Synthesis of neoflavenes by ligand coupling reactions with aryllead triacetates

Article abstract of DOI:10.1016/S0040-4020(00)00955-8

The reaction of 4-methoxycarbonylchroman-3-one with aryllead triacetates gave the 4-aryl derivatives after 3-4h reaction times in moderate to good yields. Unexpectedly, 2,4-diarylated derivatives were also obtained after longer reaction times. The activating methyl ester group proved difficult to remove by standard decarboxylation procedures. 4-Benzyloxycarbonylchroman-3-ones were therefore prepared and reacted with aryllead triacetates to afford the corresponding 4-aryl derivatives. These were subsequently decarboxylated, reduced and dehydrated to afford neoflavenes in modest overall yields.

Full text of DOI:10.1016/S0040-4020(00)00955-8

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 413±423
Synthesis of neo¯avenes by ligand coupling reactions with
aryllead triacetates
a
a
Dervilla M. X. Donnelly,a Jean-Pierre Finet,b, Patrick J. Guiry and Karl Nesbitt
*
aDepartment of Chemistry, University College Dublin, Bel®eld, Dublin 4, Ireland
   Ã
Laboratoire `Chimie, Biologie et Radicaux Libres', UMR 6517-CNRS Universites d'Aix-Marseille 1 et 3, Faculte des Sciences St Jerome,
13397 Marseille Cedex 20, France
b
Received 14 March 2000; revised 1 June 2000; accepted 11 July 2000
AbstractÐThe reaction of 4-methoxycarbonylchroman-3-one with aryllead triacetates gave the 4-aryl derivatives after 3-4 h reaction times
in moderate to good yields. Unexpectedly, 2,4-diarylated derivatives were also obtained after longer reaction times. The activating methyl
ester group proved dif®cult to remove by standard decarboxylation procedures. 4-Benzyloxycarbonylchroman-3-ones were therefore
prepared and reacted with aryllead triacetates to afford the corresponding 4-aryl derivatives. These were subsequently decarboxylated,
reduced and dehydrated to afford neo¯avenes in modest overall yields. q 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
have been isolated from Dalbergia and Machaerium genera
of the Leguminosae family.3±6 The related 4-aryl-3-hydro-
xychroman skeleton is also found in members of the homo-
¯avonoid family, such as in brazilin 2, isolated from
Cesalpinia sappan and haematoxylin 3, isolated from
Haematoxylon campechianum.7 Other examples of 3-hy-
droxy-4-arylchroman structures are observed in the 4-aryl-
¯avan-3-ol 4 isolated from the South African plant Nelia
The neo¯avene [4-arylchromene or (4-aryl-2H-1-benzo-
pyran)] skeleton is one of the ®ve main structural types
found in the group of neo¯avonoid derivatives.1,2 Neo-
¯avenes are thought to be important intermediates in the
biosynthetic transformation of dalbergiquinols or dalber-
giones into 4-arylcoumarins, and a few representatives
Scheme 1.
Keywords: arylation; a,g-diarylation; neo¯avonoids; organolead reagents.
* Corresponding author. Fax: 133-4-91-98-85-12; e-mail: ®net@srepir.1.univ-mrs.fr
0040±4020/01/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00955-8

414
D. M. X. Donnelly et al. / Tetrahedron 57 (2001) 413±423
Scheme 2.
meyeri,8 and in the more complex proanthocyanidin dimers
derived from catechin and epicatechin such as procyanidin
B2 59±11 (Scheme 1).
the aryl and enolic groups makes the ligand coupling
process possible leading to ketone 9. This non-synchronous
concerted elimination is triggered by the development of a
partial positive charge on the aryl group. Formally an oxida-
tive activation of the aromatic ring is associated with the
change of oxidation state from Pb(IV) to Pb(II) being the
driving force of the reaction15 (Scheme 2).
In principle, formation of an aryl link to the C-4 can be
obtained either by electrophilic arylation at a benzylic
cation generated on C-4, or by reaction of a benzylic
anion on C-4 with an aryl cation equivalent. The former
approach has been the most generally applied in the syn-
thesis of 4-arylchroman derivatives.9±11 The latter system
can be realised by the ligand coupling reactions of a nucleo-
philic species with aryllead triacetates, a reaction which was
discovered and extensively exploited by Pinhey and his
group.12±15 In recent years, we have applied this ligand
coupling procedure to the synthesis of a number of iso-
¯avonoid derivatives.15±21 We have observed that the
highest yields are obtained in the reaction of C-3 chroman
anions with the more electron-rich aryllead triacetates, such
as 2,4,6-trimethoxyphenyllead triacetate. Aryllead tri-
acetates, which act as the active aryl cationic species, are
prepared either by direct oxidation of the parent arene with
lead tetraacetate, or by an indirect sequence involving
metalation of the arene, followed by metal±lead exchange
reaction. The ligand coupling reaction occurs selectively on
the ipso-carbon substituted by the lead group and does not
involve the intermediacy of free radical species.12±15
Although no intermediates have ever been detected with
these organolead reagents, it is likely that various topo-
isomers of the short-lived intermediates are involved in
the reaction pathway. In the ®rst step, the aryllead triacetate
6 (RˆH or MeO) undergoes a ligand exchange with the
enolic substrate 7 (R0ˆacyl, R00ˆalkyl in the case of b-di-
carbonyl compounds) to afford the species 8a in which the
aryl substituent and the enolic moiety possess a trans-
diaxial con®guration. Then thermal pseudorotation (C) of
the enolic group leads to the cis-conformer 8b, in which the
enolic group occupies an equatorial position. In this favour-
able transition state, overlap between the two p-systems of
2. Results and discussion
We therefore decided to extend the application of this ligand
coupling reaction to the synthesis of neo¯avenes 10, as this
would constitute an attractive approach toward the selective
synthesis of structurally complex proanthocyanidin dimers.
In this paper, we describe the synthesis of 4-arylchroman-3-
ones 11, and their elaboration into 4-arylchromenes or
neo¯avenes (Schemes 3 and 4). The key step is the ligand
coupling reaction between the aryllead(IV) triacetates and a
suitably activated chroman-3-one moiety. Previous work
had shown that conversion of ketones into b-ketoesters
was a convenient means of activating them for reaction
with aryllead(IV) triacetates.22
Therefore, methyl b-ketoesters 15±17 were chosen as suit-
able substrates and were obtained in 62±81% yields by
Dieckmann condensation of the diesters 12±14 with potas-
sium tert-butoxide in tetrahydrofuran. This condensation
led directly to the 4-methoxycarbonyl-2H-1-benzopyran-
3(4H)-one structure, with the required activating ester
group at the 4-position.
A series of arylation reactions was carried out on the methyl
b-keto ester 15 with 1.1 molar equivalent of the aryllead(IV)
triacetates 18±20 and 3 molar equivalents of pyridine in dry
chloroform at 608C. The arylation reactions with the lead
reagents 19 and 20 were complete within 3±4 h and afforded
the arylated products in good yields. Even the bulky 2,4,6-
trimethoxyphenyl group was transferred in an impressive
83% yield in the reaction of 15 with aryllead triacetate 20.
However, the reaction involving the less reactive 4-meth-
oxyphenyllead triacetate gave only moderate yields of the
aryl derivatives after 4 h (60±65%) (Table 1). Thus, the
more electron-rich aryl groups of the aryllead(IV) tri-
acetates 19 and 20 are transferred in higher yields than the
4-methoxyphenyl group of 18, a reactivity pattern which is
in good agreement with our previous ®ndings.16±21
Scheme 3.

D. M. X. Donnelly et al. / Tetrahedron 57 (2001) 413±423
415
Scheme 4.
In order to obtain this product 26 (which contains two bulky
2,4,6-trimethoxyphenyl groups), arylation of the monoaryl
product 23 with the aryllead triacetate 20 was carried out at
608C for 12 h. Under these conditions, 26 was isolated in
16% yield, with recovery of 23 in 83% yield. Similarly,
reaction of the C-4 monoaryl derivatives 21 and 22 with
their corresponding aryllead triacetates 18 and 19 led to
the diaryl derivatives in better yields. However, even after
12 h the monoaryl substrate was still isolated from each
reaction.
These results show that the reactivity pattern of aryllead
triacetates is reversed in the case of a-aryloxyketones; the
less electron-rich and the less sterically-hindered 4-meth-
oxyphenyl group is transferred in higher yields. Such a
pattern was already observed in the reaction of non-
activated benzofuran-2-ones with aryllead triacetates.22,23
In an attempt to increase the yield of the 4-methoxyphenyl
derivative 21, the reaction of the methyl b-keto ester 15 with
4-methoxyphenyllead(IV) triacetate 18 was performed for
12 rather than 3 h at 608C. Under these conditions, two
products were obtained: the expected monoaryl product 21
in a poor 40% yield and an unexpected product of diaryl-
ation 24, 4-methoxycarbonyl-2-(4-methoxyphenyl)-4-(4-
methoxyphenyl)-2H-1-benzopyran-3(4H)-one, in 38%
yield. Therefore under long enough reaction times, the
2-position is reactive enough for g-arylation to take place.
In contrast, when chroman-3-one, prepared by acid-cata-
lyzed hydrolysis of 15 and in situ decarboxylation (10%
aqueous H2SO4 under re¯ux, 82% yield), was treated with
various aryllead triacetates under the same reaction con-
ditions, no 2-aryl nor 4-aryl product was formed. Under
these conditions, either one of the two possible enolic
forms of the ketone leading to the corresponding inter-
mediate enoxylead derivatives is not formed.
Unfortunately, all the decarboxylation methods which were
attempted to decarboxylate the methyl esters 21±23 failed
or gave intractable mixtures. The failure of these methods
con®rmed the unsuitability of the b-methoxycarbonyl group
for the a-arylation of ketones, not because of its inability to
activate a-arylation, but due to its dif®culty in removal, an
observation which we had also noted with the ethoxycarbo-
nyl group in the iso¯avone and benzofuranone series.17,22
We therefore turned our attention to an alternative acti-
vating group, the benzyloxycarbonyl group, which was
successfully used in lead mediated arylations by Suginome
et al.24 and was removed in high yields by palladium cata-
lysed hydrogenolysis. The 4-benzyloxycarbonyl-2H-1-
benzopyran-3(4H)-ones 27±29 were prepared in 78±82%
yields after 9 to 24 h by the 4-dimethylaminopyridine cata-
lysed transesteri®cation of their corresponding 4-methoxy-
carbonyl derivatives 15±17 with benzyl alcohol in re¯uxing
toluene, following the procedure of Taber et al.25 Treatment
of these esters with aryllead triacetates under the same reac-
tion conditions as with the methyl esters proceeded in higher
The in¯uence of the reaction time on the outcome of the
arylation was then studied with the two other lead reagents
19 and 20. When b-ketoester 15 was treated with 19 and 20
for 12 h at 608C, the yields of the monoaryl derivatives were
again lower than after 3 h. However, only the 2,4-dimeth-
oxyphenyl reagent 19 led to the diaryl product 25, and none
of the diaryl product 26 was detected in the reaction with 20.
Table 1. Structure of the 4-aryl-2H-1-benzopyrane derivatives 21±26 and 30±59
R1
R2
Substituents on 4-Ar
Me esters
2,4-diaryl
Benzyl esters
Ketones
3-Hydroxy
Neo¯avenes
4-aryl
H
H
H
OMe
OMe
OMe
OMe
OMe
OMe
H
H
H
H
H
H
OMe
OMe
OMe
40-MeO
21
22
23
24
25
26
30
31
32
33
34
35
36
37
38
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
20,40-(MeO)2
20,40,60-(MeO)3
40-MeO
39
40
41
20,40-(MeO)2
20,40,60-(MeO)3
40-MeO
20,40-(MeO)2
20,40,60-(MeO)3

416
D. M. X. Donnelly et al. / Tetrahedron 57 (2001) 413±423
Table 2. Reaction of aryllead(IV) triacetates with b-keto esters
product underwent further reduction to give the correspond-
ing 4-(4-methoxyphenyl)- or 4-(2,4-dimethoxyphenyl)-3,4-
dihydro-2H-1-benzopyran-3-ols in 76-91% yields, respec-
tively. The 4-(2,4,6-trimethoxyphenyl)-2H-1-benzopyran-
3(4H)-ones 39±41 were then reduced by sodium boro-
hydride in THF and water at room temperature for 1 h to
give the corresponding 4-(2,4,6-trimethoxyphenyl)-3,4-
dihydro-2H-1-benzopyran-3-ol derivatives in 89±91%
a
Substrate
ArPb(OAc)3
Time (h)
Products, (%)
Methyl esters
15
15
15
15
15
15
15
18
18
19
19
19b
20
20
18
19
20
4
12
3
12
12
3
12
12
12
12
21, (65)
21, (40); 24, (36)
22, (86)
22, (43); 25, (38)
22, (36); 25, (30)
23, (83)
1
yields. H NMR analysis of alcohols 42±50 indicated the
23, (71)
presence of only one detectable isomer in all cases. The J
values for the H3±H4 coupling constants were all in the
range 4.2±4.95 Hz. Assignment of the C3±C4 relative
stereochemistry in these conformationally ¯exible systems
cannot be de®nitively drawn from these values, which are
compatible with an axial±equatorial relationship as well as
with an equatorial±equatorial one between the coupled
H3±H4 protons. However, mechanistic arguments would
be in favour of the 3,4-cis isomers. Indeed, approach of
the ketone by the reducing agent (Pd/H2 or NaBH4) will
be favoured on the less congested face of the pyran ring
opposite from the 4-aryl substituent. The last step in the
synthetic pathway towards 4-aryl-2H-1-benzopyrans was
the dehydration of the 4-aryl-3,4-dihydro-2H-1-benzo-
pyran-3-ols 42±50 obtained either in one or two steps
from b-keto esters 30±38. Attempts to employ acid-cata-
lysed dehydration led either to recovery of the starting
alcohol (p-toluenesulfonic acid in toluene under re¯ux) or
to intractable mixtures (10% HCl or 10% H2SO4 under
re¯ux). Successful dehydration was eventually realised by
treating the 4-aryl-3,4-dihydro-2H-1-benzopyran-3-ols with
phosphorus oxychloride (26 equiv.) in dry pyridine, follow-
ing the procedure of Dauben and Boswell.26,27 The 4-aryl-
2H-1-benzopyrans 51±59 were obtained in relatively
modest yields (33±50%), although, after each reaction, no
trace of the starting material was found. The low yields of
these reactions could possibly be attributed to competing
polymerisation reaction of these diarylethylene type deriva-
tives.
21
22
21, (14); 24, (46)
22, (46); 25, (21)
23, (83); 26, (16)
23
Benzyl esters
27
27
27
28
28
28
29
29
29
18
19
20
18
19
20
18
19
20
3
30, (74)
31, (87)
32, (92)
33, (70)
34, (80)
35, (81)
36, (55)
37, (63)
38, (72)
2.5
2.5
3
2.5
2.5
3
2.5
2.5
a All reactions were performed with 1.1 mol equiv. of the lead reagent and
3.3 mol equiv. of pyridine, unless otherwise reported.
b 2.2 mol equiv. of the lead reagent and 6.6 mol equiv. of pyridine were
used.
yields than for the equivalent methyl b-keto ester series.
The arylations also appeared to require slightly shorter
reaction times. Again, no dif®culties occurred in the intro-
duction of the bulky 2,4,6-trimethoxyphenyl group. The
highest yield observed for each of the substrates was for
the reaction with 2,4,6-trimethoxyphenyllead(IV) triacetate
20, which afforded products 32, 35 and 38 in 72, 81 and 92%
yields, respectively (Table 2, Scheme 5).
The benzyloxycarbonyl group was then conveniently
removed from the compounds 30±38 by palladium cata-
lysed hydrogenolysis, using 10% palladium on charcoal in
methanol under a hydrogen atmosphere. Each of the starting
benzyl esters was hydrogenated for three days and high
yields were obtained in all cases (Table 3). When the
4-aryl group was the 2,4,6-trimethoxyphenyl group, the
expected ketones 39±41 were obtained in 75±79% yields.
However, when the 4-aryl group was the 4-methoxyphenyl
group or the 2,4-dimethoxyphenyl group, the debenzylation
In conclusion, the aryllead triacetate mediated arylation of
conveniently activated 3-oxochromane derivatives affords
an easy and ef®cient synthesis of 4-arylchroman-3-one
derivatives. This sequence should be useful for the synthesis
of proanthocyanidin structures from 3-oxo¯avanes. More-
over, an a,g-diarylation was observed for the ®rst time in
Scheme 5.

D. M. X. Donnelly et al. / Tetrahedron 57 (2001) 413±423
Table 3. Yields of the debenzylation, reduction and dehydration steps
417
Aryl b-keto-esters
Debenzylation, (%)
NaBH4 reduction, (%)
Dehydration, (%)
30
31
32
33
34
35
36
37
38
42, (82)
43, (91)
39, (79)
45, (83)
46, (78)
40, (75)
48, (76)
49, (89)
41, (77)
51, (38)
52, (38)
53, (41)
54, (50)
55, (37)
56, (43)
57, (38)
58, (44)
59, (33)
44, (93)
47, (89)
50, (91)
the case of aryllead triacetate mediated arylation of b-keto
esters. This unexpected result could be exploited to achieve
a direct entry from chroman-3-ones into the 4-aryl¯avan-3-
one series, which are the precursors of proanthocyanidin-
type dimers. Extra ¯exibility in the introduction of aryl
groups is available with this process as the relative reaction
rates allow the selective a-monoarylation followed by
the second g-arylation which could be performed with a
different aryllead reagent.
1740; dH (270 MHz) 3.64 (s, 2H, CH2CO2), 3.68 (s, 3H,
CH2CO2Me), 3.78 (s, 3H, OCH2CO2Me), 3.85 (s, 3H,
OMe), 4.62 (s, 2H, OCH2), 6.33 (d, Jˆ2.3 Hz, 1H, 3-H),
6.52 (dd, Jˆ2.3, 8.5 Hz, 1H, 5-H), 7.10 (d, Jˆ8.5 Hz, 1H, 6-
H);dC 35.1, 51.9, 55.2, 55.4, 65.7, 99.9, 105.5, 116.2, 131.6,
156.7, 160.0, 169.1, 172.5; m/z 268 (M1, 18), 236 (20), 209
(52), 151 (16), 121 (19), 91 (14), 77 (23), 45 (100), 28 (10)
(Found: C, 57.97; H, 6.08. C13H16O6 requires: C, 58.20; H,
6.01%).
3.2. Methyl (2-methoxycarbonylmethoxy-4,5-dimethoxy-
phenyl)acetate (14)
3. Experimental
Melting points were determined on a Reichert±Jung Ther-
movar apparatus and are uncorrected. IR spectra were
recorded on a Mattson Galaxy Series FTIR 3000 spec-
trometer. 270 MHz 1H NMR and 67.8 MHz 13C NMR
were recorded on a Jeol JNM-GX 270 spectrometer, and
By the same procedure, 2-hydroxy-4,5-dimethoxyphenyla-
cetic acid28 afforded (14) as a yellow solid, 77%, mp 57±
608C; nmax(KBr)/cm21 1756, 1740; dH (270 MHz) 3.67 (s,
2H, CH2CO2), 3.69 (s, 3H, CH2CO2Me), 3.78 (s, 3H,
OCH2CO2Me), 3.83 (s, 3H, 5-OMe), 3.84 (s, 3H, 4-OMe),
4.61 (s, 2H, OCH2), 6.50 (s, 1H, 3-H), 6.74 (s, 1H, 6-H); dC
35.0, 51.9, 52.1, 56.1, 56.3, 67.6, 99.8, 114.2, 115.7, 144.1,
148.7, 150.1, 169.5, 172.4; m/z 298 (M1, 45), 239 (42), 193
(43), 151 (22), 59 (18), 45 (100), 28 (72) (Found: C, 56.28;
H, 6.17. C14H18O7 requires: C, 56.37; H, 6.08%).
1
400 MHz H NMR were recorded on a Bruker AM 400X
spectrometer. Spectra were obtained in CDCl3 with TMS as
the internal standard and are reported in ppm. All J values
are given in Hz. The sign `p' is used when assignments may
be reversed in 1H NMR attributions. In the description of the
NMR data of compounds, A0 refers to atom A of the aryl
group linked to C-4 and A00 to atom A of the benzyloxy-
carbonyl group linked to C-4. Mass spectra were determined
on a VG Analytical 770 mass spectrometer with attached
INCOS 2400 data system in the EI mode. Separations by
column chromatography (CC), preparative thin layer
chromatography (PLC) and ¯ash chromatography (FC)
were performed using Merck Kieselgel 60 (70±230 mesh
ASTM), Merck Kieselgel 60 (7748) and 60 (230±400 mesh
ASTM), respectively.
3.3. General procedure for the preparation of 4-meth-
oxycarbonyl-2H-1-benzopyran-3(4H)-ones
The diester (1 equiv.) was added to a solution of potassium
tert-butoxide (1.5 equiv.) in THF (30 mL per 5 mmol of
diester) under nitrogen. The mixture was stirred at room
temperature for 19 h. The reaction mixture was then poured
into ice-water (200 mL) and acidi®ed with 5% aqueous
hydrochloric acid to pH 2. The reaction mixture was
extracted with chloroform (2£100 mL), dried (MgSO4)
and the solvent removed. The residue was puri®ed by
chromatography on silica gel and crystallised.
3.1. Methyl (2-methoxycarboxymethoxy-4-methoxy-
phenyl)acetate (13)
A solution of 2-hydroxy-4-methoxyphenylacetic acid28
(20 g), methanol (150 mL) and sulfuric acid (5 g) was
re¯uxed for 8 h. The mixture was diluted with water
(100 mL) and extracted with dichloromethane (100 mL).
The extract was washed with a 10% NaHCO3 solution
(100 mL) and water (100 mL). Distillation of the solvents
under reduced pressure gave methyl (2-hydroxy-4-methoxy-
phenyl)acetate as a yellow oil. The crude ester was directly
treated with methyl bromoacetate (10.93 mL, 116 mmol),
potassium carbonate (20 g) and acetone (100 mL), under
re¯ux for 8 h. After ®ltration, the solvent was distilled
under reduced pressure to yield (13) as a yellow solid
(22.13 g, 75%), mp 60±628C, nmax(KBr)/cm21 1758,
3.3.1. 4-Methoxycarbonyl-2H-1-benzopyran-3(4H)-one
(15). CC (eluant: CHCl3), 81%; needles from ethanol, mp
37±388C (lit.,29 mp 34.5±36.58C); nmax(KBr)/cm21 3215,
1725, 1652; dH (270 MHz) 3.93 (s, 3H, CO2Me), 4.63 (s,
2H, 2-H), 6.89 (dd, Jˆ1.4, 7.7 Hz, 1H, 8-H), 6.97 (dt,
Jˆ1.7, 7.6 Hz, 1H, 6-H), 7.06 (dt, Jˆ1.7, 7.6 Hz, 1H, 7-
H), 7.73 (dd, Jˆ1.4, 7.9 Hz, 1H, 5-H), 12.84 (s, 1H, OH);
dC 52.1, 65.8, 97.0, 116.3, 119.7, 125.7, 126.5, 151.2, 169.3,
170.5; m/z 206 (M1, 71), 174 (100), 147 (22), 118 (78), 91
(49), 45 (20), 39 (50), 31 (26).
3.3.2. 7-Methoxy-4-methoxycarbonyl-2H-1-benzopyran-
3(4H)-one (16). CC (eluant: CHCl3), 67%; yellow solid

418
D. M. X. Donnelly et al. / Tetrahedron 57 (2001) 413±423
from ethanol, mp 56±588C; nmax(KBr)/cm21 3210, 1738,
1652; dH (270 MHz) 3.77 (s, 3H, 7-OMe), 3.93 (s, 3H,
CO2Me), 4.63 (s, 2H, 2-H), 6.48-6.57 (m, 2H, 6-H, 8-H),
7.64 (d, Jˆ8.7 Hz, 1H, 5-H), 12.63 (s, 1H, OH); dC 52.1,
55.4, 66.1, 97.0, 102.3, 108.0, 112.4, 126.5, 152.5, 158.5,
167.3, 171.2; m/z 236 (M1, 49), 204 (100), 177 (12), 148
(74), 120 (20), 91 (14), 77 (22), 51 (12), 28 (8) (Found: C,
60.81; H, 5.16. C12H12O5 requires: C, 61.02; H, 5.12%).
(KBr)/cm21 3160, 1729, 1637; dH (270 MHz) 3.44 (s, 3H,
6-OMe), 3.80 (s, 3H, 7-OMe), 4.60 (s, 2H, 2-H), 5.33 (s, 2H,
20-H), 6.48 (s, 1H, 8-H), 7.25 (s, 1H, 5-H), 7.36-7.44 (m, 5H,
C6H5), 12.68 (s, 1H, OH); dC 55.8, 55.9, 66.3, 67.5, 96.9,
100.8, 109.2, 111.3, 128.8, 128.9, 134.9, 143.8, 145.2,
147.2, 168.2, 170.3; m/z 342 (M1, 24), 251 (38), 234 (74),
207 (32), 151 (28), 107 (18), 91 (100), 65 (33), 28 (52)
(Found: C, 66.40; H, 5.39. C19H18O6 requires: C, 66.66;
H, 5.30%).
3.3.3. 6,7-Dimethoxy-4-methoxycarbonyl-2H-1-benzo-
pyran-3(4H)-one (17). CC (eluant: CHCl3), 62%; yellow
solid from ethanol, mp 109±1118C; nmax(KBr)/cm21 3212,
1733, 1647; dH (270 MHz) 3.83 (s, 3H, 6-OMe), 3.85 (s, 3H,
7-OMe), 3.95 (s, 3H, CO2Me), 4.60 (s, 2H, 2-H), 6.51 (s,
1H, 8-H), 7.34 (s, 1H, 5-H), 12.63 (s, 1H, OH); dC 52.1,
56.0, 56.7, 66.3, 96.9, 101.0, 110.1, 111.4, 143.9, 145.6,
147.6, 167.9, 171.0; m/z 266 (M1, 50), 234 (100), 191
(39), 163 (38), 135 (32), 107 (30), 69 (48), 51 (32), 29
(31) (Found: C, 58.60; H, 5.38. C13H14O6 requires: C,
58.65; H, 5.30%).
3.5. General procedure for the arylation of 4-methoxy-
and 4-benzyloxycarbonyl-2H-1-benzopyran-3(4H)-ones
Dry pyridine (3.3 equiv.) was added to a stirred mixture of
the 2H-1-benzopyran-3(4H)-one (1 equiv.) and aryllead
triacetate (1.1 equiv.) in dry chloroform (1 mL per
0.6 mmol of substrate). The mixture was stirred at 608C
for the time speci®ed. The reaction mixture was diluted
with chloroform (50 mL) and washed with 6% aqueous
sulfuric acid (2£50 mL). The aqueous phase was washed
with chloroform (2£50 mL) and the combined organic
extracts were washed with water (2£50 mL), dried
(MgSO4), ®ltered and the solvent removed in vacuo. The
residue was puri®ed by chromatography on silica using the
indicated solvent system.
3.4. General procedure for the preparation of 4-benzyl-
oxycarbonyl-2H-1-benzopyran-3(4H)-ones
A solution of the appropriate 4-methoxycarbonyl-2H-
1-benzopyran-3(4H)-one (1 equiv.), benzyl alcohol
(2 equiv.) and 4-dimethylaminopyridine (0.2 equiv.) in dry
toluene (40 mL per 5 mmol of ketone) was re¯uxed for the
speci®ed time. The cooled solution was diluted with ether
(100 mL), washed successively with 1 M aqueous H2SO4
solution (50 mL), 5% aqueous NaHCO3 solution (50 mL)
and brine (100 mL), and dried over anhydrous Na2SO4.
Distillation under reduced pressure of the volatiles gave a
residue which was puri®ed by chromatography on silica and
crystallised.
3.5.1. 4-Methoxycarbonyl-4-(4-methoxyphenyl)-2H-1-
benzopyran-3(4H)-one (21). PLC (eluant: CHCl3); plates
from ethanol, mp 84±868C; nmax (KBr)/cm21 1746, 1722;
dH (270 MHz) 3.78 (3H, s, 40-OMe), 3.80 (s, 3H, 200-H),
4.52 (d, Jˆ17.5 Hz, 1H, 2-H), 4.60 (d, Jˆ17.5 Hz, 1H,
2-H), 6.85 (dd, Jˆ2.4, 6.8 Hz, 2H, 50-H, 30-H), 6.96 (dd,
Jˆ2.4, 6.8 Hz, 2H, 60-H, 20-H), 7.02 (dd, Jˆ1.75, 8.15 Hz,
1H, 8-H), 7.09-7.14 (m, 2H, 5-H, 6-H), 7.35 (m, 1H, 7-H);
dC 53.8, 55.7, 67.2, 71.9, 114.3, 118.7, 124.0, 125.1, 126.9,
129.9, 130.3, 130.8, 154.9, 159.9, 170.7, 203.0; m/z 312
(M1, 40), 253 (92), 225 (100), 197 (99), 181 (25), 165
(34), 152 (34), 139 (22), 91 (12), 45 (16) (Found: C,
69.29; H, 4.87. C18H16O5 requires: C, 69.22; H, 5.16%).
3.4.1. 4-Benzyloxycarbonyl-2H-1-benzopyran-3(4H)-one
(27). Re¯uxed for 24 h, CC (eluant: CHCl3), 82%; amor-
phous solid, mp 58±608C; nmax (KBr)/cm21 3190, 1722,
1642; dH (270 MHz) 4.63 (s, 2H, 2-H), 5.39 (s, 2H, 20-H),
6.87-6.96 (m, 2H, 6-H, 8-H), 7.05 (app. dt, Jˆ1.7, 7.6 Hz,
1H, 7-H), 7.34±7.43 (m, 5H, C6H5), 7.76 (dd, Jˆ1.7,
7.9 Hz, 1H, 5-H), 12.86 (s, 1H, OH); dC 66.0, 67.1, 97.1,
116.4, 119.9, 122.3, 125.8, 126.6, 128.3, 128.6, 128.8,
135.2, 151.3, 169.8, 170.7; m/z 282 (M1, 20), 174 (18),
147 (7), 118 (9), 91 (100), 65 (19), 39 (8) (Found: C,
72.33; H, 4.92. C17H14O4 requires: C, 72.33; H, 5%).
3.5.2. 4-Methoxycarbonyl-4-(2,4-dimethoxyphenyl)-2H-
1-benzopyran-3(4H)-one (22). PLC (eluant: Et2O±light
petroleum 8:2); needles from ethanol, mp 105±1078C;
nmax (KBr)/cm21 1752, 1736; dH (400 MHz) 3.49 (s, 3H,
20-OMe), 3.78 (s, 3H, 40-OMe), 3.81 (s, 3H, 200-H), 4.48 (d,
Jˆ 17.1 Hz, 1H, 2-H), 4.80 (d, Jˆ17.1 Hz, 1H, 2-H), 6.47
(d, Jˆ2.5 Hz, 1H, 30-H), 6.54 (dd, Jˆ2.5, 8.6 Hz, 1H, 50-H),
6.85 (dd, Jˆ1.5, 7.75 Hz, 1H, 8-H), 6.95 (dt, Jˆ1.2,
7.55 Hz, 1H, 6-H), 7.03 (dd, Jˆ1.1, 8.1 Hz, 1H, 5-H),
7.17 (d, Jˆ8.6 Hz, 1H, 60-H), 7.21±7.27 (m, 1H, 7-H); dC
53.3, 55.4, 55.6, 64.4, 71.8, 100.3, 104.5, 117.5, 118.0,
123.1, 126.6, 128.8, 129.0, 130.3, 153.9, 157.5, 161.0,
168.9, 202.7; m/z 342 (M1, 36), 283 (21), 255 (94), 227
(16), 152 (19), 139 (14), 91 (100), 28 (24) (Found: C,
66.49; H, 5.30. C19H18O6 requires: C, 66.66; H, 5.30%).
3.4.2. 4-Benzyloxycarbonyl-7-methoxy-2H-1-benzopyran-
3(4H)-one (28). Re¯uxed for 9 h; CC (eluant: CHCl3), 78%;
amorphous solid, mp 57±608C; nmax (KBr)/cm21 3126,
1734, 1650; dH (270 MHz) 3.74 (s, 3H, 7-OMe), 4.61 (s,
2H, 2-H), 5.37 (s, 2H, 20-H), 6.48-6.51 (m, 2H, 6-H, 8-H),
7.36-7.41 (m, 5H, C6H5), 7.67 (d, Jˆ9 Hz, 1H, 5-H), 12.64
(s, 1H, OH); dC 55.4, 66.1, 67.0, 97.0, 102.4, 108.0, 112.5,
126.5, 128.3, 128.5, 128.8, 135.3, 152.5, 158.5, 167.7,
170.6; m/z 312 (M1, 18), 221 (31), 204 (32), 177 (15),
121 (28), 91 (100), 77 (14), 65 (18), 39 (8) (Found: C,
69.02; H, 5.09. C18H16O5 requires: C, 69.22; H, 5.16%).
3.5.3. 4-Methoxycarbonyl-4-(2,4,6-trimethoxyphenyl)-2H-
1-benzopyran-3(4H)-one (23). PLC (eluant: CHCl3);
needles from ethanol, mp 144±1468C; nmax (KBr)/cm21
1747, 1730; dH (270 MHz) 3.63 (s, 6H, 20-OMe, 60-OMe),
3.73 (s, 3H, 40-OMe), 3.80 (s, 3H, 200-H), 4.47 (d,
Jˆ16.7 Hz, 1H, 2-H), 4.68 (d, Jˆ16.7 Hz, 1H, 2-H), 6.18
(s, 2H, 30-H, 50-H), 6.89±7.04 (m, 3H, 5-H, 6-H, 8-H),
3.4.3. 4-Benzyloxycarbonyl-6,7-dimethoxy-2H-1-benzo-
pyran-3(4H)-one (29). Re¯uxed for 9 h; CC (eluant:
CHCl3), 79%; amorphous solid, mp 103±1058C; nmax

D. M. X. Donnelly et al. / Tetrahedron 57 (2001) 413±423
419
7.19±7.26 (m, 1H, 7-H); dC 53.3, 55.4, 56.1, 63.0, 71.9,
92.5, 108.7, 117.4, 122.9, 127.3, 128.6, 128.9, 154.1,
158.5, 161.2, 168.6, 202.6; m/z 372 (M1, 41), 313 (12),
285 (100), 255 (15), 152 (12), 139 (14), 91 (66), 69 (22),
28 (39) (Found: C, 64.64; H, 5.48. C20H20O7 requires: C,
64.51; H, 5.41%).
petroleum 8:2); rods from ethanol, mp 137±1388C; nmax
(KBr)/cm21 1746, 1733; dH (270 MHz) 3.46 (s, 3H,
20-OMe), 3.80 (s, 3H, 40-OMe), 4.46 (d, Jˆ17.2 Hz, 1H,
2-H), 4.75 (d, Jˆ17.2 Hz, 1H, 2-H), 5.22 (s, 2H, 200-H),
6.44 (d, Jˆ2.4 Hz, 1H, 30-H), 6.46 (dd, Jˆ2.4, 5.6 Hz,
1H, 50-H), 6.84 (dd, Jˆ1.45, 7.9 Hz, 1H, 8-H), 6.95 (dt,
Jˆ1.3, 7.5 Hz, 1H, 6-H), 7.03 (dd, Jˆ1.1, 8.05 Hz, 1H,
5-H), 7.10 (d, Jˆ5.6 Hz, 1H, 60-H), 7.18±7.32 (m, 6H,
7-H, C6H5); dC 55.4, 55.6, 66.2, 67.9, 71.8, 100.3, 100.4,
117.6, 117.9, 123.2, 126.6, 127.9, 128.3, 128.5, 128.9,
129.0, 130.4, 135.0, 153.9, 157.6, 161.1, 168.3, 202.7; m/z
418 (M1, 18), 327 (23), 283 (24), 255 (39), 227 (9), 152
(10), 91 (100), 65 (12), 28 (9) (Found: C, 71.57; H, 5.27.
C25H22O6 requires: C, 71.76; H, 5.30%).
3.5.4. 4-Methoxycarbonyl-2-(4-methoxyphenyl)-4-(4-meth-
oxyphenyl)-2H-1-benzopyran-3(4H)-one
(24).
PLC
(eluant: CHCl3); amorphous powder from ethanol±water,
mp 150±1528C; nmax (KBr)/cm21 1745, 1734; dH
(270 MHz) 3.72 (s, 3H, 40-OMe), 3.76 (s, 3H, 400-OMe),
3.78 (s, 3H, CO2Me), 5.58 (s, 1H, 2-H), 6.62-7.30 (m,
12H, Ar-H); m/z 418 (M1, 3), 390 (20), 330 (100), 180
(48), 165 (22), 151 (24), 121 (29), 91 (20) (Found: C,
72.0; H, 5.49. C25H22O6 requires: C, 71.76; H, 5.30%).
3.5.9. 4-Benzyloxycarbonyl-4-(2,4,6-trimethoxyphenyl)-
2H-1-benzopyran-3(4H)-one (32). PLC (eluant: CHCl3);
needles from ethanol, mp 156±1598C; nmax (KBr)/cm21
1743, 1729; dH (270 MHz) 3.50 (s, 6H, 20-OMe, 60-OMe),
3.79 (s, 3H, 40-OMe), 4.46 (d, Jˆ16.75 Hz, 1H, 2-H), 4.65
(d, Jˆ 16.75 Hz, 1H, 2-H), 5.17 (s, 2H, 200-H), 6.15 (s, 2H,
30-H, 50-H), 6.91±7.04 (m, 3H, 5-H, 6-H, 8-H), 7.18±7.28
(m, 6H, 7-H, C6H5); dC 55.3, 55.9, 62.6, 67.5, 71.9, 92.4,
108.9, 117.4, 122.8, 127.5, 127.6, 127.8, 128.3, 128.5,
128.9, 135.6, 154.1, 158.6, 161.2, 168.0, 202.5; m/z 448
(M1, 32), 357 (31), 313 (22), 285 (40), 181 (8), 107 (12),
91 (100), 28 (5) (Found: C, 69.48; H, 5.39. C26H24O7
requires: C, 69.63; H, 5.39%).
3.5.5.
4-Methoxycarbonyl-2-(2,4-dimethoxyphenyl)-4-
(2,4-dimethoxyphenyl)-2H-1-benzopyran-3(4H)-one (25).
PLC (eluant: Et2O±light petroleum 8:2); needles from
ethanol, mp 169±1728C; nmax (KBr)/cm21 1747, 1736; dH
(400 MHz) 3.52 (s, 6H, 200-OMe, 20-OMe), 3.79 (s, 3H, 40-
OMe), 3.80 (s, 3H, 400-OMe), 3.81 (s, 3H, CO2Me), 5.72 (s,
1H, 2-H), 6.46 (d, Jˆ2.3 Hz, 1H, 30-H), 6.48 (d, Jˆ2.3 Hz,
1H, 300-H), 6.52 (t, Jˆ2.2 Hz, 1H, 50-H), 6.54 (t, Jˆ2.2 Hz,
1H, 500-H), 6.81 (dd, Jˆ1.5, 7.75 Hz, 1H, 8-H), 6.97 (dt,
Jˆ1.2, 7.55 Hz, 1H, 6-H), 7.07 (dd, Jˆ1.1, 8.05 Hz, 1H,
5-H), 7.17 (d, Jˆ8.6 Hz, 1H, 60-H), 7.21±7.28 (m, 1H,
7-H), 7.33 (d, Jˆ8.5 Hz, 1H, 600-H); m/z 478 (M1, 5), 450
(20), 390 (100), 363 (20), 269 (18), 225 (23), 180 (55), 151
(50), 121 (38), 91 (29), 77(32) (Found: C, 67.82; H, 5.55.
C27H26O8 requires: C, 67.77; H, 5.48%).
3.5.10. 4-Benzyloxycarbonyl-7-methoxy-4-(4-methoxy-
phenyl)-2H-1-benzopyran-3(4H)-one (33). PLC (eluant:
CHCl3); amorphous powder from ethanol, mp 103±1048C;
nmax (KBr)/cm21 1748, 1736; dH (270 MHz) 3.78 (s, 3H,
40-OMe),p 3.82 (s, 3H, 7-OMe),p 4.48 (d, Jˆ16.6 Hz, 1H,
2-H), 4.56 (d, Jˆ16.6 Hz, 1H, 2-H), 5.21 (d, Jˆ12.45 Hz,
1H, 200-H), 5.28 (d, Jˆ12.45 Hz, 1H, 200-H), 6.60 (d,
Jˆ8.6 Hz, 2H, 30-H, 50-H), 6.81±6.85 (m, 3H, 5-H, 6-H,
8-H), 6.97 (d, Jˆ8.6 Hz, 2H, 20-H, 60-H), 7.23-7.32 (m,
5H, C6H5); dC 55.3, 55.5, 66.2, 67.8, 71.4, 103.1, 110.2,
113.9, 116.3, 127.0, 128.2, 128.4, 128.5, 130.4, 130.5,
135.1, 155.5, 159.5, 160.9, 169.8, 202.4; m/z 418 (M1, 5),
327 (10), 283 (68), 255 (11), 227 (24), 139 (5), 115 (6), 91
(100), 65 (18) (Found: C, 71.49; H, 5.37. C25H22O6 requires:
C, 71.76; H, 5.30%).
3.5.6. 4-Methoxycarbonyl-2-(2,4,6-trimethoxyphenyl)-4-
(2,4,6-trimethoxyphenyl)-2H-1-benzopyran-3(4H)-one
(26). PLC (eluant: CHCl3); amorphous powder from
ethanol, mp 197±1998C; nmax (KBr)/cm21 1744, 1734; dH
(270 MHz) 3.66 (s, 6H, 20-OMe, 60-OMe), 3.73 (s, 6H, 200-
OMe, 600-OMe), 3.76 (s, 3H, 40-OMe), 3.80 (s, 3H, 400-
OMe), 3.81 (s, 3H, CO2Me), 5.92 (s, 1H, 2-H), 6.15 (s,
2H, 30-H, 50-H), 6.19 (s, 2H, 300-H, 500-H), 6.78 (dd,
Jˆ1.45, 7.7 Hz, 1H, 8-H), 6.92-6.97 (m, 1H, 6-H), 7.10
(d, Jˆ6.95 Hz, 1H, 5-H), 7.21±7.26 (m, 1H, 7-H); m/z
538 (M1, 3), 510 (25), 451 (100), 299 (15), 211 (80), 181
(23), 151 (18), 121 (22), 91 (17) (Found: C, 64.61; H, 5.91.
C29H30O10 requires: C, 64.68; H, 5.61%).
3.5.11. 4-Benzyloxycarbonyl-7-methoxy-4-(2,4-dimethoxy-
phenyl)-2H-1-benzopyran-3(4H)-one (34). PLC (eluant:
Et2O±light petroleum 8:2); amorphous powder from etha-
nol, mp 124±1268C; nmax (KBr)/cm21 1743, 1733; dH
(270 MHz) 3.49 (s, 3H, 20-OMe), 3.78 (s, 3H, 40-OMe),p
3.80 (s, 3H, 7-OMe),p 4.46 (d, Jˆ16.7 Hz, 1H, 2-H), 4.72
(d, Jˆ 16.7 Hz, 1H, 2-H), 5.22 (s, 2H, 200-H), 6.46±6.56 (m,
4H, 6-H, 8-H, 50-H, 30-H), 6.76 (d, Jˆ8.6 Hz, 1H, 5-H), 7.10
(d, Jˆ9.15 Hz, 1H, 60-H), 7.24-7.30 (m, 5H, C6H5); dC 55.4,
55.6, 63.8, 67.7, 71.8, 100.3, 102.5, 104.4, 109.6, 118.1,
118.2, 127.9, 128.3, 128.5, 129.7, 130.3, 135.5, 155.4,
158.4, 159.9, 161.0, 168.6, 202.6; m/z 448 (M1, 10), 357
(8), 313 (33), 285 (18), 257 (16), 121 (38), 91 (100), 65 (12)
(Found: C, 69.62; H, 5.47. C26H24O7 requires: C, 69.63; H,
5.39%).
3.5.7. 4-Benzyloxycarbonyl-4-(4-methoxyphenyl)-2H-1-
benzopyran-3(4H)-one (30). PLC (eluant: CHCl3); needles
from ethanol, mp 124±1268C; nmax (KBr)/cm21 1739, 1724;
dH (270 MHz) 3.77 (s, 3H, 40-OMe), 4.49 (d, Jˆ17.5 Hz,
1H, 2-H), 4.57 (d, Jˆ17.5 Hz, 1H, 2-H), 5.22 (d, Jˆ
12.45 Hz, 1H, 200-H), 5.29 (d, Jˆ12.45 Hz, 1H, 200-H), 6.83
(dd, Jˆ2.2, 6.8 Hz, 2H, 50-H, 30-H), 6.90-7.10 (m, 4H, 5-H,
6-H, 20-H, 60-H), 7.21-7.38 (m, 6H, 7-H, C6H5); dC 55.5, 67.8,
67.9, 71.4, 113.9, 118.2, 123.6, 124.9, 126.5, 128.2, 128.4,
128.5, 129.7, 130.0, 130.5, 135.1, 154.3, 159.5, 169.1,
202.6; m/z 388 (M1, 8), 297 (20), 253 (36), 225 (22), 197
(32), 181 (10), 165 (19), 152 (18), 91 (100), 28 (20) (Found: C,
74.52; H, 4.89. C24H20O5 requires: C, 74.22; H, 5.19%).
3.5.8. 4-Benzyloxycarbonyl-4-(2,4-dimethoxyphenyl)-2H-
1-benzopyran-3(4H)-one (31). PLC (eluant: Et2O±light
3.5.12. 4-Benzyloxycarbonyl-7-methoxy-4-(2,4,6-trimeth-
oxyphenyl)-2H-1-benzopyran-3(4H)-one (35). PLC (eluant:

420
D. M. X. Donnelly et al. / Tetrahedron 57 (2001) 413±423
CHCl3); plates from ethanol, mp 151±1538C; nmax (KBr)/
cm21 1744, 1734; dH (270 MHz) 3.51 (s, 6H, 20-OMe,
60-OMe), 3.77 (s, 3H, 40-OMe),p 3.79 (s, 3H, 7-OMe),p
4.47 (d, Jˆ16.7 Hz, 1H, 2-H), 4.60 (d, Jˆ16.7 Hz, 1H,
2-H), 5.18 (s, 2H, 200-H), 6.14 (s, 2H, 30-H, 50-H), 6.57 (m,
2H, 6-H, 8-H), 6.82 (d, Jˆ8.6 Hz, 1H, 5-H), 7.25±7.27 (m,
5H, C6H5); dC 55.4, 55.9, 62.5, 67.6, 72.1, 92.5, 102.5, 108.9,
109.5, 119.3, 127.9, 128.0, 128.4, 129.8, 135.8, 155.1, 158.6,
160.0, 161.2, 167.9, 202.5; m/z 478 (M1, 18), 387 (12), 343
(69), 315 (18), 287 (5), 137 (15), 121 (46), 91 (100), 65 (10)
(Found: C, 68.03; H, 5.55. C27H26O8 requires: C, 67.77; H,
5.47%).
3.6. General procedure for the debenzyloxycarbonylation
of 4-benzyloxycarbonyl-4-aryl-2H-1-benzopyran-3(4H)-
ones
A mixture of the 4-benzyloxycarbonyl-4-aryl-2H-1-benzo-
pyran-3(4H)-one and 10% palladium on charcoal (0.110 g
per 1 mmol of ketone) in methanol (200 mL per 1 mmol of
ketone) was hydrogenated at room temperature and atmos-
pheric pressure for 3 d. The catalyst was ®ltered off, the
®ltrate was evaporated and the residue puri®ed by chroma-
tography on silica using the indicated solvent system.
3.6.1. 3,4-Dihydro-4-(4-methoxyphenyl)-2H-1-benzopyran-
3-ol (42). PLC (eluant: Et2O); plates from ethanol, mp 77±
808C; nmax (KBr)/cm21 3386; dH (270 MHz) 1.76 (bs, 1H,
3-OH), 3.79 (s, 3H, 40-OMe), 4.13 (m, 3H, 3-H, 2-H), 4.31
(d, Jˆ4.25 Hz, 1H, 4-H), 6.83-6.91 (m, 5H, 5-H, 6-H, 8-H,
30-H, 50-H), 7.09-7.15 (m, 3H, 7-H, 20-H, 60-H); dC 46.6,
55.3, 66.0, 67.5, 114.0, 116.6, 121.0, 122.8, 128.1, 128.2,
130.9, 131.2, 154.3, 158.9; m/z 256 (M1, 48), 211 (86), 197
(23), 181 (100), 168 (8), 152 (10), 115 (12), 91 (7)
(Found: C, 75.01; H, 6.44. C16H16O3 requires: C, 74.98;
H, 6.29%).
3.5.13. 4-Benzyloxycarbonyl-6,7-dimethoxy-4-(4-meth-
(36).
oxyphenyl)-2H-1-benzopyran-3(4H)-one
PLC
(eluant: CHCl3); amorphous powder from ethanol±water,
mp 95±988C; nmax (KBr)/cm21 1745, 1733; dH (270 MHz)
3.50 (3H, s, 6-OMe), 3.78 (3H, s, 40-OMe),p 3.89 (3H, s,
7-OMe),p 4.45 (d, Jˆ16.6 Hz, 1H, 2-H), 4.54 (d,
Jˆ16.6 Hz, 1H, 2-H), 5.15 (d, Jˆ12.3 Hz, 1H, 200-H), 5.35
(d, Jˆ12.3 Hz, 1H, 200-H), 6.29 (s, 1H, 8-H), 6.63 (s, 1H,
5-H), 6.83 (d, Jˆ9 Hz, 2H, 30-H, 50-H), 6.99 (d, Jˆ9 Hz,
2H, 20-H, 60-H), 7.26-7.30 (m, 5H, C6H5); dC 55.3, 56.1,
56.2, 66.7, 67.9, 71.5, 101.7, 111.1, 113.9, 114.4, 127.0,
128.4, 128.5, 128.6, 130.5, 135.2, 145.3, 148.7, 150.2,
159.5, 169.9, 202.3; m/z 448 (M1, 18), 313 (84), 285 (12),
257 (44), 213 (12), 121 (9), 91 (100), 65 (20), 28 (45)
(Found: C, 69.35; H, 5.42. C26H24O7 requires: C, 69.63;
H, 5.39%).
3.6.2. 3,4-Dihydro-4-(2,4-dimethoxyphenyl)-2H-1-benzo-
pyran-3-ol (43). PLC (eluant: Et2O±light petroleum 6:4);
needles from ethanol, mp 86±888C; nmax (KBr)/cm21 3358;
dH (270 MHz) 2.58 (d, Jˆ3.3 Hz, 1H, 3-OH), 3.79 (s, 3H,
40-OMe), 3.86 (s, 3H, 20-OMe), 4.08 (m, 2H, 2-H), 4.27 (m,
1H, 3-H), 4.80 (d, Jˆ4.45 Hz, 1H, 4-H), 6.43 (dd, Jˆ 2.4,
8.45 Hz, 1H, 50-H), 6.53 (d, Jˆ2.4 Hz, 1H, 30-H), 6.75-6.92
(m, 4H, 5-H, 6-H, 8-H, 60-H), 7.12-7.18 (m, 1H, 7-H); dC
40.0, 55.4, 55.6, 65.7, 66.8, 98.5, 104.4, 116.6, 120.6, 120.8,
122.6, 127.8, 130.8, 132.0, 154.8, 158.3, 159.9; m/z 286
(M1, 23), 268 (5), 241 (12), 227 (14), 211 (100), 168 (8),
139 (6), 91 (5) (Found: C, 71.16; H, 6.41. C17H18O4
requires: C, 71.31; H, 6.33%).
3.5.14. 4-Benzyloxycarbonyl-6,7-dimethoxy-4-(2,4-dimeth-
oxyphenyl)-2H-1-benzopyran-3(4H)-one
(37).
PLC
(eluant: Et2O±light petroleum 8:2); plates from ethanol±
water, mp 121±1238C; nmax (KBr)/cm21 1744, 1733; dH
(270 MHz) 3.51 (s, 3H, 20-OMe), 3.58 (s, 3H, 6-OMe),
3.80 (s, 3H, 40-OMe),p 3.86 (s, 3H, 7-OMe),p 4.43 (d,
Jˆ16.75 Hz, 1H, 2-H), 4.71 (d, Jˆ16.75 Hz, 1H, 2-H),
5.22 (s, 2H, 200-H), 6.34 (s, 1H, 8-H), 6.46 (m, 2H, 30-H,
50-H), 6.58 (s, 1H, 5-H), 7.07 (d, Jˆ8.6 Hz, 1H, 60-H),
7.25-7.30 (m, 5H, C6H5); dC 55.4, 55.7, 56.0, 56.3,
63.7, 67.7, 72.0, 100.2, 101.3, 104.5, 111.4, 116.7,
118.0, 128.0, 128.3, 128.5, 130.4, 135.1, 144.9, 148.3,
149.7, 157.9, 161.0, 168.6, 202.2; m/z 478 (M1, 17),
343 (54), 315 (18), 287 (19), 151 (28), 91 (100), 65
(18), 28 (6) (Found: C, 67.91; H, 5.66. C27H26O8 requires: C,
67.77; H, 5.47%).
3.6.3. 4-(2,4,6-Trimethoxyphenyl)-2H-1-benzopyran-3(4H)-
one (39). PLC (eluant: CHCl3); needles from ethanol, mp
130±1328C; nmax (KBr)/cm21 1721; dH (270 MHz) 3.68 (s,
6H, 20-OMe, 60-OMe), 3.81 (s, 3H, 40-OMe), 4.46 (d,
Jˆ16.5 Hz, 1H, 2-H), 4.61 (d, Jˆ16.5 Hz, 1H, 2-H), 5.14
(s, 1H, 4-H), 6.17 (s, 2H, 30-H, 50-H), 6.75 (m, 1H, 8-H),
6.88 (dt, Jˆ1.3, 6.9 Hz, 1H, 6-H), 7.02 (dd, Jˆ1.3, 8.05 Hz,
1H, 5-H), 7.12-7.18 (m, 1H, 7-H); dC 44.4, 55.5, 55.6
72.6, 91.2, 107.3, 117.0, 122.6, 126.1, 127.4, 127.5,
154.0, 158.7, 161.1, 208.5; m/z 314 (M1, 100), 286
(82), 255 (25), 241 (17), 179 (14), 168 (18), 137 (16), 91
(18), 28 (22) (Found: C, 68.80; H, 5.80. C18H18O5 requires:
C, 68.78; H, 5.77%).
3.5.15. 4-Benzyloxycarbonyl-6,7-dimethoxy-4-(2,4,6-tri-
methoxyphenyl)-2H-1-benzopyran-3(4H)-one (38). PLC
(eluant: CHCl3); amorphous solid from ether, mp 149±
1518C; nmax (KBr)/cm21 1745, 1731; dH (270 MHz) 3.52
(s, 6H, 20-OMe, 60-OMe), 3.62 (s, 3H, 6-OMe), 3.80 (s,
3H, 40-OMe),p 3.85 (s, 3H, 7-OMe),p 4.47 (d,
Jˆ16.72 Hz, 1H, 2-H), 4.58 (d, Jˆ16.72 Hz, 1H, 2-H),
5.16 (d, Jˆ12.38 Hz, 1H, 200-H), 5.22 (d, Jˆ12.38 Hz,
1H, 200-H), 6.14 (s, 2H, 30-H, 50-H), 6.49 (s, 1H, 8-H),
6.57 (s, 1H, 5-H), 7.26-7.27 (m, 5H, C6H5); dC 55.4,
55.9, 56.3, 62.1, 67.5, 72.3, 92.5, 101.3, 108.8, 112.0,
118.1, 127.9, 128.0, 128.4, 135.8, 144.6, 148.3, 149.2,
158.6, 161.1, 168.4, 202.4; m/z 508 (M1, 14), 373 (28),
345 (10), 317 (8), 151 (16), 91 (100), 65 (12), 28 (7)
(Found: C, 65.84; H, 5.69. C28H28O9 requires: C, 66.13;
H, 5.55%).
3.6.4. 3,4-Dihydro-7-methoxy-4-(4-methoxyphenyl)-2H-
1-benzopyran-3-ol (45). PLC (eluant: Et2O); plates from
ethanol, mp 100±1028C; nmax (KBr)/cm21 3307; dH
(270 MHz) 1.68 (bs, 1H, 3-OH), 4.11 (m, 3H, 2-H, 3-H),
4.25 (d, Jˆ4.2 Hz, 1H, 4-H), 6.43±6.46 (m, 2H, 30-H, 50-H),
6.77±6.90 (m, 3H, 5-H, 6-H, 8-H), 7.10 (d, Jˆ8.45 Hz, 2H,
20-H, 60-H); dC 46.1, 55.3, 66.1, 67.5, 101.1, 108.2, 114.1,
114.8, 131.2, 131.4, 131.8, 155.2, 158.9, 159.6; m/z 286
(M1, 47), 241 (100), 227 (25), 211 (98), 198 (12), 184
(8), 168 (10), 152 (8), 121 (18), 91 (6) (Found: C, 71.55;
H, 6.36. C17H18O4 requires: C, 71.31; H, 6.34%).

D. M. X. Donnelly et al. / Tetrahedron 57 (2001) 413±423
421
3.6.5. 3,4-Dihydro-7-methoxy-4-(2,4-dimethoxyphenyl)-
2H-1-benzopyran-3-ol (46). PLC (eluant: Et2O±light
petroleum 8:2); needles from ethanol, mp 116±1188C;
nmax (KBr)/cm21 3515; dH (270 MHz) 2.58 (s, 1H, 3-OH),
3.77 (s, 3H, 40-OMe),p 3.78 (s, 3H, 7-OMe),p 3.85 (s, 3H, 20-
OMe), 4.07 (m, 2H, 2-H), 4.24 (m, 1H, 3-H), 4.73 (d, Jˆ
4.75 Hz, 1H, 4-H), 6.40-6.46 (m, 4H, 6-H, 8-H, 30-H, 50-H),
6.51±6.78 (m, 2H, 5-H, 60-H); dC 39.5, 55.0, 55.5, 55.6, 65.9,
66.9, 98.6, 101.1, 104.5, 108.2, 114.7, 120.9, 131.4, 132.0,
155.7, 158.4, 159.5, 160.0; m/z 316 (M1, 20), 298 (5), 271
(6), 257 (5), 241 (75), 198 (8), 149 (6), 121 (5), 28 (100)
(Found: C, 68.08; H, 6.14. C18H20O5 requires: C, 68.34; H,
6.37%).
2-H), 5.07 (s, 1H, 4-H), 6.17 (s, 2H, 30-H, 50-H), 6.28 (s,
1H, 8-H), 6.59 (s, 1H, 5-H); dC 43.8, 55.4, 55.8, 56.0, 56.4,
73.0, 91.3, 101.3, 107.9, 110.9, 116.8, 144.6, 147.8, 148.4,
158.9, 161.0, 208.6; m/z 374 (M1, 100), 359 (22), 346 (20),
331 (18), 315 (19), 301 (25), 206 (13), 167 (12), 151 (18),
137 (12), 69 (20) (Found: C, 63.87; H, 6.10. C20H22O7
requires: C, 64.16; H, 5.92%).
3.7. General procedure for the reduction of 4-aryl-2H-1-
benzopyran-3(4H)-ones
Sodium borohydride (5 equiv.) was added to a stirred
mixture of the 4-aryl-2H-1-benzopyran-3(4H)-one
(1 equiv.) in THF (20 mL per 0.5 mmol of ketone) and
water (4 mL per 0.5 mmol of ketone). The mixture was
stirred at room temperature for 1 h and then acetone
(10 mL) was added slowly. After addition of water
(20 mL), the mixture was extracted with ethyl acetate
(2£30 mL), washed with dilute hydrochloric acid (40 mL),
brine (40 mL) and dried over anhydrous sodium sulfate.
Removal of the solvent gave a solid or oil which was crys-
tallised as indicated.
3.6.6. 7-Methoxy-4-(2,4,6-trimethoxyphenyl)-2H-1-benzo-
pyran-3(4H)-one (40). PLC (eluant: CHCl3); needles from
ethanol, mp 140±1428C; nmax (KBr)/cm21 1718; dH
(270 MHz) 3.69 (s, 6H, 20-OMe, 60-OMe), 3.76 (s, 3H, 40-
OMe),p 3.81 (s, 3H, 7-OMe),p 4.47 (d, Jˆ16.55 Hz, 1H,
2-H), 4.58 (d, Jˆ16.55 Hz, 1H, 2-H), 5.07 (s, 1H, 4-H),
6.16 (s, 2H, 30-H, 50-H), 6.48±6.58 (m, 2H, 6-H, 8-H),
6.64 (d, Jˆ 8.6 Hz, 1H, 5-H); dC 43.7, 55.4, 55.8, 72.8,
91.2, 102.3, 108.0, 109.1, 118.0, 128.5, 154.7, 158.6,
159.2, 161.0, 208.5; m/z 344 (M1, 42), 316 (18), 285
(16), 271 (13), 167 (12), 137 (13), 121 (15), 69 (10),
28 (100) (Found: C, 66.19; H, 5.65. C19H20O6 requires:
C, 66.27; H, 5.85%).
3.7.1. 3,4-Dihydro-4-(2,4,6-trimethoxyphenyl)-2H-1-benzo-
pyran-3-ol (44). Needles from ethanol, mp 133±1358C;
nmax (KBr)/cm21 3506; dH (270 MHz) 3.35 (s, 3H, 40-
OMe), 3.81 (s, 6H, 20-OMe, 60-OMe), 3.98 (s, 1H, 3-OH),
4.15 (d, Jˆ11.2 Hz, 2H, 2-H), 4.30 (m, 1H, 3-H), 4.99 (d,
Jˆ4.4 Hz, 1H, 4-H), 6.15 (s, 1H, 50-H), 6.26 (s, 1H, 30-H),
6.70±6.73 (m, 2H, 6-H, 8-H), 6.86 (d, Jˆ7.9 Hz, 1H, 5-H),
7.04 (m, 1H, 7-H); dC 37.1, 56.0, 56.6, 67.8, 71.3, 92.3,
93.1, 109.7, 116.9, 121.0, 124.9, 127.3, 128.6, 154.7,
159.6, 159.9, 161.0; m/z 316 (M1, 28), 298 (19), 267 (10),
241 (100), 226 (8), 168 (5), 91 (8), 44 (11) (Found: C, 68.10;
H, 6.33. C18H20O5 requires: C, 68.34; H, 6.37%).
3.6.7. 3,4-Dihydro-6,7-dimethoxy-4-(4-methoxyphenyl)-
2H-1-benzopyran-3-ol (48). PLC (eluant: Et2O); plates
from ethanol, mp 93±958C; nmax (KBr)/cm21 3493; dH
(270 MHz) 1.69 (bs, 1H, 3-OH), 3.65 (s, 3H, 6-OMe),
3.80 (s, 3H, 40-OMe), 3.84 (s, 3H, 7-OMe), 4.07 (m, 3H,
2-H, 3-H), 4.24 (d, Jˆ4.3 Hz, 1H, 4-H), 6.33 (s, 1H, 8-H),
6.47 (s, 1H, 5-H), 6.88 (d, Jˆ8.7 Hz, 2H, 30-H, 50-H), 7.12
(d, Jˆ 8.7 Hz, 2H, 20-H, 60-H); dC 46.2, 55.2, 55.9, 56.3,
66.2, 67.3, 100.3, 112.9, 113.9, 114.0, 131.2, 131.6, 143.6,
148.4, 148.9, 158.9; m/z 316 (M1, 65), 271 (100), 257 (40),
241 (79), 227 (10), 186 (10), 145 (18), 69 (25), 44 (45)
(Found: C, 68.07; H, 6.51. C18H20O5 requires: C, 68.34;
H, 6.37%).
3.7.2. 3,4-Dihydro-7-methoxy-4-(2,4,6-trimethoxyphenyl)-
2H-1-benzopyran-3-ol (47). Needles from ethanol, mp
98±1008C; nmax (KBr)/cm21 3505; dH (270 MHz) 3.42 (s,
3H, 40-OMe),p 3.75 (s, 3H, 7-OMe),p 3.82 (s, 6H, 20-OMe,
60-OMe), 3.98 (s, 1H, 3-OH), 4.16 (d, Jˆ11.2 Hz, 2H, 2-H),
4.31 (m, 1H, 3-H), 4.93 (d, Jˆ4.6 Hz,1H, 4-H), 6.15 (s, 1H,
50-H), 6.25 (s, 1H, 30-H), 6.34 (dd, Jˆ2.55, 8.5 Hz, 1H,
6-H), 6.45 (d, Jˆ2.55 Hz, 1H, 8-H), 6.58 (d, Jˆ8.5 Hz,
1H, 5-H); dC 36.0, 55.3, 55.4, 56.1, 67.2, 70.9, 91.7, 92.5,
101.0, 107.5, 109.2, 116.2, 128.6, 154.8, 158.6, 159.3,
159.7, 160.5; m/z 346 (M1, 13), 328 (8), 271 (66), 256
(5), 227 (4), 151 (4), 121 (5), 28 (100) (Found: C, 65.93;
H, 6.69. C19H22O6 requires: C, 65.88; H, 6.40%).
3.6.8. 3,4-Dihydro-6,7-dimethoxy-4-(2,4-dimethoxyphe-
nyl)-2H-1-benzopyran-3-ol (49). PLC (eluant: Et2O±light
petroleum 8:2); needles from ethanol, mp 128±1308C; nmax
(KBr)/cm21 3527; dH (270 MHz) 2.23 (bs, 1H, 3-OH), 3.67
(s, 3H, 6-OMe), 3.79 (s, 3H, 40-OMe), 3.85 (s, 3H, 7-OMe),
3.87 (s, 3H, 20-OMe), 4.04 (m, 2H, 2-H), 4.25 (m, 1H, 3-H),
4.72 (d, Jˆ4.95 Hz, 1H, 4-H), 6.34 (s, 1H, 8-H), 6.43 (dd,
Jˆ2.4, 8.45 Hz, 1H, 50-H), 6.47 (s, 1H, 5-H), 6.52 (d,
Jˆ2.4 Hz, 1H, 30-H), 6.78 (d, Jˆ8.45 Hz, 1H, 60-H); dC
39.7, 55.4, 55.6, 55.9, 56.4, 65.9, 66.7, 98.5, 100.4, 104.4,
112.8, 112.9, 120.6, 132.0, 143.6, 148.8, 148.9, 158.4, 159.9;
m/z 346 (M1, 32), 328 (4), 287 (6), 271 (100), 227 (9), 185
(7), 151 (16), 69 (16), 44 (21) (Found: C, 65.60; H, 6.55.
C19H22O6 requires: C, 65.88; H, 6.40%).
3.7.3. 3,4-Dihydro-6,7-dimethoxy-4-(2,4,6-trimethoxy-
phenyl)-2H-1-benzopyran-3-ol (50). Needles from
ethanol, mp 145±1478C; nmax (KBr)/cm21 3497; dH
(270 MHz) 3.42 (s, 3H, 6-OMe), 3.61 (s, 3H, 40-OMe),
3.83 (s, 3H, 7-OMe), 3.84 (s, 3H, 60-OMe), 3.85 (s, 3H,
20-OMe), 3.89 (s, 1H, 3-OH), 4.12 (d, Jˆ10.1 Hz, 2H,
2-H), 4.31 (m, 1H, 3-H), 4.93 (d, Jˆ4.85 Hz, 1H, 4-H),
6.16 (s, 1H, 50-H), 6.21 (s, 1H, 30-H), 6.27 (s, 1H, 8-H),
6.48 (s, 1H, 5-H); dC 36.1, 55.3, 55.4, 55.8, 56.0, 56.7,
67.2, 70.7, 91.6, 92.3, 100.5, 108.8, 111.2, 114.9, 143.2,
147.9, 159.3, 159.6, 160.5; m/z 376 (M1, 34), 358 (6), 301
(100), 285 (7), 257 (8), 167 (7), 121 (5), 69 (13), 44 (19)
3.6.9. 6,7-Dimethoxy-4-(2,4,6-trimethoxyphenyl)-2H-1-
benzopyran-3(4H)-one (41). PLC (eluant: CHCl3); needles
from ethanol, mp 112±1148C; nmax (KBr)/cm21 1731; dH
(270 MHz) 3.65 (s, 3H, 6-OMe), 3.71 (s, 6H, 20-OMe,
60-OMe), 3.82 (s, 3H, 40-OMe),p 3.85 (s, 3H, 7-OMe),p
4.47 (d, Jˆ16.7 Hz, 1H, 2-H), 4.55 (d, Jˆ16.7 Hz, 1H,

422
D. M. X. Donnelly et al. / Tetrahedron 57 (2001) 413±423
(Found: C, 63.61; H, 6.61. C20H24O7 requires: C, 63.82; H,
6.43%).
Jˆ8.79 Hz, 2H, 20-H, 60-H); dC 55.3, 55.4, 65.6, 102.0,
106.9, 113.8, 116.3, 117.2, 126.8, 130.0, 130.9, 136.5,
156.2, 159.3, 160.5; m/z 268 (M1, 38), 267 (34), 253 (15),
241 (21), 237 (10), 151 (22), 135 (22), 83 (30), 28 (100).
3.8. General procedure for the dehydration of 4-aryl-3,4-
dihydro-2H-1-benzopyran-3-ols
3.8.5. 7-Methoxy-4-(2,4-dimethoxyphenyl)-2H-1-benzo-
pyran (55). PLC (eluant: Et2O±light petroleum 1:1); yellow
oil; nmax (CH2Cl2)/cm21 1645; dH (270 MHz) 3.70 (s, 3H,
20-OMe), 3.75 (s, 3H, 40-OMe),p 3.83 (s, 3H, 7-OMe),p 4.87
(d, Jˆ3.84 Hz, 2H, 2-H), 5.57 (t, Jˆ3.84 Hz, 1H, 3-H), 6.33
(dd, Jˆ2.56, 8.61 Hz, 1H, 50-H), 6.42 (d, Jˆ 2.56 Hz, 1H,
30-H), 6.49±6.52 (m, 2H, 6-H, 8-H), 6.63 (d, Jˆ8.61 Hz,
1H, 5-H), 7.08 (d, Jˆ8.61 Hz, 1H, 60-H); dC 55.3, 55.4,
55.5, 65.8, 98.8, 101.5, 103.9, 106.7, 117.2, 118.0, 120.1,
125.5, 131.1, 133.7, 155.2, 158.2, 160.2, 160.7; m/z 298
(M1, 36), 297 (33), 283 (8), 267 (18), 241 (100), 198
(18), 161 (24), 121 (12), 43 (22).
A cooled (0±58C) solution of the 4-aryl-3,4-dihydro-2H-1-
benzopyran-3-ol (1 equiv.) in dry pyridine (7.5 mL per
1 mmol of alcohol) was treated, dropwise, with phosphorus
oxychloride (26 equiv.). The mixture was stirred at 0±58C
for 2 h and then at room temperature for 24 h. Water
(15 mL) was carefully added and the solution was extracted
with ether (2£15 mL), washed with 10% hydrochloric acid
(30 mL), water (30 mL), brine (30 mL) and dried over
magnesium sulfate. After distillation of the solvent under
reduced pressure, the residue was puri®ed by chroma-
tography on silica using the indicated solvent system.
3.8.6. 7-Methoxy-4-(2,4,6-trimethoxyphenyl)-2H-1-benzo-
pyran (56). PLC (eluant: CHCl3); needles from ethanol, mp
179±1818C; nmax (KBr)/cm21 1652; dH (270 MHz) 3.69 (s,
6H, 20-OMe, 60-OMe), 3.74 (s, 3H, 40-OMe),p 3.85 (s, 3H,
7-OMe),p 4.92 (d, Jˆ3.65 Hz, 2H, 2-H), 5.52 (t, Jˆ 3.65 Hz,
1H, 3-H), 6.19 (s, 2H, 30-H, 50-H), 6.30 (dd, Jˆ2.55,
8.55 Hz, 1H, 6-H), 6.41 (d, Jˆ2.55 Hz, 1H, 8-H), 6.51 (d,
Jˆ8.55 Hz, 1H, 5-H); dC 55.3, 55.4, 56.0, 66.0, 90.9, 101.6,
106.7, 108.3, 117.4, 119.5, 125.8, 128.7, 155.4, 159.1,
160.1, 160.9; m/z 328 (M1, 100), 327 (92), 313 (18), 297
(86), 281 (22), 254 (8), 161 (18), 139 (12), 69 (32) (Found:
C, 69.27; H, 6.29. C19H20O5 requires: C, 69.50; H, 6.14%).
3.8.1. 4-(4-Methoxyphenyl)-2H-1-benzopyran (51). PLC
(eluant: Et2O±light petroleum 2:3); pale yellow plates from
ethanol, mp 89±928C (lit.,30 mp 928C); nmax (KBr)/cm21
1635; dH (270 MHz) 3.82 (s, 3H, 40-OCH3), 4.81 (d,
Jˆ4.03 Hz, 2H, 2-H), 5.74 (t, Jˆ4.03 Hz, 1H, 3-H), 6.84-
6.93 (m, 4H, 6-H, 8-H, 30-H, 50-H), 7.02 (dd, Jˆ1.65,
7.69 Hz, 1H, 5-H), 7.13 (m, 1H, 7-H), 7.26 (dd, Jˆ2.19,
6.59 Hz, 2H, 20-H, 60-H); dC 55.4, 65.3, 113.8, 116.3,
119.3, 121.2, 124.0, 125.9, 129.2, 129.8, 130.7, 136.7,
154.9, 159.3; m/z 238 (M1, 82), 237 (100), 223 (30), 207
(33), 194 (22), 165 (38), 152 (20), 139 (22), 131 (35), 119
(22), 89 (21), 28 (23).
3.8.7. 6,7-Dimethoxy-4-(4-methoxyphenyl)-2H-1-benzo-
pyran (57). PLC (eluant: Et2O±light petroleum 2:3); yellow
oil; nmax (CH2Cl2)/cm21 1638; dH (270 MHz) 3.66 (s, 3H,
6-OMe), 3.79 (s, 3H, 40-OMe),p 3.84 (s, 3H, 7-OMe),p 4.76
(d, Jˆ4 Hz, 2H, 2-H), 5.66 (t, Jˆ4 Hz, 1H, 3-H), 6.32 (s,
1H, 8-H), 6.43 (s, 1H, 5-H), 6.83 (d, Jˆ8.8 Hz, 2H, 30-H, 50-
H), 7.05 (d, Jˆ8.8 Hz, 2H, 20-H, 60-H); dC 55.2, 55.8, 56.3,
63.6, 100.5, 113.0, 113.9, 114.0, 115.0, 129.6, 135.7, 138.0,
143.1, 148.7, 149.1, 158.1; m/z 298 (M1, 100), 297 (95), 283
(32), 267 (78), 251 (21), 164 (22), 127 (20), 69 (21), 28 (18).
3.8.2. 4-(2,4-Dimethoxyphenyl)-2H-1-benzopyran (52).
PLC (eluant: Et2O±light petroleum 1:1); plates from etha-
nol, mp 124±1268C; nmax (KBr)/cm21 1643; dH (270 MHz)
3.61 (s, 3H, 20-OMe), 3.75 (s, 3H, 40-OMe), 4.80 (d,
Jˆ3.65 Hz, 2H, 2-H), 5.63 (t, Jˆ3.65 Hz, 1H, 3-H), 6.41±
6.45 (m, 2H, 30-H, 50-H), 6.63-6.76 (m, 3H, 5-H, 6-H, 8-H),
6.96±7.15 (m, 2H, 7-H, 60-H); dC 55.4, 55.5, 65.6, 98.8,
104.4, 115.9, 120.0, 121.0, 121.1, 124.0, 125.8, 128.8,
131.4, 133.9, 154.0, 158.3, 160.8; m/z 268 (M1, 44), 267
(46), 253 (14), 237 (73), 221 (12), 152 (12), 127 (23), 28
(100) (Found: C, 75.78; H, 6.06. C17H16O3 requires: C,
76.10; H, 6.01%).
3.8.8. 6,7-Dimethoxy-4-(2,4-dimethoxyphenyl)-2H-1-benzo-
pyran (58). PLC (eluant: Et2O±light petroleum 1:1);
amorphous powder from ethanol±water, mp 134±1378C;
nmax (KBr)/cm21 1644; dH (270 MHz) 3.64 (s, 3H,
6-OMe), 3.71 (s, 3H, 20-OMe), 3.85 (s, 6H, 7-OMe,
40-OMe), 4.82 (d, Jˆ4 Hz, 2H, 2-H), 5.62 (t, Jˆ4 Hz, 1H,
3-H), 6.30 (s, 1H, 8-H), 6.48 (s, 1H, 5-H), 6.51-6.53 (m, 2H,
30-H, 50-H), 7.12 (d, Jˆ88 Hz, 1H, 60-H); dC 55.4, 55.5,
56.0, 56.6, 65.6, 98.8, 100.5, 104.4, 109.7, 116.1, 118.3,
120.0, 130.0, 131.5, 143.2, 148.7, 149.5, 158.2, 160.8; m/z
328 (M1, 89), 327 (46), 313 (28), 297 (100), 281 (8), 266
(15), 164 (19), 156 (22), 127 (18), 115 (18), 69 (23) (Found:
C, 69.04; H, 6.38. C19H20O5 requires: C, 69.50; H, 6.14%).
3.8.3. 4-(2,4,6-Trimethoxyphenyl)-2H-1-benzopyran (53).
PLC (eluant: CHCl3); needles from ethanol, mp 163±1668C;
n
max (KBr)/cm21 1652; dH (270 MHz) 3.69 (s, 6H, 20-OMe,
60-OMe), 3.85 (s, 3H, 40-OMe), 4.94 (d, Jˆ3.65 Hz, 2H,
2-H), 5.66 (t, Jˆ3.65 Hz, 1H, 3-H), 6.19 (s, 2H, 30-H,
50-H), 6.58-6.84 (m, 3H, 5-H, 6-H, 8-H), 7.25 (m, 1H,
7-H); dC 55.4, 55.9, 65.7, 90.8, 108.9, 115.7, 120.9, 122.5,
124.1, 124.9, 128.4, 128.8, 154.2, 159.0, 160.9; m/z 298 (M1,
100), 297 (26), 283 (28), 267 (96), 252 (18), 181 (10), 152
(12), 139 (12), 131 (28), 91 (11) (Found: C, 72.43; H, 6.17.
C18H18O4 requires: C, 72.47; H, 6.08%).
3.8.9. 6,7-Dimethoxy-4-(2,4,6-trimethoxyphenyl)-2H-1-
benzopyran (59). PLC (eluant: CHCl3); yellow oil; nmax
(CH2Cl2)/cm21 1653; dH (270 MHz) 3.62 (s, 3H, 6-OMe),
3.71 (s, 6H, 20-OMe, 60-OMe), 3.83 (s, 3H, 40-OMe),p 3.86
(s, 3H, 7-OMe),p 4.87 (d, Jˆ3.85 Hz, 2H, 2-H), 5.57 (t,
Jˆ3.85 Hz, 1H, 3-H), 6.2 (s, 3H, 8-H, 30-H, 50-H), 6.47 (s,
1H, 5-H); dC 55.4, 55.9, 56.0, 56.1, 65.8, 90.9, 100.5, 108.1,
3.8.4. 7-Methoxy-4-(4-methoxyphenyl)-2H-1-benzopyran
(54). PLC (eluant: Et2O±light petroleum 2:3); amorphous
powder from ethanol, mp 101±1038C (lit.,30 mp 1058C);
nmax (KBr)/cm21 1636; dH (270 MHz) 3.78 (s, 3H, 40-
OCH3),p 3.83 (s, 3H, 7-OCH3),p 4.79 (d, Jˆ4.03 Hz, 2H,
2-H), 5.60 (t, Jˆ4.03 Hz, 1H, 3-H), 6.39±6.48 (m, 2H, 30-H,
50-H), 6.89-6.96 (m, 3H, 5-H, 6-H, 8-H), 7.26 (d,

D. M. X. Donnelly et al. / Tetrahedron 57 (2001) 413±423
423
15. Finet, J.-P. Ligand Coupling Reactions with Heteroatomic
Compounds; Pergamon: Oxford, 1998; pp 205±247, Chapter 7.
16. Barton, D. H. R.; Donnelly, D. M. X.; Finet, J.-P.; Guiry, P. J.
J. Chem. Soc., Perkin Trans. 1 1992, 1365±1375.
17. Donnelly, D. M. X.; Finet, J.-P.; Rattigan, B. A. J. Chem. Soc.,
Perkin Trans. 1 1993, 1729±1735.
108.7, 116.4, 119.7, 128.8, 143.2, 148.8, 149.3, 159.1,
161.0; m/z 358 (M1, 52), 357 (45), 343 (31), 327 (100),
312 (20), 221 (18), 164 (18), 127 (18), 69 (19), 28 (30).
References
18. Donnelly, D. M. X.; Fitzpatrick, B. M.; O'Reilly, B. A.; Finet,
J.-P. Tetrahedron 1993, 49, 7967±7976.
1. Eyton, W. B.; Ollis, W. D.; Sutherland, I. O.; Gottlieb, O. R.;
MagalhaÄes, M. T.; Jackman, L. M. Tetrahedron 1966, 21,
2683±2696.
19. Donnelly, D. M. X.; Fitzpatrick, B. M.; Ryan, S. M.; Finet,
J.-P. J. Chem. Soc., Perkin Trans. 1 1994, 1797±1801.
20. Donnelly, D. M. X.; Finet, J.-P.; Rattigan, B. A. J. Chem. Soc.,
Perkin Trans. 1 1995, 1679±1683.
2. Donnelly, D. M. X.; Boland, G. The Flavonoids: Advances in
Research since 1986; Harborne, J. B., Ed.; Chapman & Hall:
London, 1994; pp 239±258.
21. Donnelly, D. M. X.; Molloy, D. J.; Reilly, J. P.; Finet, J.-P.
J. Chem. Soc., Perkin Trans. 1 1995, 2531±2534.
22. Barton, D. H. R.; Donnelly, D. M. X.; Finet, J.-P.; Guiry, P. J.;
Kielty, J. M. Tetrahedron Lett. 1990, 31, 6637±6640.
23. Donnelly, D. M. X.; Kielty, J. M.; Cormons, A.; Finet, J.-P.
J. Chem. Soc., Perkin Trans. 1 1993, 2069±2073.
24. Suginome, H.; Orito, K.; Yorita, K.; Ishikawa, M.;
Shimoyama, N.; Sasaki, T. J. Org. Chem. 1995, 60, 3052±
3064.
3. Ollis, W. D.; Redman, B. T.; Roberts, R. J.; Sutherland, I. O.;
Gottlieb, O. R. J. Chem. Soc., Chem. Commun. 1968, 1392±
1393.
4. Mukerjee, S. K.; Saroja, T.; Seshadri, T. R. Tetrahedron 1971,
27, 799±803.
5. Dhingra, V. K.; Mukerjee, S. K.; Saroja, T.; Seshadri, T. R.
Phytochemistry 1971, 10, 2551.
6. Ogiyama, K.; Yasue, M. Phytochemistry 1973, 12, 2544±
2545.
25. Taber, D. F.; Amedio Jr., J. C.; Patel, Y. K. J. Org. Chem.
1985, 50, 3618±3619.
7. Perkin Jr., W. H.; Robinson, R. J. Chem. Soc. 1908, 93, 489±
517.
26. Dauben, W. G.; Boswell, G. A. J. Am. Chem. Soc. 1961, 83,
5003±5005.
8. Kolodziej, H. Phytochemistry 1984, 23, 1745±1752.
9. Foo, L. Y.; Porter, L. J. J. Chem. Soc., Perkin Trans. 1 1983,
1535±1543.
27. Padwa, A.; Au, A.; Lee, G. A.; Owens, W. J. Org. Chem.
1975, 40, 1142±1149.
10. Young, D. A.; Young, E.; Roux, D. G.; Brandt, V.; Ferreira, D.
J. Chem. Soc., Perkin Trans. 1 1987, 2345±2351.
11. TuÈckmantel, W.; Kozikowski, A. P.; Romanczyk Jr., L. J.
J. Am. Chem. Soc. 1999, 121, 12073±12081.
12. Pinhey, J. T. Aust. J. Chem. 1991, 44, 1353±1382.
13. Pinhey, J. T.; Lead. In Comprehensive Organometallic
Chemistry II, Abel, E. W., Stone, F. G. A., Wilkinson, G.,
Eds.; Pergamon Press: Oxford, 1995; Vol. 11, pp 461±485.
14. Pinhey, J. T. Pure Appl. Chem. 1996, 68, 819±824.
28. Verhe, R.; De Kimpe, N.; De Buyck, L.; Steurbaut, W.;
Sadones, M.; Willaert, R.; Verbeek, J. P.; Schamp, N. Bull.
Soc. Chim. Belg. 1980, 89, 459±485.
29. Padwa, A.; Au, A.; Lee, G. A.; Owens, W. J. Am. Chem. Soc.
1976, 98, 3555±3564.
30. Kirkiacharian, B. S.; Danan, A.; Koutsourakis, P. G. Synthesis
1991, 879±881.