Bargellini condensation of coumarins. Expeditious route to o-carboxyvinylphenoxyisobutyric acids and application to the synthesis of sesquiterpenes helianane, heliannuol A and heliannuol C

Article abstract of DOI:10.1016/j.tet.2007.09.006

The direct Bargellini condensation of coumarins involving reaction with chloroform and acetone in the presence of aqueous sodium hydroxide furnished o-carboxyvinylphenoxyisobutyric acids in good yields. The utility of this new useful protocol was demonstrated by the transformation of the three diesters 9b, 9f and 9g to the sesquiterpenes helianane 4, heliannuol A 2 and heliannuol C 3, respectively.

Full text of DOI:10.1016/j.tet.2007.09.006

Tetrahedron 63 (2007) 12026–12036
Bargellini condensation of coumarins. Expeditious
route to o-carboxyvinylphenoxyisobutyric acids
and application to the synthesis of sesquiterpenes
helianane, heliannuol A and heliannuol C
Bidyut Biswas,a Prabir K. Senb and Ramanathapuram V. Venkateswarana,
*
aDepartment of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, West Bengal, India
bChemistry Department, Haldia Government College, Midnapore, West Bengal, India
Received 16 April 2007; revised 22 August 2007; accepted 6 September 2007
Available online 11 September 2007
Abstract—The direct Bargellini condensation of coumarins involving reaction with chloroform and acetone in the presence of aqueous
sodium hydroxide furnished o-carboxyvinylphenoxyisobutyric acids in good yields. The utility of this new useful protocol was demonstrated
by the transformation of the three diesters 9b, 9f and 9g to the sesquiterpenes helianane 4, heliannuol A 2 and heliannuol C 3, respectively.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
synthesis had not been forthcoming. A recent report dis-
closes application to the synthesis of a dual PPARa/g ago-
nist by employing this condensation in a sterically
congested phenol.8 However, the acceptability of this
method as a useful protocol in synthesis came with the recent
isolation of heliannuol A 2 and heliannuol C 3,9 important
allelochemicals from cultivar sunflowers and the related ses-
quiterpene helianane 4,10 from marine sponge. These com-
pounds contain an a-phenoxyisobutyl component and can
readily serve as appropriate target molecules to attest to
the viability of Bargellini condensation for incorporation
of this unit. Indeed the early approaches to these sesquiter-
penes featuring a novel benzoxocane ring system have
employed this condensation to install the crucial gem-
dimethyl functionality in a suitable substrate that was
A century ago Bargellini reported the interesting condensa-
tion of phenols with chloroform and acetone in the presence
of sodium hydroxide to furnish a-phenoxyisobutyric acids 1
(Scheme 1).1 In fact, however, he was modifying the
structure attributed to this condensation product by Link2
a few years earlier. Although initial studies were confined
to phenolic substrates, later investigators have extended
this to aliphatic alcohols and with better yields from conden-
sation with acetonechloroform (chloretone).3 Thus, a simple
methodology for the general conversion of alcohols to a-al-
koxyisobutyric acid systems was developed. Dealkoxylation
of these products provided an access to methacrylic acids.
Besides acetone, other ketonic substrates were also found
to respond identically to this reaction condition.3 Further
transformations of the phenoxyisobutyric acids to amides
for possible exploration as plant hormones4 and also to pro-
vide an alternative to Birch reduction have been described.5
In the case of aminoethanols, the amine functionality served
as the nucleophile and the resultant acids underwent an intra-
molecular lactonisation to afford 2-oxomorpholines.6 An
unusual case of a para-carbon atom functioning as a nucleo-
phile in a hindered phenol has also been reported.7 Despite
the ready incorporation of an isobutyric acid system onto
an alcoholic oxygen, the demonstration of its utility in
HO
HO
OH
R
O
O
H
R =
heliannuol A 2,
heliannuol K 26,
heliannuol C 3
OH
R = O
O
Keywords: Bargellini condensation; o-Carboxyvinylphenoxyisobutyric
acids; Heliannuols; Helianane; Ring-closing metathesis.
* Corresponding author. Fax: +91 33 24732805; e-mail: ocrvv@iacs.res.in
helianane 4
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.006

B. Biswas et al. / Tetrahedron 63 (2007) 12026–12036
12027
expanded to the requisite ring system.11 Our previous syn-
thesis of 2 and 4 also had relied on this condensation to trans-
form the styrenol(s) 5 to the phenoxyisobutyric acid(s) 6,
which were subsequently elaborated to the natural products
(Scheme 2).12 The styrenols 5a and 5b were obtained from
decarboxylative alkaline hydrolysis of coumarins 7b and
7f. Coumarins undergo an initial ring opening under alkaline
hydrolytic conditions to generate an intermediate phenolate.
Hence it occurred to us that if coumarins are subjected to
Bargellini reaction conditions involving the use of base,
the intermediate phenolates on further reaction with acetone
and chloroform will finally provide a novel one-step route to
a-phenoxyisobutyric acids with the additional advantage of
an acrylic acid functionality on the adjacent carbon atom of
the phenyl ring for further useful transformations. We de-
scribe in this article the successful realization of this strat-
egy13 and demonstrate the utility of the methodology by
applying it to the synthesis of helianane 4, heliannuol A 2
and heliannuol C 3.
the preparation of functionalized phenoxy acids. To under-
score the preparative utility of this novel procedure, appro-
priately substituted products were transformed to the
natural products, helianane 4, heliannuols A 2 and C 3 as
detailed below.
R1
O
R1
O
i. CHCl3, NaOH
acetone
R2
R3
R2
R3
CO2R
CO2R
ii. HCl
O
7
8, R = H
CH2N2,
Et2O
9, R = Me
R
1 = R2 = R3 = H
(75%)
a,
b,
c,
R
1 = R3 = Me, R2 = H
1 = R2 = Me, R3 = H
(74%)
(72%)
R
R
1 = H, R2 = OMe, R3 = H
(68%)
(74%)
(73%)
(73%)
d,
e,
f,
R1 = R2 = Me, R3 = OMe
R1 = R3 = Me, R2 = OMe
1 =H, R2 = OMe, R3 = Me
g,
R
i. CHCl3, NaOH,
acetone
O
CO2R
O
R1
R1
i. CHCl3, NaOH
acetone
ii. HCl
CO2R
O
O
OH
CO2H
1
ii. HCl
Scheme 1.
11, R = H
10
CH2N2,
Et2O
12, R = Me
R1
R1 = Me
=
(64%)
(68%)
a
b
i. CHCl3, NaOH,
acetone
H
R
R
ii. HCl
OH
O
CO2H
Scheme 3. Yields reported are overall for 9 and 12.
5
6
a R = H
b R = OMe
Catalytic hydrogenation of the diester 9b furnished the sat-
urated diester 13 in quantitative yield. This diester 13 was
then reduced to the diol 14 with lithium aluminium hydride
in refluxing ether in excellent yield (98%). This diol 14
underwent smooth oxidation under Swern conditions to the
dialdehyde 15 (93%), which was subjected to a double Wit-
tig reaction with triphenylmethylene phosphorane to afford
the diene 16 in 70% yield. This diene 16 had previously
been taken to helianane 4 by Snieckus and Stefinovic,11b
thus concluding in the present case a formal synthesis of
this sesquiterpene. We also carried out the reported steps
to complete the synthesis. However, our efforts on cycliza-
tion by employing Grubbs first generation catalyst (A)
were unsuccessful and furnished only a complex product
profile. The second generation of Grubbs catalyst (B) proved
successful and led to a smooth ring-closure furnishing the
cyclized alkene 17 in 85% yield (Scheme 4). This alkene
was spectroscopically identical to a sample previously syn-
thesized in this laboratory and which had been hydrogenated
to helianane 4.12b
Scheme 2.
2. Results and discussion
Coumarin 7a was subjected to reaction with chloroform and
acetone in the presence of sodium hydroxide under Barge-
llini conditions and the product acidified to afford the diacid
8a in 75% yield as a crystalline solid. The structural assign-
ment was adequately supported by analytical and spectral
data. The HRMS showed a molecular weight correlating to
1
the desired molecular formula and the H NMR spectrum
showed a 6 proton singlet at d 1.57 for the gem-dimethyl
group along with other associated features further attesting
to the assigned structure. This diacid 8a was additionally
characterized as the dimethyl ester 9a, obtained on treatment
with diazomethane. The double bond in 8a was assigned the
cis stereochemistry based on the coupling constant value in
1
the H NMR spectrum (12 Hz). The trans product shows
a much higher value for the coupling constant.14 The meth-
odology was extended to a variety of coumarins 7a–g and in
all cases the desired diacids 8a–g were obtained in yields
ranging from 70–75% and were characterized as the corre-
sponding dimethyl esters 9a–g. The benzocoumarins 10a
and 10b also responded similarly to the reaction conditions
affording the expected diacids 11a and 11b in 65–70%
yields and were characterized as dimethyl esters 12a and
12b (Scheme 3). Thus, the direct Bargellini condensation
with coumarins provided a useful single-step protocol for
The above sequence of reactions starting with hydrogenation
was applied on the diester 9f to eventually afford the benzoxo-
cene 22, incorporating the basic structural framework of
heliannuol A 2 (Scheme 4). Shishido et al. had, in their
enantioselective synthesis of 2, employed a similar substrate
having a different protecting group for the C-5 hydroxy
function to elaborate to the final compound.15 Thus, treat-
ment of this benzoxocene 22 with m-chloroperbenzoic
acid in the presence of NaHCO3 in dichloromethane

12028
B. Biswas et al. / Tetrahedron 63 (2007) 12026–12036
The direct Bargellini condensation of coumarins resulted in
R
R
CO2Me
CO2Me
CO2Me
CO2Me
the generation of an acrylic acid functionality on the adja-
cent carbon of the phenolic group, which takes part in the re-
action. This feature was advantageously exploited to install
the crucial vinyl moiety in a synthesis of heliannuol C 3.16
10% Pd-C,
MeOH, H2
O
O
9b, R = H
9f, R = OMe
13, R = H (99%)
18, R = OMe (98%)
The diester 9g was reduced with lithium aluminium hydride
in ether at À20 ꢀC to furnish the diol 27 in 90% yield. In the
next step of the synthesis the differential status of the two
hydroxyl groups present in 27 was suitably exploited to
install the vinyl group through an ortho-ester Claisen rear-
rangement. Thus, refluxing a mixture of the diol with triethyl
orthoacetate in the presence of a catalytic amount of pro-
pionic acid smoothly afforded the rearranged ester 28 in
good yield. The acetate 29 was obtained as a minor compo-
nent in some of the runs. This could be easily separated and
mild base treatment (aqueous methanolic potassium hydrox-
ide) of this acetate 29 hydrolyzed it back to the hydroxyester
28. The ester alcohol 28 was subjected to Jones oxidation to
furnish the carboxylic acid 30 (70%), which on treatment
with diazomethane afforded the diester 31. When this diester
31 was treated with LDA in THF, it underwent the expected
Dieckmann cyclization to deliver the b-ketoester 32, which
on heating in dimethyl sulfoxide with added lithium chloride
and water resulted in a smooth Krapcho deethoxycarbony-
lation17 to furnish the benzoxepanone 33 in an overall yield
of 61% from 31. In contrast to the hydride reduction of the
heliannuol A precursor 25, reduction of ketone 33 with so-
dium borohydride in methanol was non-stereoselective and
afforded a mixture of O-methyl heliannuol C 34 and its epi-
mer 35 in a 1:3 proportion in 98% yield. An efficient separa-
tion of the components could be achieved by preparative thin
layer chromatography and the spectral data of 34 and 35
fully matched with those reported previously (Scheme
6).18 Since 34 had been demethylated to heliannuol C 3,18
the present efforts concluded a synthesis of this allelochem-
ical. The larger presence of the undesired epimer 35 in the
final step of reduction adversely affected the overall yield.
Hence efforts were directed for inversion of the configura-
tion of the hydroxyl group in 35. Various experimental con-
ditions involving the application of the Mitsunobu reaction
for effecting this inversion were unfruitful. Hence, as a viable
alternative 35 was oxidized back to the ketone 33 in near
quantitative yield employing Jones reagent and reduced
with sodium borohydride as before to yield a mixture of
34 and 35. This sequence of oxidation and reduction was
repeated and after four such runs the combined yields of
the desired 34 was improved to 62–65%.
LiAlH4, THF
(COCl)2,
DMSO,
Et3N,
R
R
CHO
CHO
15, R = H (93%)
20, R = OMe (95%)
CH2OH
O
O
CH2OH
CH2Cl2
14, R = H (98%)
19, R = OMe (98%)
CH3P(C6H5)3I,
n-BuLi, THF
Catalyst B,
CH2Cl2
R
R
O
O
17, R = H (85%)
22, R = OMe (94%)
16, R = H (71%)
21, R = OMe (70%)
Scheme 4.
furnished a single epoxide 23. This was reduced with lithium
aluminium hydride to furnish O-methyl heliannuol A 24 in
80% yield (Scheme 5). This was spectroscopically identical
to the sample previously prepared in this laboratory.12 Jones
oxidation of this alcohol afforded O-methyl heliannuol K 25,
which had been converted to heliannuols K 26 and A 2 con-
cluding another useful approach to their synthesis.12b
PCy3
Mes-N
Cl
N-Mes
Cl
Cl
Ru
Ru
Ph
Cl
Ph
PCy3
PCy3
Catalyst B
Catalyst A
m-CPBA, NaHCO3,
MeO
CH2Cl2
O
22
80%
O
23
The direct Bargellini condensation of coumarins was then
extended to dihydrocoumarins also. Catalytic hydrogenation
of coumarins 7a–d,f,g in acetic acid furnished the corre-
sponding dihydrocoumarins 36a–f in excellent yield
(Scheme 7). When these dihydro derivatives, 36a–f were
subjected to interaction with chloroform and acetone in the
presence of sodium hydroxide as per already established
conditions, they afforded the expected diacids in yields rang-
ing between 70 –75% and were fully characterized as the
corresponding dimethyl esters 37a–d, 13 and 18 obtained
from reaction with diazomethane (Scheme 8). The diesters
13 and 18 were identical in all respects with the correspond-
ing diesters obtained from hydrogenation of the unsaturated
diesters 9b and 9f, respectively.
LiAlH4, THF
80%
CrO3,
H2SO4,
Me2CO
MeO
RO
80%
O
O
O
OH
24
25, R = Me
26, R = H
Ref. 12b
Scheme 5.

B. Biswas et al. / Tetrahedron 63 (2007) 12026–12036
12029
R1
O
LiAlH4, Et2O,
-20 °C
OH
R1
O
MeO
MeO
i. CHCl3, NaOH
acetone
R2
R3
CO2Me
CO2Me
R2
R3
CO2Me
CO2Me
90%
OH
O
O
HCl
ii.
iii. CH2N2
O
27
9g
36
CH3C(OEt)3,
C2H5CO2H,
140 °C
a,
b,
37a (75%)
37b (74%)
37c (72%)
37d (70%)
13 (75%)
18 (75%)
R
R
1 = R2 = R3 = H
75%
1 = R2 = Me, R3 = H
CrO3,
H2SO4,
Me2CO
c, R1 =H, R3 = Me, R2 = OMe
CO2Et
OR
MeO
CO2Et
CO2R
MeO
d,
R
1 = H, R2 = OMe, R3 = H
R1 = R3 = Me, R2 = H
e,
f,
70%
O
O
R1 = R3 = Me, R2 = OMe
CH2N2,
Et2O
98%
30, R = H
28, R = H
Scheme 8.
29, R = COCH3
31, R = Me
LDA, THF
72%
3. Experimental
R
3.1. General
MeO
O
All non-aqueous reactions were carried out under an inert at-
mosphere (nitrogen). Melting points were taken in open cap-
illary tubes in a sulfuric acid bath and are uncorrected. Dry
solvents and reagents were prepared from reagent grade
materials by conventional methods. Petroleum ether refers
to the fraction of bp. 60–80 ꢀC. The purity of the products
was routinely monitored by TLC. Preparative TLC was per-
formed with silica gel HF254 (E. Merck) plates of 1-mm
thickness. Drying of organic layers was done with sodium
sulfate. 1H NMR spectra were recorded at 300 MHz in
CDCl3 solutions. 13C NMR spectra were recorded in
CDCl3 solution at 75 MHz. Peak positions are indicated
in parts per million downfield from an internal TMS stan-
dard. IR spectra of liquid products were recorded as thin
films or in CHCl3 solution. IR spectra of solids were
recorded as KBr pellets.
O
32, R = CO2Et
LiCl, DMSO,
H2O, 160 °C
85%
33, R = H
NaBH4, MeOH
98%
MeO
MeO
+
OH
OH
O
O
34
35
Scheme 6.
3.1.1. General procedure for Bargellini condensation of
coumarins. Powdered NaOH (4.56 g, 114 mmol) was added
in small portions with stirring to a solution of the required
coumarin (11.4 mmol) in acetone (50 mL). The mixture be-
came warm and was cooled to about 35 ꢀC by immersing in
a water bath. To this stirred solution, chloroform (10 mL)
was added within 10 min. The reaction mixture was then
refluxed for 5 h, cooled, concentrated to one-third of its vol-
ume and diluted with water (20 mL). It was acidified with
6 N HCl and extracted thoroughly with ether (3Â30 mL).
The combined ethereal extracts were further extracted with
saturated NaHCO3 (3Â25 mL). The alkaline aqueous part
was neutralized with cold 6 N HCl and then extracted with
ether (3Â30 mL). The organic layer was washed with satu-
rated brine (25 mL), dried, filtered and evaporated under
reduced pressure. The diacids were characterized as
dimethyl esters, which were obtained on reaction with diazo-
methane in ether and purified by column chromatography
over silica gel.
R1
O
R1
R2
R3
R2
R3
10% Pd-C,
CH3CO2H, H2
O
O
O
7
36
a,
36a (99%)
36e (97%)
36b (98%)
R
R
R
1 = R2 = R3 = H
1 = R3 = Me, R2 = H
1 = R2 = Me, R3 = H
b,
c,
d,
f,
g,
36d (99%)
36f (98%)
36c (98%)
R
1 = H, R2 = OMe, R3 = H
R1 = R3 = Me, R2 = OMe
R
1 =H, R2 = OMe, R3 = Me
Scheme 7.
In summary we have developed a novel one-step protocol for
the generation of functionalized phenoxy acids from the
direct Bargellini condensation of coumarins and dihydro-
coumarins and demonstrated the synthetic utility through
application to the synthesis of the sesquiterpenes, helianane
4 and heliannuols A 2 and C 3. It is expected that more varied
applications of this useful observations will be forthcoming
in future directed towards the development of more complex
natural product structural frameworks.
3.1.1.1. Methyl 3-[2-(1-methoxycarbonyl-1-methyl-
ethoxy)-phenyl]-acrylate (9a). Following the general pro-
cedure, coumarin 7a (1.90 g, 13.01 mmol), furnished the
diacid 8a (2.44 g, 75%) as a white solid, crystallized from
ether/petroleum ether. Mp 114–116 ꢀC. IR (KBr) 1695
(br), 1715, 2974 cmÀ1. 1H NMR (300 MHz, CDCl3) d 1.57

12030
B. Biswas et al. / Tetrahedron 63 (2007) 12026–12036
(6H, s, –CMe2–), 5.99 (1H, d, J 12.0 Hz, ]CH–), 6.80 (1H,
d, J 8.2 Hz, ArH), 6.97 (1H, t, J 7.4, ArH), 7.24 (1H, d, J
12.0 Hz, –CH]) mixed with 7.19–7.25 (1H, m, ArH),
7.47 (1H, d, J 8.2 Hz, ArH), 8.76 (2H, br s, –COOH); 13C
NMR (75 MHz, CDCl3) d 25.3 (2C), 79.8, 117.4, 119.7,
121.9, 127.2, 130.1, 131.2, 142.4, 152.8, 171.7, 179.3.
HRMS (ES +ve) calcd for C13H14O5Na [M+Na]+
273.0739, found 273.0736.
ArH), 6.84 (1H, s, ArH), 6.95 (1H, d, J 8.3 Hz, ArH); 13C
NMR (75 MHz, CDCl3) d 20.4, 25.0, 25.9 (2C), 50.7,
52.2, 79.2, 117.1, 117.9, 128.6, 128.9, 130.8, 132.9, 148.9,
154.1, 165.8, 175.0. Anal. Calcd for C17H22O5: C, 66.65;
H, 7.24. Found: C, 66.62; H, 7.25.
3.1.1.4. Methyl 3-[5-methoxy-2-(1-methoxycarbonyl-
1-methyl-ethoxy)-phenyl]-acrylate (9d). Coumarin 7d
(1 g, 5.682 mmol) furnished the diacid 8d (1.12 g, 70%) as
a gummy oil. This was esterified with diazomethane to fur-
nish the diester 9d (1.2 g, 97%) as a colourless liquid after
chromatographic purification over silica gel (10% EtOAc/
petroleum ether). Rf (10% EtOAc/petroleum ether) 0.51.
This diacid 8a was esterified with diazomethane. The prod-
uct was purified by column chromatography (10% EtOAc/
petroleum ether) to furnish the dimethyl ester 9a as a colour-
less oil (2.66 g, 98%). Rf (10% EtOAc/petroleum ether) 0.52.
IR (CHCl3) 1715, 1738 cmÀ1. 1H NMR (300 MHz, CDCl3)
d 1.58 (6H, s, –CMe2–), 3.69 (3H, s, OMe), 3.76 (3H, s,
OMe), 5.97 (1H, d, J 12.4 Hz, ]CH–), 6.96 (1H, d, J
8.2 Hz, ArH), 6.97 (1H, t, J 7.5 Hz, ArH), 7.21 (1H, t, J
7.5 Hz, ArH) mixed with 7.20 (1H, d, J 12.4 Hz, –CH]),
7.56 (1H, dd, J 8.2, 1.0 Hz, ArH); 13C NMR (75 MHz,
CDCl3) d 25.2 (2C), 51.1, 52.3, 79.6, 116.6, 119.3, 121.2,
127.1, 129.6, 130.7, 139.7, 153.1, 166.5, 174.6. HRMS
(ES +ve) calcd for C15H19O5 [M+H]+ 279.1233, found
279.1231.
IR (CHCl3) 1715, 1738 cmÀ1
;
1H NMR (300 MHz,
CDCl3) d 1.44 (6H, s, –CMe2–), 3.61 (3H, s, OMe), 3.69
(3H, s, OMe), 3.70 (3H, s, OMe), 5.89 (1H, d, J 12.6 Hz,
]CH–), 6.67–6.69 (2H, m, ArH), 7.14 (1H, d, J 12.6 Hz,
–CH]), 7.11–7.13 (1H, m, ArH); 13C NMR (75 MHz,
CDCl3) d 25.3 (2C), 51.4, 52.6, 55.7, 80.5, 115.4, 115.7,
119.7, 119.9, 129.1, 139.6, 147.3, 154.3, 166.7, 174.9.
Anal. Calcd for C16H20O6: C, 62.33; H, 6.54. Found: C,
62.31; H, 6.52.
3.1.1.5. Methyl 3-[4-methoxy-2-(1-methoxycarbonyl-
1-methyl-ethoxy)-5-methylphenyl]-but-2-enoate
3.1.1.2. Methyl 3-[2-(1-methoxycarbonyl-1-methyl-
ethoxy)-4-methylphenyl]-but-2-enoate (9b). Coumarin
7b (2 g, 11.49 mmol) furnished the diacid 8b (2.4 g, 75%)
as a colourless solid, crystallized from ether/petroleum
ether. Mp 164–166 ꢀC. IR (KBr) 1695 (br), 1712,
(9e).
Coumarin 7e (1 g, 4.90 mmol) furnished the diacid 8e
(1.13 g, 75%) as a gummy product and was esterified with
diazomethane. The product was purified by column chroma-
tography over silica gel (10% EtOAc/petroleum ether) to
furnish the diester 9e as a colourless liquid (1.21 g, 98%).
Rf (10% EtOAc/petroleum ether) 0.53. IR (CHCl3) 1715,
1
2975 cmÀ1. H NMR (300 MHz, CDCl3) d 1.59 (6H, s,
–CMe2–), 2.17 (3H, s, Me), 2.29 (3H, s, Me), 5.99 (1H, s,
]CH–), 6.53 (1H, s, ArH), 6.80 (1H, d, J 7.8 Hz, ArH),
6.97 (1H, d, J 7.8 Hz, ArH); 13C NMR (75 MHz, CDCl3)
d 21.4, 24.8, 25.0, 27.1, 79.0, 116.5, 117.6, 122.3, 127.9,
128.4, 138.7, 150.3, 155.1, 169.8, 177.3. HRMS (ES +ve)
calcd for C15H19O5 [M+H]+ 279.1237. Found 279.1236.
1
1738 cmÀ1; H NMR (300 MHz, CDCl3) d 1.49 (6H, s,
–CMe2–), 2.12 (3H, s, Me), 2.15 (3H, s, Me), 3.56 (3H,
s, OMe), 3.73 (3H, s, OMe), 3.77 (3H, s, OMe), 5.89 (1H,
s, ]CH–), 6.35 (1H, s, ArH), 6.80 (1H, s, ArH); 13C
NMR (75 MHz, CDCl3) d 15.6, 25.3, 26.4 (2C), 50.9,
52.5, 55.3, 80.2, 102.0, 118.2, 120.3, 125.3, 130.4, 150.5,
153.9, 157.6, 166.4, 175.4. Anal. Calcd for C18H24O6: C,
64.27; H, 7.19. Found: C, 64.26; H, 7.20.
This diacid 8b was esterified with diazomethane. The prod-
uct was purified by column chromatography over silica gel
(10% EtOAC/petroleum ether) to furnish the dimethyl ester
9b as a colourless oil (2.6 g, 98%). Rf (10% EtOAc/petro-
3.1.1.6. Methyl 3-[5-methoxy-2-(1-methoxycarbonyl-
1-methyl-ethoxy)-4-methylphenyl]-but-2-enoate
1
leum ether) 0.54. IR (CHCl3) 1713, 1737 cmÀ1; H NMR
(9f).
(300 MHz, CDCl3) d 1.52 (6H, s, –CMe2–), 2.16 (3H, s,
Me), 2.28 (3H, s, Me), 3.55 (3H, s, OMe), 3.75 (3H, s,
OMe), 5.91 (1H, s, ]CH–), 6.53 (1H, s, ArH), 6.78 (1H,
d, J 7.8 Hz, ArH), 6.92 (1H, d, J 7.8 Hz, ArH); 13C NMR
(75 MHz, CDCl3) d 21.3, 25.1, 25.9 (2C), 50.6, 52.2, 79.2,
117.9, 118.1, 122.4, 128.3, 130.1, 138.1, 151.2, 154.4,
165.8, 174.9. HRMS (ES +ve) calcd for C17H23O5 [M+H]+
307.1546. Found 307.1540.
Coumarin 7f (2 g, 9.804 mmol) furnished the diacid 8f
(2.26 g, 75%) as a viscous product. This was esterified
with diazomethane and subjected to column chromato-
graphy over silica gel (12% EtOAc/petroleum ether) to fur-
nish the dimethyl ester 9f as a colourless oil (2.4 g, 97%). Rf
(10% EtOAc/petroleum ether) 0.51. IR (CHCl3) 1715,
1
1738 cmÀ1. H NMR (300 MHz, CDCl3) d 1.47 (6H, s,
–CMe2–), 2.18 (3H, s, Me), 2.20 (3H, s, Me), 3.63 (3H, s,
OMe), 3.73 (3H, s, OMe), 3.78 (3H, s, OMe), 5.92 (1H,
s, ]CH–), 6.50 (1H, s, ArH), 6.62 (1H, s, ArH); 13C
NMR (75 MHz, CDCl3) d 16.1, 24.2, 24.8, 24.9, 50.6,
51.9, 55.3, 79.8, 110.2, 118.3, 121.3, 126.4, 131.6, 144.3,
152.6, 154.1, 165.8, 175.0. Anal. Calcd for C18H24O6: C,
64.27; H, 7.19. Found: C, 64.25; H, 7.18.
3.1.1.3. Methyl 3-[2-(1-methoxycarbonyl-1-methyl-
ethoxy)-5-methylphenoxy]-but-2-enoate (9c). Coumarin
7c (1 g, 5.747 mmol) was subjected to Bargellini condensa-
tion following the general procedure and the resultant diacid
8c (1.18 g, 74%) obtained as a sticky material was esterified
with diazomethane and purified by column chromatography
over silica gel (12% EtOAc/petroleum ether) to give the di-
ester 9c (1.27 g, 98%) as a colourless liquid. Rf (12% EtOAc/
3.1.1.7. Methyl 3-[5-methoxy-2-(1-methoxycarbonyl-
1-methyl-ethoxy)-4-methylphenyl]-acrylate (9g). Couma-
rin 7g (2.0 g, 10.53 mmol) furnished the diacid 8g (2.30 g,
75%) as a colourless solid, crystallized from ether/petroleum
ether. Mp 142–144 ꢀC. IR (KBr) 1695 (br), 1715,
1
petroleum ether) 0.51. IR (CHCl3) 1715, 1738 cmÀ1; H
NMR (300 MHz, CDCl3) d 1.50 (6H, s, –CMe2–), 2.16
(3H, s, Me), 2.26 (3H, s, Me), 3.54 (3H, s, OMe), 3.76
(3H, s, OMe), 5.92 (1H, s, ]CH–), 6.61 (1H, d, J 8.3 Hz,
1
2974 cmÀ1; H NMR (300 MHz, CDCl3) d 1.54 (6H, s,

B. Biswas et al. / Tetrahedron 63 (2007) 12026–12036
12031
–CMe2–), 2.17 (3H, s, Me), 3.75 (3H, s, OMe), 5.96 (1H, d, J
12.0 Hz, ]CH–), 6.72 (1H, s, ArH), 7.13 (1H, s, ArH), 7.26
(1H, d, J 12.0 Hz, –CH]); 13C NMR (75 MHz, CDCl3)
d 16.8, 25.5 (2C), 55.9, 80.2, 112.6, 119.9, 121.5, 126.2,
128.9, 138.9, 147.4, 152.5, 166.8, 176.8. Anal. Calcd for
C15H18O6: C, 61.22; H, 6.16. Found: C, 61.20; H, 6.17.
purified by column chromatography (10% EtOAc/petroleum
ether) to furnish the saturated diester 13 (0.99 g, 99%) as
a colourless oil. Rf (10% EtOAc/petroleum ether) 0.56. IR
1
(CHCl3) 1739 cmÀ1. H NMR (300 MHz, CDCl3) d 1.26
(3H, d, J 6.9 Hz, –HCMe), 1.63 (6H, s, –CMe2–), 2.24 (3H,
s, Me), 2.45 (1H, dd, J 9.1, 15.0 Hz, –CHMeCH2–), 2.70
(1H, dd, J 5.5, 15.0 Hz, –CMeCH2–), 3.51–3.88 (1H, m,
ArCHMe), 3.64 (3H, s, OMe), 3.76 (3H, s, OMe), 6.40 (1H,
s, ArH), 6.73 (1H, d, J 7.8 Hz, ArH), 7.04 (1H, d, J 7.8 Hz,
ArH); 13C NMR (75 MHz, CDCl3) d 19.8, 21.0, 25.1, 25.1,
29.8, 41.1, 51.2, 52.2, 78.5, 116.5, 122.1, 126.7, 132.9,
136.3, 152.5, 173.1, 175.0. HRMS (ES +ve) calcd for
C17H25O5 [M+H]+ 309.1703. Found 309.1719.
This diacid 8g was esterified with diazomethane to furnish
the dimethyl ester 9g (2.5 g, 98%) as a colourless oil after
purification by column chromatography over silica gel
(12% EtOAc/petroleum ether). Rf (12% EtOAc/petroleum
ether) 0.53. IR (CHCl3) 1716, 1737 cmÀ1 1H NMR
;
(300 MHz, CDCl3) d 1.51 (6H, s, –CMe2–), 2.16 (3H, s,
Me), 3.70 (3H, s, OMe), 3.78 (3H, s, OMe), 3.79 (3H, s,
OMe), 5.92 (1H, d, J 12.7 Hz, ]CH–), 6.61 (1H, s, ArH),
7.19 (1H, d, J 12.7 Hz, –CH]), 7.32 (1H, s, ArH); 13C
NMR (75 MHz, CDCl3) d 16.4, 25.0 (2C), 51.1, 52.2,
55.4, 80.2, 111.8, 118.3, 121.2, 125.9, 128.9, 139.4, 146.8,
152.3, 166.6, 174.6. HRMS (ES +ve) Calcd for C17H23O6
[M+H]+ 323.1495. Found 323.1492.
3.1.1.11. 3-[2-(2-Hydroxy-1,1-dimethylethoxy)-4-meth-
ylphenoxy]-1-butanol (14). To a magnetically stirred slurry
of LiAlH4 (230 mg, 6.06 mmol) in dry ether (15 mL) was
added dropwise a solution of the diester 13 (1 g,
3.25 mmol) in dry ether (10 mL) and the reaction mixture
was heated to reflux for 4 h, cooled and then quenched
with cold aqueous saturated Na2SO4 solution (5 mL). The
ether layer was separated and the aqueous layer was ex-
tracted with ether (3Â20 mL). The combined ether extracts
were washed with saturated brine (20 mL), dried and con-
centrated. The residual oil was purified by column chroma-
tography over silica gel (50% EtOAc/petroleum ether) to
furnish the diol 14 (800 mg, 98%) as a colourless solid.
Mp 96–98 ꢀC. Rf (50% EtOAc/petroleum ether) 0.47. IR
3.1.1.8. Methyl-3-[2-(1-methoxycarbonyl-1-methyl-
ethoxy)-naphthalen-1-yl]-acrylate (12a). Coumarin 10a
(1 g, 5.102 mmol) furnished the diacid 11a (0.99 g, 65%)
as a gummy liquid and was esterified with diazomethane.
The product was purified by column chromatography
(12% EtOAc/petroleum ether) to furnish the diester 12a as
a colourless liquid (1.06 g, 98%). Rf (12% EtOAc/petroleum
ether) 0.49. IR (CHCl3) 1715, 1738 cmÀ1
;
1H NMR
(KBr) 3400 cmÀ1 1H NMR (300 MHz, CDCl3) d 1.16
;
(300 MHz, CDCl3) d 1.56 (6H, s, –CMe2–), 3.47 (3H, s,
OMe), 3.79 (3H, s, OMe), 6.33 (1H, d, J 12.0 Hz, ]CH–),
7.05 (1H, d, J 9.0 Hz, ArH), 7.27 (1H, d, J 12.0 Hz,
–CH]), 7.33–7.45 (2H, m, ArH), 7.70 (1H, d, J 9.0 Hz,
ArH), 7.76 (2H, d, J 9.0 Hz, ArH); 13C NMR (75 MHz,
CDCl3) d 25.5 (2C), 51.0, 52.3, 79.9, 118.3, 123.9, 124.0,
124.1, 124.1, 126.3, 128.0, 128.9, 129.27, 131.7, 137.9,
149.6, 166.2, 174.9. Anal. Calcd for C19H20O5: C, 69.50;
H, 6.14. Found: C, 69.51; H, 6.13.
(3H, d, J 6.5 Hz, –CHMe), 1.17 (3H, s, –CMe2–), 1.29
(3H, s, –CMe2–), 1.37–1.46 (1H, m, –CHMeCH2–), 1.64–
1.71 (1H, m, ArCHMeCH2–), 2.21 (3H, s, Me), 3.17–3.25
(1H, m, ArCHMe–), 3.38–3.64 (4H, m, –CH2OH), 6.77
(1H, s, ArH), 6.78 (1H, d, J 7.6 Hz, ArH), 7.01 (1H, d, J
7.6 Hz, ArH); 13C NMR (75 MHz, CDCl3) d 20.9, 21.6,
22.4, 24.3, 27.2, 42.5, 60.6, 71.1, 81.5, 122.8, 124.7,
126.8, 136.3, 137.4, 153.1. HRMS (ES +ve) calcd for
C15H25O3 [M+H]+ 253.1804. Found 253.1797.
3.1.1.9. Methyl-3-[2-(1-methoxycarbonyl-1-methyl-
ethoxy)-naphthalen-1-yl]-but-2-enoate (12b). Coumarin
10b (1 g, 4.76 mmol) furnished the diacid 11b (1.05 g,
70%), which was esterified with diazomethane to furnish
the diester 12b (1.11 g, 97%) as a colourless liquid after pu-
rification by column chromatography over silica gel (10%
EtOAc/petroleum ether). Rf (10% EtOAc/petroleum ether)
3.1.1.12. 3-[2-(1,1-Dimethyl-2-oxo-ethoxy)-4-methyl-
phenyl]-butyraldehyde (15). To a magnetically stirred
and cooled (À78 ꢀC) solution of oxalyl chloride (530 mg,
4.17 mmol) in dichloromethane (8 mL), a solution of di-
methyl sulfoxide (640 mg, 8.12 mmol) in dichloromethane
(2 mL) was added dropwise. After stirring at À78 ꢀC for
15 min a solution of the diol 14 (260 mg, 1.032 mmol) in di-
chloromethane (5 mL) was added and stirred for 45 min, at
this temperature. Triethylamine (1.4 mL, 10 mmol) was
then added and stirring was continued for another 2 h at
À78 ꢀC. The reaction mixture was allowed to warm to
room temperature. After 2 h, the reaction mixture was
poured into cold water (10 mL) and the organic layer sepa-
rated. The aqueous part was extracted with dichloromethane
(3Â25 mL). The combined organic layers were washed with
water (20 mL), dried and concentrated. The residual oil was
subjected to column chromatography. Elution with EtOAc/
petroleum ether (1:9) afforded the dialdehyde 15 (240 mg,
93%) as a colourless oil. Rf (10% EtOAc/petroleum ether)
1
0.52. IR (CHCl3) 1716, 1739 cmÀ1; H NMR (300 MHz,
CDCl3) d 1.53 (3H, s, –CMe2–), 1.60 (3H, s, –CMe2–),
2.25 (3H, s, Me), 3.37 (3H, s, OMe), 3.79 (3H, s, OMe),
6.24 (1H, s, ]CH–), 7.15 (1H, d, J 9.0 Hz, ArH), 7.30–
7.41 (2H, m, ArH), 7.62 (1H, d, J 8.4 Hz, ArH), 7.67 (1H,
d, J 9.0 Hz, ArH), 7.76 (1H, d, J 8.4 Hz, ArH); 13C NMR
(75 MHz, CDCl3) d 24.1, 25.6, 26.8, 50.6, 52.3, 79.4,
117.9, 119.8, 123.8, 123.8, 126.3, 127.8, 127.9, 129.2,
130.9, 147.7, 153.2, 153.2, 165.3, 175.2. Anal. Calcd for
C20H22O5: C, 70.16; H, 6.48. Found: C, 70.14; H, 6.45.
3.1.1.10. Methyl-3-[2-(1-methoxycarbonyl-1-methyl-
ethoxy)-4-methylphenoxy]-butanoate (13). A methanolic
solution of the ene-diester 9b (1.0 g, 3.268 mmol) containing
Pd–C (10%, 50 mg) was stirred under a hydrogen atmosphere
(1 atm) until hydrogen uptake was completed. The catalyst
was filtered off, the solvent removed and the residue was
1
0.48. IR (Neat) 1732 cmÀ1; H NMR (300 MHz, CDCl3)
d 1.28 (3H, d, J 6.9 Hz, –CHMe), 1.46 (6H, s, –CMe2–),
2.22 (3H, s, Me), 2.55–2.75 (2H, m, –CHMeCH2–), 3.69–
3.76 (1H, m, ArCHMe), 6.39 (1H, s, ArH), 6.77 (1H, d,
J 7.7 Hz, ArH), 7.07 (1H, d, J 7.7 Hz, ArH), 9.69 (1H, t,

12032
B. Biswas et al. / Tetrahedron 63 (2007) 12026–12036
J 1.9 Hz, –CH2CHO), 9.82 (1H, s, –CHO); 13C NMR
(75 MHz, CDCl3) d 21.0, 21.8, 22.2, 22.4, 28.1, 51.3, 83.3,
117.1, 123.4, 127.7, 132.9, 137.4, 152.8, 202.6, 204.0.
Anal. Calcd for C15H20O3: C, 72.55; H, 8.12. Found: C,
72.53; H, 8.13.
HRMS (ES +ve) calcd for C18H27O6 [M+H]+ 339.1809.
Found 339.1807.
3.1.1.16. 3-[2-(2-Hydroxy-1,1-dimethylethoxy)-5-me-
thoxy-4-methylphenyl]-1-butanol (19). The diester 18
(500 mg, 1.49 mmol) was subjected to reduction with
LiAlH4 (112 mg, 2.96 mmol) following conditions as for
13 and afforded the diol 19 (410 mg, 98% yield) as a colour-
less solid after purification by column chromatography (50%
EtOAc/petroleum ether), crystallized from ether/petroleum
ether. Mp 58–60 ꢀC. Rf (50% EtOAc/petroleum ether)
3.1.1.13. 2-[2-(1,1-Dimethylallyloxy)-4-methylphenyl]-
pent-4-ene (16). n-BuLi (0.7 mL of 1.6 M solution in
hexane, 1.12 mmol) was added dropwise to a solution of
methyltriphenylphosphonium iodide (486 mg, 1.20 mmol)
in freshly distilled THF (8 mL) at 0 ꢀC under argon. The mix-
ture was stirred for 1 h at the same temperature. A solution of
the dialdehyde 15 (100 mg, 0.403 mmol) in THF (8 mL) was
charged into the solution at 0 ꢀC and the resulting solution
was stirred overnight. The reaction mixture was quenched
with saturated NH4Cl (5 mL) and extracted with ether
(3Â20 mL). The organic layer was washed with brine
(30 mL) and dried over Na2SO4. The residual oil was sub-
jected to column chromatography. Elution with EtOAc/petro-
leum ether (1:100) afforded the diene 16 (70 mg, 71%) as
1
0.45. IR (KBr) 3380 cmÀ1; H NMR (300 MHz, CDCl3)
d 1.22 (3H, s, –CMe2–), 1.26 (3H, d, J 7.0 Hz, –CHMe),
1.31 (3H, s, –CMe2–), 1.42–1.50 (1H, m, CHMeCH2–),
1.77–1.86 (1H, m, CHMeCH2–), 2.16 (3H, s, Me), 3.23–
3.30 (1H, m, ArCHMe), 3.50–3.61 (4H, m, CH2OH),
3.71–3.79 (2H, m, OH), 3.87 (3H, s, OMe), 6.64 (1H, s,
ArH), 6.81 (1H, s, ArH); 13C NMR (75 MHz, CDCl3)
d 15.8, 20.5, 21.7, 23.7, 27.2, 41.8, 55.4, 60.1, 70.2, 80.1,
107.6, 124.2, 124.8, 137.9, 145.2, 154.1. HRMS (ES +ve)
calcd for C16H27O4 [M+H]+ 283.1910. Found 283.1911.
1
a colourless oil. Rf (1% EtOAc/petroleum ether) 0.71; H
NMR (300 MHz, CDCl3) d 1.18 (3H, d, J 6.9 Hz, –CHMe),
1.48 (6H, s, –CMe2–), 2.10–2.43 (2H, m, –CHMeCH2–),
2.25 (3H, s, Me), 3.20–3.27 (1H, m, ArCHMe–), 4.93 (1H,
d, J 11.3 Hz, –CH2CH]CH2), 5.00 (1H, d, J 18.8 Hz,
–CH2CH]CH2), 5.14 (1H, d, J 10.9 Hz, –CMe2CH]CH2),
5.22 (1H, d, J 17.6 Hz, –CMe2CH]CH2), 5.69–5.89 (1H, m,
3.1.1.17.
3-[2-(1,1-Dimethyl-2-oxo-ethoxy)-5-meth-
oxy-4-methylphenyl]-butyraldehyde (20). Oxidation of
the diol 19 (230 mg, 0.816 mmol) was carried out following
the procedure for 14 and furnished the dialdehyde 20
(220 mg, 95%) as a colourless oil. Rf (10% EtOAc/petro-
–CH2CH]CH2), 6.16 (1H, dd,
J
10.9, 17.6 Hz,
leum ether) 0.51. IR (Neat) 1732 cmÀ1 1H NMR
;
–CMe2CH]CH2), 6.74 (1H, d, J 7.8 Hz, ArH), 6.86 (1H,
s, ArH), 7.04 (1H, d, J 7.8 Hz, ArH); 13C NMR (75 MHz,
CDCl3) d 20.6, 21.6, 27.8, 27.8, 32.4, 42.0, 79.6, 113.2,
115.7, 120.0, 122.5, 126.9, 135.8, 135.8, 138.3, 145.5,
153.9. HRMS (ES +ve) calcd for C17H25O [M+H]+
245.1905. Found 245.1901.
(300 MHz, CDCl3) d 1.30 (3H, d, J 6.9 Hz, –CHMe), 1.39
(3H, s, –CMe2–), 1.41 (3H, s, –CMe2–), 2.11 (3H, s, Me),
2.61–2.76 (2H, m, CHMeCH2–), 3.71–3.78 (1H, m,
ArCHMe), 3.86 (3H, s, OMe), 6.45 (1H, s, ArH), 6.64
(1H, s, ArH), 9.72 (1H, t, J 2.1 Hz, –CHO), 9.86 (1H, s,
–CHO); 13C NMR (75 MHz, CDCl3) d 15.8, 20.5, 21.5,
21.8, 27.7, 50.9, 55.6, 83.0, 109.0, 120.2, 125.1, 134.1,
145.3, 153.0, 201.9, 203.4. Anal. Calcd for C16H22O4: C,
69.04; H, 7.97. Found: C, 69.05; H, 7.96.
3.1.1.14. 2,2,6,9-Tetramethyl-5,6-dihydro-2H-benzo-
[b]oxocene (17). A round bottom flask charged with second
generation Grubbs catalyst (catalyst B) (16 mg, 0.018 mmol)
was evacuated and filled with argongas three times before the
addition of a solution of the diene 16 (60 mg, 0.246 mmol) in
degassed dichloromethane (20 mL). The resulting solution
was stirred at room temperature for 6 h. The solvent was
removed under reduced pressure, and the dark residue was
purified by preparative thin layer chromatography (1%
EtOAc/petroleum ether) to give the benzoxocene 17
(45 mg, 85%) as a colourless liquid. Rf (1% EtOAc/petro-
leum ether) 0.64. The spectral data of 17 were identical
with the reported values.12b
3.1.1.18.
2-[2-(1,1-Dimethylallyloxy)-5-methoxy-4-
methylphenyl]-pent-4-ene (21). The dialdehyde 20
(210 mg, 0.755 mmol) was subjected to a double Wittig re-
action as for 15 to afford the diene 21 (145 mg, 70%) as a col-
1
ourless oil. Rf (1% EtOAc/petroleum ether) 0.74; H NMR
(300 MHz, CDCl3) d 1.87 (3H, d, J 6.6 Hz, –CHMe), 1.41
(6H, s, –CMe2–), 2.11 (3H, s, Me), 2.14–2.25 (1H, m,
CHMeCH2–), 2.31–2.40 (1H, m, CHMeCH2–), 3.20–3.30
(1H, m, ArCHMe), 3.78 (3H, s, OMe), 4.93–5.21 (4H, m,
]CH2), 5.72–5.77 (1H, m, –CH]), 6.08–6.17 (1H, m,
–CH]), 6.54 (1H, s, ArH), 6.83 (1H, s, ArH); 13C NMR
(75 MHz, CDCl3) d 15.9, 20.4, 27.1, 27.2, 32.1, 41.9, 55.6,
79.1, 108.5, 112.7, 115.5, 122.9, 123.5, 137.3, 137.7,
145.1, 146.5, 152.0. Anal. Calcd for C18H26O2: C, 78.79;
H, 9.55. Found: C, 78.75; H, 9.57.
3.1.1.15. Methyl 3-[5-methoxy-2-(1-methoxycarbonyl-
1-methyl-ethoxy)-4-methylphenyl]-butanoate (18). The
ene-diester 9f (1.2 g, 3.57 mmol) was hydrogenated as for
9b to furnish the saturated diester 18 (1.18 g, 98%) as a col-
ourless oil. Rf (10% EtOAc/petroleum ether) 0.54. IR
1
(CHCl3) 1738 cmÀ1; H NMR (300 MHz, CDCl3) d 1.26
3.1.1.19. 8-Methoxy-2,2,6,9-tetramethyl-5,6-dihydro-
2H-benzo[b]oxocene (22). Ring-closing metathesis of the
diene 21 (25 mg, 0.091 mmol) was carried out using second
generation Grubbs catalyst (catalyst B) as per conditions for
17 to give the benzoxocene 22 (21 mg, 94%) as a colourless
liquid. Rf (1% EtOAc/petroleum ether) 0.70; 1H NMR
(300 MHz, CDCl3) d 1.26 (3H, d, J 6.0 Hz, –CHMe), 1.39
(3H, s, –CMe2–), 1.58 (3H, s, –CMe2–), 2.13 (3H, s, Me),
2.89 (1H, m, –CHMeCH2–), 3.28 (1H, m, –CHMeCH2–),
(3H, d, J 6.9 Hz, –CHMe), 1.56 (3H, s, –CMe2–), 1.57
(3H, s, –CMe2–), 2.11 (3H, s, Me), 2.47 (1H, dd, J 16.3,
9.3 Hz, –CHMeCH2–), 2.68 (1H, dd, J 16.3, 5.7 Hz,
–CHMeCH2–), 3.63 (1H, m, ArCHMe), 3.65 (3H, s,
OMe), 3.72 (3H, s, OMe), 3.77 (3H, s, OMe), 6.48 (1H, s,
ArH), 6.68 (1H, s, ArH); 13C NMR (75 MHz, CDCl3)
d 15.9, 20.1, 25.2, 25.3, 30.0, 41.3, 51.2, 52.2, 55.5, 79.0,
108.8, 119.9, 124.4, 134.6, 145.7, 152.6, 172.9, 175.2.

B. Biswas et al. / Tetrahedron 63 (2007) 12026–12036
12033
3.79 (3H, s, OMe), 3.82 (1H, m, ArCHMe–), 5.26 (1H, d, J
9.0 Hz, –OCMe2CH]), 5.64–5.73 (1H, m, –CMe2CH]
CH–), 6.48 (1H, s, ArH), 6.70 (1H, s, ArH); 13C NMR
(75 MHz, CDCl3) d 15.7, 25.1, 26.9, 28.4, 29.6, 34.2, 55.3,
80.9, 123.9, 126.4, 127.6, 128.6, 128.9, 134.9, 137.6,
154.2. Anal. Calcd for C16H22O2: C, 78.01; H, 9.00. Found:
C, 77.98; H, 8.99.
3.1.1.23. 3-[2-(2-Hydroxy-1,1-dimethylethoxy)-5-me-
thoxy-4-methylphenyl]-prop-2-en-1-ol (27). A suspension
of LiAlH4 (570 mg, 15.02 mmol) in ether (15 mL) was
stirred for 1 h and allowed to settle. The clear solution
(13 mL) was removed via syringe and added dropwise to
a stirred and cooled (À20 ꢀC) solution of the diester 9g
(1.0 g, 3.76 mmol) in ether (15 mL). After stirring for 4 h
at this temperature, the reaction mixture was quenched by
addition of aqueous saturated Na2SO4 solution (5 mL).
The ether layer was carefully decanted. The residue after re-
moval of solvent was subjected to column chromatography
over silica gel. Elution with EtOAc/petroleum ether (1:1)
furnished the diol 27 (750 mg, 90%) as a gummy oil. Rf
3.1.1.20. 5-Methoxy-3,6,9,9-tetramethyl-2,3,9,9a-tet-
rahydro-1aH-1,8-dioxabenzo[a]cyclopropa[e]-cyclooc-
tene (23). A stirred mixture of the alkene 22 (20 mg,
0.0812 mmol) and NaHCO3 (55 mg, 0.655 mmol) in dry di-
chloromethane (2 mL) was cooled to 0 ꢀC and slowly treated
with m-CPBA (41.14 mg, 0.32 mmol) such that temperature
never rose above 0 ꢀC. Stirring was continued for 12 h at
room temperature. The reaction mixture was quenched
with water (5 mL) and extracted with ether (3Â10 mL).
The organic layer was washed with saturated aqueous
Na2CO3 solution (10 mL), saturated brine (10 mL) and dried
over Na2SO4. The residual oil was subjected to column chro-
matography (petroleum ether/EtOAc 19:1) to give the epox-
ide 23 (16 mg, 80%) as a colourless liquid. Rf (5% EtOAc/
1
(50% EtOAc/petroleum ether) 0.41; H NMR (300 MHz,
CDCl3) d 1.20 (6H, s, –CMe2–), 2.18 (3H, s, Me), 3.53
(2H, s, –CMe2CH2OH), 3.78 (3H, s, OMe), 4.18 (2H, d, J
6.9 Hz, ]CHCH2OH), 5.89–5.92 (1H, m, ]CH–), 6.56
(1H, s, ArH), 6.57 (1H, d, J 9.9 Hz, ArCH]CH–), 6.81
(1H, s, ArH); 13C NMR (75 MHz, CDCl3) d 15.9, 22.9
(2C), 55.4, 59.6, 70.0, 81.7, 111.1, 126.0, 126.3, 128.2,
129.2, 131.0, 144.9, 153.4. HRMS (ES +ve) calcd for
C15H22O4Na [M+Na]+ 289.1416. Found 289.1416.
1
petroleum ether) 0.51; H NMR (300 MHz, CDCl3) d 1.20
(3H, d, J 6.9 Hz, –CHMe–), 1.44 (3H, s, –CMe2–), 1.55
(3H, s, –CMe2–), 2.16 (3H, s, Me), 2.26–2.33 (2H, m,
–CHMeCH2–), 2.54–2.56 (1H, m, –OCH), 2.93–2.99 (1H,
m, –OCH), 3.08–3.13 (m, 1H), 3.80 (3H, s, OMe), 6.52
(1H, s, ArH), 6.74 (1H, s, ArH); 13C NMR (300 MHz,
CDCl3) d 16.2, 25.4, 27.8, 29.9, 34.6, 37.8, 55.9, 58.1,
59.7, 80.0, 112.4, 124.9, 129.1, 137.7, 145.6, 154.7. Anal.
Calcd for C16H22O3: C 73.25; H 8.45. Found: C 73.22;
H 8.46.
3.1.1.24. Ethyl 3-[2-(2-hydroxy-1,1-dimethylethoxy)-
5-methoxy-4-methylphenyl]-4-pentenoate (28) and ethyl
3-[2-(2-acetoxy-1,1-dimethylethoxy)-5-methoxy-4-meth-
ylphenyl]-4-pentenoate (29). A mixture of the diol
27 (500 mg, 1.88 mmol), triethyl orthoacetate (3.0 g,
18.8 mmol) and propionic acid (5 mg, 0.07 mmol) was
heated with stirring maintaining the temperature of the liq-
uid at 138–142 ꢀC. Heating was continued for 24 h, the reac-
tion mixture was allowed to cool to room temperature and
excess orthoacetate was removed by distillation under re-
duced pressure (w50–60 ꢀC at 20 mmHg). The residue was
purified by column chromatography. Elution with EtOAc/
petroleum ether (1:19) afforded the acetoxyester 29
(100 mg, 14%) as a colourless oil. Rf (5% EtOAc/petroleum
3.1.1.21. O-Methyl heliannuol A (24). To a magnetically
stirred slurry of LiAlH4 (5.8 mg, 0.152 mmol) in dry THF
(1 mL) was added dropwise a solution of the epoxide 23
(20 mg, 0.076 mmol) in dry THF (1 mL). The reaction mix-
ture was refluxed for 8 h, cooled and then decomposed with
cold saturated aqueous Na2SO4 solution (2 mL). The ether
layer was separated and the aqueous layer extracted with
ether (3Â5 mL). The combined ether extracts were washed
with saturated brine (5 mL), dried and concentrated. The
residual oil was purified by column chromatography over
silica gel (petroleum ether/EtOAc 19:1) to furnish O-methyl
heliannuol A 24 (16 mg, 80%) as a colourless oil. Rf (5%
EtOAc/petroleum ether) 0.35.
ether) 0.61. IR (Neat) 1738 cmÀ1 1H NMR (300 MHz,
;
CDCl3) d 1.22 (3H, t, J 7.1 Hz, –OCH2Me), 1.34 (6H, s,
–CMe2–), 2.15 (6H, s, Me and OCOMe), 2.57–2.71 (2H,
m, –CH2CO2Et), 3.77 (3H, s, OMe), 4.10 (2H, q, J 7.1 Hz,
OCH2CH3), 4.18 (2H, d, J 2.5 Hz, –CMe2CH2OAc), 4.40
(1H, dd, J 6.6, 14.9 Hz, ArCH(CH]CH2)CH2–), 5.07
(1H, d, J 16.7 Hz, ]CH2), 5.08 (1H, d, J 11.0 Hz,
]CH2), 5.91–6.03 (1H, m, –CH]), 6.58 (1H, s, ArH),
6.83 (1H, s, ArH); 13C NMR (75 MHz, CDCl3) d 14.2,
16.1, 20.9, 24.0 (2C), 38.4, 39.7, 55.6, 60.3, 70.6, 78.7,
109.2, 114.7, 124.9, 125.1, 133.9, 139.9, 145.4, 153.6,
171.0, 171.9. Anal. Calcd for C21H30O6: C, 66.65; H, 7.99.
Found: C, 66.62; H, 8.01.
The spectral data of 24 were identical with the reported
values.12b
3.1.1.22. O-Methyl heliannuol K (25). Jones reagent
(aqueous solution of CrO3 and H2SO4) was added drop-
wise to a cooled (ice) solution of the alcohol 24 (16 mg,
0.061 mmol) in acetone (0.5 mL) until orange colour per-
sisted. Stirring was continued at room temperature for 2 h.
Acetone was removed by distillation. The residue was
extracted with ether (3Â10 mL), dried and solvent
removed and the product purified by column chromato-
graphy over silica gel (petroleum ether/EtOAc 19:1) to
furnish the ketone, O-methyl heliannuol K 25 (12.7 mg,
80%) as a colourless liquid. Rf (5% EtOAc/petroleum
ether) 0.46. The spectral data of 25 were identical with
the reported values.12b
Further elution with EtOAc/petroleum ether (1:9) afforded
the hydroxyester 28 (480 mg, 75%) as a colourless oil. Rf
(10% EtOAc/petroleum ether) 0.42. IR (Neat) 1735, 3450
1
(br) cmÀ1; H NMR (300 MHz, CDCl3) d 1.20 (3H, t, J
7.2 Hz, –OCH2Me), 1.27 (3H, s, –CMe2–), 1.34 (3H, s,
–CMe2–), 2.16 (3H, s, Me), 2.59 (1H, dd, A of ABX, JAB
14.4 Hz, JAX 6.5 Hz, –CHAHBCO2Et), 2.65 (1H, dd, B of
ABX, JBA 14.4 Hz, JBX 8.5 Hz, –CHAHBCO2Et), 3.57
(1H, dd, J 11.5, 4.8 Hz, –CMe2CH2OH), 3.70 (1H, d, J
11.5 Hz, –CMe2CH2OH), 3.77 (3H, s, OMe), 4.11 (2H, q,
J 7.2 Hz, OCH2Me), 4.35–4.42 (1H, m, X of ABX,
ArCH(CH]CH2)CH2–), 5.08–5.15 (2H, m, ]CH2),

12034
B. Biswas et al. / Tetrahedron 63 (2007) 12026–12036
5.93–6.05 (1H, m, –CH]), 6.58 (1H, s, ArH), 6.83 (1H, s,
ArH); 13C NMR (75 MHz, CDCl3) d 13.9, 15.9, 22.3, 23.8,
38.5, 39.8, 55.4, 60.5, 70.8, 80.8, 109.1, 114.8, 124.2,
125.0, 133.6, 139.4, 145.4, 153.3, 172.6. HRMS (ES +ve)
calcd for C19H28O5Na [M+Na]+ 359.1835. Found 359.1834.
3.1.1.27.
7-Methoxy-2,2,8-trimethyl-5-vinyl-4,5-di-
hydrobenzo[b]oxepan-3-one (33). A mixture of the b-
ketoester 32 (40 mg, 0.12 mmol), dimethyl sulfoxide
(0.4 mL), water (1 drop), and lithium chloride (6 mg,
0.14 mmol) was heated with stirring in an oil bath at 150–
160 ꢀC for 5 h. The reaction mixture was cooled, diluted
with water (5 mL) and extracted with ether (3Â15 mL) after
saturation with sodium chloride. The organic extract was
dried and concentrated. The residual oil was purified by pre-
parative thin layer chromatography (petroleum ether/EtOAc
49:1) to afford the ketone 33 (27 mg, 85%) as a colourless
oil. Rf (5% EtOAc/petroleum ether) 0.62. IR (Neat)
3.1.1.25. Ethyl 3-[5-methoxy-2-(1-methoxycarbonyl-
1-methyl-ethoxy)-4-methylphenyl]-4-pentenoate
(31).
Jones reagent (aqueous solution of CrO3 and H2SO4) was
added dropwise to a cooled (ice) and stirred solution of the
hydroxyester 28 (200 mg, 0.59 mmol) in acetone (4 mL) un-
til the orange colour persisted. It was then allowed to stir at
room temperature for 12 h. Excess reagent was decomposed
by addition of few drops of methanol and acetone was
removed by distillation under reduced pressure. The residue
was diluted with water (10 mL) and extracted with ether
(3Â20 mL). The ethereal extract was washed with brine
(15 mL), dried and the solvent removed to furnish the acid
30 (145 mg, 70%) as a viscous material and was esterified
with diazomethane and purified by column chromatography
over silica gel eluting with EtOAc/petroleum ether (1:9) to
give the diester 31 (150 mg, 98%) as a colourless oil. Rf
1720 cmÀ1; H NMR (300 MHz, CDCl3) d 1.27 (3H, s,
1
–CMe2–), 1.40 (3H, s, –CMe2–), 2.14 (3H, s, Me), 2.85
(1H, dd, J 10.8, 5.8 Hz, ArCH(CH]CH2)CH2–), 3.42
(1H, t, J 10.8 Hz, –CH(CH]CH2)CH2–), 3.63–3.75 (1H,
m, ArCH(CH]CH2)CH2–), 3.75 (3H, s, OMe), 5.08 (1H,
d, J 10.0 Hz, ]CH2), 5.13 (1H, d, J 17.0 Hz, ]CH2),
5.83–5.95 (1H, m, –CH]), 6.50 (1H, s, ArH), 6.74 (1H, s,
ArH); 13C NMR (75 MHz, CDCl3) d 15.7, 22.6, 25.1,
42.7, 43.9, 55.5, 87.9, 111.9, 114.9, 126.4, 126.6, 129.0,
141.3, 146.7, 154.4, 214.1. HRMS (ES +ve) calcd for
C16H21O3 [M+H]+ 261.1491. Found 261.1485.
(10% EtOAc/petroleum ether) 0.61. IR (Neat) 1735 cmÀ1
;
1H NMR (300 MHz, CDCl3) d 1.21 (3H, t, J 7.2 Hz,
OCH2Me), 1.53 (3H, s, –CMe2–), 1.56 (3H, s, –CMe2–),
2.11 (3H, s, Me), 2.69 (2H, d, J 7.5 Hz, –CH2CO2Et), 3.76
(3H, s, OMe), 3.79 (3H, s, OMe), 4.10 (2H, q, J 7.2 Hz,
OCH2Me), 4.25–4.28 (1H, m, ArCH(CH]CH2)CH2–),
5.05–5.12 (2H, m, ]CH2), 5.95–6.06 (1H, m, –CH]),
6.49 (1H, s, ArH), 6.59 (1H, s, ArH); 13C NMR (75 MHz,
CDCl3) d 14.1, 16.0, 25.0, 25.5, 39.2, 39.4, 52.3, 55.6,
60.2, 79.2, 110.0, 114.7, 120.2, 125.0, 131.7, 139.6, 145.9,
152.7, 172.0, 175.3. HRMS (ES +ve) calcd for C20H29O6
[M+H]+ 365.1965. Found 365.1959.
3.1.1.28. O-Methyl heliannuol C (34) and epi-O-methyl
heliannuol C (35). To a stirred and cold (0 ꢀC) solution of
the ketone 33 (27 mg, 0.104 mmol) in methanol (0.5 mL),
NaBH4 (5 mg, 0.13 mmol) was added portionwise and stir-
ring continued for 5 min at that temperature. The reaction
mixture was then quenched with twice its volume of water
and extracted with ether (3Â15 mL). The ethereal extract
was washed with water, dried and concentrated. The residual
oil was purified by preparative thin layer chromatography
(petroleum ether/EtOAc 19:1) to afford O-methyl heliannuol
C 34 (7 mg, 26%) and its epimer 35 (19 mg, 70%) as viscous
liquids.
3.1.1.26.
Ethyl-7-methoxy-2,2,8-trimethyl-3-oxo-5-
vinyl-2,3,4,5-tetrahydrobenzo[b]oxepane-4-carboxylate
(32). To a well stirred solution of LDA [prepared from n-bu-
tyl lithium (0.6 mL of 1.6 M solution in hexane, 0.96 mmol)
and diisopropylamine (110 mg, 1.09 mmol)] in THF (1 mL)
at –20 ꢀC, a solution of diester 31 (130 mg, 0.36 mmol) in
THF (1 mL) was added dropwise under argon atmosphere.
The reaction mixture was stirred for 2 h at that temperature
and then allowed to warm to room temperature and stirred
for 12 h. It was then quenched with dilute HCl (6 N)
(5 mL) and extracted with ether (3Â15 mL). The combined
ethereal extract were washed with water (10 mL), dried and
the solvent removed. The residue was subjected to column
chromatography over silica gel. Elution with EtOAc/petro-
leum ether (1:9) afforded the b-ketoester 32 (86 mg, 72%)
as a viscous oil. Rf (10% EtOAc/petroleum ether) 0.51. IR
1
Spectral data for 34: H NMR (300 MHz, CDCl3) d 1.15
(3H, s, –CMe2–), 1.30 (3H, s, –CMe2–), 1.95 (1H, ddd,
J 13.8, 9.0, 3.3 Hz, –CH(CH]CH2)CH2–), 2.02 (1H, ddd,
J 13.8, 7.7, 3.3 Hz, –CH(CH]CH2)CH2–), 2.14 (3H, s,
Me), 3.62 (1H, br m, ArCH(CH]CH2)CH2–), 3.78 (3H, s,
OMe), 3.81 (1H, m, CHOH), 5.02 (1H, d, J 17.1 Hz,
]CH2), 5.11 (1H, d, J 10.2 Hz, ]CH2), 6.13 (1H, ddd, J
17.2, 10.2, 7.3 Hz, CH]), 6.53 (1H, s, ArH), 6.72 (1H, s,
ArH); 13C NMR (75 MHz, CDCl3) d 15.6, 21.2, 26.7,
36.2, 42.7, 55.6, 74.7, 79.6, 110.2, 115.2, 125.2, 126.3,
133.8, 139.7, 147.3, 153.9.
1
Spectral data for 35: H NMR (300 MHz, CDCl3) d 1.13
(3H, s, –CMe2–), 1.31 (3H, s, –CMe2–), 1.92 (1H, m,
ArCH(CH]CH2)CH2–), 2.08 (1H, dt, J 13.8, 3.3 Hz,
ArCH(CH]CH2)CH2–), 2.15 (3H, s, Me), 3.53 (1H, br
m, ArCH(CH]CH2)CH2–), 3.76 (1H, m, CHOH), 3.77
(3H, s, OMe), 4.96 (1H, d, J 17.1 Hz, ]CH2), 5.15 (1H, d,
J 10.5 Hz, ]CH2), 6.13 (1H, ddd, J 17.1, 10.5, 6.9 Hz,
CH]), 6.52 (1H, s, ArH), 6.75 (1H, s, ArH); 13C
NMR (75 MHz, CDCl3) d 15.7, 21.7, 26.5, 35.8, 43.1,
55.6, 78.1, 79.3, 109.9, 114.9, 125.2, 126.3, 133.6, 141.0,
147.5, 153.9.
(Neat) 1722, 1753 cmÀ1 1H NMR (300 MHz, CDCl3)
;
d 1.24 (3H, s, –CMe2–), 1.26 (3H, t, J 7.4 Hz, OCH2Me),
1.50 (3H, s, –CMe2–), 2.13 (3H, s, Me), 3.74 (3H, s,
OMe), 4.05 (1H, t, J 9.0 Hz, ArCH(CH]CH2)CH2–), 4.23
(2H, q, J 7.4 Hz, OCH2Me), 4.69 (1H, d, J 9.9 Hz,
CHCO2Et), 5.04 (1H, d, J 10.2 Hz, ]CH2), 5.11 (1H, d, J
16.2 Hz, ]CH2), 5.79–5.90 (1H, m, ]CH2), 6.49 (1H, s,
ArH), 6,72 (1H, s, ArH); 13C NMR (75 MHz, CDCl3)
d 14.5, 16.2, 21.7, 25.8, 46.4, 55.9, 56.7, 61.7, 89.4, 112.8,
116.4, 126.9, 127.1, 128.6, 140.5, 146.7, 155.2, 169.5,
208.7. HRMS (ES +ve) calcd for C19H25O5 [M+H]+
333.1703. Found 333.1696.
The spectral data of 34 and 35 were in agreement with the
reported values.17

B. Biswas et al. / Tetrahedron 63 (2007) 12026–12036
12035
3.1.2. General procedure for the preparation of dihydro-
coumarins from coumarins. A solution of coumarin
(5 mmol, 1 equiv) in acetic acid (15 mL) containing Pd–C
(10%, 50 mg) was stirred under a hydrogen atmosphere
(1 atm) until hydrogen uptake was completed (w12 h). The
catalyst was filtered and acetic acid was neutralized by addi-
tion of solid Na2CO3, diluted with water (30 mL) and ex-
tracted with chloroform (3Â40 mL). The organic layer was
washed with water (25 mL), dried and evaporated. The res-
idue was subjected to column chromatography over silica
gel (petroleum ether/EtOAc 9:1) to furnish the dihydrocou-
marins.
107.5, 118.8, 125.2, 126.6, 144.3, 154.3, 168.66. Anal. Calcd
for C12H14O3: C, 69.88; H, 6.84. Found: C, 69.84; H, 6.85.
3.1.2.5. Bargellini condensation of dihydrocoumar-
ins. Following the general procedure for Bargellini conden-
sation of coumarins, dihydrocoumarins 36a–e furnished the
saturated diacids and were characterized as dimethyl esters
13, 18 and 37a—d, which were obtained on reaction with di-
azomethane and purified by column chromatography over
silica gel.
3.1.2.6. Methyl-2-[2-(2-methoxycarbonyl-ethyl)-phen-
oxy]-2-methylpropionate (37a). Dihydrocoumarin 36a
(500 mg, 3.38 mmol) furnished the diacid, which was ester-
ified with diazomethane. The product was purified by col-
umn chromatography (12% EtOAc/petroleum ether) to
furnish the diester 37a (710 mg, 75%) as a colourless liquid.
Rf (12% EtOAc/petroleum ether) 0.56. IR (CHCl3)
3.1.2.1. 4,6-Dimethyl-dihydrocoumarin (36b). Couma-
rin 7c (1 g, 5.747 mmol) on hydrogenation furnished the di-
hydrocoumarin 36b (0.99 g, 98%) as a colourless oil. Rf
(15% EtOAc/petroleum ether) 0.51. IR (CHCl3)
1
1768 cmÀ1; H NMR (300 MHz, CDCl3) d 1.30 (3H, d, J
1
6.96, ArCHMeCH2–), 2.31 (3H, s, Me), 2.53 (1H, dd, J
15.7, 7.1 Hz, –CHMeCH2–), 2.79 (1H, dd, J 15.7, 5.4 Hz,
–CHMeCH2–), 3.11 (1H, m, ArCHMe), 6.90 (1H, d, J
7.9 Hz, ArH), 7.01 (1H, s, ArH) 7.02 (1H, d, J 7.9 Hz,
ArH); 13C NMR (75 MHz, CDCl3) d 19.9, 20.8, 29.5,
36.9, 116.7, 127.0, 127.6, 128.7, 134.2, 149.2, 168.6. Anal.
Calcd for C11H12O2: C, 74.98; H, 6.86. Found: C, 74.99;
H, 6.87.
1738 cmÀ1; H NMR (300 MHz, CDCl3) d 1.26 (6H, s,
–CMe2–), 2.56 (2H, t, J 8.0 Hz, ArCH2CH2–), 2.95 (2H, t,
J 8.0 Hz, ArCH2CH2–), 3.67 (3H, s, OMe), 3.76 (3H, s,
OMe), 6.59 (1H, d, J 7.5 Hz, ArH), 6.89 (1H, d, J 7.3 Hz,
ArH), 7.08 (1H, t, J 7.3 Hz, ArH), 7.19 (1H, d, J 7.5 Hz,
ArH); 13C NMR (75 MHz, CDCl3) d 25.4 (2C), 26.4, 34.0,
51.4, 52.4, 78.6, 115.4, 121.4, 127.0, 130.3, 131.1, 153.4,
173.7, 174.9. Anal. Calcd for C15H20O5: C, 64.27; H, 7.19.
Found: C, 64.22; H, 7.16.
3.1.2.2. 6-Methoxy-7-methyl-dihydrocoumarin (36c).
Coumarin 7g (1 g, 5.263 mmol) on hydrogenation furnished
dihydrocoumarin 36c (0.99 g, 98%) as a colourless solid,
crystallized from ether/petroleum ether. Mp 88–90 ꢀC. Rf
(15% EtOAc/petroleum ether) 0.54. IR (CHCl3)
3.1.2.7. Methyl-2-[4-methoxy-2-(2-methoxycarbonyl-
ethyl)-5-methylphenoxy]-butanoate (37b). Dihydrocou-
marin 36b (500 mg, 2.84 mmol) furnished the saturated
diester 37b (650 mg, 74%) as a colourless liquid after puri-
fication by column chromatography (12% EtOAc/petroleum
ether). Rf (12% EtOAc/petroleum ether) 0.55. IR (CHCl3)
1767 cmÀ1 1H NMR (300 MHz, CDCl3) d 2.17(3H, s,
;
Me), 2.75 (2H, t, J 7.0 Hz, ArCH2CH2–), 2.94 (2H, t, J
7.0 Hz, ArCH2CH2–), 3.79 (3H, s, OMe), 6.60 (1H, s,
ArH), 6.80 (1H, s, ArH); 13C NMR (75 MHz, CDCl3)
d 15.7, 23.6, 29.2, 55.6, 108.9, 118.6, 119.8, 126.4, 145.1,
154.1, 168.9. Anal. Calcd for C11H12O3: C, 68.74; H, 6.29.
Found: C, 68.68; H, 6.58.
1
1738 cmÀ1; H NMR (300 MHz, CDCl3) d 1.32 (3H, d, J
6.8 Hz, ArCHMe–), 1.60 (6H, s, –CMe2–), 2.25 (3H, s,
Me), 2.46 (1H, dd, J 9.2, 15.0 Hz, –CHMeCH2–), 2.70
(1H, dd, J 5.4, 15.0 Hz, –CHMeCH2–), 3.61 (1H, m,
ArCHMe), 3.63 (3H, s, OMe), 3.76 (3H, s, OMe), 6.49
(1H, d, J 8.3 Hz, ArH), 6.86 (1H, d, J 8.3 Hz, ArH), 6.97
(1H, s, ArH); 13C NMR (75 MHz, CDCl3) d 20.6, 21.1,
25.2, 31.5, 40.5, 52.3, 52.3, 78.6, 115.8, 121.1, 126.9,
127.6, 130.8, 135.8, 150.4, 173.1, 175.1. HRMS (ES +ve)
calcd for C17H25O5 [M+H]+ 309.1703. Found 309.1719.
3.1.2.3. 4,7-Dimethyl-dihydrocoumarin (36e). Couma-
rin 7b (1 g, 5.75 mmol) furnished dihydrocoumarin 36e
(0.98 g, 97%) on hydrogenation as a colourless oil. Rf
(15% EtOAc/petroleum ether) 0.52. IR (CHCl3)
1
1767 cmÀ1; H NMR (300 MHz, CDCl3) d 1.31 (3H, d, J
6.9 Hz, CHMe), 2.34 (3H, s, Me), 2.55 (1H, dd, J 15.7,
7.3 Hz, –CHMeCH2–), 2.81 (1H, dd, J 15.7, 5.4 Hz,
–CHMeCH2–), 3.15 (1H, m, ArCHMe), 6.87 (1H, s, ArH),
6.93 (1H, d, J 7.7 Hz, ArH), 7.09 (1H, d, J 7.7 Hz, ArH);
13C NMR (75 MHz, CDCl3) d 20.4, 21.4, 29.5, 37.4,
117.8, 125.2, 125.7, 126.6, 138.9, 151.5, 169.0. Anal. Calcd
for C11H12O2: C, 74.98; H, 6.86. Found: C, 74.97; H, 6.87.
3.1.2.8. Methyl-2-[4-methoxy-2-(2-methoxycarbonyl-
ethyl)-5-methylphenoxy]-2-methylpropionate
(37c).
Dihydrocoumarin 36c (500 mg, 2.60 mmol) furnished the
diester 37c (610 mg, 72%) as a colourless liquid after puri-
fication by column chromatography (12% EtOAc/petroleum
ether). Rf (12% EtOAc/petroleum ether) 0.56. IR (CHCl3)
1
1738 cmÀ1; H NMR (300 MHz, CDCl3) d 1.55 (6H, s,
–CMe2–), 2.10 (3H, s, Me), 2.59–2.64 (2H, m,
ArCH2CH2–), 2.87–2.92 (2H, m, ArCH2CH2–), 3.67 (3H,
s, OMe), 3.72 (3H, s, OMe), 3.78 (3H, s, OMe), 6.48 (1H,
s, ArH), 6.63 (1H, s, ArH); 13C NMR (75 MHz, CDCl3)
d 16.0, 25.1, 25.3, 26.9, 34.4, 51.7, 52.2, 55.6, 79.1, 112.0,
120.0, 124.8, 129.8, 146.5, 152.5, 172.2, 175.2. Anal. Calcd
for C17H24O6: C, 62.95; H, 7.46. Found: C, 62.92; H, 7.44.
3.1.2.4. 6-Methoxy-4,7-methyl-dihydrocoumarin (36f).
Hydrogenation of coumarin 7f furnished dihydrocoumarin
36f as a colourless crystalline solid. Mp 76–78 ꢀC.
Rf (15% EtOAc/petroleum ether) 0.53. IR (CHCl3)
1
1767 cmÀ1; H NMR (300 MHz, CDCl3) d 1.24 (3H, d, J
6.8 Hz, CHMe), 2.11 (3H, s, Me), 2.47 (1H, dd, J 6.8,
15.8 Hz, ArCHMeCH2–), 2.73 (1H, dd, J 6.8, 15.8 Hz,
ArCHMeCH2–), 3.01–3.07 (1H, m, ArCHMeCH2–), 3.82
(3H, s, OMe), 6.56 (1H, s, ArH), 6.70 (1H, s, ArH); 13C
NMR (75 MHz, CDCl3) d 15.8,19.9, 29.5, 36.8, 55.6,
3.1.2.9. Methyl 2-[4-methoxy-2-(2-methoxycarbonyl-
ethyl)-phenoxy]-2-methylpropionate (37d). Dihydrocou-
marin 36d (500 mg, 2.81 mmol) furnished the saturated

12036
B. Biswas et al. / Tetrahedron 63 (2007) 12026–12036
4. Gilman, H.; Wilder, G. R. J. Am. Chem. Soc. 1955, 77, 6644–
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91, 4782–4786.
6. Lai, J. T. Synthesis 1984, 122–123.
7. Lai, J. T. Tetrahedron Lett. 2001, 42, 557–560.
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diester 37d (615 mg, 71%) as a colourless liquid after puri-
fication by column chromatography (12% EtOAc/petroleum
ether). Rf (12% EtOAc/petroleum ether) 0.53. IR (CHCl3)
1
1738 cmÀ1; H NMR (300 MHz, CDCl3) d 1.49 (6H, s,
–CMe2–), 2.55 (2H, t, J 7.5 Hz, ArCH2CH2–), 2.84 (2H, t,
J 7.5 Hz, ArCH2CH2–), 3.60 (3H, s, OMe), 3.67 (3H, s,
OMe), 3.70 (3H, s, OMe), 6.53 (2H, s, ArH), 6.65 (1H, s,
ArH); 13C NMR (75 MHz, CDCl3) d 25.7 (2C), 27.0, 51.9,
52.9, 55.9, 79.6, 111.9, 116.3, 118.1, 133.4, 147.7, 154.8,
174.1, 175.6. Anal. Calcd for C16H22O6: C, 61.92; H, 7.15.
Found: C, 61.93; H, 7.15.
Acknowledgements
12. (a) Tuhina, K.; Bhowmik, D. R.; Venkateswaran, R. V. Chem.
Commun. 2002, 634–635; (b) Ghosh, S.; Tuhina, K.; Bhowmik,
D. R.; Venkateswaran, R. V. Tetrahedron 2007, 63, 644–651.
13. Preliminary report: Sen, P. K.; Biswas, B.; Venkateswaran,
R. V. Tetrahedron Lett. 2005, 46, 8741–8743.
We sincerely thank the Department of Science and Technol-
ogy, Government of India for financial support. B.B. thanks
the CSIR for a research fellowship. P.K.S. thanks the UGC
for a Minor Research Grant.
14. Imashiro, R.; Seki, M. J. Org. Chem. 2004, 69, 4216–4226.
15. Kishuku, H.; Shindo, M.; Shishido, K. Chem. Commun. 2003,
350–351.
References and notes
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R. V. Tetrahedron Lett. 2006, 47, 4019–4021.
17. Krapcho, A. P. Synthesis 1982, 805–822, 893–914.
18. Vyvyan, J. R.; Oaksmith, J. M.; Parks, B. W.; Peterson, E. M.
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