Synthetic Route to Enaminones via Metal-Free Four-Component Sequential Reactions of Aryl Olefins with CHCl3, Et3N, and TBHP

Article abstract of DOI:10.1021/acs.joc.1c00823

An efficient and modular strategy was used to obtain enaminones with a wide range of functional groupsviaa four-component sequential reaction. This reaction proceeded under mild conditions without a catalyst in one pot. Furthermore, the products could be transformed into thiadiazoles.

Full text of DOI:10.1021/acs.joc.1c00823

pubs.acs.org/joc
Article
Synthetic Route to Enaminones via Metal-Free Four-Component
Sequential Reactions of Aryl Olefins with CHCl3, Et3N, and TBHP
Jiantao Zhang, Peng Zhou, Aiguo Yin,* Shuhua Zhang, and Weibing Liu*
Cite This: J. Org. Chem. 2021, 86, 8980−8986
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: An efficient and modular strategy was used to obtain
enaminones with a wide range of functional groups via a four-
component sequential reaction. This reaction proceeded under
mild conditions without a catalyst in one pot. Furthermore, the
products could be transformed into thiadiazoles.
environmentally benign conditions remains highly desirable
and challenging.
INTRODUCTION
■
Enaminones are important synthetic intermediates for the
synthesis of various heterocyclic compounds.1 Furthermore, the
enaminone skeleton is present in drug molecules and natural
products. Some new methods for enaminone synthesis have
been developed in recent years.2−6 For example, in 2016, Jang
and co-workers reported the stereocontrolled Brønsted-acid-
catalyzed rearrangement of hemiaminals to afford synthetically
and biologically useful enaminones (Scheme 1a).2 In 2019, the
Multicomponent reactions have received much attention in
molecular synthesis owing to their notable features regarding
cost, atom and step economy, and synthetic divergence.7
Furthermore, this powerful strategy can reliably construct highly
functionalized compounds with structural complexity from
simple and readily available starting materials in one pot.8
Additionally, the direct vicinal difunctionalization of alkenes,
which installs two functional groups on a CC bond in a single
process, has emerged as a powerful tool for the generation of
highly useful and complex skeletons.9 Owing to renewed interest
in radical chemistry, the radical difunctionalization of alkenes
has attracted increasing research attention.10 Continuing our
research interest in alkene difunctionalization,11−13 we
envisaged that 1,4-diketones could be obtained by reacting
olefins, tert-butyl hydroperoxide (TBHP), and CHCl3 in a one-
pot manner (Scheme 2a).
Scheme 1. Synthetic Routes to Enaminones
Scheme 2. Difunctionalization of Alkenes with TBHP
Maji group developed a phenol-directed Umpolung reactivity
strategy for the Cp*Rh(III)-catalyzed C−H functionalization of
aldehydes to obtain stereospecific acyclic Z-enaminones
(Scheme 1b).6b An iron-catalyzed process for the synthesis of
enaminones from ketones and amines was reported by the Chen
group in the same year (Scheme 1c).6e Despite remarkable
progress in this field, some drawbacks remain, such as the use of
expensive transition-metal catalysts, superstoichiometric
amounts of oxidant reagents, and harsh reaction conditions.
Therefore, the development of concise and efficient methods for
the synthesis of enaminones under metal-free, mild, and
Received: April 21, 2021
Published: June 14, 2021
https://doi.org/10.1021/acs.joc.1c00823
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 8980−8986
8980

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
a
RESULTS AND DISCUSSION
Table 2. Substrate Scope for the Synthesis of 7
■
To examine the feasibility of this hypothesis, we conducted
initial trials using styrene (1a) and CHCl3 as model substrates
with TBHP (4.0 equiv) as the radical initiator and Et3N as the
solvent at 70 °C. Although expected product 6a was not
obtained, enaminone 7a was isolated as the major product
(Scheme 2b), suggesting that Et3N acted as a substrate in the
reaction. Encouraged by these results, the reaction was
conducted using styrene (1a), CHCl3 (2a), Et3N (3a), and
TBHP (4a) as benchmark substrates to screen for optimal
reaction conditions (Table 1). To our delight, four-component
a
Table 1. Optimization of Reaction Conditions
entry
solvent
2a/3a (equiv)
t/°C
TBHP (equiv)
7a/%
b
1
70
70
70
70
70
70
70
70
70
70
70
70
70
70
r.t.
50
60
80
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
2.0
3.0
5.0
8.0
4.0
4.0
4.0
4.0
56
12
65
59
73
56
69
37
67
70
42
57
69
72
49
53
62
58
2
3
4
5
6
7
8
9
10
11
12
13
14
DMSO
DMF
dioxane
PhCl
toluene
CH3CN
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
3.0/3.0
3.0/3.0
3.0/3.0
3.0/3.0
3.0/3.0
3.0/3.0
2.0/2.0
4.0/4.0
5.0/5.0
3.0/3.0
3.0/3.0
3.0/3.0
3.0/3.0
3.0/3.0
3.0/3.0
3.0/3.0
3.0/3.0
c
15
16
17
18
a
Unless otherwise specified, all reactions were carried out by using 1
(0.5 mmol), 2a (1.5 mmol), 3 (1.5 mmol), and 4a (2.0 mmol) in
a
Unless noted otherwise, the reaction was performed in air by using
1a (0.5 mmol), 2a (1.5 mmol), 3a (1.5 mmol), and 4a (2.0 mmol) in
b
c
PhCl (1.0 mL) at 70 °C for 8 h. 5 mmol of 1a was used, 12 h. 1.5
b
c
d
the solvent (1.0 mL) at 70 °C for 8 h. 2a (1.0 mL), 3a (1.0 mL). 30
h.
mmol CHBr3 was used instead of CHCl3. 7v could be detected in
e
the crude product. N-methyl-N-phenylaniline was used instead of
f
Et3N. Hunig’s base (diisopropylethylamine) was used instead of
product 7a was delivered in 56% yield in a one-pot manner
(Table 1, entry 1). To improve the efficiency, we examined the
solvent effect by screening various reaction media [DMSO,
DMF, dioxane, chlorobenzene (PhCl), toluene (PhMe), and
CH3CN] using 2a (3.0 equiv) and 3a (3.0 equiv), with PhCl
(73% yield) performing better than the other solvents (entries
2−7). No improvement was obtained by increasing or
decreasing the amounts of 2a and 3a (entries 8−10). As the
next optimization step, we investigated using different amounts
of TBHP, which resulted in lower yields of 7a (entries 11−14).
Unfortunately, the desired product 7a was obtained in a lower
yield (49%) when the reaction was conducted at room
temperature (entry 15). The yield of 7a clearly decreased at
reaction temperatures above or below 70 °C (entries 16−18).
With optimized reaction conditions in hand (Table 1, entry
5), we examined the substrate scope of this four-component
sequential reaction, with the results summarized in Table 2.
Substituents with different electronic properties at the para-
position of the aromatic ring were examined, with all tolerated
well to give the desired products in moderate to good yields
(7b−l). Electron-rich groups (1b−g) resulted in better yields
Et3N.
than electron-deficient groups (1h−l). Furthermore, all
substrates with electron-donating or electron-withdrawing
groups on the meta-position of the phenyl ring were smoothly
transformed into the corresponding desired products in 48%−
68% yields (7m−q). Additionally, 3,5-disubstituted substrate 1r
furnished the corresponding product 7r. However, 2,4,6-
trisubstituted styrene 1s could not provide the desired product
under the optimized conditions, which was attributed to the
steric effect of the olefin. We also tried 2-substituted substrates
(2-F, 2-Cl); it turned out that only a trace amount of the desired
product was obtained and it could not be separated from the
impurity substance (see the Supporting Information for details).
Pleasingly, 2-naphthyl-substituted substrate 1t participated in
the reaction, affording 7t in 57% yield. 1,2-Disubstituted olefins
failed to react under the standard conditions (7u and 7v).
Indanone derivative 7w was obtained in 60% yield from the
reaction of indene 1w. To our delight, replacing the phenyl
group in 1a with a heterocycle (thiophene) in 1x caused only a
8981
https://doi.org/10.1021/acs.joc.1c00823
J. Org. Chem. 2021, 86, 8980−8986

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
slight drop in yield (43%). In contrast, the desired product 7y
containing a pyridine ring was not formed, with the starting
material mostly recovered. Tripropylamine and tributylamine
were also compatible with this mild metal-free protocol, giving
corresponding products 7z and 7aa in 61 and 57% yields,
respectively. Unfortunately, N-methyl-N-phenylaniline was not
a good candidate for this transformation (7ab). When the
reaction was operated with diisopropylethylamine instead of
Et3N, however, neither 7ac nor 7ad was formed. No desired
product 7ae was detected when the alkyl olefin was used as the
substrate, only the 7ae′ was obtained in 62% yield.12
agent 2,2,6,6-(tetramethylpiperidin-1-yl)oxyl (TEMPO) to the
reaction under the optimized conditions led to no formation of
product 7a (Scheme 3a). Furthermore, enaminone 7a was
obtained when 5a11 was treated with Et3N, suggesting that 5a
might be the intermediate product and that Et3N acted as a
nucleophilic reagent (Scheme 3b). Other than the expected
product 7a (12%), 8a was also detected in 25% yield when the
reaction was performed in CH3OH using 2.0 equiv of Et3N
(Scheme 3c). Compound 8a14 was also generated in 58% yield
when Et3N was replaced by 1,5-diazabicyclo[5.4.0]undecene-5-
ene (DBU) (Scheme 3d). Furthermore, no reaction occurred in
the absence of Et3N or DBU (Scheme 3e). In order to further
explore the scope of the substrates, several other halogenated
substrates were tested (2c and 2d); all of the tested reactions did
not work at all (Scheme 3f,g).
Further experiments were conducted to better understand the
mechanistic pathway (Scheme 3). First, adding radical trap
Scheme 3. Mechanistic Investigations
Based on the above results and related work,11,12,15 we
proposed a tentative mechanism for the formation of enaminone
t
7a (Scheme 4). First, •CHCl2 and BuOO• radicals are
generated by the reaction with TBHP, which then add to the
styrene sequentially, forming the intermediate product 5a.11
Intermediate 5a then undergoes a Kornblum−DeLaMare
rearrangement7,16 to give G in the presence of Et3N.
Subsequently, intermediate G goes through elimination by an
amine to provide a β-chloro-α,β-unsaturated ketone H. Next,
intermediate I is formed via conjugate addition of the amine to
this α,β-unsaturated ketone, and then ethyl is removed by the aid
of Cl− to give J. Finally, J undergoes elimination to furnish the
desired product 7a, accompanied by HCl release.
To highlight the synthetic utility of these enaminone
products, a further transformation of 7a was performed (Scheme
5). When 7a was treated with elemental sulfur, I2, and p-
toluenesulfonyl hydrazide in DMSO at 100 °C, thiadiazole 10
was obtained in 75% yield.17
Scheme 5. Synthetic Transformation of 7a
Scheme 4. Possible Mechanism for the Synthesis of 7a
8982
https://doi.org/10.1021/acs.joc.1c00823
J. Org. Chem. 2021, 86, 8980−8986

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
CONCLUSIONS
■
In conclusion, we have developed a novel one-pot, catalyst-free,
four-component sequential reaction for the construction of
enaminones in moderate to good yields from aryl olefins using
TBHP, chloroform, and triethylamine. Using this approach,
multiple bonds were broken and formed under a single set of
reaction conditions without any modification or adding other
reagents. Mechanistically, the experimental results showed that
the reaction proceeded via a radical addition/nucleophilic
substitution/elimination process. In addition, the products
could be further transformed into thiadiazoles. We anticipate
that these transformations will be of high value in heterocycle
and medicinal chemistry.
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 7.92−7.87 (m, 2H), 7.82
(d, J = 12.5 Hz, 1H), 6.94−6.89 (m, 2H), 5.78 (d, J = 12.5 Hz, 1H), 4.10
(q, J = 7.0 Hz, 2H), 3.34 (q, J = 7.1 Hz, 4H), 1.45 (t, J = 7.0 Hz, 3H), and
1.25 (t, J = 7.2 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ 187.6,
161.3, 151.9, 133.2, 129.4, 113.8, 91.2, 63.5, and 14.8. HRMS (ESI) m/
z: [M + H]+ calcd for C15H22NO2, 248.1645; found, 248.1646.
(E)-1-(4-(tert-Butoxy)phenyl)-3-(diethylamino)prop-2-en-1-one
(7d). Yield: 80% (110 mg), yellow liquid; Rf = 0.39 (EtOAc/petroleum
EXPERIMENTAL SECTION
■
1
General Information. Unless otherwise stated, compounds 1−4
and solvents were commercially available and used without purification,
and styrene derivatives 1 are known compounds. All reactions (for the
synthesis of 7) were carried out at 70 °C for 8 h in a round-bottom flask
equipped with a magnetic stir bar. 1H, 13C, and 19F NMR spectra were
recorded on a Bruker AVANCE NMR spectrometer (400 or 500 MHz
for 1H; 100 or 126 MHz for 13C; and 376 MHz for 19F) in CDCl3 with
tetramethylsilane as the internal standard. Chemical shifts (δ) are
reported in ppm, and coupling constants (J) are in Hertz (Hz). Mass
spectra were obtained from high-resolution ESI mass spectrometer.
HR-MS were obtained on a quadrupole time-of-flight (Q-TOF) micro
spectrometer.
ether = 1/2). H NMR (400 MHz, CDCl3): δ 7.87−7.80 (m, 3H),
7.05−7.00 (m, 2H), 5.78 (d, J = 12.5 Hz, 1H), 3.38−3.31 (m, 4H), 1.40
(s, 9H), and 1.25 (d, J = 7.2 Hz, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 188.0, 158.2, 152.1, 135.6, 128.6, 122.9, 91.5, 79.1, 50.5,
42.9, 28.9, 14.7, and 11.5. HRMS (ESI) m/z: [M + H]+ calcd for
C17H26NO2, 276.1958; found, 276.1960.
(E)-3-(Diethylamino)-1-(p-tolyl)prop-2-en-1-one (7e). Yield: 75%
(81.4 mg), yellow liquid; Rf = 0.41 (EtOAc/petroleum ether = 1/2). 1H
General Procedures for the Preparation of 7. A mixture of
styrene (1) (0.5 mmol), CHCl3 (1.5 mmol, 179 mg), Et3N (1.5 mmol,
151.8 mg), TBHP (2.0 mmol, 257.5 mg, 70% in water), and
chlorobenzene (1.0 mL) was added successively in a round-bottom
flask, and the resulting solution was stirred for 8 h at 70 °C. The mixture
was purified by column chromatography on silica gel to afford the
product.
Larger Scale Reaction. A mixture of styrene (1a, 5 mmol, 0.52 g),
CHCl3 (2a, 15 mmol, 1.79 g), Et3N (3a, 15 mmol, 1.518 g), TBHP (4a,
20 mmol, 2.575 g, 70% in water), and chlorobenzene (10 mL) was
added successively in a round-bottom flask, and the resulting solution
was stirred for 12 h at 70 °C. The mixture was purified by column
chromatography on silica gel to afford product 7a (65%, 0.659 g).
(E)-3-(Diethylamino)-1-phenylprop-2-en-1-one (7a).3 Yield: 73%
(74.1 mg), yellow liquid; Rf = 0.40 (EtOAc/petroleum ether = 1/2). 1H
NMR (400 MHz, CDCl3): δ 7.85−7.80 (m, 3H), 7.23 (d, J = 7.9 Hz,
2H), 5.78 (d, J = 12.5 Hz, 1H), 3.34 (q, J = 7.0 Hz, 4H), 2.40 (s, 3H),
and 1.25 (t, J = 7.2 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ
188.6, 152.2, 141.1, 138.0, 128.8, 127.6, 91.6, 50.6, 43.0, 14.7, and 11.6.
HRMS (ESI) m/z: [M + H]+ calcd for C14H20NO, 218.1539; found,
218.1539.
(E)-1-(4-(tert-Butyl)phenyl)-3-(diethylamino)prop-2-en-1-one
(7f). Yield: 82% (106.2 mg), yellow liquid; Rf = 0.43 (EtOAc/petroleum
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 7.87−7.81 (m, 3H), 7.45
(dd, J = 8.6, 2.0 Hz, 2H), 5.79 (d, J = 12.6 Hz, 1H), 3.34 (q, J = 7.0 Hz,
4H), 1.35 (s, 9H), and 1.25 (t, J = 7.2 Hz, 6H). 13C{1H} NMR (101
MHz, CDCl3): δ 188.6, 154.2, 152.1, 138.0, 127.3, 125.0, 91.7, 50.5,
42.8, 34.9, 31.2, 14.9, and 11.5. HRMS (ESI) m/z: [M + H]+ calcd for
C17H26NO, 260.2009; found, 260.2002.
NMR (400 MHz, CDCl3): δ 7.89 (dt, J = 6.6, 1.6 Hz, 2H), 7.82 (d, J =
12.5 Hz, 1H), 7.48−7.38 (m, 3H), 5.77 (d, J = 12.5 Hz, 1H), 3.38−3.27
(m, 4H), and 1.24 (t, J = 7.2 Hz, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 188.8, 152.4, 140.8, 130.8, 128.1, 127.5, 91.7, 50.6, 42.9,
14.8, and 11.6. HRMS (ESI) m/z: [M + H]+ calcd for C13H18NO,
204.1383; found, 204.1386.
(E)-1-([1,1′-Biphenyl]-4-yl)-3-(diethylamino)prop-2-en-1-one
(7g). Yield: 68% (94.9 mg), yellow liquid; Rf = 0.41 (EtOAc/petroleum
(E)-3-(Diethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one (7b).
Yield: 76% (88.5 mg), yellow liquid; Rf = 0.37 (EtOAc/petroleum ether
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 8.02−7.98 (m, 2H), 7.87
(d, J = 12.5 Hz, 1H), 7.68−7.62 (m, 4H), 7.46 (td, J = 6.8, 6.4, 1.6 Hz,
2H), 7.40−7.35 (m, 1H), 5.84 (d, J = 12.5 Hz, 1H), 3.34 (q, J = 7.0 Hz,
4H), and 1.25 (t, J = 7.2 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ
188.2, 152.4, 143.5, 140.5, 139.5, 128.8, 128.0, 127.7, 127.2, 126.8, 91.7,
50.6, 42.9, 14.8, and 11.6. HRMS (ESI) m/z: [M + H]+ calcd for
C19H22NO, 280.1696; found, 280.1693.
(E)-3-(Diethylamino)-1-(4-fluorophenyl)prop-2-en-1-one (7h).
Yield: 64% (70.7 mg), yellow liquid; Rf = 0.40 (EtOAc/petroleum
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 7.89 (td, J = 6.0, 2.8 Hz,
2H), 7.84−7.77 (m, 1H), 7.05 (td, J = 8.7, 2.7 Hz, 2H), 5.71 (d, J = 12.5
Hz, 1H), 3.31 (s, 4H), and 1.22 (s, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 187.1, 164.4 (d, J = 250.4 Hz), 152.5, 136.9 (d, J = 3.0 Hz),
= 1/2). 1H NMR (400 MHz, CDCl3): δ 7.91−7.87 (m, 2H), 7.80 (d, J
= 12.5 Hz, 1H), 6.93−6.89 (m, 2H), 5.76 (d, J = 12.5 Hz, 1H), 3.84 (s,
3H), 3.32 (q, J = 7.1 Hz, 4H), and 1.23 (t, J = 7.2 Hz, 6H). 13C{1H}
NMR (101 MHz, CDCl3): δ 187.6, 161.9, 152.0, 133.3, 129.4, 113.3,
91.2, 55.3, 50.4, 42.9, 14.9, and 11.7. HRMS (ESI) m/z: [M + H]+ calcd
for C14H20NO2, 234.1489; found, 234.1481.
(E)-3-(Diethylamino)-1-(4-ethoxyphenyl)prop-2-en-1-one (7c).
Yield: 72% (88.9 mg), yellow liquid; Rf = 0.37 (EtOAc/petroleum
8983
https://doi.org/10.1021/acs.joc.1c00823
J. Org. Chem. 2021, 86, 8980−8986

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(m, 1H), 5.77 (d, J = 12.5 Hz, 1H), 3.88 (s, 3H), 3.41−3.29 (m, 4H),
and 1.26 (t, J = 6.9 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ
188.5, 159.6, 152.5, 142.4, 129.0, 119.9, 117.0, 112.4, 91.8, 55.4, 50.6,
42.9, 14.8, and 11.6. HRMS (ESI) m/z: [M + H]+ calcd for C14H20NO2,
234.1489; found, 234.1512.
136.9, 129.7 (d, J = 8.8 Hz), 114.9 (d, J = 21.5 Hz). 91.1, 50.6, 42.8,
14.8, and 11.5. 19F NMR (376 MHz, CDCl3): δ −109.80. HRMS (ESI)
m/z: [M + H]+ calcd for C13H17FNO, 222.1289; found, 222.1307.
(E)-1-(4-Chlorophenyl)-3-(diethylamino)prop-2-en-1-one (7i).
Yield: 67% (79.4 mg), yellow liquid; Rf = 0.40 (EtOAc/petroleum
(E)-3-(Diethylamino)-1-(m-tolyl)prop-2-en-1-one (7n). Yield: 68%
(73.8 mg), yellow liquid; Rf = 0.41 (EtOAc/petroleum ether = 1/2). 1H
NMR (400 MHz, CDCl3): δ 7.82 (d, J = 12.6 Hz, 1H), 7.71 (s, 1H),
7.67 (d, J = 7.3 Hz, 1H), 7.33−7.26 (m, 2H), 5.77 (d, J = 12.6 Hz, 1H),
3.34 (q, J = 6.9 Hz, 4H), 2.41 (s, 3H), and 1.25 (t, J = 7.2 Hz, 7H).
13C{1H} NMR (101 MHz, CDCl3): δ 189.1, 152.4, 140.8, 137.8, 131.5,
128.1, 128.0, 124.6, 91.9, 50.5, 42.9, 21.4, 14.8, and 11.7. HRMS (ESI)
m/z: [M + H]+ calcd for C14H20NO, 218.1539; found, 218.1540.
(E)-3-(Diethylamino)-1-(3-fluorophenyl)prop-2-en-1-one (7o).
Yield: 52% (57.5 mg), yellow liquid; Rf = 0.40 (EtOAc/petroleum
1
ether = 1/2). H NMR (400 MHz, CDCl3): δ 7.85−7.79 (m, 3H),
7.39−7.33 (m, 2H), 5.71 (d, J = 12.5 Hz, 1H), 3.33 (d, J = 7.3 Hz, 4H),
and 1.23 (t, J = 7.0 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ
187.2, 152.7, 139.1, 136.8, 128.9, 128.3, 91.2, 50.7, 42.9, 14.8, and 11.6.
HRMS (ESI) m/z: [M + H]+ calcd for C13H17ClNO, 238.0993; found,
238.0995.
(E)-1-(4-Bromophenyl)-3-(diethylamino)prop-2-en-1-one (7j).
Yield: 63% (88.5 mg), yellow liquid; Rf = 0.40 (EtOAc/petroleum
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 12.5 Hz, 1H),
7.67 (d, J = 7.7 Hz, 1H), 7.59 (dt, J = 9.9, 1.9 Hz, 1H), 7.39 (td, J = 7.9,
5.7 Hz, 1H), 7.15 (td, J = 8.0, 2.6 Hz, 1H), 5.73 (d, J = 12.5 Hz, 1H),
3.56−3.28 (m, 4H), and 1.27 (s, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 187.1, 162.8 (d, J = 246.1 Hz), 152.8, 143.2 (d, J = 5.9 Hz),
129.6 (d, J = 7.7 Hz), 123.0 (d, J = 2.9 Hz), 117.6 (d, J = 21.5 Hz), 114.3
(d, J = 21.9 Hz), 91.3, 50.7, 42.9, 14.8, and 11.6. 19F NMR (376 MHz,
CDCl3): δ −113.33. HRMS (ESI) m/z: [M + H]+ calcd for
C13H17FNO, 222.1289; found, 222.1310.
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 12.5 Hz, 1H),
7.74 (d, J = 8.5 Hz, 2H), 7.51 (d, J = 8.5 Hz, 2H), 5.69 (d, J = 12.5 Hz,
1H), 3.32 (d, J = 16.9 Hz, 4H), and 1.21 (t, J = 6.6 Hz, 6H). 13C{1H}
NMR (101 MHz, CDCl3): δ 187.2, 152.7, 139.5, 131.2, 129.1, 125.3,
91.1, 50.6, 42.9, 14.8, and 11.6. HRMS (ESI) m/z: [M + H]+ calcd for
C13H17BrNO, 282.0488; found, 282.0484.
(E)-3-(Diethylamino)-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-
one (7k). Yield: 56% (75.9 mg), yellow liquid; Rf = 0.41 (EtOAc/
(E)-1-(3-Chlorophenyl)-3-(diethylamino)prop-2-en-1-one (7p).
Yield: 59% (69.9 mg), yellow liquid; Rf = 0.40 (EtOAc/petroleum
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 7.84−7.76 (m, 2H), 7.72
(d, J = 7.6 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.30 (t, J = 7.7 Hz, 1H),
5.67 (d, J = 12.5 Hz, 1H), 3.30 (s, 4H), and 1.20 (t, J = 6.6 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3): δ 186.9, 152.8, 142.5, 134.2, 130.6,
129.4, 127.6, 125.5, 91.2, 50.7, 42.9, 14.7, and 11.6. HRMS (ESI) m/z:
[M + H]+ calcd for C13H17ClNO, 238.0993; found, 238.1015.
petroleum ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 8.1
Hz, 2H), 7.87 (d, J = 12.4 Hz, 1H), 7.68 (d, J = 8.1 Hz, 2H), 5.75 (d, J =
12.5 Hz, 1H), 3.42−3.33 (m, 4H), and 1.30−1.25 (m, 6H). 13C{1H}
NMR (101 MHz, CDCl3): δ 187.3, 153.0, 144.0, 132.2 (q, J = 32.3 Hz),
127.7, 125.4, 125.1 (q, J = 3.8 Hz), 122.7, 120.0, 91.5, 50.8, 43.0, 14.7,
and 11.6. HRMS (ESI) m/z: [M + H]+ calcd for C14H17F3NO,
272.1257; found, 272.1256.
(E)-1-(3-Bromophenyl)-3-(diethylamino)prop-2-en-1-one (7q).
Yield: 48% (67.4 mg), yellow liquid; Rf = 0.40 (EtOAc/petroleum
(E)-4-(3-(Diethylamino)acryloyl)benzonitrile (7l). Yield: 48% (54.7
mg), yellow liquid; Rf = 0.36 (EtOAc/petroleum ether = 1/2). 1H NMR
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 8.01 (s, 1H), 7.87−7.79
(m, 2H), 7.61−7.55 (m, 1H), 7.31−7.27 (m, 1H), 5.70 (d, J = 12.5 Hz,
1H), 3.36 (s, 4H), and 1.26 (t, J = 6.9 Hz, 6H). 13C{1H} NMR (101
MHz, CDCl3): δ 186.9, 152.9, 142.8, 133.6, 130.5, 129.7, 126.0, 122.4,
91.3, 50.7, 42.9, 14.8, and 11.6. HRMS (ESI) m/z: [M + H]+ calcd for
C13H17BrNO, 282.0488; found, 282.0509.
(400 MHz, CDCl3): δ 7.96 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 12.4 Hz,
1H), 7.73−7.69 (m, 2H), 5.72 (d, J = 12.4 Hz, 1H), 3.42−3.33 (m,
4H), and 1.26 (t, J = 6.9 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ
186.5, 153.3, 144.6, 132.0, 127.9, 118.7, 113.9, 91.3, 50.9, 43.1, 14.7,
and 11.6. HRMS (ESI) m/z: [M + H]+ calcd for C14H17N2O, 229.1335;
found, 229.1351.
(E)-1-(3,5-Bis(trifluoromethyl)phenyl)-3-(diethylamino)prop-2-
en-1-one (7r). Yield: 45% (76.3 mg), yellow solid; Rf = 0.42 (EtOAc/
(E)-3-(Diethylamino)-1-(3-methoxyphenyl)prop-2-en-1-one
(7m). Yield: 63% (73.4 mg), yellow liquid; Rf = 0.37 (EtOAc/
petroleum ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J =
12.5 Hz, 1H), 7.51−7.44 (m, 2H), 7.33 (t, J = 8.0 Hz, 1H), 7.05−6.98
petroleum ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 8.31 (s, 2H),
7.93 (d, J = 11.8 Hz, 2H), 5.72 (d, J = 12.3 Hz, 1H), 3.41 (dt, J = 14.2,
8984
https://doi.org/10.1021/acs.joc.1c00823
J. Org. Chem. 2021, 86, 8980−8986

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
7.1 Hz, 4H), and 1.29 (q, J = 7.0 Hz, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 184.7, 153.7, 142.6, 131.5 (q, J = 33.4 Hz), 127.50, 127.47,
127.4, 124.7, 124.0−123.9 (m), 122.0, 119.2, 90.4, 50.8, 43.1, 14.7, and
11.6. 19F NMR (376 MHz, CDCl3): δ −62.81. HRMS (ESI) m/z: [M +
H]+ calcd for C15H16F6NO, 340.1131; found, 340.1144.
19.6, and 13.8. HRMS (ESI) m/z: [M + H]+ calcd for C17H26NO,
260.2009; found, 260.2009.
1-(4,4-Dichlorobutyl)-4-fluorobenzene (7ae′).12
(E)-3-(Diethylamino)-1-(naphthalen-2-yl)prop-2-en-1-one (7t).
Yield: 57% (72.1 mg), yellow liquid; Rf = 0.41 (EtOAc/petroleum
Yield: 62% (68.2 mg), pale yellow liquid; Rf = 0.40 (EtOAc/petroleum
ether = 1/20). H NMR (400 MHz, CDCl3): δ 7.17−7.09 (m, 2H),
1
7.02−6.92 (m, 2H), 5.74 (t, J = 6.0 Hz, 1H), 2.64 (t, J = 7.6 Hz, 2H),
2.27−2.09 (m, 2H), and 1.91−1.77 (m, 2H). 13C{1H} NMR (101
MHz, CDCl3): δ 161.4 (d, J = 243.8 Hz), 136.8 (m), 129.7 (d, J = 7.8
Hz), 115.3 (d, J = 21.1 Hz), 73.3, 42.9, 33.9, and 27.6.
3,3-Dimethoxy-1-phenylpropan-1-one (8a).14
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 8.40 (s, 1H), 8.03 (dd, J =
8.6, 1.7 Hz, 1H), 7.97 (dd, J = 6.4, 2.7 Hz, 1H), 7.93−7.86 (m, 3H),
7.56−7.50 (m, 2H), 5.95 (d, J = 12.5 Hz, 1H), 3.39 (q, J = 7.2 Hz, 4H),
and 1.29 (t, J = 7.2 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ
188.6, 152.5, 138.1, 134.7, 132.8, 129.1, 127.8, 127.71, 127.65, 127.1,
126.2, 124.7, 91.9, 50.6, 42.8, 14.8, and 11.6. HRMS (ESI) m/z: [M +
H]+ calcd for C17H20NO, 254.1539; found, 254.1537.
General Procedure for the Synthesis of 8a. A mixture of 5a (0.5
mmol, 138 mg), DBU (0.4 mmol, 152 mg), and CH3OH (1.0 mL) was
added successively in a round-bottom flask, and the resulting solution
was stirred for 8 h at 70 °C. The mixture was purified by column
chromatography on silica gel to afford the product. Yield: 58% (56.3
mg), colorless liquid; Rf = 0.40 (EtOAc/petroleum ether = 1/10). 1H
NMR (400 MHz, CDCl3): δ 7.99−7.94 (m, 2H), 7.58 (m, 1H), 7.50−
7.46 (m, 2H), 5.02 (t, J = 5.5 Hz, 1H), 3.43 (s, 6H), and 3.30 (d, J = 5.5
Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ 196.9, 137.1, 133.2,
128.6, 128.3, 102.2, 54.2, and 42.6.
General Procedure for the Synthesis of 1,2,3-Thiadiazole
10.17 The mixture of enaminone 7a (0.2 mmol, 40.6 mg), p-
toluenesulfonyl hydrazide (0.24 mmol, 44.6 mg), S (0.4 mmol, 12.8
mg), I2 (0.2 mmol, 25.4 mg), and DMSO (1.0 mL) was stirred at 100
°C for 12 h under air atmosphere in an oil bath. After the completion of
the reaction, the reaction mixture was washed with water and extracted
by ethyl acetate three times. The obtained top organic layer was dried
with anhydrous Na2SO4. The mixture was concentrated in vacuo, and
the residue was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) to afford the pure product 10
(75%, 28.5 mg). 1H NMR (500 MHz, CDCl3): δ 9.06 (s, 1H), 7.99−
7.88 (m, 3H), 7.72 (t, J = 7.5 Hz, 1H), and 7.58 (t, J = 7.8 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 184.6, 153.2, 149.1, 136.7, 134.6,
(E)-2-((Diethylamino)methylene)-2,3-dihydro-1H-inden-1-one
(7w). Yield: 60% (64.5 mg), yellow liquid; Rf = 0.41 (EtOAc/petroleum
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 7.6 Hz, 1H),
7.62 (t, J = 1.1 Hz, 1H), 7.51−7.45 (m, 2H), 7.39 (td, J = 7.6, 1.8 Hz,
1H), 3.83 (s, 2H), 3.47 (q, J = 7.1 Hz, 4H), and 1.29 (t, J = 7.2 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3): δ 192.4, 147.4, 145.5, 140.3, 131.6,
126.9, 125.1, 123.0, 103.3, 31.3, and 14.7. HRMS (ESI) m/z: [M + H]+
calcd for C14H18NO, 216.1383; found, 216.1384.
(E)-3-(Diethylamino)-1-(thiophen-2-yl)prop-2-en-1-one (7x).
Yield: 43% (44.9 mg), yellow liquid; Rf = 0.39 (EtOAc/petroleum
ether = 1/2). 1H NMR (400 MHz, CDCl3): δ 7.82 (d, J = 12.5 Hz, 1H),
7.64 (d, J = 3.7 Hz, 1H), 7.48 (d, J = 4.9 Hz, 1H), 7.12−7.07 (m, 1H),
5.70 (d, J = 12.5 Hz, 1H), 3.39−3.32 (m, 4H), and 1.26 (t, J = 7.1 Hz,
6H). 13C{1H} NMR (101 MHz, CDCl3): δ 180.9, 151.8, 147.6, 130.1,
128.2, 127.5, 91.2, 50.5, 42.8, 14.8, and 11.6. HRMS (ESI) m/z: [M +
H]+ calcd for C11H16NOS, 210.0947; found, 210.0963.
129.4, and 129.2.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00823.
■
sı
(E)-3-(Dipropylamino)-1-phenylprop-2-en-1-one (7z). Yield: 61%
(70.5 mg), yellow liquid; Rf = 0.42 (EtOAc/petroleum ether = 1/2). 1H
1H NMR and 13C{1H} NMR spectra of compounds
(PDF)
AUTHOR INFORMATION
Corresponding Authors
■
NMR (400 MHz, CDCl3): δ 7.87 (d, J = 6.7 Hz, 2H), 7.81 (d, J = 12.5
Hz, 1H), 7.41 (q, J = 7.4, 6.4 Hz, 3H), 5.75 (d, J = 12.5 Hz, 1H), 3.26−
3.16 (m, 4H), 1.65 (s, 4H), and 0.99−0.89 (m, 6H). 13C{1H} NMR
(101 MHz, CDCl3): δ 188.8, 153.5, 140.8, 130.7, 128.1, 127.4, 91.8,
58.2, 50.4, 22.5, 19.7, 11.5, and 11.0. HRMS (ESI) m/z: [M + Na]+
calcd for C15H21NONa, 254.1515; found, 254.1517.
Aiguo Yin − College of Biological and Food Engineering,
Guangdong University of Petrochemical Technology, Maoming
525000, P. R. China; Email: yinlife8@hotmail.com
Weibing Liu − College of Chemistry, Guangdong University of
Petrochemical Technology, Maoming 525000, P. R. China;
orcid.org/0000-0003-4885-1675; Email: lwb409@
gdupt.edu.cn
(E)-3-(Dibutylamino)-1-phenylprop-2-en-1-one (7aa). Yield: 57%
(73.8 mg), yellow liquid; Rf = 0.43 (EtOAc/petroleum ether = 1/2). 1H
Authors
Jiantao Zhang − College of Chemistry, Guangdong University of
Petrochemical Technology, Maoming 525000, P. R. China;
orcid.org/0000-0002-3314-5383
Peng Zhou − College of Chemistry, Guangdong University of
Petrochemical Technology, Maoming 525000, P. R. China
Shuhua Zhang − College of Chemistry, Guangdong University of
Petrochemical Technology, Maoming 525000, P. R. China
NMR (400 MHz, CDCl3): δ 7.88 (dd, J = 7.9, 1.6 Hz, 2H), 7.81 (d, J =
12.5 Hz, 1H), 7.45−7.37 (m, 3H), 5.75 (d, J = 12.5 Hz, 1H), 3.29−3.20
(m, 4H), 1.60 (s, 4H), 1.39−1.29 (m, 4H), and 1.00−0.93 (m, 6H).
13C{1H} NMR (101 MHz, CDCl3): δ 188.7, 153.3, 140.8, 130.7, 128.1,
127.4, 91.8, 56.3, 48.5, 47.2, 41.9, 31.3, 30.7, 29.4, 28.4, 20.3, 20.2, 19.8,
8985
https://doi.org/10.1021/acs.joc.1c00823
J. Org. Chem. 2021, 86, 8980−8986

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(c) Wang, Q.; Wang, D.-X.; Wang, M.-X.; Zhu, J. Still unconquered:
enantioselective Passerini and Ugi multicomponent reactions. Acc.
Chem. Res. 2018, 51, 1290−1300. (d) Shi, H.-N.; Huang, M.-H.; He, C.-
L.; Lu, H.-P.; Hao, W.-J.; Tu, X.-C.; Tu, S.-J.; Jiang, B. Completely
stereoselective synthesis of sulfonated 1,3-dihydroisobenzofurans via
radical multicomponent reactions. J. Org. Chem. 2019, 84, 13686−
13695. (e) Li, D.; Shen, X.; Lei, J. Metal-free iodine/TEMPO-mediated
aerobic oxidative Ugi-type multicomponent reactions with tertiary
amines. J. Org. Chem. 2020, 85, 2466−2475.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00823
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by National Natural Science
Foundation of China (21602035), Guangdong Natural Science
Foundation (no. 2016A030307030), Department of Education
of Guangdong Province (no. 2020ZDZX2054) and Doctor
Startup Project of Guangdong University of Petrochemical
Technology (2019rc048).
(9) (a) Hu, T.; Xu, Y.; Zhang, S.; Xiong, H.-Y.; Zhang, G. Synthesis of
β-CF3 β-amino esters with an indane backbone by Rhenium-catalyzed
[3+2] annulation. Org. Lett. 2020, 22, 8866−8871. (b) Yin, Y.; Li, Y.;
Gonca̧ lves, T. P.; Zhan, Q.; Wang, G.; Zhao, X.; Qiao, B.; Huang, K.-
W.; Jiang, Z. All-carbon quaternary stereocenters α to azaarenes via
radical-based asymmetric olefin difunctionalization. J. Am. Chem. Soc.
2020, 142, 19451−19456.
(10) (a) Zhang, H.-Y.; Ge, C.; Zhao, J.; Zhang, Y. Cobalt-catalyzed
trifluoromethylation−peroxidation of unactivated alkenes with sodium
trifluoromethanesulfinate and hydroperoxide. Org. Lett. 2017, 19,
5260−5263. (b) Levitre, G.; Dagousset, G.; Anselmi, E.; Tuccio, B.;
Magnier, E.; Masson, G. Four-component photoredox-mediated
azidoalkoxy-trifluoromethylation of alkenes. Org. Lett. 2019, 21,
6005−6010. (c) Lux, M.; Klussmann, M. Additions of aldehyde-
derived radicals and nucleophilic N-alkylindoles to styrenes by
photoredox catalysis. Org. Lett. 2020, 22, 3697−3701. (d) Tian, T.;
Wang, X.; Lv, L.; Li, Z. Iron-catalyzed acylation-functionalization of
unactivated alkenes with aldehydes. Chem. Commun. 2020, 56, 14637−
14640.
(11) Chen, C.; Tan, H.; Liu, B.; Yue, C.; Liu, W. ATRA-like alkylation-
peroxidation of alkenes with trichloromethyl derivatives by the
combination of tBuOOH and NEt3. Org. Chem. Front. 2018, 5,
3143−3147.
(12) Chen, C.; Li, Y.; Pan, Y.; Duan, L.; Liu, W. Oxidative radical
addition-chlorination of alkenes to access 1,1-dichloroalkanes from
simple reagents. Org. Chem. Front. 2019, 6, 2032−2036.
REFERENCES
■
(1) Fu, R.-G.; Wang, Y.; Xia, F.; Zhang, H.-L.; Sun, Y.; Yang, D.-W.;
Wang, Y.-W.; Yin, P. Synthesis of 2-amino-5-acylthiazoles by a tertiary
amine-promoted one-pot three-component cascade cyclization using
elemental sulfur as a sulfur source. J. Org. Chem. 2019, 84, 12237−
12245.
(2) Kang, Y.-W.; Cho, Y. J.; Han, S. J.; Jang, H.-Y. Tunable and
diastereoselective Brønsted acid catalyzed synthesis of β-enaminones.
Org. Lett. 2016, 18, 272−275.
(3) (a) Greenhill, J. V. Enaminones. Chem. Soc. Rev. 1977, 6, 277−
294. (b) Amaye, I. J.; Haywood, R. D.; Mandzo, E. M.; Wirick, J. J.;
Jackson-Ayotunde, P. L. Enaminones as building blocks in drug
development: Recent advances in their chemistry, synthesis, and
biological properties. Tetrahedron 2021, 83, 131984.
̀
(4) Leggio, A.; Comande, A.; Belsito, E. L.; Greco, M.; Lo Feudo, L.;
Liguori, A. Alternative formation of amides and β-enaminones from
aroyl chlorides using the TiCl4-trialkylamine reagent system. Org.
Biomol. Chem. 2018, 16, 5677−5683.
(5) (a) Xu, K.; Zhang, Z.; Qian, P.; Zha, Z.; Wang, Z. Electrosynthesis
of enaminones directly from methyl ketones and amines with
nitromethane as a carbon source. Chem. Commun. 2015, 51, 11108−
11111. (b) Liu, C.; Shi, E.; Xu, F.; Luo, Q.; Wang, H.; Chen, J.; Wan, X.
Combination of fluoroalkylation and Kornblum−DeLaMare reaction: a
new strategy for the construction of (Z)-β-perfluoroalkyl enaminones.
Chem. Commun. 2015, 51, 1214−1217.
(13) Zhang, J.; Xiao, D.; Tan, H.; Liu, W.; Zhang, D.; XiaoHua, T.;
Liu, W. Highly selective synthesis of 2-tert-butoxy-1-arylethanones via
copper(I)-catalyzed oxidation/tert-butoxylation of aryl olefins with
TBHP. J. Org. Chem. 2020, 85, 3929−3935.
(14) Connors, D. M.; Goroff, N. S. Regioselective synthesis of
substituted cyclopenta[l]phenanthrenes. Org. Lett. 2016, 18, 4262−
4265.
(6) Methods with metal catalysts, see: (a) Yu, D.; Sum, Y. N.; Ean, A.
C. C.; Chin, M. P.; Zhang, Y. Acetylide Ion (C22_) as a synthon to link
electrophiles and nucleophiles: A simple method for enaminone
synthesis. Angew. Chem., Int. Ed. 2013, 52, 5125−5128. (b) Debbarma,
S.; Maji, M. S. Cp*RhIII-catalyzed directed amidation of aldehydes with
anthranils. Eur. J. Org. Chem. 2017, 3699−3706. (c) Li, M.; Fang, D.;
Geng, F.; Dai, X. Silver-catalyzed efficient synthesis of enaminones from
propargyl alcohols and amines. Tetrahedron Lett. 2017, 58, 4747−4749.
(d) Debbarma, S.; Bera, S. S.; Maji, M. S. Harnessing stereospecific Z-
enamides through silver-free Cp*Rh(III) catalysis by using isoxazoles
as masked electrophiles. Org. Lett. 2019, 21, 835−839. (e) Wu, W.;
Wang, Z.; Shen, Q.; Liu, Q.; Chen, H. Fe-catalyzed enaminone
synthesis from ketones and amines. Org. Biomol. Chem. 2019, 17,
6753−6756.
(7) (a) Ling, J.; Zhang, J.; Zhao, Y.; Xu, Y.; Wang, H.; Lv, Y.; Ji, M.;
Ma, L.; Ma, M.; Wan, X. A Cu-catalyzed four-component cascade
reaction to construct β-ester-γ-amino ketones. Org. Biomol. Chem.
2016, 14, 5310−5316. (b) Wu, C.-S.; Liu, R.-X.; Ma, D.-Y.; Luo, C.-P.;
Yang, L. Four-component radical dual difunctionalization (RDD) of
two different alkenes with aldehydes and tert-butyl hydroperoxide
(TBHP): An easy access to β,δ-functionalized ketones. Org. Lett. 2019,
21, 6117−6121.
(15) (a) Konstantinova, L. S.; Rakitin, O. A.; Rees, C. W.; Souvorova,
L. I.; Golovanov, D. G.; Lyssenko, K. A. Unprecedented conversion of
triethylamine and disulfur dichloride into a thienopentathiepin and a
heptathiocane. Org. Lett. 2003, 5, 1939−1942. (b) Gao, Q.; Han, X.;
Tong, P.; Zhang, Z.; Shen, H.; Guo, Y.; Bai, S. Aerobic α,β-C(sp3)−H
bond difunctionalization and C−N bond cleavage of triethylamine:
Difunctional ammonium iodide enabling the regioselective synthesis of
4-arylpyrimido[1,2-b]indazoles. Org. Lett. 2019, 21, 6074−6078.
(16) (a) Zhang, F.; Du, P.; Chen, J.; Wang, H.; Luo, Q.; Wan, X. Co-
catalyzed synthesis of 1,4-dicarbonyl compounds using TBHP oxidant.
Org. Lett. 2014, 16, 1932−1935. (b) Zhang, J.; Jiang, J.; Xu, D.; Luo, Q.;
Wang, H.; Chen, J.; Li, H.; Wang, Y.; Wan, X. Interception of cobalt-
based carbene radicals with α-aminoalkyl radicals: A tandem reaction
for the construction of β-ester-γ-amino ketones. Angew. Chem., Int. Ed.
2015, 54, 1231−1235.
(17) Yang, Z.; Liang, Y.; Li, A.; Liu, K.; Li, L.; Yang, T.; Zhou, C. One-
pot synthesis of 5-acyl-1,2,3-thiadiazoles from enaminones, tosylhy-
drazine, and elemental sulfur under transition-metal-free conditions. J.
Org. Chem. 2019, 84, 16262−16267.
(8) (a) Rotstein, B. H.; Zaretsky, S.; Rai, V.; Yudin, A. K. Small
heterocycles in multicomponent reactions. Chem. Rev. 2014, 114,
8323−8359. (b) Dawande, S. G.; Kanchupalli, V.; Lad, B. S.; Rai, J.;
Katukojvala, S. Synergistic Rhodium(II) carboxylate and Brønsted acid
catalyzed multicomponent reactions of enalcarbenoids: Direct syn-
thesis of α-pyrrolylbenzylamines. Org. Lett. 2014, 16, 3700−3703.
8986
https://doi.org/10.1021/acs.joc.1c00823
J. Org. Chem. 2021, 86, 8980−8986