The Copper-Catalyzed Reaction of 2-(1-Hydroxyprop-2-yn-1-yl)phenols with Sulfonyl Azides Leading to C3-Unsubstituted N-Sulfonyl-2-iminocoumarins

Article abstract of DOI:10.1021/acs.joc.1c00331

An operationally simple synthesis of Z-configured and C3-unsubstituted N-sulfonyl-2-iminocoumarins (e.g., 8a) that proceeds under mild conditions is achieved by reacting 2-(1-hydroxyprop-2-yn-1-yl)phenols (e.g., 6a) with sulfonyl azides (e.g., 7a). The cascade process involved likely starts with a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. This is followed by ring-opening of the resulting metalated triazole (with accompanying loss of nitrogen), reaction of the ensuing ketenimine with the pendant phenolic hydroxyl group, and finally dehydration of the (Z)-N-(4-hydroxychroman-2-ylidene)sulfonamide so formed.

Full text of DOI:10.1021/acs.joc.1c00331

pubs.acs.org/joc
Note
The Copper-Catalyzed Reaction of 2‑(1-Hydroxyprop-2-yn-1-
yl)phenols with Sulfonyl Azides Leading to C3-Unsubstituted
N‑Sulfonyl-2-iminocoumarins
Yu Zhao, Zitong Zhou, Lvling Liu, Man Chen, Weiguang Yang,* Qi Chen, Michael G. Gardiner,
and Martin G. Banwell*
Cite This: J. Org. Chem. 2021, 86, 9155−9162
Read Online
ACCESS
Metrics & More
Article Recommendations
*
sı Supporting Information
ABSTRACT: An operationally simple synthesis of Z-configured and
C3-unsubstituted N-sulfonyl-2-iminocoumarins (e.g., 8a) that
proceeds under mild conditions is achieved by reacting 2-(1-
hydroxyprop-2-yn-1-yl)phenols (e.g., 6a) with sulfonyl azides (e.g.,
7a). The cascade process involved likely starts with a copper-
catalyzed alkyne−azide cycloaddition (CuAAC) reaction. This is
followed by ring-opening of the resulting metalated triazole (with accompanying loss of nitrogen), reaction of the ensuing
ketenimine with the pendant phenolic hydroxyl group, and finally dehydration of the (Z)-N-(4-hydroxychroman-2-ylidene)-
sulfonamide so formed.
oumarin and its derivatives display broadly useful
However, they all lack a demonstrated capacity to generate the
3-unsubstituted N-sulfonyl-2-iminocoumarins that, as high-
lighted above (Figure 1), are notable for their therapeutic
potential. Accordingly, we now describe a related but
complementary 2-MCR-based approach that proceeds under
mild conditions to deliver 3-unsubstituted N-sulfonyl-2-
iminocoumarins 8 in high yield. This operationally simple
protocol involves stirring a mixture of the appropriate (and
readily prepared) 2-(1-hydroxy-2-propyn-1-yl)phenol 6 and
sulfonyl azide 7 in the presence of a copper(I) catalyst.
1
C
properties including by virtue of their acting as
2
3
4
5
antibacterial, antifungal, antiviral, and/or anticancer agents.
Indeed, a number of them have considerable therapeutic
potential. One subset of such compounds are the C3-
unsubstituted iminocoumarins (Figure 1) that have been
6
explored as enzyme inhibitors (e.g., 1) including, potentially,
7
of acetylcholine esterase (AChE) (2), as antimicrobial agents
8
9
10
(
3), as antitumor agents (4), and as antifungals (5).
Consequently, there is an attendant interest in the development
of flexible and concise new routes to such systems. Previous
studies have detailed multicomponent reactions (MCRs)
involving terminal alkynes, sulfonyl azides, and other species
that are combined using a copper-catalyzed alkyne−azide
Our investigations began with an examination of the synthesis
of the parent and previously unreported system N-(2H-
chromen-2-ylidene)-4-methylbenzene-sulfonamide (8a) from
2
-(1-hydroxyprop-2-yn-1-yl)phenol (6a) and p-tosyl azide
1
1
cycloaddition (CuAAC)/triazole ring-opening protocol.
(
TsN ) (7a). Initial screenings involved using CuI as catalyst
3
These have been used extensively in 3-component and 4-
and Et N as base in a range of standard solvents. These revealed
3
component MCRs to assemble N-containing heterocycles and
that the desired conversion could be effected in many solvents
12
related compounds (Scheme 1).
(
Table 1, entries 1−8) with acetonitrile delivering product 8a in
The adaptation of such chemistry to the synthesis of N-
highest yield (85%).
arylsulfonyl-2-iminocoumarins has been the subject of a number
Encouraged by these outcomes, a variety of catalysts was then
13−18
of recent reports.
For example, the copper-catalyzed three-
investigated (Table 1, entries 9−13). Among the copper
component reaction of terminal alkynes, sulfonyl azides and
I
catalysts, Cu -species such as CuI and CuBr afforded the highest
1
3
salicylaldehydes (Scheme 2, a), 3-(2-hydroxyphenyl)-
II
yields (85% and 82%, respectively) while the Cu -systems
14
propiolates (Scheme 2, b), 2-hydroxybenzonitriles (Scheme
CuBr (74%) and Cu(OAc) (70%) were not quite as effective
1
5
16
2
2
2
(
, c), benzo[d]isoxazoles (Scheme 2, d), or alcohols
17
Scheme 2, e) have provided such target compounds. Kumar’s
18
Received: February 10, 2021
Published: June 17, 2021
group has described a metal-free method for the synthesis of
N-arylsulfonyl-2-iminocoumarin derivatives by treating mix-
tures of aryl aldehydes, nitriles and p-TsCl with DABCO
1
9
(
Scheme 2, f). Each of these methods has considerable merit,
including the use of mild reaction conditions and being highly
effective in the assembly of multisubstituted iminocoumarins.
©
2021 American Chemical Society
https://doi.org/10.1021/acs.joc.1c00331
9
155
J. Org. Chem. 2021, 86, 9155−9162

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Figure 1. Examples of C3-unsubstituted iminocoumarins, 1−5, that have been explored as drug candidates.
Scheme 1. Examples of the Copper-Catalyzed MCRs of Sulfonyl Azides and Terminal Alkynes with Other Components That
Generate N-Heterocycles and Related Compounds
1
and Cu(acac) was notably less so (42%). AgTFA failed to
(R ) attached to the aromatic ring of substrates of the general
form 6 such as methyl and halogen are tolerated as evidenced by
the formation of the anticipated products, 8m−8o in serviceable
yield but the introduction of a C4-nitro group (not shown)
prevented any useful reaction from taking place. The successful
formation of products 8p and 8q in yields of 61% and 52%,
respectively, from the corresponding methyl-containing pre-
2
produce the desired product. The effect of different bases was
also assessed (Table 1, entries 14−18) and revealed that the
tertiary alkylamines Et N and N,N-di-isopropylethylamine
3
(
DIPEA) were superior to DMAP, pyridine, Cs CO , and
2 3
sodium hydroxide.
With optimized reaction conditions for the formation of the
parent reaction” having been defined, the capacity of these to
2
“
cursor 6 (R = Me) shows that the present protocol allows for
effect the coupling of a range of different substrates was
investigated. As revealed in Table 2, various structurally and
electronically distinct sulfonyl azides readily engaged in the
desired reaction with the parent 2-(1-hydroxyprop-2-yn-1-
yl)phenol (6a) to give the anticipated products (8a−8l) in
modest to good yields.
Aryl sulfonyl azides proved more effective substrates than
their simple alkyl counterparts (80−90% yield vs 58−78% yield)
with the best “performing” member of the latter group being 3-
chloropropane-1-sulfonyl azide and affording the anticipated
product 8l. Notably, the homochiral system 8k could be
obtained in 82% yield from camphorsulfonyl azide. The
structure of the participating 2-(1-hydroxyprop-2-yn-1-yl)-
phenols 6 can also be varied to a reasonable degree. Electron-
donating as well as mildly electron-withdrawing substituents
the formation of C4-substituted N-sulfonyl-2-iminocoumarins.
All of the product N-sulfonyl-2-iminocoumarins 8a−q, none
of which have been reported previously, were subject to full
spectroscopic characterization (see SI for details), and the
derived data were in complete accord with the assigned
structures, and those of congeners 8a, 8j, and 8q were confirmed
by single-crystal X-ray analysis (see Experimental Section and
Supporting Information for details). These analyses revealed
that all three incorporate Z-configured imine residues, and so it
has been assumed that all the other products formed during the
course of this study possess the same geometry about the CN
bond. The only noteworthy feature among these data was the
1
appearance, in the H NMR spectra of all products, of the
resonance due to H3 as a particularly broad signal, a feature
attributed to the impact of the proximate sulfonyl residue.
9
156
https://doi.org/10.1021/acs.joc.1c00331
J. Org. Chem. 2021, 86, 9155−9162

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Scheme 2. Synthesis of 2-Iminocoumarins 8 via MCR Pathways a−f Reported Previously and the One Used in the Present Study
a
Table 1. Optimization of Reaction Conditions
neously allowing for some level of free rotation about the C2−N
bond, a process resulting in structural change that, in turn, leads
to broadening of the resonance due to H3.
Products 8a−8q are all relatively stable species that survive
chromatographic purification under conventional conditions.
They do, however, undergo hydrolysis to the corresponding
coumarins and sulfonamides, albeit under forcing conditions.
For example, upon treatment with 1.5 equiv of p-TsOH in water
under reflux for 12 h compound 8a is converted into coumarin
(83%).
b
entry
cat.
base
solvent
yield (%) 8a
1
2
3
4
5
6
7
8
9
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
Et N
CHCl3
76
70
66
82
85
80
80
52
82
74
70
42
nd
trace
82
52
46
3
Et N
Cl(CH ) Cl
3
2 2
Et N
toluene
CH Cl
2
A possible reaction pathway for the formation of N-(2H-
chromen-2-ylidene)-4-methylbenzenesulfonamide (8a) from
3
Et N
3
2
11,12
Et N
MeCN
THF
precursors 6a and 7a that is in keeping with earlier proposals
3
Et N
is provided in the SI.
3
Et N
DMSO
1,4-dioxane
CH Cl
In summary, we have developed an operationally simple and
effective means for preparing C3-unsubstituted N-sulfonyl-2-
iminocoumarins from a mixture of the corresponding 2-(1-
hydroxyprop-2-yn-1-yl)phenol and sulfonyl azide in the
presence of CuI. This methodology appears quite flexible and
offers a capacity to generate forms of the title products that
should be particularly useful in, for example, drug development
studies.
3
Et N
3
CuBr
CuBr2
Cu(OAc)2
Et N
3
2
2
2
2
2
2
2
2
2
2
2
10
11
12
13
14
15
16
17
18
Et N
CH Cl
3
2
Et N
CH Cl
3
2
Cu(acac)2
Et N
3
CH Cl
2
c
AgTFA
Et N
CH Cl
3
2
CuI
CuI
CuI
CuI
CuI
DMAP
DIPEA
pyridine
Cs CO
CH Cl
2
CH Cl
2
CH Cl
2
EXPERIMENTAL SECTION
■
CH Cl
2
3
2
1
13
1
General Procedures. H and C{ H} NMR spectra were recorded
at ambient temperatures on a 400 MHz Bruker spectrometer using
CDCl or DMSO-d as solvent and tetramethylsilane (TMS) as the
NaOH
CH Cl
13
2
a
Reaction conditions: a solution of 6a (0.5 mmol), cat. (10 mol %),
and base (2.0 equiv) in the specified solvent (3 mL) was treated with
a (1.3 equiv) and stirred for 2 h at ambient temp. Yield of isolated
3
6
b
internal standard. Chemical shifts are presented as δ values relative to
7
1
1
c
TMS and H− H coupling constants (J values) are given in Hz. IR
spectra were recorded as KBr pellets on a Nicolet FT-IR 5DX
spectrometer while HRMS measurements were carried out on a Bruker
micrOTOF-Q II spectrometer. Melting points were determined on a
Yanaco melting point apparatus and are uncorrected. The 2-(1-
hydroxyprop-2-yn-1-yl)phenols and sulfonyl azides employed in this
work were all known compounds and prepared by established and
conventional procedures. So, in the case of the former substrates, this
involved the addition of ethynylmagnesium bromide to the relevant o-
material. nd = no product detected.
Specifically, and as shown in Figure 2, a zwitterionic resonance
contributing form, 8B, can be proposed for the sulfonyl-2-
iminocoumarin framework that is both aromatic in character
and allows for the opposing charges to exist in close spatial
proximity to one another. As such, it might be expected to
contribute significantly to the resonance hybrid and simulta-
20
hydroxybenzaldehyde or to o-hydroxyacetophenone and, in the latter
9
157
https://doi.org/10.1021/acs.joc.1c00331
J. Org. Chem. 2021, 86, 9155−9162

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
a
Table 2. Substrate Scope
a
Reactions were conducted as follows: a magnetically stirred solution of compound 6 (0.5 mmol), CuI (10 mol %), and Et N (2.0 equiv) in the
3
MeCN (3 mL) was treated at room temperature (rt) with azide 7 (1.3 equiv) and stirring continued for the specified time.
1-yl)phenol (6a, 74 mg, 0.5 mmol) and CuI (9.5 mg, 0.05 mmol) in
MeCN (3 mL) was treated with TsN (7a, 128 mg, 0.65 mmol) and
3
Et N (101 mg, 1.0 mmol). The ensuing mixture was stirred at ambient
3
temperatures for 2 h then concentrated under reduced pressure. The
residue so obtained was subjected to flash chromatography (silica gel,
1
:3 v/v ethyl acetate/60−90 petroleum ether elution) and providing,
after concentration of the relevant fractions (R = 0.3 in 1:2 v/v ethyl
f
Figure 2. Key resonance contributing forms, 8A and 8B, associated
with the N-sulfonyl-2-iminocoumarin framework.
acetate/60−90 petroleum ether), compound 8a (127 mg, 85%) as a
1
white, crystalline solid, mp = 177−180 °C. H NMR (400 MHz,
CDCl ) δ 7.96 (d, J = 8.0 Hz, 2H), 7.69 (d, J = 13.6 Hz, 1H), 7.56−7.48
3
(
complex m, 2H), 7.37−7.28 (complex m, 4H), 6.70 (broad s, 1H),
case, reaction of the appropriate sulfonyl chloride with sodium azide in
13 1
21
2.38 (s, 3H); C{ H} NMR (100 MHz, CDCl ) δ 152.8, 143.5, 142.2,
aqueous acetone.
Z)-N-(2H-Chromen-2-ylidene)-4-methylbenzenesulfona-
mide (8a). A magnetically stirred solution of 2-(1-hydroxyprop-2-yn-
3
138.8, 132.7, 129.4, 128.3, 127.4, 125.8, 119.1, 116.8, 21.6 (two signals
(
obscured or overlapping); IR νmax (KBr) 1632, 1577, 1510, 1485, 1446,
9
158
https://doi.org/10.1021/acs.joc.1c00331
J. Org. Chem. 2021, 86, 9155−9162

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
−
1
+
1
404, 1153, 1088, 830 cm ; HRMS (ESI-TOF) m/z [M + H] calcd
1H), 7.62−7.48 (complex m, 3H), 7.36 (m, 1H), 6.59 (broad s, 1H),
1
3
1
for C H NO S 300.0694, found 300.0686.
3.17 (s, 3H); C{ H} NMR (100 MHz, CDCl ) δ 153.0, 142.1, 132.9,
16
14
3
3
Gram-Scale Synthesis of Compound 8a. A magnetically stirred
solution of 1-(2-hydroxyphenyl)prop-2-yn-1-one (6a, 1.00 g, 6.76
mmol) and CuI (0.13 g, 0.68 mmol) in MeCN (20 mL) was treated
with TsN (1.73 g, 8.78 mmol) and Et N (1.36 g, 13.5 mmol). The
resulting mixture was stirred at 25 °C for 2 h after which time TLC
analysis indicated that all of the starting compound 6a had been
consumed. Accordingly, the reaction mixture was concentrated under
reduced pressure and the residue subjected to flash chromatography in
the manner detailed above. Concentration of the relevant fractions then
gave compound 8a (1.65 g, 82%) as a white, crystalline solid that was
identical, in all respects, to that obtained at the smaller scale.
128.4, 125.9, 119.1, 117.3, 43.1 (two signals obscured or overlapping);
−
1
IR νmax (KBr) 2910, 1639, 1577, 1485, 1446, 1296, 1199, 1123 cm ;
+
HRMS (ESI-TOF) m/z calcd for C H NO S, [M + H] 224.0381,
1
0
10
3
found 224.0377.
3
3
(Z)-N-(2H-Chromen-2-ylidene)ethanesulfonamide (8g). The
title compound (77 mg, 65%), was obtained as a white, crystalline solid,
mp = 92.8−94.5 °C (R = 0.4 in 1:2 v/v ethyl acetate/60−90 petroleum
f
1
ether). H NMR (400 MHz, CDCl ) δ 7.70 (d, J = 9.6 Hz, 1H), 7.60−
7.47 (complex m, 3H), 7.35 (t, J = 8.4 Hz, 1H), 6.59 (broad s, 1H), 3.22
(q, J = 7.2 Hz, 2H), 1.48 (t, J = 7.2 Hz, 3H); C{ H} NMR (100 MHz,
3
1
3
1
CDCl ) δ 153.0, 141.9, 132.8, 128.2, 125.7, 119.1, 117.4, 49.5, 8.3 (two
3
Synthesis of Compounds 8b−8q. The protocol described
immediately above was employed, at the same scale, for the synthesis
of compounds 8b−8q by using the requisite combination of 2-(1-
hydroxyprop-2-yn-1-yl)phenol and sulfonyl azide. Two or three hour
reaction times were employed (see Table 2 for specific times) and the
crude material obtained after extractive workup and drying was
subjected to flash chromatography using 1:2−4 v/v ethyl acetate/60−
signals obscured or overlapping); IR νmax (KBr) 2930, 1639, 1578,
−
1
1450, 1404, 1300, 1199, 1003, 907, 772, 737, 698 cm ; HRMS (ESI-
+
TOF) m/z calcd for C H NO S, [M + H] 238.0538, found
1
1
12
3
238.0530.
(Z)-N-(2H-Chromen-2-ylidene)propane-1-sulfonamide (8h).
The title compound (78 mg, 62%) was obtained as a white, crystalline
solid, mp = 97.0−100.2 °C (R = 0.4 in 1:2 v/v ethyl acetate/60−90
f
1
90 petroleum ether.
petroleum ether). H NMR (400 MHz, CDCl ) δ 7.70 (d, J = 9.6 Hz,
3
(
Z)-N-(2H-Chromen-2-ylidene)benzenesulfonamide (8b).
1H), 7.60−7.47 (complex m, 3H), 7.35 (m, 1H), 6.59 (broad s, 1H),
1
3
1
The title compound (117 mg, 82%) was obtained as a white, crystalline
3.17 (m, 2H), 1.99 (m, 2H), 1.09 (t, J = 8.4 Hz, 3H); C{ H} NMR
solid, mp = 173.3−177.7 °C (R = 0.3 in 1:2 v/v ethyl acetate/60−90
(100 MHz, CDCl ) δ 153.0, 141.9, 132.8, 128.2, 125.7, 119.1, 117.3,
f
3
1
petroleum ether). H NMR (400 MHz, CDCl ) δ 8.09 (d, J = 7.2 Hz,
56.8, 17.4, 13.1 (two signals obscured or overlapping); IR ν (KBr)
3
max
−
1
2
(
H), 7.02 (d, J = 9.6 Hz, 1H), 7.59−7.50 (complex m, 5H), 7.42−7.33
2882, 1620, 1574, 1480, 1460, 1130, 999, 860, 826 cm ; HRMS (ESI-
TOF) m/z calcd for C H NO S, [M + H] 252.0694, found
complex m, 2H), 6.78 (broad s, 1H); 13C{ H} NMR (100 MHz,
1
+
1
2
14
3
CDCl ) δ 153.0, 142.2, 141.9, 132.8, 128.9, 128.3, 127.4, 125.9, 119.2,
252.0687.
3
1
1
17.1 (three signals obscured or overlapping); IR ν (KBr) 1640,
(Z)-N-(2H-Chromen-2-ylidene)butane-1-sulfonamide (8i).
The title compound (95 mg, 72%) was obtained as a white, crystalline
max
−
1
550, 1485, 1450, 1240, 1087, 830, 772, 733, 698 cm ; HRMS (ESI-
+
TOF) m/z calcd for C H NO S, [M + H] 286.0538, found
2
solid, mp = 73.6−74.2 °C (R
f
= 0.4 in 1:2 v/v ethyl acetate/60−90
1
5
12
3
1
86.0537.
petroleum ether). H NMR (400 MHz, CDCl ) δ 7.70 (d, J = 9.6 Hz,
3
(
Z ) - 4 - C h l o r o - N - ( 2 H - c h r o m e n - 2 - y l i d e n e ) -
1H), 7.61−7.48 (complex m, 3H), 7.35 (m, 1H), 6.58 (broad s, 1H),
3.20 (m, 2H), 1.94 (m, 2H), 1.51 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H);
benzenesulfonamide (8c). The title compound (144 mg, 90%) was
1
3
1
obtained as a white, crystalline solid, mp = 138.8−143.3 °C (R = 0.3 in
C{ H} NMR (100 MHz, CDCl ) δ 153.1, 141.8, 132.8, 128.2, 125.7,
f
3
1
1
:2 v/v ethyl acetate/60−90 petroleum ether). H NMR (400 MHz,
119.2, 117.4, 54.9, 25.6, 21.7, 13.8 (two signals obscured or
CDCl ) δ 8.02 (d, J = 8.8 Hz, 2H), 7.74 (d, J = 9.6 Hz, 1H), 7.60 (m,
overlapping); IR ν (KBr) 2950, 1625, 1578, 1485, 1296 1126, 829,
3
max
−1
1
1
1
H), 7.54−7.47 (complex m, 3H), 7.42 (d, J = 8.4 Hz, 1H), 7.36 (m,
H), 6.85 (broad s, 1H); C{ H} NMR (100 MHz, CDCl ) δ 152.9,
42.6, 140.4, 139.2, 132.9, 129.2, 128.9, 128.4, 126.1, 119.2, 117.1 (two
signals obscured or overlapping); IR νmax (KBr) 1632, 1558, 1485,
404, 1319, 1277, 1149, 1088, 837, 756, 682 cm ; HRMS (ESI-TOF)
m/z calcd for C H ClNO S, [M + H] 320.0148, found 320.0141.
756, 595 cm ; HRMS (ESI-TOF) m/z calcd for C H NO S, [M +
H] 266.0851, found 266.0842.
13 16 3
1
3
1
+
3
(Z)-N-(2H-Chromen-2-ylidene)-1-phenylmethanesulfona-
mide (8j). The title compound (123 mg, 82%) was obtained as a white,
−
1
1
crystalline solid, mp = 142.5−146.2 °C (R = 0.3 in 1:2 v/v ethyl
f
3
5
+
1
15
11
3
acetate/60−90 petroleum ether). H NMR (400 MHz, CDCl ) δ 7.62
3
(
Z ) - 4 - B r o m o - N - ( 2 H - c h r o m e n - 2 - y l i d e n e ) -
(d, J = 9.6 Hz, 1H), 7.56 (m, 1H), 7.52−7.44 (complex m, 3H), 7.43 (d,
J = 8.4 Hz, 1H), 7.38−7.31 (complex m, 4H), 6.69 (broad s, 1H), 4.44
benzenesulfonamide (8d). The title compound (149 mg, 84%) was
1
3
1
obtained as a white, crystalline solid, mp = 159.2−161.6 °C [R = 0.2(6)
(s, 2H); C{ H} NMR (100 MHz, CDCl ) δ 152.8, 141.9, 132.7,
f
3
1
in 1:2 v/v ethyl acetate/60−90 petroleum ether]. H NMR (400 MHz,
131.2, 129.4, 128.7, 128.6, 128.2, 125.7, 119.1, 117.3, 60.8 (two signals
CDCl ) δ 7.59 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 9.6 Hz, 1H), 7.67−7.64
obscured or overlapping); HRMS (ESI-TOF) m/z calcd for
3
+
(
complex m, 2H), 7.60 (m, 1H), 7.53 (m, 1H), 7.43 (d, J = 8.4 Hz, 1H),
C H NO S, [M + H] 300.0694, found 300.0686. Satisfactory IR
1
6
14
3
1
3
1
7
1
1
1
.37 (m, 1H), 6.82 (broad s, 1H); C{ H} NMR (100 MHz, CDCl ) δ
data could not be obtained on this compound.
3
53.3, 142.9, 141.2, 133.3, 132.5, 129.3, 128.7, 128.0, 126.4, 119.5,
17.4 (two signals obscured or overlapping); IR νmax (KBr) 1743, 1631,
558, 1485, 1450, 1323, 1273, 1246, 1234, 1088, 1064, 999, 907, 710
(Z)-N-(2H-Chromen-2-ylidene)-1-((1R,4R)-7,7-dimethyl-2-
oxobicyclo[2.2.1]heptan-1-yl)methanesulfonamide (8k). The
title compound (140 mg, 82%) was obtained as a white, crystalline
−
1
79
+
cm ; HRMS (ESI-TOF) m/z calcd for C H BrNO S, [M + H]
solid, mp = 106.1−112.4 °C (R = 0.3 in 1:2 v/v ethyl acetate/60−90
1
5
11
3
f
1
3
63.9643, found 363.9637.
petroleum ether). H NMR (400 MHz, CDCl ) δ 7.74 (d, J = 9.6 Hz,
3
(
Z)-N-(2H-Chromen-2-ylidene)-4-methoxybenzenesulfona-
1H), 7.61−7.49 (complex m, 3H), 7.36 (m, 1H), 6.57 (broad s, 1H),
3.86 (d, J = 14.8 Hz, 1H), 3.18 (d, J = 14.8 Hz, 1H), 2.69 (m, 1H), 2.38
(m, 1H), 2.12−2.03 (complex m, 2H), 1.94 (d, J = 18.4 Hz, 1H), 1.79
mide (8e). The title compound (126 mg, 80%) was obtained as a
white, crystalline solid, mp = 147.6−149.8 °C [R = 0.1(6) in 1:2 v/v
f
1
13
1
ethyl acetate/60−90 petroleum ether]. H NMR (400 MHz, CDCl ) δ
(m, 1H), 1.44 (m, 1H), 1.17 (s, 3H), 0.90 (s, 3H); C{ H} NMR (100
3
8
1
.03 (d, J = 9.6 Hz, 2H), 7.69 (d, J = 9.6 Hz, 1H), 7.58 (m, 1H), 7.50 (m,
H), 7.43 (d, J = 8.4 Hz, 1H), 7.34 (m, 1H), 7.00 (m, 2H), 6.66 (broad
MHz, CDCl ) δ 215.1, 152.9, 141.9, 132.6, 128.2, 125.7, 119.1, 117.2,
3
58.4, 51.0, 48.1, 42.7, 42.7, 27.0, 24.6, 20.1, 19.8 (two signals obscured
1
3
1
s, 1H), 3.86 (s, 3H); C{ H} NMR (100 MHz, CDCl ) δ 163.1, 153.0,
41.9, 133.6, 132.7, 129.6, 128.8, 128.3, 125.8, 119.2, 117.1, 114.4,
14.1, 55.8; IR νmax (KBr) 3074, 2825, 1640, 1550, 1493, 1404, 1258,
150, 1088, 1015, 972, 903, 800, 756 cm ; HRMS (ESI-TOF) m/z
or overlapping); IR νmax (KBr) 2970, 1740, 1640, 1520, 1280, 1211,
3
−
1
1
1
1
1134, 826, 756, 645 cm ; HRMS (ESI-TOF) m/z calcd for
+
C H NO S, [M + H] 360.1270, found 360.1259.
19
22
4
−
1
(Z)-3-Chloro-N-(2H-chromen-2-ylidene)propane-1-sulfona-
mide (8l). The title compound (117 mg, 78%) was obtained as a white,
+
calcd for C H NO S, [M + H] 316.0644, found 316.0634.
16
14
4
(
Z)-N-(2H-Chromen-2-ylidene)methanesulfonamide (8f).
crystalline solid, mp = 113.4−115.0 °C (R = 0.3 in 1:2 v/v ethyl
f
1
The title compound (65 mg 58%) was obtained as a white, crystalline
solid, mp = 140.2−140.9 °C [R = 0.1(6) in 1:2 v/v ethyl acetate/60−
0 petroleum ether]. H NMR (400 MHz, CDCl ) δ 7.73 (d, J = 9.6 Hz,
acetate/60−90 petroleum ether). H NMR (400 MHz, CDCl ) δ 7.74
3
(d, J = 9.6 Hz, 1H), 7.61−7.47 (complex m, 3H), 7.36 (m, 1H), 6.78
f
1
13
1
9
(broad s, 1H), 3.75 (m, 2H), 3.37 (m, 2H), 2.43 (m, 2H); C{ H}
3
9
159
https://doi.org/10.1021/acs.joc.1c00331
J. Org. Chem. 2021, 86, 9155−9162

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
NMR (100 MHz, CDCl ) δ 152.9, 142.3, 132.9, 128.3, 125.9, 119.1,
ether) to give 2H-chromen-2-one (coumarin) (121 mg, 83%) as a
1d
3
1
1
17.3, 52.2, 43.1, 27.0 (two signals obscured or overlapping); IR ν
white, crystalline solid, mp = 67−69 °C (lit. mp = 70−72 °C). H
max
−
1
(
(
2
KBr) 2953, 1639, 1570, 1450, 1400, 1118, 825, 756 cm ; HRMS
NMR (400 MHz, CDCl ) δ 7.72 (d, J = 9.6 Hz, 1H), 7.54−7.48
3
+
ESI-TOF) m/z calcd for C H ClNO S, [M + H] 286.0305, found
(complex m, 2H), 7.35−7.27 (complex m, 2H), 6.43 (d, J = 9.6 Hz,
1
2
13
3
1
3
1
86.0299.
1H); C{ H} NMR (100 MHz, CDCl ) δ 160.9, 154.2, 143.6, 132.0,
3
(
Z)-4-Methyl-N-(6-methyl-2H-chromen-2-ylidene)-
128.0, 124.6, 119.0, 117.1, 116.9. This material was identical, in all
respects, with an authentic sample.
benzenesulfonamide (8m). The title compound (135 mg, 86%) was
obtained as a white, crystalline solid, mp = 170.3−175.1 °C (R = 0.3 in
Crystallographic Data. Compound 8a. C H NO S, M = 299.33,
f
16 13
3
1
1
:2 v/v ethyl acetate/60−90 petroleum ether). H NMR (400 MHz,
T = 296 K, monoclinic, space group P2 /c, Z = 12, a = 10.721(3) Å, b =
1
3
CDCl ) δ 7.97 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 9.6 Hz, 1H), 7.37 (m,
8.754(2) Å, c = 45.493(12) Å; β = 90.004(5); V = 4270(2) Å , D =
3
x
−
3
1
H), 7.31−7.28 (complex m, 4H), 6.68 (broad s, 1H), 2.40 (s, 6H);
C{ H} NMR (100 MHz, CDCl ) δ 151.2, 143.4, 142.1, 139.0, 135.8,
1.397 Mg m , 9705 unique data (2θ = 55.432°), R = 0.0579 [for
max
13
1
4055 reflections with I > 2.0σ(I)]; Rw = 0.1616 (all data), S = 0.995.
3
1
33.8, 129.4, 128.1, 127.5, 119.0, 116.7, 21.7, 20.9 (two signals
Compound 8j. C16
group P1, Z = 2, a = 7.6011(4) Å, b = 8.6114(5) Å, c = 11.7562(6) Å; α
= 95.672(5)°, β = 97.474(5)°, γ = 111.982(5)°; V = 698.34(7) Å , D =
x
H13NO S, M = 299.33, T = 150 K, triclinic, space
3
obscured or overlapping); IR νmax (KBr) 2910, 1640, 1565, 1365, 1288,
̅
−
1
3
1
230, 1150, 1088, 999, 868 745, 660 cm ; HRMS (ESI-TOF) m/z
+
−3
calcd for C H NO S, [M + H] 314.0851, found 314.0846.
1.424 Mg m , 3225 unique data (2θmax = 58.774°), R = 0.0414 [for
17
16
3
(
Z)-N-(6-Chloro-2H-chromen-2-ylidene)-4-methylbenzene-
2696 reflections with I > 2.0σ(I)]; Rw = 0.1007 (all data), S = 1.034.
sulfonamide (8n). The title compound (125 mg, 75%) was obtained
Compound 8q. C11
space group P2 /n, Z = 4, a = 6.8798(3) Å, b = 8.0785(5) Å, c =
19.1741(13) Å; β = 94.770(5); V = 1061.98(11) Å , D
H11NO S, M = 237.27, T = 153 K, monoclinic,
3
as a white, crystalline solid, mp = 210.9−216.8 °C [R = 0.4(5) in 1:2 v/
1
f
1
3
v ethyl acetate/60−90 petroleum ether]. H NMR (400 MHz, DMSO-
= 1.484 Mg
x
−
3
d ) δ 8.08 (d, J = 9.6 Hz, 1H), 7.93−7.89 (complex m, 3H), 7.72 (m,
m , 2734 unique data (2θmax = 148.23°), R = 0.0340 [for 2577
reflections with I > 2.0σ(I)]; Rw = 0.0926 (all data), S = 1.079.
Structure Determination. Data for compounds 8a, 8j and 8q were
collected on a Bruker APEX-II CCD or a Rigaku Super Nova X-ray
diffractometer employing either Mo Kα or Cu Kα radiation and a
graphite monochromator (λ = 0.71073 Å or 1.54184, respectively).
6
1
1
1
H), 7.56 (d, J = 9.6 Hz, 1H), 7.41 (d, J = 8.4 Hz, 2H), 6.94 (broad s,
1
3
1
H), 2.37 (s, 3H); C{ H} NMR (100 MHz, DMSO-d ) δ 151.3,
43.9, 142.9, 138.9, 132.9, 130.2, 130.0, 128.6, 127.6, 121.0, 118.7, 21.5
6
(two signals obscured or overlapping); IR ν (KBr) 3020, 1650, 1580,
max
−
1
1
285, 1240, 1180, 814, 775, 698 cm ; HRMS (ESI-TOF) m/z calcd
22
35
13
+
for C H ClNO S, [M + H] 334.0305, found 334.0301.
Using OLEX2, structures were solved by dual-space with the
16
3
23
(
Z)-N-(6-Bromo-2H-chromen-2-ylidene)-4-methylbenzene-
ShelXT program and refined, using least-squares minimization, with
24
sulfonamide (8o). The title compound (148 mg, 80%) was obtained
the ShelXL package. Atomic coordinates, bond lengths and angles,
and displacement parameters have been deposited at the Cambridge
Crystallographic Data Centre (CCDC 2043700, 2060954, and
2060955).
as a white, crystalline solid, mp = 194.8−197.8 °C (R = 0.4 in 1:2 v/v
f
1
ethyl acetate/60−90 petroleum ether). H NMR (400 MHz, DMSO-
d ) δ 8.07 (m, 2H), 7.90 (d, J = 4.0 Hz, 2H), 7.83 (m, 1H), 7.49 (d, J =
6
4
.4 Hz, 1H), 7.41 (d, J = 8.4 Hz, 2H), 6.94 (broad s, 1H), 2.37 (s, 3H);
1
3
1
C{ H} NMR (100 MHz, DMSO-d ) δ 151.7, 143.9, 142.8, 138.9,
ASSOCIATED CONTENT
sı Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00331.
6
■
1
35.7, 131.5, 130.0, 127.6, 121.5, 118.9, 118.1, 21.5 (two signals
*
obscured or overlapping); IR ν (KBr) 1632, 1550, 1390, 1285, 903,
6
H] 377.9800, found 377.9797.
max
−1
79
83 cm ; HRMS (ESI-TOF) m/z calcd for C H BrNO S, [M +
16 13 3
+
(
Z)-4-Methyl-N-(4-methyl-2H-chromen-2-ylidene)-
Plots derived from the single-crystal X-ray analyses of
benzenesulfonamide (8p). The title compound (95 mg, 61%) was
1
compound 8a, 8j, and 8q together with copies of the H
obtained as a white, crystalline solid, mp = 190−191 °C [R = 0.3(5) in
13
1
f
and C{ H} NMR spectra of compounds 8a−8q (PDF)
FAIR data, including the primary NMR FID files, for
compounds 8a−8q (ZIP)
1
1
:2 v/v ethyl acetate/60−90 petroleum ether]. H NMR (400 MHz,
CDCl ) δ 7.96 (d, J = 7.6 Hz, 2H), 7.64−7.56 (complex m, 2H), 7.43−
3
7
.25 (complex m, 4H), 6.84 (broad s, 1H), 2.48 (s, 3H), 2.40 (s, 3H);
13
1
C{ H} NMR (100 MHz, CDCl ) δ 152.6, 152.1, 143.4, 139.3, 132.7,
29.5, 127.4, 125.7, 126.4, 120.4, 117.4, 21.8, 19.1 (two signals
obscured or overlapping); IR νmax (KBr) 2921, 1632, 1570, 1485, 1451,
400, 1234, 1207, 1184, 972, 764 cm ; HRMS (ESI-TOF) m/z calcd
3
Accession Codes
1
CCDC 2043700 and 2060954−2060955 contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/
cif, or by emailing data_request@ccdc.cam.ac.uk, or by
contacting The Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
−
1
1
+
for C H NO S, [M + H] 314.0851, found 314.0847.
17
16
3
(
Z ) - N - ( 4 - M e t h y l - 2 H - c h r o m e n - 2 - y l i d e n e ) -
methanesulfonamide (8q). The title compound (62 mg, 52%), was
obtained as a white, crystalline solid, mp = 142−144 °C (R = 0.3 in 1:3
f
1
v/v ethyl acetate/60−90 petroleum ether). H NMR (400 MHz,
CDCl ) δ 7.66 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.48 (d, J =
3
AUTHOR INFORMATION
Corresponding Authors
■
7
2
1
.6 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 6.84 (broad s, 1H), 3.15 (s, 3H),
.51 (s, 3H); 13C{1H} NMR (100 MHz, CDCl ) δ 152.6, 152.2, 132.9,
3
Weiguang Yang − Guangdong Key Laboratory for Research and
the Development of Natural Drugs, The Marine Biomedical
Research Institute, Guangdong Medical University, Zhanjiang,
Guangdong 524023, China; The Marine Biomedical Research
Institute of Guangdong, Zhanjiang, Guangdong 524023,
China; Southern Marine Science and Engineering Guangdong
Laboratory, Zhanjiang, Guangdong 524023, China;
Email: 09ywg@163.com
Martin G. Banwell − Guangdong Key Laboratory for Research
and the Development of Natural Drugs, The Marine
Biomedical Research Institute, Guangdong Medical University,
Zhanjiang, Guangdong 524023, China; Institute for Advanced
and Applied Chemical Synthesis, Jinan University,
25.7, 124.9, 120.3, 117.6, 43.2, 19.1 (two signals obscured or
overlapping); IR ν (KBr) 2903, 1635, 1572, 1482, 1283, 1194, 1075,
30 cm ; HRMS (ESI-TOF) m/z calcd for C H NO S, [M + H]
38.0538, found 238.0531.
Hydrolysis of (Z)-N-(2H-chromen-2-ylidene)-4-methylbenze-
nesulfonamide (8a). Formation of 2H-Chromen-2-one. A
magnetically stirred solution of N-(2H-chromen-2-ylidene)-4-methyl-
max
−
1
+
8
2
11 12 3
benzenesulfonamide (8a) (149.5 mg, 0.5 mmol) and TsOH·H O (258
2
mg, 1.35 mmol) in water (3 mL) was heated under reflux for 12 h then
cooled and diluted with water (30 mL). The resulting mixture was
extracted with ethyl acetate (3 × 20 mL) and the combined organic
phases then dried (Na SO ) and filtered before being concentrated
2
4
under reduced pressure. The residue thus obtained was subjected flash
chromatography (silica gel, 1:3 v/v ethyl acetate/60−90 petroleum
9
160
https://doi.org/10.1021/acs.joc.1c00331
J. Org. Chem. 2021, 86, 9155−9162

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Guangzhou/Zhuhai 510632/519070, China; Research
School of Chemistry, Institute of Advanced Studies, The
Australian National University, Canberra 2601, Australia;
orcid.org/0000-0002-0582-475X;
stituted-4-hydroxycoumarins as HIV-1 protease inhibitors. Farmaco
002, 57, 703−708.
5) von Angerer, E.; Kager, M.; Maucher, A. J. Antitumour activity of
2
(
coumarin in prostate and mammary cancer models. J. Cancer Res. Clin.
Oncol. 1994, 120, S14−S16.
Email: martin.banwell@anu.edu.au
(6) Gacche, R. N.; Gond, D. S.; Dhole, N. A.; DawaNE, B. S.
Coumarin Schiff-bases: As Antioxidant and Possibly Anti-inflammatory
Authors
Agents. J. Enzyme Inhib. Med. Chem. 2006, 21, 157−161.
Yu Zhao − Guangdong Key Laboratory for Research and the
Development of Natural Drugs, The Marine Biomedical
Research Institute, Guangdong Medical University, Zhanjiang,
Guangdong 524023, China
(7) Singh, A. K.; Singh, R. K. Experimental, DFT and molecular
docking studies on 2-(2-marcaptophenylimino)-4-methyl-2H-chro-
men-7-ol. J. Mol. Struct. 2016, 1122, 318−323.
(8) Jogi, P. S.; Meshram, J.; Sheikh, J.; Hadda, T. B. Synthesis,
Zitong Zhou − Guangdong Key Laboratory for Research and
the Development of Natural Drugs, The Marine Biomedical
Research Institute, Guangdong Medical University, Zhanjiang,
Guangdong 524023, China
Lvling Liu − The Marine Biomedical Research Institute of
Guangdong, Zhanjiang, Guangdong 524023, China
Man Chen − Guangdong Key Laboratory for Research and the
Development of Natural Drugs, The Marine Biomedical
Research Institute, Guangdong Medical University, Zhanjiang,
Guangdong 524023, China
biopharmaceutical characterization, and antimicrobial study of novel
azo dyes of 7-hydroxy-4-methylcoumarin. Med. Chem. Res. 2013, 22,
4202−4210.
(9) Soliman, F. M.; Said, M. M.; Youns, M.; Darwish, S. A. Chemistry
of phosphorous ylides 32: synthesis of phosphoranylidene-pyrano- and
cyclobutyl-xanthenones with potential antitumor activity. Monatsh.
Chem. 2012, 143, 965−973.
(10) Barve, A.; Noolvi, M.; Subhedar, N.; Dev Gupta, V.; Bhatia, G.
Synthesis and antimicrobial activity of novel oxime derivatives of
phenothiazine. Eur. J. Chem. 2011, 2, 388−393.
(11) (a) Kim, S. H.; Park, S. H.; Choi, J. H.; Chang, S. Sulfonyl and
Qi Chen − Institute for Advanced and Applied Chemical
Synthesis, Jinan University, Guangzhou/Zhuhai 510632/
Phosphoryl Azides: Going Further Beyond the Click Realm of Alkyl
and Aryl Azides. Chem. - Asian J. 2011, 6, 2618−2634. (b) Bae, I.; Han,
H.; Chang, S. Highly Efficient One-Pot Synthesis of N-Sulfonylami-
dines by Cu-Catalyzed Three-Component Coupling of Sulfonyl Azide,
Alkyne and Amine. J. Am. Chem. Soc. 2005, 127, 2038−2039. (c) Cho,
S. H.; Yoo, E. J.; Bae, I.; Chang, S. Copper-Catalyzed Hydrative Amide
Synthesis with Terminal Alkyne, Sulfonyl Azide, and Water. J. Am.
Chem. Soc. 2005, 127, 16046−16047.
5
19070, China
Michael G. Gardiner − Research School of Chemistry, Institute
of Advanced Studies, The Australian National University,
Canberra 2601, Australia
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00331
(12) For examples of relevant recent work, see: (a) Wang, C.-G.; Wu,
R.; Li, T.-P.; Jia, T.; Li, Y.; Fang, D.; Chen, X.; Gao, Y.; Ni, H.-L.; Hu, P.;
Wang, B.-Q.; Cao, P. Copper(I)-Catalyzed Ketenimine Formation/
Aza-Claisen Rearrangement Cascade for Stereoselective Synthesis of α-
Allylic Amidines. Org. Lett. 2020, 22, 3234−3238. (b) Massaro, N. P.;
Chatterji, A.; Sharma, I. Three-Component Approach to Pyridine-
Stabilized Ketenimines for the Synthesis of Diverse Heterocycles. J. Org.
Chem. 2019, 84, 13676−13685. (c) Xu, L.; Zhou, T.; Liao, M.; Hu, R.;
Tang, B. Z. Multicomponent Polymerizations of Alkynes, Sulfonyl
Azides, and 2-Hydroxybenzonitrile/2-Aminobenzonitrile toward Mul-
tifunctional Iminocoumarin /Quinoline-Containing Poly(N-
sulfonylimine)s. ACS Macro Lett. 2019, 8, 101−106. (d) Guo, S.;
Dong, P.; Chen, Y.; Feng, X.; Liu, X. Chiral Guanidine/Copper
Catalyzed Asymmetric Azide-Alkyne Cycloaddition/[2 + 2] Cascade
Reaction. Angew. Chem., Int. Ed. 2018, 57, 16852−16856. (e) Nem-
atpour, M.; Dastjerdi, H. F.; Rabbani, S. M. I. M.; Tabatabai, S. A.
Copper-Catalyzed N-Arylation of Polysubstituted Pyridines Synthe-
sized by the Novel Reaction of N-Sulfonyl Ketenimine and
Malononitrile-Trichloroacetonitrile Adduct. J. Heterocycl. Chem.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Applied and Basic Research Fund of Guangdong
Province (2019A1515110918), the Medical Scientific Research
Foundation of Guangdong Province (A2020202), and the
Science and Technology Planning Program of Zhanjiang
(
2019A01018) for support. Funds provided, in 2019, for
Ph.D.-level researchers of the Guangdong Medical University
are also gratefully acknowledged (B2019015). Professor
Gottfried Otting (ANU) is thanked for helpful discussions.
REFERENCES
■
(
1) (a) Murray, R. D. H.; Méndez, J.; Brown, S. A. The Natural
2019, 56, 2604. (f) Cheng, D.; Ling, F.; Zheng, C.; Ma, C. Tuning of
Coumarins; Wiley: Chichester, UK, 1982. (b) O’Kennedy, R., Thornes,
R. D., Eds.; Coumarins: Biology, Applications and Mode of Action; Wiley:
Chichester, UK, 1997. (c) Yu, D.; Suzuki, M.; Xie, L.; Morris-Natschke,
S. L.; Lee, K. H. Recent Progress in the Development of Coumarin
Derivatives as Potent Anti-HIV Agents. Med. Res. Rev. 2003, 23, 322−
Copper-Catalyzed Multicomponent Reactions toward 3-Function-
alized Oxindoles. Org. Lett. 2016, 18, 2435−2438. (g) Murugavel, G.;
Punniyamurthy, T. Microwave-Assisted Copper-Catalyzed Four-
Component Tandem Synthesis of 3-N-Sulfonylamidine Coumarins. J.
Org. Chem. 2015, 80, 6291−6299. (h) Husmann, R.; Na, Y. S.; Bolm,
C.; Chang, S. Copper-catalyzed one-pot synthesis of α-functionalzed
imidates. Chem. Commun. 2010, 46, 5494. (i) Song, W.; Lu, W.; Wang,
J.; Lu, P.; Wang, Y. A Facile Route to γ-Nitro Imidates via Four-
Component Reaction of Alkynes with Sulfonyl Azides, Alcohols and
Nitroolefins. J. Org. Chem. 2010, 75, 3481−3483.
(13) Cui, S.-L.; Lin, X.-F.; Wang, Y.-G. Novel and Efficient Synthesis
of Iminocoumarins via Copper-Catalyzed Multicomponent Reaction.
Org. Lett. 2006, 8, 4517−4520.
(14) Shen, Y.; Cui, S. L.; Wang, J.; Chen, X. P.; Lu, P.; Wang, Y. G.
Copper-Catalyzed Three-Component Synthesis of 2-Iminodihydro-
coumarins and 2-Iminocoumarins. Adv. Synth. Catal. 2010, 352, 1139−
1144.
3
45. (d) Cervi, A.; Vo, Y.; Chai, C. L. L.; Banwell, M. G.; Lan, P.; Willis,
A. C. The Gold(I)-Catalyzed Intramolecular Hydroarylation (IMHA)
of Phenol-derived Propiolates and Certain Related Ethers as a Route to
Selectively Functionalized Coumarins and 2H-Chromenes. J. Org.
Chem. 2021, 86, 178−198.
(2) Singh, I.; Kaur, H.; Kumar, S.; Kumar, A.; Lata, S.; Kumar, A.
Synthesis of New Coumarin Derivatives as Antibacterial Agents. Int. J.
ChemTech Res. 2010, 2, 1745−1752.
(3) Sardari, S.; Mori, Y.; Horita, K.; Micetich, R. G.; Nishibe, S.;
Daneshtalab, M. Synthesis and Antifungal Activity of Coumarins and
Angular Furanocoumarins. Bioorg. Med. Chem. 1999, 7, 1933−1940.
(4) Kirkiacharian, S.; Thuy, D. T.; Sicsic, S.; Bakhchinian, R.; Kurkjian,
R.; Tonnaire, T. Structure-activity relationships of some 3-unsub-
9
161
https://doi.org/10.1021/acs.joc.1c00331
J. Org. Chem. 2021, 86, 9155−9162

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
(15) Yi, F.; Zhang, S.; Huang, Y.; Zhang, L.; Yi, W. An Efficient One-
Pot Protocol for the Synthesis of Polysubstituted 4-Amino-
iminocoumarins and 4-Aminoquinolines by a Copper-Catalyzed
Three-Component Reaction. Eur. J. Org. Chem. 2017, 2017, 102−110.
(16) Chen, Z.; Han, C.; Fan, C.; Liu, G.; Pu, S. Copper-Catalyzed
Diversity-Oriented Synthesis (DOS) of 4-Amino-2H-chrome-2-
imines: Application of Kemp Elimination toward O-Heterocycles.
ACS Omega 2018, 3, 8160−8168.
(17) Murugavel, G.; Punniyamurthy, T. Novel Copper-Catalyzed
Multicomponent Cascade Synthesis of Iminocoumarin Aryl Methyl
Ethers. Org. Lett. 2013, 15, 3828−3831.
(18) Mandal, P. S.; Kumar, A. V. Three-component one-pot synthesis
of N-arylsulfonyl-2-iminocoumarins. Tetrahedron 2018, 74, 1900−
907.
19) For a related rhodium-catalyzed route to iminocoumarins, see:
1
(
Chen, Z.; Jin, S.; Jiang, W.; Zhu, F.; Chen, Y.; Zhao, Y. Multicomponent
Synthesis of Iminocoumarins via Rhodium-Catalyzed C-H Bond
Activation. J. Org. Chem. 2020, 85, 11006−11013.
(20) (a) Gabriele, B.; Mancuso, R.; Salerno, G.; Costa, M. Cascade
Reactions: Sequential Homobimetallic Catalysis Leading to Benzofur-
ans and β,γ-Unsaturated Esters. Adv. Synth. Catal. 2006, 348, 1101−
1109. (b) Thirupathi, N.; Babu, M. H.; Dwivedi, V.; Kant, R.; Reddy,
M. S. Palladium-Catalyzed Tandem Intramolecular Oxy/Amino-
Palladation/Isocyanide Insertion: Synthesis of α-Benzofuranyl/Indo-
lylacetamides. Org. Lett. 2014, 16, 2908−2911. (c) Tian, T.; Li, L.; Xue,
J.; Zhang, J.; Li, Y. Enantioselective Syntheses of Spiroketals via a
Tandem Reaction of Cu(I)-Catalyzed Cycloetherification and Hydro-
gen-Bond-Induced [4 + 2] Cyclization. J. Org. Chem. 2015, 80, 4189−
4
200. (d) Zhang, M.; Yang, J.; Xu, Q.; Dong, C.; Han, L.-B.; Shen, R.
Copper-Catalyzed Dehydrative Cyclization of 1-(2-hydroxyphenyl)-
propargyl Alcohols with P(O)H Compounds for the Synthesis of 2-
Phosphorylmethylbenzofurans. Adv. Synth. Catal. 2018, 360, 334−345.
(
21) Das, D.; Samanta, R. Iridium(III)-Catalyzed Regiocontrolled
Direct Amidation of Isoquinolines and Pyridones. Adv. Synth. Catal.
018, 360, 379−384.
22) Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.;
2
(
Puschmann, H. OLEX2: a complete structure solution, refinement and
analysis program. J. Appl. Crystallogr. 2009, 42, 339−341.
(23) Sheldrick, G. M. ShelXT-Integrated space-group and crystal-
structure determination. Acta Crystallogr., Sect. A: Found. Adv. 2015,
A71, 3−8.
(24) Sheldrick, G. M. Crystal structure refinement with SHELXL. Acta
Crystallogr., Sect. C: Struct. Chem. 2015, C71, 3−8.
9
162
https://doi.org/10.1021/acs.joc.1c00331
J. Org. Chem. 2021, 86, 9155−9162