedure, 3-
(4-acetylphenyl)-N-(4-methoxyphenyl)-N-methylpropiolamide 1h
(93 mg, 0.3 mmol), AgSCN (102 mg, 0.6 mmol), and CAN (495
mg, 0.9 mmol) were reacted in DMSO (3 mL). Column
chromatography purification gave 2h as a white solid (89 mg, 84%
1,4-Dimethyl-3-thiocyanato-1-azaspiro[4.5]deca-3,6,9-triene-
2,8-dione (2m). Following the general procedure, N-(4-methox-
yphenyl)-N-methylbut-2-ynamide 1m (61 mg, 0.3 mmol), AgSCN
(102 mg, 0.6 mmol), and CAN (491 mg, 0.9 mmol) were reacted in
DMSO (3 mL). After the workup, column chromatography
purification gave 2m as a white solid (60 mg, 81% yield). Mp:
1
yield). Mp: 179−181 °C; Rf = 0.4 (hexane:ethyl acetate = 5:5); H
NMR (500 MHz, CDCl3): δ 8.01−7.98 (m, 2H), 7.39−7.36 (m, 2H),
6.56−6.50 (m, 4H), 2.97 (s, 3H), 2.62 (s, 3H); 13C{1H} NMR (101
MHz, CDCl3): δ 196.8, 183, 164.6, 155.2, 142.6, 138.7, 134.3, 133,
128.9, 128.3, 123.8, 105.8, 68.4, 26.7 (2C); IR (KBr): νmax = 2921,
2165, 1679, 1630, 1371, 1265, 722 cm−1; HRMS (ESI/Q-TOF): m/z
calcd for C19H15N2O3S (M + H)+ 351.0803, found 351.0804.
4-(3,5-Dimethylphenyl)-1-methyl-3-thiocyanato-1-azaspiro-
[4.5]deca-3,6,9-triene-2,8-dione (2i). Following the general proce-
dure, 3-(3,5-dimethylphenyl)-N-(4-methoxyphenyl)-N-methylpropio-
lamide 1i (89 mg, 0.3 mmol), AgSCN (103 mg, 0.6 mmol), and CAN
(496 mg, 0.9 mmol) were reacted in DMSO (3 mL). After the
workup, column chromatography purification gave 2i as a white solid
(77 mg, 76% yield). Mp: 128−130 °C; Rf = 0.3 (hexane:ethyl acetate
1
146−148 °C; Rf = 0.3 (hexane:ethyl acetate = 5:5); H NMR (400
MHz, CDCl3): δ 6.65−6.60 (m, 2H), 6.38−6.34 (m, 2H), 2.92 (s,
3H), 2.06 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 183.3,
165.4, 158.1, 143.5, 134.2, 121.4, 106.9, 68.8, 26.9, 12.3; IR (KBr):
νmax = 2958, 2170, 1713, 1674, 1388, 860 cm−1; HRMS (ESI/Q-
TOF): m/z calcd for C12H11N2O2S (M + H)+ 247.0541, found
247.0542.
4-Ethyl-1-methyl-3-thiocyanato-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (2n). Following the general procedure, N-(4-
methoxyphenyl)-N-methylpent-2-ynamide 1n (66 mg, 0.3 mmol),
AgSCN (103 mg, 0.6 mmol), and CAN (497 mg, 0.9 mmol) were
reacted in DMSO (3 mL). After the workup, column chromatography
purification gave 2n as a white solid (66 mg, 83% yield). Mp: 128−
1
= 7:3); H NMR (500 MHz, CDCl3): δ 7.09−7.08 (m, 1H), 6.83−
6.81 (m, 2H), 6.54−6.51 (m, 2H), 6.50−6.47 (m, 2H), 2.94 (s, 3H),
2.30 (s, 3H), 2.30 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ
183.5, 165.0, 157.6, 143.2, 138.9, 133.9, 132.9, 128.9, 125.3, 121.9,
106.5, 68.3, 26.6, 21.4 (2C); IR (KBr): νmax = 2921, 2163, 1711,
1271, 1023, 760 cm−1; HRMS (ESI/Q-TOF): m/z calcd for
C19H17N2O2S (M + H)+: 337.1011, found 337.1010.
1
130 °C; Rf = 0.3 (hexane:ethyl acetate = 5:5); H NMR (400 MHz,
CDCl3): δ 6.62 (d, J = 10.0 Hz, 2H), 6.37 (d, J = 6.4 Hz, 2H), 2.90 (s,
3H), 2.39 (q, J = 7.6 Hz, 2H), 1.17 (t, J = 7.6 Hz, 3H); 13C{1H}
NMR (101 MHz, CDCl3): δ 183.5, 165.5, 162.9, 143.3, 134.2, 121.1,
106.8, 68.8, 26.8, 20.2, 13.4; IR (KBr): νmax = 2980, 2163, 1708, 1603,
1382, 762 cm−1; HRMS (ESI/Q-TOF): m/z calcd for C13H13N2O2S
(M + H)+ 261.0698, found 261.0698.
1-Methyl-3-thiocyanato-4-(3-(trifluoromethyl)phenyl)-1-
azaspiro[4.5]deca-3,6,9-triene-2,8-dione (2j). Following the general
procedure, N-(4-methoxyphenyl)-N-methyl-3-(3-(trifluoromethyl)-
phenyl)propiolamide 1j (100 mg, 0.3 mmol), AgSCN (101 mg, 0.6
mmol), and CAN (491 mg, 0.9 mmol) were reacted in DMSO (3
mL). After the workup, column chromatography purification gave 2j
as a white solid (92 mg, 81% yield). Mp: 102−104 °C; Rf = 0.3
(hexane:ethyl acetate = 6:4); 1H NMR (400 MHz, CDCl3): δ 7.75 (d,
J = 7.9 Hz, 1H), 7.59 (t, J = 7.8 Hz, 1H), 7.52 (s, 1H), 7.47 (d, J = 7.8
Hz, 1H), 6.58−6.51 (m, 4H), 2.97 (s, 3H); 13C{1H} NMR (101
MHz, CDCl3): δ 182.9, 164.6, 154.5, 142.6, 134.4, 131.8, 131.5,
131.2, 129.9, 129.6, 127.8, 124.9, 124.8, 124.2, 121.9, 105.6, 68.5,
26.7; 19F NMR (377 MHz, CDCl3): δ −62.61; IR (KBr): νmax = 2925,
2165, 1708, 1672, 1631, 1331, 1129, 758 cm−1; HRMS (ESI/Q-
1-Benzyl-4-phenyl-3-thiocyanato-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (2o). Following the general procedure, N-benzyl-N-(4-
methoxyphenyl)-3-phenylpropiolamide 1o (103 mg, 0.3 mmol),
AgSCN (102 mg, 0.6 mmol), and CAN (493 mg, 0.9 mmol) were
reacted in DMSO (3 mL). After the workup, column chromatography
purification gave 2o as a brown solid (100 mg, 86% yield). Mp: 108−
1
110 °C; Rf = 0.4 (hexane:ethyl acetate = 7:3); H NMR (400 MHz,
CDCl3): δ 7.47−7.42 (m, 1H), 7.42−7.36 (m, 2H), 7.30−7.23 (m,
5H), 7.19−7.14 (m, 2H), 6.35−6.27 (m, 4H), 4.59 (s, 2H); 13C{1H}
NMR (101 MHz, CDCl3): δ 183.5, 165.2, 157.2, 143.3, 136.6, 133.1,
131.1, 129.0, 128.8, 128.7, 128.5, 128.3, 127.8, 122.4, 106.2, 68.9,
45.5; IR (KBr): νmax = 2923, 2163, 1701, 1671, 754 cm−1; HRMS
F
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(ESI/Q-TOF): m/z calcd for C23H17N2O2S (M + H)+ 385.1011,
found 385.1013.
NMR (400 MHz, CDCl3): δ 7.53−7.43 (m, 3H), 7.25−7.22 (m, 2H),
6.57−6.51 (m, 2H), 6.12−6.08 (m, 1H), 2.98 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3): δ 176.3, 164.5, 157.4, 156.2, 144.3, 133.0, 133.0,
131.4, 129.3, 128.5, 127.7, 122.9, 119.3, 119.2, 105.9, 69.9, 26.6; 19F
NMR (377 MHz, CDCl3): δ −119.75; IR (KBr): νmax = 3050, 2164,
1714, 1380, 1173, 760 cm−1; HRMS (ESI/Q-TOF): m/z calcd for
C17H12FN2O2S (M + H)+ 327.0604, found 327.0611.
1-(2-Iodobenzyl)-4-phenyl-3-thiocyanato-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (2p). Following the general procedure, N-(2-
iodobenzyl)-N-(4-methoxyphenyl)-3-phenylpropiolamide 1p (144
mg, 0.3 mmol), AgSCN (101 mg, 0.6 mmol), and CAN (489 mg,
0.9 mmol) were reacted in DMSO (3 mL). After the workup, column
chromatography purification gave 2p as a brown solid (131 mg, 86%
1-(2-Iodobenzyl)-7-methyl-4-phenyl-3-thiocyanato-1-azaspiro-
[4.5]deca-3,6,9-triene-2,8-dione (2u). Following the general proce-
dure, N-(2-iodobenzyl)-N-(4-methoxy-3-methylphenyl)-3-phenylpro-
piolamide 1u (128 mg, 0.3 mmol), AgSCN (102 mg, 0.6 mmol), and
CAN (494 mg, 0.9 mmol) were reacted in DMSO (3 mL). After the
workup, column chromatography purification gave 2u as a white solid
(141 mg, 89% yield). Mp: 143−145 °C; Rf = 0.3 (hexane:ethyl acetate
1
yield). Mp: 113−115 °C; Rf = 0.4 (hexane:ethyl acetate = 7:3); H
NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.8 Hz, 1H), 7.47−7.35 (m,
4H), 7.30 (d, J = 7.4 Hz, 1H), 7.18 (d, J = 7.3 Hz, 2H), 6.97 (t, J = 7.4
Hz, 1H), 6.29 (q, J = 10.2 Hz, 4H), 4.77 (s, 2H); 13C{1H} NMR (101
MHz, CDCl3) δ 183.5, 165.2, 157.7, 142.4, 139.7, 138.9, 133.5, 131.1,
130.3, 129.9, 129.0, 128.8, 128.6, 127.8, 122.2, 106.2, 99.7, 68.8, 49.7;
IR (KBr): νmax = 3055, 2163, 1709, 1389, 756 cm−1; HRMS (ESI/Q-
TOF): m/z calcd for C23H16N2O2SI (M + H)+ 510.9977, found
510.9988.
1
= 7:3); H NMR (500 MHz, CDCl3): δ 7.77 (dd, J = 8.0, 1.1 Hz,
1H), 7.45−7.41 (m, 2H), 7.39−7.35 (m, 2H), 7.31− 7.29 (m, 1H),
7.17−7.14 (m, 2H), 6.97−6.93 (m, 1H), 6.30−6.25 (m, 2H), 5.98−
5.96 (m, 1H), 4.86 (d, J = 15.3 Hz, 1H), 4.68 (d, J = 15.3 Hz, 1H),
1.72 (d, J = 1.4 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 184.4,
165.2, 158.5, 142.2, 140.9, 139.6, 139.3, 137.3, 133.4, 131, 130.3,
129.9, 128.9, 128.9, 128.8, 127.7, 121.6, 106.4, 99.8, 69.2, 49.5, 16.0;
IR (KBr): νmax = 2923, 2167, 1707, 1643, 1386, 757 cm−1; HRMS
(ESI/Q-TOF): m/z calcd for C24H18N2O2SI (M + H)+ 525.0134,
found 525.0136.
7-Methyl-4-phenyl-3-thiocyanato-1-(2-(trifluoromethyl)benzyl)-
1-azaspiro[4.5]deca-3,6,9-triene-2,8-dione (2q). Following the
general procedure, N-(4-methoxy-3-methylphenyl)-3-phenyl-N-(2-
(trifluoromethyl)benzyl)propiolamide 1q (127 mg, 0.3 mmol),
AgSCN (102 mg, 0.6 mmol), and CAN (494 mg, 0.9 mmol) were
reacted in DMSO (3 mL). After the workup, column chromatography
purification gave 2q as a yellow solid (114 mg, 81% yield). Mp: 139−
1
141 °C; Rf = 0.5 (hexane:ethyl acetate = 7:3); H NMR (400 MHz,
1-Phenyl-2-thiocyanato-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-
3,9(5H)-dione (4). Following the general procedure, 1-(6-methoxy-
3,4-dihydroquinolin-1(2H)-yl)-3-phenylprop-2-yn-1-one 3 (88 mg,
0.3 mmol), AgSCN (101 mg, 0.6 mmol), and CAN (489 mg, 0.9
mmol) were reacted in DMSO (3 mL). After the workup, column
chromatography purification gave 4 as a brown solid (80 mg, 80%
CDCl3): δ 7.54 (t, J = 8.5 Hz, 2H), 7.48−7.36 (m, 5H), 7.19−7.13
(m, 2H), 6.39−6.33 (m, 2H), 6.01 (dd, J = 2.4, 1.4 Hz, 1H), 4.78 (d,
J = 15.1 Hz, 1H), 4.44 (d, J = 15.1 Hz, 1H), 1.74 (d, J = 1.5 Hz, 3H);
13C{1H} NMR (101 MHz, CDCl3): δ 184.0, 165.3, 158.3, 142.6,
140.7, 138.0, 137.8, 133.4, 132.6, 131.3, 131.1, 130.9, 129.4, 129.0,
128.7, 127.7, 125.7, 125.0, 121.7, 106.3, 69.2, 44.9, 15.6; 19F NMR
(377 MHz, CDCl3) δ −62.99; IR (KBr): νmax = 3063, 2164, 1700,
1
yield). Mp: 147−149 °C; Rf = 0.3 (hexane:ethyl acetate = 6:4); H
NMR (500 MHz, CDCl3): δ 7.47−7.43 (m, 1H), 7.41−7.37 (m, 2H),
7.08−7.05 (m, 2H), 6.54−6.52 (m, 1H), 6.40 (t, J = 1.5 Hz 1H),
6.28−6.24 (m, 1H), 4.28−4.22 (m, 1H), 2.90−2.82 (m, 1H), 2.59−
2.50 (m, 2H), 2.08−2.00 (m, 1H), 1.94−1.87 (m, 1H); 13C{1H}
NMR (101 MHz, CDCl3): δ 183.9, 168.7, 158.6, 156.4, 144.5, 132.9,
131.0, 129.9, 128.9, 128.3, 127.9, 122.9, 106.2, 72.3, 37.2, 26.8, 26.2;
IR (KBr): νmax 2951, 2163, 1709, 1667, 1377, 753 cm−1; HRMS
(ESI/Q-TOF): m/z calcd for C19H15N2O2S (M + H)+ 335.0854,
found 335.0857.
1670, 737 cm−1
; HRMS (ESI/Q-TOF): m/z calcd for
C25H18F3N2O2S (M + H)+ 467.1041, found 467.1040.
1,6-Dimethyl-4-phenyl-3-thiocyanato-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (2r). Following the general procedure, N-(4-
methoxy-2-methylphenyl)-N-methyl-3-phenylpropiolamide 1r (84
mg, 0.3 mmol), AgSCN (102 mg, 0.6 mmol), and CAN (492 mg,
0.9 mmol) were reacted in DMSO (3 mL). After the workup, column
chromatography purification gave 2r as a white solid (85 mg, 88%
1
yield). Mp: 163-165 °C; Rf = 0.3 (hexane:ethyl acetate = 7:3); H
4-Phenyl-3-thiocyanato-1-oxaspiro[4.5]deca-3,6,9-triene-2,8-
dione (6a). Following the general procedure, 4-methoxyphenyl 3-
phenylpropiolate 5a (76 mg, 0.3 mmol), AgSCN (102 mg, 0.6 mmol),
and CAN (493 mg, 0.9 mmol) were reacted in DMSO (3 mL). After
the workup, column chromatography purification gave 6a as a brown
NMR (500 MHz, CDCl3): δ 7.50−7.46 (m, 1H), 7.45−7.41 (m, 2H),
7.28−7.27 (m, 1H), 7.26−7.25 (m, 1H), 6.54 (dd, J = 9.9, 1.7 Hz,
1H), 6.46 (d, J = 9.9 Hz, 1H), 6.40−6.38 (m, 1H), 2.86 (s, 3H), 1.76
(d, J = 1.4 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 184.1,
165.5, 157.4, 151.5, 143.2, 133.5, 132.6, 131.4, 129.3, 128.7, 127.6,
122.4, 106.3, 70.5, 26.2, 17.7; IR (KBr): νmax = 3016, 2163, 1709,
1389, 757 cm−1; HRMS (ESI/Q-TOF): m/z calcd for C18H15N2O2S
(M + H)+ 323.0854, found 323.0858.
1
liquid (73 mg, 82% yield), Rf = 0.4 (hexane:ethyl acetate = 7:3); H
NMR (400 MHz, CDCl3): δ 7.57−7.52 (m, 1H), 7.51-7.45 (m, 2H),
7.36−7.31 (m, 2H), 6.71−6.65 (m, 2H), 6.50−6.43 (m, 2H);
13C{1H} NMR (101 MHz, CDCl3): δ 183.1, 165.9, 165.7, 140.6,
1,7-Dimethyl-4-phenyl-3-thiocyanato-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (2s). Following the general procedure, N-(4-
methoxy-3-methylphenyl)-N-methyl-3-phenylpropiolamide 1s (84
mg, 0.3 mmol), AgSCN (112 mg, 0.6 mmol), and CAN (492 mg,
0.9 mmol) were reacted in DMSO (3 mL). After the workup, column
chromatography purification gave 2s as a white solid (86 mg, 89%
139.7, 132.7, 132.3, 129.5, 127.5, 116.4, 105.2, 83.1; IR (neat): νmax =
3058, 2924, 2105, 1772, 1672, 1214, 746 cm−1; HRMS (ESI/Q-
TOF): m/z calcd for C16H10NO3S (M + H)+ 296.0381, found
296.0383.
4-(4-Chlorophenyl)-3-thiocyanato-1-oxaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (6b). Following the general procedure, 4-Methox-
yphenyl 3-(4-chlorophenyl)propiolate 5b (86 mg, 0.3 mmol), AgSCN
(102 mg, 0.6 mmol), and CAN (492 mg, 0.9 mmol) were reacted in
DMSO (3 mL). After the workup, column chromatography
purification gave 6b as a white solid (77 mg, 78% yield). Mp: 137−
1
yield). Mp: 129−131 °C; Rf = 0.3 (hexane:ethyl acetate = 7:3); H
NMR (500 MHz, CDCl3): δ 7.49−7.44 (m, 1H), 7.44−7.39 (m, 2H),
7.24−7.21 (m, 2H), 6.51−6.45 (m, 2H), 6.28 (dd, J = 2.7, 1.4 Hz,
1H), 2.93 (s, 3H), 1.95 (d, J = 1.4 Hz, 3H); 13C{1H} NMR (101
MHz, CDCl3): δ 184.2, 165, 157.7, 142.9, 141.5, 137.7, 133.7, 131.0,
129.0 (2C), 127.8, 121.9, 106.5, 68.9, 26.5, 16; IR (KBr): νmax = 2923,
2164, 1706, 1642, 1371, 750 cm−1; HRMS (ESI/Q-TOF): m/z calcd
for C18H15N2O2S (M + H)+ 323.0854, found 323.0858.
1
139 °C; Rf = 0.4 (hexane:ethyl acetate = 7:3); H NMR (400 MHz,
CDCl3) δ 7.46 (d, J = 8.5 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 6.66 (d, J
= 10.1 Hz, 2H), 6.48 (d, J = 10.0 Hz, 2H); 13C{1H} NMR (101 MHz,
CDCl3): δ 182.9, 165.7, 164.2, 140.4, 138.9, 132.9, 129.9, 128.9,
125.7, 116.9, 104.9, 83.0; IR (KBr): νmax = 3058, 2166, 1766, 1674,
7-Fluoro-1-methyl-4-phenyl-3-thiocyanato-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (2t). Following the general procedure, N-(3-
fluoro-4-methoxyphenyl)-N-methyl-3-phenylpropiolamide 1t (85 mg,
0.3 mmol), AgSCN (101 mg, 0.6 mmol), and CAN (491 mg, 0.9
mmol) were reacted in DMSO (3 mL). After the workup, column
chromatography purification gave 2t as a yellow solid (90 mg, 92%
1216, 759 cm−1
; HRMS (ESI/Q-TOF): m/z calcd for
C16H12ClN2O3S+ (M + NH4)+: 347.0257, Found: 347.0254.
4-(4-Acetylphenyl)-3-thiocyanato-1-oxaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (6c). Following the general procedure, 4-methox-
yphenyl 3-(4-acetylphenyl)propiolate 5c (89 mg, 0.3 mmol), AgSCN
(102 mg, 0.6 mmol), and CAN (494 mg, 0.9 mmol) were reacted in
1
yield). Mp 125−127 °C; Rf = 0.3 (hexane:ethyl acetate = 7:3); H
G
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Article
DMSO (3 mL). After the workup, column chromatography
7.38 (m, 3H), 7.25−7.21 (m, 2H), 6.52 (s, 4H), 2.96 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3): δ 183.4, 166.2, 157.7, 143.2,
133.9, 131.0, 129.6, 129.1, 127.7, 122.3, 96.8, 69.7, 26.7; IR (KBr):
νmax = 3098, 1706, 1673, 1380, 1217, 767 cm−1; HRMS (ESI/Q-
TOF): m/z calcd for C17H13N2O2Se (M + H)+ 357.0142, found
357.0138.
purification gave 6c as a brownish white solid (74 mg, 72% yield).
1
Mp: 129−131 °C; Rf = 0.3 (hexane:ethyl acetate = 7:3); H NMR
(400 MHz, CDCl3): δ 8.04 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz,
2H), 6.68 (d, J = 10.0 Hz, 2H), 6.47 (d, J = 10.0 Hz, 2H), 2.63 (s,
3H); 13C{1H} NMR (101 MHz, CDCl3): δ 196.5, 182.7, 165.6,
164.1, 140.2, 139.4, 133.0, 131.4, 129.1, 127.9, 118, 104.6, 83.2, 26.7;
IR (KBr): νmax = 2924, 2168, 1778, 1681, 1632, 1267, 757 cm−1;
HRMS (ESI/Q-TOF): m/z calcd for C18H12NO4S (M + H)+
338.0487, found 338.0492.
4-(4-Fluorophenyl)-1-methyl-3-selenocyanato-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (7b). Following the general procedure, 3-
(4-fluorophenyl)-N-(4-methoxyphenyl)-N-methylpropiolamide 1d
(85 mg, 0.3 mmol), KSeCN (86 mg, 0.6 mmol), and CAN (491
mg, 0.9 mmol) were reacted in DMSO (3 mL) for 4 h. After the
workup, column chromatography purification gave 7b as a white solid
(88 mg, 78% yield). Mp: 140−142 °C; Rf = 0.3 (hexane:ethyl acetate
4-(3,5-Dimethylphenyl)-3-thiocyanato-1-oxaspiro[4.5]deca-
3,6,9-triene-2,8-dione (6d). Following the general procedure, 4-
methoxyphenyl 3-(3,5-dimethylphenyl)propiolate 5d (84 mg, 0.3
mmol), AgSCN (101 mg, 0.6 mmol), and CAN (490 mg, 0.9 mmol)
were reacted in DMSO (3 mL). Column chromatography purification
gave 6d as a white solid (83 mg, 86% yield). Mp: 127−129 °C; Rf =
1
= 7:3); H NMR (400 MHz, CDCl3) δ 7.29−7.24 (m, 2H), 7.15−
7.09 (m, 2H), 6.52 (s, 4H), 2.95 (s, 3H); 13C{1H} NMR (101 MHz,
CDCl3) δ 183.2, 166.1, 165.2, 162.7, 156.5, 143.1, 134.0, 130.1, 130.0,
125.6, 125.5, 122.7, 116.6, 116.3, 96.8, 69.8, 26.7; 19F NMR (377
MHz, CDCl3) δ −107.72; IR (KBr): νmax = 3016, 1696, 1667, 1373,
1
0.3 (hexane:ethyl acetate = 8:2); H NMR (400 MHz, CDCl3): δ
7.15 (s, 1H), 6.89 (s, 2H), 6.68−6.63 (m, 2H), 6.48−6.43 (m, 2H),
2.32 (s, 6H); 13C{1H} NMR (101 MHz, CDCl3): δ 183.2, 166.3,
166.0, 140.8, 139.3, 134.0, 132.6, 127.5, 125.0, 115.8, 105.3, 83.0, 21.3
(2C); IR (KBr): νmax = 2968, 2162, 2918, 1782, 1678, 1382 cm−1;
HRMS (ESI/Q-TOF): m/z calcd for C18H14NO3S (M + H)+
324.0694, found 324.0695.
1280, 751 cm−1
; HRMS (ESI/Q-TOF): m/z calcd for
C17H12FN2O2Se (M + H)+ 375.0048, found 375.0045.
1-Methyl-3-selenocyanato-4-(thiophen-2-yl)-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (7c). Following the general procedure,
N-(4-methoxyphenyl)-N-methyl-3-(thiophen-2-yl)propiolamide 1l
(82 mg, 0.3 mmol), KSeCN (86 mg, 0.6 mmol), and CAN (494
mg, 0.9 mmol) were reacted in DMSO (3 mL) for 4 h. After the
workup, column chromatography purification gave 7c as a yellow solid
(84 mg, 77% yield). Mp: 133−135 °C; Rf = 0.2 (hexane:ethyl acetate
= 7:3); 1H NMR (500 MHz, CDCl3) δ 7.62 (dd, J = 5.1, 1.1 Hz, 1H),
7.46 (dd, J = 3.9, 1.1 Hz, 1H), 7.14 (dd, J = 5.1, 3.9 Hz, 1H), 6.65−
6.62 (m, 2H), 6.56−6.53 (m, 2H), 2.93 (s, 3H); 13C{1H} NMR (101
MHz, CDCl3) δ 183.6, 166.3, 151.5, 144.1, 133.8, 131.8, 131.3, 131.1,
128.2, 117.3, 97.4, 68.1, 26.2; IR (KBr): νmax = 2924, 2158, 1696,
1584, 1373, 758 cm−1; HRMS (ESI/Q-TOF): m/z calcd for
C15H11N2O2SSe (M + H)+ 362.9706, found 362.9702.
4-(Naphthalen-1-yl)-3-thiocyanato-1-oxaspiro[4.5]deca-3,6,9-
triene-2,8-dione (6e). Following the general procedure, 4-methox-
yphenyl 3-(naphthalen-1-yl)propiolate 5e (91 mg, 0.3 mmol), AgSCN
(102 mg, 0.6 mmol), and CAN (492 mg, 0.9 mmol) were reacted in
DMSO (3 mL). Column chromatography purification gave 6e as a
brown solid (81 mg, 78% yield). Mp: 176−178 °C; Rf = 0.3
1
(hexane:ethyl acetate = 8:2); H NMR (500 MHz, CDCl3): δ 8.01−
7.95 (m, 2H), 7.66−7.59 (m, 2H), 7.51−7.45 (m, 2H), 7.28−7.27
(m, 1H), 6.87 (dd, J = 10.1, 3.2 Hz, 1H), 6.68 (dd, J = 10.1, 3.2 Hz,
1H), 6.57 (dd, J = 10.1, 1.7 Hz, 1H), 6.09 (dd, J = 10.1, 1.7 Hz, 1H);
13C{1H} NMR (101 MHz, CDCl3): δ 182.8, 165.8, 164.2, 140.3,
1,6-Dimethyl-4-phenyl-3-selenocyanato-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (7d). Following the general procedure, N-(4-
methoxy-2-methylphenyl)-N-methyl-3-phenylpropiolamide 1r (84
mg, 0.3 mmol), KSeCN (86 mg, 0.6 mmol), and CAN (492 mg,
0.9 mmol) were reacted in DMSO (3 mL) for 4 h. After the workup,
column chromatography purification gave 7d as a white solid (82 mg,
74% yield). Mp: 158−160 °C; Rf = 0.3 (hexane:ethyl acetate = 7:3);
1H NMR (500 MHz, CDCl3) δ 7.49−7.40 (m, 3H), 7.23 (dd, J = 5.2,
3.3 Hz, 2H), 6.55−6.47 (m, 2H), 6.39−6.37 (m, 1H), 2.86 (s, 3H),
1.78 (d, J = 1.3 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 184.1,
166.6, 158.2, 151.6, 143.4, 133.4, 132.5, 131.2, 129.5, 129.2, 127.5,
122.2, 97.0, 71.9, 26.3, 17.7; IR (KBr): νmax = 3015, 2161, 1655, 1648,
1374, 1277, 748 cm−1; HRMS (ESI/Q-TOF): m/z calcd for
C18H15N2O2Se (M + H)+ 371.0299, found 371.0298.
139.9, 133.4, 133.3, 132.3, 132.1, 129.7, 129.2, 128.4, 127.1, 126.4,
124.6, 123.7, 123.1, 120.2, 104.3, 84.8; IR (KBr): νmax = 3055, 2167,
1779, 1673, 1222, 756 cm−1; HRMS (ESI/Q-TOF): m/z calcd for
C20H12NO3S (M + H)+ 346.0538, found 346.0539.
3-Thiocyanato-4-(thiophen-2-yl)-1-oxaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (6f). Following the general procedure, 4-methox-
yphenyl 3-(thiophen-2-yl)propiolate 5f (78 mg, 0.3 mmol), AgSCN
(102 mg, 0.6 mmol), and CAN (493 mg, 0.9 mmol) were reacted in
DMSO (3 mL). After the workup, column chromatography
purification gave 6f as a yellow liquid (59 mg, 65% yield). Rf = 0.3
(hexane:ethyl acetate = 7:3); 1H NMR (400 MHz, CDCl3): δ 7.85 (d,
J = 4.9 Hz, 1H), 7.66 (d, J = 3.7 Hz, 1H), 7.25−7.21 (m, 1H), 6.70
(d, J = 10.0 Hz, 2H), 6.58 (d, J = 10.0 Hz, 2H); 13C{1H} NMR (101
MHz, CDCl3): δ 183.4, 166.4, 158.8, 141.8, 135.6, 134, 132.7, 129.1,
128.9, 108.8, 105.6, 80.8; IR (neat): νmax = 2924, 2159, 1706, 1672,
1378, 758 cm−1; HRMS (ESI/Q-TOF): m/z calcd for C14H8NO3S2
(M + H)+ 301.9946, found 301.9945.
General Procedure for Synthesis of 3-Selenocyanato[4,5]-
spirotrienones (7). N-(4-Methoxyaryl)-propiolamide 1 (0.3 mmol),
potassium selenocyanate (0.6 mmol), and ceric ammonium nitrate
(0.9 mmol) were taken in a reaction vessel, and DMSO (3 mL) was
added. The reaction mixture was stirred at 60 °C (oil bath
temperature) for 4−15 h. After completion of the reaction
(monitored by TLC), water was added to the mixture, and the
mixture was extracted with ethyl acetate (3 × 10 mL). The combined
organic layers were dried over Na2SO4 and concentrated to get the
crude product, which was purified by column chromatography on
silica gel using ethyl acetate and hexane as an eluent to afford the
corresponding 3-selenocyanato [4,5] spirotrienones.
1-Benzyl-4-phenyl-3-selenocyanato-1-azaspiro[4.5]deca-3,6,9-
triene-2,8-dione (7e). Following the general procedure, N-benzyl-N-
(4-methoxyphenyl)-3-phenylpropiolamide 1o (103 mg, 0.3 mmol),
KSeCN (86 mg, 0.6 mmol), and CAN (493 mg, 0.9 mmol) were
reacted in DMSO (3 mL) for 15 h. After the workup, column
chromatography purification gave 7e as a white solid (75 mg, 58%
1
yield). Mp: 95−97 °C; Rf = 0.4 (hexane:ethyl acetate = 7:3); H
NMR (500 MHz, CDCl3) δ 7.44 (t, J = 7.4 Hz, 1H), 7.38 (t, J = 7.5
Hz, 2H), 7.31−7.22 (m, 5H), 7.14 (d, J = 7.4 Hz, 2H), 6.34 (d, J =
10.0 Hz, 2H), 6.28 (d, J = 10.1 Hz, 2H), 4.59 (s, 2H); 13C{1H} NMR
(101 MHz, CDCl3) δ 183.6, 166.4, 158.0, 143.4, 136.6, 133.0, 130.9,
129.4, 129.0, 128.9, 128.7, 128.3, 127.8, 122.2, 96.8, 70.2, 45.5; IR
(KBr): νmax = 3019, 2159, 1696, 1667, 1385, 738 cm−1; HRMS (ESI/
Q-TOF): m/z calcd for C23H17N2O2Se (M + H)+ 433.0455, found
433.0456.
1-Methyl-4-phenyl-3-selenocyanato-1-azaspiro[4.5]deca-3,6,9-
triene-2,8-dione (7a). Following the general procedure, N-(4-
methoxyaryl)-propiolamide 1a (80 mg, 0.3 mmol), KSeCN (87 mg,
0.6 mmol), CAN (493 mg, 0.9 mmol) were reacted in DMSO (3 mL)
for 12 h. After the workup, column chromatography purification gave
7a as a brown solid (78 mg, 72% yield). Mp: 140−142 °C; Rf = 0.3
Gram-Scale Synthesis. 1-Methyl-4-phenyl-3-thiocyanato-1-
azaspiro[4.5]deca-3,6,9-triene-2,8-dione (2a). N-(4-Methoxyaryl)-
propiolamide 1a (1.18 g, 4.5 mmol), AgSCN (1.5 g, 9 mmol), and
CAN (7.3 g, 13.5 mmol) were taken in a 100 mL round-bottomed
flask, and 25 mL of DMSO was added. The round-bottomed flask was
fitted with a condenser, and the reaction mixture was stirred at 60 °C
(oil bath temperature) for 30 min. After completion of the reaction
1
(hexane:ethyl acetate = 6:4); H NMR (500 MHz, CDCl3): δ 7.49−
H
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(monitored by TLC), water was added to the mixture, and the
mixture was extracted with ethyl acetate (30 mL × 3). The combined
organic layers were dried over Na2SO4. The organic layer was
concentrated, and the crude reaction mixture was purified by column
chromatography on silica gel by using ethyl acetate and hexane as an
eluent to afford the corresponding product 2a as a white solid (1.2 g)
in 92% yield.
40% yield). Mp: 158−160 °C; Rf = 0.3 (hexane:ethyl acetate = 2:8);
1H NMR (500 MHz, CDCl3) δ 7.39 (d, J = 7.2 Hz, 2H), 7.34 (t, J =
7.5 Hz, 5H), 7.28 (d, J = 6.0 Hz, 3H), 6.49−6.44 (m, 8H), 2.87 (s,
6H); 13C{1H} NMR (101 MHz, CDCl3) δ 183.9, 167.7, 157.3, 144.7,
133.8, 133.2, 130.8, 130.2, 128.6, 128.4, 67.7, 26.2; IR (KBr): νmax
=
3094, 1707, 1672, 1218, 771 cm−1; HRMS (ESI/Q-TOF): m/z calcd
for C32H25N2O4S2 (M + H)+ 565.1256, found 565.1250.
1-Methyl-4-phenyl-3-((trifluoromethyl)thio)-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (8). A mixture of 2a (50 mg, 0.16 mmol)
and CsF (25 mg, 0.16 mmol) was taken in a 10 mL round-bottomed
flask and dissolved in acetonitrile (3 mL) and cooled to 0 °C. Then,
trifluoromethyl trimethylsilane (45 mg, 0.32 mmol) was added at
once via a syringe and stirred at room temperature for 2 h. After
completion of the reaction (indicated by TLC), the reaction mixture
was filtered using a pad of Celite and extracted with ethyl acetate and
concentrated. The residue was purified by column chromatography to
obtain 8 as a white solid (46 mg, 80% yield). Mp: 105−107 °C; Rf =
1-Methyl-4-phenyl-3-((phenylethynyl)selanyl)-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (12). Following the procedure used for
the synthesis of 10, 1-methyl-4-phenyl-3-selenocyanato-1-
azaspiro[4.5]deca-3,6,9-triene-2,8-dione 7a (50 mg, 0.14 mmol) in
acetonitrile (4 mL), phenylacetylene (22 mg, 0.21 mmol), CuI (20
mol %), and Cs2CO3 (46 mg, 0.14 mmol) were added sequentially at
room temperature. After the workup, column chromatography
purification gave the desired product 12 as a white solid (54 mg,
89% yield). Mp 169−171 °C; Rf = 0.4 (hexane:ethyl acetate = 6:34);
1H NMR (400 MHz, CDCl3) δ 7.33−7.30 (m, 2H), 7.30−7.25 (m,
1
0.3 (hexane:ethyl acetate = 7:3); H NMR (400 MHz, CDCl3) δ
3H), 7.25−7.16 (m, 3H), 7.03−6.99 (m, 2H), 6.55−6.51 (m, 2H),
6.48−6.43 (m, 2H), 2.93 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3)
δ 183.9, 167.9, 151.8, 144.7, 133.3, 131.7, 130.3, 129.7, 128.5, 128.3,
7.46−7.37 (m, 3H), 7.27−7.23 (m, 2H), 6.51 (s, 4H), 2.95 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 183.4, 166.7, 165.1, 143.4,
133.8, 130.7, 129.8, 129.6, 128.7, 128.0, 126.8, 123.9, 68.4, 26.6; 19F
NMR (376 MHz, CDCl3) δ −39.27; IR (KBr): νmax = 3055, 1709,
1670, 1374, 1101, 759 cm−1; HRMS (ESI/Q-TOF): m/z calcd for
C17H13F3NO2S (M + H)+ 352.0619, found 352.0620.
128.2, 127.9, 126.9, 122.5, 103.3, 69.8, 65.0, 26.3; IR (KBr): νmax
=
3058, 1698, 1383, 1037, 760 cm−1; HRMS (ESI/Q-OTF): m/z calcd
for C24H18NO2Se (M + H)+ 432.0503, found 432.0502.
3-((1H-Tetrazol-5-yl)thio)-1-methyl-4-phenyl-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (9). A solution of 2a (50 mg, 0.16
mmol), ZnCl2 (22 mg, 0.16 mmol), and NaN3 (13 mg, 0.19 mmol)
was taken in a reaction vessel, and i-PrOH (3 mL) was added and left
for stirring at 60 °C for 1.5 h. After completion of the reaction, the
mixture was diluted with ethyl acetate and concentrated under
vacuum. The residue was purified by column chromatography on
silica gel using methanol and DCM as an eluent to provide 9 as a
white solid (47 mg, 84% yield). Mp: 185−187 °C; Rf = 0.3 (DCM:
MeOH = 7:3); 1H NMR (500 MHz, CD3OD) δ 7.37−7.30 (m, 5H),
6.93−6.89 (m, 2H), 6.49−6.46 (m, 2H), 2.92 (s, 3H); 13C{1H} NMR
(101 MHz, CD3OD) δ 184.4, 167.8, 155.4, 145.4, 132.7, 130.5, 129.4,
128.5, 128.1, 127.8, 115.8, 68.6, 25.4; IR (KBr): νmax = 3437, 3377,
2924, 1668, 1384, 757 cm−1; HRMS (ESI/Q-TOF): m/z calcd for
C17H14N5O2S (M + H)+ 352.0868, found 352.0866.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02270.
■
sı
Structures of propiolamides and propiolates; control
experiment-procedure; copies of H, 13C, and 19F NMR
1
spectra of all of the new compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Chada Raji Reddy − Department of Organic Synthesis &
Process Chemistry, CSIR-Indian Institute of Chemical
Technology (CSIR-IICT), Hyderabad 500007, India;
Academy of Scientific and Innovative Research (AcSIR),
Ghaziabad 201002, India; orcid.org/0000-0003-1491-
7381; Email: rajireddy@iict.res.in
1-Methyl-4-phenyl-3-((phenylethynyl)thio)-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (10). An oven-dried 25 mL round-bottomed
flask fitted with a stirring bar was charged with 2a (50 mg, 0.16
mmol) in acetonitrile (4 mL), and phenylacetylene (24 mg, 0.24
mmol), CuI (20 mol %), and Cs2CO3 (52 mg, 0.16 mmol) were
added successively to this solution at room temperature and stirred
for 1.5 h. After confirming the completion of the reaction by TLC, the
solvent was removed under reduced pressure and the residue was
purified by column chromatography on silica gel using ethyl acetate
and hexane as an eluent to obtain the desired product 10 as a white
solid (55 mg, 90% yield). Mp: 162−164 °C; Rf = 0.4 (hexane:ethyl
Authors
Uprety Ajaykumar − Department of Organic Synthesis &
Process Chemistry, CSIR-Indian Institute of Chemical
Technology (CSIR-IICT), Hyderabad 500007, India;
Academy of Scientific and Innovative Research (AcSIR),
Ghaziabad 201002, India
Dattahari H. Kolgave − Department of Organic Synthesis &
Process Chemistry, CSIR-Indian Institute of Chemical
Technology (CSIR-IICT), Hyderabad 500007, India;
Academy of Scientific and Innovative Research (AcSIR),
Ghaziabad 201002, India
1
acetate = 7:3); H NMR (500 MHz, CDCl3): δ 7.34−7.28 (m, 5H),
7.27−7.23 (m, 1H), 7.21−7.17 (m, 2H), 7.04−7.01 (m, 2H), 6.55−
6.51 (m, 2H), 6.48−6.44 (m, 2H), 2.93 (s, 3H); 13C{1H} NMR (101
MHz, CDCl3): δ 183.9, 166.9, 148.9, 144.8, 133.3, 131.6, 129.9,
129.8, 129.1, 128.6, 128.4, 128.2, 128, 122.2, 97.7, 71.8, 68.4, 26.3; IR
(KBr): νmax = 3053, 1701, 1672, 1380, 1271, 758 cm−1; HRMS (ESI/
Q-TOF): m/z calcd for C24H18NO2S (M + H)+ 384.1058, found
384.1057.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02270
3,3′-Disulfanediylbis(1-methyl-4-phenyl-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione) (11). To a stirred solution of Et2NH (71 mg,
0.97 mmol) in dry THF at 0 °C under a N2 atmosphere was added n-
BuLi (0.2 mL, 0.65 mmol 2.5 M) in hexane dropwise, and the stirring
was continued for 0.5 h. A solution of 2a (100 mg, 0.33 mmol) in
THF was added dropwise via a syringe to the reaction mixture and
allowed to warm to room temperature, and the reaction was
continued for 3 h. After completion of the reaction (confirmed by
TLC), the reaction was quenched with a saturated solution of NH4Cl,
extracted with ethyl acetate and dried over Na2SO4. The concentrated
residue was purified by silica gel column chromatography using ethyl
acetate and hexane as an eluent to obtain 11 as a yellow solid (75 mg,
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
U.A. thanks the Department of Science and Technology
(DST), New Delhi, for a research fellowship (DST-INSPIRE/
03/2018/001338). D.H.K. thanks the University Grants
Commission (UGC), New Delhi, for a research fellowship.
C.R.R. is thankful to the Council of Scientific & Industrial
I
https://dx.doi.org/10.1021/acs.joc.0c02270
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pubs.acs.org/joc
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