Chromone studies. Part 17. Tricyclic scaffolds from reactions of chromone- 3-carbaldehydes and methyl vinyl ketone under Baylis-Hillman conditions

Article abstract of DOI:10.3184/030823409X465277

Reaction of a series of chromone-3-carbaldehydes with methyl vinyl ketone under Baylis-Hillman conditions, sing 3-hydroxyquinuclidine in chloroform or DABCO in 1-methyl-2-pyrrolidinone, affords unprecedented tricylic hromone derivatives which, depending on the conditions, may be accompanied by the normal Baylis-Hillman roducts or their respective tricycl ic dimers.

Full text of DOI:10.3184/030823409X465277

4
52 RESEARCH PAPER
JULY, 452-456
JOURNAL OF CHEMICAL RESEARCH 2009
Chromone studies. Part 17. Tricyclic scaffolds from reactions of chromone-
-carbaldehydes and methyl vinyl ketone under Baylis-Hillman conditions
3
Duduzile M. Molefe, Mlungiseleli M. Ganto, Kevin A. Lobb and Perry T. Kaye*
Department of Chemistry and Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown,
6140, South Africa
Reaction of
a
series of chromone-3-carbaldehydes
with methyl vinyl ketone under Baylis-Hillman
conditions,
using 3-hydroxyquinuclidine
in chloroform or DABCO in 1-methyl-2-pyrrolidinone,
affords unprecedented tricylic
chromone derivatives which, depending on the conditions, may be accompanied by the normal Baylis-Hillman
products or their respective tricycl ic dimers.
Keywords: Baylis-Hillman reaction, chromone-3-carbaldehydes, methyl vinyl ketone, tricyclic products
Many naturally occurring chromones have been found to
exhibit interesting biological activity.l,2 Examples include
khellin, a furochromone with vasodilator and smooth muscle
relaxing properties3 isolated from the fruits and seeds
Baylis-Hillman reactions are known to be sensItive to
variations in the catalyst and solvent system7 and we now
report the results of reactions of a series of chromone-3-
carbaldehydes with methyl vinyl ketone conducted using
3-hydroxyquinuclidine in chloroform and DABCO in the
solvent, l-methyl-2-pyrrolidinone (NMP), and in chloroform.
The chromone-3-carbaldehydes 2a-e, obtained by "double"
Vilsmeier-Haak formyiation10 of the corresponding 2-
hydroxyacetophenone precursors la-e, were first reacted
with MVK 3 and 3-hydroxyquinuclidine in chloroform for
24 hours.ll Work-up and purification of the crude products
afforded the novel tricyclic adducts 4a-e (31-52%) and the
chromone dimers 6a-e (12-25%), which contain isomeric
tricyclic skeletons. Surprisingly, none of the Baylis-Hillman
products 5a-e appeared to be present after 24 hours, 11and it
was assumed that they had been formed as intermediates but
converted insitu into the corresponding chromone dimers 6a-e.
The unusual, oxygenated, tricyclic skeleton in the former
series (4a-e) has been found in natural metallo-13-lactamase
inhibitors, such as 8,12 and in more complex semaphorin
inhibitors,13
of Ammi visnaga
4
and used to treat bronchial asthma,3-5
and styrylchromone derivatives isolated from the marine
cyanophyte, Hormothamnion enteromorphoides,6 which have
proved to be potent cytotoxic agents against P388 lymphocytic
leukaemia and HL-60 human promyelocytic leukaemia cell
lines. As part of ongoing synthetic and physical organic
studies of chromone derivatives,7 we have previously reported
the formation of novel dimeric and bis-chromone adducts
during 1,4-diazabicyclo[2.2.2]octane (DABCO) catalysed
Baylis-Hillman reactions of chromone-3-carbaldehydes with
methyl acrylate8 and acrylonitrile,9 respectively. In the latter
study,9 treatment of chromone-3-carbaldehyde 2a (Scheme I)
with methyl vinyl ketone (MVK) in the presence of DABCO
afforded the expected Baylis-Hillman product Sa in very low
yield (3%) together with the corresponding condensation
dimer 6a (33%), while a trace quantity of a completely
different, bis(chromone)-acrylonitrile adduct was isolated
from a reaction with acrylonitrile and formulated, on the basis
of the HRMS and NMR data, as the polycyclic compound 7.
Use of DABCO, as catalyst, and NMP, as solvent, resulted
in the isolation of the tricyclic adducts 4a-e chemoselectively,
0
R
a
b
c
H
CI
RV::
I ~
1a-e
Br
OH
d
e
F
OMe
0
i,ii
1
0
0
~
•
I ~
I
H
iii R'Clf
lR~]
~
0
2a-e
III
-j ~
j
I
3
R
0
R
R
Scheme
1
Reagents and conditions: (i) POCI3, DMF; (ii) H
2
0; (iii) 3-hydroxyquinuclidine,
CHCI
3
*
Correspondent. E-mail: P.Kaye@ru.ac.za

JOURNAL OF CHEMICAL RESEARCH 2009 453
o
MeO
H0 x Xt t H0 2~0 OMe
I
0
HO
f i
0
Me
8
OMe
but in slightly lower yield (30-45%).10 When 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) was employed as
the catalyst, however, the reaction failed to take place at all,
confirming the observation by Aggarwal et aUs that MVK is
not reactive as a Baylis-Hillman substrate in the presence of
DBU. When the reactions of the chromone-3-carbaldehydes
(Fig. I) reveals interactions between the I-methine and 12-
methyl protons, and between the 4a-methine and one of the
3-methylene protons; however, neither of these interactions
provides definitive information pertinent to the stereochemistry
of the stereogenic centres C-4 and C-4a. The NOESY spectrum
of the diasteromeric tricyclic adduct 4a2 (Fig. 2), on the other
hand, reveals interactions between the 4a-methine and the B-
and 14-methylene protons, clearly indicating that they occupy
the same face of the molecule. These observations justify
the 4R,4aR (or 4S,4aS) configurational assignment(s) to the
enantiomers 4a2 and, by inference, the 4S,4aR (or 4R,4aS)
configuration( s) to the enantiomers of diastereomer 4a1'
Semi-preparative HPLC of the brominated and chlorinated
analogues 4b and 4c, respectively, afforded only one fraction
in each case. The brominated analogue 4b exhibited similar
IH NMR signal patterns to the parent system 4a1>whereas
the chlorinated analogue 4c exhibited similar IH NMR signal
patterns to the diastereomeric system 4a2' However, since the
reaction and work-up conditions for these transformations
have yet to be optimised, generalisations about the relative
diastereoselectivities would be premature.
The formation of the bis-MVK tricyclic products 4a-e
and the trace product 79 presents interesting mechanistic
possibilities; firm conclusions, however, would be premature
at this stage and must await the results of detailed kinetic-
mechanistic studies. The tricyclic derivatives 6a-e, on the
other hand, are bis-Baylis-Hillman adducts and are, in
fact, analogues of the dimeric products obtained during
DABCO-catalysed Baylis-Hillman reactions of chromone-
3-carbaldehydes with methyl acrylate.8 Their formation
is presumed to follow the mechanistic sequence proposed
earlier,8 the only difference being the presence of CO.Me
2
a-c,e were repeated using 3-hydroxyquinuclidine in
chloroform,14 work-up and chromatography of the crude
products afforded the chromone dimers 6a-c,e (34-72%)
and the tricyclic products 4a-c,e in lower yields (:s 16%)
than those observed earlier.l l Increasing the relative quantity
of MVK (from l.l to 2.0 equivalents) failed to improve the
yields of the tricyclic adducts 4 but, surprisingly, resulted
in the formation of the Baylis-Hillman products 5a-c,e as
competition products instead of the dimers 6a-c,e. When
the chromone-3-carbaldehydes 2a-e were reacted with
MVK using DABCO as catalyst in chloroform for 21 days,
work-up and chromatography afforded the chromone dimers
6
a-e in yields (24-49%) comparable to those obtained for
dimer 6a (33%) in our earlier study; 9 however, none of the
Baylis-Hillman products were isolated. All products were
fully characterised by spectroscopic (IR, 1- and 2-dimensional
NMR) and elemental (HREIMS) analysis.
In addition to possessing isomeric tricyclic skeletons, the
compounds in both series of products (4a-e and 6a-e) each
contain two new stereogenic centres, and diastereomeric
products may be expected in each case. Semi-preparative
HPLC of the parent tricyclic product 4a (R
=
H) afforded
two fractions shown to be the diastereomeric products, the
relative configurations of which have been assigned following
examination of their 2-dimensional n.O.e. (NOESY) spectra.
While the stereochemistry of the latter compounds (6a-e) is
further complicated by E- and Z-configurational options about
the exocyclic double bond, diastereoselective formation of the
E-products seems likely, based on the NMR spectra and the
E-configuation observed in the X-ray structure of a diester
analogue.9 The NOESY spectrum of the tricyclic adduct 4a1
rather than C0 Me moieties. Thus, a pair of the MVK-derived
2
Baylis-Hillman adducts 5 are proposed to combine via a six-
centred transition state complex, as outlined in Scheme 2,
leading to intermediate 9. Attack of the hemi-acetal hydroxyl
oxygen on the a,13-unsaturated carbonyl moiety then results
R
Fig. 1 Assigned relative configuration
and computer-modelled
structure of diastereomer 4al' showing observed n.O.e. interactions.
o
R
Fig.2
Assigned relative configuration
and computer-modelled
structure of diastereomer 4a2' showing observed n.O.e. interactions.

4
54 JOURNAL OF CHEMICAL RESEARCH 2009
COMe
~
0
~l
0
R
5
a-e
HO
I
r I
o
~
COMe
L
R
R
9a-e
III
R
R
R
6a-e
Scheme
2
Proposed mechanism for the formation of compounds 6.
in intramolecular
cyclisation via an SN 2' (as shown) or
sequence to afford the dimer
similar treatment of an isolated, methyl acrylate-derived
Baylis-Hillman analogue afforded the corresponding dimer.s
a
4-A cetyl-4-(3 -oxobutyl)-4, 4a-dihydro- 3H-pyrano [4,3 -bJ benzopyran-
1
0-one 4a and the corresponding
dimer (6a): general procedure
conjugate addition-elimination
Methyl vinyl ketone (0.56 mL, 8.6 mmol) was added to a stirred
solution of chromone-3-carbaldehyde 2a (1.0 g, 5.8 mmol) and
6
;
3
-hydroxyquinuclidine (3.7 g, 29 mmol) in CHCI3 (7.0 mL).
While
variations
in reactant
concentrations,
techniques
reaction
The resulting mixture was stirred vigorously at room temperature
for 24 h. Evaporation of solvent in vacuo gave a brown oily residue
which was purified by flash chromatography [on silica; elution with
hexane-EtOAc (I :2)] afforded two fractions.
conditions
and, possibly, separation
appear to
influence the yields and product distribution in these reactions,
optimisation of the methodology could well provide efficient
(
i) The tricyclic product 4a as a brown viscous oil (0.67 g, 38%)
Found M+: 314.1131. Cl8Hl80S requires, M: 314.1154) Vmax (KBr)/
cm-11700, 1665 and 1650 (3 x C=O); OH (400 MHz; CDCI3) 1.98 and
.25 (2H, 2 x m, CH 2.07 (3H, s, CH2CH2COCH3), 2.39
3H, s, COCH3), 2.40 and 2.60 (2H, 2xm, CH CH CO), 4.59 (lH,
access to unusual and complex poly-heterocyclic
targets,
(
including analogues of the biologically
inhibitors!3 and the metallo-13-lactamase
active semaphorin
inhibitor 8.!2
2
2CH2CO),
(
2
2
dd, J = 17.2 and 1.9 Hz, 3-H,), 4.79 (lH, dd, J = 17.2 and 1.5 Hz,
3-Hb), 5.13 (lH, s, 4a-H), 7.13 (2H, m, 6-H and 8-H), 7.30 (lH, br
s, I-H), 7.57 (lH, t" J= 6.9 Hz, 7-H) and 7.90 (lH, d, J= 6.5 Hz,
Experimental
NMR spectra were recorded on Bruker AMX400 or AVANCE 600
MHz spectrometers at 303K in CDCI3 and calibrated using solvent
signals. Carbon-13 signal multiplicity assignments are based on
DEPT, signal intensity or comparative shift data. In the case of the
fluorinated analogues 4d and 6d, the cited multiplicities reflect the
expected presence (or absence) of 13C_IH coupling; the reported
coupling constants (JCF), however, refer to the 13C_19Fcoupling
observed as doublets in the p.n.d. spectra. IR spectra were recorded on
a Perkin Elmer FT-IR Spectrum 2000 spectrometer. Low-resolution
mass spectra were obtained on Finnigan-Mat GCQ (EI) and LCQ
9
-H); Oc (100 MHz; CDCI3) 24.8 (t), 25.5 (t), 30.0 (q), 37.8 (t), 49.1
(
(
s), 65.9 (t), 99.9 (d), 118.2 (d), 119.5 (s), 123.0 (d), 127.9 (d), 135.4
d), 136.8 (d), 138.3 (s), 157.6 (s), 192.6 (s), 196.6 (s) and 206.7 (s);
m/z 314 (M+, 2%) and 193 (100).
ii) The chromone dimer 6a as a yellow solid (0.32 g, 12%), m.p.
93-195°C (lit} 193-194°C) (Found M+: 470.1364. C28H2207
(
1
requires M: 470.1366); Vmax (KBr)/cm-1, 1698, 1669, 1642 and 1606 (4
x C=O); OH (400 MHz; CDCI3) 2.29 and 2.42 (6H, 2xs, 2xCH3), 3.23
(
5
(
2H, 2x d, J = 14.7 Hz, CH2), 4.52 (2H, dd, J = 17 and 1.7 Hz, OCH2),
.00 (lH, s, OCHO), 6.83-6.90 (2H, m, ArH), 7.17 (lH, s, ArH), 7.27
lH, m, ArH), 7.40-7.47 (3H, m, C=CH and ArH), 7.69-7.75 (2H, m,
(ES) mass spectrometers; high-resolution (EI) mass spectra were
recorded by the Mass Spectrometry Units at the Cape Technikon, the
University of the Witwatersrand or the University of the North-West.
The structures of the diastereomers 4al and 4a2, illustrated in Figs I
and 2, were modelled at the AMI1evel using the software package,
PC SPARTAN-pro.16
prepared as described previously.8-10
ArH), 7.90 (lH, s, ArH), and 8.13 (2H, dd, J= 8.0 and 1.3 Hz, ArH);
Oc (100 MHz; CDCI3) 25.3 (q), 25.8 (t), 25.9 (q), 50.1 (s), 65.9 (t),
99.9 (d), 117.5 (d), 118.1 (d), 120.0 (s), 120.3 (s), 122.9 (d), 123.5 (s),
125.8 (d), 126.1 (d), 128.0 (d), 133.6 (d), 134.2 (d), 136.1 (d), 136.5
(s), 136.7 (d), 139.0 (s), 154.1 (d), 155.9 (s), 157.0 (s), 175.6 (s), 191.5
(s), 196.9 (s) and 199.0 (s); m/z 470 (M+, 24%) and 185 (100).
The chromone-3-carbaldehydes
2a-e were

JOURNAL OF CHEMICAL RESEARCH 2009
455
When DABCO (0.38 g, 2.9 mmol) was used as catalyst and
I-NMP (3 mL) as solvent, work-up afforded compound 4a as a light
brown viscous oil (0.82 g, 45%).
(i) The tricyclic product 4d as a light brown oil (0.53 g, 31%) (Found:
M+, 332.1051. CI8H17FOs requires, M: 332.1060), vmax (KBr)/cm'l,
1674, 1687 and 1699 (3 x C=O); OH(400 MHz; CDCI3) 1.97-2.23 (2H,
2
xm, CH2CH2CO), 2.08 (3H, 5, CH2CH2COCH3), 2.35-2.45 (2H, 2xm,
4
-Acetyl-8-chloro-4-(3-oxobutyl}-4,
4a-dihydro- 3H-pyrano[ 4,3 -bJ
CH2CH2CO), 2.39 (3H, 5, COCH3), 4.57 (lH, dd, J = 17.2 and 1.9 Hz,
3-H,), 4.79 (lH, dd, J = 17.2 and 1.7 Hz, 3-Hb), 5.11 (lH, 5,4a-H), 7.12
(lH, dd,J= 9.1 and 4.2 Hz, 6-H), 7.27 (lH, brs, I-H), 7.30 (lH, m, 7-H)
and 7.54 (lH, dd, J = 8.0 and 3.1 Hz, 9-H); Oc(100 MHz; CDCI3) 24.7
(t), 25.5 (q), 30.0 (q), 37.6 (t), 49.0 (5), 65.9 (t), 100.1 (d), 113.0 (JCF=
benzopyran-10-one 4b and the corresponding dimer 6b
The general procedure was followed, using 6-chlorochromone-3-
carbaldehyde 2b. Work-up and flash chromatography afforded two
fractions.
(
i) The tricyclic product 4b as a reddish oil (0.73 g, 44%) (Found
MH+: 349.0843. CI8HI8CIOs requires, M: 349.0848); vmax(KBr)/cm'l
717, 1699 and 1674 (3 x C=O); OH(400 MHz; CDCI3) 2.13 (3H, 5,
CH2CH2COCH3), 2.15-2.25 (2H, 2 x m, CH2CH2CO), 2.31 (3H, 5,
2
5
3.6 Hz, C-7, d), 120.0 (JCF= 7.7 Hz, C-6, d), 120.2 (JCF= 6.5 Hz, C-IO,
), 124.4 (JCF = 24.7 Hz, C-9, d), 126.2 (5), 134.9 (d), 153.8 (5), 158.0
1
(JCF= 244.1 Hz, C-8, 5), 191.9 (5), 196.5 (5)and 206.5 (5).
(ii) The chromone dimer 6d as a yellow solid oil (0.37 g, 21%)
COCH3), 2.46-2.59 (2H, 2xm, CH2CH2CO), 4.48 (lH, dd, J= 17.1
and 2.0 Hz, 3-H,), 4.63 (lH, dd, J = 17.0 and 1.5 Hz, 3-Hb), 5.40
(
Found MH+: 507.1251. C28H2oF207requires, M + 1: 507.1255); Vmax
(KBr)/cm' 1, 1674, 1683, 1699 and 1717 (4 x C=O); OH(400 MHz;
(lH, 5, 4a-H), 6.65 (lH, br 5, I-H), 6.69 (lH, d, J = 8.8 Hz, 6-H),
CDCI3) 2.32 and 2.45 (6H, 2 x 5, 2xCH3), 3.52 (2H, 2xd, J = 14.7 Hz,
CH2), 5.18 (2H, dd, J= 17 and 1.7 Hz, OCH2), 5.85 (lH, 5, OCHO),
7
7
9
.48 (lH, dd, J = 8.8 and 2.7 Hz, 7-H) and 7.80 (lH, d, J = 2.7 Hz,
-H); ocClOO MHz; CDCI3) 25.2 (q), 27.6 (t), 30.0 (q), 37.6 (t), 48.8
.17 (lH, 5, C=CH), 7.26 (lH, d, J = 8.9 and 2.0 Hz, ArH), 7.30 (lH,
, C=CH), 7.48 (lH, d, J = 8.9 Hz, ArH), 7.72 (lH, d, J = 8.9 Hz,
(
(
5),62.7 (t), 99.6 (d), 118.8 (5), 120.0 (d), 126.6 (d), 135.4 (d), 136.9
d), 139.4 (5), 143.5 (5), 155.9 (5), 192.0 (5), 196.4 (5) and 205.3 (5);
5
ArH), 7.64 (lH, dd, J = 8.0 and 2.0 Hz, ArH), 7.93 (lH, 5, ArH),
.94 (lH, d, J = 2.0 Hz, ArH), and 7.96 (lH, d, J = 1.3 Hz, ArH);
ocCIOOMHz; CDCI3) 25.3 (q), 25.79 (t), 25.85 (q), 49.9 (5), 66.0 (t),
9.9 (d), 110.8 (JCF= 23.8 Hz, d), 113.1 (JCF= 23.6 Hz, d), 119.3 (JCF
8.1 Hz, d), 119.7 (5), 120.3 (JCF= 8.1 Hz, d), 120.6 (JCF= 6.6 Hz,
),122.7 (JCF= 25.1 Hz, d), 123.6 (JCF= 24.8 Hz, d), 124.6 (JCF= 7.4
Hz,s), 133.4 (d), 136.0 (d), 136.7 (5), 139.3 (5), 152.0 (5), 153.1 (5),
54.2 (d), 157.8 (JCF= 244.8 Hz,s), 159.8 (JCF= 248.7 Hz,s), 174.8
m/z 349 (MW, 9%) and 154 (100).
ii) The chromone dimer 6b as a yellow solid (0.45 g, 17%),
m.p. 112-114°C (Found M+: 538.0587. C28H2oCl207 requires, M:
38.0586); Vmax (KBr)/cm'l, 1653,1678, 1684 and 1701 (4 x C=O);
OH(400 MHz; CDCI3) 2.31 and 2.44 (6H, 2xs, 2xCH3), 3.00 (2H,
7
(
9
=
5
5
2
5
xd, J = 14.7 Hz, CH2), 5.16 (2H, dd, J = 17 and 1.7 Hz, OCH2),
.39 (lH, 5, OCHO), 6.93 (lH, 5, C=CH), 7.12 (lH, d, J = 8.9 Hz,
1
ArH), 7.30 (lH, 5, C=CH), 7.44 (lH, d, J= 8.9 Hz, ArH), 7.45 (lH,
d, J= 8.9 and 2.0 Hz, ArH), 7.76 (lH, dd, J= 8.0 and 2.0 Hz, ArH),
(5), 190.7 (5),196.8 (5) and 198.8 (5).
When DABCO (0.26 g, 2.0 mmol) was used as catalyst and 1-
8
.08 (lH, d, J = 2.0 Hz, ArH), 8.66 (lH, 5, ArH), and 8.18 (lH, d,
J= 1.3 Hz, ArH); ocCIOO MHz; CDCI3) 25.4 (q), 25.9 (q), 31.2 (t),
0.5 (5), 66.I(t), 100.2 (d), 116.6 (d), 118.0 (d), 121.6 (5), 122.2 (5),
24.4 (d), 128.4 (d), 128.5 (d), 133.6 (d), 134.0 (5), 136.6 (5), 136.7
d), 139.3 (5), 141.4 (5), 143.7 (d), 148.6 (5), 154.2 (d), 156.2 (5),
NMP (3 mL) as solvent, work-up afforded compound 4d as a light
brown viscous oil (0.40 g, 30%).
5
1
(
1
4
-Acetyl-8-methoxy-4-(3-oxobutyl}-4,
4a-dihydro-3H -pyrano [4,3-bJ
benzopyran-10-one 4e and the corresponding dimer 6e
The general procedure was followed, using 6-bromochromone-3-
carbaldehyde 2e. Work-up and flash chromatography afforded two
fractions.
58.5 (5), 174.8 (5),190.8 (5), 196.9 (5) and 199.0 (5).
When DABCO (0.31 g, 2.4 mmol) was used as the catalyst and
I-NMP (3 mL) as solvent, work-up afforded compound 4b as a light
brown viscous oil (0.67 g, 40%).
(i) The tricyclic product 4e as a reddish oil (0.57 g, 34%) (Found:
4
-Acetyl-8-bromo-4- (3-oxobutyl)-4, 4a-dihydro-3H -pyrano [4,3-bJ
M+, 344.1252. CI9H2006 requires, M: 344.1259), Vmax (KBr)/cm'l,
1652, 1665 and 1674 (3 x C=O); OH(400 MHz; CDCI3) 2.09-2.23
benzopyran-10-one 4c and the corresponding dimer 6c
The general procedure was followed, using 6-bromochromone-3-
carbaldehyde 2c. Work-up and flash chromatography afforded two
fractions.
(2H, 2xm, CH2CH2CO), 2.15 (3H, 5, CH2CH2COCH3),
2.39-2.51
(2H, 2xm, CH2CH2CO), 2.44 (3H, 5, COCH3), 3.91 (3H, 5, 6-0CH3),
4.55 (lH, dd, 3-H, and Hb), 4.94 (lH, 5, 4a-H), 6.69 (lH, br 5, I-H),
7.08 (lH, d, J= 9.11 Hz, 6-H), 7.33 (lH, dd, J = 2.32 and 9.11 Hz,
7-H) and 7.85 (lH, d, J= 2.32 Hz, 9-H); ocCIOOMHz; CDCI3) 24.7
(t), 25.5 (q), 30.0 (q), 37.6 (t), 50.1 (5),55.9 (q), 65.9 (t), 99.8 (d),
118.5 (5), 119.4 (d), 124.1 (d), 133.9 (d), 137.3 (d), 139.0 (5), 143.5
(5), 154.8 (5), 191.4 (5), 197.1 (5) and 199.2 (5); m/z (M+, 33%) and
193 (100).
(
i) The tricyclic product 4c as a reddish oil (0.81 g, 52%) (Found:
M+,392.0257. C18H177 9B rOs requires, M: 392.0259), Vmax(KBr)/cm'l,
600, 1674 and 1716 (3 x C=O); OH(400 MHz; CDCI3) 1.94-2.24
2H, 2xm, CH2CH2CO), 2.08 (3H, 5, CH2CH2COCH3), 2.26-2.58
2H, m, CH2CH2CO), 2.39 (3H, 5, COCH3), 4.58 (lH, dd, J = 17.2
and 1.7 Hz, 3-H,), 4.79 (lH, dd, J = 17.2 and 1.5 Hz, 3-Hb), 5.11
1
(
(
(
(
lH, 5, 4a-H), 6.73 (lH, m, I-H), 7.02 (lH, d, J= 8.81 Hz, 6-H), 7.64
lH, dd, J = 8.8 and 2.5 Hz, 7-H) and 7.99 (lH, d, J = 2.4 Hz, 9-H);
(ii) The chromone dimer 6e as a yellow oil (0.49 g, 19%) (Found
M+: 530.1578. C30H2609 requires, M:530.1576);
Vmax (KBr)/cm'
Oc(100 MHz; CDCI3) 24.7 (t), 25.5 (q), 30.0 (q), 37.6 (t), 49.0 (5),
5.9 (t), 100.0 (d), 118.1 (5), 120.2 (d), 130.3 (d), 134.8 (d), 139.4
d), 138.4 (5), 143.5 (5), 156.5 (5), 191.4 (5), 196.4 (5) and 206.5 (5);
m/z 392 (M+, 2%) and 194 (100).
ii) The chromone dimer 6c as a yellow oil (0.53 g, 21%) (Found
M+:625.9579. C28H2079Br207requires,M: 625.9576); vmax(KBr)/cm'l,
600,1670,1675 and 1710 (4 x C=O); OH(400 MHz; CDCI3) 2.31
and 2.44 (6H, 2 x 5, 2xCH3), 3.50 (2H, 2xd, J = 14.7 Hz, CH2), 5.17
2H, dd, J = 17 and 1.7 Hz, OCH2), 5.81 (lH, 5, 9a-H), 7.16 (lH, 5,
I, 1653, 1674, 1677 and 1700 (4 x C=O); OH(400 MHz; CDCI3)
2.28 and 2.33 (6H, 2x 5, 2xCH3), 3.14 (2H, 2xd, J= 14.7 Hz, CH2),
3.68 and 3.80 (6H, 2xs, 2xOCH3), 5.09 (2H, dd, J= 17 and 1.7 Hz,
OCH2), 5.25 (lH, 5, OCHO), 6.95 (lH, 5, C=CH), 6.98 (lH, d,
J= 8.9 Hz, ArH), 7.27 (lH, 5, C=CH), 7.44 (lH, d, J= 8.9 and 2.0 Hz,
ArH), 7.64 (lH, d, J= 8.9 Hz, ArH), 7.73 (lH, dd, J= 8.0 and 2.0 Hz,
ArH), and 8.16 (lH, d, J = 1.3 Hz, ArH), 8.33 (lH, d, J = 2.0 Hz,
ArH), and 8.70 (lH, 5, ArH); Oc(100 MHz; CDCI3) 25.4 (q), 25.86
6
(
(
1
(
(t), 25.93 (q), 50.1 (5),55.5 (q), 55.9 (q), 65.8 (t), 99.7 (d), 105.0 (d),
C=CH), 7.28 (lH, 5, C=CH), 7.38 (lH, d, J= 8.9 Hz, ArH), 7.61 (lH,
d, J = 8.9 Hz, ArH), 7.62 (lH, d, J = 8.9 and 2.0 Hz, ArH), 7.79 (lH,
1
08.1 (d), 118.5 (d), 119.2 (5), 119.3 (d), 119.8 (5),124.05 (5),124.13
(d), 125.1 (d), 133.9 (d), 136.0 (5), 137.3 (5), 139.0 (d), 150.6 (5),
5
, ArH), 8.00 (lH, dd, J = 8.0 and 2.0 Hz, ArH), 8.35 (lH, d, J = 2.0
Hz, ArH), and 8.32 (lH, d, J = 1.3 Hz, ArH); Oc(100 MHz; CDCI3)
5.4 (q), 25.89 (q), 25.91 (t), 50.0 (5), 66.0 (t), 99.8 (d), 115.9 (5),
18.3 (d), 119.4 (d), 120.0 (d), 120.4 (5), 121.2 (5), 124.6 (5), 128.7
d), 130.4 (d), 133.3 (d), 136.2 (d), 136.5 (5), 137.3 (d), 138.8 (d),
39.4 (5),154.1 (5), 154.5 (5), 155.9 (5),174.1 (5), 190.3 (5), 196.8 (5)
1
57.4 (5),153.8 (d), 154.7 (5),157.2 (5),175.3 (5),191.4 (5),197.1 (5)
and 199.2 (5); m/z 548 (M+, 5%) and 43 (100).
2
1
(
1
When DABCO (0.32 g, 2.5 mmol) was used as the catalyst and
I-NMP (3 mL) as solvent, work-up afforded compound 4e as a light
brown viscous oil (0.6 g, 37%).
and 198.9 (5); m/z 626 (M+, 16%) and 136 (100).
We thank the National Research Foundation
(NRF; GUN
When DABCO (0.26 g, 2.0 mmol) was used as the catalyst and
I-NMP (3 mL) as solvent, work-up afforded compound 4c as a light-
brown viscous oil (0.51 g, 33%).
2069255)
Africa (MRC) for bursaries
Rhodes University,
financial support. Any opinion, findings and conclusions or
recommendations expressed in this material are those of the
and the Medical Research
Council of South
(to M.G. and D.M.M) and
the NRF and the MRC for generous
4
-Acetyl-8-jluoro-4-(3-oxobutyl}-4,
4a-dihydro- 3H-pyrano[ 4,3 -bJ
benzopyran-10-one 4d and the corresponding dimer 6d
The general procedure was followed, using 6-fluorochromone-3-
carbaldehyde 2d. Work-up and flash chromatography afforded two
fractions.
authors and therefore the NRF does not accept any liability in
regard thereto.

4
56 JOURNAL OF CHEMICAL RESEARCH 2009
Received 3 March 2009; accepted 22 April 2009
Paper09/0472 doi: 10.3184/030823409X465277
Published online: 15 July 2009
7
8
D. Mo1efe and P.T. Kaye, Synth. Cornrnun., in press.
P.T. Kaye, A.T. Nchinda, L.Y. Sabbagh and J. Bacsa,
J Chern. Res.(S),
2
003, 111; J Chern. Res. (M), 2003, 0301.
P.T. Kaye, D.M. Mo1efe, A.T. Nchinda and L.Y. Sabbagh,
004,303.
9
J Chern. Res.,
2
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