Synthesis of C-ring substituted xanthones from the [4 + 2] cycloaddition reaction of vinylchromones and acyclic enamines

Article abstract of DOI:10.1039/b004422i

A novel approach to the synthesis of C-ring substituted xanthones utilising the [4 + 2] cycloaddition reactions of enamines with aromatically substituted vinylchromones has been developed. 1-Methyl-, 1-ethyl-, 2-methyl- and 2-ethyl-substituted xanthones are obtained in a one-pot synthesis from the reaction of pyrrolidine enamines derived from acetone, butan-2-one, propanal and butanal respectively, when taken as solvent incorporating a catalytic amount of pyrrolidine. Some 1-methylidene- and 1-methylidene-2-methyl-substituted tetrahydroxanthohes were also obtained and these compounds are proposed to be intermediates in the reaction, since they undergo facile conversion to 1-methyl- and 1,2-dimethyl-xanthones. Further evidence for the proposed reaction pathway was obtained from the isolation of a 1-pyrrolidino-2,2-dimethyl substituted tetrahydroxanthone from the reaction between a vinylchromone and the pyrrolidine enamine of 2-methylpropanal. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/b004422i

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Synthesis of C-ring substituted xanthones from the [4 ؉ 2]
cycloaddition reaction of vinylchromones and acyclic enamines
Avijit S. Kelkar,† Roy M. Letcher,‡ Kung-Kai Cheung, Kwei-Fung Chiu and
Geoffrey D. Brown*
1
Department of Chemistry, The University of Hong Kong, Pokfulam Rd., Hong Kong
Received (in Cambridge, UK) 2nd June 2000, Accepted 17th August 2000
First published as an Advance Article on the web 26th October 2000
A novel approach to the synthesis of C-ring substituted xanthones utilising the [4 ϩ 2] cycloaddition reactions
of enamines with aromatically substituted vinylchromones has been developed. 1-Methyl-, 1-ethyl-, 2-methyl- and
-ethyl-substituted xanthones are obtained in a one-pot synthesis from the reaction of pyrrolidine enamines derived
2
from acetone, butan-2-one, propanal and butanal respectively, when taken as solvent incorporating a catalytic
amount of pyrrolidine. Some 1-methylidene- and 1-methylidene-2-methyl-substituted tetrahydroxanthones were also
obtained and these compounds are proposed to be intermediates in the reaction, since they undergo facile conversion
to 1-methyl- and 1,2-dimethyl-xanthones. Further evidence for the proposed reaction pathway was obtained from the
isolation of a 1-pyrrolidino-2,2-dimethyl substituted tetrahydroxanthone from the reaction between a vinylchromone
and the pyrrolidine enamine of 2-methylpropanal.
Introduction
nucleus was also isolated in low yield from the reaction of com-
pounds 1b and 1h (yielding 3b and 3h respectively). This class of
product is believed to be the precursor to the fully aromatised
The xanthones are a large group of natural products with
varied biological activities. General synthetic approaches to
1
1
-methylxanthones (2a–2j) - via migration of the exocyclic
2,3
xanthones have been reviewed and several syntheses of alkyl-
substituted xanthone natural products have been reported in
double bond and oxidation of the C-ring (Fig. 1) (facile
dehydrogenation of di- and tetrahydroxanthones has been
4
the literature. 2-Vinylchromones have often been used as start-
6
observed previously). Indeed, the 1-methylidenetetrahydrox-
5,6
7,8
ing materials for synthesis of xanthones and Letcher has
recently reported the effective use of the Diels–Alder reactions
of 2-vinylchromones and pre-formed cycloalkylenamines in
the synthesis of cycloalkano[a]xanthones. In continuation of
these studies we herein report a modified procedure employing
anthone 3k was the only product isolated from the reaction of
vinylchromone 1k. 1-Methyl-3-arylxanthones 2b and 2h were
readily obtained by treating the corresponding 1-methylidene-
tetrahydroxanthone side-products 3b and 3h with strong acid;
the conversion was followed by observing the disappearance in
2
-vinylchromones (1a–1k) and enamines which are obtained
1
the H NMR spectrum of the exo-methylene signals at δ 6.7
H
in situ from the corresponding alkyl ketones or aldehydes in
the presence of a catalytic amount of pyrrolidine, to synthesise
and 5.3 ppm (the large difference in the observed chemical shift
of the two alkene protons arises because of the proximity of
one member of the pair to the carbonyl group, which is consist-
ent with the location of this substituent at the 1-position) and
1
-methyl- (2a–2j), 2-methyl- (8a), 1,2-dimethyl- (7a), 1-ethyl-
(
5b, 5f and 5i) and 2-ethyl-(9b) substituted xanthones in a
one-pot process.
the appearance of a methyl singlet at δ 3.0 ppm.
H
It was anticipated that if butan-2-one was used as the solvent
in place of acetone, with pyrrolidine as catalyst, then 2-styryl-
chromone (1a) would yield the corresponding 1,2-dimethyl-
substituted xanthone directly. Somewhat surprisingly, this
reaction instead yielded the 1-methylidene-2-methyltetrahydrox-
anthone 4a in moderate yield (Scheme 2). As previously, the
structure of 4a was rigorously characterized by 2D-NMR and,
in particular, it was possible to unambiguously confirm the
location of the methylidene group at the 1-position and the
methyl group at the 2-position (see Tables 3 and 4 for complete
Results and discussion
The synthesis of 1-methyl-3-phenylxanthone (2a) was achieved
in good yield by refluxing 2-styrylchromone (1a) and 2-pyrrol-
idinoprop-1-ene, which was generated in situ from acetone
(
(
taken as solvent) and a catalytic quantity of pyrrolidine
Scheme 1). The structure of 2a—in particular the location
of the methyl substituent at the 1-position of the xanthone
C-ring—was rigorously established by 2D-NMR, which also
1
13
resulted in unambiguous H and C NMR assignments for all
resonances (see Tables 1 and 2). Several other xanthones which
are variously substituted at the 3-position and in the xanthone
A-ring (2b–2j) were obtained in similar yields by this procedure.
NMR spectra of these compounds (Tables 1 and 2) have been
assigned by analogy with compound 2a: in all cases the methyl
group was found to be substituted at the 1-position.
1
13
H and C NMR assignments). As noted above, compound 4a
probably represents the initial product of elimination of
pyrrolidine from the Diels–Alder adduct (Fig. 1), which in this
case has failed to undergo subsequent rearrangement and
aromatisation under the conditions of the reaction. This find-
ing was quite general and tetrahydroxanthones 4b, 4c, 4f, 4i and
4
k were obtained from chromones 1b, 1c, 1f, 1i and 1k respect-
An additional kind of reaction product incorporating a
methylidene group substituted on
ively, in comparable yields. NMR assignments of 4b, 4c, 4f, 4i
and 4k (Tables 3 and 4) were made by analogy with 4a, and
were consistent with 1-methylidene- and 2-methyl-substitution
of the xanthone C-ring in all cases.
The 1-methylidene-2-methyltetrahydroxanthone 4a could
easily be converted to the desired 1,2-dimethylxanthone 7a
a tetrahydroxanthone
†
Current address: Chemistry Department, The University of Sheffield,
Sheffield, UK S3 7HF.
‡
Current address: Sans Souci, North Rd., Bath, UK BA2 6HW.
3
732
J. Chem. Soc., Perkin Trans. 1, 2000, 3732–3741
This journal is © The Royal Society of Chemistry 2000
DOI: 10.1039/b004422i

View Article Online
Fig. 1 Proposed mechanism involved in the formation of 1-methyl-
and 1,2-dimethyl-substituted xanthones from vinylchromones and
acyclic ketones in the presence of pyrrolidine.
Scheme 1
(
(
fully assigned by 2D-NMR) by treatment with strong acid
Scheme 3). Quenching the reaction after a short period of time
also yielded 1,2-dimethyl-3-phenyl-3,4-dihydroxanthen-9-one
a as a minor product. Treatment of 6a with acid gave 7a in
6
almost quantitative yields, thus establishing its status as a reac-
tion intermediate, and confirming that aromatisation of the
xanthone C-ring occurs by conversion of an exocyclic to an
endocyclic double bond. Logically, this endocyclic diene must
then undergo oxidation to the resulting xanthone (Fig. 1),
although this was not explicitly demonstrated.
1
-Ethyl-substituted xanthones (Scheme 2) were also recorded
as minor side-products from the reaction of vinylchromone
substrates 1b, 1f and 1i with the pyrrolidine enamine of butan-
2
-one. It is known that more than one isomer may sometimes be
9
produced during enamine formation with acyclic ketones; we
propose that although the (E)-isomer of 2-pyrrolidinobut-2-ene
is the major component of this reaction, small amounts of the
terminal methylene isomer (2-pyrrolidinobut-1-ene) are also
formed. The isolation of 1-ethyl-substituted xanthones 5b, 5f
and 5i requires that this less substituted enamine must also be
generated in significant quantities under the conditions of
Scheme 2
J. Chem. Soc., Perkin Trans. 1, 2000, 3732–3741
3733

1
a
Table 1 H NMR assignments for 1-methylxanthones 2a–2j
Atom
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
b
2
3
4
5
6
7.33 (d, J = 1.6
7.33 (d, J = 1.5
7.31 (d, J = 1.1
7.35 (s)
—
7.31 (d, J = 0.9
7.34 (d, J = 1.7
7.39 (d, J = 1.4
7.32 (d, J = 1.4
7.34 (d, J = 1.2
7.31 (dd, J = 8.3,
1.5 Hz)
Hz)
Hz)
Hz)
Hz)
Hz)
Hz)
Hz)
Hz)
—
—
—
—
—
—
—
—
7.53 (dd, J = 8.3,
.5 Hz)
7.11 (dd, J = 7.5,
1.5 Hz)
7.42 (d, J = 8.1
Hz)
7.67 (ddd,
J = 8.1, 7.2, 1.6
Hz)
7.33 (dd, J = 8.0,
7.2 Hz)
7
b
7.51 (d, J = 1.6
Hz)
7.44 (d, J = 7.5
Hz)
7.51 (d, J = 1.5
Hz)
7.40 (d, J = 8.5
Hz)
7.66 (ddd,
J = 8.5, 7.5, 1.6
Hz)
7.33 (dd, J = 7.5,
7.5 Hz)
7.51 (d, J = 1.1
Hz)
7.37 (d, J = 8.0
Hz)
7.63 (ddd,
J = 8.0, 7.5, 1.5
Hz)
7.29 (dd, J = 8.0,
7.5 Hz)
7.58 (s)
7.35 (br s)
—
7.53 (d, J = 0.9
Hz)
7.39 (d, J = 8.8
Hz)
7.61 (dd, J = 8.8,
2.6 Hz)
7.53 (d, J = 1.7
Hz)
7.39 (d, J = 8.9
Hz)
7.62 (dd, J= 8.9,
2.6 Hz)
7.61 (d, J = 1.4
Hz)
—
7.47 (d, J = 1.4
7.52 (d, J = 1.2
Hz)
7.38 (d, J = 9.0
Hz)
7.29 (dd, J = 9.0,
1.8 Hz)
Hz)
b
7.02 (dd, J = 8.3,
0.8 Hz)
7.66 (ddd, J = 7.5,
7.69 (d, J = 2.1
Hz)
7.57 (dd, J = 8.3,
8.3 Hz)
7
.5, 1.5 Hz)
b
7
8
7.33 (dd, J = 7.5,
.5 Hz)
8.27 (dd, J = 7.5,
.5 Hz)
—
—
—
—
6.78 (dd, J = 8.3,
—
7
0.8 Hz)
—
8.25 (dd, J = 7.5,
1.6 Hz)
8.22 (dd, J = 8.0,
1.5 Hz)
7.92 (s)
8.24 (d, J = 2.6
Hz)
8.21 (d, J = 2.6
Hz)
8.11 (d, J = 2.1
Hz)
7.67 (d, J = 1.8
Hz)
8.27 (dd, J = 8.0,
1.6 Hz)
1
1
2
-Me
Ј
2.97 (3H, s)
2.95 (3H, s)
—
2.91 (3H, s)
—
2.99 (3H, s)
7.69 (d, J = 7.6
Hz)
7.50 (d, J = 7.5,
7.5 Hz)
7.43 (dd J = 7.5,
7.5 Hz)
2.97 (3H, s)
—
2.96 (3H, s)
—
2.95 (3H, s)
7.68 (d, J = 7.8
Hz)
7.49 (dd, J = 7.8,
7.8 Hz)
7.46 (dd, J = 7.8,
7.8 Hz)
2.98 (3H, s)
7.68 (dd, J = 7.5,
1.7 Hz)
7.49 (dd, J = 7.5,
7.5 Hz)
7.42 (dddd,
J = 7.5, 7.5, 1.7,
1.7 Hz)
7.49 (dd, J = 7.5,
7.5 Hz)
7.68 (dd, J = 7.5,
1.7 Hz)
4.03 (3H, s) 8-
OMe
3.00 (3H, s)
7.68 (d, J = 8.0
Hz)
7.49 (dd, J = 8.0,
7.5 Hz)
7.43 (dd, J = 7.5,
7.5 Hz)
2.93 (3H, s)
7.67 (dd, J = 7.5,
1
.5 Hz)
b
3
Ј
Ј
7.49 (dd, J = 7.5,
7.48 (dd, J = 3.7,
6.82 (d, J = 3.4
Hz)
6.52 (dd, J= 3.4,
1.5 Hz)
7.02 (d, J = 8.0
Hz)
7.39 (dd, J = 8.0,
7.5 Hz)
7.17 (s)
7
.5 Hz)
1.0 Hz)
4
7.42 (dddd,
7.13 (dd, J = 4.9,
3.7 Hz)
—
J = 7.5, 7.5, 1.5,
1
.5 Hz)
b
b
5
Ј
Ј
7.49 (dd, J = 7.5,
.5 Hz)
7.67 (dd, J = 7.5,
.5 Hz)
7.39 (dd, J = 4.9,
7.52 (d, J = 1.5
Hz)
7.50 (d, J = 7.5,
7.5 Hz)
7.07 (dd, J = 7.5,
7.5 Hz)
7.38 (d, J = 7.5
Hz)
3.86 (3H, s)
2Ј-OMe
7.40 (d, J = 8.5
7.49 (dd, J = 7.8,
7.8 Hz)
7.68 (d, J = 7.8
Hz)
7.49 (dd, J = 8.0,
7.5 Hz)
7.68 (d, J = 8.0
Hz)
3.91 (3H, s)
7-OMe
7
1.0 Hz)
Hz) b
6
7.69 (d, J = 7.6
7.35 (d, J = 8.5
Hz)
1
Hz) b
Others
2.51 (3H, s)
b
6
-Me; 2.42
(
3H, s) 7-Me
a
b
Splitting pattern and coupling in Hz indicated in parentheses. Interchangeable within column.

View Article Online
13
a
Table 2
C NMR assignments for 1-methylxanthones 2a–2j
Atom
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
1
2
3
4
4
5
5
6
7
8
8
9
9
1
1
2
3
4
5
6
(C)
(CH)
(C)
142.5 142.7b
125.6 128.4
146.4 142.1
114.0 112.1
157.9 157.9
155.4 155.3
117.4 117.3
134.3 134.2
123.7 123.7
126.7 126.6
122.9 122.9
178.6 178.2
119.0 118.9
142.5
121.8
135.2
112.2
157.9
155.3
117.3
134.1
123.6
126.6
122.9
178.2
118.9
23.5
142.3
125.4
146.1
114.1
157.8
152.1
123.6
132.8 (C)b
126.4 (C)
136.5
122.4
179.1
118.8
23.5
141.6c
126.1
142.3
128.1
144.0
116.9
157.1
153.8
119.3
134.6
129.7 (C)
126.2
123.7
177.5
Nr
142.7
124.9
147.1
114.2
157.4
149.7
123.4 (C) 109.6
134.1 134.4b
123.4 (C) 105.2
126.3
124.5
176.6
118.2
23.4
138.6
127.3
129.1
128.9
129.1
127.3
142.4
125.8
145.9
113.4
157.5
156.8b
142.3
125.5
146.2
114.0
157.9
155.9
142.1
126.7
133.7 (CH)
b
b
144.7d
(CH)
a (C)
a (C)
(CH)
(CH)
(CH)
(CH)
a (C)
(C)
a (C)
-Me (CH3) 23.5
Ј (C)
Ј (CH)
Ј (CH)
Ј (CH)
Ј (CH)
Ј (CH)
116.8
116.1
157.6
155.4
117.5
134.4
123.7
126.8
122.8
178.8
120.3
23.3
157.2
156.5d
119.2
124.3b
b
134.3
105.9
b
c
129.4 (C)
150.2 (C)
118.9
c
b
121.0
160.7 (C)
c
123.8
177.5
118.5
23.4
120.2
123.2
178.5
118.5
23.5
139.2
127.3
129.0
128.6
129.0
127.3
55.9 (CH3)
7-OMe
178.6c
118.4
23.4
—
23.4
23.7
139.3
127.3
129.0
128.5
129.0
127.3
56.4 (CH3)
8-OMe
b
b
139.1
—
139.3
130.7
134.9 (C)b
127.3 139.2 (C) 152.1 (C) 127.3
153.9 (C)
111.4c
129.9c
128.5c
128.6
55.6 (CH3)
2Ј-OMe
127.7 (C)
b
b
c
129.0 125.2b
110.2b
129.0
128.5
129.0
127.3
127.4
b
128.6 124.0b
129.0 126.9
108.3
143.6
—
133.1 (C)
c
130.1c
127.3
—
131.8
c
Others
20.9 (CH3)
-Me
5.6 (CH3)
- Me
6
1
7
c
a
bcd
Multiplicity determined from DEPT. Interchangeable within column; Nr = not resolved.
Fig. 2 ORTEP diagram for 4a.
Thus, 1-methylxanthones and 1,2-dimethylxanthones can
be synthesized in good to moderate yields in one or two steps
respectively from the reaction of vinylchromones and acyclic
ketones in the presence of a catalytic amount of pyrrolidine
(1-ethyl-substituted xanthones are obtained as side-products
in a few cases). A slight modification to this strategy was
required in order to synthesise 2-methyl- and 2-ethyl-
xanthones. Since the regioselectivity and stereoselectivity in
the [4 ϩ 2] cycloaddition reaction of enamine and vinyl-
chromone is expected to remain fixed (as discussed above),
the synthesis of 2-alkylxanthones is only possible from an
enamine in which the pyrrolidine group is located at the end
of the alkyl chain i.e. enamines generated from aldehydes
rather than ketones should give 2-alkyl-substituted xanthones.
This was indeed found to be the case and two examples of
this reaction, using propanal and butanal as solvent in the
presence of a catalytic amount of pyrrolidine, for the formation
of 2-methyl- and 2-ethyl-xanthones 8a and 9b respectively,
are shown in Scheme 4. An extension of this procedure was
used to further confirm the reaction mechanism proposed in
Fig. 1. Thus, when 2-styrylchromone (1a) is treated with the
pyrrolidine enamine of 2-methylpropanal (Scheme 4) elimin-
ation of pyrrolidine from the predicted Diels–Alder adduct
should be impossible since there are no hydrogens available α to
the nitrogen atom to participate in this reaction (the 2-position
Scheme 3
reaction when pyrrolidine is employed as catalyst because this is
the only way to account for formation of such xanthones if a
Diels–Alder process is invoked (cf. Fig. 1).
The X-ray structure of the 1-methylidene-2-methyltetra-
hydroxanthone 4a (Fig. 2) indicated a trans geometry between
the aromatic 3-substituent and the 2-methyl group (and also
showed that the exo-methylene group is not co-planar with
respect to the chromone system). This relative stereochemistry
for 4a can be explained by assuming that [4 ϩ 2] inverse elec-
tron demand cycloaddition of the (E)-isomer of the enamine
derived from pyrrolidine and methyl ethyl ketone over the diene
system of the chromone 1a occurs regioselectively such that the
pyrrolidine is located at the 1-position in the initial addition
product (as already indicated) and from an endo transition
state, which would account for the trans stereochemistry
observed between the 3-R- and the 2-methyl substituents in the
newly formed ring. An alternative mechanism, which cannot be
ruled out on the basis of our results, is that of a stepwise 1,6-
conjugate addition of the enamine to the vinylchromone, result-
ing in a six-membered ring in which the 3-R- and 2-methyl
substituents adopt the thermodynamically more stable trans
configuration.
J. Chem. Soc., Perkin Trans. 1, 2000, 3732–3741
3735

1
a
Table 3 H NMR assignments for 1-methylidenexanthones 3b, 3h, 3k, 4a–c, 4f, 4i and 4k
Atom
3b
3h
3k
4a
4b
4c
4f
4i
4k
2
2
α
β
2.85 (dd, J = 14.0,
2.70–2.65
(2H, m)
2.51 (dd, J = 18.7,
5.2 Hz)
2.48 (dd, J = 18.7,
8.6 Hz)
—
—
—
—
—
—
1
.9 Hz)
2.68 (dddd,
2.62 (dq, J = 8.1,
6.8 Hz)
2.69 (dq, J = 6.6,
6.9 Hz)
2.80 (dq, J = 6.6,
7.1 Hz)
2.68 (dq, J = 6.8,
6.9 Hz)
2.62 (dq, J = 6.8, 6.8
Hz)
2.24 (dq, J = 6.1,
6.9 Hz)
J = 14.0, 11.7,
1
.7, 1.7 Hz)
3
α
α
β
3.52 (m)
3.20 (m)
2.30 (m)
2.90 (ddd,
J = 8.1, 7.9, 6.6
Hz)
3.16 (dd, J = 18.8,
6.6 Hz)
3.29 (m)
3.32 (m)
3.10 (ddd,
J = 7.1, 6.7, 6.6
Hz)
3.14 (dd,
J = 18.2, 7.1 Hz)
3.52 (ddd, J = 6.8,
2.89 (ddd, J = 8.0,
1.93 (ddd, J = 6.1,
6.5, 6.1 Hz)
6.8, 6.8 Hz)
6.1, 4.2 Hz)
b
4
3.19 (ddd,
J = 17.6, 5.4, 1.5
Hz)
3.05–2.90
(2H, m)
2.88 (dd, J = 18.4,
3.8 Hz)
3.22 (dd, J = 19.8,
6.5 Hz)
3.15 (dd, J = 18.7, 6.8
Hz)
3.03 (dd, J = 18.6,
6.1 Hz)
b
4
5
6
3.04 (dd, J = 17.6,
2.82 (dd, J = 18.4,
9.3 Hz)
7.36 (m)
3.04 (dd, J = 18.8,
7.9 Hz)
7.38 (dd, J = 8.5,
1.3 Hz)
7.62 (ddd,
J = 8.5, 7.0, 1.5
Hz)
7.38 (ddd,
J = 8.2, 7.0, 1.3
Hz)
3.07 (dd,
J = 18.1, 7.0 Hz)
7.36 (m)
3.11 (dd,
2.92 (dd, J = 19.8,
6.1 Hz)
7.36 (d, J = 8.7 Hz)
3.02 (dd, J = 18.7, 8.0
Hz)
7.31 (d, J = 8.7 Hz)
2.47 (dd, J = 18.6,
4.2 Hz)
7.37 (d, J = 8.3 Hz)
1
0.1 Hz)
J = 18.2, 6.7 Hz)
7.36 (d, J = 8.7
Hz)
7.60 (ddd,
J = 8.7, 7.2, 1.5
Hz)
b
7.39 (m)
6.92 (dd, J = 8.3,
1
.0 Hz)
7.62 (ddd,
J = 7.4, 7.4, 1.8
Hz)
7.50 (dd, J = 8.3,
8.3 Hz)
7.59 (ddd,
J = 8.4, 7.5,
1.7 Hz)
7.61 (ddd,
J = 8.4, 7.6, 1.6
Hz)
7.58 (d, J = 8.7 Hz)
7.21 (dd, J = 8.7, 2.0
Hz)
7.60 (ddd, J = 8.3,
7.3, 1.6 Hz)
b
7
7.39 (m)
6.79 (dd, J = 8.3,
7.36 (m)
7.36 (m)
7.35 (dd, J = 8.2,
7.2 Hz)
—
—
7.35 (dd, J = 7.8,
7.3 Hz)
1
.0 Hz)
8
1
1
2
3
4
8.24 (dd, J = 8.3,
—
8.22 (dd, J = 8.4,
1.7 Hz)
6.63 (s)
8.27 (dd, J = 8.2,
8.24 (dd, J = 8.4,
1.6 Hz)
6.71 (s)
8.23 (dd, J = 8.2,
1.5 Hz)
6.66 (d, J = 1.6
Hz)
8.23 (s)
6.61 (s)
5.36 (s)
—
7.63 (d, J = 2.0 Hz)
6.64 (s)
8.24 (dd, J = 7.8,
1.6 Hz)
6.62 (d, J = 2.0 Hz)
1
.8 Hz)
1.5 Hz)
c
-CH (a)
6.74 (t, J = 1.8
Hz)
5.35 (s)
6.73 (d, J = 2.2
Hz)
5.28 (s)
6.63 (s)
2
-CH (b)
5.27 (d, J = 1.9
Hz)
—
5.36 (s)
5.39 (d, J = 0.9
Hz)
—
5.37 (s)
5.36 (s)
5.35 (s)
2
Ј
Ј
Ј
—
7.30 (m)
7.30 (m)
7.21 (dd, J = 7.7,
—
7.20 (d, J = 7.4 Hz)
3
.1 Hz)
6.93 (dd, J = 3.6,
—
—
7.33 (dd, J = 7.7,
7.7 Hz)
7.25 (dddd,
6.87 (dd, J = 3.2,
1.1 Hz)
6.90 (dd, J = 5.0,
3.2 Hz)
6.10 (d, J = 3.2
Hz)
6.26 (dd, J = 3.2,
1.8 Hz)
7.43 (s)
—
7.33 (dd, J = 7.4, 7.4
Hz)
7.24 (dd, J = 7.4, 7.4
Hz)
1
.0 Hz)
6.98 (dd, J = 5.1,
7.36 (dd, J = 7.2,
7.2 Hz)
3
.6 Hz)
J = 7.7, 7.7, 1.3,
1
.3 Hz)
b
5
Ј
Ј
7.21 (dd, J = 5.1,
.0 Hz)
7.30 (m)
—
7.33 (dd, J = 7.7,
7.7 Hz)
7.15 (dd, J = 5.0,
1.1 Hz)
7.32 (d, J = 1.8
Hz)
7.20 (d, J = 8.1
7.33 (dd, J = 7.4, 7.4
Hz)
7.20 (d, J = 7.4 Hz)
1
Hz)
b
6
7.30 (m)
7.21 (dd, J = 7.1,
7.11 (d, J = 8.1
Hz)
1
.3 Hz)
Others
4.00 (3H, s)
1.09 (3H, d,
J = 6.1 Hz) 3-Me
1.06 (3H, d,
J = 6.8 Hz) 2-Me
1.17 (3H, d, J=
6.9 Hz) 2-Me
1.15 (3H, d,
J = 7.1 Hz) 2-Me
1.16 (3H, d, J = 6.9
Hz) 2-Me
3.90 (3H, s) 7-OMe
1.14 (3H, d, J = 6.9
Hz) 2-Me
1.03 (3H, d, J = 6.2
Hz) 3-Me
8
-OMe
1
.06 (3H, d, J = 6.8
Hz) 2-Me
a
b
c
Splitting pattern and coupling in Hz indicated in parentheses. Interchangeable within column. 1-CH (a) next to C᎐O.
2

View Article Online
13
a
Table 4
C NMR assignments for 1-methylidenexanthones 3b, 3h, 3k, 4a–c, 4f, 4i and 4k
Atom
3b
3h
3k
4a
4b
4c
4f
4i
4k
1
2
3
4
4
5
5
6
7
8
8
9
9
1
1
2
3
4
5
6
(C)
134.9
42.2 (CH2)
34.5
135.4
41.6 (CH2)
39.2
36.9
163.3
135.7
42.1 (CH2)
28.0
139.4
41.3
45.4
138.7
40.2
43.1
138.8b
40.1b
38.1
138.3b
40.7b
40.2
139.6
41.4
45.5
139.1
43.2
32.2
(CH)
(CH)
(CH2)
a (C)
a (C)
(CH)
(CH)
(CH)
(CH)
a (C)
(C)
37.9
37.7
35.6
35.2
31.4
33.4
35.6
33.9
164.6
154.7
117.4
133.2
124.9
126.4
124.0
176.4
116.6
116.5
—
165.8
154.8
117.4
132.9
124.7
126.3
124.8
176.5
117.5
115.5
164.1
154.8
117.4
133.1
124.8
126.4
124.1
176.3
117.0
115.0
143.8
127.3
128.7
126.8
128.7
127.3
17.5 (CH3)
2-Me
163.2
154.8
117.4
133.1
124.8
126.4
124.6
176.4
116.3
116.2
—
163.3
154.8
117.4
133.1
124.8
126.4
124.0
176.5
116.0
115.7
—
163.7
153.4
119.4
133.7
120.3 (C)
126.1
125.2
175.3
117.0
116.8d
139.8
164.0
156.7
123.2b
105.6
149.7 (C)
163.9
155.0
117.4
132.9
124.7
126.5
124.2
176.7
114.6
115.6
156.8b
109.6
133.1b
106.2
160.2 (C)
124.6
176.4
117.4
116.0
143.8
126.7
128.7
b
118.9
124.6
176.2
116.3
114.8
143.8
127.4
128.7
126.8
a (C)
-CH2
Ј (C)
d
Ј (CH) 147.4 (C)
147.3 (C)
156.3 (C)
133.2 (C)
a
b
b
c
Ј (CH) 126.8a
126.6b
110.1b
129.8
d
Ј (CH) 123.5a
Ј (CH) 123.2
Ј (CH)
126.9
128.7
126.7
124.1b
123.6
105.7
141.3
131.1 (C)
c
128.6 (CH) 128.7
c
127.5 (CH) 127.4
Others
56.4 (CH3)
-OMe
20.9 (CH3)
3-Me
18.5 (CH3)
2-Me
18.4 (CH3)
2-Me
18.4 (CH3)
2-Me
55.9 (CH3)
7-OMe; 17.6 3-Me; 18.8
20.3 (CH3)
8
(
CH ) 2-Me
(CH ) 2-Me
3
3
a
bcd
Multiplicity determined from DEPT. Interchangeable within column.
Experimental
General
1
13
H NMR (500, 300 and 270 MHz) and C NMR (125, 75 and
6
7.5 MHz) spectra were recorded on JEOL or Bruker spectro-
meters in CDCl3 and were referenced to tetramethylsilane;
1
1
chemical shifts are reported in ppm (δ), H– H coupling con-
13
stants (J) are given in Hz, and multiplicities in C spectra were
determined from DEPT and are reported as C, CH, CH and
2
CH . Mass spectra and accurate mass measurements were
3
recorded on a Finnigan MAT-95 instrument using the EI mode
with a direct inlet system and operating at 70 eV. Infrared
spectra were recorded for KBr discs. All melting points were
determined with a Kofler hotstage microscope apparatus and
are uncorrected. Column chromatography was carried out
using Merck Kieselgel 60 (70–230 mesh) and n-hexane–diethyl
ether (9:1 v/v) as the mobile phase; thin layer chromatography
was performed on precoated silica gel 60 GF2 (E. Merck 7730)
54
3
plates (20 cm ) which had been activated at 120 ЊC for 3 hours.
Substituted vinylchromones (1a–1k)
All the aromatically 2-substituted vinylchromones (1a–1i) were
prepared from cyclization of the corresponding α,β-unsatur-
10
ated 1,3-diketones in acid in almost quantitative yields (the
α,β-unsaturated 1,3-diketones were in turn synthesised by
the Baker–Venkatraman reaction of esters prepared from
2
-hydroxyacetophenones and appropriately substituted acry-
11
loyl chlorides). Chromones 1j and 1k, for which there is no
aromatic substituent at the 2-position of the chromone, were
12
prepared by the procedure of Hercouet et al.
1
-Methyl-3-phenyl-9H-xanthen-9-one (2a)
(
E)-2-Styryl-4-chromone (1a) (0.2 g, 0.80 mmol) was refluxed in
Scheme 4
acetone (25 ml) with a drop of pyrrolidine for 4 h. The product
mixture was rotary evaporated and the resulting gum was sub-
jected to column chromatography yielding 1-methyl-3-phenyl-
of the dihydroxanthone nucleus is “blocked” by the presence of
two methyl groups). The tetrahydroxanthone product of this
reaction (10a), which was obtained in good yield, did indeed
retain the pyrrolidine group at the 1-position and is believed
to be derived from this proposed intermediate by double bond
rearrangement.
9H-xanthen-9-one (2a) (R = 0.85) as colourless needles
f
Ϫ1
(0.18 g, 76%) (mp 154–155 ЊC, EtOH). νmax/cm 1665, 1656,
1620, 1606, 1552 (HRMS: found M , 286.0989. C H O
requires M, 286.0994); m/z 286 (M , 100%), 285 (24), 257 (13);
δ see Table 1; δ see Table 2.
ϩ
20
14
2
ϩ
H
C
J. Chem. Soc., Perkin Trans. 1, 2000, 3732–3741
3737

View Article Online
1
-Methyl-3-(2Ј-thienyl)-9H-xanthen-9-one (2b) and 1-methyl-
99%), 357/355/353 (1/7/9), 291/289 (2/6); δH see Table 1; δ see
C
Table 2.
idene-1,2,3,4-tetrahydro-3-(2Ј-thienyl)-9H-xanthen-9-one (3b)
(
E)-2-[2Ј-(2Љ-Thienyl)ethenyl]-4-chromone (1b) (0.2 g, 0.78
1
-Methyl-3-phenyl-5,7-dichloro-9H-xanthen-9-one (2g)
mmol) was refluxed in acetone (25 ml) with a drop of pyrrol-
idine for 2 h. The product mixture was rotary evaporated and
the resulting gum was subjected to column chromatography
yielding two products: (i) 1-methyl-3-(2Ј-thienyl)-9H-xanthen-
9
7
1
2
δC see Table 2; (ii) 1-methylidene-1,2,3,4-tetrahydro-3-(2Ј-
thienyl)-9H-xanthen-9-one (3b) (R = 0.50) was also obtained
as a colourless oil (0.05 g, 21%). νmax/cm 1654, 1637, 1560,
1
2
(E)-6,8-Dichloro-2-styryl-4-chromone (1g) (0.2 g, 0.63 mmol)
was refluxed in acetone (25 ml) with a drop of pyrrolidine for
24 h. The product mixture was rotary evaporated and the result-
ing gum was subjected to column chromatography yielding
1-methyl-3-phenyl-5,7-dichloro-9H-xanthen-9-one (2g) (R =
0.90) as colourless needles (0.13 g, 57%) (mp 195–196 ЊC, 95%
EtOH-CHCl ). νmax/cm 1660, 1623, 1607 (HRMS: found M ,
354.0212. C H O Cl requires M, 354.0214), m/z 358/356/354
(M , 12/66/100%), 321/319 (3/10); δ see Table 1; δ see Table 2.
-one (2b) (R = 0.80) was obtained as colourless needles (0.16 g,
f
Ϫ1
0%) (mp 145–146 ЊC, EtOH). νmax/cm 1654, 1618, 1608,
560 (HRMS: found M , 292.0553. C H O S requires M,
92.0558), m/z 292 (M , 100%), 291 (23), 263 (8); δ see Table 1;
f
ϩ
18
12
2
ϩ
Ϫ1
ϩ
H
3
20
12
2
2
ϩ
f
H C
Ϫ1
ϩ
508 (HRMS: found M , 294.0715. C H SO requires M,
1
8
14
2
1-Methyl-3-phenyl-8-methoxy-9H-xanthen-9-one (2h) and
1-methylidene-1,2,3,4-tetrahydro-3-phenyl-8-methoxy-9H-
xanthen-9-one (3h)
ϩ
94.0715), m/z 294 (M , 100%), 293 (53), 279 (69); δH see
Table 3; δ see Table 4. Treatment of 3b with refluxing AcOH
containing a drop of H SO resulted in quantitative conversion
into 2b.
C
2
4
(
E)-2-Styryl-5-methoxy-4-chromone (1h) (0.2 g, 0.72 mmol)
was refluxed in acetone (25 ml) with a drop of pyrrolidine for 28
h. The product mixture was rotary evaporated and the resulting
gum was subjected to column chromatography yielding two
products: (i) 1-methyl-3-phenyl-8-methoxy-9H-xanthen-9-one
(2h) (R = 0.90) was obtained as colourless needles (0.13 g, 59%)
(mp 200–201 ЊC, EtOH). νmax/cm 1653, 1607, 1551 (HRMS:
found M , 316.1103. C H O requires M, 316.1099); m/z 316
(M , 48%), 298 (100), 270 (11); δH see Table 1; δ see Table 2;
(ii) 1-methylidene-1,2,3,4-tetrahydro-3-phenyl-8-methoxy-9H-
xanthen-9-one (3h) (R = 0.70) was also obtained as colourless
1
-Methyl-3-(2Ј-furyl)-9H-xanthen-9-one (2c)
E)-2-[2Ј-(2Љ-Furyl)ethenyl]-4-chromone (1c) (0.2 g, 0.84 mmol)
was refluxed in acetone (25 ml) with a drop of pyrrolidine for
h. The product mixture was rotary evaporated and the result-
ing gum was subjected to column chromatography yielding
-methyl-3-(2Ј-furyl)-9H-xanthen-9-one (2c) (R = 0.70) as
(
f
Ϫ1
4
ϩ
21
16
3
ϩ
1
f
C
colourless needles (0.13 g, 56%) (mp 144–145 ЊC, EtOH). ν
cm
2
2
/
max
ϩ
Ϫ1
1655, 1624, 1610, 1559, 1555 (HRMS: found M ,
76.0781. C H O requires M, 276.0786), m/z 276 (M , 100%),
f
ϩ
18
12
3
needles (0.055 g, 24%) (mp 174–175 ЊC, 95% EtOH-CHCl )
(HRMS: found M , 318.1256. C H O requires M, 318.1256),
m/z 318 (M , 100%), 317 (29), 303 (42), 227 (40); δ see Table
3
ϩ
75 (24), 247 (13); δ see Table 1; δ see Table 2.
H
C
21 18
3
ϩ
H
1
,6,7-Trimethyl-3-phenyl-9H-xanthen-9-one (2d)
3; δ
C
see Table 4. Treatment of 3h with refluxing AcOH contain-
ing a drop of H SO resulted in quantitative conversion into
2
4
(
E)-2-Styryl-6,7-dimethyl-4-chromone (1d) (0.2 g, 0.72 mmol)
was refluxed in acetone (25 ml) with a drop of pyrrolidine for
h. The product mixture was rotary evaporated and the result-
2
1
h.
4
-Methyl-3-phenyl-7-methoxy-9H-xanthen-9-one (2i)
ing gum was subjected to column chromatography [elution with
n-hexane–diethyl ether (9:1 v/v)] yielding 1,6,7-trimethyl-3-
phenyl-9H-xanthen-9-one (2d) (R = 0.85) as pinkish needles
(E)-2-Styryl-6-methoxy-4-chromone (1i) (0.2 g, 0.72 mmol)
was refluxed in acetone (25 ml) with a drop of pyrrolidine for
20 h. The product mixture was rotary evaporated and the
resulting gum was subjected to column chromatography yield-
ing 1-methyl-3-phenyl-7-methoxy-9H-xanthen-9-one (2i) (R =
0.85) as colourless needles (0.14 g, 63%) (mp 144–145 ЊC, 95%
f
Ϫ1
(
0.17 g, 75%) (mp 157–158 ЊC, EtOH). νmax/cm 1656, 1605,
ϩ
1562 (HRMS: found M , 314.1306. C H O requires M,
22 18 2
ϩ
314.1301), m/z 314 (M , 100%), 313 (22), 299 (12), 285 (5); δH
f
see Table 1; δ see Table 2.
C
Ϫ1
EtOH–CHCl ). νmax/cm 1653, 1647, 1616, 1597 (HRMS:
3
ϩ
1
-Methyl-3-(2Ј-methoxyphenyl)-7-chloro-9H-xanthen-9-one (2e)
found M , 316.1098. C21
H
16
O
3
requires M, 316.1099); m/z 316
ϩ
(
M , 100%), 315 (24), 301 (20), 245 (11), 158 (5); δ see Table 1;
H
(
(
E)-2-[2Ј-(2Љ-Methoxyphenyl)ethenyl]-6-chloro-4-chromone
1e) (0.2 g, 0.64 mmol) was refluxed in acetone (25 ml) with a
δC see Table 2.
drop of pyrrolidine for 8 h. The product mixture was rotary
evaporated and the resulting gum was subjected to column
chromatography yielding 1-methyl-3-(2Ј-methoxyphenyl)-7-
1
-Methyl-9H-xanthen-9-one (2j)
2-Ethenyl-4-chromone (1j) (0.082 g, 0.47 mmol) was refluxed in
acetone (25 ml) with a drop of pyrrolidine for 48 h. The product
mixture was rotary evaporated and the resulting gum was
subjected to column chromatography yielding 1-methyl-9H-
xanthen-9-one (2j) (R = 0.60) as colourless needles (0.038 g,
58%) (mp 100–101 ЊC, EtOH). νmax/cm 1653, 1646, 1616,
chloro-9H-xanthen-9-one (2e) (R = 0.65) as colourless needles
f
Ϫ1
(
1
0.14 g, 63%) (mp 123–124 ЊC, EtOH). νmax/cm 1647, 1620,
599, 1558 (HRMS: found M , 350.0708. C H O Cl requires
21 15 3
ϩ
M, 350.0710), m/z 352/350 (M , 42/100%), 337/335 (23/32), 321
ϩ
f
Ϫ1
(
6); δ see Table 1; δ see Table 2.
H
C
ϩ
1
597, 1560, 1543, 1508 (HRMS: found M , 210.0678. C H O
14
10
2
ϩ
1
-Methyl-3-(2Ј,4Ј-dichlorophenyl)-7-chloro-9H-xanthen-9-one
requires M, 210.0681), m/z 210 (M , 100%), 209 (56), 181 (23),
152 (10), 105 (6); δ see Table 1; δ see Table 2.
(
2f)
H
C
(
(
E)-2-[2Ј-(2Љ,4Љ-Dichlorophenyl)ethenyl]-6-chloro-4-chromone
1f) (0.23 g, 0.64 mmol) was refluxed in acetone (25 ml) with a
(
9
3R/S)-1-Methylidene-1,2,3,4-tetrahydro-3-methyl-9H-xanthen-
-one (3k)
drop of pyrrolidine for 24 h. The product mixture was rotary
evaporated and the resulting gum was subjected to column
chromatography [elution with n-hexane–diethyl ether (9:
(E)-2-(Prop-1Ј-enyl)-4-chromone (1k) (0.2 g, 1.07 mmol) was
refluxed in acetone (25 ml) with a drop of pyrrolidine for 15 h.
The product mixture was rotary evaporated and the resulting
gum was subjected to column chromatography yielding (3R/S)-
1-methylidene-1,2,3,4-tetrahydro-3-methyl-9H-xanthen-9-one
(3k) (R = 0.70) as a yellow oil (0.092 g, 58%). νmax/cm 1645,
1
v/v)] yielding 1-methyl-3-(2Ј,4Ј-dichlorophenyl)-7-chloro-9H-
xanthen-9-one (2f) (R = 0.75) as colourless needles (0.144 g,
5
1
f
Ϫ1
8%) (mp 200–201 ЊC, 95% EtOH–CHCl ). νmax/cm 1650,
626, 1611, 1556 (HRMS: found M , 387.9820. C H O Cl
3
ϩ
Ϫ1
20
11
2
3
f
ϩ
ϩ
requires M, 387.9824), m/z 394/392/390/388 (M , 4/35/100/
1630, 1610, 1562 (HRMS: found M , 226.0990. C H O
15
14
2
3
738 J. Chem. Soc., Perkin Trans. 1, 2000, 3732–3741

View Article Online
ϩ
requires M, 226.0993), m/z 226 (M , 64%), 225 (50), 211 (100);
obtained as white needles (0.093 g, 36%) (mp 134–135 ЊC, 95%
Ϫ1 ϩ
δ see Table 3; δ see Table 4.
EtOH–CHCl ). νmax/cm 1647, 1618 (HRMS: found M ,
3
H
C
4
04.0133. C H O Cl requires M, 404.0138), m/z 410/408/406/
21 15 2 3
ϩ
(
2S/R,3R/S)-1-Methylidene-1,2,3,4-tetrahydro-2-methyl-3-
404 (M , 3/27/78/81%), 395/393/391/389 (1/6/50/54), 247/245
phenyl-9H-xanthen-9-one (4a)
(34/100); δH see Table 3; δC see Table 4; (ii) 1-ethyl-3-(2Ј,4Ј-
dichlorophenyl)-7-chloro-9H-xanthen-9-one (5f) (R = 0.70)
f
(
E)-2-Styryl-4-chromone (1a) (0.2 g, 0.80 mmol) was refluxed in
was obtained as colourless needles (0.033 g, 13%) (mp 167–
butan-2-one (25 ml) with a drop of pyrrolidine for 70 min. The
product mixture was rotary evaporated and the resulting gum
was subjected to column chromatography yielding (2S/R,3R/S)-
Ϫ1
1
68 ЊC, 95% EtOH–CHCl ). νmax/cm 1649, 1610 (HRMS:
3
ϩ
found M , 401.9983. C H O Cl requires M, 401.9981), m/z
08/406/404/402 (M , 4/33/98/100%), 391/389/387/385 (2/21/50/
8); δ 8.25 (1H, d, J = 2.0 Hz, H-8), 7.62 (1H, dd, J = 8.8, 2.0
21
13
2
3
ϩ
4
4
1
-methylidene-1,2,3,4-tetrahydro-2-methyl-3-phenyl-9H-
H
xanthen-9-one (4a) (R = 0.65) as a colourless oil (0.11 g, 55%).
νmax/cm 1643, 1614 (HRMS: found M , 302.1307. C H O
2
f
Hz, H-6), 7.53 (1H, d, J = 1.8 Hz, H-4), 7.40 (2H, m, H-5Ј/6Ј),
Ϫ1
ϩ
21
18
7
7
.39 (1H, d, J = 8.8 Hz, H-5Ј), 7.34 (1H, d, J = 1.8 Hz, H-2),
.21 (1H, s, H-3Ј), 3.43 (2H, q, J = 7.3 Hz, 1-CH CH ), 1.33
ϩ
requires M, 302.1306), m/z 302 (M , 100%), 301 (19), 287 (77),
73 (22), 211 (53); δ see Table 3; δ see Table 4.
2
3
2
H
C
(
3H, t, J = 7.3 Hz, 1-CH CH ); δ 177.0 (C, C-9), 157.3 (C,
2 3 C
C-4a), 153.6 (C, C-5a), 148.4 (C, C-1), 144.2 (C, C-3), 137.2 (C,
C-2Ј/4Ј), 134.9 (C, C-1Ј), 134.6 (CH, C-6), 133.1 (C, C-2Ј/4Ј),
(
2S/R,3R/S)-1-Methylidene-1,2,3,4-tetrahydro-2-methyl-3-(2Ј-
thienyl)-9H-xanthen-9-one (4b) and 1-ethyl-3-(2Ј-thienyl)-9H-
xanthen-9-one (5b)
1
31.8 (CH, C-5Ј/6Ј), 130.1 (CH, C-5Ј/6Ј), 129.6 (C, C-7), 127.5
(
CH, C-2), 126.7 (CH, C-3Ј), 126.2 (CH, C-8), 123.7 (C, C-8a),
(
E)-2-[2Ј-(2Љ-Thienyl)ethenyl]-4-chromone (1b) (0.2 g, 0.78
119.2 (CH, C-5), 118.6 (C, C-9a), 117.0 (CH, C-4), 28.7 (CH2,
mmol) was refluxed in butan-2-one (25 ml) with a drop of
pyrrolidine for 6 h. The product mixture was rotary evaporated
and the resulting gum was subjected to column chromato-
graphy yielding two products: (i) (2S/R,3R/S)-1-methylidene-
1-CH CH ), 15.5 (CH , 1-CH CH ).
2
3
3
2
3
(
2S/R,3R/S)-1-Methylidene-1,2,3,4-tetrahydro-2-methyl-3-
phenyl-7-methoxy-9H-xanthen-9-one (4i) and 1-ethyl-3-phenyl-
-methoxy-9H-xanthen-9-one (5i)
1
,2,3,4-tetrahydro-2-methyl-3-(2Ј-thienyl)-9H-xanthen-9-one
7
(
4b) (R = 0.55) was obtained as a yellowish oil (0.097 g, 40%).
f
Ϫ1
ϩ
(E)-2-Styryl-6-methoxy-4-chromone (1i) (0.2 g, 0.72 mmol) was
refluxed in butan-2-one (25 ml) with a drop of pyrrolidine for
νmax/cm 1647, 1632, 1612 (HRMS: found M , 308.0875.
C H SO requires M, 308.0871), m/z 308 (M , 100%), 293
ϩ
1
9
16
2
3
days. The product mixture was rotary evaporated and the
(
1
61), 279 (17), 211 (45); δH see Table 3; δC see Table 4; (ii)
-ethyl-3-(2Ј-thienyl)-9H-xanthen-9-one (5b) (R = 0.83) was
resulting gum was subjected to column chromatography
yielding two products: (i) (2S/R,3R/S)-1-methylidene-1,2,3,4-
tetrahydro-2-methyl-3-phenyl-7-methoxy-9H-xanthen-9-one
f
obtained as colourless needles (0.036 g, 15%) (mp 113–114 ЊC,
Ϫ1
9
5% EtOH-CHCl ). νmax/cm 1655, 1619, 1605 (HRMS: found
3
ϩ ϩ
(4i) (R = 0.55) was obtained as colourless needles (0.088 g,
f
M , 306.0713. C H SO requires M, 306.0715), m/z 306 (M ,
19
14
2
Ϫ1
3
1
3
7%) (mp 200–201 ЊC, 95% EtOH). νmax/cm 1645, 1605, 1597,
1
00%), 305 (41), 289 (62), 278 (15); δ 8.27 (1H, dd, J = 7.9, 1.6
H
ϩ
561 (HRMS: found M , 332.1404. C H O requires M,
2
2
20
3
Hz, H-8), 7.67 (1H, ddd, J = 8.8, 7.5, 1.6 Hz, H-6), 7.56 (1H, d,
J = 1.6 Hz, H-4), 7.51 (1H, dd, J = 3.7, 0.8 Hz, H-3Ј), 7.43 (1H,
d, J = 8.8 Hz, H-5), 7.42 (1H, dd, J = 5.0, 0.8 Hz, H-5Ј), 7.39
ϩ
32.1410), m/z 332 (M , 100%), 331 (18), 317 (74), 241 (46);
δH see Table 3; δ see Table 4; (ii) 1-ethyl-3-phenyl-7-methoxy-
C
9
H-xanthen-9-one (5i) (R = 0.75) was obtained as colourless
f
Ϫ1
(
1H, d, J = 1.6 Hz, H-2), 7.35 (1H, dd, J = 7.9, 7.5 Hz, H-7),
needles (0.037 g, 16%) (mp 144–145 ЊC, 95% EtOH). νmax/cm
7
1
.14 (1H, dd, J = 5.0, 3.7 Hz, H-4Ј), 3.42 (2H, q, J = 7.3 Hz,
-CH CH ), 1.35 (3H, t, J = 7.3 Hz, 1-CH CH ); δ 178.2 (s,
ϩ
1
3
654, 1608 (HRMS: found M , 330.1252. C H O requires M,
22 18 3
ϩ
2
3
2
3
C
30.1256), m/z 330 (M , 100%), 329 (29), 313 (37); δ 7.69 (2H,
H
C-9), 158.2 (C, C-4a), 155.3 (C, C-5a), 149.0 (C, C-1), 142.5 (C,
C-3), 139.5 (C, C-2Ј), 134.3 (CH, C-6), 128.4 (CH, C-2), 127.0
dd, J = 8.0, 1.5 Hz, H-2Ј/6Ј), 7.69 (1H, d, J = 1.8 Hz, H-8), 7.54
1H, d, J = 1.1 Hz, H-4), 7.50 (2H, dd, J = 8.0, 7.5 Hz, H-3Ј/5Ј),
.43 (1H, dd, J = 7.5, 7.5 Hz, H-4Ј), 7.38 (1H, d, J = 8.9 Hz,
(
7
(
(
(
CH, C-3Ј/4Ј/5Ј), 126.8 (CH, C-8), 125.2 (CH, C-3Ј/4Ј/5Ј), 123.7
CH, C-7), 122.9 (C, C-8a), 122.8 (CH, C-3Ј/4Ј/5Ј), 118.9
C-9a), 117.3 (CH, C-5), 112.4 (CH, C-4), 28.9 (CH , 1-CH -
H-5), 7.38 (1H, d, J = 1.1 Hz, H-2), 7.29 (1H, d, J = 8.9 Hz,
H-6), 3.91 (3H, s, 7–OMe), 3.45 (2H, q, J = 7.4 Hz, 1-CH CH ),
2
2
2
3
CH ), 15.7 (CH , 1-CH CH ).
3
3
2
3
1
.37 (3H, t, J = 7.4 Hz, 1-CH CH ); δ 178.0 (C, C-9), 158.1 (C,
2 C
3
C-4a), 155.9 (C, C-5a), 150.1 (C, C-7), 148.6 (C, C-1), 146.4 (C,
C-3), 139.3 (C, C-1Ј), 129.0 (CH, C-3Ј/5Ј), 128.6 (CH, C-4Ј),
(
2S/R,3R/S)-1-Methylidene-1,2,3,4-tetrahydro-2-methyl-3-(2Ј-
furyl)-9H-xanthen-9-one (4c)
1
(
27.4 (CH, C-2Ј/6Ј), 124.4 (CH, C-2), 124.2 (CH, C-5), 123.2
CH, C-8a), 118.8, (CH, C-8/6), 117.9 (C, C-9a), 114.1 (CH,
C-4), 105.9 (CH, C-6/8), 55.8 (CH , 7-OMe), 29.0 (CH , 1-CH -
(
E)-2-[2Ј-(2Љ-Furyl)ethenyl]-4-chromone (1c) (0.2 g, 0.84 mmol)
was refluxed in butan-2-one (25 ml) with a drop of pyrrolidine
for 2 h. The product mixture was rotary evaporated and the
resulting gum was subjected to column chromatography yield-
ing (2S/R,3R/S)-1-methylidene-1,2,3,4-tetrahydro-2-methyl-3-
3
2
2
CH ), 15.9 (CH , 1-CH CH ).
3
3
2
3
(
9
2S/R,3R/S)-1-Methylidene-1,2,3,4-tetrahydro-2,3-dimethyl-
H-xanthen-9-one (4k)
(
(
2Ј-furyl)-9H-xanthen-9-one (4c) (R = 0.60) as a yellowish oil
f
ϩ
0.11 g, 46%) (HRMS: found M , 292.0943. C H O requires
19
16 3,
ϩ
(
E)-2-(Prop-1Ј-enyl)-4-chromone (1k) (0.2 g, 1.07 mmol) was
refluxed in butan-2-one (25 ml) with a drop of pyrrolidine for
h. The product mixture was rotary evaporated and the result-
M, 292.1099), m/z 292 (M , 100%), 263 (7), 213 (68); δH see
Table 3; δ see Table 4.
C
6
ing gum was subjected to column chromatography yielding (2S/
R,3R/S)-1-methylidene-1,2,3,4-tetrahydro-2,3-dimethyl-9H-
(
(
1
2S/R,3R/S)-1-Methylidene-1,2,3,4-tetrahydro-2-methyl-3-
2Ј,4Ј-dichlorophenyl)-7-chloro-9H-xanthen-9-one (4f) and
-ethyl-3-(2Ј,4Ј-dichlorophenyl)-7-chloro-9H-xanthen-9-one (5f)
xanthen-9-one (4k) (R = 0.65) as a colourless oil (0.12 g, 48%).
f
Ϫ1
ϩ
νmax/cm 1645, 1615, 1597 (HRMS: found M , 240.1146.
C H O requires M, 240.1150), m/z 240 (M , 49%), 239 (12),
(
(
E)-2-[2Ј-(2Љ,4Љ-Dichlorophenyl)ethenyl]-6-chloro-4-chromone
1f) (0.23 g, 0.64 mmol) was refluxed in butan-2-one (25 ml)
ϩ
16
16
2
2
25 (100); δ see Table 3; δ see Table 4.
H C
with a drop of pyrrolidine for 30 h. The product mixture was
rotary evaporated and the resulting gum was subjected to
column chromatography yielding two products: (i) (2S/R,3R/
S)-1-methylidene-1,2,3,4-tetrahydro-2-methyl-3-(2Ј,4Ј-dichloro-
1
3
,2-Dimethyl-3-phenyl-9H-xanthen-9-one (7a) and 1,2-dimethyl-
-phenyl-3,4-dihydro-9H-xanthen-9-one (6a)
phenyl)-7-chloro-9H-xanthen-9-one (4f) (R = 0.55) was
Compound 4a (0.175 g, 0.57 mmol) was dissolved in AcOH–
f
J. Chem. Soc., Perkin Trans. 1, 2000, 3732–3741 3739

View Article Online
H SO4 and heated at 100 ЊC for 3 h. The reaction was
247 (19); δH 8.37 (1H, dd, J = 8.0, 1.5 Hz, H-8), 8.26 (1H, s,
2
neutralized with NaOH (4 M, 20 ml) and extracted with CHCl3.
The product mixture was rotary evaporated and the resulting
gum was subjected to column chromatography yielding 1,2-
H-1), 7.74 (1H, ddd, J = 8.5, 7.0, 1.5 Hz, H-6), 7.55 (1H, s, H-4),
7.50 (1H, dd, J = 8.5, 1.0 Hz, H-5), 7.46 (1H, dd, J = 5.0, 1.2
Hz, H-5Ј), 7.39 (1H, ddd, J = 8.0, 7.0, 1.0 Hz, H-7), 7.20 (1H,
dd, J = 3.5, 1.2 Hz, H-3Ј), 7.16 (1H, dd, J = 5.0, 3.5 Hz, H-4Ј),
2.90 (2H, q, J = 7.5 Hz, 1-CH CH ), 1.27 (3H, t, J = 7.5 Hz,
dimethyl-3-phenyl-9H-xanthen-9-one (7a) (R = 0.84) as colour-
f
less needles (0.086 g, 89%) (mp 129–130 ЊC, 95% EtOH–
2
3
Ϫ1
ϩ
CHCl ). νmax/cm 1653, 1646, 1616, 1597 (HRMS: found M ,
1-CH CH ); δ 177.0 (C, C-9), 156.4 (C, C-4a), 154.0 (C, C-5a),
3
2 3 C
ϩ
3
00.113. C H O requires M, 300.1151), m/z 300 (M , 61%),
141.1 (C, C-2/2Ј/3), 140.9 (C, C-2/2Ј/3), 138.5 (C, C-2/2Ј/3),
134.8 (CH, C-6), 127.4 (CH, C-1), 127.4 (CH, C-3Ј/4Ј/5Ј), 126.8
(CH, C-8), 126.6 (CH, C-3Ј/4Ј/5Ј), 126.6 (CH, C-3Ј/4Ј/5Ј), 123.8
(CH, C-7), 122.0 (C, C-8a), 121.0 (C, C-9a), 119.7 (CH, C-4),
118.0 (CH, C-5), 29.2 (CH , 2-CH CH ), 15.4 (CH , 2-CH -
21
16
2
2
99 (100), 285 (7), 255 (9), 142 (8); δ 8.31 (1H, dd, J = 8.0, 1.5
H
Hz, H-8), 7.67 (1H, ddd, J = 8.5, 7.0, 1.5 Hz, H-6), 7.46 (2H, dd,
J = 7.5, 7.5 Hz, H-3Ј/5Ј), 7.41 (1H, dd, J = 8.5, 1.0 Hz, H-5),
7.41 (1H, dd, J = 7.5, 7.5 Hz, H-4Ј), 7.35 (1H, ddd, J = 8.0, 7.0,
1.0 Hz, H-7), 7.34 (2H, d, J = 7.5 Hz, H-2Ј/6Ј), 7.25 (1H, s, H-
4), 2.98 (3H, s, 1-Me), 2.24 (3H, s, 2-Me); δC 178.0 (C, C-9),
155.3 (C, C-4a and C-5a), 148.7 (C, C-3), 141.3 (C, C-1Ј), 140.8
2
2
3
3
2
CH ).
3
(1R/S,3R/S)-1-Pyrrolidino-1,2,3,4-tetrahydro-2,2-dimethyl-3-
phenyl-9H-xanthen-9-one (10a)
(
1
(
1
C, C-1), 134.1 (CH, C-6), 130.9 (C, C-2), 128.9 (CH, C-2Ј/6Ј),
28.3 (CH, C-3Ј/5Ј), 127.6 (CH, C-4Ј), 126.9 (CH, C-8), 123.5
CH, C-7), 123.2 (C, C-8a), 119.2 (C, C-9a), 117.3 (CH, C-5),
16.6 (CH, C-4), 18.2 (CH , 1-Me), 17.3 (CH , 2-Me). Quench-
(
E)-2-Styryl-4-chromone (1a) (0.43 g, 1.73 mmol) and freshly
prepared 2-methyl-1-pyrrolidinoprop-1-ene (5.46 g, 43.7 mmol)
in EtOH (95%, 25 ml) were refluxed for 24 h. The product
mixture was rotary evaporated and the resulting gum was sub-
jected to column chromatography yielding (1R/S,3R/S)-
3
3
ing the reaction after 20 min produced a gum (after rotary
evaporation) which was subjected to column chromatography
yielding in addition to 7a, 1,2-dimethyl-3-phenyl-3,4-dihydro-
1
-pyrrolidino-1,2,3,4-tetrahydro-2,2-dimethyl-3-phenyl-9H-
9
H-xanthen-9-one (6a) (R = 0.54) as an oil (0.02g). νmax/
f
Ϫ1 ϩ
xanthen-9-one (10a) as yellow crystals (0.42 g, 65%) (mp 148–
cm 1654, 1608, 1560 (HRMS: M , 302.1307. C H O
requires M, 302.1307), m/z 302 (M , 58%), 301 (20), 287 (100);
δH 8.21 (1H, dd, J = 8.0, 1.5 Hz, H-8), 7.53 (1H, ddd, J = 8.5,
21
18
2
Ϫ1
ϩ
150 ЊC, 95% EtOH–CHCl
). νmax/cm 1635 (Found C, 80.06;
3
H, 7.33; N, 3.72%. C H NO requires C, 80.40; H, 7.29; N,
25
27
2
ϩ
3
.75%); m/z 373 (M , 19%), 305 (20), 304 (88), 302 (20), 242
7
.0, 1.5 Hz, H-6), 7.33 (1H, ddd, J = 8.0, 7.0, 1.0 Hz, H-7), 7.27
(
17), 241 (100); δ 8.24 (1H, dd, J = 7.8, 1.7 Hz, H-8), 7.64 (1H,
H
(
1H, dd, J = 8.5, 1.0 Hz, H-5), 7.23 (2H, dd, J = 7.5, 7.5 Hz,
m, H-6), 7.43–7.24 (7H, m, H-5/7/2Ј/6Ј/3Ј/5Ј/4Ј), 3.77 (1H, s,
H-1), 3.36 (1H, dd, J = 12.2, 6.4 Hz, H-3), 3.12 (1H, dd,
J = 19.0, 12.2 Hz, H-4), 2.91–2.87 (2H, m), 2.81 (1H, dd,
J = 19.0, 6.4 Hz, H-4), 2.74–2.71 (2H, m), 1.74–1.68 (4H, m),
H-3Ј/5Ј), 7.17 (3H, m, H-2Ј/4Ј/6Ј), 3.51 (1H, br d, J = 8.2 Hz,
H-3), 3.36 (1H, dd, J = 16.6, 8.2 Hz, H-4β), 2.81 (1H, dd,
J = 16.6, 2.6 Hz, H-4α), 2.36 (3H, d, J = 0.9 Hz, 1-Me), 1.81
(
3H, d, J = 0.7 Hz, 2-Me); δ 175.4 (C, C-9), 163.3 (C, C-4a),
C
0
.86 (3H, s, 2-Me), 0.81 (3H, s, 2-Me); δ 178.0 (C, C-9), 164.1
C
155.2 (C, C-5a), 140.9 (C, C-1Ј), 132.5 (CH, C-6), 129.6 (C, C-1/
2), 128.7 (CH, C-3Ј/5Ј), 127.8 (CH, C-2Ј/6Ј), 126.9 (CH, C-4Ј),
126.2 (CH, C-8), 125.8 (C, C-2/1), 125.2 (C, C-8a), 124.7 (CH,
(C, C-4a), 155.9 (C, C-5a), 140.9 (C, C-1Ј), 133.2 (CH), 129.3
(CH, C-3Ј and 5Ј), 128.0 (CH, C-2Ј and 6Ј), 126.7 (CH), 126.1
(CH), 124.7 (CH), 123.3 (C), 118.8 (C), 117.7 (CH), 62.7 (CH,
C-7), 118.5 (C, C-9a), 117.5 (CH, C-5), 45.0 (CH, C-3), 36.1
C-1), 53.3 (CH , pyrrolidine), 53.3 (CH , pyrrolidine), 43.2
2
2
(
CH , C-4), 18.4 (CH , 1-Me), 16.3 (CH , 2-Me). Treatment of
2
3
3
(
CH, C-3), 32.1 (CH , C-4), 25.1 (CH , 2-Me), 24.2 (CH ,
2
3
2
6
a with refluxing AcOH containing a drop of H SO resulted in
2 4
pyrrolidine), 24.2 (CH , pyrrolidine), 19.8 (CH , 2-Me).
2
3
quantitative conversion to 7a.
Crystal data for 4a
2
-Methyl-3-phenyl-9H-xanthen-9-one (8a)
A colourless crystal of dimensions 0.30 × 0.15 × 0.10 mm
mounted on a glass fibre. C H O , M = 302.37. Monoclinic,
(
E)-2-Styryl-4-chromone (1a) (0.2 g, 0.80 mmol) was refluxed in
21
18
2
propanal (25 ml) with a drop of pyrrolidine for 4 days. The
product mixture was rotary evaporated and the resulting gum
was subjected to column chromatography yielding 2-methyl-3-
a = 14.408(2), b = 7.933(2), c = 14.544(2) Å, β = 107.88(2)Њ,
3
V = 1594.0(5) Å , F0 = 640, λ = 0.710 73 Å, T = 301.2 K, space
00
Ϫ3
group P2 /n (no. 14), Z = 4, D = 1.260 g cm , µ(Mo-Kα) =
1
c
phenyl-9H-xanthen-9-one (8a) (R = 0.64) as colourless needles
f
Ϫ1
Ϫ1
0.08 m . Data collected on a MAR diffractometer with a 300
mm image plate. A total of 22412 reflections was measured, of
which 2946 were unique (Rint = 0.067). Final least-squares
refinement for 208 parameters using 1661 reflections gave
R = 0.071, wR = 0.097 and GOF = 1.99. All calculations were
performed using the teXsan crystallographic software package
(
1
0.027 g, 12%) (mp 86–87 ЊC, 95% EtOH–CHCl ). νmax/cm
3
ϩ
655, 1611 (HRMS: found M , 286.0980. C H O requires M,
20 14 2
ϩ
2
86.0994), m/z 286 (M , 100%), 285 (16), 271 (34); δ 8.36 (1H,
H
dd, J = 8.0, 1.5 Hz, H-8), 8.21 (1H, s, H-1), 7.71 (1H, ddd,
J = 8.5, 7.5, 1.5 Hz, H-6), 7.47 (2H, dd, J = 7.5, 7.5 Hz, H-3Ј/5Ј),
7
Hz, H-4Ј), 7.38 (1H, s, H-4), 7.37 (3H, m, H-2Ј/6Ј/7), 2.36 (3H,
s, 2-Me); δ 177.0 (C, C-9), 156.4 (C, C-4a and C-7), 154.4 (C,
C-5a), 149.3 (C, C-3), 140.3 (C, C-1Ј), 134.6 (CH, C-6), 131.9
.46 (1H, dd, J = 8.5, 1.0 Hz, H-5), 7.42 (1H, dd, J = 7.5, 7.5
13
of Molecular Structure Corporation. CCDC reference num-
ber 207/476. See http://www.rsc.org/suppdata/p1/b0/b004422i/
for crystallographic files in .cif format.
C
(
C, C-2), 128.8 (CH, C-2Ј/6Ј), 128.4 (CH, C-3Ј/5Ј), 127.8 (CH,
C-1), 127.5 (CH, C-4Ј), 126.8 (CH, C-8), 123.8 (CH, C-7), 122.0
C, C-8a), 120.6 (C, C-9a), 118.7 (CH, C-4), 118.0 (CH, C-5),
Acknowledgements
This work was funded by a grant from the CRCG.
(
2
0.1 (CH , 2-Me).
3
2
-Ethyl-3-(2Ј-thienyl)-9H-xanthen-9-one (9b)
References
(
E)-2-[2Ј-(2Љ-Thienyl)ethenyl]-4-chromone (1b) (0.2 g, 0.78
1
M. U. S. Sultanbawa, Tetrahedron, 1980, 36, 1465.
mmol) was refluxed in butanal (25 ml) with a drop of pyrrol-
idine for 4 days. The product mixture was rotary evaporated
and the resulting gum was subjected to column chromato-
2 M. Afzal and J. M. Al-Hassan, Heterocycles, 1980, 14, 1173.
3 J. D. Hepworth, C. D. Gabbutt and B. M. Heron, in Comprehensive
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E. F. V. Scriven, Pergamon, 1996, vol. 5, pp. 351–467.
graphy yielding 2-ethyl-3-(2Ј-thienyl)-9H-xanthen-9-one (9b)
4
(a) J. A. Elix, H. W. Musidlak, T. Sala and M. V. Sargent, Aust. J.
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1978, 34, 2491; (d) J. A. Elix and V. J. Portelli, Aust. J. Chem.,
Ϫ1
(
1
R = 0.54) as a yellowish oil (0.036 g, 15%). νmax/cm 1648,
f
ϩ
597, 1518 (HRMS: found M , 306.0718. C H SO requires
19 14 2
ϩ
M, 306.0715), m/z 306 (M , 94%), 291 (100), 273 (15), 261 (15),
740 J. Chem. Soc., Perkin Trans. 1, 2000, 3732–3741
3

View Article Online
1
4
1
990, 43, 1773; (e) J. A. Elix and H. Jiang, Aust. J. Chem., 1990,
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Commun., 1993, 159.
9 S. F. Dyke, The Chemistry of Enamines, Cambridge University
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