One-Pot Synthesis of B-Ring Ortho-Hydroxylated Sappanin-Type Homoisoflavonoids

Article abstract of DOI:10.1021/acs.joc.9b00814

A reliable method for the synthesis of B-ring hydroxylated homoisoflavonoids and 3-hetarylmethyl chromones has been developed. The method involves an initial oxa-Diels-Alder reaction of ortho-quinone methides generated from aryl/hetaryl-substituted ortho-(N,N-dimethylaminomethyl)phenols with (2E)-3-(N,N-dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-ones and the subsequent cascade of reactions. This synthetic strategy avoids conventional multistep protocols and does not require the protection of hydroxyl groups, thus allowing the facile synthesis of a library of various aromatic and heterocyclic analogues of naturally occurring homoisoflavonoids.

Full text of DOI:10.1021/acs.joc.9b00814

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Article
One-Pot Synthesis of B-Ring ortho-
Hydroxylated Sappanin-type Homoisoflavonoids
Galyna P Mrug, Nataliia V Myshko, Svitlana P. Bondarenko, Vitaliy M Sviripa, and Mykhaylo S. Frasinyuk
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00814 • Publication Date (Web): 15 May 2019
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The Journal of Organic Chemistry
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One-Pot Synthesis of B-Ring ortho-Hydroxylated Sappanin-type Ho-
moisoflavonoids
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Galyna P. Mrug,† Nataliia V. Myshko,‡ Svitlana P. Bondarenko,§ Vitaliy M. Sviripa, *ǁ,ꢀ and Mykhaylo
S. Frasinyuk *†.
† Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, V. P. Kukhar Institute of Bioorganic
Chemistry and Petrochemistry, National Academy of Science of Ukraine, Kyiv 02094, Ukraine
‡ Institute of High Technologies, Taras Shevchenko Kyiv National University, Kyiv 03022, Ukraine
§ Department of Food Chemistry, National University of Food Technologies, Kyiv 01601, Ukraine
ǁCenter for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40536-
0509, USA
┴ Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0509, USA
Supporting Information Placeholder
ABSTRACT: A reliable method for the synthesis of B-ring hy-
droxylated homoisoflavonoids and 3-hetarylmethyl chromones has
been developed. The method involves an initial oxa-Diels–Alder
reaction of ortho-quinone methides generated from aryl/hetaryl-
substituted ortho-(N,N-dimethylaminomethyl)phenols with (2E)-3-
(N,N-dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-ones and
the subsequent cascade of reactions. This synthetic strategy avoids
conventional multistep protocols and does not require the protec-
tion of hydroxyl groups, thus allowing the facile synthesis of a
library of various aromatic and heterocyclic analogs of naturally occurring homoisoflavonoids.
tion of the corresponding 1-(2-hydroxyphenyl)-3-
phenylpropan-1-ones in Vilsmayer–Haak reaction,4 Claisen
INTRODUCTION
condensation,5 ortho-ether condensation6 reactions, and in
The homoisoflavonoids are a small but diverse family of
natural compounds that derive biosynthetically from 2'-
methoxychalcones and usually classified into five main
structural subtypes including sappanin-, scillascillin-, brazi-
lin-, caesalpin-, and protosappanin-types.1 Among them, the
sappanin-type homoisoflavonoids (Fig. 1), that contain
chromanone or chromone ring with 3-benzyl substituents,
are the most diverse and well-studied ones. They are often
used in biosynthetic pathways as precursors for the synthesis
of other types.2 Like other flavonoid counterparts, naturally
occurring homoisoflavonoids typically bear hydroxylic,
methoxy, and methylenedioxy groups in rings A and B 3 and
possess a broad spectrum of biological activities, ranging
from anti-oxidant, anti-microbial, anti-diabetic and im-
munomodulatory effects, to specific effects as protein kinase
inhibitors. Therefore, the development of innovative and
efficient approaches to the natural/semisynthetic homoiso-
flavonoids continues to be an active synthetic direction for
the discovery of novel analogs with unique bioactivities.
cyclization
with
anhydrides7.
Alternatively,
9-
hydroxyderivatives have been synthesized by Baylis–
Hillman reaction of chromones with aromatic aldehydes.8
These approaches include multiple steps and require the
introduction of B-ring fragment at the initial stage of the
synthesis
1-(2-hydroxyphenyl)-3-(aryl/hetaryl)propan-1-
ones, and therefore, they are often inconvenient for the syn-
thesis of B-ring hydroxylated homoisoflavonoids and their
hydroxylated heteroaryl analogs.
Figure 1. Chemical structures of some sappanin-type natu-
ral homoisoflavonoids
Methodology in the literature for the synthesis of homoiso-
flavonoids follows patterns seen in the synthesis of the cor-
responding isoflavones from 2-hydroxydeoxybenzoines by
the ring-closure reactions and typically involves an applica-
On the other hand, 2'-hydroxy derivatives of (E)-1-phenyl-
3-(N,N-dimethylamino)prop-2-en-1-ones
2
(commonly
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named as enaminones) have proven to be efficient substrates 1-(2-hydroxyphenyl)prop-2-en-1-ones and the subsequent
1
for constructing chromone frameworks. Thus, treatment of
enaminones with acids is a common pathway to the for-
mation of 2,3-unsubstituted naphtopyrones and chromones.9
Oxidative reactions of enaminones with halogens or tert-
butyl hypochlorite10 are simple methods for the synthesis of
3-halogenochromones11 which in turn are useful compounds
for the synthesis of isoflavones by Suzuki coupling reac-
tions. A related oxidative reaction for the synthesis of 3-
thiocyanatochromones from enaminones with KSCN in the
presence of K2S2O8 was also reported.12 At last, alkyla-
tion/acylation of the enamine fragment and subsequent cy-
clization reactions are effective methods for the preparation
of alkylchromones13 and 3-acylchromones.14 As example, the
alkylation of 2-hydroxylated enaminones with benzyl bro-
mides led to the formation of homoisoflavones13a,15 (Scheme
1a) and recently reported interaction of b-naphthol Mannich
bases with enaminoketones provided access to the synthesis
of 3-acyl-4H-chromenes (Scheme 1b).16 The latter transfor-
mation was achieved by inverse-electron-demand hetero-
Diels–Alder reaction of enaminones with ortho-quinone
methides (o-QMs), which have found to be useful in the
syntheses of oxygen-containing heterocycles.17,18
cascading reactions.
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Scheme 2. Retrosynthetic Pathway
RESULTS AND DISCUSSION
To optimize the reaction conditions, we investigated the
reaction between (E)-3-(dimethylamino)-1-(2-hydroxy-5-
methylphenyl)prop-2-en-1-one
((dimethylamino)methyl)naphthalen-2-ol (3d). A screen of
various solvents revealed that DMF was the best choice for
this transformation to afford the desired product 4da in 44%
yield. The reaction could also proceed in other solvents, such
as diglyme and dimethylacetamide (DMA), but the yields of
4da were lower (data not shown). All attempts to improve
the yield by extending the reaction time were unsuccessful.
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(2a)
and
1-
Table 1. Substrate Scope of Enaminoketones 2 and Man-
nich Bases 3 a
Scheme 1. Application of enaminones in the synthesis of
chromones
Taking into account this information and our previous re-
port,19 we anticipated that utilizing of ortho-hydroxyphenyl
enaminones in Diels–Alder addition with thermally generat-
ed o-QMs from Mannich bases would provide adducts simi-
lar to the ones shown in Scheme 1b. However, these adducts
due to the presence of ortho-hydroxyl could undergo the
subsequent intramolecular rearrangement involving nucleo-
philic attack of the hydroxylic group at position 2 of 4H-
chromene ring that resulted in the formation of the 3-(2-
hydroxybenzyl)-4H-chromen-4-one skeleton (Scheme 1c).
The retrosynthetic pathway of such homoisoflavonoids syn-
thesis is presented in Scheme 2.
a Isolated yield
Herein, in continuation of our research program aimed at
the development of novel flavonoids for the search of phar-
maceutical agents, we report a one-pot approach for the
synthesis of hydroxylated homoisoflavonoids. This approach
involves initial inverse-electron-demand Diels-Alder reac-
tion of thermally generated from phenolic Mannich bases
ortho-quinone methides with (2E)-3-(N,N-dimethylamino)-
To define the scope of this approach to homoisoflavonoids
4, we studied the reactions of methyl- and halogen-
substituted
(E)-1-(2-hydroxyphenyl)-3-(N,N-dimethyl-
amino)prop-2-en-1-ones 2a-2d with ortho-N,N-dimethyl-
aminomethyl derivatives of various carbocyclic/heterocyclic
phenols 3a-3j (Table 1).
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In all cases, the oxa-Diels-Alder addition of the ortho-
Taking into account Michael addition of o-QMs to 2-
aminochromones reported earlier,20 we could not ignore the
possible Michael addition reaction of o-QMs 5 with chro-
mones 9 as a plausible pathway in the formation of homoiso-
flavonoids 4 (Scheme 4).
1
quinone methides, generated from 3a-j, with the enaminones
2a-d in diglyme, DMF or DMA at temperatures more than
150°C led to the formation of the homoisoflavonoids 4 in
yields ranging from moderate to high (Table 1). Thus, the
reaction of enaminones 2a-2d with phenolic Mannich bases
3a-3c provided better yields of the corresponding products 4
by refluxing in diglyme, whereas the reaction of the same
enaminones 2a-2d with bases 3d-3i gave higher yields of 4
by refluxing in DMF or DMA (in case of the reaction with
compound 3j).
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3
4
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Scheme 3. Proposed Reaction Mechanism
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The substituents on the aryl ring of the enaminoketones 2
had little influence on the reaction outcome. The reaction
mainly depended on nature of Mannich bases. For example,
the reaction of 2a-2d with the Mannich bases that contained
condensed aromatic rings such as 3d, 3g, 3h, and 3j fur-
nished higher yields of corresponding 4 compared to their
reaction with Mannich base 3a (Table 1). Such results could
be rationalized by their propensity to the charges delocaliza-
tion effects that contributed to the stabilization of o-QM
intermediates.
The molecular structure of products 4 was unambiguously
confirmed by 2D NMR techniques. Thus, the presence of
HMBC correlations between H-2, H-5, H-7 and C-8a in
compound 4ga confirmed the formation of chromone ring
(Fig. 2, see Supporting Information for spectra and detailed
information).
It is important to notice that during the conditions optimiz-
ing studies of the reaction of ortho-hydroxyphenyl enami-
nones 2 with Mannich bases we indeed isolated traces of
chromones 9a-d in those cases when the reaction was not
completed at low temperatures. In order to determine a con-
tribution of such mechanism to the synthesis of 4, we per-
formed additional studies and carried out the reactions of
enaminone 2a with 3a or 3d (Table 2) and Michael addition
reactions of chromone 9a with 3a or 3d (Table 3) at different
conditions during 4 h. According to our observations, this
time was usually insufficient for full conversion of enami-
nones 2 or chromones 9 to homoisoflavonoids 4, therefore,
we expected to isolate intermediates of the reaction of enam-
inone 2a with Mannich bases 3a or 3d.
Figure 2. Principal 2D NMR correlations for 4ga
In our opinion, the initial steps of such transformation pro-
ceeded in the same manner as it was described for the
aforementioned reaction of non-hydroxylated enamino-
ketones with phenol or naphtol Mannich bases.16 Obviously,
that initial thermal generation of o-QMs 5 from carbocyclic
or heterocyclic phenolic Mannich bases 3 and their following
inverse electron-demand oxa-Diels-Alder addition to the
Scheme 4. Alternate Reaction Mechanism via Michael
Addition of o-QMs 5 to Chromones 9
hydroxylated enaminoketones
2 furnished hemi-aminal
adducts 6 (Scheme 3).
Such unstable Diels–Alder adducts 6 underwent further
deamination and afforded 4H-benzopyrane derivatives 7,
which underwent a base-catalyzed intramolecular nucleo-
philic attack of the hydroxylic group at position 2 of 4H-
chromene ring and provided the desired products 4. (Scheme
3, Path A) We also can consider an alternate rearrangement
of adducts 6 to intermediates 8A-8C and their further deami-
nation to derivatives 4 (Scheme 3, Path B). The preferable
formation of compounds 4 from intermediates 7 can be ex-
plained by the thermodynamic control. The formation of 10p
electron aromatic system for 4 is more energetically favora-
ble than the 6p+2p electrоn non-conjugated system for com-
pounds 7. It should be also noted, that in all cases we only
isolated compounds 4 as the final products and did not detect
the formation of compounds 6-8.
Thus, the reaction of enaminone 2a with 2-(N,N-
dimethylaminomethyl)phenol (3a) at temperatures less than
1200C, led to the increased amounts of 9a relative to the
target homoisoflavonoids 4aa (Table 2, entries 1–3). How-
ever, the direct addition of 5a generated from 3a to chro-
mone 9a at the same conditions did not occur (Table 3, en-
tries 1–3). Moreover, the reaction of enaminone 2a with 3a
at temperatures 154-160 ºC gave much higher yields of 4aa
(Table 2, entries 4,5) compared to the reaction of chromone
9a with 3a that resulted in very low yield of 4aa (Table 3,
entries 4,5). The similar results were observed for the reac-
tions of enaminone 2a or chromone 9a with 1-(N,N-
dimethylaminomethyl)-2-naphthol (3d) that forms more
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stable o-QM intermediate 5d. In all cases, the direct addition sponding Mannich bases 3a and 3d. Otherwise, the yields of
1
2
3
4
5
6
7
8
of o-QM 5d generated from 3d to chromone 9a provided
much lower yields of the desired homoisoflavonoid 4da
(Table 3, entries 6–10) than the corresponding reactions of
enaminone 2a with 3d (Table 2, entries 6–10).
4aa or 4ad obtained in the reactions of enaminone 2a or
chromone 9a with 3a and 3d under the same reaction condi-
tions would be comparable. These results indicate that, alt-
hough possible, the alternative conversion of enaminone 2a
to chromone 9a and its further Michael addition to o-QMs
(path 2а®9a®4aa, Scheme 4) cannot be the primary syn-
thetic route to homoisoflavonoid 4aa. With respect to the
aforementioned studies, we conclude that the most appropri-
ate pathway is based on oxa-Diels-Alder addition of thermal-
ly generated o-QMs 5 to enaminones 2 with formation of
hemiaminals 6, followed by their deamination to 4H-
chromene derivatives 7, and their subsequent intramolecular
base-catalyzed rearrangement to the target compounds 4.
Despite the moderate yields of the synthesized homoflavo-
noids, the simplicity, accessibility, and available variety of
starting reagents make this method an attractive choice for
the synthesis of various aromatic and heterocyclic analogs of
naturally occurring homoisoflavonoids that would be diffi-
cult or impossible to synthesize by other methods.
Table 2. Screening Conditions for the Reaction of Enam-
inone 2a with Mannich Bases 3a, 3da
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entry
solvent
temp
(0C)
Mannich
base
4aa or 9a
4da
yield
yield
(%)b
(%)b
1
MeOCH2CH2OMe
1,4-Dioxane
EtOCH2CH2OEt
DMF
80
3a
3a
3a
3a
3a
3d
3d
3d
3d
3d
-
32
78.6
86.1
24.1
56.4
-
2
100
121
154
160
80
5.6
3
10.1
75.9
43.6
81.5
87.5
72.5
90.8
95
In conclusion, we have developed an efficient one-pot
method for the synthesis of B-ring hydroxylated homoisofla-
vonoids that does not require the protection of the phenolic
groups. The reaction provides a novel preparative route for
the synthesis of sappanin-type flavonoids and their heteroar-
yl analogs in moderate yields. Further practical scope and
potential application of these promising homoisoflavonoids
are currently under investigation in our laboratory.
4
5
Diglyme
6
MeOCH2CH2OMe
1,4-Dioxane
EtOCH2CH2OEt
DMF
7
100
121
154
160
1.9
-
8
9
-
10
Diglyme
-
EXPERIMENTAL SECTION
a All reactions were carried out using 2a (1 mmol), 3a or 3d
(1 mmol), and corresponding solvent (5mL) for 4 h at the indi-
cated temperatures. b Yields were determined by the LC-MS
Chemicals were purchased from Sigma Aldrich or Fisher
Scientific or were synthesized according to literature proce-
dures. Solvents were used from commercial vendors without
further purification unless otherwise noted. H and 13C{1H}
1
Table 3. Screening Conditions for Michael Addition of 9a
with Mannich Bases 3a, 3da
NMR spectra were recorded on a Bruker 500 (500 MHz /
125 MHz) or Bruker 400 (400 MHz / 100 MHz) spectrome-
ters in CDCl3 or DMSO-d6. 19F NMR spectra were recorded
on a Bruker 400 (376 MHz) relative to CFCl3. Melting
points were determined in open capillarity tubes using a
Buchi B-535 apparatus and were uncorrected. Mass spectra
were obtained with an Agilent 1100 spectrometer under
chemical ionization conditions. Elemental analysis was
en-
try
solvent
temp
(0C)
Mannich product
base
yield
(%)b
-
performed on
a varioMICROсube automated CHNS-
analyzer. Column chromatography was performed using
Macherey-Nagel Silica 60, 0.04-0.063 mm silica gel.
The enaminones 2a-2d21 and Mannich adducts 3a,22 3d,23
3f,24 3h,25 3i,26 and 3j27 were prepared as previously de-
scribed.
1
MeOCH2CH2OMe
1,4-Dioxane
EtOCH2CH2OEt
DMF
80
3a
3a
3a
3a
3a
3d
3d
3d
3d
3d
4aa
4aa
4aa
4aa
4aa
4da
4da
4da
4da
4da
2
100
121
154
160
80
-
3
-
4
7.6
2.8
6.4
14.2
39.7
70.0
30.9
5
Diglime
6-[(Dimethylamino)methyl]-1,3-benzodioxol-5-ol (3b).
A solution of sesamol (966 mg, 7 mmol), paraformaldehyde
(210 mg, 7 mmol), and dimethylamine (0.840 mL, 40%
aqueous solution, 7.4 mmol) in ethanol (10 mL) was stirred
at room temperature for 24 h. The solvent was evaporated in
vacuo and residue was purified by recrystallization from
isopropanol-hexanes mixture (1:5). Yield 1.110 g (82%).
6
MeOCH2CH2OMe
1,4-Dioxane
EtOCH2CH2OEt
DMF
7
100
121
154
160
8
9
10
Diglime
0
1
Beige solid, mp 87 - 89 C. H NMR (400 MHz, CDCl3) δ:
2.26 (s, 6H), 3.47 (s, 2H), 5.81 (s, 2H), 6.37 (s, 1H), 6.40 (s,
1H), 10.81 ppm (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ:
44.2, 62.6, 98.4, 100.7, 107.8, 113.0, 139.9, 147.5, 153.1
ppm. MS (APCI) m/z: 196.0 [M+H]+. Anal. Calcd (%) for
C10H13NO3: C, 61.53; H, 6.71; N, 7.18. Found (%): C, 61.38;
H, 6.89; N, 6.92.
a All reactions were carried out using 9a (1 mmol), either 3a
or 3d (1 mmol), and corresponding solvent (5 mL) for 4 h at the
indicated temperatures.b Yields were determined by the LC-MS.
Such observations suggested that 6-methyl-4H-chromen-4-
one (9a) was not a dominant player in the reactions of enam-
inones 2 with o-QMs 5a and 5d generated from the corre-
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5-[(Dimethylamino)methyl]-1,3-benzodioxol-4-ol (3c)
3.63 (s, 2H), 6.69 (t, J = 7.4 Hz, 1H), 6.82 (d, J = 7.9 Hz,
1H), 7.01 (t, J = 7.8 Hz, 1H), 7.08 (d, J = 7.5 Hz, 1H), 7.51 –
7.73 (m, 3H), 8.09 (s, 1H), 9.51 ppm (s, 1H). 13C{1H} NMR
(125 MHz, DMSO-d6) δ: 25.3, 109.4 (d, JC-F = 23.5 Hz),
1
2
3
4
5
6
7
8
was synthesized by the similar procedure described for 3b
from 4-hydroxy-1,3-benzodioxol. Yield 675 mg (49%).
Beige solid, 1H mp 125 - 127 0C. NMR (400 MHz, CDCl3) δ:
2.31 (s, 6H), 3.61 (s, 2H), 5.93 (s, 2H), 6.30 (d, J = 7.8 Hz,
1H), 6.43 (d, J = 7.8 Hz, 1H), 10.55 ppm (s, 1H). 13C{1H}
NMR (100 MHz, CDCl3) δ: 44.4, 62.8, 99.5, 101.3, 117.6,
120.7, 134.2, 142.5, 148.5 ppm. MS (APCI) m/z: 196.0
[M+H]+. Anal. Calcd (%) for C10H13NO3: C, 61.53; H, 6.71;
N, 7.18. Found (%): C, 61.77; H, 6.99; N, 7.24.
115.1, 118.9, 121.1 (d, JC-F = 8.3 Hz), 122.0, 122.0 (d, JC-F
=
25.5 Hz), 124.2 (d, JC-F = 7.1 Hz), 124.8, 127.4, 130.1,
152.3, 154.4, 155.2, 158.8 (d, JC-F = 244.1 Hz), 175.8 ppm
(d, J = 2.2 Hz). 19F NMR (376 MHz, DMSO-d6) δ: -116.1
ppm. MS (APCI) m/z: 271.0 [M+H]+. Anal. Calcd (%) for
C16H11FO3: C, 71.11; H, 4.10. Found (%): C, 70.93; H, 4.35.
9
7-[(Dimethylamino)methyl]-6-hydroxy-2-(1-
6-Chloro-3-(2-hydroxybenzyl)-4H-chromen-4-one
(4ac). Purified by column chromatography using 1:100
methanol-dichloromethane. Yield 201 mg (35%). Off-white
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methylethylidene)-1-benzofuran-3(2H)-one (3e). To
a
stirred suspension of 6-hydroxy-2-(1-methylethylidene)-1-
benzofuran-3(2H)-one (950 mg, 5 mmol) in 10 mL of iso-
propanol were added 0.816 mL (6 mmol, 1.2 eq) of bis(N,N-
dimethylamino)methane at 70oC. After stirring at 80oC for 2
h the mixture was cooled, triturated with hexane and formed
precipitate collected by filtration to afford 3e that was re-
crystalized from isopropanol-hexane. Yield 888 mg (72%).
Yellow solid, mp 153 - 155 0C. 1H NMR (400 MHz, CDCl3)
δ: 2.05 (s, 3H), 2.32 (s, 3H), 2.41 (s, 6H), 3.81 (s, 2H), 6.56
(d, J = 8.5 Hz, 1H), 7.52 (d, J = 8.5 Hz, 1H), 10.65 ppm (s,
1H). 13C{1H} NMR (100 MHz, CDCl3) δ: 17.2, 20.0, 44.6,
54.8, 104.0, 112.7, 115.5, 124.6, 129.2, 145.7, 163.9, 166.9,
182.5 ppm. MS (APCI) m/z: 248.0 [M+H]+. Anal. Calcd (%)
for C14H17NO3: C, 68.00; H, 6.93; N, 5.66. Found (%): C,
68.21; H, 6.78; N, 5.49.
0
1
solid, mp 197 - 199 C. H NMR (400 MHz, DMSO-d6) δ:
3.64 (s, 2H), 6.69 (t, J = 7.4 Hz, 1H), 6.82 (d, J = 8.0 Hz,
1H), 7.02 (t, J = 7.8 Hz, 1H), 7.08 (d, J = 7.5 Hz, 1H), 7.60
(d, J = 9.0 Hz, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.93 (s, 1H),
8.08 (s, 1H), 9.48 ppm (s, 1H). 13C{1H} NMR (125 MHz,
DMSO-d6) δ: 25.3, 115.1, 118.9, 120.8, 122.7, 124.0, 124.1,
124.6, 127.4, 129.7, 130.0, 133.8, 154.4, 154.4, 155.2, 175.3
ppm. MS (APCI) m/z: 287.0 [M+H]+. Anal. Calcd (%) for
C16H11ClO3: C, 67.03; H, 3.87. Found (%): C, 67.31; H,
4.12.
6-Bromo-3-(2-hydroxybenzyl)-4H-chromen-4-one
(4ad). Purified by column chromatography using 1:100
methanol-dichloromethane. 126 mg (19%). Off-white solid,
mp 171 - 173 0C. 1H NMR (400 MHz, DMSO-d6) δ: 3.63 (s,
2H), 6.69 (t, J = 7.4 Hz, 1H), 6.80 (d, J = 8.0 Hz, 1H), 7.02
(t, J = 7.7 Hz, 1H), 7.07 (d, J = 7.6 Hz, 1H), 7.58 (d, J = 8.6
Hz, 1H), 7.85 – 7.94 (m, 1H), 8.04 – 8.16 (m, 2H), 9.48 ppm
(s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ: 25.3, 115.0,
117.6, 118.9, 121.1, 122.8, 124.6, 124.6, 127.1, 127.4, 130.0,
136.5, 154.4, 154.8, 155.1, 175.2 ppm. MS (APCI) m/z:
331.0 [M+H]+. Anal. Calcd (%) for C16H11BrO3: C, 58.03; H,
3.35. Found (%): C, 57.88; H, 3.42.
8-Dimethylaminomethyl-7-hydroxy-chromen-2-one (3g)
was synthesized similar to compound 3e. Yield 613 mg
0
1
(56%). Beige solid, mp 117 - 119 C. H NMR (400 MHz,
CDCl3) δ: 2.40 (s, 6H), 4.01 (s, 2H), 6.17 (d, J=9.4 Hz, 1H),
6.75 (d, J=8.5 Hz, 1H), 7.27 (d, J=8.5 Hz, 1H), 7.61 (d,
J=9.4 Hz, 1H), 12.37 ppm (s, 1H). 13C{1H} NMR (100 MHz,
CDCl3) δ: 44.5, 55.0, 108.2, 111.1, 111.3, 113.8, 128.0,
144.3, 153.0, 161.3, 163.3 ppm. MS (APCI) m/z: 220.0
[M+H]+. Anal. Calcd (%) for C14H17NO3: C, 65.74; H, 5.98;
N, 6.39. Found (%): C, 65.93; H, 7.06; N, 5.24.
3-[(6-Hydroxy-1,3-benzodioxol-5-yl)methyl]-6-methyl-
4H-chromen-4-one (4ba). Purified by column chromatog-
raphy using 1:100 methanol-dichloromethane. Yield 366 mg
General Procedure for the synthesis of Homoisoflavo-
noids 4. A mixture of enaminone 2a-d (2 mmol) and corre-
sponding Mannich base 3a-j (2.4 mmol) in appropriate sol-
vent (10 mL) was stirred at reflux for the indicated period of
time (Tab.1). The reaction mixture was cooled, solvent was
evaporated, and formed residue was washed with water and
purified by recrystallization from EtOH or column chroma-
tography.
0
1
(59%). Pale yellow solid, mp 239 - 241 C. H NMR (400
MHz, DMSO-d6) δ: 2.38 (s, 3H), 3.54 (s, 2H), 5.85 (s, 2H),
6.45 (s, 1H), 6.71 (s, 1H), 7.45 (d, J = 8.6 Hz, 1H), 7.54 (dd,
J = 8.6, 2.2 Hz, 1H), 7.82 (d, J = 2.2 Hz, 1H), 8.04 (s, 1H),
9.23 ppm (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ:
20.4, 25.4, 97.8, 100.5, 109.6, 116.5, 118.1, 122.8, 124.2,
134.7, 135.0, 139.6, 145.9, 149.5, 153.9, 154.2, 176.7 ppm.
MS (APCI) m/z: 311.0 [M+H]+. Anal. Calcd (%) for
C18H14O5: C, 69.67; H, 4.55. Found (%): C, 69.49; H, 4.69.
3-(2-Hydroxybenzyl)-6-methyl-4H-chromen-4-one
(4aa). Purified by column chromatography using 1:100
methanol-dichloromethane. Yield 154 mg (29%). Off-white
6-Fluoro-3-[(6-hydroxy-1,3-benzodioxol-5-yl)methyl]-
4H-chromen-4-one (4bb). Purified by column chromatog-
raphy using 1:100 methanol-dichloromethane. Yield 283 mg
0
1
solid, mp 175 - 177 C. H NMR (400 MHz, DMSO-d6) δ:
2.38 (s, 3H), 3.64 (s, 2H), 6.70 (t, J = 7.4 Hz, 1H), 6.82 (d, J
= 8.0 Hz, 1H), 7.02 (t, J = 7.7 Hz, 1H), 7.05 – 7.14 (m, 1H),
7.44 (d, J = 8.6 Hz, 1H), 7.53 (dd, J = 8.6, 2.2 Hz, 1H), 7.82
(d, J = 2.2 Hz, 1H), 8.04 (s, 1H), 9.48 ppm (s, 1H). 13C{1H}
NMR (125 MHz, DMSO-d6) δ: 20.4, 25.4, 115.1, 118.1,
118.9, 122.4, 122.8, 124.2, 125.1, 127.4, 130.0, 134.7, 135.0,
153.9, 154.2, 155.1, 176.5 ppm. MS (APCI) m/z: 267.2
[M+H]+. Anal. Calcd (%) for C17H14O3: C, 76.68; H, 5.30.
Found (%): C, 76.84; H, 5.11.
0
1
(45%). Pale yellow solid, mp 229 - 231 C. H NMR (400
MHz, DMSO-d6) δ: 3.54 (s, 2H), 5.84 (s, 2H), 6.44 (d, J =
1.9 Hz, 1H), 6.70 (d, J = 1.9 Hz, 1H), 7.46 – 7.76 (m, 3H),
8.07 (s, 1H), 9.22 ppm (s, 1H). 13C{1H} NMR (100 MHz,
DMSO-d6) δ: 25.4, 97.7, 100.5, 109.4 (d, JC-F = 23.5 Hz),
109.7, 116.2, 121.1 (d, JC-F = 8.3 Hz), 122.1 (d, JC-F = 25.5
Hz), 122.3, 124.2 (d, JC-F = 7.1 Hz), 139.6, 146.0, 149.6,
152.4, 154.3, 158.8 (d, JC-F = 244.1 Hz), 176.0 ppm (d, J =
2.3 Hz). 19F NMR (376 MHz, DMSO-d6) δ: -116.1 ppm. MS
(APCI) m/z: 315.0 [M+H]+. Anal. Calcd (%) for C17H11FO5:
C, 64.97; H, 3.53. Found (%): C, 65.11; H, 3.27.
6-Fluoro-3-(2-hydroxybenzyl)-4H-chromen-4-one
(4ab). Purified by column chromatography using 1:100
methanol-dichloromethane. Yield 114 mg (21%). Off-white
0
1
solid, mp 194 - 196 C. H NMR (400 MHz, DMSO-d6) δ:
ACS Paragon Plus Environment

The Journal of Organic Chemistry
6-Chloro-3-[(6-hydroxy-1,3-benzodioxol-5-yl)methyl]- 6-Bromo-3-[(4-hydroxy-1,3-benzodioxol-5-yl)methyl]-
Page 6 of 10
1
4H-chromen-4-one (4bc). Purified by column chromatog-
4H-chromen-4-one (4cd). Purified by column chromatog-
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4
5
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8
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raphy using 1:100 methanol-dichloromethane. Yield 337 mg
raphy using 1:100 methanol-dichloromethane. Yield 398 mg
0
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0
1
(51%). Pale yellow solid, mp 208 - 210 C. H NMR (400
MHz, DMSO-d6) δ: 3.55 (s, 2H), 5.84 (s, 2H), 6.44 (s, 1H),
6.70 (s, 1H), 7.67 (d, J = 9.0 Hz, 1H), 7.81 (d, J = 9.0 Hz,
1H), 7.98 (s, 1H), 8.09 (s, 1H), 9.15 ppm (s, 1H). 13C{1H}
NMR (100 MHz, DMSO-d6) δ: 25.3, 97.7, 100.5, 109.7,
116.1, 120.7, 123.0, 123.9, 124.1, 129.7, 133.7, 139.6, 146.0,
149.6, 154.2, 154.4, 175.5 ppm. MS (APCI) m/z: 331.0
[M+H]+. Anal. Calcd (%) for C17H11ClO5: C, 61.74; H, 3.35.
Found (%): C, 61.97; H, 3.48.
(53%). Pale yellow solid, mp 208 - 210 C. H NMR (400
MHz, DMSO-d6) δ: 3.59 (s, 2H), 5.94 (s, 2H), 6.35 (d, J =
8.0 Hz, 1H), 6.62 (d, J = 8.0 Hz, 1H), 7.55 (d, J = 8.9 Hz,
1H), 7.87 (dd, J = 8.9, 2.6 Hz, 1H), 8.02 – 8.13 (m, 2H), 9.55
ppm (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ: 25.1,
100.0, 100.6, 117.7, 121.0, 121.1, 122.4, 123.2, 124.5, 127.1,
134.7, 136.6, 138.8, 146.9, 154.4, 154.8, 175.4 ppm. MS
(APCI) m/z: 375.0 [M+H]+. Anal. Calcd (%) for C17H11BrO5:
C, 54.42; H, 2.96. Found (%): C, 54.70; H, 3.22.
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6-Bromo-3-[(6-hydroxy-1,3-benzodioxol-5-yl)methyl]-
4H-chromen-4-one (4bd). Purified by column chromatog-
raphy using 1:100 methanol-dichloromethane. Yield 270 mg
3-[(2-Hydroxy-1-naphthyl)methyl]-6-methyl-4H-
chromen-4-one (4da). Yield 278 mg (44%). Pale yellow
0
1
solid, mp 193 - 195 C. H NMR (400 MHz, DMSO-d6) δ:
2.38 (s, 3H), 4.12 (s, 2H), 7.16 – 7.30 (m, 2H), 7.31 – 7.43
(m, 2H), 7.45 – 7.56 (m, 2H), 7.72 (d, J = 8.8 Hz, 1H), 7.77
(d, J = 8.1 Hz, 1H), 7.84 (d, J = 8.5 Hz, 1H), 7.90 (s, 1H),
9.93 ppm (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ:
20.1, 20.4, 115.5, 118.0, 118.3, 122.4, 122.5, 122.7, 124.3,
126.4, 128.3, 128.3, 128.4, 133.1, 134.8, 135.0, 153.0, 153.4,
154.0, 176.7 ppm. MS (APCI) m/z: 317.3 [M+H]+. Anal.
Calcd (%) for C21H16O3: C, 79.73; H, 5.10. Found (%): C,
79.45; H, 5.23.
0
1
(36%). Pale yellow solid, mp 224 - 226 C. H NMR (400
MHz, DMSO-d6) δ: 3.55 (s, 2H), 5.84 (s, 2H), 6.44 (s, 1H),
6.70 (s, 1H), 7.58 (d, J = 8.9 Hz, 1H), 77.84 – 7.94 (m, 1H),
8.03 – 8.17 (m, 2H), 9.14 ppm (s, 1H). 13C{1H} NMR (125
MHz, DMSO-d6) δ: 25.3, 97.7, 100.5, 109.7, 116.1, 117.6,
121.1, 123.0, 124.6, 127.1, 136.5, 139.5, 145.9, 149.6, 154.3,
154.8, 175.4 ppm. MS (APCI) m/z: 375.0 [M+H]+. Anal.
Calcd (%) for C17H11BrO5: C, 54.42; H, 2.96. Found (%): C,
54.18; H, 3.17.
3-[(4-Hydroxy-1,3-benzodioxol-5-yl)methyl]-6-methyl-
4H-chromen-4-one (4ca). Purified by column chromatog-
raphy using 1:100 methanol-dichloromethane. Yield 149 mg
6-Fluoro-3-[(2-hydroxy-1-naphthyl)methyl]-4H-
chromen-4-one (4db). Yield 218 mg (34%). Pale yellow
0
1
solid, mp 202 - 204 C. H NMR (400 MHz, DMSO-d6) δ:
4.12 (s, 2H), 7.20 – 7.29 (m, 2H, ), 7.34 – 7.43 (m, 1H), 7.55
(s, 1H), 7.56 – 7.68 (m, 2H), 7.72 (d, J = 8.9 Hz, 1H), 7.75 –
7.81 (m, 1H), 7.83 (d, J = 8.6 Hz, 1H), 9.91 ppm (s, 1H).
13C{1H} NMR (100 MHz, DMSO-d6) δ: 20.0, 109.5 (d, JC-F
= 23.5 Hz), 115.2, 118.3, 121.1 (d, JC-F = 8.4 Hz), 122.1,
122.3, 122.5, 122.7, 123.9 (d, JC-F = 7.2 Hz), 126.5, 128.3,
0
1
(24%). Pale yellow solid, mp 198 - 200 C. H NMR (400
MHz, DMSO-d6) δ: 2.39 (s, 3H), 3.54 (s, 2H), 5.84 (s, 2H),
6.45 (s, 1H), 6.71 (s, 1H), 7.46 (d, J = 8.6 Hz, 1H), 7.55 (dd,
J = 8.6, J = 2.2 Hz, 1H), 7.82 (d, J = 2.2 Hz, 1H), 8.04 (s,
1H), 9.22 ppm (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6)
δ: 20.5, 25.1, 100.1, 100.6, 118.1, 121.5, 122.3, 122.7, 122.9,
124.2, 134.8, 134.9, 135.2, 138.8, 146.9, 154.1, 154.2, 176.7
ppm. MS (APCI) m/z: 311.0 [M+H]+. Anal. Calcd (%) for
C18H14O5: C, 69.67; H, 4.55. Found (%): C, 69.88; H, 4.78.
128.3, 128.4, 133.1, 152.2, 153.1, 153.8, 158.8 (d, JC-F
=
244.1 Hz), 176.1 ppm. 19F NMR (376 MHz, DMSO-d6) δ: -
115.9 ppm. MS (APCI) m/z: 321.0 [M+H]+. Anal. Calcd (%)
for C20H13FO3: C, 74.99; H, 4.09. Found (%): C, 75.26; H,
4.30.
6-Fluoro-3-[(4-hydroxy-1,3-benzodioxol-5-yl)methyl]-
4H-chromen-4-one (4cb). Purified by column chromatog-
raphy using 1:100 methanol-dichloromethane. Yield 151 mg
6-Chloro-3-[(2-hydroxy-1-naphthyl)methyl]-4H-
0
1
(24%). Pale yellow solid, mp 236 - 237 C. H NMR (400
MHz, DMSO-d6) δ: 3.61 (s, 2H), 5.93 (s, 2H), 6.36 (d,
J=8.0, 1H), 6.62 (d, J=8.0, 1H), 7.57 – 7.78 (m, 3H), 8.12 (s,
1H), 9.53 (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ =
25.0, 100.0, 100.6, 109.5 (d, JC-F = 23.5 Hz), 121.2, 121.2 (d,
JC-F = 8.5 Hz), 122.3 (d, JC-F = 25.6 Hz), 122.4, 124.1 (d, JC-F
chromen-4-one (4dc). Yield 290 mg (43%). Pale yellow
0
1
solid, mp 211 - 213 C. H NMR (400 MHz, DMSO-d6) δ:
4.11 (s, 2H), 7.17 – 7.29 (m, 2H), 7.38 (t, J = 7.7 Hz, 1H),
7.44 – 7.59 (m, 2H), 7.66 – 7.85 (m, 4H), 8.02 (s, 1H), 9.90
ppm (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ: 20.0,
115.0, 118.2, 120.7, 122.4, 122.7, 123.0, 123.9, 124.0, 126.5,
128.2, 128.4, 129.7, 133.1, 133.8, 153.1, 153.8, 154.3, 175.6
ppm. MS (APCI) m/z: 337.0 [M+H]+. Anal. Calcd (%) for
C20H13ClO3: C, 71.33; H, 3.89. Found (%): C, 71.09; H,
4.07.
= 7.1 Hz), 134.7, 138.8, 146.9, 152.4, 154.5, 158.9(d, JC-F
=
244.0 Hz), 176.0 ppm. 19F NMR (376 MHz, DMSO-d6) δ: -
116.0 ppm. MS (APCI) m/z: 315.0 [M+H]+. Anal. Calcd (%)
for C17H11FO5: C, 64.97; H, 3.53. Found (%): C, 64.86; H,
3.78.
6-Bromo-3-[(2-hydroxy-1-naphthyl)methyl]-4H-
6-Chloro-3-[(4-hydroxy-1,3-benzodioxol-5-yl)methyl]-
4H-chromen-4-one (4cc). Purified by column chromatog-
raphy using 1:100 methanol-dichloromethane. Yield 278 mg
chromen-4-one (4dd). Yield 480 mg (63%). Pale yellow
0
1
solid, mp 210 - 212 C. H NMR (400 MHz, DMSO-d6) δ:
4.12 (s, 2H), 7.16 – 7.31 (m, 2H), 7.38 (t, J = 7.8 Hz, 1H),
7.44 (d, J = 8.9 Hz, 1H), 7.52 (s, 1H), 7.64 – 7.90 (m, 4H),
8.15 (s, 1H), 9.89 ppm (s, 1H). 13C{1H} NMR (125 MHz,
DMSO-d6) δ: 20.1, 115.1, 117.6, 118.3, 120.7, 122.4, 122.7,
123.1, 124.2, 126.4, 127.1, 128.2, 128.3, 133.1, 136.4, 153.1,
153.7, 154.5, 175.4 ppm. MS (APCI) m/z: 381.0 [M+H]+.
Anal. Calcd (%) for C20H13BrO3: C, 63.01; H, 3.44. Found
(%): C, 79.48; H, 4.82.
0
1
(42%). Pale yellow solid, mp 230 - 232 C. H NMR (400
MHz, DMSO-d6) δ: 3.60 (s, 2H), 5.94 (s, 2H), 6.36 (d, J =
8.0 Hz, 1H), 6.62 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 8.9 Hz,
1H), 7.81 (d, J = 8.9 Hz, 1H), 7.97 (s, 1H), 8.11 (s, 1H), 9.53
ppm (s, 1H). 13C{1H} NMR (100 MHz, DMSO-d6) δ: 25.0,
100.0, 100.6, 120.9, 121.1, 122.4, 123.1, 124.0, 124.1, 129.7,
133.9, 134.7, 138.8, 146.9, 154.4, 175.5 ppm. MS (APCI)
m/z: 331.0 [M+H]+. Anal. Calcd (%) for C17H11ClO5: C,
61.74; H, 3.35. Found (%): C, 61.52; H, 3.09.
3-{[6-Hydroxy-2-(1-methylethylidene)-3-oxo-2,3-
dihydro-1-benzofuran-7-yl]methyl}-6-methyl-4H-
ACS Paragon Plus Environment

Page 7 of 10
The Journal of Organic Chemistry
chromen-4-one (4ea). Yield 167 mg (23%). Off-white solid,
MS (APCI) m/z: 455.2 [M+H]+. Anal. Calcd (%) for
C28H22O6: C, 74.00; H, 4.88. Found (%): C, 74.27; H, 5.12.
mp 204 - 206 0C. 1H NMR (500 MHz, DMSO-d6) δ: 1.87 (s,
3H), 2.19 (s, 3H), 2.37 (s, 3H), 3.76 (s, 2H), 6.73 (d, J = 8.5
Hz, 1H), 7.33 – 7.46 (m, 2H), 7.46 – 7.56 (m, 1H), 7.81 (s,
1H), 7.94 (s, 1H), 10.87 ppm (s, 1H). 13C{1H} NMR (125
MHz, DMSO-d6) δ: 16.37, 18.66, 19.36, 20.41, 107.89,
111.79, 115.08, 117.96, 121.28, 122.57, 123.19, 124.18,
128.74, 134.73, 134.98, 144.74, 153.48, 154.13, 163.20,
164.38, 176.36, 181.47 ppm. MS (APCI) m/z: 363.1 [M+H]+.
Anal. Calcd (%) for C22H18O5: C, 72.92; H, 5.01. Found (%):
C, 73.20; H, 5.30.
1
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Ethyl 4-[(6-Fluoro-4-oxo-4H-chromen-3-yl)methyl]-5-
hydroxy-2-phenyl-1-benzofuran-3-carboxylate
(4fb).
0
1
Yield 321 mg (35%). Off-white solid, mp 177 - 178 C. H
NMR (400 MHz, DMSO-d6) δ: 0.93 (t, J = 7.1 Hz, 3H), 3.93
– 4.07 (m, 4H), 7.04 (d, J = 8.8 Hz, 1H), 7.38 – 7.54 (m,
5H), 7.60 – 7.68 (m, 4H), 7.76 (d, J = 8.3 Hz, 1H), 9.58 ppm
(s, 1H). 13C{1H} NMR (100 MHz, DMSO-d6) δ: 13.3, 21.8,
61.4, 109.4 (d, JC-F = 23.4 Hz), 110.5, 110.7, 114.2, 114.5,
121.0 (d, JC-F = 8.3 Hz), 121.9, 122.2 (d, JC-F = 25.4 Hz),
123.8 (d, JC-F = 7.2 Hz), 126.1, 127.0, 128.8, 129.0, 129.8,
147.7, 152.3, 152.3, 153.2, 155.0, 158.8 (d, JC-F = 244.2 Hz),
165.2, 175.8 ppm (d, JC-F = 2.2 Hz). 19F NMR (376 MHz,
DMSO-d6) δ: -116.0 ppm. MS (APCI) m/z: 459.0 [M+H]+.
Anal. Calcd (%) for C27H19FO6: C, 70.74; H, 4.18. Found
(%): C, 70.97; H, 4.32.
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6-Fluoro-3-{[5-hydroxy-2-(1-methylethylidene)-3-oxo-
2,3-dihydro-1-benzofuran-4-yl]methyl}-4H-chromen-4-
one (4eb). Yield 256 mg (35%). Off-white solid, mp 239 -
241 0C. 1H NMR (400 MHz, DMSO-d6) δ: 1.87 (s, 3H), 2.19
(s, 3H), 3.76 (s, 2H), 6.72 (d, J = 8.4 Hz, 1H), 7.40 (d, J =
8.4 Hz, 1H), 7.54 – 7.80 (m, 3H), 8.04 (s, 1H), 10.92 ppm (s,
1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ: 16.4, 18.6,
19.3, 107.6, 109.4 (d, JC-F = 23.6 Hz), 111.7, 115.1, 120.9,
121.0 (d, JC-F = 8.7 Hz), 122.0 (d, JC-F = 25.5 Hz), 123.2,
124.0 (d, JC-F = 7.1 Hz), 128.6, 144.8, 152.3, 153.9, 158.8 (d,
JC-F = 244.2 Hz), 163.2, 164.4, 175.7 (d, JC-F = 2.2 Hz),
181.4 ppm. 19F NMR (376 MHz, DMSO-d6) δ: -116.0 ppm.
MS (APCI) m/z: 367.2 [M+H]+. Anal. Calcd (%) for
C21H15FO5: C, 68.85; H, 4.13. Found (%): C, 71.36; H, 4.27.
Ethyl 4-[(6-chloro-4-oxo-4H-chromen-3-yl)methyl]-5-
hydroxy-2-phenyl-1-benzofuran-3-carboxylate
(4fc).
0
1
Yield 418 mg (44%). Off-white solid, mp 179 - 181 C. H
NMR (400 MHz, DMSO-d6) δ: 0.94 (t, J = 7.1 Hz, 3H), 3.80
– 4.23 (m, 4H), 7.03 (d, J = 8.9 Hz, 1H), 7.40 – 7.53 (m,
5H), 7.61 (d, J = 9.0 Hz, 1H), 7.64 – 7.69 (m, 2H), 7.78 (dd,
J = 8.9, J = 2.7 Hz, 1H), 7.93 – 8.06 (m, 1H), 9.57 ppm (s,
1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ: 13.3, 21.8,
61.3, 110.5, 110.7, 114.1, 114.4, 120.8, 122.6, 123.8, 123.9,
126.1, 127.0, 128.8, 129.0, 129.7, 129.8, 133.9, 147.7, 152.2,
153.2, 154.3, 155.0, 165.2, 175.4 ppm. MS (APCI) m/z:
475.0 [M+H]+. Anal. Calcd (%) for C27H19ClO6: C, 68.29; H,
4.03. Found (%): C, 68.37; H, 4.29.
6-Chloro-3-{[6-hydroxy-2-(1-methylethylidene)-3-oxo-
2,3-dihydro-1-benzofuran-7-yl]methyl}-4H-chromen-4-
one (4ec). Yield 161 mg (21%). Off-white solid, mp 232 -
0
1
234 C. H NMR (500 MHz, DMSO-d6) δ: δ 1.87 (s, 3H),
2.19 (s, 3H), 3.75 (s, 2H), 6.72 (d, J = 8.4 Hz, 1H), 7.40 (d, J
= 8.4 Hz, 1H), 7.62 (d, J = 9.0 Hz, 1H), 7.76 (dd, J = 9.0, 2.9
Hz, 1H), 7.94 (s, 1H), 8.03 (s, 1H), 10.92 ppm (s, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ: 16.4, 18.6, 19.4,
107.5, 111.7, 115.0, 120.8, 121.6, 123.3, 123.9, 128.8, 129.7,
133.8, 144.7, 154.0, 154.4, 163.2, 164.3, 175.2, 181.4 ppm.
MS (APCI) m/z: 383.1 [M+H]+. Anal. Calcd (%) for
C21H15ClO5: C, 65.89; H, 3.95. Found (%): C, 66.04; H,
4.20.
Ethyl 4-[(6-bromo-4-oxo-4H-chromen-3-yl)methyl]-5-
hydroxy-2-phenyl-1-benzofuran-3-carboxylate
(4fd).
0
1
Yield 208 mg (20%). Off-white solid, mp 182 - 184 C. H
NMR (500 MHz, DMSO-d6) δ: 0.95 (t, J = 7.1 Hz, 3H), 3.95
– 4.05 (m, 4H), 7.02 (d, J = 8.9 Hz, 1H), 7.44 (s, 1H), 7.46 –
7.54 (m, 4H), 7.58 (d, J = 9.0 Hz, 1H), 7.63 – 7.73 (m, 2H),
7.93 (dd, J = 9.0, 2.5 Hz, 1H), 8.17 (d, J = 2.5 Hz, 1H), 9.53
ppm (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ: 13.3,
21.8, 61.3, 110.5, 110.7, 114.0, 114.4, 117.7, 121.0, 122.7,
124.2, 126.1, 127.0, 127.1, 128.8, 129.0, 129.8, 136.6, 147.6,
152.2, 153.2, 154.7, 155.0, 165.2, 175.2 ppm. MS (APCI)
m/z: 519.0 [M+H]+. Anal. Calcd (%) for C27H19BrO6: C,
62.44; H, 3.69. Found (%): C, 73.74; H, 4.97.
6-Bromo-3-{[5-hydroxy-2-(1-methylethylidene)-3-oxo-
2,3-dihydro-1-benzofuran-4-yl]methyl}-4H-chromen-4-
one (4ed). Yield 444 mg (52%). Off-white solid, mp 278 -
280 0C. 1H NMR (400 MHz, DMSO-d6) δ: 1.90 (s, 3H), 2.22
(s, 3H), 3.80 (s, 2H), 6.73 (d, J = 8.4 Hz, 1H), 7.40 (d, J =
8.4 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.88 (dd, J = 8.8, J =
2.5 Hz, 1H), 8.03 (s, 1H), 8.13 (s, 1H), 10.66 ppm (s, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ: 16.4, 18.7, 19.4,
107.5, 111.7, 115.0, 117.7, 121.0, 121.7, 123.3, 124.4, 127.1,
128.8, 136.6, 144.7, 154.0, 154.8, 163.2, 164.4, 175.1, 181.5
ppm. MS (APCI) m/z: 427.0 [M+H]+. Anal. Calcd (%) for
C21H15BrO5: C, 59.04; H, 3.54. Found (%): C, 58.86; H,
3.69.
7-Hydroxy-8-[(6-methyl-4-oxo-4H-chromen-3-
yl)methyl]-2H-chromen-2-one (4ga). Yield 475 mg (71%).
0
1
Off-white solid, mp 252 - 254 C. H NMR (400 MHz,
DMSO-d6) δ: 2.42 (s, 3H, CH3), 3.81 (s, 2H, CH2), 6.21 (d, J
= 9.4 Hz, 1H, H-3¢), 6.89 (d, J = 8.5 Hz, 1H, H-6¢), 7.45 –
7.50 (m, 2H, H-8, 5¢), 7.58 (dd, J = 8.5, J = 2.2 Hz, 1H, H-
7), 7.68 (s, 1H, H-2), 7.86 (d, J = 2.2 Hz, 1H, H-5), 7.94 (d,
J = 9.4 Hz, 1H, H-4¢), 10.63 ppm (s, 1H, OH-7¢). 13C{1H}
NMR (100 MHz, DMSO-d6) δ: 18.7 (CH2), 20.5 (CH3),
110.9 (C-8¢), 111.2 (CH-3¢), 111.6 (C-4a¢), 112.6 (CH-6¢),
118.1 (CH-8), 121.2 (C-3), 122.5 (C-4a), 124.2 (CH-5),
127.8 (CH-5¢), 134.9 (C-6), 135.2 (CH-7), 144.9 (CH-4¢),
153.1 (CH-2), 153.6 (C-8a¢), 154.1 (C-8a), 159.2 (C-7¢),
160.4 (C-2¢), 176.5 ppm (CO-4). MS (APCI) m/z: 335.1
[M+H]+. Anal. Calcd (%) for C20H14O5: C, 71.85; H, 4.22.
Found (%): C, 71.97; H, 4.03.
Ethyl
5-Hydroxy-4-[(6-methyl-4-oxo-4H-chromen-3-
(4fa).
yl)methyl]-2-phenyl-1-benzofuran-3-carboxylate
0
1
Yield 355 mg (39%). Off-white solid, mp 150 - 152 C. H
NMR (400 MHz, DMSO-d6) δ: 0.92 (t, J = 7.1 Hz, 3H), 2.40
(s, 3H), 3.80 – 4.10 (m, 4H), 7.03 (d, J = 8.9 Hz, 1H), 7.32
(s, 1H), 7.37 – 7.58 (m, 6H), 7.56 – 7.72 (m, 2H), 7.89 (s,
1H), 9.56 (s, 1H) ppm. 13C{1H} NMR (100 MHz, DMSO-d6)
δ: 13.3, 20.4, 21.9, 61.3, 110.4, 110.7, 114.4, 114.5, 118.0,
122.3, 122.5, 124.2, 126.1, 126.9, 128.8, 129.0, 129.8, 134.7,
135.0, 147.6, 152.2, 152.5, 154.1, 154.8, 165.2, 176.4 ppm.
8-[(6-Fluoro-4-oxo-4H-chromen-3-yl)methyl]-7-
hydroxy-2H-chromen-2-one (4gb). Yield 453 mg (67%).
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0
1
Off-white solid, mp 254 - 256 C. H NMR (400 MHz,
DMSO-d6) δ: 3.82 (s, 2H), 6.20 (d, J = 9.4 Hz, 1H), 6.88 (d,
J = 8.4 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.60 – 7.75 (m,
3H), 7.77 (s, 1H), 7.93 (d, J = 9.4 Hz, 1H), 10.62 ppm (s,
1H). 13C{1H} NMR (100 MHz, DMSO-d6) δ: 18.5, 109.2 (d,
JC-F = 23.4 Hz), 110.5, 111.0, 111.4, 112.3, 120.6, 120.9 (d,
175.0, 175.4 ppm. MS (APCI) m/z: 461.0 [M+H]+. Anal.
Calcd (%) for C26H17ClO6: C, 67.76; H, 3.72. Found (%): C,
67.53; H, 3.99.
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Ethyl 5-hydroxy-1,2-dimethyl-4-[(6-methyl-4-oxo-4H-
chromen-3-yl)methyl]-1H-indole-3-carboxylate
(4ia).
0
1
Yield 300 mg (37%). Off-white solid, mp 157 - 159 C. H
NMR (400 MHz, DMSO-d6) δ: 1.01 (t, J = 7.1 Hz, 3H), 2.40
(s, 3H), 2.50 (s, 3H), 3.64 (s, 3H), 3.95 (q, J = 7.1 Hz, 2H),
4.15 (s, 2H), 6.87 (d, J = 8.7 Hz, 1H), 7.06 (s, 1H), 7.26 (d, J
= 8.7 Hz, 1H), 7.38 (d, J = 8.6 Hz, 1H), 7.52 (d, J = 8.6 Hz,
1H), 7.89 (s, 1H), 8.96 ppm (s, 1H). 13C{1H} NMR (100
MHz, DMSO-d6) δ: 11.9, 14.0, 20.5, 22.7, 29.7, 59.2, 104.8,
109.0, 111.6, 113.1, 117.9, 122.6, 123.4, 124.2, 125.2, 131.3,
134.5, 134.8, 143.0, 150.4, 152.1, 154.0, 165.6, 176.8 ppm.
MS (APCI) m/z: 406.2 [M+H]+. Anal. Calcd (%) for
C24H23NO5: C, 71.10; H, 5.72; N, 3.45. Found (%): C, 71.34;
H, 5.99; N, 3.73.
J
C-F = 8.2 Hz), 122.0 (d, JC-F = 25.7 Hz), 123.7 (d, JC-F = 7.3
Hz), 127.6, 144.6, 152.1, 153.4, 153.5, 158.6 (d, JC-F = 244.1
Hz), 159.1, 160.2, 175.7 ppm. 19F NMR (376 MHz, DMSO-
d6) δ = -116.0 ppm. MS (APCI) m/z: 339.0 [M+H]+. Anal.
Calcd (%) for C19H11FO5: C, 67.46; H, 3.28. Found (%): C,
67.73; H, 3.53.
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8-[(6-Chloro-4-oxo-4H-chromen-3-yl)methyl]-7-
hydroxy-2H-chromen-2-one (4gc). Yield 468 mg (66%).
0
1
Off-white solid, mp 268 - 270 C. H NMR (400 MHz,
DMSO-d6) δ: 3.84 (s, 2H), 6.19 (d, J = 9.4 Hz, 1H), 6.89 (d,
J = 8.4 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.65 (d, J = 9.0 Hz,
1H), 7.75 – 7.86 (m, 2H), 7.93 (d, J = 9.4 Hz, 1H), 8.01 (d, J
= 2.7 Hz, 1H), 10.52 ppm (s, 1H). 13C{1H} NMR (100 MHz,
DMSO-d6) δ: 18.7, 110.6, 111.2, 111.6, 112.5, 120.9, 121.6,
123.9, 124.0, 127.9, 129.8, 133.9, 144.9, 153.6, 153.7, 154.4,
159.3, 160.4, 175.4 ppm. MS (APCI) m/z: 354.9 [M+H]+.
Anal. Calcd (%) for C19H11ClO5: C, 64.33; H, 3.13. Found
(%): C, 64.08; H, 3.02.
Ethyl 4-[(6-fluoro-4-oxo-4H-chromen-3-yl)methyl]-5-
hydroxy-1,2-dimethyl-1H-indole-3-carboxylate
(4ib).
0
1
Yield 352 mg (43%). Off-white solid, mp 179 - 180 C. H
NMR (400 MHz, DMSO-d6) δ: 1.01 (t, J = 7.1 Hz, 3H), 2.52
(s, 3H), 3.65 (s, 3H), 3.95 (q, J = 7.1 Hz, 2H), 4.14 (s, 2H),
6.86 (d, J = 8.7 Hz, 1H), 7.13 (s, 1H), 7.28 (d, J = 8.7 Hz,
1H), 7.61 – 7.69 (m, 2H), 7.80 – 7.72 (m, 1H), 8.96 ppm (s,
1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ: 11.9, 13.9,
22.6, 29.7, 59.2, 104.7, 109.0, 109.4 (d, JC-F = 23.6 Hz),
111.5, 112.8, 121.0 (d, JC-F = 7.6 Hz), 122.0 (d, JC-F = 25.6
Hz), 123.1, 123.9 (d, JC-F = 6.8 Hz), 125.2, 131.3, 143.0,
150.4, 152.2, 152.5, 158.7 (d, JC-F = 243.4 Hz), 165.5, 176.1
ppm. 19F NMR (376 MHz, DMSO-d6) δ: -116.3 ppm. MS
(APCI) m/z: 410.0 [M+H]+. Anal. Calcd (%) for
C23H20FNO5: C, 67.48; H, 4.92; N, 3.42. Found (%): C,
67.71; H, 4.66; N, 3.20.
8-[(6-Bromo-4-oxo-4H-chromen-3-yl)methyl]-7-
hydroxy-2H-chromen-2-one (4gd). Yield 615 mg (77%).
0
1
Off-white solid, mp 314 - 315 C. H NMR (400 MHz,
DMSO-d6) δ: 3.82 (s, 2H), 6.20 (d, J = 9.4 Hz, 1H), 6.89 (d,
J = 8.5 Hz, 1H), 7.47 (d, J = 8.5 Hz, 1H), 7.58 (d, J = 8.9 Hz,
1H), 7.77 (s, 1H), 7.88 – 8.00 (m, 2H), 8.14 (d, J = 2.5 Hz,
1H), 10.60 ppm (s, 1H). 13C{1H} NMR (125 MHz, DMSO-
d6) δ: 18.7, 110.6, 111.2, 111.6, 112.5, 117.7, 121.0, 121.6,
124.2, 127.1, 127.9, 136.6, 144.8, 153.6, 153.6, 154.7, 159.3,
160.4, 175.35 ppm. MS (APCI) m/z: 310.2 [M+H]+. Anal.
Calcd (%) for C19H11BrO5: C, 57.17; H, 2.78. Found (%): C,
57.43; H, 3.03.
Ethyl 4-[(6-chloro-4-oxo-4H-chromen-3-yl)methyl]-5-
hydroxy-1,2-dimethyl-1H-indole-3-carboxylate
(4ic).
0
1
Yield 196 mg (23%). Off-white solid, mp 185 - 187 C. H
NMR (400 MHz, DMSO-d6) δ: 1.01 (t, J = 7.1 Hz, 3H), 2.50
(s, 3H), 3.63 (s, 3H), 3.94 (q, J = 7.1 Hz, 2H), 4.13 (s, 2H),
6.85 (d, J = 8.7 Hz, 1H), 7.11 (s, 1H), 7.26 (d, J = 8.7 Hz,
1H), 7.57 (d, J = 8.9 Hz, 1H), 7.76 (dd, J = 8.9, J = 2.7 Hz,
1H), 8.02 (d, J = 2.7 Hz, 1H), 8.95 ppm (s, 1H). 13C{1H}
NMR (125 MHz, DMSO-d6) δ: 11.9, 13.9, 22.6, 29.7, 59.2,
104.7, 109.0, 111.5, 112.7, 120.7, 123.8, 123.9, 125.2, 129.5,
131.3, 133.7, 143.1, 150.4, 152.5, 154.3, 165.5, 175.6 ppm.
MS (APCI) m/z: 426.1 [M+H]+. Anal. Calcd (%) for
C23H20ClNO5: C, 64.87; H, 4.73; N, 3.29. Found (%): C,
65.03; H, 4.68; N, 3.40.
8-[(6-Fluoro-4-oxo-4H-chromen-3-yl)methyl]-7-
hydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one (4hb).
0
1
Yield 453 mg (51%). Off-white solid, mp 118 - 120 C. H
NMR (400 MHz, DMSO-d6) δ: 3.76 (s, 3H), 3.90 (s, 2H),
6.95 (d, J = 8.4 Hz, 2H), 7.05 (d, J = 8.7 Hz, 1H), 7.49 (d, J
= 8.4 Hz, 2H), 7.59 – 7.77 (m, 3H), 7.83 (s, 1H), 7.93 (d, J =
8.7 Hz, 1H), 8.35 (s, 1H), 10.84 ppm (s, 1H). 13C{1H} NMR
(100 MHz, DMSO-d6) δ: 18.8, 55.1, 109.5 (d, JC-F = 23.5
Hz), 110.9, 113.6, 114.5, 117.0, 120.9, 121.1 (d, JC-F = 8.2
Hz), 122.3 (d, JC-F = 25.2 Hz), 122.8, 123.9 (d, JC-F = 7.1
Hz), 124.3, 125.3, 130.0, 152.3, 153.2, 153.8, 155.6, 158.9
(d, JC-F = 244.2 Hz), 158.9, 160.4, 175.0, 175.9 ppm. 19F
NMR (376 MHz, DMSO-d6) δ: -116.0 ppm. MS (APCI) m/z:
445.0 [M+H]+. Anal. Calcd (%) for C26H17FO6: C, 70.27; H,
3.86. Found (%): C, 70.54; H, 4.11.
3-[(8-Hydroxyquinolin-7-yl)methyl]-6-methyl-4H-
chromen-4-one (4ja). Purified by column chromatography
using 1:100 methanol-dichloromethane. Yield 298 mg
0
1
(47%). Pale yellow solid, mp 156 - 158 C. H NMR (400
MHz, CDCl3) δ: 2.37 (s, 3H), 4.01 (s, 2H), 7.19 – 7.27 (m,
2H), 7.28 – 7.40 (m, 2H), 7.56 (d, J = 8.4 Hz, 1H), 7.86 (s,
1H), 7.97 (d, J = 2.1 Hz, 1H), 8.04 (dd, J = 8.4, 1.6 Hz, 1H),
8.70 ppm (dd, J = 4.2, 1.6 Hz, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ: 21.0, 26.0, 117.5, 117.8, 120.9, 121.3,
123.1, 123.6, 125.2, 127.4, 130.4, 134.6, 134.8, 136.1, 138.3,
148.0, 149.8, 153.7, 154.8, 177.8 ppm. MS (APCI) m/z:
318.2 [M+H]+. Anal. Calcd (%) for C20H15NO3: C, 75.70; H,
4.76; N, 4.41. Found (%): C, 75.90; H, 4.97; N, 4.64.
8-[(6-Chloro-4-oxo-4H-chromen-3-yl)methyl]-7-
hydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one (4hc).
0
1
Yield 802 mg (87%). Off-white solid, mp 250 - 252 C. H
NMR (400 MHz, DMSO-d6) δ: 3.77 (s, 3H), 3.91 (s, 2H),
6.97 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 8.7 Hz, 1H), 7.50 (d, J
= 8.7 Hz, 2H), 7.66 (d, J = 9.0 Hz, 1H), 7.81 (dd, J = 9.0, J =
2.7 Hz, 1H), 7.84 (s, 1H), 7.94 (d, J = 8.7 Hz, 1H), 8.01 (d, J
= 2.7 Hz, 1H), 8.37 (s, 1H), 10.84 ppm (s, 1H). 13C{1H}
NMR (125 MHz, DMSO-d6) δ: 18.8, 55.1, 110.8, 113.5,
114.4, 116.9, 120.8, 121.6, 122.8, 123.8, 123.9, 124.2, 125.3,
129.7, 129.9, 133.9, 153.1, 153.7, 154.4, 155.6, 158.9, 160.3,
6-Fluoro-3-[(8-hydroxyquinolin-7-yl)methyl]-4H-
chromen-4-one (4jb). Purified by column chromatography
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using 1:100 methanol-dichloromethane. Yield 276 mg
ACKNOWLEDGMENT
VMS was supported by grant #IRG 16-182-28 from the Ameri-
can Cancer Society (ACS). We thank the College of Pharmacy
NMR Center (University of Kentucky) for NMR support.
0
1
1
2
3
4
5
6
7
8
(43%). Pale yellow solid, mp 161 - 163 C. H NMR (400
MHz, DMSO-d6) δ: 3.89 (s, 2H), 7.33 (d, J = 8.4 Hz, 1H),
7.43 (d, J = 8.4 Hz, 1H), 7.50 (dd, J = 8.3, 4.2 Hz, 1H), 7.62
– 7.81 (m, 3H), 8.20 (s, 1H), 8.28 (d, J = 8.3 Hz, 1H), 8.83
(d, J = 4.2 Hz, 1H), 9.87 ppm (s, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ: 26.03, 110.66 (d, J C-F = 23.6 Hz), 117.62,
REFERENCES
120.22 (d, J C-F = 8.1 Hz), 120.47, 121.42, 121.67 (d, J C-F
=
(1)
(a) Castelli, M. V.; López, S. N. In Studies in Natural
25.6 Hz), 122.75, 125.10 (d, J C-F = 7.3 Hz), 127.50, 130.45,
136.12, 138.23, 148.03, 149.85, 152.76, 153.98, 159.41 (d, J
C-F = 246.4 Hz), 177.03 ppm. 19F NMR (376 MHz, CDCl3) δ:
-116.1 ppm. MS (APCI) m/z: 322.0 [M+H]+. Anal. Calcd
(%) for C19H12FNO3: C, 71.03; H, 3.76; N, 4.36. Found (%):
C, 71.31; H, 3.94; N, 4.46.
Products Chemistry; Atta-ur-Rahman, Ed.; Elsevier: 2017; Vol. 54,
p 315-354. (b) Lin, L.-G.; Liu, Q.-Y.; Ye, Y. Naturally Occurring
Homoisoflavonoids and Their Pharmacological Activities. Planta
Med. 2014, 80, 1053-1066.
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32
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44
45
46
47
48
49
50
51
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55
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59
60
(2)
Dewick, P. M. Biosynthesis of the 3-benzylchroman-4-
one eucomin in Eucomis bicolor. Phytochemistry 1975, 14, 983-
988.
6-Chloro-3-[(8-hydroxyquinolin-7-yl)methyl]-4H-
chromen-4-one (4jc). Purified by column chromatography
using 1:100 methanol-dichloromethane. Yield 365 mg
(3)
(a) Chang, J.-M.; Shen, C.-C.; Huang, Y.-L.; Chien, M.-
Y.; Ou, J.-C.; Shieh, B.-J.; Chen, C.-C. Five new homoisoflavo-
noids from the tuber of Ophiopogon japonicus. J. Nat. Prod. 2002,
65, 1731-1733. (b) González, A. G.; León, F.; Sánchez-Pinto, L.;
Padrón, J. I.; Bermejo, J. Phenolic Compounds of Dragon's Blood
from Dracaena draco. J. Nat. Prod. 2000, 63, 1297-1299. (c) Ho-
ang Anh, N. T.; Van Sung, T.; Porzel, A.; Franke, K.; Wessjohann,
L. A. Homoisofiavonoids from Ophiopogon japonicus Ker-Gawler.
Phytochemistry 2003, 62, 1153-1158. (d) Qi, J.; Xu, D.; Zhou, Y.-
F.; Qin, M.-J.; Yu, B.-Y. New features on the fragmentation pat-
terns of homoisoflavonoids in Ophiopogon japonicus by highper-
formance liquid chromatography/diode-array detection/electrospray
ionization with multi-stage tandem mass spectrometry. Rapid Com-
mun. Mass Spectrom. 2010, 24, 2193-2206.
0
1
(54%). Pale yellow solid, mp 180 - 182 C. H NMR (400
MHz, CDCl3) δ: 4.01 (s, 2H), 7.28 (d, J = 8.5 Hz, 1H), 7.32
(d, J = 8.5 Hz, 1H), 7.37 (dd, J = 8.3, 4.3 Hz, 1H), 7.52 (dd,
J = 8.5, 2.6 Hz, 1H), 7.57 (d, J = 8.5 Hz, 1H), 7.90 (s, 1H),
8.09 (d, J = 8.3 Hz, 1H), 8.16 (d, J = 2.6 Hz, 1H), 8.73 ppm
(d, J = 4.3 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ:
26.0, 117.7, 119.9, 120.3, 121.5, 123.5, 125.0, 125.4, 127.5,
130.5, 130.9, 133.7, 136.1, 138.3, 148.1, 149.9, 153.9, 154.9,
176.6 ppm. MS (APCI) m/z: 338.0 [M+H]+. Anal. Calcd (%)
for C19H12ClNO3: C, 67.57; H, 3.58; N, 4.15. Found (%): C,
67.39; H, 3.72; N, 4.23.
(4)
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6-Bromo-3-[(8-hydroxyquinolin-7-yl)methyl]-4H-
chromen-4-one (4jd). Purified by column chromatography
using 1:100 methanol-dichloromethane. Yield 298 mg
0
1
(39%). Pale yellow solid, mp 198 - 200 C. H NMR (400
MHz, DMSO-d6) δ 3.89 (s, 2H), 7.33 (d, J = 8.4 Hz, 1H),
7.43 (d, J = 8.4 Hz, 1H), 7.51 (dd, J = 8.3, 4.2 Hz, 1H), 7.63
(d, J = 8.9 Hz, 1H), 7.93 (dd, J = 9.0, 2.6 Hz, 1H), 8.11 (d, J
= 2.5 Hz, 1H), 8.21 (s, 1H), 8.29 (dd, J = 8.3, 1.7 Hz, 1H),
8.83 (dd, J = 4.2, 1.7 Hz, 1H), 9.87 ppm (s, 1H). 13C{1H}
NMR (126 MHz, DMSO-d6) δ: 25.5, 117.0, 117.6, 120.8,
121.1, 121.3, 122.6, 124.6, 127.1, 127.3, 129.3, 136.0, 136.6,
138.0, 148.1, 150.3, 154.6, 154.8, 175.2 ppm. MS (APCI)
m/z: 382.0 [M+H]+, 384.0 [M+H]+. Anal. Calcd (%) for
C19H12BrNO3: C, 59.71; H, 3.16; N, 3.66. Found (%): C,
59.87; H, 3.42; N, 3.78.
ASSOCIATED CONTENT
Supporting Information
(5)
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The Supporting Information is available free of charge on the
ACS Publications website.
1
Copies of H, 13C{1H} spectra for all new synthesized com-
pounds and 2D for compound 4ga (PDF).
AUTHOR INFORMATION
Corresponding Authors
* VMS E-mail: vitaliy.sviripa@uky.edu
* MFS E-mail: mykhaylo.frasinyuk@ukr.net
Notes
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The authors declare no competing financial interest.
Synthesis
of
Homoisoflavanones
and
(±)-Di-O-
methyldihydroeucomin. Synth. Commun. 2005, 35, 563-569. (c)
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