8-Prenylflavanones through Microwave Promoted Tandem Claisen Rearrangement/6-endo-trig Cyclization and Cross Metathesis

Article abstract of DOI:10.1002/ejoc.202001378

Prenylated flavanones were obtained from ortho-allyloxy chalcones through a one-pot sequence of Claisen rearrangement and 6-endo-trig cyclization, followed by olefin cross metathesis of the intermediate allyl flavanones with 2-methyl-2-butene. The synthet

Full text of DOI:10.1002/ejoc.202001378

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: 8-Prenylflavanones via Microwave Promoted Tandem Claisen
Rearrangement/6-endo-trig Cyclization and Cross Metathesis
Authors: Christiane Schultze, Stefan Foß, and Bernd Schmidt
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202001378
Link to VoR: https://doi.org/10.1002/ejoc.202001378
01/2020

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL
PAPER
8-Prenylflavanones via Microwave Promoted Tandem
Claisen Rearrangement/6-endo-trig Cyclization and Cross
Metathesis
Christiane Schultze,[a]c Stefan Foß[a] and Bernd Schmidt*[a]
[a]
Dr. C. Schultze, S. Foß, MSc, Prof. Dr. B. Schmidt
Institut für Chemie
Universitaet Potsdam
Karl-Liebknecht-Straße 24-25, Haus 25, D-14476 Potsdam-Golm
E-mail: bernd.schmidt@uni-potsdam.de
URL: https://www.uni-potsdam.de/en/organischesynthesechemie/index
ORCID: https://orcid.org/0000-0002-0224-6069
Supporting information for this article is given via a link at the end of the document.
Abstract: Prenylated flavanones were obtained from ortho-allyloxy
chalcones via a one-pot sequence of Claisen rearrangement and 6-
endo-trig cyclization, followed by olefin cross metathesis of the
intermediate allyl flavanones with 2-methyl-2-butene. The synthetic
utility of this route is illustrated for the synthesis of several naturally
occurring prenyl flavanones.
many prenyl flavonoids have been synthesized starting from C-
prenylated acetophenones (synthesized using Jain’s method),
which were reacted with benzaldehydes in a Claisen-Schmidt-
condensation to chalcones. In a separate step the chalcones
underwent base-catalyzed 6-endo-trig cyclization to give the
prenyl flavonoids.[14-18]
OH
HO
OH
OH
HO
Introduction
HO
O
O
O
O
O
O
Prenylated flavanones (Figure 1) are secondary metabolites
isolated mainly from medicinal plants of the families Moraceae,
Cannabaceae and Leguminosae.[1-2] Bioactivities of these
compounds such as antibacterial and anti-oxidant activity,
cytotoxicity and estrogenic activity modulation, have been
summarized and discussed in several recent reviews.[3-6] Prenyl
substituents generally increase the bioactivities of flavonoids.
This has been attributed to an enhanced membrane permeability,
which is caused by the higher lipophilicity compared to the
analogous non-prenylated natural products.[7] Due to the
beneficial effects of prenyl flavonoids on human health they are
regarded as nutraceuticals,[8] which has recently resulted in
efforts to produce these compounds through metabolic
engineering. These studies[9-10] were mainly focused on
prenylnaringenin and the isoflavonoid prenylgenistein, which are
potent phytoestrogens that may help to reduce the negative
effects of menopause.[11]
OH
8-Prenylnaringenin (1)
Isobavachin (2)
Bavachin (3)
OH
OH
OH
OCH3
HO
O
O
HO
O
HO
O
OH
OH
OH
O
O
Lespeflorin A2 (4)
6-Prenyleriodictyol (5)
8-Prenyleriodictyol (6)
O
O
O
O
O
O
6,7,2,2-dimethylchromono-
8-prenylflavanone (8)
Maximaflavanon (7)
Figure 1. Examples of naturally occurring prenyl flavonoids.
Chemical syntheses of prenyl flavonoids[12] are particularly
relevant when enzymatic routes via metabolic engineering are not
(or not yet) available, or if a flexible access to analogues of natural
products is required, e. g. with the aim to investigate structure-
activity relationships. For the introduction of the prenyl substituent
to the aromatic core Jain’s method, i. e. the reaction of phenols
with prenyl bromide under basic conditions or with 2-methyl-3-
butene-2-ol under Lewis-acidic conditions, has been widely
used.[12-13] This reaction is, however, often accompanied by the
formation of dual C-prenylated and O-prenylated products and is
limited to very electron rich aromatic systems.[14] Nevertheless
We have previously developed a microwave promoted tandem
sequence for the synthesis of 8-allyl substituted chromones
starting from ortho-allyloxyaryl-alkinyl ketones via Claisen-
rearrangement and 6-endo-dig-cyclization.[19] With ortho-allyloxy-
alkenyl ketones, 8-allyl-chroman-4-ones were obtained in a 6-
endo-trig-cyclization. The substrate scope was found to be rather
limited, because good yields were only obtained for 2,2-
dimethylchroman-4-ones, whereas the isolated yields of 8-allyl-
flavanones, chroman-4-ones with an aryl substituent at position
1
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
C2, remained low.[20] The relevance of prenylated flavanones for
natural product chemistry prompted us to revisit the microwave-
promoted tandem approach as a route to this substance class.
Investigations into the optimization of reaction conditions and
application of the method to the synthesis of naturally occurring
prenylated flavonoids are discussed herein.
from chalcones polar-protic solvents, in particular methanol, have
been used, either in combination with a base[26] or with an acid.[23]
For these reasons a modification of the one-pot sequence by a
solvent switch between the reaction steps was investigated:
removal of N,N-diethylaniline after the first period of microwave
irradiation was accomplished by extraction with diluted
hydrochloric acid. The residue was then re-dissolved in methanol
and heated in the presence of NaOAc under conventional heating
conditions (oil bath, 12 h) to give 8-allyl-2-phenyl-flavane-4-one
(12aa) in a notably higher yield of 68% (entry 10). These
conditions are, however, rather impractical because removal of
the N,N-diethylaniline by aqueous acidic extraction is quite
laborious and not compatible with acid-sensitive functionalities or
protecting groups.
Results and Discussion
The ortho-allyloxy chalcones required as starting materials for the
microwave promoted tandem sequence were synthesized via
Claisen-Schmidt condensation[21] of O-allyl salicylic aldehydes
9a[20] or 9b[22] and benzaldehydes 10a-f. The products 11 were
mostly obtained in very high yields (Table 1).
Table 2. Optimization of conditions for one-pot Claisen-rearrangement / 6-endo-
trig-cyclization.
Table 1. Synthesis of ortho-allyloxy chalcones 10.
R2
R2
NaOH (1.5 equiv.)
ethanol/water (5 : 3)
20 °C, 16 h
R1
O
O
R1
O
O
MW, 250 °C, 1 h
solvent; additive
O
O
O
O
OH
O
+
+
O
9
10
11
11aa
entry
12aa
Additive (equiv.)
13aa
Solvent[a]
Yield of
12aa [%]
Yield of
13aa [%]
entry
9
R1 [a]
H
10
R2 [a]
11[b]
Yield [%]
1
2
3
4
5
6
7
8
9
10
9a
9b
9a
9a
9a
9a
9b
9b
9b
9b
10a
10a
10b
10c
10d
10e
10b
10c
10d
10f
H
11aa[20]
11ba
11ab
11ac
98
1
N,N-DEA
N,N-DEA
N,N-DEA
N,N-DEA
N,N-DEA
N,N-DEA
N,N-DEA
N,N-DEA
N,N-DEA
N,N-DEA
toluene
--
42
32
42
41
42
21
33
12
44
68
41
40
68
67
15
2
43
--[c]
--[c]
43
--[c]
--[c]
--[c]
--[c]
42
19
52
45
11
12
5
OMOM
H
H
Quant.
62
2[b]
3[d]
4
--
OCH3
Br
--
H
82
CuI (1)
H
Cl
11ad[20]
11ae
81
5
piperidine (0.05)
piperidine (1)
NaOAc (1)
AlCl3 (1)
H
NO2
OCH3
Br
58
6
OMOM
OMOM
OMOM
OMOM
11bb
11bc
11bd
11bf
95
7
96
8
Cl
97
9[e]
10[f]
11
NaOAc (10)
NaOAc (10)
--
OMOM
84
[a] OMOM: OCH2OCH3. [b] References with spectroscopic data of the
compound.
12[g]
13[h]
14[i]
15[j]
16[k]
17[l]
18[m]
toluene
NaOAc (10)
NaOAc (10)
NaOAc (10)
--
The reaction conditions for the envisaged microwave promoted
tandem sequence were optimized for chalcone 11aa (Table 2).
Under the standard conditions previously established for tandem
Claisen-rearrangement/6-endo-trig cyclization sequences with
other substrates we found that the Claisen-rearrangement step
proceeds quantitatively, but that the subsequent 6-endo-trig
cyclization stops at ca 50% conversion. This results in the
formation of a 1:1 mixture of the desired chroman-4-one 12aa and
allyl chalcone 13aa (entry 1). Increasing the reaction temperature
or the reaction time did not improve the yield of 12aa (entries 2
and 3). We then tested a variety of Lewis-acidic[23-24] or basic
additives[25] that were previously reported to promote
intramolecular oxa-Michael-additions (entries 4 - 9), but to no
avail. At this point we suspected that the proven solvent for the
first step of the microwave promoted tandem sequence, N,N-
diethylaniline, is less suitable for the second step, the oxa-Michael
addition. In previous reports on the synthesis of simple flavanones
toluene
toluene
methanol
methanol
cyrene
NaOAc (10)
--
11
22
--
14
--
cyrene
NaOAc (10)
[a] N,N-DEA: N,N-diethylaniline. [b] T = 270 °C. [c] not determined. [d] t = 2 h.
[e] NaOAc added after microwave irradiation, and mixture was stirred at 20 °C
for 12 h. [f] Solvent was removed by extraction with HCl (aq.), residue was re-
dissolved in methanol (6 mL/mmol), NaOAc (10 equiv.) was added and the
mixture was stirred at 65 °C for 12 h. [g] NaOAc added after MW-irradiation for
1 h at 250 °C, then MW-irradiation for 1 h at 100 °C. [h] Solvent was evaporated
after MW-irradiation; residue was re-dissolved in methanol (6 mL/mmol);
2
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
NaOAc (10 equiv.) was added and heated at 65 °C for 12 h. [i] Solvent was
evaporated after MW-irradiation; residue was re-dissolved in methanol (6
mL/mmol); NaOAc (10 equiv.) was added; MW-irradiation for 1 h at 100 °C. [j]
Allowed max. pressure (30 bar) reached at 180 °C; 11aa (73%) was recovered.
[k] Allowed max. pressure (30 bar) reached at 180 °C; 11aa (42%) was
recovered. [l] Unreacted starting material 11aa was formed but not quantified.
[m] Sharp increase of pressure (> 40 bar) after 8 min of reaction time led to
automatic shutdown; complex mixture of products.
The results summarized in Table 3 show that these optimized
reaction conditions can be applied to a variety of substituted
ortho-allyloxy chalcones 11 to give, in total, ten 8-allyl-flavan-4-
ones 12 in fair to good yields using the standard protocol.
In the next step the conversion of the 8-allyl-flavan-4-ones 12 to
their 8-prenyl derivatives 14 via olefin cross metathesis (CM) was
investigated.[35] Construction of ,-dimethylsubstituted C-C-
double bonds by olefin cross metathesis was first reported by
Grubbs and co-workers, who found that 2-methyl-2-butene is far
more reactive than 2,3-dimethyl-2-butene and more conveniently
For these reasons we sought an alternative solvent that could be
removed by simple evaporation after the first step but should still
have a sufficiently high boiling point to allow overheating (>
200 °C) without exceeding the allowed maximum pressure.
Toluene is a non-polar solvent with a very low dielectric loss
tangent (tan  = 0.040), which means that it is nearly transparent
for microwave irradiation. It would normally be considered to be
less suitable for microwave chemistry, because its heating
efficiency is low.[27] Nevertheless, toluene and other non-polar
solvents can be used in microwave-promoted transformations if
the reactants are polar and present at sufficiently high
concentrations,[28] or if passive heating elements are added.[29]
Microwave transparent solvents can even be advantageous
because they allow a specific absorption by the reactants.[30]
Indeed, microwave irradiation of chalcone 11aa in toluene at
250 °C for 1 h resulted in the formation of 12aa and 13aa in a ratio
of 0.8 : 1.0 and a combined yield of 93% (entry 11), which is even
higher than the yield obtained in N,N-DEA under otherwise
identical conditions (entry 1). Addition of NaOAc did not improve
the yield of the flavanone (entry 12). A solvent switch to methanol
in combination with added base, however, led to a yield of 68% of
12aa under conventional heating conditions (entry 13). The
reaction time of the oxa-Michael addition can be drastically
reduced from 12 h to 1 h if this step is also conducted under
microwave conditions at 100°C (entry 14). Attempts to avoid the
solvent switch by performing the entire sequence in methanol
failed both under non-basic (entry 15) and basic conditions (entry
16), because the highest attainable temperature with the test
substrate was 180 °C at an allowed maximum pressure (30 bar).
This temperature is to low to promote the Claisen rearrangement
effectively. Recently, dihydrolevoglucosenone, also known under
the trade name cyrene®, has attracted considerable attention as
a non-toxic biobased polar aprotic solvent with a very high boiling
point (T = 203 °C).[31] Although it has found several applications
as a reaction medium[32] or for liquid-liquid extractions[33] it has
apparently not been used as a solvent for microwave accelerated
reactions thus far and no information about the stability under
these conditions is available. In general, information about the
stability of cyrene under various conditions is scarce. The solvent
has been reported to be stable towards weak acids and bases
according to the manufacturers product information sheet, but
undergoes decomposition in the presence of stronger bases,
such as KOH.[34] Microwave irradiation of chalcone 11aa in cyrene
furnished the Claisen-rearrangement products 12aa and 13aa in
only 36% combined yield and an unsatisfactory product ratio
(entry 17), but the solvent appears to be stable at this temperature
over a period of one hour. When the test reaction was run in the
presence of NaOAc a sharp increase of the internal pressure to
40 bar, which is well beyond the allowed maximum pressure, was
observed after a few minutes, which led to an automatic shutdown
of the microwave reactor. In summary, neither methanol nor
cyrene appear to be suitable solvents for conducting the one-pot
Claisen-rearrangement/6-endo-trig cyclization sequence and we
therefore resumed to the conditions listed in entry 14.
to handle than isobutene, which is
a gas at ambient
temperature.[36] According to Grubbs’ general selectivity model for
cross metathesis reactions,[37] our 8-allyl-flavan-4-ones 12 are
Type I olefins (sterically unhindered, electronically neutral,
undergo fast self metathesis in the absence of other CM partners),
whereas 2-methyl-2-butene is a Type III olefin (sterically
hindered, does not undergo self metathesis, but can react with
other olefins). The combination of Type I and Type III olefins in
CM is generally expected to proceed selectively. With 2-methyl-
2-butene as CM partner of a Type I olefin a Ru-ethylidene is the
propagating species, rather than a Ru-isopropylidene, due to
lower steric hindrance in the ruthenacyclobutane intermediate.
This explains why CM reactions of allyl groups with 2-methyl-2-
butene can be expected to give ,-dimethylallyl- rather than
crotyl-substituted products.[36] The cross metathesis approach
has been used in some total syntheses of natural products,
including prenylated flavonoids[38-39] and coumarins.[22, 40-42] We
used two different protocols for the synthesis of 8-
prenylflavonoids from their 8-allyl counterparts (Table 4). Allyl
flavonoids 12 without OMOM-substituents were reacted with 2-
methyl-2-butene in the presence of second generation Grubbs’
catalyst[43] (A) at ambient temperature. Starting materials 12 with
MOM-protected OH groups (entries 2 and 7 – 10) underwent
cross metathesis under the same conditions, but were treated
with methanol in the presence of HCl (aq.) immediately after the
CM to cleave off the protecting group without isolation of the
MOM-protected intermediates. For the one-pot CM-deprotection
protocol slightly lower isolated yields (62% - 77%) were obtained
compared to the CM conditions without in situ deprotection
(entries 1 and 3 – 6, 84% - quant.).
Table 3. Synthesis of 8-allyl-2-arylflavan-4-ones 12.
R2
R2
R1
O
O
R1
O
O
toluene (0.15 M)
MW, 250 °C, 1 h
evaporate, methanol
NaOAc (10 equiv.)
MW, 100 °C, 1 h
11
12
entry
11
R1 [a]
H
R2 [a]
H
12[b]
Yield [%]
1
2
3
4
5
6
11aa
11ba
11ab
11ac
11ad
11ae
12aa[20]
12ba
67
46
66
76
53
66
OMOM
H
H
H
H
H
OCH3
Br
12ab[44]
12ac
Cl
12ad[20]
12ae
NO2
3
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
We then investigated if the sequence of microwave promoted
Claisen-rearrangement/oxa-Michael addition and olefin cross
metathesis can also be applied to obtain more complex flavonoids
with two prenyl groups. We aimed at a synthesis that would allow
the installation of both prenyl substituents (or their allyl
precursors) in one microwave promoted step. As an exemplary
target structure we chose 6,7,2,2-dimethylchromono-8-
prenylflavan-4-one (8). This linear prenylated chromonoflavonoid
has been isolated from the leaves[53] and bark[54] of Lannea acida,
a tree indigenous in North Nigeria that plays an important role in
traditional medicine to treat inflammation and fever. The same
natural product was later isolated from the stem bark of the tree
Pongamia pinnata, a medicinal plant found in Southeast Asia and
Australia.[55-56] Although 8 has only one actual prenyl substituent
it is nevertheless a double prenylated flavonoid, because the
chromene part is biosynthetically derived from an ortho-prenyl
phenol through a cyclase catalysed cyclization.[57-58]
7
11bb
11bc
11bd
11bf
OMOM
OMOM
OMOM
OMOM
OCH3
Br
12bb
62
48
50
60
8
12bc
9
Cl
12bd[45]
12bf[45]
10
OMOM
[a] OMOM: OCH2OCH3. [b] References reporting spectroscopic data of the
compound.
Out of the ten 8-prenyl flavonoids listed in Table 4 six have not
been described in the literature so far. Compound 14aa (entry 1)
is a synthetic 8-prenylflavonoid that was tested for its nematicidal
activity.[46] 7-Hydroxy-8-(,-dimethylallyl)-flavanone (entry 2,
14ba) was first isolated from Milletia ovalifolia seeds[47] and later
from the pods of Tephrosia falciformis.[48] It was demonstrated
that 14ba is one of the most potent inhibitors of adenosine cyclic
monophosphate (cAMP) phosphodiesterase out of more than
sixty flavonoids tested.[49] Lespeflorin A2 (4) was isolated from the
roots of the plant Lespedeza floribunda Bunge and found to inhibit
melanin synthesis (entry 7).[50] Isobavachin (2) was isolated from
Psoralea corylifolia seeds[51] and shows antioxidative activities.[52]
This compound has previously been synthesized via C-
prenylation of a substituted acetophenone, as outlined in the
introduction, to obtain a sufficient quantity to determine its
estrogenic potency.[16]
Allyl bromide
O
OH
O
K2CO3, acetone
50 °C, 12 h
O
O
O
15
16 (89%)
Benzaldehyde
ethanol, NaOH (aq.)
0 °C to 20 °C, 16 h
O
O
O
Table 4. Synthesis of 8-prenyl-2-arylflavan-4-ones 14 via cross metathesis.
17 (90%)
R4
toluene, MW, 250 °C, 1 h, evaporate;
methanol, NaOAc (10 equiv.)
MW, 100 °C, 1 h
R2
R3
O
O
R1
O
O
Method 1 or method 2
14
12
O
O
O
O
O
O
MesN
NMes
Cl
Ru
Method 1: A (5 mol-%), CH2Cl2, 2-methyl-2-butene
20 °C, 16 h.
Method 2: i) A (5 mol-%), CH2Cl2, 2-methyl-2-butene,
Ph
Cl
18 (19%)
19 (22%)
PCy3
20 °C, 16 h. ii) evaporate, add methanol,
HCl (3 M), 65 °C
A
A (5 mol-%), CH2Cl2
A (5 mol-%), CH2Cl2
2-methyl-2-butene
20 °C, 16 h
2-methyl-2-butene
20 °C, 16 h
entry
12
R3
R4
14[c]
Yield [%]
1[a]
2[b]
3[a]
4[a]
5[a]
6[a]
7[b]
8[b]
9[b]
10[b]
12aa
12ba
12ab
12ac
12ad
12ae
12bb
12bc
12bd
12bf
H
H
14aa[46]
14ba[47]
14ab
14ac
14ad
14ae
4[50]
84
O
O
O
O
O
OH
H
H
73
OCH3
Br
95
O
6,7,2,2-dimethylchromono-8-
prenylflavanone (8, 77%)
Maximaflavanon (7, 94%)
H
Quant.
89
H
Cl
Scheme 1. Synthesis of 6,7,2,2-dimethylchromono-8-prenylflavan-4-one (8)
and maximaflavanone A (7).
H
NO2
OCH3
Br
91
OH
OH
OH
OH
77
For the chemical synthesis of chromenes we[59] and others[60]
14bc
14bd
2[16]
68
have used
a
microwave promoted propargyl-Claisen
rearrangement, a transformation that starts from propargyl ethers
and proceeds through allene intermediates.[61] To install the
chromene part and the 8-allyl substituent simultaneously in the
microwave promoted tandem sequence, the chalcone 17, bearing
a propargyl and an allyl ether, was required as a starting material
(Scheme 1). This compound was synthesized in two steps from
15[59] via O-allylation and subsequent Claisen-Schmidt
condensation of 16 and benzaldehyde. Submission of 17 to the
Cl
62
OH
62
[a] Method 1. [b] Method 2. [c] References reporting spectroscopic data of the
compound.
4
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
optimized conditions for the microwave promoted Claisen-
rearrangement/6-endo-cyclization furnished a 1:1 mixture of the
desired linear product 18 and its angular isomer 19. The formation
of 19 suggests that the propargyl Claisen rearrangement is not
regioselective and notably faster than the allyl Claisen
rearrangement. Once the propargyl Claisen rearrangement has
occurred in position 8, this site is blocked for the allyl substituent.
In such situations allyl ethers are known to undergo two
successive [3,3]-sigmatropic rearrangements, first a Claisen-
NaOH (1.5 equiv.)
ethanol/water (5 : 3)
20 °C, 16 h
OMOM
OMOM
MOMO
O
O
+
O
O
9c
MOM
10e
OMOM
toluene (0.15 M)
MW, 250 °C, 1 h
MOMO
O
O
OMOM
evaporate, methanol
NaOAc (10 equiv.)
MW, 100 °C, 1 h
O
MOM
rearrangement and then
a Cope-rearrangement. Via this
11ce (83%)
sequence the allyl group ultimately migrates to the para-
position,[62-63] which is position 6 in flavonoid 19. The linear isomer
18 and the angular isomer 19 are not easily distinguishable by
their one-dimensional NMR-spectra. For these reasons a full
signal assignment was performed based on the two-dimensional
NMR-spectroscopic methods H,H-COSY, HSQC and HMBC.
Indicative for the linear structure of 18 and the angular structure
of 19 are the HMBC correlations shown in Figure 2.
OMOM
OMOM
OMOM
OMOM
MOMO
O
O
MOMO
OH
O
+
O
O
12ce (42%)
13ce (25%)
MOM
MOM
A (5 mol-%), CH2Cl2
2-methyl-2-butene
20 °C, 16 h.
9
H
H
H
8
10
1
O
1
9
O
10
10a
6a
OMOM
OH
OH
O
2
O 10a
8
2
3
7
HCl (3 M)
methanol
65 °C
9a
1a
6
MOMO
O
HO
O
O
7
5
4
5
3
6
4
OMOM
4a
5a
4a
H
H
H
O
H
H
O
18
19
O
O
OH
MOM
14ce (76%)
6 (42%)
Figure 2. HMBC-experiments for isomers 18 and 19.
Scheme 2. Synthesis of 8-prenyleriodictyol (6).
Gratifyingly, the formation of 19 enabled the synthesis of another
natural product, maximaflavanone A (7), which is the angular
regioisomer of 8. Maximaflavanone A (7) was first isolated from
the roots of the medicinal plant Tephrosia maxima Pers[64] and
later from the roots of Pongamia pinnata,[65] which is also a source
of the linear natural product 8. We are aware of one previous
synthesis of maximaflavanone A (7) that starts from a preformed
5-prenyloxy substituted chromene.[66] To complete the syntheses
of 7 and 8 the products 18 and 19 of the microwave promoted
tandem sequence were separated, which was conveniently
achieved by chromatography due to their significantly different
polarities. Olefin cross metathesis of 18 and 19 with 2-methyl-2-
butene in the presence of second generation Grubbs’ catalyst A
proceeded in 77% yield with 18 and in 94% yield with 19. The
natural products 6,7,2,2-dimethylchromono-8-prenylflavan-4-one
(8) and maximaflavanone A (7) were obtained over four steps in
11.7% and 16.6% total yield.
8-Prenyleriodictyol (6) was first isolated from the flowering plant
Wyethia helenioides.[67] It shows moderate vasorelaxant and
neuroprotective activities,[17] and antibiotic activities against
Staphylococcus aureus and Staphylococcus epidermis in the
range of 12.5 to 25 g/mL.[68] The compound has previously been
synthesized through oxa-Michael cyclization of a prenylated
chalcone[17] and via regioselective enzyme catalyzed prenylation
of eriodictyol.[69] Our synthesis started with the known compounds
9c[70] and 10e,[71] which were reacted in a Claisen-Schmidt
condensation under the previously established conditions to
furnish 11ce. Microwave promoted tandem Claisen-
rearrangement/6-endo-cyclization of 11ce gave a separable
mixture of MOM-protected flavanone 12ce and uncyclized
chalcone 13ce in a combined yield of 67%. After separation by
column chromatography, 12ce was subjected to cross metathesis
with
2-methyl-2-butene
to
yield
MOM-protected
8-
prenyleriodictyol 14ce, which was eventually deprotected to give
8-prenyleriodictyol (6) in four steps and 11.1% overall yield. All
analytical data obtained for synthetic 8-prenyleriodictyol (6) match
those previously reported for the natural product.[67, 69]
As an example for a 5-hydroxylated 8-prenylflavanone we
investigated the synthesis of 8-prenyleriodictyol (6) along the
synthetic route outlined herein (Scheme 2).
Conclusion
In summary, we report a synthesis of 8-prenylflavanones that
relies on a microwave promoted tandem sequence comprising a
Claisen-rearrangement and an oxa-Michael cyclization in
combination with a highly regioselective olefin cross metathesis
reaction using 2-methyl-2-butene to construct the prenyl
substituent. The method was applied to the synthesis of various
naturally occurring 8-prenylflavanones, including 6,7,2,2-
dimethylchromono-8-prenylflavan-4-one and its angular isomer
maximaflavanone A.
5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
mg, 2.00 mmol) were converted to 11ba (182 mg, 0.62 mmol, 62%):
yellowish oil. 1H NMR (300 MHz, CDCl3):  = 7.65 (dd, J = 7.6, 1.8 Hz, 1H),
7.62 (d, J = 15.9 Hz, 1H), 7.54 (d, J = 8.7 Hz, 2H), 7.45 (ddd, J = 8.3, 7.4,
1.8 Hz, 1H), 7.33 (d, J = 15.9 Hz, 1H), 7.04 (td, J = 7.5, 1.0 Hz, 1H), 6.98
(d, J = 8.3 Hz, 1H), 6.90 (d, J = 8.8 Hz, 1H), 6.03 (ddt, J = 17.2, 10.5, 5.0
Hz, 1H), 5.42 (dm, J = 17.2 Hz, 1H), 5.24 (dm, J = 10.5 Hz, 1H), 4.64 (dm,
J = 5.0 Hz, 2H), 3.83 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3):  = 192.9,
161.6, 157.2, 143.0, 132.8, 132.7, 130.6, 130.2, 130.1, 128.0, 125.2,
Experimental Section
General methods: all experiments involving air- and moisture sensitive
compounds were conducted in dry reaction vessels under an atmosphere
of dry nitrogen. The solvents dichloromethane, diethyl ether, methanol and
toluene were purified using an MBraun solvent purification system.
Solvents for chromatography were distilled prior to use. All reagents were
purchased and used without further purification, unless otherwise stated,
or synthesized following published procedures. 1H NMR spectra were
obtained in CDCl3 with CHCl3 ( = 7.26) as an internal standard.
Multiplicities are denoted as s (singlet), d (doublet), t (triplet), q (quartet)
and m (multiplet). Coupling constants are given in Hz. 13C NMR spectra
were recorded with proton decoupling in CDCl3 with CDCl3 ( = 77.16) as
an internal standard. Whenever the solubility or stability of the sample or
signal separation were insufficient in CDCl3, it was replaced by [D6]acetone
([D5]acetone as internal standard for 1H NMR spectroscopy,  = 2.05 ppm,
[D6]acetone as internal standard for 13C NMR spectroscopy,  = 29.8 ppm)
or [D4]methanol (CD2HOD as internal standard for 1H NMR spectroscopy,
121.1, 117.7, 114.5, 113.1, 69.5, 55.5 ppm; IR (ATR) 휈̃ = 2934 (w), 2838
(w), 1655 (m), 1596 (s), 1507 (s), 1482 (m), 1447 (m), 1422 (m), 1330 (m)
cm–1; HRMS (EI): m/z calcd for C19H18O3 [M+] 294.1256; found 294.1265.
(E)-1-(2-Allyloxyphenyl)-3-(4-bromophenyl)prop-2-en-1-on
(11ac):
following the general procedure, 9a (176 mg, 1.00 mmol) and 10c (366
mg, 2.00 mmol) were converted to 11ac (281 mg, 0.82 mmol, 82%):
yellowish oil. 1H NMR (300 MHz, CDCl3):  = 7.67 (dd, J = 7.6, 1.7 Hz, 1H),
7.58 (d, J = 15.9 Hz, 1H), 7.53 – 7.39 (m, 6H), 7.04 (td, J = 7.5, 1.0 Hz,
1H), 6.97 (d, J = 8.3 Hz, 1H), 6.02 (ddt, J = 17.2, 10.2, 5.0 Hz, 1H), 5.41
(dm, J = 17.2 Hz, 1H), 5.24 (dm, J = 10.2 Hz, 1H), 4.62 (dm, J = 5.0 Hz,
2H) ppm; 13C NMR (75 MHz, CDCl3):  = 192.2, 157.4, 141.1, 134.2, 133.2,
132.7, 132.2, 130.8, 129.8, 129.5, 127.8, 124.4, 121.2, 117.9, 113.1, 69.4

=
3.31 ppm, [D4]methanol as internal standard for 13C NMR
spectroscopy,  = 49.2 ppm). IR measurements were carried out as ATR-
FTIR spectra. Wavenumbers (휈
) are given in cm1 and the peak intensities
̃
ppm; IR (ATR) 휈̃ = 3074 (w), 1656 (m), 1602 (s), 1484 (s), 1448 (s), 1401
(m), 1323 (m), 1235 (m) cm–1; HRMS (EI): m/z calcd for C18H1579BrO2 [M+]
342.0255; found 342.0263.
are denoted as: strong (s), medium (m), weak (w). High-resolution mass
spectra were obtained by ESI-TOF or EI-TOF. Microwave reactions were
carried out in an Anton-Paar-monowave-300 or an Anton-Paar-
monowave-400 reactor (monowave, maximum power 850 W, temperature
control by IR-sensor, vial volume 20 mL). These starting materials were
synthesized following literature procedures: 9a,[20] 9b,[22] 9c[70] and 10e.[71]
(E)-1-(2-Allyloxyphenyl)-3-(4-chlorphenyl)prop-2-en-1-on (11ad):[20]
following the general procedure, 9a (176 mg, 1.00 mmol) and 10d (280
mg, 2.00 mmol) were converted to 11ad (241 mg, 0.81 mmol, 81%):
yellowish oil. 1H NMR (300 MHz, CDCl3):  = 7.67 (dd, J = 7.6, 1.9 Hz, 1H),
7.60 (d, J = 15.9 Hz, 1H), 7.53 – 7.41 (m, 4H), 7.35 (d, J = 8.5 Hz, 2H),
7.05 (td, J = 7.5, 1.0 Hz, 1H), 6.99 (d, J = 8.3 Hz, 1H), 6.03 (ddt, J = 17.2,
10.3, 5.0 Hz, 1H), 5.41 (dm, J = 17.2 Hz, 1H), 5.25 (dm, J = 10.3 Hz, 1H),
4.64 (dm, J = 5.0 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3):  = 192.4,
157.4, 141.2, 136.2, 133.9, 133.2, 132.7, 130.8, 129.6, 129.3, 127.8,
General procedure for the synthesis of chalcones 11: A solution of the
appropriate acetophenone
9
(1.00 mmol) and the appropriate
benzaldehyde 10 (2.00 mmol) in ethanol (0.5 mL) was cooled to 0 °C. A
solution of NaOH (59 mg, 1.50 mmol) in water (0.26 mL) was added over
a period of 10 min. The mixture was warmed to ambient temperature and
stirred for 12 h. An aqueous solution of HCl (1 M, 1.00 mL) was added and
the mixture was diluted with MTBE (10 mL). The aqueous layer was
separated, extracted with MTBE (twice, 10 mL each) and the combined
organic extracts were dried with MgSO4, filtered and evaporated. The
residue was purified by chromatography on silica, using hexanes/MTBE
mixtures of increasing polarity as eluent, to furnish the chalcones 11.
121.3, 118.2, 117.9, 113.1, 69.5 ppm; IR (ATR) 휈̃ = 3073 (w), 1656 (m),
1602 (s), 1483 (s), 1448 (s), 1405 (w), 1324 (s), 1283 (m) cm–1; HRMS
(EI): m/z calcd for C18H1535ClO2 [M+] 298.0761; found 298.0771.
(E)-1-(2-Allyloxyphenyl)-3-(4-nitrophenyl)prop-2-en-1-on
(11ae):
following the general procedure, 9a (176 mg, 1.00 mmol) and 10e (302
mg, 2.00 mmol) were converted to 11ae (179 mg, 0.58 mmol, 58%):
yellowish solid; mp = 113 - 115 °C. 1H NMR (300 MHz, CDCl3):  = 8.23
(d, J = 8.9 Hz, 2H), 7.74 – 7.63 (5H), 7.49 (ddd, J = 8.4, 7.4, 1.8 Hz, 1H),
7.04 (td, J = 7.5, 1.0 Hz, 1H), 7.00 (d, J = 8.4 Hz, 1H), 6.04 (ddt, J = 17.2,
10.4, 5.1 Hz, 1H), 5.42 (dm, J = 17.2 Hz, 1H), 5.27 (dm, J = 10.4 Hz, 1H),
4.65 (dm, J = 5.1 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3):  = 191.6,
157.7, 148.5, 141.7, 139.0, 133.9, 132.6, 131.1, 131.0, 129.0, 128.9,
(E)-1-(2-Allyloxyphenyl)-3-phenylprop-2-en-1-on (11aa):[20] following
the general procedure, 9a (176 mg, 1.00 mmol) and 10a (212 mg, 2.00
mmol) were converted to 11aa (259 mg, 0.98 mmol, 98%): yellowish oil.
1H NMR (300 MHz, CDCl3): = 7.70 – 7.55 (m, 4H), 7.51 – 7.34 (m, 5H),
7.05 (td, J = 7.6, 1.0 Hz, 1H), 6.99 (d, J = 8.5 Hz, 1H), 6.04 (ddt, J = 15.6,
10.2, 5.0 Hz, 1H), 5.42 (dq, J = 17.3, 1.6 Hz, 1H), 5.25 (dq, J = 10.6, 1.5
Hz, 1H), 4.64 (d, J = 5.0 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3)  = 192.8,
157.6, 142.9, 135.3, 133.0, 132.8, 130.7, 130.3, 129.9, 129.0, 128.5,
124.2, 121.4, 118.2, 113.1, 69.6 ppm; IR (ATR): 휈̃ = 3108 (w), 3077 (w),
2869 (w), 1658 (m), 1595 (s), 1509 (s), 1481 (m), 1450 (m), 1424 (w), 1335
(s) cm–1; HRMS (EI): m/z calcd for C18H15O3N [M+] 309.1001; found
309.1011.
127.4, 121.2, 117.9, 113.2, 69.5 ppm; IR 휈̃ = 3026 (w), 1658 (m), 1600 (s),
1482 (m), 1448 (s), 1331 (m), 1289 (m), 1236 (m) cm–1; HRMS (EI): m/z
calcd for C18H16O2 [M+] 264.1150; found 264.1158.
(E)-1-(2-(Allyloxy)-4-(methoxymethoxy)phenyl)-3-(4-methoxyphenyl)-
prop-2-en-1-on (11bb): following the general procedure, 9b (236 mg, 1.00
mmol) and 10b (272 mg, 2.00 mmol) were converted to 11bb (336 mg,
0.95 mmol, 95%): yellowish oil. 1H NMR (300 MHz, CDCl3):  = 7.72 (d, J
= 8.6 Hz, 1H), 7.66 (d, J = 15.8 Hz, 1H), 7.53 (d, J = 8.8 Hz, 2H), 7.45 (d,
J = 15.8 Hz, 1H), 6.90 (d, J = 8.7 Hz, 2H), 6.71 (dd, J = 8.6, 2.1 Hz, 1H),
6.64 (d, J = 2.0 Hz, 1H), 6.05 (ddt, J = 15.7, 10.2, 5.1 Hz, 1H), 5.45 (dm, J
= 17.3 Hz, 1H), 5.27 (dm, J = 10.6 Hz, 1H), 5.21 (s, 2H), 4.62 (d, J = 5.0
Hz, 2H), 3.84 (s, 3H), 3.49 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3):  =
190.8, 161.6, 161.4, 159.2, 142.1, 132.7, 132.6, 130.1, 128.3, 125.3,
(E)-1-(2-(Allyloxy)-4-(methoxymethoxy)phenyl)-3-phenylprop-2-en-1-
on (11ba): following the general procedure, 9b (236 mg, 1.00 mmol) and
10a (212 mg, 2.00 mmol) were converted to 11ba (324 mg, 1.00 mmol,
quant.): yellowish oil. 1H NMR (300 MHz, CDCl3):  = 7.76 (d, J = 8.6 Hz,
1H), 7.70 (d, J = 15.8 Hz, 1H), 7.63 – 7.55 (m, 3H), 7.40 – 7.35 (m, 3H),
6.72 (d, J = 8.6 Hz, 1H), 6.65 (s, 1H), 6.05 (ddt, J = 15.7, 10.3, 5.1 Hz, 1H),
5.45 (d, J = 17.3 Hz, 1H), 5.27 (d, J = 10.6 Hz, 1H), 5.22 (s, 2H), 4.62 (d,
J = 4.9 Hz, 2H), 3.49 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3):  = 190.7,
161.8, 159.4, 142.0, 135.5, 132.8. 132.5, 130.0, 128.9, 128.4, 127.4,
123.5, 118.2, 108.4, 101.4, 94.4, 69.6, 56.3 ppm; IR (ATR) 휈̃ = 2902 (w),
123.8, 118.1, 114.4, 108.4, 101.5, 94.5, 69.6, 56.4, 55.5 ppm; IR (ATR): 휈
̃
1652 (m), 1603 (s), 1494 (m), 1448 (m), 1421 (m), 1330 (m), 1246 (m),
1151 (s), 986 (s) cm–1; HRMS (EI): m/z calcd for C20H20O4 [M+] 324.1362;
found 324.1376.
= 2933 (w), 2837 (w), 1650 (m), 1597 (s), 1509 (s), 1421 (m), 1246 (s),
1210 (m), 1170 (s), 1077 (m) cm–1; HRMS (EI): m/z calcd forC21H22O5 [M+]
354.1467; found 354.1477.
(E)-1-(2-Allyloxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-on (11ab):
following the general procedure, 9a (176 mg, 1.00 mmol) and 10b (272
6
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
(E)-1-(2-(Allyloxy)-4-(methoxymethoxy)phenyl)-3-(4-bromophenyl)-
prop-2-en-1-on (11bc): following the general procedure, 9b (236 mg, 1.00
mmol) and 10c (366 mg, 2.00 mmol) were converted to 11bc (386 mg,
0.96 mmol, 96%): yellowish oil. 1H NMR (300 MHz, CDCl3):  = 7.75 (d, J
= 8.6 Hz, 1H), 7.63 (d, J = 16.0 Hz, 1H), 7.57 (d, J = 16.0 Hz, 1H), 7.50 (d,
J = 8.6 Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H), 6.71 (dd, J = 8.6, 2.2 Hz, 1H),
6.64 (d, J = 2.1 Hz, 1H), 6.05 (ddt, J = 17.2, 10.4, 5.1 Hz, 1H), 5.44 (dm, J
= 17.2 Hz, 1H), 5.28 (dm, J = 10.6 Hz, 1H), 5.21 (s, 2H), 4.62 (d, J = 5.1
Hz, 2H), 3.49 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3):  = 190.2, 162.0,
159.5, 140.4, 134.6, 132.9, 132.5, 132.2, 129.8, 128.0, 124.2, 123.3,
temperature water (10 mL) and ethyl acetate (10 mL) were added to the
mixture. The organic layer was separated and the aqueous layer was
extracted twice with ethyl acetate (10 mL each). The combined organic
extracts were dried with MgSO4, filtered and evaporated. The residue was
purified by chromatography on silica, using hexanes / MTBE mixtures of
increasing polarity as eluents, to furnish the corresponding 8-allyl-flavan-
4-ones 12.
8-Allyl-2-phenylchroman-4-one (12aa):[20] following the general
procedure, 11aa (264 mg, 1.00 mmol) was converted to 12aa (177 mg,
0.67 mmol, 67%) and 13aa (32 mg, 0.12 mmol, 12%). Analytical data of
12aa: yellowish oil. 1H NMR (300 MHz, CDCl3):  = 7.84 (dd, J = 7.8, 1.6
Hz, 1H), 7.53 – 7.35 (m, 6H), 7.01 (t, J = 7.6 Hz, 1H), 6.06 – 5.91 (m, 1H),
5.50 (dd, J = 12.9, 3.3 Hz, 1H), 5.14 – 5.04 (m, 2H), 3.45 (d, J = 6.6 Hz,
2H), 3.03 (dd, J = 16.8, 12.9 Hz, 1H), 2.95 (dd, J = 16.8, 3.4 Hz, 1H) ppm;
13C NMR (75 MHz, CDCl3):  = 192.4, 159.5, 139.3, 136.4, 136.1, 129.6,
128.9, 128.7, 126.0, 125.3, 121.4, 121.1, 116.4, 79.4, 44.8, 34.0 ppm; IR
118.3, 108.5, 101.4, 94.4, 69.6, 56.4 ppm; IR (ATR) 휈̃ = 2926 (w), 1654
(m), 1603 (s), 1486 (m), 1421 (m), 1318 (m), 1247 (m), 1209 (m), 1152
(m), 1071 (m), 1007 (s) cm–1; HRMS (EI): m/z calcd for C20H1979BrO4 [M+]
402.0467; found 402.0476.
(E)-1-(2-(Allyloxy)-4-(methoxymethoxy)phenyl)-3-(4-chlorophenyl)-
prop-2-en-1-on (11bd): following the general procedure, 9b (236 mg, 1.00
mmol) and 10d (280 mg, 2.00 mmol) were converted to 11bd (347 mg,
0.97 mmol, 97%): yellowish oil. 1H NMR (300 MHz, CDCl3):  = 7.75 (d, J
= 8.6 Hz, 1H), 7.64 (d, J = 15.9 Hz, 1H), 7.56 (d, J = 15.9 Hz, 1H), 7.52 (d,
J = 8.6 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H), 6.72 (dd, J = 8.6, 2.2 Hz, 1H),
6.64 (d, J = 2.1 Hz, 1H), 6.05 (ddt, J = 17.2, 10.4, 5.1 Hz, 1H), 5.44 (dm, J
= 17.3 Hz, 1H), 5.28 (dm, J = 10.5 Hz, 1H), 5.22 (s, 2H), 4.62 (d, J = 5.1
Hz, 2H), 3.49 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3):  = 190.3, 162.0,
159.5, 140.4, 135.9, 134.1, 132.9, 132.5, 129.6, 129.2, 128.0, 123.3,
(ATR) 휈̃ = 3066 (w), 1689 (s), 1595 (s), 1475 (s), 1442 (s), 1298 (s), 1221
(s), 1070 (m) cm–1; HRMS (EI): m/z calcd for C18H16O2 [M+] 264.1150;
1
found 264.1155. Analytical data of 13aa:[5] yellowish solid. H NMR (400
MHz, CDCl3):  = 13.19 (s, 1H), 7.92 (d, J = 15.5 Hz, 1H), 7.82 (dd, J =
8.1, 1.2 Hz, 1H), 7.71 – 7.63 (m, 3H), 7.47 – 7.42 (m, 3H), 7.39 (dm, J =
7.4 Hz, 1H), 6.92 (t, J = 7.7 Hz, 1H), 6.07 (ddt, J = 16.9, 10.3, 6.6 Hz, 1H),
5.16 – 5.09 (m, 2H), 3.48 (d, J = 6.6 Hz, 2H) ppm; 13C NMR (100 MHz,
CDCl3):  = 194.1, 161.8, 145.4, 136.6, 136.3, 134.9, 131.0, 129.8, 129.2,
118.3, 108.5, 101.4, 94.5, 69.6, 56.4 ppm; IR (ATR) 휈
̃
= 2927 (w), 1654
128.8, 127.9, 120.7, 119.7, 118.5, 116.2, 33.7 ppm; IR (ATR): 휈̃ = 2923
(m), 1605 (s), 1490 (m), 1421 (m), 1321 (m), 1247 (m), 1208 (m), 1153
(m), 1079 (m), 1011 (s) cm–1; HRMS (EI): m/z calcd for C20H1935ClO4 [M+]
358.0972; found 358.0982.
(w), 1636 (s), 1594 (m), 1571 (s), 1476 (m), 1434 (m), 1345 (s), 1305 (m),
1231 (s), 1105 (m) cm–1; HRMS (EI): m/z calcd for C18H15O2 [M-H]+
263.1067; found 263.1061.
(E)-1-(2-(Allyloxy)-4-(methoxymethoxy)phenyl)-3-(4-(methoxy-
8-Allyl-7-(methoxymethoxy)-2-phenylchroman-4-one (12ba): following
the general procedure, 11ba (324 mg, 1.00 mmol) was converted to 12ba
(149 mg, 0.46 mmol, 46%): yellowish oil. H NMR (300 MHz, CDCl3):  =
7.84 (d, J = 8.8 Hz, 1H), 7.51 – 7.37 (m, 5H), 6.84 (d, J = 8.9 Hz, 1H), 5.94
(ddt, J = 16.3, 10.1, 6.3 Hz, 1H), 5.47 (dd, J = 12.6, 3.5 Hz, 1H), 5.27 (s,
2H), 5.06 – 4.94 (m, 2H), 3.48 (s, 3H), 3.48 (d, J = 6.3 Hz, 2H), 3.01 (dd, J
= 16.8, 12.6 Hz, 1H), 2.88 (dd, J = 16.8, 3.6 Hz, 1H) ppm; 13C NMR (75
MHz, CDCl3)  = 191.4, 161.0, 160.6, 139.4, 135.9, 128.9, 128.6, 126.6,
125.9, 117.0, 116.0, 115.0, 107.9, 94.1, 79.5, 56.5, 44.6, 27.5 ppm; IR
methoxy)phenyl)prop-2-en-1-on (11bf): following the general procedure,
9b (236 mg, 1.00 mmol) and 10f (332 mg, 2.00 mmol) were converted to
11bf (323 mg, 0.84 mmol, 84%): yellowish oil. 1H NMR (400 MHz, CDCl3):
 = 7.73 (d, J = 8.6 Hz, 1H), 7.65 (d, J = 15.8 Hz, 1H), 7.53 (d, J = 8.8 Hz,
2H), 7.46 (d, J = 15.8 Hz, 1H), 7.03 (d, J = 8.7 Hz, 1H), 6.71 (dd, J = 8.6,
2.2 Hz, 1H), 6.64 (d, J = 2.1 Hz, 1H), 6.05 (ddt, J = 17.1, 10.4, 5.1 Hz, 1H),
5.45 (dm, J = 17.3 Hz, 1H), 5.28 (dd, J = 10.6 Hz, 1H), 5.21 (s, 2H), 5.20
(s, 2H), 4.62 (d, J = 5.1 Hz, 2H), 3.49 (s, 3H), 3.48 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3):  = 190.8, 161.6, 159.3, 158.9, 141.9, 132.7, 132.6,
130.0, 129.3, 125.7, 123.7, 118.1, 116.6, 114.4, 108.4, 101.5, 94.4, 94.3,
1
(ATR) 휈̃ = 2906 (w), 1682 (s), 1596 (s), 1435 (m), 1256 (s), 1154 (m), 1110
(m), 1036 (m) cm–1; HRMS (EI): m/z calcd for C20H20O4 [M+] 324.1362;
69.6, 56.4, 56.3 ppm; IR (ATR) 휈
̃
= 2901 (w), 1650 (m), 1598 (s), 1508 (s),
found 324.1356.
1422 (m), 1239 (m), 1207 (m), 1149 (s), 1076 (s), 979 (s) cm–1; HRMS (EI):
m/z calcd for C22H24O6 [M+] 384.1573; found 384.1571.
8-Allyl-2-(4-methoxyphenyl)chroman-4-one (12ab):[44] following the
general procedure, 11ab (294 mg, 1.00 mmol) was converted to 12ab (194
mg, 0.66 mmol, 66%): yellowish oil. 1H NMR (600 MHz, CDCl3):  = 7.82
(dd, J = 7.9, 1.7 Hz, 1H), 7.41 (d, J = 8,7 Hz, 2H), 7.38 (dm, J = 7.4 Hz,
1H), 6.99 (dd, J = 7.6, 7.6 Hz, 1H), 6.96 (d, J = 8.9 Hz, 2H), 5.97 (ddt, J =
17.2, 10.6, 6.7 Hz, 1H), 5.43 (dd, J = 13.3, 2.9 Hz, 1H), 5.09 – 5.05 (m,
2H), 3.84 (s, 3H), 3.42 (d, J = 6.7 Hz, 2H), 3.06 (dd, J = 16.8, 13.3 Hz, 1H),
2.89 (dd, J = 16.8, 2.9 Hz, 1H) ppm; 13C NMR (150 MHz, CDCl3):  = 192.7,
159.9, 159.5, 136.3, 136.1, 131.2, 129.6, 127.5, 125.2, 121.2, 121.0,
1-(2-Allyloxy-4,6-bis(methoxymethoxy)phenyl)-3-(3,4-bis(methoxy-
methoxy)-phenyl)-prop-2-en-1-on (11ce): following the general
procedure, 9c (300 mg, 1.00 mmol) and 10e (452 mg, 2.00 mmol) were
converted to 11ce (420 mg, 0.83 mmol, 83%): yellowish oil. 1H NMR (300
MHz, CDCl3):  = 7.34 (s, 1H), 7.27 (d, J = 16.0 Hz, 1H), 7.15 – 7.09 (m,
2H), 6.86 (d, J = 16.0 Hz, 1H), 6.49 (d, J = 1.9 Hz, 1H), 6.35 (d, J = 2.0 Hz,
1H), 5.90 (ddt, J = 17.3, 10.3, 5.0 Hz, 1H), 5.30 (dm, J = 17.3 Hz, 1H), 5.24
(s, 2H), 5.22 (s, 2H), 5.16 (s, 2H), 5.16 (dm, J = 10.3 Hz, 1H), 5.09 (s, 2H),
4.49 (d, J = 5.1 Hz, 2H), 3.50 (s, 3H), 3.49 (s, 3H), 3.49 (s, 3H), 3.37 (s,
3H) ppm; 13C NMR (75MHz, CDCl3):  = 194.2, 159.7, 157.5, 156.0, 149.3,
147.4, 144.5, 132.7, 129.5, 128.0, 123.7, 117.5, 116.2, 116.0, 114.3, 96.3,
116.3, 114.2, 79.1, 55.5, 44.6. 34.0 ppm; IR (ATR): 휈̃ = 2905 (w), 2836 (w),
1687 (s), 1595 (s), 1514 (s), 1475 (m), 1443 (s), 1300 (s), 1249 (s) cm–1
HRMS (EI): m/z calcd for C19H18O3 [M+] 294.1256; found 294.1252.
;
95.6, 95.4, 95.2, 94.7, 94.7, 69.4, 56.4, 56.4, 56.3, 56.3 ppm; IR (ATR) 휈
̃
8-Allyl-2-(4-bromophenyl)chroman-4-one (12ac): following the general
procedure, 11ac (343 mg, 1.00 mmol) was converted to 12ac (261 mg,
0.76 mmol, 76%): yellowish oil. 1H NMR (300 MHz, CDCl3):  = 7.82 (dd,
J = 7.9, 1.7 Hz, 1H), 7.57 (d, J = 8.5 Hz, 2H), 7.43 – 7.33 (m, 3H), 7.01 (t,
J = 7.6 Hz, 1H), 5.97 (ddt, J = 17.1, 10.6, 6.6 Hz, 1H), 5.45 (dd, J = 12.5,
3.5 Hz, 1H), 5.13 – 5.01 (m, 2H), 3.43 (d, J = 6.7 Hz, 2H), 3.00 (dd, J =
16.8, 12.6 Hz, 1H), 2.90 (dd, J = 16.8, 3.6 Hz, 1H) ppm; 13C NMR (75 MHz,
CDCl3):  = 191.9, 159.2, 138.2, 136.5, 136.0, 132.1, 129.6, 127.7, 125.4,
= 2955 (w), 2919 (m), 2850 (w), 1648 (w), 1601 (w), 1508 (w), 1464 (w),
1433 (w), 1398 (w), 1256 (w), 1227 (w), 1151 (w), 1126 (w), 1072 (w) cm–
1; HRMS (EI): m/z calcd for C26H32O10 [M+] 504.1990; found 504.1980.
General procedure for the synthesis of 8-allyl-2-flavanones 12: A
solution of the appropriate chalcone 11 (1.00 mmol) in toluene (7 mL) was
placed in a vessel suited for microwave irradiation. The vial was sealed,
placed in a microwave reactor and irradiated at 250 °C for 1 h. The solvent
was evaporated and the residue redissolved in methanol (10 mL). NaOAc
(0.82 g, 10.0 mmol) was added, the vial was sealed, again placed in a
microwave reactor and irradiated at 100 °C for 1 h. After cooling to ambient
122.7, 121.6, 121.0, 116.4, 78.7, 44.6, 34.0 ppm; IR (ATR): 휈
2901 (w), 1689 (s), 1595 (s), 1475 (s), 1445 (s), 1300 (s), 1219 (m) cm–1
HRMS (EI): m/z calcd for C18H1579BrO2 [M+] 342.0255; found 342.0263.
̃ = 3078 (w),
;
7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
8-Allyl-2-(4-chlorophenyl)chroman-4-one (12ad):[20] following the
general procedure, 11ad (298 mg, 1.00 mmol) was converted to 12ac (158
mg, 0.53 mmol, 53%): yellowish oil. 1H NMR (600 MHz, CDCl3):  = 7.82
(dd, J = 7.9, 1.8 Hz, 1H), 7.43 (d, J = 8.7 Hz, 2H), 7.41 (d, J = 8.7 Hz, 2H),
7.40 (dm, J = 7.5 Hz, 1H), 7.01 (t, J = 7.6 Hz, 1H), 5.97 (ddt, J = 17.0, 10.2,
6.6 Hz, 1H), 5.46 (dd, J = 13.2, 3.1 Hz, 1H), 5.10 – 5.05 (2H), 3.43 (d, J =
6.6 Hz, 2H), 3.01 (dd, J = 16.8, 13.2 Hz, 1H), 2.91 (dd, J = 16.8, 3.1 Hz,
1H) ppm; 13C NMR (75 MHz, CDCl3):  = 192.0, 159.2, 137.7, 136.5, 136.0,
134.5, 129.5, 129.1, 127.4, 125.3, 121.6, 120.9, 116.4, 78.6, 44.6, 34.0
1.00 mmol) was converted to 12bf (230 mg, 0.60 mmol, 60%): yellowish
oil. 1H NMR (400 MHz, [D6]acetone):  = 7.74 (d, J = 8.8 Hz, 1H), 7.52 (d,
J = 8.9 Hz, 2H), 7.11 (d, J = 8.9 Hz, 2H), 6.89 (d, J = 8.8 Hz, 1H), 5.93
(ddt, J = 17.0, 10.1, 6.3 Hz, 1H), 5.55 (dd, J = 12.7, 3.2 Hz, 1H), 5.33 (s,
2H), 5.23 (s, 2H), 4.99 (dq, J = 17.0, 1.8 Hz, 1H), 4.92 (dq, J = 10.1, 1.8
Hz, 1H), 3.45 (s, 3H), 3.45 (s, 3H), 3.43 (dm, J = 6.4 Hz, 2H), 3.05 (dd, J
= 16.8, 12.7 Hz, 1H), 2.85 – 2.77 (m, 3H) ppm; 13C NMR (100 MHz,
[D6]acetone):  = 191.1, 161.5, 161.2, 158.4, 136.8, 133.7, 128.5, 126.7,
117.4, 117.1, 116.7, 115.2, 108.5, 95.1, 94.9, 80.1, 56.5, 56.1, 44.6, 28.0
ppm; IR (ATR): 휈
̃
= 3076 (w), 2905 (w), 1688 (s), 1596 (s), 1492 (m), 1475
ppm; IR (ATR): 휈̃ = 2902 (w), 2827 (w), 1682 (m), 1596 (s), 1511 (m), 1438
(m), 1233 (s), 1150 (s) cm–1; HRMS (EI): m/z calcd for C22H24O6 [M+]
(s), 1444 (s), 1299 (s) cm–1; HRMS (EI): m/z calcd for C18H1535ClO2 [M+]
298.0761; found 298.0766.
384.1573; found 384.1569.
8-Allyl-2-(4-nitrophenyl)chroman-4-one (12ae): following the general
procedure, 11ae (309 mg, 1.00 mmol) was converted to 12ae (204 mg,
0.66 mmol, 66%): orange-yellow solid, mp = 83 - 86 °C. 1H NMR (400 MHz,
CDCl3):  = 8.31 (d, J = 8.8 Hz, 2H), 7.83 (dd, J = 7.9, 1.7 Hz, 1H), 7.68
(d, J = 8.4 Hz, 2H), 7.43 (dd, J = 7.3, 1.7 Hz, 1H), 7.04 (t, J = 7.6 Hz, 1H),
5.98 (ddt, J = 17.0, 10.1, 6.6 Hz, 1H), 5.60 (dd, J = 11.9, 4.4 Hz, 1H), 5.12
– 5.05 (m, 2H), 3.46 (d, J = 6.2 Hz, 2H), 3.00 (dd, J = 16.8, 11.9 Hz, 1H),
2.96 (dd, J = 16.8, 3.9 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3):  = 191.1,
158.8, 148.0, 146.2, 136.8, 135.8, 129.5, 126.7, 125.4, 124.2, 122.0,
8-Allyl-5,7-bis(methoxymethoxy)-2-(3,4-bis(methoxymethoxy)-
phenyl)-chroman-4-one (12ce) and (E)-1-(3-allyl-2-hydroxy-4,6-
bis(methoxymethoxy))-3-(3,4-bis(methoxy-methoxy)-phenyl)-prop-2-
ene-1-one (13ce): following the general procedure, 11ce (252 mg, 0.50
mmol) was converted to 12ce (107 mg, 0.21 mmol, 42%) and 13ce (62
mg, 0.12 mmol, 25%). The products were separated by column
chromatography on silica, using hexanes-MTBE mixtures of increasing
polarity as eluents. Analytical data of 12ce: yellowish oil. 1H NMR (300
MHz, CDCl3):  = 7.30 (d, J = 2.1 Hz, 1H), 7.19 (d, J = 8.4 Hz, 1H), 7.04
(dd, J = 8.5, 2.1 Hz, 1H), 6.58 (s, 1H), 5.93 (ddt, J = 16.4, 10.0, 6.2 Hz,
1H), 5.35 (dd, J = 12.8, 3.2 Hz, 1H), 5.27 (s, 2H), 5.25 (s, 2H), 5.25 (s, 2H),
5.24 (s, 2H), 5.07 – 4.90 (m, 2H), 3.56 – 3.50 (m, 9H), 3.47 (s, 3H), 3.38
(d, J = 6.0 Hz, 2H), 2.96 (dd, J = 16.5, 12.9 Hz, 1H), 2.81 (dd, J = 16.5, 3.3
Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3):  = 189.9, 161.2, 160.7, 158.0,
147.5, 147.3, 136.3, 133.6, 119.9, 116.7, 114.7, 114.6, 110.8, 107.6, 96.0,
95.6, 95.5, 95.5, 94.2, 78.3, 56.6, 56.5, 56.3, 56.3, 45.9, 27.3 ppm; IR
121.0,116.5, 78.2, 44.6, 34.0 ppm; IR (ATR): 휈̃ = 3079 (w), 2913 (w), 1689
(s), 1597 (s), 1518 (s), 1475 (m), 1446 (m), 1344 (s), 1299 (m), 1291(m)
cm–1; HRMS (EI): m/z calcd for C18H15NO4 [M+] 309.1001; found 309.1004.
8-Allyl-7-(methoxymethoxy)-2-(4-methoxyphenyl)chroman-4-one
(12bb): following the general procedure, 11bb (354 mg, 1.00 mmol) was
converted to 12bb (219 mg, 0.62 mmol, 62%): yellowish oil. 1H NMR (300
MHz, CDCl3):  = 7.82 (d, J = 8.9 Hz, 1H), 7.40 (d, J = 8.7 Hz, 2H), 6.95
(d, J = 8.7 Hz, 2H), 6.82 (d, J = 8.9 Hz, 1H), 5.92 (ddt, J = 16.8, 10.0, 6.3
Hz, 1H), 5.41 (dd, J = 12.7, 3.1 Hz, 1H), 5.26 (s, 2H), 5.05 – 4.92 (2H),
3.83 (s, 3H), 3.47 (s, 3H), 3.44 (d, J = 6.3 Hz, 2H), 3.01 (dd, J = 16.8, 12.7
Hz, 1H), 2.85 (dd, J = 16.8, 3.2 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3):
 = 191.6, 161.0, 160.7, 159.9, 136.0, 131.4, 127.5, 126.6, 117.0, 116.0,
(ATR): 휈̃ = 3344 (br), 2930 (m), 1606 (s), 1509 (m), 1437 (m), 1261 (m),
1151 (s), 1061 (s), 988 (s), 920 (s), 818 (w) cm–1; HRMS (EI): m/z calcd
for C26H32O10 [M+] 504.1995; found 504.1991. Analytical data of 13ce:
1
yellowish solid, mp 111 – 113 °C; H NMR (400 MHz, CDCl3):  = 13.94
(s, 1H), 7.85 (d, J = 15.6 Hz, 1H), 7.73 (d, J = 15.5 Hz, 1H), 7.50 (d, J =
1.8 Hz, 1H), 7.21 (dd, J = 8.4, 1.9 Hz, 1H), 7.17 (d, J = 8.4 Hz, 1H), 6.42
(s, 1H), 5.96 (ddt, J = 16.2, 10.0, 6.0 Hz, 1H), 5.29 (s, 2H), 5.28 (s, 2H),
5.27 (s, 2H), 5.24 (s, 2H), 5.02 (dq, J = 17.0, 1.9 Hz, 1H), 4.95 (dq, J =
10.0, 1.9 Hz, 1H), 3.53 (s, 3H), 3.53 (s, 3H), 3.52 (s, 3H), 3.47 (s, 3H), 3.39
(dm, J = 6.1 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3):  = 193.2, 164.1,
160.9, 158.7, 149.2, 147.6, 142.2, 136.5, 130.1, 126.4, 124.2, 116.3,
115.4, 114.3, 110.2, 107.7, 95.6, 95.4, 95.3, 94.0, 92.2, 56.9, 56.5, 56.5,
114.9, 114.2, 107.8, 94.2, 79.3, 56.5, 55.5, 44.3, 27.5 ppm; IR (ATR): 휈̃ =
2907 (w), 2835 (w), 1681 (s), 1595 (s), 1514 (s), 1438 (m), 1334 (m), 1252
(s) cm–1; HRMS (EI): m/z calcd for C21H22O5 [M+] 354.1467; found
354.1473.
8-Allyl-2-(4-bromophenyl)-7-(methoxymethoxy)chroman-4-one
(12bc): following the general procedure, 11bc (403 mg, 1.00 mmol) was
converted to 12bc (193 mg, 0.48 mmol, 48%): yellowish oil. 1H NMR (300
MHz, CDCl3):  = 7.82 (d, J = 8.9 Hz, 1H), 7.56 (d, J = 8.5 Hz, 2H), 7.35
(d, J = 8.3 Hz, 2H), 6.84 (d, J = 8.9 Hz, 1H), 5.92 (ddt, J = 17.0, 10.1, 6.2
Hz, 1H), 5.42 (dd, J = 12.1, 3.8 Hz, 1H), 5.26 (s, 2H), 5.04 – 4.92 (m, 2H),
3.47 (s, 3H), 3.45 (dm, J = 6.4 Hz, 2H), 2.95 (dd, J = 16.8, 12.1 Hz, 1H),
2.85 (dd, J = 16.8, 3.8 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3):  = 190.9,
161.1, 160.3, 138.4, 135.8, 132.0, 127.7, 126.7, 122.5, 117.0, 115.9,
56.4, 26.8 ppm; IR (ATR): 휈̃ = 3299 (br), 2921 (m), 1595 (s), 1514 (m),
1445 (m), 1284 (m), 1111 (m), 984 (m), 814 (w), 631 (w) cm–1; HRMS (EI):
m/z calcd for C26H32O10 [M+] 504.1995; found 504.1986.
General procedure for the synthesis of 8-prenyl-2-arylflavan-4-ones
14: method 1: To a solution of the corresponding 8-allyl flavan-4-one 12
(1.00 mmol) in CH2Cl2 (5 mL) was added 2-methyl-2-butene (11.60 mL,
110.0 mmol) and second generation Grubbs’ catalyst A (42 mg, 5.0
mol %). The mixture was stirred at ambient temperature for 16 h, all
volatiles were evaporated and the residue was purified by chromatography
on silica, using hexanes / MTBE mixtures of increasing polarity as eluents,
to furnish the corresponding 8-prenyl-flavan-4-ones 14. Method 2: To a
solution of the corresponding 8-allyl flavan-4-one 12 (1.00 mmol) in CH2Cl2
(5 mL) was added 2-methyl-2-butene (11.60 mL, 110.0 mmol) and second
generation Grubbs’ catalyst A (42 mg, 5.0 mol %). The mixture was stirred
at ambient temperature for 16 h, all volatiles were evaporated and the
residue was redissolved in methanol (20 mL). Aq. HCl (3 M, 0.10 mL) was
added and the solution was heated to 65 °C for 1 h. After cooling to
ambient temperature the mixture was diluted with water (30 mL) and
extracted with ethyl acetate (3 times, 30 mL each). The combined organic
extracts were dried with MgSO4, filtered and evaporated. The residue was
purified by chromatography on silica, using hexanes / MTBE mixtures of
increasing polarity as eluents, to furnish the corresponding deprotected 8-
prenyl-flavan-4-ones 14.
115.0, 108.1, 94.1, 78.9, 56.5, 44.4, 27.5 ppm; IR (ATR) 휈̃ = 2905 (w),
1682 (m), 1594 (s), 1488 (m), 1437 (m), 1256 (m), 1199 (m), 1154 (m) cm–
1; HRMS (EI): m/z calcd for C20H1979BrO4 [M+] 402.0467; found 402.0461.
8-Allyl-2-(4-Chlorophenyl)-7-(methoxymethoxy)chroman-4-one
(12bd):[45] following the general procedure, 11bd (358 mg, 1.00 mmol) was
converted to 12bd (179 mg, 0.50 mmol, 50%): yellowish oil. 1H NMR (300
MHz, CDCl3):  = 7.82 (d, J = 8.9 Hz, 1H), 7.44 – 7.38 (m, 4H), 6.84 (d, J
= 8.9 Hz, 1H), 5.92 (ddt, J = 17.0, 10.1, 6.2 Hz, 1H), 5.44 (dd, J = 12.2, 3.8
Hz, 1H), 5.26 (s, 2H), 5.04 – 4.93 (m, 2H), 3.47 (s, 3H), 3.45 (dm, J = 6.1
Hz, 2H), 2.96 (dd, J = 16.8, 12.2 Hz, 1H), 2.86 (dd, J = 16.8, 3.8 Hz, 1H)
ppm; 13C NMR (125 MHz, CDCl3):  = 190.9, 161.1, 160.3, 137.8, 135.8,
134.4, 129.1, 127.4, 126.7, 117.0, 115.9, 115.0, 108.1, 94.1, 78.8, 56.5,
44.4, 27.5 ppm; IR (ATR): 휈̃ = 2906 (w), 1682 (s), 1595 (s), 1492 (m), 1437
(m), 1256 (m), 1199 (m), 1154 (m) cm–1; HRMS (EI): m/z calcd for
C20H1935ClO4 [M+] 358.0972; found 358.0970.
8-(3-Methylbut-2-en-1-yl)2-phenylchroman-4-one (14aa):[46] following
the general procedure, method 1, 12aa (264 mg, 1.00 mmol) was
8-Allyl-7-(methoxymethoxy)-2-(4-(methoxymethoxy)phenyl)-
chroman-4-one (12bf):[45] following the general procedure, 11bf (384 mg,
8
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
converted to 14aa (245 mg, 0.84 mmol, 84%): yellowish oil. 1H NMR (300
MHz, CDCl3):  = 7.80 (dm, J = 7.9 Hz, 1H), 7.54 – 7.35 (m, 6H), 6.99 (t, J
= 7.6 Hz, 1H), 5.50 (dd, J = 12.9, 3.2 Hz, 1H), 5.30 (t, J = 7.4 Hz, 1H), 3.38
(d, J = 7.3 Hz, 2H), 3.05 (dd, J = 16.8, 12.9 Hz, 1H), 2.95 (dd, J = 16.8, 3.2
Hz, 1H), 1.75 (s, 3H), 1.64 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3):  =
192.5, 159.5, 139.3, 136.0, 133.4, 131.1, 128.9, 128.7, 126.1, 124.9,
1H), 7.04 (t, J = 7.6 Hz, 1H), 5.85 (dd, J = 12.6, 3.5 Hz, 1H), 5.32 (tm, J =
7.4 Hz, 1H), 3.41 (d, J = 7.4 Hz, 2H), 3.13 (dd, J = 16.8, 12.6 Hz, 1H), 3.00
(dd, J = 16.8, 3.5 Hz, 1H), 1.72 (s, 3H), 1.65 (s, 3H) ppm; 13C NMR (75
MHz, [D6]acetone):  = 191.3, 159.7, 148.8, 147.8, 136.6, 133.6, 131.7,
128.2, 125.2, 124.6, 122.7, 122.2, 121.8, 79.1, 44.7, 28.9, 25.9, 17.9 ppm;
IR (ATR): 휈̃ = 2970 (w), 2913 (w), 1688 (s), 1595 (s), 1519 (s), 1475 (s),
121.8, 121.0, 120.8, 79.4, 44.8, 28.3, 25.9, 17.9 ppm; IR (ATR): 휈
̃
= 2912
1442 (s), 1344 (s), 1303 (s), 1220 (m) cm–1; HRMS (EI): m/z calcd for
(w) 1689 (s), 1595 (m), 1475 (m), 1440 (m), 1304 (m), 1221 (m), 1071(m)
cm–1; HRMS (EI): m/z calcd for C20H20O2 [M+] 292.1463; found 292.1467.
C20H19NO4 [M+] 337.1314; found 337.1316.
7-Hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)chroman-4-
one (Lespeflorin A2, 4):[50] following the general procedure, method 2,
12bb (354 mg, 1.00 mmol) was converted to 4 (260 mg, 0.77 mmol, 77%):
yellowish solid, mp 85 – 87 °C. 1H NMR (400 MHz, CDCl3):  = 11.60 (s,
1H), 7.39 (dm, J = 8.8 Hz, 2H), 7.26 (d, J = 8.7 Hz, 1H), 6.96 (dm, J = 8.8
Hz, 2H), 6.48 (d, J = 8.7 Hz, 1H), 5.41 (dd, J = 12.9, 3.1 Hz, 1H), 5.23 (tm,
J = 7.2 Hz, 1H), 3.83 (s, 3H), 3.23 (d, J = 7.1 Hz, 2H), 3.12 (dd, J = 16.9,
12.9 Hz, 1H), 2.87 (dd, J = 16.9, 3.1 Hz, 1H), 1.73 (s, 3H), 1.62 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3):  = 198.6, 160.3, 160.0, 158.6, 138.7,
132.9, 130.8, 127.6, 122.2, 120.1, 114.2, 109.0, 108.1, 78.6, 55.5, 43.8,
7-Hydroxy-8-(3-methylbut-2-en-1-yl)-2-phenylchroman-4-one
(14ba):[47] following the general procedure, method 2, 12ba (324 mg, 1.00
mmol) was converted to 14ba (225 mg, 0.73 mmol, 73%): yellowish oil. 1H
NMR (400 MHz, CDCl3):  = 7.76 (d, J = 8.7 Hz, 1H), 7.51 – 7.36 (m, 5H),
6.56 (d, J = 8.7 Hz, 1H), 6.25 (s(br.), 1H), 5.47 (dd, J = 12.9, 3.2 Hz, 1H),
5.26 (t, J = 7.2 Hz, 1H), 3.43 (d, J = 7.1 Hz, 2H), 3.02 (dd, J = 16.8, 12.9
Hz, 1H), 2.87 (dd, J = 16.8, 3.3 Hz, 1H), 1.74 – 1.71 (m, 6H) ppm; 13C NMR
(100 MHz, CDCl3):  = 191.9, 161.9, 161.1, 139.3, 134.7, 128.9, 128.7,
126.6, 126.1, 121.3, 115.1, 114.9, 110.8, 79.7, 44.3, 26.0, 22.4, 18.0 ppm;
IR (ATR): 휈
̃
= 3224 (br), 2968 (w), 2926 (w), 1657 (m), 1583 (s), 1438 (s),
27.6, 25.9, 17.9 ppm; IR (ATR): 휈̃ = 3282 (br), 2982 (w), 1733 (w), 1675
1368 (m), 1335 (m), 1279 (s), 1218 (m) cm–1; HRMS (EI): m/z calcd for
(w), 1588 (m), 1515 (m), 1441 (m), 1373 (m), 1373 (w), 1250 (m) cm–1
;
C20H20O3 [M+ 308.1412; found 308.1417.
HRMS (EI): m/z calcd for C21H22O4 [M+] 338.1518; found 338.1522.
2-(4-Methoxyphenyl)-8-(3-methylbut-2-en-1-yl)chroman-4-one (14ab):
following the general procedure, method 1, 12ab (294 mg, 1.00 mmol) was
converted to 14ab (306 mg, 0.95 mmol, 95%): yellowish oil. 1H NMR (300
MHz, [D6]acetone):  = 7.70 (dd, J = 7.8, 1.8 Hz, 1H), 7.52 (d, J = 8.4 Hz,
2H), 7.42 (dm, J = 7.3 Hz, 1H), 7.04 – 6.98 (m, 3H), 5.55 (dd, J = 12.9, 3.0
Hz, 1H), 5.29 (tm, J = 7.4 Hz, 1H), 3.83 (s, 3H), 3.43 (d, J = 7.3 Hz, 2H),
3.13 (dd, J = 16.8, 12.9 Hz, 1H), 2.83 (dd, J = 16.8, 3.0 Hz, 1H), 1.70 (s,
3H), 1.62 (s, 3H) ppm; 13C NMR (125 MHz, [D6]acetone):  = 192.3, 160.8,
160.3, 136.3, 133.4, 132.4, 131.7, 128.7, 125.1, 122.8, 121.8, 121.7,
2-(4-Bromophenyl)-7-hydroxy-8-(3-methylbut-2-en-1-yl)chroman-4-
on (14bc): following the general procedure, method 2, 12bc (403 mg, 1.00
mmol) was converted to 14bc (263 mg, 0.68 mmol, 68%): yellowish solid,
mp 162 – 164 °C. 1H NMR (300 MHz, CDCl3):  = 7.74 (d, J = 8.7 Hz, 1H),
7.55 (dm, J = 8.5 Hz, 2H), 7.35 (dm, J = 8.2 Hz, 2H), 6.82 (s, 1H), 6.58 (d,
J = 8.7 Hz, 1H), 5.43 (dd, J = 12.9, 3.1 Hz, 1H), 5.24 (tm, J = 7.2 Hz, 1H),
3.41 (d, J = 7.2 Hz, 2H), 2.96 (dd, J = 16.9, 12.9 Hz, 1H), 2.84 (dd, J =
16.9, 3.2 Hz, 1H), 1.73 (d, J = 1.0 Hz, 3H), 1.72 (d, J = 1.3 Hz, 3H) ppm;
13C NMR (75 MHz, CDCl3):  = 191.4, 161.9, 160.8, 138.2, 134.9, 132.0,
127.8, 126.7, 122.6, 121.2, 115.0, 114.9, 111.0, 79.0, 44.1, 26.0, 22.4,
114.7, 79.9, 55.6, 44.7, 28.9, 25.9, 17.9 ppm; IR (ATR): 휈̃ = 2965 (w), 1687
(s), 1593 (s), 1514 (s), 1475 (s), 1440 (s), 1303 (s), 1250 (s), 1175 (s) cm–
18.1 ppm; IR (ATR): 휈̃ = 3227 (br), 2925 (w), 1660 (m), 1586 (s), 1489 (m),
1; HRMS (EI): m/z calcd for C21H22O3 [M+] 322.1569; found 322.1559.
1441 (s), 1284 (s), 1095 (m), 1067 (m), 1010 (m), 906 (m) cm–1; HRMS
(EI): m/z calcd for C20H1979BrO3 [M+] 386.0518; found 386.0527.
2-(4-Bromophenyl)-8-(3-methylbut-2-en-1-yl)chroman-4-on
(14ac):
following the general procedure, method 1, 12ac (343 mg, 1.00 mmol) was
converted to 14ac (371 mg, 1.00 mmol, quant.): yellowish oil. 1H NMR (300
MHz, [D6]acetone):  = 7.70 (dd, J = 7.8, 1.8 Hz, 1H), 7.65 (dm, J = 8.7 Hz,
2H), 7.57 (dm, J = 8.7 Hz, 2H), 7.44 (dm, J = 7.4 Hz, 1H), 7.01 (t, J = 7.6
Hz, 1H), 5.65 (dd, J = 12.9, 3.1 Hz, 1H), 5.30 (tm, J = 7.4 Hz, 1H), 3.37 (d,
J = 7.4 Hz, 2H), 3.10 (dd, J = 16.8, 12.9 Hz, 1H), 2.89 (dd, J = 16.8, 3.1
Hz, 1H), 1.71 (s, 3H), 1.64 (s, 3H) ppm; 13C NMR (75 MHz, [D6]acetone):
 = 191.7, 159.9, 139.9, 136.4, 133.4, 132.5, 131.7, 129.2, 125.1, 122.7,
2-(4-Chlorophenyl)-7-hydroxy-8-(3-methylbut-2-en-1-yl)chroman-4-
on (14bd): following the general procedure, method 2, 12bd (358 mg, 1.00
mmol) was converted to 14bd (212 mg, 0.62 mmol, 62%): yellowish solid,
mp 128 – 130 °C. 1H NMR (300 MHz, [D6]acetone):  = 9.30 (s, 1H), 7.63
(dm, J = 8.6 Hz, 2H), 7.60 (d, J = 8.6 Hz, 1H), 7.49 (d, J = 8.6 Hz, 2H),
6.65 (d, J = 8.6 Hz, 1H), 5.59 (dd, J = 12.9, 3.1 Hz, 1H), 5.24 (tm, J = 7.3
Hz, 1H), 3.36 (d, J = 7.1 Hz, 2H), 2.99 (dd, J = 16.8, 12.6 Hz, 1H), 2.79
(dd, J = 16.8, 3.2 Hz, 1H), 1.64 (s, 3H), 1.63 (s, 3H) ppm; 13C NMR (75
MHz, [D6]acetone):  = 190.3, 162.3, 161.6, 139.8, 134.4, 131.8, 129.5,
128.9, 126.4, 123.1, 116.6, 115.4, 110.7, 79.7, 44.6, 25.9, 22.8, 18.0 ppm;
122.6, 122.0, 121.8, 79.4, 44.7, 28.9, 25.9, 17.9 ppm; IR (ATR): 휈̃ = 2967
(w), 2912 (w), 1689 (s), 1594 (s), 1489 (m), 1475 (s), 1441 (s), 1304 (s),
1219 (s), 1070 (s) cm–1; HRMS (EI): m/z calcd for C20H1979BrO2 [M+]
370.0568; found 370.0560.
IR (ATR): 휈̃ = 3180 (br), 2924 (w), 1655 (w), 1585 (s), 1492 (m), 1441 (s),
1334 (m), 1278 (s), 1092 (m), 1068 (m), 1044 (m) cm–1; HRMS (EI): m/z
calcd for C20H1935ClO3 [M+] 342.1023; found 342.1034.
2-(4-Chlorophenyl)-8-(3-methylbut-2-en-1-yl)chroman-4-on
(14ad):
following the general procedure, method 1, 12ad (298 mg, 1.00 mmol) was
converted to 14ad (290 mg, 0.89 mmol, 89%): yellowish oil. 1H NMR (400
MHz, CDCl3):  = 7.79 (dd, J = 7.8, 1.8 Hz, 1H), 7.46 – 7.36 (m, 5H), 6.99
(dd, J = 7.5, 7.5 Hz, 1H), 5.47 (dd, J = 12.9, 3.1 Hz, 1H), 5.27 (tm, J = 7.4
Hz, 1H), 3.37 (d, J = 7.4 Hz, 2H), 3.10 (dd, J = 16.8, 12.9 Hz, 1H), 2.89
(dd, J = 16.8, 3.1 Hz, 1H), 1.71 (s, 3H), 1.63 (s, 3H) ppm; 13C NMR (100
MHz, CDCl3)  = 192.1, 159.3, 137.8, 136.2, 134.5, 133.5, 131.1, 129.1,
127.5, 124.9, 121.6, 121.5, 120.9, 78.6, 44.6, 28.3, 25.9, 18.0 ppm; IR
7-Hydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-en-1-yl)chroman-4-
one (Isobavachin, 2):[16] following the general procedure, method 2, 12bf
(384 mg, 1.00 mmol) was converted to 2 (201 mg, 0.62 mmol, 62%):
yellowish oil. 1H NMR (400 MHz, CDCl3):  = 11.65 (s, 1H), 7.35 (d, J = 8.5
Hz, 2H), 7.29 (dm, J = 8.9 Hz, 1H), 6.90 (dm, J = 8.5 Hz, 2H), 6.51 (d, J =
8.6 Hz, 1H), 6.08 (s(br.), 1H), 5.41 (dd, J = 13.1, 2.9 Hz, 1H), 5.23 (tm, J =
7.3 Hz, 1H), 3.24 (d, J = 7.3 Hz, 2H), 3.14 (dd, J = 17.1, 13.1 Hz, 1H), 2.90
(dd, J = 17.1, 3.0 Hz, 1H), 1.74 (s, 3H), 1.63 (s, 3H) ppm; 13C NMR (100
MHz, CDCl3):  = 199.0, 160.1, 158.7, 156.3, 138.9, 133.0, 130.7, 127.8,
122.1, 120.3, 115.7, 108.9, 108.1, 78.6, 43.7, 27.6, 25.9, 17.9 ppm; IR
(ATR): 휈̃ = 2968 (w), 2913 (w), 1688 (s), 1595 (s), 1492 (m), 1475 (s), 1440
(s), 1304 (s), 1220 (s), 1072 (s) cm–1; HRMS (EI): m/z calcd for
C20H1935ClO2 [M+] 326.1074; found 326.1073.
(ATR): 휈̃ = 3251 (br), 2924 (w), 1689 (w), 1654 (w), 1585 (s), 1516 (m),
1438 (s), 1334 (m), 1246 (s), 1168 (s) cm–1; HRMS (EI): m/z calcd for
C20H20O4 [M+] 324.1362; found 324.1354.
8-(3-Methylbut-2-en-1-yl)-2-(4-nitrophenyl)chroman-4-on
(14ae):
following the general procedure, method 1, 12ae (309 mg, 1.00 mmol) was
converted to 14ae (307 mg, 0.91 mmol, 91%): yellowish solid, mp 78 –
80 °C. 1H NMR (300 MHz, [D6]acetone):  = 8.34 (dm, J = 8.8 Hz, 2H) 7.93
(dm, J = 8.8 Hz, 2H), 7.72 (dd, J = 7.8, 1.8 Hz, 1H), 7.47 (dm, J = 7.4 Hz,
8-Prenyl-5,7-bis(methoxymethoxy)-2-(3,4-bis(methoxymethoxy)-
phenyl)-chroman-4-one (14ce): following the general procedure, method
1, 12ce (200 mg, 0.40 mmol) was converted to 14ce (160 mg, 0.30 mmol,
9
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
1
76%): yellowish oil. H NMR (400 MHz, CDCl3):  = 7.28 (d, J = 2.1 Hz,
4H,8H-pyrano[2,3-f]chromen-4-one (19): following the general
procedure for the microwave promoted synthesis of 8-allylflavanones 12,
compound 17 (346 mg, 1.00 mmol) was converted to a 1 : 1 mixture of the
linear product 18 and the angular product 19. Separation of the products
was achieved by column chromatography on silica, using hexanes / MTBE
mixtures of increasing polarity, to furnish 18 (65 mg, 0.19 mmol, 19%) and
19 (78 mg, 0.23 mmol, 22%). Analytical data of 18: yellowish oil. 1H NMR
(600 MHz, CDCl3):  = 7.50 (s, 1H, H5), 7.47 (dm, J = 7.1 Hz, 2H, o-H(Ph)),
7.43 (tm, J = 7.3 Hz, m-H(Ph)), 7.37 (tt, J = 7.2, 1.4 Hz, 1H, p-H(Ph)), 6.33
(d, J = 9.9 Hz, 1H, H4), 5.92 (ddt, J = 16.5, 10.0, 6.5 Hz, 1H, CH=CH2),
5.61 (d, J = 9.9 Hz, 1H, H3), 5.46 (dd, J = 13.0, 3.1 Hz, 1H, H8), 5.04 (dq,
J = 17.0, 1.4 Hz, 1H, =CHHtrans), 4.97 (dq, J = 10.1, 1.5 Hz, 1H, =CHHcis),
3.42 (ddt, J = 14.3, 6.4, 1.5 Hz, -CHHCH=), 3.38 (ddt, J = 14.3, 6.4, 1.5
Hz, -CHHCH=), 2.98 (dd, J = 16.9, 13.1 Hz, 1H, H7trans), 2.86 (dd, J = 16.9,
1H), 7.17 (d, J = 8.4 Hz, 1H), 7.04 (dd, J = 8.4, 2.2 Hz, 1H), 6.56 (s, 1H),
5.33 (dd, J = 13.0, 2.9 Hz, 1H), 5.26 – 5.23 (m, 6H), 5.23 (s, 2H), 5.18 (t,
J = 7.3 Hz, 1H), 3.54 – 3.49 (m, 9H), 3.46 (s, 3H), 3.36 – 3.26 (m, 2H),
2.97 (dd, J = 16.5, 13.0 Hz, 1H), 2.79 (dd, J = 16.5, 3.0 Hz, 1H), 1.68 –
1.61 (m, 6H) ppm; 13C NMR (101 MHz, CDCl3):  = 189.9, 161.1, 160.6,
157.7, 147.6, 147.4, 133.6, 131.5, 122.4, 120.2, 116.6, 114.9, 112.6,
107.7, 96.2, 95.7, 95.6, 95.5, 94.2, 78.5, 56.6, 56.4, 56.3, 56.3, 45.9, 25.9,
22.3, 17.8 ppm; IR (ATR): 휈̃ = 2928 (m), 1679 (m), 1594 (s), 1511 (m),
1261 (m), 1151 (s), 1066 (s), 984 (s), 920 (s), 811 (w), 730 (w) cm–1; HRMS
(EI): m/z calcd for C28H36O10 [M+] 532.2308; found 532.2319.
8-Prenyleriodictyol (6):[67, 69] to a solution of 14ce (53 mg, 0.100 mmol) in
methanol (2.0 mL) was added aq. HCl (3 M, 40 L). The mixture was
heated at 65 °C for 2 h, cooled to ambient temperature and diluted with
water (10 mL). The mixture was extraced with ethyl acetate (3 times, 10
mL each), and the combined organic extracts were dried with MgSO4,
filtered and evaporated. The residue was purified by column
chromatography on silica, using hexanes – ethyl acetate mixture (9 : 1
(v/v)) as eluent, to furnish 6 (15 mg, 0.042 mmol, 42%): colourless solid,
mp 197 °C. 1H NMR (400MHz, [D4]methanol):  = 6.94 (d, J = 1.7 Hz, 1H),
6.81 (dd, J = 8.3, 1.7 Hz, 1H), 6.78 (d, J = 8.4 Hz, 1H), 5.92 (s, 1H), 5.25
(dd, J = 12.7, 3.1 Hz, 1H), 5.14 (tm, J = 7.3 Hz, 1H), 3.24 – 3.13 (m, 2H),
3.03 (dd, J = 17.1, 12.7 Hz, 1H), 2.70 (dd, J = 17.1, 3.1 Hz, 1H), 1.62 (s,
3H), 1.58 (s, 3H) ppm; 13C NMR (101MHz, [D4]methanol):  = 198.0, 166.4,
163.1, 161.5, 146.8, 146.5, 132.1, 131.6, 123.9, 119.7, 116.2, 114.7,
3.0 Hz, 1H, H7cis), 1.46 (s, 3H, C2(CH3)), 1.44 (s, 3H, C2(CH3)) ppm; 13
C
NMR (150 MHz, CDCl3):  = 191.2 (C6), 160.9 (C9a), 157.8 (C4a), 139.4
(ipso-C, Ph), 136.0 (CH=CH2), 129.5 (C3), 128.8 (m-C, Ph), 128.5 (p-C,
Ph), 126.0 (o-C, Ph), 122.7 (C5), 121.8 (C4), 115.9 (C10a), 115.5 (C10),
115.0 (=CH2), 114.7 (C5a), 79.5 (C8), 77.9 (C2), 44.5 (C7), 28.7
(C2(CH3)), 28.6 (C2(CH3)), 27.2 (CH2CH=) ppm; IR (ATR): 휈̃ = 2956 (s),
2919 (s), 2870 (w), 2851 (m), 1739 (m), 1691 (m), 1639 (m), 1591 (m),
1463 (m) cm–1; HRMS (EI): m/z calcd for C23H22O3 [M+] 346.1569; found
346.1562. Analytical data of 19: yellowish oil. 1H NMR (600 MHz, CDCl3):
 = 7.63 (s, 1H, H5), 7.48 (d, J = 7.4 Hz, 2H, o-H(Ph)), 7.43 (tm, J = 7.4
Hz, 2H, m-H(Ph)), 7.38 (tm, J = 7.3 Hz, 1H, p-H(Ph)), 6.67 (d, J = 9.8 Hz,
1H, H10), 5.96 (ddt, J = 16.6, 9.9, 6.7 Hz, 1H, CH=CH2), 5.58 (d, J = 10.3
Hz, 1H, H9), 5.46 (dd, J = 13.5, 2.8 Hz, 1H, H2), 5.09 (dm, J = 16.7 Hz,
1H, =CHHtrans), 5.05 (dm, J = 9.9 Hz, 1H, =CHHcis), 3.30 (d, J = 6.8 Hz,
2H, -CH2CH=), 3.00 (dd, J = 16.6, 13.5 Hz, 1H, H3trans), 2.84 (dd, J = 16.6,
3.0 Hz, 1H, H3cis), 1.47 (s, 3H, C8(CH3)), 1.45 (s, 3H, C8(CH3)); 13C NMR
(150 MHz, CDCl3):  = 190.8 (C4), 157.5 (C6a), 156.5 (C1a), 139.2 (ipso-
C, Ph), 136.5 (CH=CH2), 128.9 (m-C, Ph), 128.7 (C9), 128.6 (p-C, Ph),
127.5 (C5), 126.1 (o-C, Ph), 122.5 (C6), 116.3 (C10), 115.9 (=CH2), 114.3
(C4a), 109.3 (C10a), 79.8 (C2), 77.6 (C8), 44.5 (C3), 33.6 (CH2CH=), 28.5
109.1, 103.3, 96.4, 80.3, 44.1, 26.0, 22.5, 17.9 ppm; IR (ATR): 휈̃ = 3312
(br), 2968 (m), 2920 (m), 1633 (s), 1601 (s), 1519 (m), 1439 (m), 1381 (m),
1347 (m), 1269 (m), 1178 (m), 1075 (m), 818 (w), 780 (w) cm–1; HRMS
(ESI): m/z calcd for C20H21O6 [M+H]+ 357.1338; found 357.1337.
Synthetic procedures and analytical data for maximaflavanone A (7)
and 6,7,2,2-dimethylchromono-8-prenylflavan-4-one (8)
(C8(CH3)), 28.2 (C8(CH3)) ppm; IR (ATR): 휈̃ = 2923 (s), 2853 (m), 1682
1-(2-(Allyloxy)-4-((2-methylbut-3-yn-2-yl)oxy)phenyl)ethan-1-one (16):
To a solution of 15 (1.09 g, 5.0 mmol) in acetone (25 mL) were added
K2CO3 (1.40 g, 10.0 mmol) and allyl bromide (0.65 mL, 7.5 mmol). The
mixture was heated to 50 °C for 16 h, cooled to ambient temperature, and
diluted by addition of brine (10 mL) and water (10 mL). The mixture was
extracted with ethyl acetate (3 times, 20 mL each), the combined organic
extracts were dried with MgSO4, filtered and evaporated. The residue was
purified by chromatography on silica using hexanes / MTBE mixtures of
increasing polarity as eluent to furnish compound 16 (1.15 g, 4.5 mmol,
89%): pale yellow oil. 1H NMR (300 MHz, CDCl3):  = 7.77 (d, J = 8.7 Hz,
1H), 6.87 (dd, J = 8.7, 2.2 Hz, 1H), 6.79 (d, J = 2.2 Hz, 1H), 6.08 (ddt, J =
17.4, 10.6, 5.3 Hz, 1H), 5.44 (dm, J = 17.3 Hz, 1H), 5.32 (dm, J = 10.5 Hz,
1H), 4.61 (d, J = 5.3 Hz, 2H), 2.64 (s, 1H), 2.60 (s, 3H), 1.69 (s, 6H) ppm;
13C NMR (75 MHz, CDCl3):  = 198.2, 160.8, 159.5, 132.7, 131.8, 122.5,
(s), 1639 (m), 1605 (s), 1467 (m), 1192 (m), 1160 (s) cm–1; HRMS (EI):
m/z calcd for C23H22O3 [M+] 346.1569; found 346.1560.
6,7,2,2-Dimethylchromono-8-prenylflavan-4-one (8):[53] following the
general procedure, method 1, 18 (346 mg, 1.00 mmol) was converted to 8
(288 mg, 0.77 mmol, 77%): yellowish solid, mp 113 – 114 °C. 1H NMR (400
MHz, CDCl3):  = 7.50 – 7.46 (m, 2H), 7.43 (dd, J = 7.4, 7.4 Hz, 2H), 7.37
(tt, J = 7.3, 1.5 Hz, 1H), 6.32 (d, J = 9.9 Hz, 1H), 5.60 (d, J = 9.9 Hz, 1H),
5.46 (dd, J = 13.0, 3.2 Hz, 1H), 5.21 (tm, J = 7.4 Hz, 1H), 3.36 (dd, J =
13.6, 6.9 Hz, 1H), 3.31 (dd, J = 13.6, 7.3 Hz, 1H), 2.99 (dd, J = 16.7, 13.0
Hz, 1H), 2.85 (dd, J = 16.9, 3.2 Hz, 1H), 1.68 (s, 3H), 1.67 (s, 3H), 1.46 (s,
3H), 1.44 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3):  = 191.3, 160.9,
157.7, 139.4, 131.7, 129.4, 128.8, 128.6, 126.1, 122.4, 122.0, 121.9,
117.3, 115.9, 114.7, 79.6, 77.8, 44.5, 28.7, 28.6, 26.0, 22.2, 18.0 ppm; IR
118.4, 111.9, 104.4, 85.5, 74.7, 72.5, 69.6, 32.2, 29.7 ppm; IR (ATR): 휈̃ =
1665 (m), 1595 (s), 1257 (s), 1181 (m), 1132 (s) (w) cm–1; HRMS (EI): m/z
calcd for C16H18O3 [M+] 258.1256; found 258.1254.
(ATR): 휈̃ = 2972 (br), 1679 (s), 1603 (s), 1445 (m), 1315 (w), 1156 (s),
1118 (m), 1072 (w), 895 (w), 754 (w), 697 (w) cm–1; HRMS (EI): m/z calcd
for C25H26O3 [M+] 374.1882; found 374.1875.
(E)-1-(2-(Allyloxy)-4-((2-methylbut-3-yn-2-yl)oxy)phenyl)-3-phenyl-
prop-2-en-1-one (17): following the general procedure for the synthesis of
chalcones 11, compound 16 (904 mg, 3.50 mmol) and benzaldehyde (0.70
mL, 7.0 mmol) were converted to 17 (1100 mg, 3.20 mmol, 90%): pale
Maximaflavanone A (7):[66] following the general procedure, method 1, 19
(237 mg, 0.68 mmol) was converted to 7 (239 mg, 0.64 mmol, 94%):
yellowish oil. 1H NMR (400MHz, CDCl3):  = 7.61 (s, 1H), 7.51 – 7.34 (m,
5H), 6.66 (d, J = 10.0 Hz, 1H), 5.57 (d, J = 10.0 Hz, 1H), 5.45 (dd, J = 13.2,
3.0 Hz, 1H), 5.26 (tm, J = 7.4 Hz, 1H), 3.23 (d, J = 7.2 Hz, 2H), 2.99 (dd, J
= 16.8, 13.1 Hz, 1H), 2.83 (dd, J = 16.8, 3.1 Hz, 1H), 1.73 (s, 6H), 1.47 (s,
3H), 1.44 (s, 3H) ppm; 13C NMR (101MHz, CDCl3):  = 191.0, 157,7, 156.4,
139.3, 132.6, 128.9, 128.7, 128.7, 127.2, 126.2, 126.1, 124.1, 122.3,
116.4, 114.2, 109.3, 79.8, 77.6, 44.6, 28.5, 28.2, 26.0, 18.0 ppm; IR (ATR)
1
yellow oil. H NMR (300 MHz, CDCl3):  = 7.73 (d, J = 8.6 Hz, 2H), 7.70
(d, J = 15.8 Hz, 1H), 7.64 – 7.54 (m, 3H), 7.45 – 7.33 (m, 3H), 6.94 (dd, J
= 8.6, 2.2 Hz, 1H), 6.84 (d, J = 2.2 Hz, 1H), 6.06 (ddt, J = 17.3, 10.4, 5.1
Hz, 1H), 5.45 (dm, J = 17.2 Hz, 1H), 5.27 (dm, J = 10.5 Hz, 1H), 4.62 (d, J
= 5.1 Hz, 2H), 2.66 (s, 1H), 1.71 (s, 6H) ppm; 13C NMR (75 MHz, CDCl3):
 = 190.9, 160.5, 158.9, 142.0, 135.5, 132.6, 132.1, 130.1, 128.9, 128.4,
127.4, 123.6, 118.1, 112.3, 104.8, 85.6, 74.7, 72.5, 69.5, 29.7 ppm; IR
휈̃ = 2973 (br), 1681 (s), 1637 (m), 1592 (s), 1449 (m), 1377 (m), 1274 (m),
1155 (s), 1119 (m), 1067 (m), 899 (w), 754 (w), 727 (w), 697 (w) cm–1
;
(ATR): 휈̃
= 2924 (m), 1713 (m), 1655 (m), 1603 (s), 1123 (m) cm–1; HRMS
(EI): m/z calcd for C23H22O3 [M+] 346.1569; found 346.1550.
HRMS (EI): m/z calcd for C25H26O3 [M+] 374.1882; found 374.1888.
10-Allyl-2,2-dimethyl-8-phenyl-7,8-dihydro-2H,6H-pyrano[3,2-g]-
chromen-6-one (18) and 6-allyl-8,8-dimethyl-2-phenyl-2,3-dihydro-
Acknowledgments
10
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
[43]
[44]
M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1,
953-956.
We thank Evonik Oxeno for generous donations of solvents.
A. Ceccaldi, A. Rajavelu, C. Champion, C. Rampon, R. Jurkowska,
G. Jankevicius, C. Sénamaud-Beaufort, L. Ponger, N. Gagey, H.
Dali Ali, J. Tost, S. Vriz, S. Ros, D. Dauzonne, A. Jeltsch, D.
Guianvarc'h, P. B. Arimondo, ChemBioChem 2011, 12, 1337-
1345.
Keywords: Tandem reactions • Arenes • Oxygen heterocycles •
Microwave chemistry • Rearrangement
[45]
[46]
[47]
[48]
[49]
X. Dong, T. Liu, J. Yan, P. Wu, J. Chen, Y. Hu, Bioorg. Med.
Chem. Lett. 2009, 17, 716-726.
J. H. Yang, S. Z. Jiang, Y. M. Zhao, Y. F. Li, C. B. Ji, W. Y. Liu,
Chin. Chem. Lett. 2009, 20, 1062-1064.
R. Kumar Gupta, M. Krishnamurti, Phytochemistry 1976, 15, 832-
833.
[1]
[2]
D. Barron, R. K. Ibrahim, Phytochemistry 1996, 43, 921-982.
T. Nomura, T. Fukai, Y. Hano in Studies in Natural Products
Chemistry, Vol. 28 (Ed.: A.-u. Rahman), Elsevier, 2003, pp. 199-
256.
X. Chen, E. Mukwaya, M.-S. Wong, Y. Zhang, Pharm. Biol. 2014,
52, 655-660.
O. Lozinski, C. Bennetau-Pelissero, S. Shinkaruk, ChemistrySelect
2017, 2, 6577-6603.
L. Molčanová, D. Janošíková, S. Dall´Acqua, K. Šmejkal,
Phytochem. Rev. 2019, 18, 1051-1100.
H. A. Khan, I. Chandrasekharan, A. Ghanim, Phytochemistry 1986,
25, 767-768.
[3]
[4]
[5]
T. Nikaido, T. Ohmoto, T. Kinoshita, U. Sankawa, F. D. Monache,
B. Botta, T. Tomimori, Y. Miyaichi, Y. Shirataki, I. Yokoe, M.
Komatsu, Chem. Pharm. Bull. 1989, 37, 1392-1395.
M. Mori-Hongo, H. Takimoto, T. Katagiri, M. Kimura, Y. Ikeda, T.
Miyase, J. Nat. Prod. 2009, 72, 194-203.
V. K. Bhalla, U. R. Nayak, S. Dev, Tetrahedron Lett. 1968, 9,
2401-2406.
H. Haraguchi, J. Inoue, Y. Tamura, K. Mizutani, Phytother. Res.
2002, 16, 539-544.
S. Sultana, M. Ilyas, Phytochemistry 1986, 25, 963-964.
H. M. H. Muhaisen, Der Pharma Chem. 2013, 5, 88-96.
H. Yin, S. Zhang, J. Wu, Z. Naturforsch. B 2005, 60, 356.
H. Yin, S. Zhang, J. Wu, H. Nan, J. Braz. Chem. Soc. 2006, 17,
1432-1435.
P. M. Dewick, Medicinal Natural Products, Wiley, New York, 1997.
L. Crombie, D. A. Whiting, Phytochemistry 1998, 49, 1479-1507.
B. Schmidt, C. Schultze, Eur. J. Org. Chem. 2018, 223-227.
J. Garcia, S. Barluenga, K. Beebe, L. Neckers, N. Winssinger,
Chem. Eur. J. 2010, 16, 9767-9771.
M. Harfenist, E. Thom, J. Org. Chem. 1972, 37, 841-848.
A. Wunderli, T. Winkler, H.-J. Hansen, Helv. Chim. Acta 1977, 60,
2436-2459.
B. Schmidt, M. Riemer, Synthesis 2016, 48, 141-149.
E. Venkata Rao, Y. Rajendra Prasad, M. Sree Rama Murthy,
Phytochemistry 1994, 37, 111-112.
R. Wen, H. Lv, Y. Jiang, P. Tu, Planta Med. 2018, 84, 1174-1182.
R. S. Mali, P. Kulkarni-Joshi, Indian J. Chem. 1999, 38B, 596-599.
F. Bohlmann, C. Zdero, H. Robinson, R. M. King, Phytochemistry
1981, 20, 2245-2248.
B. Zhou, C.-X. Wan, J. Asian Nat. Prod. Res. 2015, 17, 256-261.
R. Chen, X. Liu, J. Zou, Y. Yin, B. Ou, J. Li, R. Wang, D. Xie, P.
Zhang, J. Dai, Adv. Synth. Catal. 2013, 355, 1817-1828.
M. S. Malefo, T. E. Ramadwa, I. M. Famuyide, L. J. McGaw, J. N.
Eloff, M. S. Sonopo, M. A. Selepe, J. Nat. Prod. 2020, 83, 2508-
2517.
[50]
[51]
[52]
[6]
[7]
[8]
C. M. M. Santos, A. M. S. Silva, Molecules 2020, 25, 696.
R. Mukai, Biosci. Biotechnol. Biochem. 2018, 82, 207-215.
X. Yang, Y. Jiang, J. Yang, J. He, J. Sun, F. Chen, M. Zhang, B.
Yang, Trends Food Sci. Tech. 2015, 44, 93-104.
A. Sugiyama, P. J. Linley, K. Sasaki, T. Kumano, H. Yamamoto, N.
Shitan, K. Ohara, K. Takanashi, E. Harada, H. Hasegawa, T.
Terakawa, T. Kuzuyama, K. Yazaki, Metab. Eng. 2011, 13, 629-
637.
M. Levisson, C. Araya-Cloutier, W. J. C. de Bruijn, M. van der
Heide, J. M. Salvador López, J.-M. Daran, J.-P. Vincken, J.
Beekwilder, J. Agric. Food Chem. 2019, 67, 13478-13486.
G. Kretzschmar, O. Zierau, J. Wober, S. Tischer, P. Metz, G.
Vollmer, J. Steroid Biochem. Mol. Biol. 2010, 118, 1-6.
O. Talhi, A. M. S. Silva, Curr. Org. Chem. 2013, 17, 1067-1102.
A. C. Jain, M. K. Zutshi, Tetrahedron 1972, 28, 5589-5593.
L. Xiao, W. Tan, Y. Li, Synth. Commun. 1998, 28, 2861-2869.
Á. Kenéz, S. Antus, Nat. Prod. Commun. 2006, 1, 51-55.
X. Dong, Y. Fan, L. Yu, Y. Hu, Arch. Pharm. Chem. Life Sci. 2007,
340, 372-376.
X. Dong, L. Qi, C. Jiang, J. Chen, E. Wei, Y. Hu, Bioorg. Med.
Chem. Lett. 2009, 19, 3196-3198.
C. Huang, Z. Zhang, Y. Li, J. Nat. Prod. 1998, 61, 1283-1285.
B. Schmidt, M. Riemer, U. Schilde, Eur. J. Org. Chem. 2015, 7602-
7611.
B. Schmidt, M. Riemer, U. Schilde, Synlett 2014, 25, 2943-2946.
S. Nasir Abbas Bukhari, M. Jasamai, I. Jantan, W. Ahmad, Mini-
Rev. Org. Chem. 2013, 10, 73-83.
C. Schultze, B. Schmidt, J. Org. Chem. 2018, 83, 5210-5224.
K. Hemanth Kumar, P. T. Perumal, Tetrahedron 2007, 63, 9531-
9535.
[9]
[53]
[54]
[55]
[56]
[10]
[11]
[57]
[58]
[59]
[60]
[12]
[13]
[14]
[15]
[16]
[61]
[62]
[63]
[64]
[17]
[65]
[66]
[67]
[18]
[19]
[20]
[21]
[68]
[69]
[22]
[23]
[70]
[71]
[24]
[25]
[26]
[27]
[28]
Z. Du, H. Ng, K. Zhang, H. Zeng, J. Wang, Org. Biomol. Chem.
2011, 9, 6930-6933.
X. Zheng, H. Jiang, J. Xie, Z. Yin, H. Zhang, Synth. Commun.
2013, 43, 1023-1029.
K. G. Bedane, R. R. T. Majinda, I. B. Masesane, Synth. Commun.
2016, 46, 1803-1809.
J. M. Kremsner, A. Stadler, A Chemist's Guide to Microwave
Synthesis, 2nd ed., Anton Paar GmbH, Graz, 2016.
D. Dallinger, H. Lehmann, J. D. Moseley, A. Stadler, C. O. Kappe,
Org. Process Res. Dev. 2011, 15, 841-854.
L. X. Yang, K. X. Huang, H. B. Li, J. X. Gong, F. Wang, Y. B. Feng,
Q. F. Tao, Y. H. Wu, X. K. Li, X. M. Wu, S. Zeng, S. Spencer, Y.
Zhao, J. Qu, J. Med. Chem. 2009, 52, 7732-7752.
[29]
[30]
J. M. Kremsner, C. O. Kappe, J. Org. Chem. 2006, 71, 4651-4658.
L. Perreux, A. Loupy, A. Petit in Microwaves in Organic Synthesis,
Vol. 1 (Eds.: A. De la Hoz, A. Loupy), Wiley-VCH, Weinheim, 2012,
pp. 127-207.
[31]
J. Sherwood, M. De bruyn, A. Constantinou, L. Moity, C. R.
McElroy, T. J. Farmer, T. Duncan, W. Raverty, A. J. Hunt, J. H.
Clark, Chem. Commun. 2014, 50, 9650-9652.
J. E. Camp, ChemSusChem 2018, 11, 3048-3055.
T. Brouwer, B. Schuur, ACS Sustainable Chem. Eng. 2020,
10.1021/acssuschemeng.0c04159.
[32]
[33]
[34]
[35]
[36]
[37]
L. Mistry, K. Mapesa, T. W. Bousfield, J. E. Camp, Green Chem.
2017, 19, 2123-2128.
K. Żukowska, K. Grela in Comprehensive Organic Synthesis II
(Second Edition), Elsevier, Amsterdam, 2014, pp. 1257-1301.
A. K. Chatterjee, D. P. Sanders, R. H. Grubbs, Org. Lett. 2002, 4,
1939-1942.
A. K. Chatterjee, T.-L. Choi, D. P. Sanders, R. H. Grubbs, J. Am.
Chem. Soc. 2003, 125, 11360-11370.
[38]
[39]
S. Tischer, P. Metz, Adv. Synth. Catal. 2007, 349, 147-151.
J. M. Hastings, M. K. Hadden, B. S. J. Blagg, J. Org. Chem. 2008,
73, 369-373.
[40]
[41]
[42]
P. Pahari, J. Rohr, J. Org. Chem. 2009, 74, 2750-2754.
J. Magolan, M. J. Coster, J. Org. Chem. 2009, 74, 5083-5086.
G.-L. Liu, B. Hao, S.-P. Liu, G.-X. Wang, Eur. J. Med. Chem. 2012,
54, 582-590.
11
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001378
European Journal of Organic Chemistry
FULL PAPER
Key topic: Prenylflavanones
Graphic for Table of Contents:
Text for Table of Contents:
Microwave irradiation of ortho-allyloxy chalcones promotes a tandem sequence of Claisen rearrangement and 6-endo-trig-cyclization.
Olefin cross metathesis then furnishes prenylated flavonoids. The method has, inter alia, been applied to the synthesis of an angular
chromene-annellated natural product and its linear isomer. Both occur in medicinal plants indigenous in India and Nigeria
respectively.
12
This article is protected by copyright. All rights reserved.