The synthesis of various cycloalkana[d]xanthones and conversion of the cyclohexa-analogue to a 7,7a-dimethylcyclohexa-[d]xanthene

Article abstract of DOI:10.1039/a804365e

The synthesis of cyclo-penta-, -hexa- and -hepta-[d]xanthones 5 from (E)-(2-hydroxyphenyl)-5-arylpent-4-ene-1,3-diones 4, cycloalkanones and pyrrolidine is described. Reactions to modify 5 in an attempt to synthesize analogues of the five naturally occurr

Full text of DOI:10.1039/a804365e

View Article Online / Journal Homepage / Table of Contents for this issue
The synthesis of various cycloalkana[d]xanthones and conversion
of the cyclohexa-analogue to a 7,7a-dimethylcyclohexa-
[d]xanthene†
Roy M. Letcher,* Tai-Yuen Yue, Kwei-Fung Chiu, Avijit S. Kelkar and Kung-Kai Cheung
Department of Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong
Received (in Cambridge) 9th June 1998; Accepted 7th August 1998
The synthesis of cyclo-penta-, -hexa- and -hepta-[d]xanthones 5 from (E)-(2-hydroxyphenyl)-5-arylpent-4-ene-1,3-
diones 4, cycloalkanones and pyrrolidine is described. Reactions to modify 5 in an attempt to synthesize analogues
of the five naturally occurring cyclohexa[d]xanthenes (with general formula 1) are also described: these reactions
include C-methylations at C-7 and C-7a, hydride reduction of the 8-keto group, dehydroxylations and finally catalytic
reduction to give 16. The stereochemistry of 16 established by NOE and an X-ray crystal structure of 9aB differs
from 1 at two contiguous C-atoms.
From natural sources (fungi and sponges), five cyclohexa[d]-
xanthenes with the general structure 1, have been reported1–5
stereochemistry of ring C is in the most stable arrangement
with both substituents at C-3a and C-4 (in the A series) and
C-4a and C-5 (in the B series), in equatorial positions and
furthermore the trans-hydrogens at C-4a and C-5 (for the
B series) are indicative of these [d] fused xanthones 5 having
been formed firstly by a 4ϩ2 cycloaddition reaction in which
exo-addition had occurred to create ring C, followed by elimin-
ation of pyrrolidine and finally a Michael addition of the
phenolic hydroxy to the resulting αβ-unsaturated ketone to give
the heterocyclic ring B as shown in Scheme 1. The latter process
can potentially occur via attack of the hydroxy from either
the top or bottom face of ring C, but we appear to have only
isolated adducts in which the D ring is cis-fused. Noting the
polar nature of the reactants in these 4ϩ2 cycloaddition reac-
tions this process is most likely to have occurred in a stepwise
manner and overall the reaction can be considered to have
taken place with inverse electron demand. The procedure for
the synthesis of 5 reported earlier,6 has now been simplified by
replacing the enamine with the unreacted cyclic ketone and
pyrrolidine and carrying out the reaction by mixing all three
reactants in refluxing dichloromethane. Using this procedure,
reactants 4(a–c) with cyclo-pentanone and -hexanone gave
slightly improved yields of the corresponding compound 5 and
furthermore we have succeeded in making 5aC, 5bC and 5cC
from 4(a–c) and cycloheptanone. The reaction however fails to
give 5D analogues from the reaction of N-(cyclooct-1-en-1-yl)-
pyrrolidine (or cyclooctanone and pyrrolidine) with 4(a–c), and
instead cycloocta[a]xanthones 6aD, 6bD and 6cD are formed,
presumably via rotation of the cyclohexenone ring before ring B
is formed, as described in our earlier communication6 except
that the final elimination of water produces a double bond in
ring C and not in ring D (as in 8) which was observed with
smaller rings (n = 1,2).6 The change in the product formed
is very likely to be due to 6D being the thermodynamically
preferred product because the cyclooctene unit contains two
sp2 centres and thus has much lower strain than the fully
saturated cyclooctane found in 5D.‡ The structures of the 6D
analogues were deduced from their spectra including the infra-
red absorption (at ca. 1641 cmϪ1) for a chromone. Treatment
of 6aD, and 6bD with pyrrolidine in boiling ethanol causes ring
C to readily aromatise giving 7a and 7b respectively.
with several possessing physiological properties. For example,
strongylin A 2,4,5 from the marine sponge Smenospongia hart-
mani, has been found to be active against P388 murine leukemia
tumour cells and the influenza PR-8 strain. The total synthesis
of this tetracyclic ring system including stereochemistry, is
clearly a formidable challenge. We have however briefly
reported6 a one step synthesis of the tetracyclic cyclohexa[d]-
xanthene-7,8-dione 5aB in 62% yield from simple starting
materials viz. the enamine 3B, and the dione 4a which is readily
obtained via a Baker–Venkataraman rearrangement7 of the
ester formed from 2-hydroxyacetophenone and (E)-cinnamoyl
chloride. In this paper the full details and generality of this
cycloalkana[d]xanthone synthesis is reported as well as reac-
tions of 5B which are aimed at synthesising a closer analogue
of 1.
The synthesis of 5aB was first extended to include 4 with
other aromatic substituents viz. b and c, and another enamine,
3A, in reactions which were carried out in boiling ethanol and
required only half a minute (for case A) or five minutes (for case
B). In this way, compounds 5aA, 5bB, 5cA and 5cB were also
obtained and from a comparison of all their spectra, especially
NMR resonances, with those of 5aB, the structure of which
had been established by X-ray crystallography,6 all appeared to
have the same stereochemistry as 5aB. Thus in all cases, the
† Full crystallographic details for crystal 9aB, excluding structure
factor tables, have been deposited at the Cambridge Crystallographic
Data Centre (CCDC). For details of the deposition scheme, see ‘Instruc-
tions for Authors’, J. Chem. Soc., Perkin Trans. 1, available via the RSC
Web page (http://www.rsc.org/authors). Any request to the CCDC for
this material should quote the full literature citation and the reference
number 207/252.
When considering dehydroxylation and C-methylation reac-
tions to transform 5 into an analogue of 1 it is important to
‡ Referees comment.
J. Chem. Soc., Perkin Trans. 1, 1998, 3267–3276
3267

View Article Online
Fig. 1 X-Ray structure of compound 9aB revealing the stereo-
chemistry at C-13a.
iodide gave a monomethylated compound A (62%) and a
dimethyl compound B (2%). This result was obtained on
numerous occasions but on using a certain bottle of thallium()
ethoxide the products were A (65%) and another monoalkyl-
ated product C (21%). Both products A and C have the formula
1
C24H24O3 and their H and 13C NMR spectra (Tables 1 and 2)
reveal that they both possess methyl groups at C-7a and that
they are stereoisomers. Furthermore products A and C exhibit
similar NOE enhancement on irradiating the methyl group: in
both cases only the H-4a and H-6Ј signals are enhanced show-
ing that the methyl group is on the same side as H-4a. Since the
methylation reaction could not directly epimerise C-4a or C-5,
the difference in A and C is clearly due to a difference in C-13a
stereochemistry. As the relative stereochemistry at C-13a could
not be solved by spectroscopic means a single crystal X-ray
determination was carried out on A which revealed its structure
to be 9aB (see Fig. 1), and consequently C must have structure
10a. The only explanation we can offer for the epimerisation at
C-13a is that the somewhat basic thallium() ethoxide must be
responsible for opening the heterocyclic ring prior to methyl-
ation as shown in Scheme 2. Analysis of the methylation reac-
tion which gave 9aB and 10a reveals that it must have occurred
by the more favoured axial attack in both cases. Compound B
with formula C25H26O3 having two methyl groups, one of which
1
is a singlet and the other a doublet in the H NMR spectrum
exhibits NMR spectral data (Tables 1 and 2) suggesting a
6,7a-dimethylxanthone derivative. The 1H NMR signal at δ 3.16
(double quartet) was identified as H-6 since irradiation of the
methyl doublet at δ 0.84 caused the signal to collapse to a doub-
let (J 11.47 Hz). Furthermore the coupling constant of J 11.47
Hz, also observed at δ 2.72 (H-5), indicates that the hydrogen
atoms at C-6 and C-5 are trans to one another. The remaining
parts of the 1H and 13C NMR spectra are very similar to those
of 9aB, rather than to 10a, and therefore we propose struc-
ture 11a for compound B. Furthermore, on irradiating the
singlet methyl NOE enhancement was observed for only the
H-6 and H-4a signals. The thallium() ethoxide/methyl iodide
C-methylation reaction on the analogous tetracyclic xanthones
5aA, 5bB and 5cB also gave crystalline monomethylated
products which from their spectra (see Tables 1 and 2) were
deduced as having structures 9aA, 9bB and 9cB respectively.
A dimethylated derivative, 11c analogous to 11a was also
obtained in low yield (6%) from the methylation of 5cB. An
alternative C-methylation procedure, using lithium diiso-
propylamide (LDA) and hexamethylphosphorous triamide
(HMPT) was also successful in methylating analogues of 5 on
the carbon atom attached to both carbonyl groups: successful
reactions included the conversions of 5aA to 9aA, 5aB to 9aB,
5bB to 9bB, and 5cB to 9cB and in no case was isomer 10 or
dimethyl-derivative 11 observed.
Scheme 1
realize that acids and bases readily convert the [d]xanthone 5
into an [a]xanthone 8 as we reported earlier.6,8 The first step
in converting 5aB into a 7,7a-dimethylcyclohexa[d]xanthene
would therefore have to be a C-methylation reaction (at C-7a)
under neutral conditions to form a non-labile product. Taylor
and McKillop have shown9,10 that on treatment with thallium()
ethoxide, β-diketones form thallium() salts which react with
alkylating agents to give mono-C-alkylation at the dicarbonyl
bearing C-atom. We have found that with thallium() ethoxide,
5aB formed a yellow salt which on treatment with methyl
Compound 9 with two carbonyl functions would be expected
to react with a methyl Grignard reagent, but with only one of
the carbonyls being a ketone, the other being a vinylogous ester,
3268
J. Chem. Soc., Perkin Trans. 1, 1998, 3267–3276

Table 1 1H NMR Spectral data of compounds 9, 10 and 11 recorded at 300 MHz
A, 9aA
9aB
9bB
9cB
C, 10a
B, 11a
11c
7.97 (1 H, dd, J 1.71, 7.81,
Ar-H)
7.49 (1 H, ddd, J 1.71, 7.32,
8.30, Ar-H)
7.97 (1 H, dd, J 1.71, 7.81,
Ar-H)
7.51 (1 H, ddd, J 1.71, 7.32,
8.79, Ar-H)
7.96 (1 H, dd, J 1.71,
7.82, Ar-H)
7.50 (1 H, ddd, J 1.71,
7.32, 8.30, Ar-H)
7.96 (1 H, dd, J 1.71, 7.81,
Ar-H)
7.51 (1 H, ddd, J 1.71, 7.33,
8.30, Ar-H)
7.94 (1 H, dd, J 1.71, 7.82,
Ar-H)
7.48 (1 H, ddd, J 1.71, 7.32,
8.79, Ar-H)
7.98 (1 H, dd, J 1.71, 7.81, 7.97 (1 H, dd, J 1.71, 7.82,
Ar-H) Ar-H)
7.50 (1 H, ddd, J 1.71, 7.33, 7.50 (1 H, ddd, J 1.71, 7.33,
8.31, Ar-H)
8.30, Ar-H)
7.42–7.36 (2 H, m, Ar-H)
7.41–7.38 (2 H, m, Ar-H)
7.39 (1 H, dd, J 0.73,
1.95, Ar-H)
7.25 (1 H, dd, J 0.97, 4.89,
Ar-H)
7.40–7.37 (2 H, m, Ar-H)
7.41–7.24 (5 H, m, Ar-H)
7.27 (1 H, dd, J 1.46, 5.13,
Ar-H)
7.32–7.27 (3 H, m, Ar-H)
7.09–7.03 (1 H, m, Ar-H)
7.37–7.27 (3 H, m, Ar-H)
7.09–6.99 (2 H, m, Ar-H)
7.03 (2 H, m, Ar-H)
6.33 (1 H, dd, J 1.71,
3.18, Ar-H)
7.09–6.96 (3 H, m, Ar-H)
6.92 (1 H, dd, J 1.22, 3.42,
Ar-H)
7.36–7.25 (3 H, m, Ar-H)
7.07–6.97 (2 H, m, Ar-H)
7.08– 6.97 (2 H, m, Ar-H)
3.16 (1 H, qd, J 6.35, 11.47, 6.98 (1 H, m, Ar-H)
H-6)
7.06 (1 H, m, Ar-H)
6.94 (1 H, dd, J 0.49, 8.30,
Ar-H)
3.12 (1 H, t, J 13.43, H-5Ј)
3.31 (1 H, ddd,
12.45, 12.70, H-5)
3.07 (1 H, dd,
13.67, H-6Ј)
J
5.61,
6.14 (1 H, dd, J 0.74,
3.17, Ar-H)
3.45 (1 H, ddd, J 5.86,
12.45, 12.45, H-5)
3.22 (1 H, dd, J 12.45,
14.16, H-6Ј)
3.66 (1 H, ddd,
12.45, 12.45, H-5)
3.10 (1 H, dd,
14.16, H-6Ј)
2.83 (1 H, td, J 2.20, 12.45,
H-4a)
J
5.61,
3.34 (1 H, ddd,
11.47, 13.18, H-5)
2.88 (1 H, dd,
14.40, H-6Ј)
2.52 (1 H, dd, J 4.88, 14.40, 2.09 (1 H, br d, J 13.19)
H-6)
J
4.88,
2.90 (1 H, td, J 2.20, 12.45, 6.97 (1 H, dd, J 3.42, 5.13,
H-4a)
Ar-H)
J
12.94,
J
12.45,
J 13.18, 2.72 (1 H, dd, J 11.47, 12.45, 6.89 (1 H, dd, J 1.22, 3.42,
H-5)
Ar-H)
2.97 (1 H, ddd, J 0.97, 6.10,
11.53, H-3a)
2.91 (1 H, m, H-4a)
3.14–3.01 (2 H, m, H-5, H-6)
2.65 (1 H, ddd,
11.53, 13.43, H-4)
2.46 (1 H, dd, J 5.13, 13.42,
H-5)
J
5.13,
2.52 (1 H, dd, J 5.61, 13.92,
H-6)
2.12 (1 H, m)
2.94 (1 H, m, H-4a)
2.64 (1 H, dd, J 5.61, 14.16,
H-6)
2.11 (2 H, m)
2.32 (1 H, dt, J 3.91, 11.47,
H-4a)
1.93 (1 H, m)
1.95 (1 H, m)
2.85 (1 H, br d, J 7.33, H-4a)
2.50 (1 H, dd, J 5.86,
14.16, H-6)
1.76 (3 H, s, Me)
2.10–2.05 (2 H, m)
2.17–2.00 (2 H, m)
1.92–1.67 (3 H, m)
1.79 (3 H, s, Me)
1.58–1.49 (1 H, m)
1.99 (1 H, m)
1.74 (3 H, s, Me)
1.45 (5 H, m)
2.09 (2 H, m)
1.70 (3 H, s, Me)
1.47–1.26 (6 H, m)
1.70 (3 H, s, Me)
1.57–1.22 (6 H, m)
1.68 (1 H, m)
1.71–1.29 (5 H, m)
1.23 (1 H, br d, J 13.92)
0.84 (3 H, d, J 6.35, Me)
1.72 (3 H, s, Me)
1.61 (3 H, s, Me)
1.59–1.33 (5 H, m)
1.26–1.20 (1 H, m)
1.45–1.42 (5 H, m)
1.28–1.19 (1 H, m)
0.95 (3 H, d, J 5.86, Me)
1.33 (1 H, d, J 14.16)

View Article Online
Table 2 13C NMR chemical shifts of compounds 9, 10 and 11
magnesium iodide gave only one product, with formula C23H26-
O3S (89% yield) revealing mono-methylation, and furthermore
it exhibited a characteristic low field aromatic NMR signal at δH
7.78 (1H, dd, J 1.7 and 7.8 Hz) for chromanones, indicating that
the C-8 carbonyl had not reacted; its stereochemistry was estab-
lished in the following experiment leading to structure 12c
for the Grignard adduct (see Scheme 3). Lithium aluminium
recorded at 75.5 MHz
δC/ppm
A, 9aA 9aB
9bB
9cB
C, 10a B, 11a 11c
C᎐O
204.6
189.8
157.1
141.8
121.0
135.8
129.0
129.0
128.0
127.7
127.7
127.3
121.8
118.2
94.8
204.6 204.3 203.7 209.0
190.3 190.3 190.2 192.5
156.3 156.3 156.2 157.5
142.1 154.1 146.0 142.4
120.9 120.9 120.8 120.7
135.8 141.9 135.8 135.8
129.1 135.8 127.7 129.0
129.1 127.7 126.9 129.0
127.7 121.8 124.8 127.5
127.3 118.0 124.1 127.5
127.3 110.2 121.8 127.1
127.3 106.6 117.9 127.0
206.1
190.5
156.4
141.8
120.9
135.7
129.0
129.0
129.0
127.8
127.8
127.2
121.7
118.0
83.6
61.0
50.1
45.8
40.6
24.7
21.9
20.9
18.8
205.2
190.4
156.3
145.7
120.8
135.8
127.8
126.7
125.8
124.2
121.8
117.9
᎐
sp2-C
sp2-CH
121.8
117.9
83.8
60.8
41.7
39.6
121.6
118.2
87.6
63.5
45.9
43.2
sp3-C
83.3
60.7
38.0
35.1
83.4
60.7
41.4
37.0
83.2
60.9
47.2
45.5
42.3
24.7
22.1
20.8
18.7
57.7
46.9
44.9
sp3-CH
sp3-CH2
45.6
29.6
26.3
20.0
45.7
24.7
21.7
20.9
18.9
19.0
42.5
24.7
22.1
20.8
18.8
18.9
46.8
24.8
21.9
20.8
18.7
19.0
45.2
27.7
25.4
25.3
20.6
15.7
sp3-CH3
21.2
18.9
13.0
19.0
13.0
Scheme 3 Reagents and conditions: i, LDA/MeI/HMPT; ii, MeMgI;
iii, LiAlH4; iv, Et3Si/HNH4F/CF3CO2H; v, H2/Pt.
hydride reduction of 12c gave a crystalline diol in quantitative
yield, which on irradiation of the 7a-methyl signal (at δH 1.12
ppm) resulted in NOE enhancements of the signals at 1.53 ppm
(C-7 methyl), 2.16 ppm (H-6Ј), 2.25 ppm (H-4a) and 5.31
ppm (H-8), showing its structure to be 13c. Similarly 9aB with
methylmagnesium iodide gave 12a which on lithium aluminium
hydride reduction gave 13a.
Scheme 2 Reagents: i, Tl(OEt)/MeI.
some difference in reactivity could be expected; if methylation
of 9B occurred selectively at the C-7 ketone group, this would
result in the desired insertion of the C-7 methyl group which is
present in 1. In the event, treatment of 9cB with excess methyl-
For the dehydroxylation of 13 the ionic hydrogenation
method of Olah et al.11 using triethylsilane, ammonium fluoride
3270
J. Chem. Soc., Perkin Trans. 1, 1998, 3267–3276

View Article Online
and trifluoroacetic acid was employed. Reaction with 13c gave
a quantitative mixture of isomeric products with formula
C23H26OS and complex NMR spectra which included over 40
carbon resonances, and signals for alkene functions viz. at δH
4.82 (d, J 20 Hz), 5.23 (br s) and at δC 107.6 for a terminal
methylene group. The two alkene structures 14c and 15c fit all
the spectral data for the mixture. Similarly 13a yielded a mix-
ture of 14a and 15a. Catalytic hydrogenation (5% Pd on C) of
the mixture of 14a and 15a gave a single crystalline product
16 (C25H30O) with stereochemistry following from an NOE
experiment: irradiation at δH 3.08 ppm (H-5) had no effect on
either of the two methyl groups showing that the two methyl
groups are on the same side as the 5-phenyl group and with the
methyl group at C-7 in the more stable equatorial position.
The stereochemistry of 16 unfortunately differs from the
target 1 in two places, viz. C-13a, C-4a or at C-7, C-7a. In an
attempt to obtain the stereoisomer of 16 with the correct
stereochemistry, we have considered synthesizing the stereo-
isomers of 5 starting from the (Z)-dione 4. An analysis of all
the reactions involved suggests that if (Z)-4 and 3B reacted in a
4ϩ2 cycloaddition reaction in the expected exo-manner to give
a stereoisomer of 5, then assuming that the large aryl group
would again be in the equatorial position in ring C the product
would be epimeric with 5 at both C-13a and C-4a. We also had
reason to believe that the subsequent methylations, beginning
with an axial methylation at C-7, would again give methyl
groups on the same side as the aryl group, and hence the desired
stereoisomer of 16. Unfortunately all our attempts to obtain
(Z)-4 by photolysis of either (E)-cinnamic acid or (E)-4
have been unsuccessful. For example irradiation of a solution
of (E)-4a, followed by pyrrolidine and cyclopentanone yielded
5aA and 6aA.
anhydrous conditions. To the resulting mixture was added 10%
acetic acid (100 cm3) and the yellow solid which precipitated
was filtered, dried and crystallised from ethanol–chloroform
giving yellow needles (6.85 g, 86%) of 4a, mp 131–132.5 ЊC
(lit.12 mp 133–134 ЊC); νmax/cmϪ1 1620 (br); λmax/nm 216 (log
ε 3.9), 264 (3.9), 328 (3.9); m/z 266 (Mϩ, 24%), 131 (100), 121
(53); δH (90 MHz) 12.23 (1 H, s, OH), 7.72–7.33 (8 H, m), 7.01–
6.77 (2 H, m), 6.55 (1 H, d, J 15.8), 6.28 (2 H, s); δC (22.6 MHz)
195.9 (s, CO), 174.5 (s, CO), 162.6 (s), 139.9 (d), 135.7 (d), 135.0
(s), 130.0 (d), 128.9 (d), 128.9 (d), 128.5 (d), 128.0 (d), 128.0 (d),
122.1 (d), 119.1 (s), 119.0 (d), 118.7 (d), 97.0 (d).
(E)-1-(2-Hydroxyphenyl)-5-(2-furyl)pent-4-ene-1,3-dione 4b
Following the procedure described for 4a, 2-hydroxyaceto-
phenone and (E)-3-(2-furyl)acryloyl chloride gave 4b as yellow
needles (90% yield), mp 129–131 ЊC (ethanol–chloroform) (lit.13
mp 122 ЊC); νmax/cmϪ1 1620; m/z 256 (Mϩ, 37%), 121 (100); δH
(90 MHz) 12.24 (1 H, s, OH), 7.68 (1 H, dd, J 1.8, 7.9), 7.54–
7.25 (3 H, m), 6.97–6.79 (2 H, m), 6.65–6.40 (3 H, m), 6.28 (2 H,
s); δC (22.6 MHz) 195.8 (s, CO), 174.3 (s, CO), 162.6 (s), 151.7
(s), 144.8 (d), 135.7 (d), 128.5 (d), 126.2 (d), 120.1 (d), 119.2 (s),
119.0 (d), 118.7 (d), 114.7 (d), 112.6 (d), 97.0 (d).
(E)-1-(2-Hydroxyphenyl)-5-(2-thienyl)pent-4-ene-1,3-dione 4c
Following the procedure described for 4a, 2-hydroxyaceto-
phenone and (E)-3-(2-thienyl)acryloyl chloride gave 4c, as
yellow needles (85% yield), mp 134.5–135.5 ЊC (ethanol–
chloroform) (HRMS: found Mϩ, 272.0509. C15H12SO3 requires
M, 272.0507); νmax/cmϪ1 1625; λmax/nm (log ε) 229 (3.6), 278
(3.6), 328 (3.6); m/z 272 (Mϩ, 73%), 254 (44), 237 (50), 151 (69),
138 (23), 121 (100), 109 (60), 65 (36); δH (90 MHz) 12.23 (1 H, s,
OH), 7.77 (1 H, d, J 17.2), 6.79–7.74 (7 H, m), 6.37 (1 H, d,
J 17.2), 6.27 (2 H, s); δC (22.6 MHz) 195.8 (s, CO), 174.2 (s,
CO), 162.6 (s), 140.6 (s), 135.7 (d), 132.5 (d), 130.6 (d), 128.4
(d), 128.4 (d), 128.3 (d), 121.2 (d), 119.1 (s), 119.0 (d), 118.7 (d),
96.8 (d).
Experimental
General
All melting points were determined with a Kofler hotstage
microscope apparatus and are uncorrected. H NMR (90, 270
1
(4aRS,5SR,13aSR)-5-Phenyl-1,2,3,4,4a,5,6,7,7a,8-decahydro-
benzo[d]xanthene-7,8-dione 5aB
MHz) and 13C NMR (22.6 and 67.9 MHz) spectra were
recorded on JEOL spectrometers, or on a Bruker DPX spec-
trometer at 300 and 75.5 MHz respectively, in CDCl3 and were
referenced against tetramethylsilane; chemical shifts are
reported in ppm on the δ scale, coupling constants (J) are given
in Hz, and multiplicity was determined from off-resonance
decoupled or DEPT spectra. Mass spectra and accurate mass
measurements were recorded on a Finnigan MAT-95 instru-
ment using the EI mode with a direct inlet system and operating
at 70 eV. Infrared spectra were recorded for KBr discs and UV
spectra were recorded in 95% ethanol (ε values are given in dm3
molϪ1 cmϪ1). Column chromatography was carried out using
Merck Kieselgel 60 (70–230 mesh) and thin layer chrom-
atography was performed on precoated silica gel 60 GF254 (E.
Merck 7730) plates (20 cm2) which had been activated at 120 ЊC
for 3 hours. Thallium() ethoxide was obtained from the Aldrich
Chemical Co., UK. All compounds reported were found to be
homogeneous on TLC analysis, and their NMR spectra
revealed no spurious signals.
Compound 4a (1.33 g, 5.00 mmol) and freshly prepared
N-(cyclohex-1-en-1-yl)pyrrolidine 3B (3.82 g, 25.30 mmol) were
heated in refluxing 95% ethanol (50 cm3) for 5 minutes, by
which time all 4a had been consumed as shown by TLC analy-
sis. Ice–water (200 cm3) was added and the reaction mixture
extracted with chloroform (2 × 100 cm3) and the combined
organic extracts were washed with water and dried over
anhydrous magnesium sulfate. Removal of solvent gave an
orange gum which was purified by column chromatography
[elution with light petroleum (40–60 ЊC)–diethyl ether 7:3]
giving orange plates of 5aB (1.1 g, 62%), mp 159–160 ЊC
(ethanol) (HRMS: found Mϩ, 346.1562. C23H22O3 requires M,
346.1568); νmax/cmϪ1 1601; λmax/nm 260 (log ε 4.0), 308 (4.3), 355
(4.2); m/z 346 (Mϩ, 60%), 303 (100), 289 (33); δH (270 MHz)
15.29 (1 H, s, OH), 7.88 (1 H, dd, J 1.71, 7.81), 7.47–7.22 (6 H,
m), 7.06–6.95 (2 H, m), 3.27 (1 H, dd, J 8.8, 8.8, 12.7, H-5), 2.70
(2 H, d, J 8.79), 2.50 (1 H, dd, J 4.64, 12.45), 2.25 (1 H, d,
J 10.99), 2.02–1.89 (1 H, m), 1.66–1.21 (6 H, m); δC (67.9 MHz)
181.2 (s, CO), 180. 6 (s, CO), 158.2 (s), 142.2 (s), 135.2 (d), 128.9
(d), 127.6 (d), 127.6 (d), 127.0 (d), 126.5 (d), 121.4 (d), 120.7 (d),
118.9 (d), 118.0 (d), 109.6 (s), 79.5 (s), 43.2 (d), 39.7 (d), 39.8 (t),
32.5 (t), 22.4 (t), 21.5 (t), 19.4 (t). Compound 5aB (69%) was
also obtained as the only product after heating a mixture of 4a
(5 mmol), pyrrolidine (5 mmol) and cyclohexanone (5 mmol) in
refluxing dichloromethane for 1 h following the procedure for
synthesis of 5cA below.
(E)-1-(2-Hydroxyphenyl)-5-phenylpent-4-ene-1,3-dione 4a
A mixture of 2-hydroxyacetophenone (6.93 g, 50.96 mmol) and
(E)-cinnamoyl chloride (8.49 g, 50.99 mmol) in dry pyridine (5
cm3) was stirred at room temperature for 1 h before heating at
100 ЊC for 0.5 h under anhydrous conditions. The resulting
solution was poured into 0.5 M HCl (350 cm3) containing
crushed ice (200 g) which yielded a solid cinnamate (10.79 g,
81%) as pale brown crystals, mp 69–70 ЊC (ethanol). Potassium
tert-butoxide (6.88 g, 61.4 mmol) was slowly added in small
portions to a magnetically stirred solution of the cinnamate
(7.98 g, 30.0 mmol) in dry pyridine (10 cm3) at 50 ЊC under
(3aRS,4SR,12aSR)-4-Phenyl-2,3,3a,4,5,6,6a,7-octahydro-1H-
cyclopenta[d]xanthene-6,7-dione 5aA
Following the procedure described for 5aB, 4a (1.63 g, 6.13
J. Chem. Soc., Perkin Trans. 1, 1998, 3267–3276
3271

View Article Online
mmol) and freshly prepared N-(cyclopent-1-en-1-yl)pyrrolidine
3A (4.2 g, 30.66 mmol) after 30 s gave 5aA (0.92 g, 45%) as
pale yellow plates, mp 91–92 ЊC (ethanol–chloroform) (HRMS:
found Mϩ, 332.1430. C22H20O3 requires M, 332.1412); νmax/cmϪ1
1601; λmax/nm 262 (log ε 3.9), 308 (4.1), 355 (4.0); m/z 332 (Mϩ,
41%), 303 (50), 290 (92), 289 (100); δH (90 MHz) 15.22 (1 H, s,
OH), 7.89 (1 H, dd, J 7.7, 1.7), 7.53–6.86 (8 H, m), 2.70 (4 H,
m), 2.64–1.37 (6 H, m); δC (22.6 MHz) 181.2 (s, CO), 179.5 (s,
CO), 158.8 (s), 142.3 (s), 135.0 (d), 128.9 (d), 128.9 (d), 127.8
(d), 127.8 (d), 127.0 (d), 126.7 (d), 121.5 (d), 121.3 (s), 118.3 (d),
106.3 (s), 89.6 (s), 48.8 (d), 39.4 (t), 39.3 (d), 37.2 (t), 27.1 (t),
21.3 (t).
(5aRS,6RS,14aSR)-6-Phenyl-2,3,4,5,5a,6,7,8,8a,9-decahydro-
1H-cyclohepta[d]xanthene-8,9-dione 5aC
Following the procedure described for 5cA, 4a (0.50 g, 1.8
mmol), cycloheptanone (0.21 g, 1.8 mmol) and pyrrolidine
(0.13 g, 1.8 mmol) gave 5aC (0.31 g, 48%) as yellow needles, mp
137–138 ЊC (ethanol) (HRMS: found Mϩ, 360.1725. C24H24O3
requires M, 360.1722); νmax/cmϪ1 1605; m/z 360 (Mϩ, 39%), 303
(100), 290 (18), 289 (27); δH (300 MHz) 15.33 (1 H, s, OH), 7.88
(1 H, dd, J 1.6, 7.7), 7.49–7.23 (6 H, m), 7.06–6.95 (2 H, m),
3.16 (1 H, ddd, J 11.5, 11.5, 6.3, H-6), 2.75–2.55 (2 H, m), 2.43–
2.46 (1 H, m), 2.08 (1 H, dt, J 10.9, 3.7), 1.73–1.30 (9 H, m);
δC (75.5 MHz) 181.6 (s, CO), 180.0 (s, CO), 158.2 (s), 142.7 (s),
135.5 (d), 128.8 (d), 128.8 (d), 127.8 (d), 127.8 (d), 126.8 (d),
126.4 (d), 121.4 (s), 121.4 (d), 118.1 (d), 110.5 (s), 82.6 (s),
46.7 (d), 40.7 (d), 40.3 (t), 36.7 (t), 26.9 (t), 22.9 (t), 20.5 (t),
20.3 (t).
(3aRS,4SR,12aSR)-4-(2-Thienyl)-2,3,3a,4,5,6,6a,7-octahydro-
1H-cyclopenta[d]xanthene-6,7-dione 5cA
Compound 4c (0.2 g, 0.7 mmol) in dichloromethane (20 cm3)
was added to pyrrolidine (0.052 g, 0.7 mmol) and cyclo-
pentanone (0.061 g, 0.7 mmol) and the mixture heated at
reflux for 1 h, by which time TLC analysis showed that all 4c
had been consumed. The solvent was evaporated and the result-
ing gum purified by column chromatography (elution with light
petroleum–diethyl ether 3:1) giving 5cA (0.135 g, 57%) as
orange plates, mp 91–93 ЊC (ethanol) (HRMS: found Mϩ,
338.0976. C20H18O3S requires M, 338.0972); νmax/cmϪ1 1602;
m/z 338 (Mϩ, 16%), 309 (28), 296 (60), 295 (100); δH (300 MHz)
14.80 (1 H, s, OH), 7.88 (1 H, dd, J 1.7, 7.7), 7.46–7.39 (1 H, m),
7.25–7.19 (1 H, m), 7.03 (1 H, t, J 7.5), 6.96–6.84 (3 H, m), 3.15
(1 H, ddd, J 7.4, 9.4, 11.9, H-4), 2.74–2.60 (3 H, m), 2.38–2.12
(2 H, m), 1.89–1.49 (4 H, m); δC (75.5 MHz) 180.3 (s, CO), 180.2
(s, CO), 158.6 (s), 146.3 (s), 135.2 (d), 126.7 (d), 126.6 (d), 124.7
(d), 124.0 (d), 121.5 (d), 121.0 (s), 118.3 (d), 106.2 (s), 89.1 (s),
50.4 (d), 40.0 (t), 38.6 (d), 37.4 (t), 27.5 (t), 21.3 (t).
(5aRS,6SR,14aSR)-6-(2-Furyl)-2,3,4,5,5a,6,7,8,8a,9-deca-
hydro-1H-cyclohepta[d]xanthene-8,9-dione 5bC
Following the procedure described for 5cA, 4b (0.25 g, 0.98
mmol), cycloheptanone (0.106 g, 0.98 mmol) and pyrrolidine
(0.074 g, 0.98 mmol) gave 5bC (0.14 g, 41%) as an orange gum
(HRMS: found Mϩ, 350.1518. C22H22O4 requires M, 350.1513);
νmax/cmϪ1 1601; m/z 350 (Mϩ, 10%), 293 (100), 279 (31); δH (300
MHz) 15.28 (1 H, s, OH), 7.87 (1 H, dd, J 1.4, 7.7), 7.45 (2 H,
dt, J 1.6, 7.9), 7.05–6.94 (2 H, m), 6.31 (1 H, dd, J 1.9, 2.0), 6.13
(1 H, d, J 3.1), 3.28 (1 H, ddd, J 6.1, 11.3, 11.7, H-6), 2.88–2.60
(3 H, m), 2.33 (2 H, m), 2.11–2.03 (1 H, m), 1.74–1.25 (7 H, m);
δC (75.5 MHz) 180.3 (s, CO), 179.6 (s, CO), 158.1 (s), 143.1 (s),
141.5 (d), 135.5 (d), 126.5 (d), 121.4 (d), 121.3 (s), 118.1 (d),
110.0 (d), 109.4 (s), 106.5 (d), 81.5 (s), 46.2 (d), 36.6 (d), 46.1 (t),
36.1 (t), 34.3 (t), 26.8 (t), 20.7 (t), 20.6 (t).
(4aRS,5SR,13aSR)-5-(2-Furyl)-1,2,3,4,4a,5,6,7,7a,8-deca-
hydrobenzo[d]xanthene-7,8-dione 5bB
(5aRS,6SR,14aSR)-6-(2-Thienyl)-2,3,4,5,5a,6,7,8,8a,9-deca-
hydro-1H-cyclohepta[d]xanthene-8,9-dione 5cC
Following the procedure described for 5aB, 4b (1.28 g, 5.00
mmol) and freshly prepared N-(cyclohex-1-en-1-yl)pyrrolidine
3B (3.80 g, 25.17 mmol) after 5 minutes gave 5bB (0.84 g, 60%)
as pale yellow plates, mp 124–125 ЊC (ethanol–chloroform)
(HRMS: found Mϩ, 336.1364. C21H20O4 requires M, 336.1362);
νmax/cmϪ1 1601; λmax/nm 262 (log ε 3.9), 308 (4.3), 355 (4.2); m/z
336 (Mϩ, 37), 293 (100), 279 (31); δH (90 MHz) 15.27 (1 H, s,
OH), 7.85 (1 H, dd, J 7.8, 1.8), 7.46–7.37 (2 H, m), 7.04–6.93
(2 H, m), 6.33 (1 H, dd, J 3.0, 1.7), 6.15 (1 H, d, J 3.0), 3.43
(1 H, ddd, J 5.6, 12.0, 12.0, H-5), 2.84 (1 H, dd, J 5.7, 8.9), 2.63
(1 H, dd, J 9.0, 5.6), 2.47 (1 H, dt, J 2.5, 12.5, H-4a), 2.21 (1 H,
d, J 10.3), 2.03–1.96 (1 H, m), 1.52–1.24 (6 H, m); δC (22.6
MHz) 181.0 (s, CO), 180.5 (s, CO), 158.1 (s), 154.9 (s), 141.7(d),
135.2 (d), 126.5 (s), 121.4 (d), 120.6 (s), 118.0 (d), 110.1 (d),
109.4 (s), 106.4 (d), 79.1 (s), 42.6 (d), 36.5 (t), 33.2 (d), 32.4 (t),
22.9 (t), 21.5 (t), 19.5 (t).
Following the procedure described for 5cA, 4c (0.2 g, 0.7 mmol),
cycloheptanone (0.08 g, 0.7 mmol) and pyrrolidine (0.052 g, 0.7
mmol) gave 5cC (0.128 g, 50%) as yellow plates, mp 137–138 ЊC
(ethanol) (HRMS: found Mϩ, 366.1719. C22H22O3S requires M,
366.1712); νmax/cmϪ1 1604; m/z 366 (Mϩ, 52%), 310 (19), 309
(100), 296 (22), 295 (48); δH (300 MHz) 15.27 (1 H, s, OH), 7.85
(1 H, dd, J 1.7, 8.8), 7.45 (1 H, dt, J 1.7, 6.6), 7.22 (1 H, m),
7.05–6.90 (4 H, m), 3.46 (1 H, ddd, J 6.6, 11.5, 11.5, H-6), 2.87–
2.57 (3 H, m), 2.46 (1 H, m), 2.38–2.34 (1 H, m), 1.7–1.42 (8 H,
m); δC (75.5 MHz) 181.7 (s, CO), 178.8 (s, CO), 158.0 (s), 146.5
(s), 135.9 (d), 126.9 (d), 126.5 (d), 124.8 (d), 121.8 (d), 120.7 (s),
118.0 (d), 110.7 (d), 110.2 (s), 82.3 (s), 48.8 (d), 41.3 (t), 36.6 (t),
36.2 (d), 27.2 (t), 23.9 (t), 20.9 (t), 20.9 (t).
7-Phenyl-1,2,3,4,5,6,7,8-octahydro-14H-cycloocta[a]xanthen-
14-one 6aD and 7-phenyl-1,2,3,4,5,6-hexahydro-14H-cyclo-
octa[a]xanthen-14-one 7a
(4aRS,5SR,13aSR)-5-(2-Thienyl)-1,2,3,4,4a,5,6,7,7a,8-deca-
hydrobenzo[d]xanthene-7,8-dione 5cB
Compound 4a (0.5 g, 1.9 mmol) and freshly prepared N-(cyclo-
oct-1-en-1-yl)pyrrolidine 3D (1.7 g, 9.5 mmol) were heated to
reflux in 95% ethanol (30 cm3) for 24 h by which time TLC
analysis showed that all 4a had been consumed. Evaporation of
the solvent and purification of the resulting gum by preparative
TLC (eluted with light petroleum–diethyl ether 4:1) gave the
following products. (i) The band with Rf 0.6 gave 6aD (0.148 g,
22%) as colourless prisms, mp 145–146 ЊC (ethanol) (HRMS:
found Mϩ, 356.1758. C25H24O2 requires M, 356.1775); νmax/cmϪ1
1641; λmax/nm 332 (log ε 3.72), 300 (3.93), 274 (4.14), 260 (4.15),
250 (4.16); m/z 356 (Mϩ, 100%), 273 (20), 265 (35); δH (300
MHz) 8.21 (1 H, dd, J 7.8, 1.7), 7.51 (1 H, t, J 7.5), 7.33–7.13
(7 H, m), 3.80 (1 H, dt, J 13.9, 4.2), 3.58 (1 H, dd, J 8.8, 1.5,
H-7), 3.49 (1 H, dd, J 16.9, 8.8, H-8a), 2.88–2.69 (2 H, m), 2.53–
2.49 (1 H, m), 1.99–1.95 (1 H, m), 1.79–1.21 (8 H, m); δC (75.5
MHz) 175.2 (s, CO), 164.0 (s), 155.0 (s), 140.8 (s), 135.4 (s),
Following the procedure described for 5aB, 4c (1.36 g, 5.00
mmol) and freshly prepared N-(cyclohex-1-en-1-yl)pyrrolidine
3B (3.78 g, 25.03 mmol) after 5 minutes gave 5cB (0.90 g,
51%) as pale yellow plates, mp 133–133.5 ЊC (ethanol–chloro-
form) (HRMS: found Mϩ, 352.1120. C21H20O3S requires M,
352.1133); νmax/cmϪ1 1602; λmax/nm 262 (log ε 3.8), 308 (4.1), 359
(4.0); m/z 352 (Mϩ, 48%), 309 (100), 295 (36); δH (270 MHz)
15.25 (1 H, s, OH), 7.87 (1 H, dd, J 1.68, 7.72), 7.4–7.5 (1 H, m),
7.23 (1 H, d, J 5.0), 7.06–6.9 (4 H, m), 3.64 (1 H, ddd, J 7.1,
10.4, 12.4, H-5), 2.82 (1 H, d, J 1.35), 2.79 (1 H, d, J 4.70), 2.58
(1 H, dd, J 4.70, 12.42), 2.25 (1 H, d, J 9.74), 2.01 (1 H, m),
1.62–1.38 (6 H, m); δC (67.9 MHz) 180.8 (s, CO), 180.2 (s, CO),
158.1 (s), 145.9 (s), 135.3 (d), 126.7 (d), 126.5 (s), 124.7 (d),
123.9 (d), 121.5 (d), 120.5 (s), 118.0 (d), 109.5 (s), 79.2 (s), 45.1
(d), 40.6 (t), 35.2 (d), 32.6 (t), 22.4 (t), 21.4 (t), 19.4 (t).
3272
J. Chem. Soc., Perkin Trans. 1, 1998, 3267–3276

View Article Online
132.4 (d), 128.6 (d), 128.6 (d), 128.0 (s), 127.8 (d), 127.8 (d),
126.9 (d), 126.2 (d), 125.1 (s), 124.7 (d), 117.4 (d), 117.0 (s), 43.0
(d), 36.7 (t), 32.1 (t), 30.4 (t), 29.7 (t), 27.3 (t), 26.2 (t), 25.1 (t).
(ii) The band with Rf 0.5 gave 7a (94 mg, 14%) as colourless
plates, mp 157–158 ЊC (ethanol) (Found: C, 84.97, H, 6.37%.
C25H22O2 requires C, 84.71, H, 6.26%); νmax/cmϪ1 1648; λmax/nm
345 (log ε 3.97), 265 (4.34), 248 (4.70), 238 (4.70); m/z 354 (Mϩ,
100%), 353 (90), 325 (20), 311 (28), 287 (20); δH (300 MHz) 8.32
(1 H, dd, J 8.3, 1.7), 7.86 (1 H, t, J 6.6), 7.46–7.22 (8 H, m), 3.67
(2 H, br t, J 6.1), 2.82 (2 H, br s), 1.96 (2 H, br s), 1.42 (6 H, br
s); δC (75.5 MHz) 178.6 (s), 155.7 (s), 155.2 (s), 148.9 (s), 145.0
(s), 141.6 (s), 136.2 (s), 134.0 (d), 128.6 (d), 128.6 (d), 128.0 (d),
128.0 (d), 127.4 (d), 127.0 (d), 123.5 (d), 123.2 (s), 118.7 (s),
117.5 (d), 117.2 (d), 31.5 (t), 30.9 (t), 28.4 (t), 28.0 (t), 26.7 (t),
26.5 (t). Compound 7a was also obtained, and in quantitative
yield, by heating 6aD in refluxing ethanol and one drop of
pyrrolidine for 24 h.
C-Methylation of 5aB
(a) Thallium() ethoxide (2.83 g, 11.3 mmol) was added to a
magnetically stirred solution of compound 5aB (0.68 g, 1.97
mmol) in benzene (20 cm3) and the resulting mixture stirred for
5 minutes before cooling in ice. The resulting yellow precipitate
was filtered and heated under reflux as a suspension in methyl
iodide (15 cm3) for 7 hours. After cooling, the mixture was
filtered and the filtrate passed through a short column of
Florisil (ASTM 100–200 mesh) (10 g). Concentration of the
eluent gave a pale yellow gum which on column chrom-
atography [elution with light petroleum (40–60 ЊC)–diethyl
ether 4:1] gave two products.
(i) The less polar fraction gave (4aRS,5SR,7aRS,13aRS)-7a-
methyl-5-phenyl-1,2,3,4,4a,5,6,7,7a,8-decahydrobenzo[d]xan-
thene-7,8-dione 10a (0.15 g, 21%) as colourless plates, mp 188–
189 ЊC (ethanol) (HRMS: found Mϩ, 360.1740. C24H24O3
requires M, 360.1725); νmax/cmϪ1 1712, 1683; λmax/nm 211 (log ε
4.6), 252 (4.2), 312 (3.7); m/z 360 (Mϩ, 100%), 240 (82), 228
(52); 1H and 13C NMR data are reported in Tables 1 and 2.
(ii) The more polar fraction gave (4aRS,5SR,7aRS,13aSR)-
7a-methyl-5-phenyl-1,2,3,4,4a,5,6,7,7a,8-decahydrobenzo[d]-
xanthene-7,8-dione 9aB (0.46 g, 65%) as colourless rods, mp
172.5–173.5 ЊC (ethanol) (HRMS: found Mϩ, 360.1726. C24H24-
O3 requires M, 360.1725); νmax/cmϪ1 1727, 1683; λmax/nm 215
(log ε 4.1), 251 (4.0) and 317 (3.5); m/z 360 (Mϩ, 38%), 228 (23),
7-(2-Furyl)-1,2,3,4,5,6,7,8-octahydro-14H-cycloocta[a]xanthen-
14-one 6bD
Following the procedure for 5cA, 4b (0.5 g, 1.96 mmol), cyclo-
octanone (0.24 g, 1.96 mmol) and pyrrolidine (0.14 g, 1.96
mmol) gave after refluxing for 1.5 h, 6bD (0.25 g, 37%) as
colourless plates, mp 99–100 ЊC (ethanol) (HRMS: found Mϩ,
346.1568. C23H22O3 requires M, 346.1560); νmax/cmϪ1 1648; m/z
(Mϩ 346, 100%); δH (300 MHz) 8.20 (1 H, dd, J 1.7, 8.7), 7.57
(1 H, t, J 7.7), 7.36–7.26 (3 H, m), 6.16 (1 H, m), 6.00 (1 H, m),
3.71–3.62 (2 H, m), 3.19 (1 H, dd J 7.6, 16.8), 3.03 (1 H, dd
J 2.8, 16.8), 2.69 (1 H, dt, J 3.7, 12.7), 2.55 (1 H, dt, J 11.5, 3.1),
2.16–2.10 (1 H, m), 1.80–1.27 (8 H, m); δC (75.5 MHz) 175.4 (s,
CO), 164.3 (s), 155.1 (s), 154.2 (s), 141.9 (d), 133.4 (s), 132.6 (d),
130.1 (s), 126.3 (d), 125.1 (s), 124.8 (d), 117.5 (d), 116.5 (s),
110.2 (d), 106.3 (d), 36.9 (d), 33.5 (t), 32.0 (t), 30.4 (t), 29.6 (t),
27.2 (t), 26.2 (t), 25.1 (t).
213 (29), 167 (21), 149 (47), 148 (100); H and 13C NMR data
are reported in Tables 1 and 2.
1
The above results were obtained on two occasions but only
when a particular bottle of thallium() ethoxide was used.
(b) Following the procedure described in (a), 5aB (1.22 g,
3.53 mmol) gave two products.
(i) The less polar band gave (4aRS,5SR,6SR,7aRS,13aRS)-
6,7a-dimethyl-5-phenyl-1,2,3,4,4a,5,6,7,7a,8-decahydrobenzo-
[d]xanthene-7,8-dione 11a (0.026 g, 2%) as colourless prisms,
mp 198 ЊC (ethanol) (HRMS: found Mϩ, 374.1893. C25H26O3
requires M, 374.1882); νmax/cmϪ1 1733, 1685; λmax/nm 212 (log ε
4.2), 251 (3.8), 314 (3.4); m/z 374 (Mϩ, 29%), 227 (28), 148
(100); 1H and 13C NMR data are reported in Tables 1 and 2.
(ii) The more polar band gave 9aB (0.79 g, 62%).
7-(2-Furyl)-1,2,3,4,5,6-hexahydro-14H-cycloocta[a]xanthen-14-
one 7b
Compound 6bD (0.1 g) in 95% ethanol (30 cm3) was heated
under reflux for 5 h with one drop of pyrrolidine. Evaporation
of the solvent followed by column chromatography (eluted with
n-hexane–diethyl ether 9:1) gave 7b (0.09 g, 80%) as colourless
plates, mp 130–131 ЊC (ethanol) (HRMS: found Mϩ, 344.1412.
C23H20O3 requires M, 344.1409); νmax/cmϪ1 1646; m/z 344 (Mϩ,
100%), 327 (27), 315 (30), 301 (36); δH (300 MHz) 8.15 (1 H, dd,
J 1.5, 8.0), 7.54–7.49 (4 H, m), 7.47 (1 H, d, J 1.5), 7.27–7.16
(4 H, m), 6.57 (1 H, d, J 3.4), 6.43 (1 H, dd, J 1.8, 3.3), 2.93
(2 H, t, J 5.8), 1.85 (2 H, m), 1.67 (2 H, br s), 1.46–1.39 (2 H, m);
δC (75.5 MHz) 177.2 (s), 154.7 (s), 154.3 (s), 151.3 (s), 144.1 (s),
141.1 (d), 134.8 (s), 134.2 (s), 132.9 (d), 125.8 (d), 122.3 (d),
122.0 (s), 117.5 (s), 116.0 (d), 114.4 (d), 110.6 (d), 109.7 (d), 30.1
(t), 29.6 (t), 27.2 (t), 26.8 (t), 26.2 (t), 25.0 (t).
These results were obtained using different thallium() ethox-
ide bottles and on numerous occasions.
(c) Compound 5aB (0.2 g, 0.57 mmol) and a hexane solution
of LDA (0.74 g, 0.69 mmol) in toluene (25 cm3) was stirred at
Ϫ78 ЊC for 1 h before adding HMPT (0.51 g, 2.9 mmol) and
stirring for a further 1 h. Methyl iodide (5 cm3) was added and
the mixture stirred at room temperature for 40 h by which time
TLC analysis showed that all 5aB had been consumed. Dilute
0.5 M hydrochloric acid (10 cm3) was added to the mixture
before extracting with chloroform (3 × 20 cm3). Evaporation of
the solvent followed by column chromatography (eluted with n-
hexane–ether 7:3) gave 9aB (0.12 g, 53%).
(3aRS,4SR,6aRS,12aSR)-6a-Methyl-4-phenyl-2,3,3a,4,5,6,6a,
7-octahydro-1H-cyclopenta[d]xanthene-6,7-dione 9aA
7-(2-Thienyl)-1,2,3,4,5,6,7,8-octahydro-14H-cycloocta[a]-
xanthen-14-one 6cD
(a) Following the thallium() ethoxide/methyl iodide pro-
cedure described for 9aB, 5aA (0.84 g, 2.53 mmol) yielded only
one product 9aA (0.44 g, 50%) as colourless needles, mp
160.5–161.5 ЊC (ethanol–chloroform) (HRMS: found Mϩ,
346.1563. C23H22O3 requires M, 346.1569); νmax/cmϪ1 1736,
1689; λmax/nm 216 (log ε 4.2), 251 (4.1), 318 (3.7); m/z 346 (Mϩ,
15%), 148 (100); 1H and 13C NMR data are reported in Tables 1
and 2.
Following the procedure described for 5cA, 4c (0.2 g, 0.73
mmol), cyclooctanone (0.092 g, 0.73 mmol) and pyrrolidine
(0.052 g, 0.72 mmol) gave after heating for 2.5 h 6cD (0.09 g,
34%) as yellow plates, mp 118–119 ЊC (ethanol) (HRMS: found
Mϩ, 362.1340 C23H22O2S requires M, 362.1335); νmax/cmϪ1
1644; m/z (Mϩ 362, 100%); δH (300 MHz) 8.22 (1 H, dd, J 1.6,
8.6), 7.56 (1 H, t, J 7.7), 7.37–7.26 (2 H, m), 7.04 (1 H, dd J 1.5,
4.7), 6.80 (2 H, m), 3.81–3.68 (2 H, m), 3.45 (1 H, dd, J 6.6, 7.9),
2.93 (1 H, dd, J 1.6, 16.7), 2.67 (1 H, dt, J 3.8, 12.8), 2.54 (1 H,
t, J 11.2), 2.17–2.11 (1 H, m), 1.80–1.25 (8 H, m); δC (75.5 MHz)
175.3 (s, CO), 163.8 (s), 155.1 (s), 144.2 (s), 135.9 (s), 132.6 (d),
129.4 (s), 126.6 (d), 126.3 (d), 125.1 (s), 125.1 (d), 124.8 (d),
124.0 (d), 117.5 (d), 116.8 (s), 38.5 (d), 37.0 (t), 32.1 (t), 30.5 (t),
29.6 (t), 27.3 (t), 26.2 (t), 25.0 (t).
(b) Following the LDA/MeI procedure (c) for 9aB, 5aA gave
9aA (46%).
(4aRS,5SR,7aRS,13aSR)-7a-Methyl-5-(2-furyl)-1,2,3,4,4a,5,6,
7,7a,8-decahydrobenzo[d]xanthene-7,8-dione 9bB
(a) Following the thallium() ethoxide/methyl iodide procedure
described for the C-methylation of 5aB, reaction with 5bB
J. Chem. Soc., Perkin Trans. 1, 1998, 3267–3276
3273

View Article Online
yielded only one product, 9bB (42%) as pale orange plates, mp
169.5–170.5 ЊC (95% ethanol) (HRMS: found Mϩ, 350.1513.
C22H22O4 requires M, 350.1518); νmax/cmϪ1 1740, 1725, 1690,
1670; λmax/nm 214 (log ε 4.9), 252 (4.4), 318 (3.9); m/z 350 (Mϩ,
30%), 148 (100), 121 (31); 1H and 13C NMR data are reported in
Tables 1 and 2.
iodide (0.2 ml, 3.1 mmol) gave 12c (176.5 mg, 89%) as colour-
less prisms, mp 169.5–171 ЊC (ethanol–chloroform); (HRMS,
found Mϩ, 382.1603. C23H26O3S requires M, 382.1603); νmax
/
cmϪ1 3541, 1688; λmax/nm 216 (log ε 4.5), 320 (3.7); m/z 382
(Mϩ, 47%), 339 (28), 325 (40), 230 (30), 229 (100); δH (270
MHz) 7.78 (1 H, dd, J 1.71, 7.81), 7.49 (1 H, ddd, J 1.71,
7.33, 9.04), 7.18 (1 H, d, J 4.40), 7.02 (1 H, dd, J 0.98, 7.81),
6.97–6.93 (2 H, m), 6.88 (1 H, dd, J 0.98, 3.42), 3.70 (1 H,
ddd, J 7.08, 12.45, 17.33), 3.31 (1 H, br s, OH), 2.61 (1 H,
m), 2.37 (1 H, br d, J 12.45), 2.01–1.94 (3 H, m), 1.84 (1 H,
br d, J 15.63), 1.54 (3 H, s, Me), 1.51–1.36 (5 H, m), 1.41
(3 H, s, Me); δC (67.9 MHz) 199.8 (s, CO), 157.4 (s), 147.9 (s),
135.7 (d), 126.7 (d), 126.5 (d), 124.2 (d), 123.1 (d), 121.7 (s),
120.8 (d), 117.8 (d), 85.7 (s), 73.8 (s), 54.2 (s), 45.8 (t), 41.7
(d), 35.0 (d), CH), 28.4 (q), 26.10 (t), 22.3 (t), 21.6 (t), 19.3
(t), 17.5 (q).
(b) Following the LDA/MeI procedure (c) for 9aB, 5bB gave
9bB (44%).
C-Methylation of 5cB
(a) Following the procedure described for the C-methylation of
5aB using thallium() ethoxide/methyl iodide, reaction with 5cB
yielded two products.
(i) The less polar band gave (4aRS,5SR,6SR,7aRS,13aRS)-
6,7a-dimethyl-5-(2-thienyl)-1,2,3,4,4a,5,6,7,7a,8-decahydro-
benzo[d]xanthene-7,8-dione 11c (6%) as colourless prisms, mp
191.5–193 ЊC (ethanol) (HRMS: found Mϩ, 380.1454. C23H24-
O3 requires M, 380.1446); νmax/cmϪ1 1730, 1680; λmax/nm 215
(log ε 4.6), 235 (4.5), 310 (4.1), 356 (3.8); m/z 380 (Mϩ, 42%),
(4aRS,5SR,7SR,7aRS,8SR,13aSR)-7,7a-Dimethyl-5-phenyl-
1,2,3,4,4a,5,6,7,7a,8-decahydrobenzo[d]xanthene-7,8-diol 13a
A solution of 12a (0.91 g, 2.42 mmol) in dry THF (25 cm3) was
slowly added to a magnetically stirred slurry of lithium alu-
minium hydride (0.79 g, 20.79 mmol) in dry THF (25 cm3) over
15 minutes at room temperature under dry nitrogen. The result-
ing mixture was refluxed for 2 h, by which time TLC analysis
showed that all 12a had been consumed. Ice-cooled water
was added to the mixture until gas evolution ceased before
filtering through a thin layer of Celite and extracting the fil-
trate with ethyl acetate (3 × 70 cm3). The combined organic
extracts were washed with water and then dried over
anhydrous magnesium sulfate. Evaporation of the solvent
gave 13a (0.91 g, 100%) as colourless needles, mp 196–
197.5 ЊC (ethanol); (HRMS: found Mϩ, 378.2204. C25H30O3
requires M, 378.2195); νmax/cmϪ1 3398, 3338; λmax/nm 205 (log
ε 4.6), 274 (3.7), 282 (3.6); m/z 379 (Mϩ1, 25%), 378 (Mϩ,
94), 360 (51), 317 (46), 214 (30), 213 (100), 171 (49), 121 (88);
δH (270 MHz) 7.53 (1 H, d, J 7.57), 7.36–7.31 (2 H, m), 7.27–
7.18 (4 H, m), 6.97 (1 H, td, J 7.57, 1.22), 6.84 (1 H, dd,
J 8.06, 1.22), 5.33 (1 H, s, H-8), 3.34 (1 H, ddd, J 12.94,
12.70, 4.40, H-5), 2.51 (1 H, m), 2.39 (1 H, br d, J 12.70), 2.11
(1 H, dd, J 12.94, 14.41, H-6Ј), 2.01–1.60 (5 H, m), 1.67 (1 H,
dd, J 4.40, 14.40), 1.52 (3 H, s, Me), 1.41–1.34 (4 H, m),
1.15 (3 H, s, Me); δC (67.9 MHz) 151.8 (s), 144.4 (s), 128.9
(d), 128.7 (d), 128.7 (d), 127.4 (d), 127.3 (s), 126.3 (d), 120.7
(d), 116.8 (d), 83.0 (s), 74.9 (s), 67.5 (d), 47.1 (t), 45.2 (s),
40.1 (d), 39.6 (d), 29.5 (q), 25.8 (t), 22.6 (t), 21.6 (t), 19.6 (t),
12.0 (q).
1
233 (27), 148 (100); H and 13C NMR data are reported in
Tables 1 and 2.
(ii) The more polar band gave (4aRS,5SR,7aRS,13aSR)-7a-
methyl-5-(2-thienyl)-1,2,3,4,4a,5,6,7,7a,8-decahydrobenzo[d]-
xanthene-7,8-dione 9cB (56%) as orange plates, mp 179.5–
180.5 ЊC (95% ethanol) (HRMS: found Mϩ, 366.1296. C22H22O3
requires M, 366.1290); νmax/cmϪ1 1744, 1728, 1692, 1677;
λmax/nm 230 (log ε 4.3), 317 (4.0); m/z 366 (Mϩ, 43%), 228
1
(23), 148 (100); H and 13C NMR data are reported in Tables
1 and 2.
(b) Following the LDA/MeI procedure for 9aB, 5cB gave 9cB
(51%).
(4aRS,5SR,7SR,7aRS,13aSR)-7,7a-Dimethyl-7-hydroxy-5-
phenyl-1,2,3,4,4a,5,6,7,7a,8-decahydrobenzo[d]xanthen-8-one
12a
To a magnetically stirred mixture of magnesium turnings (0.22
g, 9.17 mmol) in dry diethyl ether (10 cm3) was added methyl
iodide (0.6 cm3 9.63 mmol) and the resulting mixture allowed to
stand until the formation of bubbles ceased. A solution of 9aB
(1.06 g, 2.94 mmol) in dry benzene (17 cm3) and dry diethyl
ether (15 cm3) was then added dropwise and the resulting mix-
ture stirred for 14 h at room temperature. When no further
reaction was observed (from TLC analysis) the reaction mixture
was poured onto crushed ice (50 g) and dilute hydrochloric acid
(40 cm3). The aqueous mixture was extracted with diethyl ether
(2 × 100 cm3) and the combined extracts washed with water
(200 cm3) and dried. Removal of solvent gave a yellow gum
which on column chromatography (elution with light petroleum
(40–60 ЊC)–diethyl ether 7:3) gave 12a (0.91 g, 82%) as colour-
less rods, mp 178.5–179.5 ЊC (ethanol–chloroform) (HRMS:
found Mϩ, 376.2047. C25H28O3 requires M, 376.2038); νmax/cmϪ1
3540, 1685; λmax/nm 215 (log ε 4.5), 247 (4.1), 320 (3.7); m/z 376
(Mϩ, 42%), 333 (20), 319 (44), 230 (31), 229 (100); δH (270 MHz)
7.79 (1 H, dd, J 1.71, 7.57), 7.49 (1 H, m), 7.36–7.31 (2 H, m),
7.27–7.21 (3 H, m), 7.04–6.95 (2 H, m), 3.37 (1 H, td, J 12.21,
5.37), 3.30 (1 H, d, J 1.71), 2.68 (1 H, m), 2.51 (1 H, dt, J 12.45,
2.20), 1.96–1.78 (4 H, m), 1.53 (3 H, s, Me), 1.44 (3 H, s, Me),
1.49–1.27 (4 H, m), 1.22 (1 H, br d, J 11.96); δC (67.9 MHz)
199.9 (s, CO), 157.5 (s), 143.9 (s), 135.7 (d), 128.7 (d), 128.7 (d),
127.5 (d), 126.7 (d), 126.5 (d), 121.8 (s), 120.7 (d), 117.7 (d), 86.0
(s), 73.9 (s), 54.4 (s), 44.6 (t), 39.4 (d), 39.4 (d) , 28.5 (q), 26.1 (t),
22.2 (t), 21.7 (t), 19.3 (t), 17.4 (q).
(4aRS,5SR,7SR,7aRS,8SR,13aSR)-7,7a-Dimethyl-5-(2-
thienyl)-1,2,3,4,4a,5,6,7,7a,8-decahydrobenzo[d]xanthene-7,8-
diol 13c
Following the procedure described for 13a, 12c (440 mg, 1.15
mmol) and lithium aluminium hydride (410 mg, 10.79 mmol)
gave 13c (0.44 g, 100%) as colourless needles (ethanol),
mp 150–151 ЊC; (HRMS: found Mϩ, 384.1764. C23H28SO3
requires M, 384.1759); νmax/cmϪ1 3487, 3371; λmax/nm 204 (log
ε 4.4), 227 (4.3), 274 (3.6), 282 (3.5); m/z 385 (Mϩ1, 100%),
366 (49), 323 (48), 214 (33), 213 (87), 121 (60); δH (270 MHz)
7.52 (1 H, d, J 7.81), 7.21 (1 H, dd, J 1.22, 7.81), 7.17 (1 H,
dd, J 1.22, 5.13), 6.98 (1 H, dd, J 1.22, 7.57), 6.94 (1 H, dd,
J 3.42, 5.13), 6.88 (1 H, dd, J 1.22, 3.42), 6.83 (1 H, dd, J 1.22,
8.06), 5.31 (1 H, s, H-8), 3.69 (1 H, ddd, J 12.69, 12.21, 4.15,
H-5), 2.44 (1 H, m), 2.25 (1 H, br d, J 12.21, H-4a), 2.16
(1 H, dd, J 12.69, 14.41, H-6Ј), 1.90 (1 H, m), 1.82 (1 H, dd,
J 4.15, 14.41), 1.71 (3 H, br s), 1.53 (3 H, s, Me), 1.50–1.30 (5 H,
m), 1.12 (3 H, s, Me); δC (67.9 MHz) 151.7 (s), 148.7 (s),
128.9 (d), 127.5 (d), 127.3 (s), 126.5 (d), 123.9 (d), 122.9 (d),
120.7 (d), 116.8 (d), 82.8 (s), 74.8 (s), 67.5 (d), 48.2 (t), 45.1
(s), 42.5 (d), 35.1 (d), 29.3 (q), 25.8 (t), 22.7 (t), 21.6 (t), 19.6
(t), 12.0 (q).
(4aRS,5SR,7SR,7aRS,13aSR)-7,7a-Dimethyl-7-hydroxy-5-(2-
thienyl)-1,2,3,4,4a,5,6,7,7a,8-decahydrobenzo[d]xanthen-8-one
12c
Following the procedure described for 12a, 9cB (190 mg, 0.52
mmol), magnesium turnings (70 mg, 2.92 mmol) and methyl
3274
J. Chem. Soc., Perkin Trans. 1, 1998, 3267–3276

View Article Online
Dehydroxylation of (4aRS,5SR,7SR,7aRS, 8SR,13aSR)-7,7a-
dimethyl-5-phenyl-1,2,3,4,4a,5,6,7,7a,8-decahydrobenzo[d]-
xanthene-7,8-diol 13a
was filtered and the solvent was removed under reduced pres-
sure giving a colourless gum which on purification by column
chromatography [elution with light petroleum (40–60 ЊC)
diethyl ether 1:1] gave 16 as colourless rods (346 mg, 100%),
mp 135–136 ЊC (ethanol–chloroform); (HRMS: found Mϩ,
346.2296. C25H30O requires M, 346.2297); νmax/cmϪ1 1232, 1168;
λmax/nm 210 (log ε 4.5), 274 (4.0), 281 (4.0); m/z 346 (Mϩ, 39%),
240 (20), 239 (100), 238 (23), 133 (26); δH (270 MHz) 7.34–7.28
(2 H, m), 7.24–7.18 (3 H, m), 7.15–7.04 (2 H, m), 6.88–6.83
(2 H, m), 3.08 (1 H, ddd, J 12.45, 6.84, 10.26, H-5), 2.62 (1 H, d,
J 16.36), 2.50 (1 H, d, J 16.36), 2.34 (1 H, br d, J 12.45), 1.93–
1.70 (3 H, m), 1.67–1.21 (7 H, m), 1.13 (1 H, br d, J 13.18), 1.01
(3 H, s, Me), 0.90 (3 H, d, J 6.59, Me); δC (67.9 MHz) 152.6 (s),
145.4 (s), 130.1 (d), 128.6 (d), 128.6 (d), 127.5 (br d), 127.1 (d),
126.2 (d), 122.4 (s), 120.0 (d), 117.2 (d), 79.9 (s), 42.9 (d), 39.4
(d), 39.4 (t), 37.9 (s), 36.2 (d), 35.7 (t), 23.2 (t), 22.5 (t), 21.4 (t),
19.3 (t), 14.3 (q), 13.2 (q).
Trifluoroacetic acid (2.1 cm3, 27.3 mmol) was added dropwise
to a magnetically stirred solution of 13a (405 mg, 1.07 mmol),
triethylsilane (811 mg, 7.0 mmol) and ammonium fluoride (270
mg, 7.3 mmol) in dichloromethane (4 cm3) at 0 ЊC. The result-
ing mixture was stirred at 0 ЊC for 0.5 h and then at room tem-
perature for 19 h, by which time TLC analysis showed that all
13a had been consumed. Ice-cooled water (30 cm3) was added
and the reaction mixture extracted with dichloromethane
(3 × 25 cm3). The combined organic extracts were washed with
10% aqueous sodium hydrogen carbonate (160 cm3), followed
by water (200 cm3) and dried over anhydrous magnesium
sulfate. Evaporation of the solvent gave a colourless gum
which on column chromatography [eluted with light petroleum
(40–60 ЊC)–diethyl ether 7:3] gave a gum (368.6 mg, 100%)
which was homogeneous by TLC analysis consisting of a
mixture of (4aRS,5SR,7aRS,13aSR)-7,7a-dimethyl-5-phenyl-
1,2,3,4,4a,5,7a,8-octahydrobenzo[d]xanthene 14a and (4aRS,
5SR,7aRS,13aSR)-7a-methyl-7-methylidene-5-phenyl-1,2,3,4,
4a,5,6,7,7a,8-decahydrobenzo[d]xanthene 15a in the ratio of
3:2 (from 1H NMR as shown below) (HRMS: found Mϩ,
344.2140. C25H28O requires M, 344.2140); νmax/cmϪ1 1643, 1601;
m/z 344 (Mϩ, 60%), 238 (26), 237 (83), 212 (24), 209 (32), 133
(100); δH (270 MHz) 7.32–7.18 (5 H, m, 14aϩ15a), 7.17–7.03
(2 H, m, 14aϩ15a), 6.89–6.81 (2 H, m, 14aϩ15a), 5.23 (0.6 × 1
H, br s, 14a), 4.83 (0.4 × 1 H, s, 15a), 4.76 (0.4 × 1 H, s, 15a),
3.50 (0.6 × 1 H, br d, J 10.25, 14a), 3.11 (0.6 × 1 H, d, J 16.36,
14a), 3.06 (0.4 × 1 H, td, J 12.45, 5.13, 15a), 2.89 (0.6 × 1 H, d,
J 16.11, 14a), 2.70 (0.4 × 1 H, br t, J 13.18, 15a), 2.53 (0.6 × 1
H, d, J 16.11, 14a), 2.52 (0.6 × 1 H, m, 14a), 2.43 (0.4 × 1 H, d,
J 16.36, 15a), 2.38 (0.4 × 1 H, dd, J 5.13, 13.91, 15a), 2.29
(0.4 × 1 H, br d, J 10.50, 15a), 2.09 (0.6 × 3 H, s, Me 14a), 2.05–
1.85 (1 H, m, 14aϩ15a), 1.24 (0.4 × 3 H, s, Me 15a), 1.21
(0.6 × 3 H, s, Me 14a).
4-Phenyl-2,3,4,5-tetrahydrocyclopenta[a]xanthen-11(1H)-one
6aA
Compound 4a (0.2g, 0.75 mmol) in toluene was stirred under
ultraviolet light for 2 h before N-(cyclopent-1-en-1-yl)pyrrol-
idine 3A (0.053 g, 0.75 mmol) was added dropwise over a period
of 1 h. The reaction was stirred under ultraviolet light for 4 days
by which time TLC analysis showed that all of 4a had been
consumed. Removal of solvent gave an orange gum which on
column chromatography [elution with light petroleum (40–
60 ЊC) diethyl ether 3:1 v/v] gave two products.
(i) The less polar fraction gave 5aA (0.068 g, 28%).
(ii) The more polar fraction yielded 6aA as colourless prisms
(0.074 g, 31%), mp 126–127 ЊC (ethanol) (HRMS: found Mϩ,
314.1334. C22H18O2 requires M 314.1335); νmax/cm3 1625; m/z
314 (Mϩ, 100%), 312 (42), 285 (29), 237 (31), δH (300 MHz) 8.22
(1 H, dd, J 1.8, 8.6), 7.61–7.57 (1 H, m), 7.41–7.06 (7 H, m),
6.82 (1 H, m), 3.76 (1 H, m), 3.40 (1 H, dd, J 9.5, 17.0), 3.37
(1 H, d, J 9.4), 3.27 (1 H, dt, J 2.6, 4.8), 3.14–3.02 (1 H, m), 3.01
(1 H, d, J 5.8), 2.95 (1 H, d, J 5.9), 2.00 (1 H, d, J 7.2); δC (75.5
MHz) 174.6 (s), 163.7 (s), 155.5 (s), 142.0 (s), 136.6 (s), 132.7
(d), 128.76 (d), 128.7 (d), 127.4 (d), 127.4 (d), 126.9 (d), 126.0
(d), 124.8 (d), 124.6 (s), 120.3 (s), 117.7 (d), 114.8 (s), 40.75 (d),
36.7 (t), 33.9 (t), 33.4 (t), 23.4 (t).
Dehydroxylation of (4aRS,5SR,7SR,7aRS,8SR,13aSR)-7,7a-
dimethyl-5-(2-thienyl)-1,2,3,4,4a,5,6,7,7a,8-decahydrobenzo-
[d]xanthene-7,8-diol 13c
Following the procedure described for the dehydroxylation of
13a, 13c (400 mg, 1.05 mmol) gave a colourless solid (363 mg,
100%) consisting of a mixture of (4aRS,5SR,7aRS,13aSR)-
7,7a-dimethyl-5-(2-thienyl)-1,2,3,4,4a,5,7a,8-octahydrobenzo-
[d]xanthene 14c and (4aRS,5SR,7aRS,13aSR)-7a-methyl-7-
methylidene-5-(2-thienyl)-1,2,3,4,4a,5,6,7,7a,8-decahydro-
X-Ray crystal structure determination of 9aB
Crystal data. Colourless prisms with dimensions 0.30 ×
0.20 × 0.10 mm, C24H24O3, M = 360.45, monoclinic, a =
6.004(2), b = 8.863(2), c = 17.725(3) Å, β = 95.56(2)Њ, V =
938.8(4) Å3, space group Pn (No. 17), Z = 2, Dx = 1.275 g cmϪ3
,
1
benzo[d]xanthene 15c in the ratio of 1:2 (from H NMR data
µ(Mo-Kα) = 0.83 cmϪ1. Data were measured on a MAR dif-
fractometer with a 300 mm image plate detector using graphite
monochromatised Mo-Kα radiation (λ = 0.71073 Å) on 60
plates with 3Њ oscillation at 120 mm distance and 330 s
exposure. 1835 unique reflections [1606 with I > 3σ(I)] were
obtained from 8274 measured reflections. The structure was
solved by direct methods (SIR9214) and refined by full-matrix
least-squares refinement on F (TEXSAN15) with all non-
hydrogen atoms anisotropic and 24 hydrogen atoms in calcu-
lated positions using riding model with Biso(H) = 1.3 B(eq) for
the attached atom. Final R = 0.042 and wR = 0.047 and
as shown below) (HRMS: found Mϩ, 350.1705. C23H26OS
requires M, 350.1704); m/z 350 (Mϩ, 75%), 243 (67), 215 (72),
133 (100), 97 (23); δH (270 MHz) 7.19 (3 H, m, 14c ϩ 15c),
6.96–6.84 (4 H, m, 14c ϩ 15c), 5.31 (0.33 × 1 H, br s, 14c),
4.82 (0.67 × 2 H, d, J 20, 15c), 3.83 (0.33 × 1 H, br dt, J 10.01,
2.93, 14c), 3.43 (0.67 × 1 H, td, J 12.45, 5.13, 15c), 3.11
(0.67 × 1 H, d, J 16.11, 15c), 2.90 (0.33 × 1 H, d, J 15.60, 14c),
2.76 (0.67 × 1 H, dd, J 12.45, 15.63, 15c), 2.53 (0.33 × 1 H, d, J
15.61, 14c), 2.53 (0.67 × 1 H, dd, J 15.63, 5.31, 15c), 2.45
(0.67 × 1 H, d, J 16.12, 15c), 2.40 (1 H, br d 14c ϩ 15c), 2.09–
1.96 (1 H, m, 14c ϩ 15c), 1.78 (0.33 × 3 H, dd, J 1.22, 2.44, Me
14c), 1.66–1.24 (7 H, m, 14c ϩ 15c), 1.22 (0.67 × 3 H, s, Me
15c), 1.18 (0.33 × 3 H, s, Me 14c); δC (67.9 MHz) signals
included 107.6 for an sp2-CH2.
GOF = 2.99 for 1606 reflections, where w = 4Fo /[σ2(I) ϩ
2
2
(0.022Fo )2], maximum residual electron density 0.27 e ÅϪ3. An
ORTEP16 drawing of the molecule is shown in Fig. 1.
References
(4aRS,5SR,7RS,7aRS,13aSR)-7,7a-Dimethyl-5-phenyl-1,2,3,4,
4a,5,6,7,7a,8-decahydrobenzo[d]xanthene 16
1 H. A. Weber, N. C. Baenziger and J. B. Glober, J. Org. Chem., 1988
53, 4567.
2 P. Djura, D. B. Stierle, B. Sullivan, D. J. Faulkner, E. Arnold and
J. Clardy, J. Org. Chem., 1980, 45, 1435.
3 A. Aiello, E. Fattorusso and M. Menna, Z. Naturforsch., Teil. B,
1993, 48, 209.
The mixture of 14a and 15a (345 mg, 100 mmol) and 5% pal-
ladium on carbon (100 mg) in ethanol (35 cm3) and ethyl acet-
ate (15 cm3) was shaken in an atmosphere of hydrogen at 40 psi
for two days using a Parr hydrogenator. The resulting solution
J. Chem. Soc., Perkin Trans. 1, 1998, 3267–3276
3275

View Article Online
4 A. E. Wright, S. A. Rueth and S. S. Cross, J. Nat. Prod., 1991, 54,
1108.
5 M. L. B. Kondracki, M. T. Martin and M. Guyot, Tetrahedron Lett.,
1992, 33, 8079.
6 R. M. Letcher, T. Y. Yue and K. K. Cheung, J. Chem. Soc., Chem.
Commun., 1993, 159.
7 R. M. Letcher, J. Chem. Educ., 1980, 220.
8 R. M. Letcher and T. Y. Yue, J. Chem. Soc., Chem. Commun., 1992,
1310.
13 D. Desai, P. Lakhlani, D. Mendes, K. S. Varma and P. S. Fernandes,
Indian J. Chem., Sect. B, 1981, 20B, 1005.
14 A. Altomare, M. Cascarano, C. Giacovazzo, A. Guagliardi,
M. C. Burla, G. Polidori and M. Camalli, J. Appl. Cryst., 1994, 27,
435.
15 TEXSAN: Crystal Structure Analysis Package, Molecular Structure
Corporation, 3200 Research Forest Drive, The Woodland, TX, USA,
1985 and 1992.
16 C. K. Johnson: ORTEPII, Report ORNL-5318. Oak Ridge
National Laboratory, Tennessee, USA, 1976.
9 A. McKillop and E. C. Taylor, Chem. Br., 1973, 4.
10 E. C. Taylor, G. H. Hawks III and A. McKillop, J. Am. Chem. Soc.,
1968, 90, 2421.
11 G. A. Olah, Q. Wang and G. K. S. Prakash, Synlett, 1992, 647.
12 H. L. Gaggad, K. N. Wadodkor and B. J. Ghiya, Indian J. Chem.,
Sect. B, 1985, 24B, 1244.
Paper 8/04365E
3276
J. Chem. Soc., Perkin Trans. 1, 1998, 3267–3276