Intramolecular Diels-Alder additions to 2-benzopyran-3-ones; anti-selectivity induced by the phenylsulfonyl group

Article abstract of DOI:10.1039/a701589e

Intramolecular Diels-Alder additions of the 2-benzopyran-3-ones 2d, 2e and 2f with an E-SO₂Ph substituent on the dienophile (X = SO₂Ph in 2) show greatly enhanced exo-addition of the tether than is shown in the absence of the E-SO₂Ph group (X = H in 2). For 2e and 2f, exo-chain addition becomes preferred, and for 2d, endo-chain addition much less preferred, than in related cases with X = H. An E-CO₂Me group on the dienophile is also effective in enhancing exo-chain addition, but less effective than an E-SO₂Ph group. The adducts 4e and 4f undergo reductive elimination (5% Na-Hg) to give the diterpene related products 32 and 33 respectively.

Full text of DOI:10.1039/a701589e

View Article Online / Journal Homepage / Table of Contents for this issue
Intramolecular Diels–Alder additions to 2-benzopyran-3-ones;
anti-selectivity induced by the phenylsulfonyl group1
Edward J. Bush, David W. Jones* and Tracie C. L. M. Ryder
School of Chemistry, The University, Leeds, UK LS2 9JT
Intramolecular D iels–Alder additions of the 2-benzopyran-3-ones 2d, 2e and 2f with an E-SO2Ph
substituent on the dienophile (X = SO2Ph in 2) show greatly enhanced exo-addition of the tether than is
shown in the absence of the E-SO2Ph group (X = H in 2). For 2e and 2f, exo-chain addition becomes
preferred, and for 2d, endo-chain addition much less preferred, than in related cases with X = H . An
E-CO2M e group on the dienophile is also effective in enhancing exo-chain addition, but less effective than
an E-SO2Ph group. The adducts 4e and 4f undergo reductive elimination (5% N a–H g) to give the diterpene
related products 32 and 33 respectively.
Although simple o-quinodimethanes like 1 (n = 0 or 1) undergo
( )n
predominant exo-selective Diels–Alder reactions to give trans-
R
O
Y
BC fused products (Scheme 1),2 we found that related addition
R
A
O
X
( )n
H
( )n
H
C
2
B
1
Scheme 1
( )n
( )n
C
C
R
Y
Y
R
in 2-benzopyran-3-ones 2 (X = H) gave mostly the product 3 of
endo-chain addition (Scheme 2).1b
R
R
O
O
A
A
H
X
H
+
B
B
O
O
The products 3 with a cis-BC ring fusion were unsuitable for
the synthesis of pisiferic acid 53 and related diterpenoids (e.g.
carnosol4 and taxodione5) which had been one of our goals in
exploring the intramolecular Diels–Alder (IMDA) reactions of
2-benzopyran-3-ones.1b The different behaviour of 1 and 2 is
most simply attributed to repulsion between the bridging
᎐C(O)O᎐ moiety in 2 and an exo oriented tether. Moreover,
steric clash with the pyrone ring A must be less significant than
that with the ᎐C(O)O᎐ group.† This agrees with theoretical cal-
culations on the addition of butadiene to ethylene8 which sug-
gest a product-like transition state rather than a parallel planes
approach of the diene and dienophile. As a consequence there is
closest approach between an exo directed hydrogen on the
ethylene and the proximate Z-hydrogen of the diene. Whilst the
detailed geometry of the Diels–Alder transition state will no
doubt vary with the substituents on the diene and dienophile it
seems likely that interaction between an exo-dienophile sub-
stituent and the proximate Z-substituent on the diene will
remain an important factor in determining endo–exo selectivity.
Accordingly we argued that if group X in 2 was bulky, its steric
clash with the ᎐C(O)O᎐ moiety in an endo-chain addition
would favour an exo-chain, endo-X transition state. It is note-
worthy that in simple decatrienes 6 (Scheme 3) in which the Z-
positions of the diene are occupied by hydrogens, a bulky E-
SO2Ph group on the dienophile favours the exo-position pre-
X
(minor X = H)
4
3(major X = H)
Y
X
n
1
R
a
b
c
d
e
OMe
H
Me
H
H
H
H
1
0
H
H
SO2Ph
SO2Ph
SO2Ph
CO2Me
H
H
0
1
1
1
OMe
OMe
OMe
H
f
Me
H
g
Scheme 2
HO2C
C
HO
A
B
H
5
sumably due to greater steric interaction with the diene C-2–C-3
moiety in an endo-SO2Ph (exo-chain) transition state.9 This is a
useful way of diverting the evenly balanced endo–exo (chain)
preference in the IMDA reactions of decatrienes to obtain
mostly cis ring fused products (Scheme 3) i.e. to achieve the
opposite stereoselectivity to that required in the additions of
the pyrones 2.
† The preferred endo-chain additions observed when X = H echoes the
strong endo-selectivity in the addition of cyclopentene to the parent 2-
benzopyran-3-one.6 In both the intramolecular and the intermolecular
reactions repulsion involving the lactone C(O)O group is one important
factor. The existence of a second factor favouring endo-addition is sug-
gested by the endo-preference observed for addition of E-α-cyano- and
E-α-methoxycarbonyl-o-quinodimethane to cyclopentene. This other
factor may be a secondary MO–MO interaction (steric attraction).7
Because of its bulk and anticipated easy removal we chose
the phenylsulfonyl group as X in an attempt to divert the
J. Chem. Soc., Perkin Trans. 1, 1997
1929

View Article Online
required acids 13a and 13b. The acids were than obtained by
hydrolysis (K2CO3–H2O–MeOH, reflux, 1 h).
H
R = Me
R = H
ca.1:1 exo:endo
An attempt to open the lactone ring in 12c foundered due to
a more rapid intramolecular Michael addition. After a work-
up involving acidification at 0–5 ЊC and reaction with diazo-
methane, the cis–trans isomers corresponding to structure 14
were isolated as well as 24% of the desired hydroxy ester. This
suggests faster closure of five- compared to six-membered rings
via Michael addition although both these ring sizes are readily
obtained via such additions.10 In seeking other routes to struc-
tures like 13c we found that the problem of dialkylation experi-
enced with isochroman-3-ones [KN(SiMe3)2, THF–HMPT)]1b
disappeared when the ethylene acetal of ethyl o-formylphenyl-
acetate was alkylated with 7a and 7c under the same conditions;
the monoalkylated products 16 and 17 were obtained in 60 and
53% yield respectively. Upon base hydrolysis these gave the
ethylene acetals of acids 18 and 19 which readily underwent
acid-catalysed hydrolysis to 18 and 19. Reaction of the ethylene
acetal of 19 with PhSeSO2Ph (irradiation with a water-cooled
125 W medium pressure mercury lamp)11 and subsequent H2O2
oxidation–selenoxide elimination of the resulting seleno-
sulfones gave the α,β-unsaturated sulfone 20; acid hydrolysis
then gave 13c. In a related, but not identical, sequence ester 16
underwent selenosulfonation–selenoxide elimination to give the
ethyl ester of 21 which underwent acetal hydrolysis (THF–
HCl–H2O), followed by ester hydrolysis (K2CO3–MeOH–H2O),
to give acid 13d.
chain addition
H
X = SO2Ph
X = H or CO2Et
SO2Ph
X
R
Me
6
mainly
Scheme 3
stereochemistry of IMDA addition within the pyrones 2a–c.
Several routes were used to prepare the precursors (o-
formylphenylacetic acids) required to generate the pyrones 2
(X = SO2Ph). Alkylation of 6-methoxyisochroman-3-one [KN-
(SiMe3)2, THF–hexamethylphosphorous triamide (HMPT)]
with the iodides 7a–c gave mixtures of the required mono-
alkylated products 8 with corresponding dialkylated products
( )n
R
R
X
I
X
O
( )n
R
R
O
a R = H, n = 2, X = H
b R = Me, n = 2, X = H
c R = H, n = 1, X = H
d R = H, n = 1, X = SO2Ph
8
a R = H, n = 1, X = OMe
b R = Me, n = 1, X = OMe
c R = H, n = 0, X = OMe
7
An attempt was made to introduce the intact α,β-unsaturated
sulfone side chain by reacting 7d with 15 [KN(SiMe3)2, THF–
HMPT]. The compound 7d was prepared from the TBDMS
ether of pent-4-en-1-ol using selenosulfonation–selenoxide
elimination (see Experimental section). Unfortunately reaction
of 7d with 15 gave two products neither of which was the
required mono-alkylation product. After hydrolysis of the
CO2Et
O
EtO2C
O
MeO
MeO
O
O
9
10
1
acetal one product had H NMR spectral characteristics con-
sistent with structure 22 derived by Michael addition of the
anion from 15 to give 23 followed by intramolecular displace-
ment of iodide ion, as shown by the mechanism in 23, and acetal
hydrolysis. There are precedents for this behaviour involving
α,β-unsaturated carbonyl compounds.12 In the present case
Michael addition to the α,β-unsaturated sulfone is clearly more
rapid than SN 2 displacement of iodide.
( )n
R
( )n
R
O
R
O
R
Y
Y
O
O
O
PhO2S
11 a R = H, n = 1, Y = OMe
b R = Me, n = 1, Y = OMe
c R = H, n = 0, Y = OMe
12 a R = H, n = 1, Y = OMe
b R = Me, n = 1, Y = OMe
The other product from this reaction does not have 1H NMR
spectral characteristics consistent with structure 24 derived
from the desired product via intramolecular Michael addition
(25; mechanism) and acetal hydrolysis. This product was sub-
jected to careful chromatography but was never obtained com-
pletely pure. The high field resonances and proton–proton con-
nectivity (COSY) shown by the product are consistent with
structure 26. Presumably 7d is deprotonated and its anion
undergoes rapid ring closure to the cyclopropane 27 which sub-
sequently adds to the anion of 15 in a Michael reaction.
Reaction of the aldehyde 11a with the sodium salt of tri-
methyl phosphonoacetate gave the α,β-unsaturated ester 28.
Upon lactone ring opening, acidification at 0–5 ЊC and methyl-
ation with diazomethane 28 gave the diester 29. Swern
oxidation gave the aldehyde 30 and a remarkably selective
hydrolysis of this diester with K2CO3–MeOH–H2O at 20 ЊC
(1 h) gave the required aldehydo acid 31.
In boiling acetic anhydride the acids 13a, 13b and 13c under-
went smooth dehydration to pyrones as indicated by the for-
mation of yellow colours which faded with formation of the
adducts of type 3 and 4. As described in our earlier paper 1b the
1H NMR spectra of adducts of this type provide excellent evi-
dence for their stereochemistry. The spectra upon which our
current assignments are based are detailed in the Experimental
section.
c
R = H, n = 0, Y = OMe
( )n
R
CH2SO2Ph
O
R
Y
O
MeO
OH
CHO
PhO2S
O
14
a R = H, n = 1, Y = OMe
b R = Me, n = 1, Y = OMe
c R = H, n = 0, Y = H
d R = H, n = 1, Y = H
13
that had to be removed by chromatography.1b An attempt to
avoid dialkylation involved ethoxycarbonylation of 6-methoxy-
isochroman-3-one [(CO2Et)2, NaH, benzene, reflux] and gave 9
in 48% yield. Alkylation of 9 with 7a gave 10 (64%) which was
smoothly hydrolysed and decarboxylated to 8a (95%). However
the overall yield was inferior to that from direct alkylation of 6-
methoxyisochroman-3-one (~50%).
Ozonolysis of the compounds 8a, 8b and 8c gave the corre-
sponding aldehydes 11a, 11b and 11c which upon addition of
PhSO2CH2Li (THF, Ϫ78 ЊC) and dehydration of the resulting
hydroxy sulfones (MeSO2Cl, Et3N, THF, Ϫ5 ЊC, 30 min) gave
12a, 12b and 12c. For 12a and 12b lactone ring opening
(K2CO3–H2O–MeOH, reflux, 1 h), esterification with diazo-
methane and Swern oxidation then gave the methyl esters of the
The ratios for endo–exo addition of the connecting chain
observed for the compounds with an E-sulfonyl substituted
dienophile are collected in Table 1 (entries 4–6) together with
1930
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
Table 1
R
( )n
CO2Et
Ratio of endo:exo
chain addition, 3:4
CO2H
CHO
O
Entry
Pyrone
O
1
2
3
4
5
6
7
2a
2b
2c
2d
2e
2f
6.0:1
4.5:1
7.0:1
1.4:1
1.0:4.2
1.0:2.6
1.0:3.4
15 R = H
18 n = 1
19 n = 0
CH CH2
CH CH2
16 R = (CH2)4
17 R = (CH2)3
CO2Et
( )n
2g
H
CO2H
H
H
O
For the pyrones with three atoms in the tether (n = 0) the
effect of introducing an SO2Ph group is smaller but still well
defined (entries 3 and 4). When the tether is longer (n = 1) the
addition transition state is likely to involve greater synchrony of
bond formation at the α and β positions of the α,β-unsaturated
sulfone than when n = 0. In the latter case, bond formation at
the β-carbon is likely to run ahead of that at the α-carbon.
Consequently steric effects due to the SO2Ph group at C-α will
be less keenly felt in the transition state for the shorter tether.
Having served its purpose, the phenylsulfonyl group can
be removed from 4e and 4f by treatment with 5% sodium–
amalgam, when reductive β-elimination with the lactone in the
manner of a Julia reaction provides the carboxylic acids 32
and 33 in good yield (>80%). In these cases the trans coplanar
SO2Ph
SO2Ph
H
O
O
20 n = 0
21 n = 1
22
CO2Et
EtO2C
H
I
H
O
CH2SO2Ph
SO2Ph
H
H
O
O
24
23
EtO2C
EtO2C
HO2C
HO2C
H
Me
Me
R
R
MeO
MeO
O
SO2Ph
H
H
O
CHO
SO2Ph
SO2Ph
34
R = H
32
25
26
33 R = Me
HO2C
PhO2S
H
MeO
O
Me
Me
MeO
O
MeO2C
35
27
28
arrangement of the eliminated groups leads to smooth reaction.
In contrast, reaction of 3e with sodium–amalgam gave mostly
the saturated sulfone 34 (57%) and only 30% of the acid 35.
This failure is not of preparative significance as compounds
like 35 are easily prepared via acid catalysed elimination of the
readily available endo-chain adducts 3 (X = H).1b
MeO
CO2R
X
In conclusion, we have shown that IMDA additions to 2-
benzopyran-3-ones 2 allow preparation of either cis- or trans-
fused hydrophenanthrenes related to natural diterpenoids. Our
results may extend to other dienes linked between their termini.
Such systems include important Diels–Alder dienes like cyclo-
pentadienes, cyclohexadienes, furans, simple pyrones and other
o-quinodimethanes. We also suggest that any diene with a Z-
substituent will show an increased tendency to endo-addition
of the larger group of a trans-dienophile in both inter- and
intra-molecular addition. Indeed this may explain why o-quino-
dimethanes with a Z-cyano group break the general rule of exo-
chain preference in IMDA additions to o-quinonoid dienes.13
MeO2C
29 X = CH2OH, R = Me
30 X = CHO, R = Me
31 X = CHO, R = H
data for related compounds lacking the phenylsulfonyl group
(entries 1–3). In entry 7 the effect of an E-CO2Me group on the
dienophile is determined. All ratios were obtained from well
1
resolved H NMR spectra (400 MHz) of the unpurified reac-
tion product. Chromatographic isolation of the adducts agreed
with these ratios. Yields in the reactions were usually >80%. It is
clear that in all the cases examined the endo–exo (chain) ratio is
much reduced in the E-SO2Ph compounds. For the pyrones
with n = 1 (four atoms in the tether) the E-SO2Ph group gives
mostly the exo-chain adduct whereas in the absence of the
E-SO2Ph group the endo-chain adduct is dominant (cf. entry 2
vs. 5 and entry 1 vs. 6). Entry 7 shows the E-CO2Me group is
somewhat less effective in inducing the same change in stereo-
chemistry, suggesting a steric rather than a secondary MO–MO
interaction effect for the sulfones.
Experimental
Mps were determined with a Kofler hot-stage apparatus and
are uncorrected. Infrared spectra were recorded on a Philips
PU 8706 infrared spectrophotometer, and referenced to a peak
at 1601 cmϪ1 of polystyrene. Only significant absorbances are
reported. Ultraviolet and visible spectra were recorded on a
Pye-Unicam PU 8800 UV–VIS spectrophotometer; log ε values
J. Chem. Soc., Perkin Trans. 1, 1997
1931

View Article Online
1
are in parentheses. Unless otherwise stated H NMR spectra
heated at 50 ЊC (bath temperature) (6 h). The mixture was acid-
were measured in CDCl3 with tetramethylsilane as internal
standard; 400 MHz NMR spectra were measured on a Bruker
WH-400 instrument and 300 MHz spectra on a General Elec-
tric Nicolet QE 300 spectrometer. The position of NMR reson-
ances are expressed in parts per million (δ), and coupling con-
stants J are given in Hz. Mass spectra were obtained on an
Autospec mass spectrometer. Chromatography on silica refers
to short-column chromatography14 over Kieselgel G60
(Merck). Thin layer chromatography was carried out on glass
plates (15 × 5 cm2), dipped in an ethyl acetate suspension of
Kieselgel G60 and dried in an air oven at 120 ЊC for at least 1 h.
Ether refers to diethyl ether and light petroleum to the fraction
bp 60–80 ЊC. All solvents were distilled and dried before use by
standard procedures.15 Unless otherwise stated, all reactions
were conducted under an atmosphere of dry, oxygen free argon.
For procedures requiring anhydrous conditions all glassware
was oven dried at 120 ЊC (18 h) prior to use. Solvents were
removed under reduced pressure using a Buchi rotary evapor-
ator at water pump pressure followed by heating on a steam
bath at water pump pressure.
ified to pH 1 with dilute hydrochloric acid (2 mol dmϪ3),
extracted with ether, washed (water), dried (MgSO4) and con-
centrated. The crude product was heated on a steam bath
(100 ЊC) (10 min) to give the decarboxylated product 8a (52 mg,
1
95%). The H NMR spectrum of the product was identical to
that of a previously prepared sample.1b
Preparation of the aldehyde 11a
The olefin 8a (2.0 g, 7.69 mmol) was dissolved in dry dichloro-
methane (27 ml) and dry methanol (40 ml) and ozonolysed at
Ϫ78 ЊC (0.5 h). Dry argon was bubbled through the solution
(1 h) and dimethyl sulfide added. Then the solution was allowed
to reach room temperature with stirring (3 h). Chromatography
of the evaporated product on silica (40 g) in benzene–ether
(7:3) gave 4-(5-oxopentyl)-6-methoxychroman-3-one 11a (1.53
g, 76%) as an oil (Found: C, 68.9; H, 6.8. C15H18O4 requires C,
68.7; H, 6.9%); νmax(film)/cmϪ1 2740, 1740 and 1730; δH (300
MHz) 1.54 (2H, m), 1.70 (2H, m), 1.87 (1H, m), 1.98 (1H, m),
2.49 (2H, t, J 7.0, methylene-H), 3.56 (1 H, t, J 7.0, methine-H),
3.83 (3H, s, OMe), 5.21 (1H, d, J 14.0, benzylic-H), 5.38 (1H, d,
J 14.0, benzylic-H), 6.73 (1H, s, Ar-H), 6.82 (1H, dd, J 8.5 and
2.0, Ar-H), 7.14 (1H, d, J 8.5, Ar-H) and 9.77 (1H, s, CHO);
m/z 262 (Mϩ), 177, 149, 83, 70, 57, 56, 55, 43 and 41 (29.3, 22.7,
22.7, 23.3, 23.5, 100.0, 22.7, 28.6, 36.9 and 42.2%).
Ethoxycarbonylation of 6-methoxyisochroman-3-one
To a stirred solution of sodium hydride (1.27 g, of a 60% dis-
persion in mineral oil, 31.7 mmol) in benzene (20 ml) was added
diethyl carbonate (2.65 g, 22.4 mmol) in benzene (5 ml). The
reaction mixture was heated at reflux and a solution of 6-
methoxyisochroman-3-one (2.0 g, 11.2 mmol) in benzene (16
ml) was added dropwise over 2.5 h and the reaction was heated
at reflux (3 h). The contents of the flask were cooled to room
temperature and glacial acetic acid (16 ml) was added dropwise
followed by water (8 ml) and the reaction was stirred at 20 ЊC
(15 h). The solution was poured into water, extracted with
dichloromethane, dried (MgSO4) and concentrated to give an
oil (2.54 g). Chromatography on silica (80 g) eluting with
dichloromethane gave the ethyl 6-methoxy-3-oxochromane-4-
carboxylate 9 (1.34 g, 48%) (Found: C, 62.5; H, 5.7. C13H14O5
requires C, 62.4; H, 5.6%); νmax(film)/cmϪ1 1750 and 1735;
δH (300 MHz) 1.27 (3H, t, J 7.0, CO2CH2CH3), 3.83 (3H, s,
OMe), 4.21 (2H, m, CO2CH2CH3), 4.63 (1H, s, methine-H),
5.20 (1H, d, J 13.5, benzylic-H), 5.60 (1H, d, J 13.5, benzylic-
H), 6.88 (2H, m, Ar-H) and 7.16 (1H, d, J 8.0, Ar-H); m/z 250
(Mϩ), 193, 178, 177, 165, 149, 148, 121, 91 and 77 (15.4, 21.6,
29.4, 100.0, 19.2, 43.9, 27.6, 32.4, 21.1 and 21.3%).
Preparation of the aldehyde 11b
Ozonolysis of the previously described alkene 8b1b in the
manner described above and work-up as above gave 4-(4,4-
dimethyl-5-oxopentyl)-6-methoxychroman-3-one 11b (75%) as
an oil (Found: Mϩ, 290.1507. C17H22O4 requires Mϩ, 290.1518);
νmax(film)/cmϪ1 1720 and 1740; δH (300 MHz) 1.05 (6H, s, 2 ×
Me), 1.46 (2H, m), 1.54 (2H, m), 1.86 (1H, m), 1.95 (1H, m),
3.55 (1H, t, J 7.0, methine-H), 3.82 (3H, s, OMe), 5.20 (1H, d,
J 14.0, benzylic-H), 5.36 (1H, d, J 14.0, benzylic-H), 6.71 (1H,
d, J 2.0, Ar-H), 6.81 (1H, dd, J 2.0 and 8.5, Ar-H), 7.13 (1H, d,
J 8.5, Ar-H) and 9.44 (1H, s, CHO); m/z 290 (Mϩ), 180, 178,
177, 162, 159, 147, 121, 91 and 41 (59.6, 100.0, 53.7, 73.5, 49.7,
73.4, 49.4, 53.9, 54.4 and 67.8%).
Preparation of the á,â-unsaturated sulfone 12a from the aldehyde
11a
To a stirred solution of methyl phenyl sulfone (1.0 g, 6.3 mmol,
1.1 equiv.) in THF (28 ml) under argon at Ϫ78 ЊC was added
dropwise by syringe n-butyllithium (3.95 ml of a 1.60  solution
in hexanes, 6.30 mmol) to give a colourless solution of the
anion. After 10 min a solution of 11a (1.50 g, 5.73 mmol) in
THF (8 ml) was added via a cannula at Ϫ78 ЊC, rinsing with a
further portion of THF (8 ml). After 2.5 h, the reaction was
quenched by the addition of a solution of acetic acid in THF
(7.5 ml of a 1.0 M solution, 1.3 equiv.). The mixture was then
allowed to reach room temperature (1 h) and poured into a 1:1
mixture of dichloromethane and saturated aqueous sodium
hydrogen carbonate (160 ml). The aqueous layer was extracted
with CH2Cl2 (2 × 80 ml) and the combined organic layers were
washed with water (3 × 80 ml), dried (MgSO4) and concentrated
under reduced pressure to give an oil. Chromatography of the
oil on silica (310 g) in benzene–ether (3:7) gave the β-hydroxy
sulfone as an oil (1.58 g, 66%) (Found: Mϩ, 418.1458.
C22H26O6S requires Mϩ, 418.1450); νmax(film)/cmϪ1 3500 and
1735; δH (300 MHz) 1.46 (6H, m), 1.80 (1H, m), 1.93 (1H, m),
3.14–3.27 (2H, m), 3.42 (1H, m, OH), 3.53 (1H, t, J 7.0,
methine-H), 3.82 (3H, s, OMe), 4.16 (1H, m), 5.19 (1H, d, J
14.0, benzylic-H), 5.37 (1H, d, J 14.0, benzylic-H), 6.70 (1H, s,
Ar-H), 6.81 (1H, dd, J 8.5 and 2.0, Ar-H), 7.12 (1H, d, J 8.5,
Ar-H), 7.65 (3H, m, SO2Ph) and 7.94 (2H, SO2Ph); m/z 418
(Mϩ), 213, 191, 178, 177, 161, 147, 121, 91 and 77 (54.7, 45.3,
48.3, 35.6, 100.0, 23.8, 26.8, 25.4, 26.6 and 58.2%).
Alkylation of 9 with 7a
To a stirred solution of 9 (116 mg, 0.46 mmol) in dry distilled
DMF (5 ml) was added sodium hydride (21 mg, 0.53 mmol of a
60% dispersion in mineral oil) and the mixture was heated at
60 ЊC under argon (0.5 h). The solution was cooled to room
temperature and a solution of the iodide 7a (111 mg, 0.53
mmol) in DMF (2 ml) added. The mixture was heated at 55–
60 ЊC (bath temperature) (16 h) then diluted with ether, washed
with water (240 ml), dried (MgSO4) and concentrated to give an
oil. Chromatography on silica (32 g) eluting with dichloro-
methane gave ethyl 4-(hex-5-enyl)-6-methoxy-3-oxochromane-4-
carboxylate 10 (98 mg, 64%) (Found: Mϩ, 332.1623. C19H24O5
requires Mϩ, 332.1624); νmax(film)/cmϪ1 1740; δH (300 MHz)
1.19 (3H, t, J 7.0, OCH2CH3), 1.41 (2H, m), 2.01 (2H, q, J 7.0),
2.34 (2H, m), 2.47 (2H, m), 3.82 (3H, s, OMe), 4.15 (2H, q, J
7.0, OCH2CH3), 4.92 (2H, m, olefinic-H), 5.29 (1H, d, J 14.0,
benzylic-H), 5.45 (1H, d, J 14.0, benzylic-H), 5.74 (1H, m,
olefinic-H), 6.81 (1 H, s, Ar-H), 6.88 (1H, d, J 8.5, Ar-H) and
7.09 (1H, d, J 8.5, Ar-H); m/z 332 (Mϩ), 259, 249, 213, 204, 203,
173, 159, 145 and 41 (18.1, 53.4, 100.0, 60.1, 68.0, 98.8, 29.4,
36.3, 52.4 and 39.9%).
Hydrolysis of 10
The title compound (71 mg, 0.21 mmol), potassium carbonate
(59 mg, 0.43 mmol), methanol (2.2 ml) and water (1.1 ml) were
To a stirred solution of the hydroxy sulfone (1.50 g, 3.59
mmol) in dry dichloromethane (40 ml) under argon at Ϫ6 ЊC
1932
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
was added dropwise via syringe triethylamine (5.0 ml, 36.0
mmol, 10 equiv.) followed immediately by methanesulfonyl
chloride (0.84 ml, 10.8 mmol, 3 equiv.). The reaction was then
allowed to warm to room temperature (1 h). The mixture was
poured into saturated aqueous ammonium chloride (75 ml) and
extracted with dichloromethane (3 × 40 ml). The combined
organic layers were washed with saturated aqueous ammonium
chloride (2 × 75 ml) and then water (75 ml), dried (MgSO4) and
concentrated under reduced pressure. Chromatography of the
crude product on silica (30 g) in benzene–ether (2:3) gave the
4-(6-phenylsulfonylhex-5-enyl)-6-methoxychroman-3-one 12a as
an oil (1.29 g, 90%) (Found: C, 66.0; H, 6.0; S, 7.7. C22H24O5S
requires C, 66.0; H, 6.0; S, 8.0%); νmax(film)/cmϪ1 1735; δH (300
MHz) 1.53 (4H, m), 1.84 (1H, m), 1.95 (1H, m), 2.27 (2H, m),
3.53 (1H, t, J 7.0, methine-H), 3.82 (3H, s, OMe), 5.20 (1H, d, J
14.0, benzylic-H), 5.36 (1H, d, J 14.0, benzylic-H), 6.31 (1H, d,
J 15.0, olefinic-H), 6.70 (1H, s, Ar-H), 6.82 (1H, dd, J 8.5 and
2.0, Ar-H), 6.98 (1H, dt, J 15.0 and 7.0, olefinic-H), 7.14 (1H, d,
J 8.5, Ar-H), 7.54 (3H, m, SO2Ph) and 7.88 (2H, m, SO2Ph);
m/z 400 (Mϩ), 372, 231, 230, 213, 177, 147, 121, 91 and 77 (14.0,
24.0, 32.5, 49.7, 44.0, 100.0, 21.6, 31.8, 28.0 and 40.3%).
7.26 (1H, d, J 8.5, Ar-H), 7.58 (3H, m, SO2Ph) and 7.86 (2H, m,
SO2Ph); the OH signal was not recorded; m/z 432 (Mϩ), 231,
230, 213, 178, 177, 137, 121, 91 and 77 (2.5, 27.6, 39.7, 43.4,
26.1, 100.0, 43.4, 32.6, 24.9 and 40.7%). To a stirred solution of
dimethyl sulfoxide (394 mg) in dry dichloromethane (5 ml) was
added oxalyl chloride (0.32 g) in CH2Cl2 (1 ml) at Ϫ78 ЊC with
stirring under argon. The solution was stirred (4 min) then the
alcohol added dropwise (909 mg, 2.1 mmol) in CH2Cl2 (2 ml)
and the flask washed with CH2Cl2 (0.5 ml). After stirring (0.5 h)
triethylamine (1.50 ml, 5 equiv.) was added and the mixture
allowed to reach room temperature, poured into ice, diluted
with ether and the organic layer washed with dilute hydro-
chloric acid (25 ml, 0.5 mol dmϪ3) and then water. The ether
layer was separated, dried (MgSO4) and concentrated to give
an oil (870 mg). Chromatography on silica (50 g) eluting with
benzene–ether (22:3) gave the methyl ester of 13a as an oil (765
mg, 85%) (Found: C, 63.9; H, 6.1; S, 7.5. C23H26O6S requires C,
64.2; H, 6.1; S, 7.4%); νmax(film)/cmϪ1 1730 and 1680; δH (300
MHz) 1.30 (2H, m), 1.48 (2H, m), 1.70 (1H, m), 2.09 (1H, m),
2.21 (2H, m), 3.65 (3H, s, CO2Me), 3.88 (3H, s, OMe), 4.84 (1H,
t, J 7.5, methine-H), 6.29 (1H, d, J 15.0), 6.92 (3H, m), 7.58 (3H,
m, SO2Ph), 7.75 (1H, d, J 9.0, Ar-H), 7.87 (2H, m, SO2Ph) and
10.02 (1H, s, CHO); m/z 430 (Mϩ), 229, 213, 189, 161, 148, 125,
121, 91 and 77 (18.5, 58.4, 85.8, 69.0, 100.0, 51.5, 41.0, 46.5,
39.1 and 95.9%). The foregoing methyl ester (510 mg, 1.19
mmol), potassium carbonate (330 mg, 2.4 mmol), methanol
(12.5 ml) and water (6.3 ml) were stirred at room temperature
(20 h). Hydrochloric acid (2 mol dmϪ3) was added to reach pH 1
and the precipitated acid extracted into CH2Cl2. The organic
layer was separated, dried (MgSO4) and concentrated to give
the crude acid. Chromatography on silica (35 g) eluting with
benzene–ether–acetic acid (63:35:2) gave 2-(2-formyl-5-
methoxyphenyl)-8-phenylsulfonyloct-7-enoic acid 13a as an oil
(426 mg, 86%) (Found: Mϩ, 416.1297. C22H24O6S requires Mϩ,
416.1294); νmax(film)/cmϪ1 3250, 1710 and 1685; δH (300 MHz)
1.40 (4H, m), 1.73 (1H, m), 2.20 (3H, m), 3.83 (3H, s, OMe),
4.73 (1H, t, J 7.0, methine-H), 6.28 (1H, d, J 16.0), 6.93 (3H, m),
7.57 (3H, m, SO2Ph), 7.75 (1H, d, J 8.0, Ar-H), 7.86 (2H, m,
SO2Ph) and 9.95 (1H, s, CHO); the CO2H signal was not
recorded; m/z 416 (Mϩ), 306, 229, 213, 189, 161, 148, 121, 91
and 77 (5.0, 40.4, 72.4, 100.0, 45.6, 74.3, 27.9, 35.7, 39.4 and
61.8%).
Preparation of the á,â-unsaturated sulfone 12b
4-(4,4-Dimethyl-6-phenylsulfonylhex-5-enyl)-6-methoxy-
chroman-3-one was obtained in 40% yield in the manner
detailed above for 12a (Found: C, 67.2; H, 6.8; S, 7.6. C24H28O5S
requires C, 67.3; H, 6.5; S, 7.5%); νmax(film)/cmϪ1 1740; δH (300
MHz) 1.06 (6H, s, 2 × Me), 1.45 (4H, m), 1.79 (1H, m), 1.91
(1H, m), 3.51 (1H, t, J 7.0, methine-H), 3.83 (3H, s, OMe), 5.20
(1H, d, J 14.0, benzylic-H), 5.35 (1H, d, J 14.0, benzylic-H),
6.19 (1H, d, J 15.5), 6.70 (1H, s, Ar-H), 6.83 (1H, dd, J 2.0 and
8.5, Ar-H), 6.93 (1H, d, J 15.5), 7.14 (1H, d, J 8.5, Ar-H), 7.58
(3H, m, SO2Ph) and 7.87 (2H, m, SO2Ph); m/z 428 (Mϩ), 259,
258, 178, 177, 149, 125, 77, 69 and 41 (12.2, 21.6, 23.9, 26.0,
100.0, 31.5, 23.7, 40.6, 20.7 and 27.5%).
Preparation of vinyl sulfone 12c
Ozonolysis of previously prepared 1b 8c as described above for
8a gave the aldehyde (62%) as a pale yellow oil after chrom-
atography on silica in benzene–ether (7:3); δH 1.75–2.15 (4H,
m), 2.55 (2H, m), 3.60 (1H, t, J 7.0, benzylic methine), 3.90 (3H,
s), 5.20 (1H, d, J 14.0), 5.36 (1H, d, J 14), 6.82 (2H, m), 7.14
(1H, m), 7.42 (1H, m) and 9.79 (1H, s); m/z 248, 191, 175, 163,
159, 147, 145, 121 and 91 (64, 100, 33, 35, 31, 44, 63, 32 and
40%). This aldehyde was converted into the 4-(5-phenyl-
sulfonylpent-4-enyl)-6-methoxychroman-3-one 12c via the
hydroxy sulfone as described above for the preparation of 12a
Preparation of the aldehydo acid 13b from 12b
This proceeded as described above for 13a via the hydroxy-
methyl ester and the methyl ester of 13b. The hydroxymethyl
ester was obtained in 97% crude yield and was directly oxidised
to the aldehydo ester (oil, 83% yield) (Found: C, 65.0; H, 6.7; S,
7.1. C25H30O6S requires C, 65.2; H, 6.6; S, 7.0%); νmax(film)/cmϪ1
1725 and 1680; δH (300 MHz) 1.01 (6H, s, 2 × Me), 1.20 (2H,
m), 1.40 (2H, m), 1.68 (1H, m), 2.04 (1H, m), 3.65 (3H, s,
CO2Me), 3.88 (3H, s, OMe), 4.84 (1H, t, J 6.0, methine-H), 6.15
(1H, d, J 15.5, olefinic-H), 6.90 (3H, m), 7.65 (3H, m, SO2Ph),
7.74 (1H, d, J 4.5, Ar-H), 7.85 (2H, m, SO2Ph) and 10.03 (1H, s,
CHO); m/z 458 (Mϩ), 257, 241, 189, 161, 148, 125, 121, 77 and
41 (12.9, 56.6, 36.0, 82.9, 100.0, 43.6, 59.0, 36.4, 58.8 and
39.2%). Swern oxidation gave 2-(2-formyl-5-methoxyphenyl)-
6,6-dimethyl-8-phenylsulfonyloct-7-enoic acid 13b as an oil
(92%) (Found: Mϩ, 444.1586. C24H28O6S requires Mϩ,
444.1606); νmax(film)/cmϪ1 3350, 1730 and 1690; δH (300 MHz)
0.99 (6H, s, 2 × Me), 1.20 (2H, m), 1.41 (2H, m), 1.69 (1H, m),
2.10 (1H, m), 3.87 (3H, s, OMe), 4.73 (1H, t, J 7.0, methine-H),
6.13 (1H, d, J 15.5, olefinic-H), 6.87 (1H, d, J 15.5, olefinic-H),
6.93 (2H, m), 7.56 (3H, m), 7.75 (1H, d, J 8.0, Ar-H), 7.83 (2H,
m), 9.96 (1H, s, CHO); the CO2H signal was not recorded; m/z
444 (Mϩ), 334, 257, 241, 189, 171, 161, 125, 77 and 41 (6.0, 47.6,
72.5, 78.9, 78.2, 72.8, 100.0, 64.0, 77.8 and 56.6%).
(ca 30% yield over two steps) (Found: M ϩ, 386.118. C21H22O5S
᝽
requires M, 386.118); δH 1.54–2.05 (4H, m), 2.30 (2H, m), 3.52
(1H, t, J 7.0, benzylic methine), 3.80 (3H, s), 5.17 (1H, d, J
13.5), 5.30 (1H, d, J 13.5), 6.33 (1H, d, J 15.0, olefinic-H), 6.68
(1H, br s), 6.81 (1H, m), 6.95 (1H, dt, J 15.0 and 7.0, olefinic-
H), 7.11 (1H, m), 7.54 (3H, m) and 7.85 (2H, m); m/z 386, 245,
217, 216, 199, 187, 177, 77 (16, 11, 39, 79, 55, 29, 100 and 27%).
Conversion of 12a into 13a
The sulfone 12a (860 mg, 2.15 mmol), potassium carbonate
(590 mg, 4.3 mmol), methanol (21.5 ml) and water (10.75 ml)
were stirred at room temperature (3.5 h). The mixture was
cooled to 0–5 ЊC (ice–water) and transferred to a separating
funnel where ice cold dilute hydrochloric acid (50 ml, 2 mol
dmϪ3) was added. The precipitated acid was extracted into ether
(0 ЊC) and immediately treated with diazomethane. Evapor-
ation of the solvent left an oil which was dried (MgSO4) and
concentrated to give the crude ester (909 mg, 98%) (Found: Mϩ,
432.1581. C23H28O6S requires M, 432.1562); νmax(film)/cmϪ1
3480 and 1730; δH (300 MHz) 1.28 (1H, m), 1.48 (2H, m), 1.78
(1H, m), 2.19 (4H, m), 3.64 (3H, s, CO2Me), 3.79 (3H, s, OMe),
3.94 (1H, t, J 7.5, methine-H), 4.67 (2H, m, benzylic-H), 6.27
(1H, d, J 15.0), 6.77 (1H, dd, J 2.5 and 8.5, Ar-H), 6.93 (2H, m),
Attempted base catalysed ring opening of 12c
The vinyl sulfone 12c (200 mg, 0.517 mmol), potassium carbon-
J. Chem. Soc., Perkin Trans. 1, 1997
1933

View Article Online
ate (143 mg, 1.04 mmol), methanol (5 ml) and water (2.6 ml)
were stirred at 20 ЊC (15 h). The product was cooled to 0 ЊC
and acidified with hydrochloric acid (2 ). The product was
extracted into ice cold ether and treated with ethereal diazo-
methane at 0 ЊC. The evaporated product was chromato-
graphed on silica to give initially one diastereoisomer of 14 (21
mg, 10%) as a white solid; δH (400 MHz) 1.66 (1H, dt, J 14.0 and
9.5), 1.88 (2H, m), 2.06 (1H, m), 2.19 (1H, m), 2.50 (1H, dt, J
13.5 and 6.0), 3.10 (1H, dd, J 14.0 and 1.0, CH2SO2Ph), 3.22
(1H, q, J 10.0, CHCH2SO2Ph), 3.66 (1H, dd, J 14.0 and 10,
CH2SO2Ph), 3.9 (3H, s), 5.10 (1H, d, J 14.0, benzylic-H), 5.40
(1H, d, J 14, benzylic-H), 6.83 (1H, m), 7.1 (2H, m), 7.57 (2H,
m), 7.63 (1H, m) and 7.90 (2H, m); m/z 386, 245, 217, 216, 199,
177, 159 (7, 66, 30, 60, 73, 100 and 31%).
Continued elution of the column gave a second diastereo-
isomer of 14 (73 mg, 34%); δH (400 MHz) 1.84 (2H, m), 2.08
(3H, m), 2.37 (1H, m), 2.66 (1H, dd, J 14.5 and 2.5,
CH2SO2Ph), 2.84 (1H, dd, J 14.5 and 10.5, CH2SO2Ph), 2.94
(1H, m, CHCH2SO2Ph), 3.83 (3H, s), 5.01 (2H, AB system, J
14.0, benzylic-H), 6.79 (1H, m), 6.85 (1H, m), 7.08 (1H, m),
7.55 (2H, m), 7.65 (1H, m), 7.75 (2H, m).
dd, J 4.5 and 13.0), 2.05 (2H, m), 2.56 (1H, d, J 13.0), 3.83 (3H,
s, OMe), 4.12 (1H, t, J 4.5, exo-methine), 5.74 (1H, d, J 4.0,
bridgehead methine), 6.78 (1H, d, J 2.0, Ar-H), 6.86 (1H, dd,
J 2.0 and 8.5, Ar-H), 7.29 (1H, d, J 8.5, Ar-H), 7.52 (3H, m,
SO2Ph) and 7.65 (2H, m, SO2Ph); m/z 426 (Mϩ), 242, 241, 185,
172, 171, 128, 77, 55 and 41 (20.8, 34.8, 96.4, 17.8, 29.7, 100.0,
24.2, 38.6, 20.9 and 17.9%).
The endo-chain adduct 3f (24%) mp 197.0–197.5 ЊC (EtOH)
(Found: C, 67.7; H, 6.3; S, 7.6%); νmax(film)/cmϪ1 1755; δH (300
MHz) 0.14 (3H, s, Me), 1.03 (3H, s, Me), 1.33 (2H, m), 1.85
(3H, m), 2.32 (1H, d, J 4.5, exo-methine), 2.48 (1H, d, J 12.0),
3.43 (1H, d, J 4.5, endo-methine), 3.80 (3H, s, OMe), 5.64 (1H, s,
bridgehead methine), 6.76 (1H, dd, J 2.0 and 8.5, Ar-H), 6.96
(1H, d, J 2.0, Ar-H), 7.16 (1H, d, J 8.0, Ar-H), 7.68 (3H, m,
SO2Ph) and 8.07 (2H, m, SO2Ph); m/z 426 (Mϩ), 257, 242, 241,
229, 172, 171, 77, 69 and 41 (5.8, 72.6, 58.7, 100.0, 48.4, 47.9,
97.9, 67.1, 54.4 and 37.7%).
Desulfurisation of adduct 4e
To a solution of the sulfone (50 mg, 0.13 mmol) was added
anhydrous disodium orthophosphate (90 mg, 4 equiv., 0.5
mmol), dry methanol (3 ml) and dry distilled THF (3.0 ml). The
flask was cooled to 0–5 ЊC (ice–water), pulverised 5% sodium–
mercury amalgam (130 mg) was added, and the reaction stirred
under argon (18 h). The product was poured into water, acid-
ified to pH 1 with hydrochloric acid (2 mol dmϪ3), extracted
into ether, dried (MgSO4) and concentrated to give the crude
product (61 mg). Chromatography on silica (22 g) eluting with
benzene–ether–acetic acid (46:3:1) gave 6-methoxy-1,2,3,4,4a,
10a-hexahydrophenanthrene-4-carboxylic acid 32 (27 mg, 83%)
(Found: C, 74.2; H, 7.1. C16H18O3 requires C, 74.4; H, 7.0%)
Continued elution of the column gave the desired hydroxy
ester (52 mg, 24%); δH 1.77–2.29 (m, 6H), 3.64 (3H, s), 3.79 (3H,
s), 3.97 (1H, t, J 7), 4.66 (2H, s, benzylic-H), 6.30 (1H, d, J 15,
olefinic-H), 6.77 (1H, d, J 9.0, Ar-H), 6.86 (1H, s, Ar-H), 6.91
(1H, m, olefinic-H), 7.25 (1H, m, Ar-H), 7.55 (3H, m, Ar-H)
and 7.86 (2H, m, Ar-H). This compound was not further
characterised.
Intramolecular Diels–Alder addition of 2e
The aldehydo acid 13a (114 mg, 0.27 mmol) was dissolved in
freshly distilled acetic anhydride (5.5 ml) and heated at reflux
(0.5 h) under argon. The solvent was removed under reduced
pressure with heating, and chromatography on silica (32 g) elut-
ing with benzene–ether (23:2) gave initially the exo-6-methoxy-
12-oxo-10-phenylsulfonyl-2,3,4,9,10,10a-hexahydro-1H-9,4a-
(epoxymethano)phenanthrene 4e (74 mg, 68%), mp 231.5–
233.0 ЊC (methanol–dichloromethane) (Found: C, 66.2; H, 5.6;
S, 8.3. C22H22O5S requires C, 66.3; H, 5.5; S, 8.0%); νmax(film)/
cmϪ1 1745; δH (400 MHz) 1.14 (1H, qd, J 13.0 and 2.5), 1.24
(1H, m), 1.68 (2H, m), 1.87 (3H, m), 2.14 (1H, ddd, J 12.5, 6.0
and 4.0, endo-methine), 2.57 (1H, br d, J 11.0), 3.62 (1H, dd, J
3.0 and 6.0, exo-methine), 3.84 (3H, s, OMe), 5.58 (1H, d, J 3.0,
bridgehead methine), 6.85 (2H, m, Ar-H), 7.31 (1H, d, J 8.0,
Ar-H), 7.60 (2H, m, SO2Ph), 7.70 (1H, m, SO2Ph) and 7.84 (2H,
m, SO2Ph); m/z 398 (Mϩ), 214, 213, 212, 198, 184, 171, 141, 128
and 77 (7.8, 17.3, 100.0, 10.0, 5.0, 5.0, 31.4, 7.3, 6.8 and 6.5%).
Further elution of the column gave the endo-chain adduct 3e
(17.5 mg, 16%), mp 116.0–118 ЊC (dichloromethane–methanol)
(Found: Mϩ, 398.1200. C22H22O5S requires Mϩ, 398.1188);
νmax(film)/cmϪ1 1760; δH (400 MHz) 0.78 (1H, qd, J 13.0 and 3.0),
1.33 (1H, m), 1.57 (1H, m), 1.73 (2H, m), 1.87 (1H, m), 2.05
(1H, td, J 14.0 and 5.0), 2.33 (1H, ddd, J 12.0, 5.5 and 3.5, exo-
methine), 2.47 (1H, br d, J 14.0), 2.94 (1H, dd, J 5.5 and 1.0,
endo-methine), 3.82 (3H, s, OMe), 5.81 (1H, d, J 0.5, bridge-
head methine), 6.78 (1H, dd, J 8.0 and 2.5, Ar-H), 6.95 (1H, d,
J 2.5, Ar-H), 7.22 (1H, d, J 8.0, Ar-H), 7.62 (2H, m, SO2Ph),
7.72 (1H, m, SO2Ph) and 7.99 (2H, m, SO2Ph); m/z 398 (Mϩ),
229, 214, 213, 212, 201, 171, 92, 91 and 77 (6.8, 38.7, 30.9,
100.0, 14.2, 31.2, 36.8, 51.9, 66.7 and 24.4%).
mp 195.0–197.5 ЊC (dichloromethane–light petroleum); νmax
-
(Nujol)/cmϪ1 2860 and 1685; δH (400 MHz) 1.47 (2H, m), 1.68
(1H, td, J 13.0 and 3.0), 1.83 (1H, m), 1.90 (2H, br d, J 13.0),
2.16 (1H, qd, J 13.0 and 3.5), 2.53 (1H, dq, J 13.0 and 3.0,
methine-H), 2.84 (1H, br d, J 13.0), 3.88 (3H, s, OMe), 5.80
(1H, dd, J 2.5 and 9.5, olefinic-H), 6.40 (1H, dd, J 3.0 and 9.5,
olefinic-H), 6.82 (1H, dd, J 2.5 and 8.5, Ar-H) and 7.05 (2H, m,
Ar-H); the CO2H signal was not recorded; m/z 258 (Mϩ), 214,
213, 212, 171, 149, 143, 141, 125 and 113 (31.5, 23.3, 100.0,
30.8, 52.4, 18.7, 35.9, 16.3, 31.3 and 15.0%).
Desulfurisation of adduct 3e
To a solution of the sulfone 3e (25 mg, 0.063 mmol) was added
anhydrous disodium orthophosphate (45 mg, 4 equiv., 0.03
mmol), dry methanol (1.5 ml) and dry distilled THF (1.5 ml).
The flask was cooled to 0–5 ЊC (ice–water), pulverised 5%
sodium–amalgam (65 mg) was added, and the reaction stirred
under argon (2 h) after being allowed to rise to room temper-
ature. The product was poured into water, acidified to pH 1
with hydrochloric acid (2 mol dmϪ3), extracted into ether, dried
(MgSO4) and concentrated to give the crude product. Chroma-
tography on silica (20 g) eluting with benzene–ether–acetic
acid (44:5:1) gave the (4aS,10aS)-1,1-dimethyl-6-methoxy-
1,2,3,4,4a,10a-hexahydrophenanthrene-4a-carboxylic acid 35
(4.8 mg, 30%) (Found: Mϩ, 258.1252. C16H18O3 requires Mϩ,
258.1256); νmax(film)/cmϪ1 2920 and 1690; δH (400 MHz) 1.25
(2H, m), 1.40 (1H, m), 1.55 (3H, m), 1.86 (1H, m), 2.23 (1H, br
s), 2.95 (1H, br s, exo-methine), 3.80 (3H, s, OMe), 5.83 (1H,
dd, J 10.0 and 5.0, olefinic-H), 6.37 (1H, d, J 10.0, olefinic-H),
6.75 (1H, dd, J 8.0 and 2.5, Ar-H), 6.89 (1H, d, J 2.0, Ar-H)
and 7.02 (1H, d, J 8.0, Ar-H); the CO2H signal was not
recorded; m/z 258 (Mϩ), 214, 213, 212, 184, 172, 171, 141, 128
and 115 (30.0, 23.7, 100.0, 36.1, 11.5, 10.4, 54.0, 13.1, 17.4 and
14.6%).
Intramolecular Diels–Alder addition of 2f
In the same way as described above, 2f, generated by acetic
anhydride dehydration of 13b, gave endo- and exo-1,1-dimethyl-
6-methoxy-12-oxo-10-phenylsulfonyl-2,3,4,9,10,10a-hexahydro-
9,4a-(epoxymethano)phenanthrene 3f and 4f. The exo-chain
adduct 4f (32.3 mg, 60%) mp 158.5–160.0 ЊC (EtOH) (Found:
C, 67.5; H, 6.3; S, 7.5. C24H26O5S requires C, 67.6; H, 6.1; S,
7.5%); νmax(film)/cmϪ1 1750; δH (300 MHz) 0.73 (3H, s, Me), 0.88
(3H, s, Me), 1.28 (1H, m), 1.53 (1H, m), 1.75 (1H, m), 1.84 (1H,
Further elution of the column gave the (4aS,10aS)-1,1-
dimethyl-6-methoxy-10-phenylsulfonyl-1,2,3,4,4a,9,10,10a-
octahydrophenanthrene-4a-carboxylic acid 34 (14.3 mg, 57%)
(Found: Mϩ, 400.1335. C22H24O5S requires Mϩ, 400.1344);
νmax(film)/cmϪ1 3050 and 1700; δH (400 MHz) 1.18 (1H, m), 1.32
1934
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
(2H, m), 1.56 (1H, m), 1.67 (1H, m), 1.82 (1H, td, J 13.5 and
3.5), 2.23 (1H, m), 2.62 (1H, br d, J 14.0), 2.83 (1H, m, exo-
methine), 2.86 (1H, dd, J 16.5 and 6.0, benzylic-H), 3.31 (1H,
dd, J 16.5 and 13.0, benzylic-H), 3.67 (1H, ddd, J 13.0, 6.0 and
2.5, CHSO2Ph), 3.80 (3H, s, OMe), 6.80 (1H, dd, J 8.5 and 2.5,
Ar-H), 6.99 (1H, d, J 2.5, Ar-H), 7.05 (1H, d, J 8.5, Ar-H), 7.62
(3H, m, SO2Ph) and 7.92 (2H, m, SO2Ph); m/z 400 (Mϩ), 259,
258, 214, 213, 212, 172, 171, 78 and 77 (2.0, 19.8, 59.5, 26.1,
100.0, 23.9, 9.9, 35.7, 22.9 and 18.5%).
mg, 4.3 mmol), methanol (8.8 ml) and water (2.8 ml) were
heated at reflux (1.5 h). The mixture was cooled to 0–5 ЊC (ice–
water) and transferred to a separating funnel where ice cold
dilute hydrochloric acid (2 mol dmϪ3) was added. The precipi-
tated acid was extracted into ether (0 ЊC) and immediately
treated with diazomethane. Evaporation of the solvent left an
oil which was dissolved in ether, dried (MgSO4) and concen-
trated to give the crude dimethyl 8-(2-hydroxymethyl-5-methoxy-
phenyl)non-2-enedioate 29 (497 mg, 96%) (Found: Mϩ,
350.1726. C19H26O6 requires Mϩ, 350.1729); νmax(film)/cmϪ1
3470 and 1725; δH (300 MHz, C6D6) 1.11 (3H, m), 1.31 (1H, m),
1.66 (3H, m) 2.02 (1H, m), 3.19 (3H, s, CO2Me), 3.31 (3H, s,
CO2Me), 3.40 (3H, s, OMe), 3.98 (1H, t, J 7.5, methine-H), 4.53
(1H, d, J 12.5, benzylic-H), 4.62 (1H, d, J 12.5, benzylic-H),
5.78 (1H, d, J 15.5, olefinic-H), 5.60 (1H, dd, J 2.5 and 8.5,
Ar-H), 6.94 (1H, td J 7.0 and 15.5, olefinic-H), 7.07 (1H, d, J
8.5, Ar-H) and 7.23 (1H, apparent s, Ar-H); the OH signal was
not recorded; m/z 350 (Mϩ), 258, 213, 177, 161, 159, 149, 137,
121 and 91 (3.8, 33.7, 44.4, 65.6, 44.1, 34.1, 31.1, 100.0, 47.8 and
37.8%).
Desulfurisation of the adduct 4f
To a solution of the sulfone 4f (23 mg, 0.054 mmol) was added
anhydrous disodium orthophosphate (42 mg, 4 equiv., 0.22
mmol), dry methanol (1.5 ml) and dry distilled THF (1.5 ml).
The flask was cooled to 0–5 ЊC (ice–water), pulverised 5%
sodium–amalgam (60 mg) was added, and the reaction stirred
under argon (18 h). The product was poured into water, acidi-
fied to pH 1 with hydrochloric acid (2 mol dmϪ3), extracted
into ether, dried (MgSO4) and concentrated to give the crude
product (23 mg). Chromatography on silica (35 g) eluting with
benzene–ether–acetic acid (93:5:2) gave the (4aS,10aR)-1,1-
dimethyl-6-methoxy-1,2,3,4,4a,10a-hexahydrophenanthrene-4a-
carboxylic acid 33 (12.8 mg, 83%) mp 208–210 ЊC (dichloro-
methane–ethanol) (Found: C, 75.5; H, 7.8. C18H22O3 requires C,
75.7; H, 7.7%); νmax(Nujol)/cmϪ1 2880 and 1685; δH (300 MHz)
0.96 (3H, s, Me), 1.04 (3H, s, Me), 1.40 (3H, m), 1.80 (2H, m),
2.56 (1H, t, J 2.0), 2.97 (1H, d, J 12.5), 3.79 (3H, s, OMe), 6.11
(1H, dd, J 2.5 and 9.5, olefinic-H), 6.60 (1H, dd, J 3.5 and 9.6,
olefinic-H), 6.74 (1H, dd, J 2.4 and 8.3, Ar-H), 6.91 (1H, d, J
2.2, Ar-H) and 7.04 (1H, d, J 8.3, Ar-H); the CO2H signal was
not recorded; m/z 286 (Mϩ), 242, 241, 204, 202, 185, 172, 171,
128 and 115 (33.7, 30.4, 38.1, 40.5, 18.7, 15.0, 24.2, 100.0, 17.9
and 13.9%).
Swern oxidation of 29
To a stirred solution of DMSO (342 mg, 4.4 mmol) in dry
dichloromethane (4 ml) was added oxalyl chloride (278 mg, 2.2
mmol) in CH2Cl2 (4 ml) at Ϫ78 ЊC with stirring under argon.
The solution was stirred (4 min) then the alcohol 29 added
dropwise (510 mg, 1.46 mmol) in CH2Cl2 (6 ml) and the flask
washed with CH2Cl2 (1.5 ml). After stirring (0.75 h), triethyl-
amine (1.0 ml) was added and the mixture stirred at Ϫ78 ЊC (10
min) then allowed to reach room temperature, poured onto ice
and diluted with ether. The organic layer was washed with
dilute HCl and then water, dried (MgSO4) and concentrated
to give an oil. Chromatography on silica (35 g) eluting with
benzene–ether (9:1) gave dimethyl 8-(2-formyl-5-methoxy-
phenyl)non-2-enedioate 30 as an oil (448 mg, 88%) (Found: C,
65.4; H, 6.6. C19H24O6 requires C, 65.5; H, 6.9%); νmax(film)/
cmϪ1 1715 and 1680; δH (300 MHz) 1.33 (2H, m), 1.48 (2H, m),
1.74 (1H, m), 2.15 (3H, m), 3.66 (3H, s, CO2Me), 3.72 (3H, s,
CO2Me), 3.88 (3H, s, OMe), 4.85 (1H, t, J 7.5, methine-H), 5.79
(1H, d, J 15.5, olefinic-H), 6.93 (3H, m, olefinic-H and 2 ×
Ar-H), 7.77 (1H, d, J 8.0, Ar-H) and 10.05 (1H, s, CHO); m/z
348 (Mϩ), 298, 229, 213, 211, 190, 189, 162, 161 and 148 (8.4,
32.5, 32.9, 64.2, 32.2, 37.4, 64.7, 30.2, 100.0 and 47.5%).
Wadsworth–Horner–Emmons reaction of aldehyde 11a
To a stirred solution of sodium hydride (108 mg, 2.69 mmol of
a 60% dispersion in mineral oil) in dry 1,2-dimethoxyethane
(DME) (3.0 ml) was added dropwise trimethyl phosphono-
acetate (533 mg, 2.9 mmol) in DME (2.5 ml) at room temp-
erature. The aldehyde 11a (640 mg, 2.44 mmol) in DME (2.5
ml) was added dropwise and the reaction stirred (5 min). The
reaction was quenched with water, diluted with ether and the
organic layer was washed with saturated brine. The ether layer
was separated, dried (MgSO4) and concentrated to give an oil.
Chromatography on silica (60 g) eluting with benzene–ether
(4:1) gave initially a mixture of alcohols produced by intra-
molecular aldolisation (Claisen reaction) of the starting
material (13 mg, 21%) (Found: C, 68.7; H, 7.15. C15H18O4
requires C, 68.7; H, 6.9%); νmax(film)/cmϪ1 3460 and 1720;
δH (300 MHz) 1.08–1.65 (4H, m), 1.89 (1H, m), 2.19 (1H, m),
2.31 (2H, m), 2.47 (1H, m), 3.84 (3H, s, OMe), 4.21 (1H, m,
CHOH), 5.24 (1H, d, J 14.0, benzylic-H), 5.53 (1H, d, J 14.0,
benzylic-H) and 6.83 (1H, dd, J 2.5 and 8.0, Ar-H) and 7.10
(2H, m, Ar-H); m/z 262 (Mϩ), 199, 191, 163, 159, 147, 145, 121,
91 and 32 (100.0, 48.7, 38.9, 32.7, 23.9, 32.0, 61.2, 23.7, 24.4 and
32.5%).
Further elution of the column gave the methyl 7-(6-methoxy-
3-oxochroman-4-yl)hept-2-enoate 28 (489 mg, 63%) (Found:
Mϩ, 318.1476. C18H22O5 requires Mϩ, 318.1467); νmax(film)/cmϪ1
1720; δH (300 MHz) 1.53 (4H, br s), 1.85 (1H, m), 1.97 (1H, m),
2.22 (2H, d, J 5), 3.55 (1H, t, J 7.0, methine-H), 3.72 (3H, s,
CO2Me), 3.82 (3H, s, OMe), 5.20 (1H, d, J 14, benzylic-H), 5.38
(1H, d, J 14.0, benzylic-H), 5.81 (1H, d, J 15.5, olefinic-H), 6.71
(1H, d, J 2.0, Ar-H), 6.82 (1H, dd, J 2.0 and 8.5, Ar-H), 6.94
(1H, dt, J 15.5 and 7.0, olefinic-H) and 7.13 (1H, d, J 8.5, Ar-
H); m/z 318 (Mϩ), 258, 213, 177, 149, 57, 55, 43, 41 and 40 (18.7,
53.3, 48.5, 100.0, 79.7, 69.9, 58.9, 68.7, 62.0 and 67.9%).
Selective hydrolysis of 30
Compound 30 (38 mg, 0.11 mmol) was dissolved in methanol
(1.1 ml), containing potassium carbonate (60 mg, 0.44 mmol)
and water (0.3 ml) and stirred at room temperature (17 h).
Hydrochloric acid (2 mol dmϪ3) was added to reach pH 1 and
the precipitated acid extracted into CH2Cl2. The organic layer
was separated, dried (MgSO4) and concentrated to give the
crude acid. Chromatography on silica (32 g) eluting with
benzene–ether–acetic acid (45:5:1) gave 1-methyl hydrogen
8-(2-formyl-5-methoxyphenyl)non-2-enedioate 31 as an oil (33
mg, 90%) (Found: Mϩ, 334.1478. C18H22O6 requires Mϩ,
334.1421); νmax(film)/cmϪ1 3100 and 1740–1650; δH (300 MHz)
1.40 (4H, m), 1.75 (1H, m), 2.17 (3H, m), 3.72 (3H, s, CO2Me),
3.89 (3H, s, OMe), 4.76 (1H, t, J 7.0, methine-H), 5.78 (1H, d, J
15.5, olefinic-H), 6.96 (3H, m, olefinic-H and 2 × Ar-H), 7.76
(1H, d, J 8.5, Ar-H) and 9.99 (1H, s, CHO); the CO2H signal
was not recorded; m/z 334 (Mϩ), 214, 213, 212, 211, 189, 171,
162, 161 and 148 (0.5, 26.4, 100.0, 35.8, 26.5, 44.2, 27.9, 26.4,
82.8 and 32.8%).
Intramolecular Diels–Alder addition of 2g
The aldehydo acid 31 (25 mg, 0.075 mmol) was dissolved in dry
distilled acetic anhydride and heated at reflux (1 h). The solvent
was removed under reduced pressure with heating, and chrom-
atography on silica (45 g) eluting with benzene–ether (23:2)
gave initially the exo-methyl 6-methoxy-12-oxo-2,3,4,9,10,10a-
Preparation of the alcohol 29
The ester 28 (470 mg, 1.48 mmol), potassium carbonate (588
J. Chem. Soc., Perkin Trans. 1, 1997
1935

View Article Online
hexahydro-9,4a-(epoxymethano)phenanthrene-10-carboxylate 4g
(17 mg, 72%) (Found: Mϩ, 316.1426. C18H20O5 requires Mϩ,
316.1461); νmax(film)/cmϪ1 1740; δH (300 MHz) 1.28 (2H, m),
1.90 (5H, m), 2.13 (1H, br d, J 12.5), 2.57 (1H, br d, J 12.5),
3.00 (1H, dd, J 3.5 and 5.5), 3.62 (3H, s, CO2Me), 3.81 (3H, s,
OMe), 5.69 (1H, d, J 3.5, bridgehead methine), 6.76 (1H, dd, J
2.0 and 8.0), 6.81 (1H, br s) and 7.21 (1H, d, J 8.0); m/z 316
(Mϩ), 272, 214, 213, 212, 171, 161, 141, 128 and 125 (29.6, 38.6,
32.8, 100.0, 43.1, 46.8, 16.1, 17.6, 20.0 and 17.7%).
(Found: C, 71.5; H, 7.9. C19H26O4 requires C, 71.6; H, 8.2%);
νmax(film)/cmϪ1 1731; δH (300 MHz) 1.18 (3H, t, J 7), 1.25–2.10
(8H, m, side chain), 4.0–4.18 (7H, m, ethylene acetal, CH2CH3
and benzylic-H), 4.93 (2H, m, methylene-H), 5.75 (1H, m,
methine-H), 6.07 (1H, s, acetal-H) and 7.22–7.58 (4H, m, Ar-
H); m/z 318 (Mϩ), 317, 273, 175, 149, 91 and 73 (1, 2, 4, 6, 100,
19 and 17%).
Hydrolysis of the ethyl ester 17
Further elution of the column gave the endo-chain adduct 3g
(5.0 mg, 21%) (Found: Mϩ, 316.1469); νmax(film)/cmϪ1 1745;
δH (300 MHz) 0.80 (1H, m), 1.27 (1H, m), 1.43 (1H, m), 1.76
(2H, m), 1.89 (1H, m), 2.15 (1H, td, J 13.0 and 4.5), 2.31 (1H, d,
J 5.0), 2.49 (2H, m), 3.81 (3H, s, CO2Me), 3.84 (3H, s, OMe),
5.79 (1H, s, bridgehead methine), 6.79 (1H, d, J 2.0, Ar-H), 7.00
(1H, s, Ar-H), 7.25 (1H, s, Ar-H); m/z 316 (Mϩ), 272, 214, 213,
212, 184, 171, 141, 128 and 115 (12.4, 50.0, 40.5, 100.0, 52.3,
19.9, 56.4, 20.6, 25.3 and 23.0%).
The ethyl ester (50 mg, 0.16 mmol), methanol (2 ml), potassium
carbonate (45 mg, 0.32 mmol, 2 equiv.) and water (1 ml) were
refluxed under argon (2 h). Most of the methanol was removed
on a rotary evaporator and the residue acidified to pH 1 using
2  hydrochloric acid. The precipitated acid was extracted
into dichloromethane, the organic layer washed with saturated
aqueous sodium hydrogen carbonate and the aqueous layer
carefully acidified using 2  hydrochloric acid. The acid was
extracted from the aqueous layer with ether, the ethereal
extracts dried (MgSO4) and evaporated under reduced pressure
to give the 2-(2-formylphenyl)hept-6-enoic acid 19 as a colour-
less oil (25 mg, 58%); νmax(film)/cmϪ1 3690–2290 (OHbr) and
1713; δH (300 MHz) 1.25–2.16 (6H, m, side chain), 4.03–4.23
(5H, m, acetal and benzylic-H), 4.94 (2H, m, methylene-H),
5.74 (1H, m, methine-H), 6.02 (1H, s, acetal-H) and 7.26–7.56
(4H, m, Ar-H); m/z 276 (Mϩ), 275, 149, 91 and 73 (3, 5, 100,
31 and 20%).
Synthesis of the ethyl ester 15
Ethyl o-formylphenylacetate (300 mg, 1.5 mmol), ethylene
glycol (2.42 g, 37 mmol, 25 equiv.), trimethyl orthoformate (795
mg, 7.5 mmol, 5 equiv.) and a catalytic amount of toluene-p-
sulfonic acid (5 mg) were refluxed in dry benzene (15 ml) using a
Dean–Stark trap for 2 h. The reaction mixture was poured into
saturated aqueous hydrogen sodium carbonate and extracted
with ether (3 × 15 ml). The extracts were washed with brine and
then water, dried (MgSO4) and evaporated under reduced pres-
sure to give a pale yellow oil. Chromatography on silica (60 g)
eluting with light petroleum–ether (7:3) gave the ethyl 2-[2-(1,3-
dioxolan-2-yl)phenylacetate] 15 as a pale yellow oil (220 mg,
63%); νmax(film)/cmϪ1 1733; δH (300 MHz) 1.22 (3H, t, J 7,
CH2CH3), 3.78 (2H, s, benzylic-H), 3.97–4.17 (6H, m, acetal-H
and CH2CH3), 5.94 (1H, s, acetal-H) and 7.23–7.53 (4H, m, Ar-
H); m/z 236 (Mϩ), 235, 191, 149, 119, 91 and 73 (1, 5, 18, 100,
23, 52 and 20%).
Preparation of 13c
A solution of the carboxylic acid 19 (50 mg, 0.8 mmol) and
Se-phenyl benzeneselenosulfonate (53 mg, 0.8 mmol) in dry
degassed benzene (2 ml) was irradiated through Pyrex using a
water-cooled Hanovia UV lamp (125 W) for 10 min at room
temperature. The solvent was evaporated and the residue taken
up in dichloromethane (1 ml); 30% aqueous hydrogen peroxide
(0.5 ml) was added with vigorous stirring at 0 ЊC. After con-
tinued stirring for 30 min at 0 ЊC the reaction mixture was
allowed to warm to room temperature. The solution was
poured into 5% aqueous sodium hydrogen carbonate (3 ml) and
dichloromethane (3 ml) and the layers separated. The organic
layer was then washed with more aqueous sodium hydrogen
carbonate and the aqueous layer acidified using 2  HCl and
the acid taken up into ethyl acetate. The organic layer was
washed with water before drying (MgSO4) and evaporation.
The residue was dissolved in THF (90 ml) and 4  hydrochloric
acid (18 ml), and was stirred overnight before extracting into
ether. The extracts were dried (MgSO4) and evaporated to give
2-(2-formylphenyl)-7-phenylsulfonylhept-6-enoic acid 13c as an
oil (51 mg, 70%); νmax(film)/cmϪ1 3758–3158 (OHbr) and 1698;
δH (300 MHz) 1.47–2.28 [6H, m, (CH2)3 chain], 4.85 (1H, br,
benzylic-H), 6.30 (1H, d, J 14, vinylic-H), 6.93 (1H, td, J 7, 14,
vinylic-H), 7.39–7.87 (9H, m) and 9.00–9.60 (1H, br s, CO2H),
10.13 (1H, s, CHO); m/z 372 (Mϩ), 275, 149, 141 and 91 (5, 20,
100, 51 and 30%).
Synthesis of the alkylated ester 17
Potassium bis(trimethylsilyl)amide in THF (0.5 mol dmϪ3, 0.92
ml, 1.1 equiv.) was added to a stirred solution of the acetal 15
(100 mg, 0.42 mmol) in dry THF (5 ml) at room temperature
under argon. Hexamethylphosphoramide (HMPA) (0.067 ml)
and 5-iodopent-1-ene (90 mg, 0.46 mmol) were added and the
mixture stirred (20 h). The reaction mixture was quenched with
water and extracted with ether. The ethereal extracts were
washed with saturated aqueous ammonium chloride and then
water, dried (MgSO4) and evaporated under reduced pressure to
give a yellow oil. Chromatography on silica (25 g) eluting with
light petroleum–ether (3:1) gave the ethyl 2-[2-(1,3-dioxolan-2-
yl)phenyl]hept-6-enoate 17 (69 mg, 54%) (Found: Mϩ, 304.1662.
C18H24O4 requires Mϩ, 304.1674); νmax(film)/cmϪ1 1725 (s);
δH (300 MHz) 1.20 (3H, t, J 7), 1.28–2.20 (6H, m, side chain),
3.96–4.18 (7H, m, ethylene acetal, CH2CH3 and benzylic-H),
4.97 (2H, m, methylene-H), 5.98 (1H, m, methine-H), 6.10 (1H,
s, acetal-H) and 7.20–7.6 (4H, m, Ar-H); m/z 304 (Mϩ), 303,
275, 169, 149, 115, 91, 73 and 45 (1, 8, 4, 31, 30, 29, 49, 21 and
37%).
Preparation of acid 13d
Starting with ester 16 this involved a modified sequence of the
reactions used to make 13c from 17, but very similar conditions
for the individual steps. The ethyl ester 16 gave the ethyl ester of
21 which was hydrolysed first with dilute acid and then with
K2CO3–MeOH–H2O to give the 2-(2-formylphenyl)-8-phenyl-
sulfonyloct-7-enoic acid 13d (37% over 3 steps) (Found: Mϩ,
386.1726. C21H22O5S requires M, 386.1725); νmax(film)/cmϪ1
2500–3600 (br), 2210, 1710 and 1690; δH (300 MHz) 1.20–2.28
(4H, m), 1.75 (1H, m), 2.18 (3H, m), 4.72 (1H, br, benzylic-
H), 6.30 (1H, d, J 14, vinyl sulfone), 6.95 (1H, dt, J 14 and
7.4, vinyl sulfone), 7.4–7.68 (6H, m, Ar-H), 7.79–7.98 (3H, m,
Ar-H) and 10.1 (1H, br s, CHO); the CO2H signal was not
recorded; m/z 386 (Mϩ), 362, 244, 141 and 77 (8, 21, 26, 60
and 100%).
Synthesis of the alkylated ester 16
Potassium bis(trimethylsilyl)amide in THF (0.5 mol dmϪ3, 42
ml, 1.1 equiv.) was added to a stirred solution of the acetal 15
(3.1 g, 15 mmol) in dry THF (120 ml) at room temperature
under argon. HMPA (4 ml) and 6-iodohex-1-ene (3.6 g, 17
mmol) were added and the mixture stirred (20 h). The reaction
mixture was quenched with water, extracted with ether, the
ethereal extracts washed with saturated aqueous ammonium
chloride and then water, dried (MgSO4) and evaporated under
reduced pressure to give a yellow oil. Chromatography on silica
(125 g) eluting with light petroleum–ether (3:1) gave the ethyl
2-[2-(1,3-dioxolan-2-yl)phenyl]oct-7-enoate 16 (2.86 g, 60%)
1936
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
Intramolecular Diels–Alder addition of 2d
(Found: Mϩ, 380.0752. C18H20O5S2 requires Mϩ, 380.0742);
The foregoing aldehydo acid 13d (50 mg, 0.13 mmol) and
freshly distilled acetic anhydride (1 ml) were boiled under reflux
(0.5 h) under argon. The solvent was removed under reduced
pressure with heating on a steam bath. Chromatography on
silica (25 g) eluting with light petroleum–ethyl acetate (7:3)
gave initially the exo-8-methoxy-11-oxo-4-phenylsulfonyl-
1,2,3,3a,4,5-hexahydro-9b,5(epoxymethane)benz[e]indene 4d (17
mg, 38%), mp 216–218 ЊC (ethanol) (Found: C, 67.4, H, 4.6.
C19H18O4S requires C, 67.7, H, 5.0%); νmax(Nujol)/cmϪ1 1745;
δH (300 MHz) 1.20 (1H, m), 1.70 (1H, m), 1.85 (1H, m), 2.25
(2H, m), 2.30 (1H, m), 2.62 (1H, m), 3.72 (1H, dd, J 2, 5), 5.75
(1H, d, J 3, bridgehead methine) and 7.29–7.85 (9H, m, Ar-H);
m/z 354 (Mϩ), 169, 141, 115 and 77 (1, 100, 44, 14 and 23%).
Further elution of the column gave the endo-chain adduct 3d
(22 mg, 48%), mp 105–107 ЊC (dichloromethane–methanol)
(Found: C, 67.5, H, 5.1. C19H18O4S requires C, 67.7, H, 5.0%);
νmax(Nujol)/cmϪ1 1750; δH (300 MHz) 0.74 (1H, m), 1.22 (1H,
m), 1.66 (1H, m), 1.91 (2H, m), 2.30 (1H, m), 2.56 (1H, m), 3.06
(1H, d, J 7), 6.01 (1H, d, J 3, bridgehead methine) and 7.24–
7.97 (9H, m, Ar-H); m/z 354 (Mϩ), 169, 141, 115 and 77 (1, 100,
50, 17 and 21%).
νmax(film)/cmϪ1 1625, 1360 and 1145; δH (300 MHz) 1.90 (2H,
quintet, J 7), 2.37 (2H, q, J 7), 2.45 (3H, s), 4.05 (2H, t, J 7),
6.30 (1H, d, J 14, vinyl sulfone), 6.87 (1H, m, vinyl sulfone),
7.38 (2H, d, J 7, Ar-H), 7.60 (3H, m, Ar-H), 7.75 (2H, m,
Ar-H), 7.85 (2H, m, SO2Ph); m/z 380 (Mϩ), 244, 195, 143, 125,
84 and 77 (1, 12, 44, 34, 76, 100 and 99%).
With sodium iodide (2.55 mmol) in boiling acetone (15 ml)
over 20 h the foregoing toluene-p-sulfonate (1.02 mmol) gave,
after the usual work up and chromatography on silica in light
petroleum–ether (1:1), 5-iodo-1-phenylsulfonylpent-1-ene as a
colourless oil (260 mg, 76%) (Found: Mϩ, 335.9681. C11H13IO2S
requires Mϩ, 335.9697); νmax(film)/cmϪ1 1620; δH (300 MHz)
1.98 (2H, quintet, J 7), 2.39 (2H, q, J 7), 3.16 (2H, t, J 7), 6.42
(1H, d, J 14, vinyl sulfone), 6.94 (1H, m, vinyl sulfone), 7.52–
7.89 (5H, m, SO2Ph); m/z 336 (Mϩ), 209, 141, 125 and 77 (1,
100, 15, 65 and 60%).
Alkylation of ethylene acetal 15 with 7d
To a stirred solution of the ester 15 (100 mg, 0.42 mmol) in dry
THF (5 ml) at 0 ЊC under argon was added potassium bis(tri-
methylsilyl)amide in THF (0.5 mol dmϪ3, 0.92 ml) and the mix-
ture was stirred for 10 min. HMPA (0.1 ml) was added followed
immediately by the iodide 7d (156 mg, 0.46 mmol). The mix-
ture was allowed to warm to room temperature before being
quenched with water and extracted into ether. The organic layer
was washed with 2  hydrochloric acid and then water, dried
(MgSO4) and concentrated under reduced pressure. The acetal
was not isolated but was cleaved to the aldehyde as follows. The
acetal in THF (1 ml), water (1 ml) and 2  hydrochloric acid (1
ml), were stirred under argon (2 h), extracted into ether and
washed with water, dried (MgSO4) and evaporated under
reduced pressure to give an orange oil. Chromatography on
silica (25 g) in benzene–ether (9:1) gave the impure cyclo-
propane derivative 26 as a pale yellow oil (8 mg, 4%); νmax(film)/
cmϪ1 1738 and 1700; δH (300 MHz) Ϫ0.03 (1H, m), 0.165 (1H,
m), 0.30–0.35 (2H, m), 1.15 (1H, m), 1.21 (3H, t, J 7.0), 2.04
(1H, m), 3.22 (1H, dd, J 5, 14.5), 3.35 (1H, dd, J 14.5, 5.5), 4.1–
4.2 (2H, m, CO2CH2CH3), 5.23 (1H, d, J 8.0), 7.3–7.9 (9H, m,
Ar-H) and 10.31 (1H, s, CHO); the COSY spectrum established
coupling of the protons at the following resonances: δ 5.23 to
2.04; 2.04 to 5.23, 3.22, 3.35 and 1.15; 1.15 to 2.04, 0.3–0.5,
0.165 and Ϫ0.03; m/z 527 (Mϩ), 389, 258, 184, 118 and 77 (1,
37, 36, 46, 77 and 100%). Further elution of the column gave
Synthesis of 5-iodo-1-phenylsulfonylpent-1-ene
Pent-4-en-1-ol (4.5 g, 52 mmol), tert-butyldimethylsilyl chloride
(8.66 g, 57 mmol) and imidazole (3.5 g, 52 mmol) in dimethyl-
formamide (180 ml) were stirred together under argon at room
temperature (20 h). After aqueous work up, chromatography on
silica (150 g) in light petroleum (60–80 ЊC) gave the silyl ether
(8.92 g, 86%); δH (300 MHz) 0.06 (6H, s), 0.90 (9H, s), 1.62
(2H, q, J 7), 2.12 (2H, q, J 7), 3.63 (2H, t, J 6), 5.04 (2H, m,
methylene-H) and 5.83 (1H, tdd, J 7 and 14); m/z 143, 113, 101
and 85 (55, 13, 10 and 8%).
To a degassed solution of the protected alcohol (300 mg, 1.5
mmol) in dry carbon tetrachloride (10 ml) was added
PhSeSO2Ph (668 mg, 2.2 mmol). This solution was irradiated
through Pyrex (15 min) using a water cooled Hanovia lamp
(125 W) placed 5 cm away from the side of the flask. The sol-
vent was removed under reduced pressure and the yellow resi-
due was taken up into dichloromethane (6 ml), cooled to 0 ЊC
and aqueous hydrogen peroxide (30%, 6 ml) added with vigor-
ous stirring. After 30 min the reaction mixture was allowed to
warm to room temperature and poured into a 5% aqueous
sodium hydrogen carbonate (5 ml)–dichloromethane (3 ml)
mixture. The organic phase was washed with more aqueous
sodium hydrogen carbonate and then water, dried (MgSO4) and
evaporated under reduced pressure to give an oil. Chrom-
atography on silica, eluting with light petroleum–ether (7:3)
gave 5-tert-butyldimethylsilyloxy-1-phenylsulfonylpent-1-ene as
a colourless oil (390 mg, 79%); νmax(film)/cmϪ1 1632, 1318 and
1156; δH (300 MHz) 0.01 (6H, s), 0.86 (9H, s), 1.66 (2H, q, J 7),
2.33 (2H, q, J 7), 3.59 (2H, t, J 6), 6.32 (1H, d, J 15), 7.02 (1H,
td, J 7 and 14), 7.55 (3H, m, SO2Ph) and 7.87 (2H, d, J 7,
SO2Ph); m/z 339 (Mϩ Ϫ 1), 283, 199 and 135 (10, 100, 6 and
43%).
ethyl
2-(2-formylphenyl)-2-(2-phenylsulfonylcyclopent-1-yl)-
acetate 22 (80 mg, 47%) (Found: Mϩ, 400.1344. C22H24SO5
requires M, 400.1342); νmax(film)/cmϪ1 1733, 1698, 1308 and
1148; δH (C6D6, 300 MHz) 0.73 (3H, t, J 7), 1.75 (3H, m), 2.01
(1H, m), 2.30 (2H, m), 3.22 (1H, m), 3.49 (1H, m), 3.80 (2H, m,
CO2CH2CH3), 5.28 (1H, d, J 10), 6.75 (5H, m, Ar-H), 7.10 (1H,
m, Ar-H), 7.30 (1H, m, SO2Ph), 7.55 (2H, m, SO2Ph) and 9.78
(1H, s, CHO); m/z 400 (Mϩ), 399, 353, 211, 184, 166, 157, 91
and 77 (2, 6, 65, 100, 92, 83, 52, 61 and 90%).
References
The foregoing silyl ether (100 mg, 0.29 mmol), hydrogen
fluoride (40% aqueous, 0.5 ml), dichloromethane (2.5 ml) and
acetonitrile (2.5 ml) were stirred at 20 ЊC under argon (30 min).
After the usual work up, chromatography on silica (30 g) in
light petroleum–ether (3:1) gave 5-hydroxy-1-phenylsulfonyl-
pent-1-ene as a colourless oil (66 mg, 70%); νmax(film)/cmϪ1
3300–3500 (br); δH (300 MHz) 1.72 (2H, quintet, J 7), 2.08 (1H,
s, OH), 2.37 (2H, q, J 7), 3.65 (2H, t, J 6), 6.35 (1H, d, J 14,
vinyl sulfone), 7.01 (1H, m, vinyl sulfone), 7.51–7.61 (3H, m,
SO2Ph) and 7.86 (2H, d, J 7, SO2Ph); 226 (Mϩ), 208, 195, 214,
84 and 77 (2, 13, 16, 52, 100 and 45%).
1 (a) For a preliminary communication of some of these results, see
E. J. Bush, D. W. Jones and F. M. Nongrum, J. Chem. Soc., Chem.
Commun., 1994, 2145; (b) Previous paper in this series, D. W. Jones
and F. M. Nongrum, J. Chem. Soc., Perkin Trans. 1, 1996, 705.
2 W. Oppolzer, Synthesis, 1978, 793; R. L. Funk and K. P. C.
Vollhardt, Chem. Soc. Rev., 1980, 9, 41.
3 T. Kametani, H. Kondoh, M. Tsubuki and H. Honda, J. Chem. Soc.,
Perkin Trans. 1, 1990, 5.
4 J. G. Luis, L. S. Andres and W. Q. Fletcher, Tetrahedron Lett., 1994,
35, 179.
5 S. R. Harring and T. Livinghouse, J. Chem. Soc., Chem. Commun.,
1992, 502.
6 D. W. Jones and G. Kneen, J. Chem. Soc., Perkin Trans. 1, 1976,
1647.
7 R. Hoffmann, C. C. Levin and R. A. Moss, J. Am. Chem. Soc., 1973,
95, 629.
The foregoing alcohol was converted into the toluene-p-
sulfonate in the usual way [tosyl chloride–pyridine, 0 ЊC (24 h)].
After the usual work up, chromatography on silica in light
petroleum–ether (4:1) gave the toluene-p-sulfonate (81%)
J. Chem. Soc., Perkin Trans. 1, 1997
1937

View Article Online
8 F. K. Brown and K. N. Houk, Tetrahedron Lett., 1984, 25, 4609;
K. N. Houk, Y. Li and J. D. Evanseck, Angew. Chem., Int. Ed. Engl.,
1992, 31, 682.
and J. P. Springer, Tetrahedron Lett., 1980, 21, 2625; J.-F. Lavallee
and P. Deslongchamps, Tetrahedron Lett., 1987, 28, 3457.
13 E. Ciganek, Org. React., 1984, 32, 37.
9 D. Craig, D. A. Fischer, O. Kemal, A. Marsh, T. Plessner, A. M. Z.
Slawin and D. J. Williams, Tetrahedron, 1991, 47, 3095.
14 B. J. Hunt and W. Rigby, Chem. Ind. (London), 1967, 1868.
15 D. D. Perrin, W. L. F. Armagego and D. Perrin, The Purification of
Laboratory Chemicals, Pergamon Press, Oxford, 2nd edn., 1980.
10 M. E. Jung, in Comprehensive Organic Synthesis, ed. M. F.
Semmelhack, Pergamon Press, Oxford, 1991, vol. 4, pp. 1–68.
11 T. G. Back and S. Collins, J. Org. Chem., 1981, 46, 3249;
R. A. Cancarz and J. L. Kice, Tetrahedron Lett. 1980, 21, 4155.
12 J. E. Troth, P. R. Hamann and P. L. Fuchs, J. Org. Chem., 1988, 53,
4694; S. J. Danishefsky, K. Vaughan, R. C. Gadwood, K. Tsuzuki
Paper 7/01589E
Received 6th March 1997
Accepted 8th April 1997
1938
J. Chem. Soc., Perkin Trans. 1, 1997