Total synthesis of (±)-iso-trans-trikentrin B

Article abstract of DOI:10.1071/C97112

The synthesis of the title compound, a member of a family of cyclopent[g]indoles isolated from a marine sponge, is described. Most of the synthetic sequence was developed starting from the more readily available cis-l,3-dimethylindan. An X-ray crystal structure of the indanol (24), the precursor of trns-1,3-dimethylindan, confirmed its relative stereochemistry.

Full text of DOI:10.1071/C97112

C S I R O P U B L I S H I N G
Australian Journal
of Chemistry
Volume 51, 1998
© CSIRO Australia 1998
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Aust. J. Chem., 1998, 51, 177–187
.
Total Synthesis of ( )-Iso-trans-trikentrin B
John K. MacLeod,A,B Annemarie Ward A and Anthony C. Willis A
A
Research School of Chemistry, Australian National University,
Canberra, A.C.T. 0200.
B
Author to whom correspondence should be addressed.
The synthesis of the title compound, a member of a family of cyclopent[g]indoles isolated from a
marine sponge, is described. Most of the synthetic sequence was developed starting from the more
readily available cis-1,3-dimethylindan. An X-ray crystal structure of the indanol (24), the precursor
of trans-1,3-dimethylindan, con rmed its relative stereochemistry.
The trikentrins (1)–(5) are a family of novel
cyclopent[g]indoles, isolated from the marine sponge
Trikentrion abelliforme, which exhibit growth inhibi-
tory activity against Gram-positive bacteria.1 Since
the rst reported total synthesis by us of ( )-cis- and
trans-trikentrin A, (1) and (3) respectively,2,3 other
groups have published syntheses of racemic (1)4–6 and
(3)4,6 as well as syntheses of ( )-cis-trikentrin B (2),5,7
( )-trans-trikentrin B (4)5 and ( )-iso-trans-trikentrin
B (5).5 The absolute stereochemistry of the trikentrins
was established by enantioselective syntheses of either
the natural product or its enantiomer.5,8–11 These
syntheses have utilized a variety of approaches to fab-
ricate the tricyclic ring system, including aryl radical
cyclization,2,3 intramolecular Diels–Alder reactions,6,7
and acid-catalysed indole cyclization.5 We now report a
synthesis of ( )-iso-trans-trikentrin B (5) which follows
the same basic methodology that we used previously
for the elaboration of the cyclopent[g]indole system.2,3
steps leading to the target compound (5) were rst
carried out with (6a) as the starting material.
Friedel–Crafts acylation of (6a) with butyryl chlo-
ride/aluminium chloride gave a single regioisomer (7a)
in 82% yield, whose structure was veri ed by n.m.r.
and mass spectrometry. Sodium borohydride reduc-
tion of ketone (7a) gave in high yield the benzylic
alcohol (8a) as a mixture of diastereomers, which
was converted into its methoxymethyl ether (9a). All
attempts to formylate (9a) directly were unsuccessful.
Attempted ortho-directed metalation12 of (9a), with
a variety of alkyllithium reagents of increasing basic-
ity followed by quenching with methan(D)ol, showed
no deuterium incorporation in the recovered starting
material (9a), as evidenced by g.c.–m.s. analysis of the
reaction product. When the same series of reactions
was performed on the alcohol (8a), with 2 equiv. of
alkyllithium, a high incorporation of one deuterium
atom was observed, but only when t-butyllithium was
used. Replacement of methan(D)ol with dimethyl-
formamide as the quenching agent gave a product
mixture which contained some starting material (8a)
together with the lactol (10) as the major product
and the hydroxy aldehyde (11a) in minor amounts.
Although (9a) could be readily separated from (10) and
(11a), the free aldehyde itself could not be isolated.
N.m.r. studies of the equilibrium concentrations of
the interconverting aldehyde (11a) and lactol (10)
showed that, under all conditions of pH and solvent
used, the lactol form predominated. It was not sur-
prising, therefore, that no aldehyde derivates (acetal,
thioacetal) could be formed from (10), nor was any
identi able product given on attempted condensation
with ethyl azidoacetate. The formation of the lactol,
together with the presence of two aromatic singlets in
its 1H n.m.r. spectrum, did nevertheless con rm that
proton abstraction had occurred exclusively from the
6-position of (8a).
Results and Discussion
Because cis-1,3-dimethylindan (6a) could be pre-
pared more readily than the trans-isomer (6b), by using
procedures developed previously,3 exploratory reaction
R1
R1
R2
R2
N
N
H
H
R1
R2
H
R1
R2
(1) Et
(2)
(3)
(4)
Et
H
H
(E)-but-1-enyl
H
H
(E)-but-1-enyl
(5) (E)-but-1-enyl
Manuscript received 27 June 1997
᭧ CSIRO Australia 1998
0004-9425/98/030177$ 05.00

178
J. K. MacLeod, A. Ward and A. C. Willis
R1
(21a) by using diisobutylaluminium hydride was unsuc-
cessful and instead gave the corresponding alcohol (20a)
in about 90% yield. Oxidation of (20a) with manganese
dioxide16 provided the aldehyde (21a). Decarbonyla-
tion of (21a) was carried out with a catalytic amount
of bis(triphenylphosphine)(carbonyl)rhodium(I) chlo-
ride and 1,3-bis(diphenylphosphino)propane in re uxing
mesitylene,13,15 giving (19a) in yields of 60–70%.
(a) cis
(b) trans
R2
O
R1
R2
OH
(6)
H
H
H
H
H
4'
(7)
(8)
COPr
3'
(a) cis
CH(OH)Pr
(b) trans
OR1
2'
N
CO2Et
1'
4
(9) CH(OCH2OMe)Pr
(11)
(12)
CH(OH)Pr
CH(OH)Pr
CHO
Br
(10)
3
(13) CH(OCH2OMe)Pr
(14) CH(OCH2OMe)Pr
Br
5
R2
2
1
CHO
N
6
(15) CH(OCH2OMe)Pr CH=C(N3)CO2Et
8
R3
7
(17)
R1
R2
R3
To overcome the undesirable intermediacy of the
lactol, the aldehyde functionality was replaced by a
bromine atom. A number of brominating agents were
used to quench the aryllithium from (8a), with carbon
tetrabromide giving the cleanest product and best yields
of the 6-bromo compound (12a). Protection of the
benzylic hydroxy group of (12a) as its methoxymethyl
ether gave (13a), which was treated with butyllithium
followed by dimethylformamide to a ord the aldehyde
(14a) in 81% yield. The regiochemistry of (14a) was
con rmed by its n.m.r. and mass spectra.
CH2OMe CO2Et
CH2OMe CO2H
H
H
(16)
(18)
(19)
(20)
(21)
(22)
(23)
CH2OMe
H
H
CH2OMe CH2OH
CH2OMe CHO
H
H
HO
(24)
CH2OMe
H
H
H
COMe
COMe
The nal step in the model reaction sequence with
the cis-analogue was the introduction of the (E)
double bond in the C4 side chain of (19a). It was
necessary to leave this until late in the synthesis
because of the lability of the resultant ‘styryl’ system.
Natsume9,10 had shown that elimination of the C4 side
chain benzylic alcohol from an N -protected precursor
of cis- and trans-trikentrin B, (2) and (4), could be
carried out in high yield by using a catalytic amount
of p-toluenesulfonic acid in re uxing benzene. These
conditions were applied to the methoxymethyl ether
(19a) in the expectation that deprotection of the ben-
zylic alcohol and subsequent dehydration would occur
in a one-pot reaction. In the event, no identi able
products could be isolated. Since Natsume had used
an N -benzenesulfonate in the dehydration reaction, we
attempted to form the N -benzenesulfonate derivative
of (19a). This was unsuccessful probably due to
steric hindrance. It was possible, however, to form an
N -acetyl derivative (22a) with acetic anhydride. The
methoxymethyl protecting group was then removed from
(22a) with dimethylboron bromide17 and the resulting
benzylic alcohol (23a) treated with p-toluenesulfonic
acid in benzene. Only starting material and no ole nic
products could be identi ed in the reaction mixture.
By this stage, the synthesis of ( )-iso-trans-trikentrin
B (5) was well underway and further developmental
studies using the model cis-isomer were put aside.
The starting compound for the synthesis of (5),
trans-1,3-dimethylindan (6b), had previously been pre-
pared by reduction of cis-1,3-dimethylindan-1-ol (24)
Elaboration of the pyrrole ring onto the indan ring
followed the procedure developed by Moody13 and used
by us for the synthesis of (1) and (3).2,3 The aldehyde
(14a) was condensed with ethyl azidoacetate to give the
unstable azidocinnamate (15a). The nitrene generated
by heating (15a) can undergo either electrocyclization
to give the required indole ester (16a) or insertion
into the adjacent benzylic position of the alkoxybutyl
side chain to give the unwanted isoquinoline (17a).13
Thermolysis of (15a) in re uxing benzene provided the
indole (16a) and isoquinoline (17a) in approximately
equal amounts with an overall yield of >95%. When
the thermolysis was carried out in re uxing toluene,
the overall yield was lower but the isolated yield of
the indole (16a) increased considerably (60–80%).
In our earlier synthesis of (1) and (3), the ethoxy-
carbonyl group on the indole ring was removed by base
hydrolysis to give the acid, followed by decarboxylation
by ash vacuum pyrolysis.2,3 The equipment required
for the latter reaction was no longer available to us
and therefore decarboxylation of the acid (18a), from
basic hydrolysis of (16a), was attempted by using cop-
per/quinoline at high temperature.14 Less than 10% of
the desired product (19a) was recovered from the reac-
tion mixture, the rest being decomposition products.
We therefore explored the alternative procedure used
by Moody13,15 of rhodium-catalysed decarbonylation of
the indole-2-carbaldehyde derived from the ethyl ester
(16a). Direct reduction of (16a) to the carbaldehyde

Synthesis of ( )-Iso-trans-trikentrin B
179
with W7 Raney nickel.3 The indanol (24) could be
isolated and puri ed as a crystalline compound from the
mixture (c. 1 : 1) of the cis- and trans-isomers formed
from an aryl radical intramolecular cyclization of 2-
(2-bromophenyl)pent-4-en-2-ol.3 We have obtained an
X-ray crystal structure of (24) (Fig. 1) which con rms
the trans-relationship of the two methyl groups. A more
direct and stereoselective route to the cis-indanol (24)
involved treatment of 3-methylindan-1-one with methyl-
magnesium iodide; this gave a product that contained
predominantly the cis-isomer.18 3-Methylindan-1-one
was prepared in c. 80% yield in a one-pot reaction of
benzene and but-2-enoic acid, by using a modi cation
of the method of Koelsch et al.19
of the azidocinnamate (15b), proceeded satisfactorily.
Less than 10% of a minor component was present in the
reaction product and this, from H n.m.r. spectroscopy
of the crude mixture, was identi ed as the alternative
isoquinoline cyclization product (17b). The n.m.r. and
mass spectra of the major component were consistent
with its assigned structure (16b).
1
Reduction of the indole ester (16b) gave the alcohol
(20b) which was oxidized to the aldehyde (21b) with
manganese dioxide and then decarbonylated to provide
the indole (19b). It was from this point that the
model synthesis with the cis-isomer had encountered
di culties, in attempting to introduce the (E) dou-
ble bond into the C4 side chain of (19a). Since
p-toluenesulfonic acid catalysed elimination of water
from the benzylic alcohol (23a) was unsuccessful, we
proposed replacing the methoxymethyl ether protecting
group of (19b) with a good leaving group that could
be eliminated under mild conditions. To carry this
out, the ether (19b) was treated with dimethylboron
bromide followed by triethylamine, under conditions
which had been shown to remove the methoxymethyl
protecting group in the cis-compound (22a). Somewhat
surprisingly, the only identi able component isolated
from the reaction mixture in 63% yield was racemic
iso-trans-trikentrin B (5). The elimination of the
benzylic ether during the reaction could have been
triggered by removal of the proton on nitrogen by
triethylamine in the intermediate complex formed after
addition of dimethylboron bromide. This pathway
was not available to the cis-compound (22a) which is
N -acetylated. The n.m.r. and mass spectrometric data
obtained for the synthetic product were comparable
with the partial data available for natural iso-trans-
trikentrin B (5)1 (which was isolated as an inseparable
mixture with cis-trikentrin B (2)) and matched those
reported by Natsume for ( )-iso-trans-trikentrin B (5)
synthesized by an alternative route.5
Fig. 1. ORTEP projection of (24) derived from X-ray crystal-
lographic data.
Stereoselective hydrogenolysis20 of the cis-indanol
(24) by using Raney nickel to give trans-1,3-di-
methylindan (6b), that is, with retention of con-
guration, proved to be a capricious reaction which
was very dependent on the method of preparation of the
reagent. In many cases, the major reduction product
was the cis-isomer (6a). The optimum conditions for
the production of (6b) were the use of freshly prepared,
slightly alkaline Raney nickel (pH of washings between
7 5 and 8 5) and distilled, degassed ethanol as solvent.
By following the above procedures developed with
the cis-isomer, trans-1,3-dimethylindan (6b) was con-
verted into the ketone (7b), which was reduced to
a diastereomeric mixture of benzylic alcohols (8b).
Metalation of (8b) followed by treatment with carbon
tetrabromide gave (12b) which was protected as the
methoxymethyl ether (13b). The aryllithium generated
from (13b) was quenched with dimethylformamide to
give the aldehyde (14b). Annelation of (14b) to the
cyclopent[g]indole ring system of (16b), via thermolysis
Experimental
Melting points were determined on a Reichert hot-stage
apparatus and are uncorrected. Microanalyses were carried out
by the Australian National University Microanalytical Service.
Low-resolution electron-impact mass spectra and high-resolution
accurate mass measurements were recorded on either a VG
Micromass 7070F or a VG ZAB-2SEQ mass spectrometer. The
molecular ion (M+), if present, signi cant high-mass ions and the
more intense low-mass ions are reported. Chemical-ionization
mass spectra were measured on the VG Micromass 7070F mass
spectrometer, employing ammonia as the reagent gas. Infrared
spectra were recorded on a Perkin–Elmer 683 or Perkin–Elmer
1800 (Fourier transform) spectrophotometer as lms (neat) or
dichloromethane (CH2Cl2) solutions. The following abbrev-
iations were adopted to indicate the intensity and to describe
the shape of the band: s (strong), m (medium), w (weak) and
br (broad). 1H n.m.r. spectra were recorded on either a Varian
Gemini-300 (300 MHz), a Varian VXR-300 (300 MHz) or a
Varian VXR-500 (500 MHz) spectrometer. Unless otherwise
stated spectra were recorded at 300 MHz by using CDCl3 as
solvent and tetramethylsilane as the internal reference. The
chemical shifts of diastereomers are in parentheses. 13C n.m.r.

180
J. K. MacLeod, A. Ward and A. C. Willis
spectra were recorded on a Varian Gemini-300 (75 5 MHz) or a
Varian VXR-300 (75 4 MHz) spectrometer. The solvent signal
was used as the internal reference (76 9 ppm for chloroform)
and the signals are quoted as values (ppm down eld from
tetramethylsilane). The chemical shifts of diastereomers are in
parentheses. Two-dimensional n.m.r. experiments were carried
out on a Varian VXR-300 spectrometer by using standard Var-
ian pulse sequences. Ultraviolet–visible spectra were recorded
on a Shimadzu model UV-160 or a Cary 1E spectrophoto-
meter. Where necessary, solvents and reagents were puri ed
and dried according to procedures of Perrin and Armarego.21
Flash chromatography22 was carried out with 230–400 mesh
silica gel. For thin-layer chromatography, 0 25-mm Merck silica
gel F254 plates were used for analytical purposes. Thin-layer
chromatograms were visualized under ultraviolet light or by
spraying with 13% vanillin in sulfuric acid, followed by heating
at c. 200 C.
d, J 6 8 Hz, CH3; 1 32, d, J 6 8 Hz, CH3; 1 19, dt, J 12 1,
10 5 Hz, 1H, H 20b; 0 95, t, J 7 2 Hz, 3H, H 4. 13C n.m.r.
149 0, (148 9), 148 0, 143 3, 3 Ar Cquat; 124 2, (123 9),
122 7, (122 6), 120 4, (120 3), 3 Ar CH; 74 6, (74 5), OCH;
44 9, C 20; 41 0, C 2; 37 7, 37 5, C 10 and C 30; 18 98, 2 CH3;
18 98, C 3; 13 6, C 4. Mass spectrum: m/z 218 (M+, 3%),
203 (1), 176 (13), 175 (100), 145 (5), 105 (82), 91 (46).
cis-5-(1 0-Methoxymethyloxybutyl)-1,3-dimethylindan (9a)
The methoxymethyl ether (9a) was prepared by the method
of Stork and Takahashi.23 To a stirred solution of the alcohol
(8a) (1 0 g, 4 58 mmol) in dichloromethane (25 ml) at 0 C,
methoxymethyl chloride (2 09 ml, 27 48 mmol) was added.
Ethyldiisopropylamine (4 79 ml, 27 48 mmol) was added slowly
to the solution. The reaction mixture was warmed to room
temperature and it was stirred for a further 28 h until the
reaction was complete. The reaction mixture was poured onto
a mixture of ice and water (30 g) with stirring. The aque-
ous layer was separated and extracted with dichloromethane
(3 15 ml). The organic layers were combined and washed
with 10% hydrochloric acid solution (20 ml), saturated sodium
hydrogen carbonate solution (2 20 ml) and saturated sodium
chloride solution (20 ml). The organic layer was dried (MgSO4)
and the solvent was removed by distillation to give (9a) as
a yellow oil (1 13 g, 94%), b.p. 80 C/0 8 mmHg (Found: C,
1-(cis-1 0,3 0-Dimethylindan-5 0-yl)butan-1-one (7a)
Butyryl chloride (4 58 ml, 44 1 mmol) in dry dichloro-
methane (20 ml) was added dropwise to a vigorously stirred
suspension of aluminium trichloride (5 88 g, 44 1 mmol) in
dry dichloromethane (20 ml) under argon. The mixture was
stirred for 50 min and was then cooled to 0 C. A solution of
cis-1,3-dimethylindan (6a) (4 30 g, 29 4 mmol), prepared by
the method of MacLeod and Monahan,3 in dry dichloromethane
(10 ml) was added dropwise at a rate su cient to maintain
the reaction temperature at c. 2 C. The reaction mixture
turned orange and, after the addition was complete, the mix-
ture was allowed to warm to room temperature. After being
stirred for 1 5 h, the mixture was poured onto ice (100 g).
Dichloromethane (50 ml) was added to the iced reaction mixture
with stirring. The organic layer was separated and the aqueous
layer was reextracted with dichloromethane (3 40 ml). The
combined organic fractions were washed with saturated sodium
hydrogen carbonate solution (3 30 ml) and dried (MgSO4).
The dichloromethane and residual butyryl chloride were removed
by distillation which gave an oil. The oil was chromatographed
on silica (diethyl ether/hexane, 1 : 9) to give (7a) as a colourless
oil (5 20 g, 82%), b.p. 105 C/0 08 mmHg (Found: C, 83 0;
78 0; H, 9 7. C17H26O2 requires C, 77 8; H, 10 0%).
(neat) 1109 cm
max
(C–O). 1H n.m.r. 7 11, s, 3 ArH; 4 53,
1
m, OCH2O and OCH; 3 39, (3 38), s, OCH3; 3 06, m, 2H,
H 1 and H 3; 2 48, dt, J 12 0, 7 0 Hz, 1H, H 20a; 1 85, m,
1H, H 20a; 1 69–1 25, br m, 3H, H 20 and H 30; 1 30, d, J
b
6 7 Hz, CH3; 1 29, d, J 6 7 Hz, CH3; 1 16, m, 1H, H 2b;
0 93, t, J 7 3 Hz, 3H, H 40. 13C n.m.r. 148 8, 148 0, 140 4,
3
Ar Cquat; 125 1, 122 6, 121 4, (121 2), 3 Ar CH; 93 9,
OCH2O; 77 8, CHO; 55 3, OCH3; 45 0, C 2; 40 2, C 20; 37 7,
37 6, C 1 and C 3; 19 0, C 30; 18 9, 2 CH3; 13 6, C 40. Mass
spectrum: m/z 262 (M+, 2%), 247 (1), 220 (15), 219 (70), 201
(10), 175 (21), 145 (27), 105 (52), 91 (100).
General Procedure used for Metalation Reactions with
Butyllithium Reagents
H, 9 5.
1683s cm
C
15H20O requires C, 83 3; H, 9 3%).
(neat)
max
An excess of the appropriate butyllithium was added under
strictly anhydrous conditions to a stirred solution of the sub-
strate in dry solvent under argon at 0 C. The reaction mixture
was heated, usually to the boiling point of the solvent, and
maintained at this temperature until a colour developed. The
solution was then cooled, quenched with an electrophile, and
stirred for a further 20 min. It was then diluted with diethyl
ether and washed with water. After the aqueous washings were
back-extracted with diethyl ether, the organic fractions were
combined and dried (MgSO4).
1
(C=O). 1H n.m.r. 7 83, d, J 8 0 Hz, 1H, H 60;
7 78, s, 1H, H 40; 7 25, d, J 8 0 Hz, 1H, H 70; 3 12, m, 2H,
H 10 and H 30; 2 93, t, J 7 4 Hz, 2H, H 2; 2 50, dt, J 12 1,
7 0 Hz, 1H, H 20a; 1 78, sextet, J 7 4 Hz, 2H, H 3; 1 35, d,
J 7 4 Hz, CH3; 1 32, d, J 7 0 Hz, CH3; 1 18, dt, J 12 1,
10 5 Hz, 1H, H 20b; 1 02, t, J 7 4 Hz, 3H, H 4. 13C n.m.r.
200 9, C=O; 154 3, 149 2, 135 7, 3 Ar Cquat; 127 0, 122 8,
122 5, 3 Ar CH; 44 7, C 20; 40 4, C 2; 38 0, 37 7, C 10 and
C 30; 18 9, 18 7, 2 CH3; 17 7, C 3; 13 6, C 4. Mass spectrum:
m/z 216 (M+, 11%), 188 (3), 173 (100), 145 (11), 91 (7).
cis-5,7-Dimethyl-3-propyl-3,5,6,7-tetrahydro-1 H-indeno[5,6-
c]furan-1-ol (10)/cis-6-(1 0-Hydroxybutyl)-1,3-dimethylindan-
5-carbaldehyde (11a)
1-(cis-1 0,3 0-Dimethylindan-5 0-yl)butan-1-ol (8a)
The butanone (7a) (2 50 g, 11 56 mmol) was dissolved
in methanol (25 ml) and the solution was cooled to 10 C.
Sodium borohydride (0 66 g, 17 36 mmol) was added to the
stirred solution in portions at a rate su cient to maintain the
reaction temperature between 0 and 2 C. Once the addition
was complete, the mixture was stirred for 50 min as it warmed
to room temperature. The reaction mixture was then poured
onto water (40 ml) and the methanol was removed under
reduced pressure. The aqueous residue was extracted with
dichloromethane (3 30 ml), dried (MgSO4) and the solvent
removed to give the title compound (8a) as a colourless oil
(2 47 g, 98%), b.p. 154 C/0 08 mmHg (Found: C, 82 2; H,
The general metalation procedure was followed for the lithi-
ation of the alcohol (8a). The amounts of reagents and solvents
used were as follows: alcohol (8a) (30 mg, 137 mol) in dry,
distilled heptane (2 5 ml) and 1 4 M t-butyllithium in pentane
(880 l, 1 23 mmol). The mixture was heated to re ux for 1 h.
It was cooled and an excess of N,N-dimethylformamide (120 l)
was added. After workup, the residue was chromatographed
(silica; ethyl acetate/light petroleum, 1 : 4) to a ord an insep-
arable mixture of the title compounds (10) and (11a) as a
colourless oil (29 mg, 85%), b.p. 79–80 C/0 8 mmHg (Found:
C, 78 5; H, 8 8%; M+
, 246 1619. C16H22O2 requires
(neat) 3380br
Minor component (11a): 10 09,
C, 78 0; H, 9 0%; M+ , 246 1620).
10 0.
3385br cm
C
15H22O requires C, 82 5; H, 10 2%).
1
(neat)
max
max
(OH). 1H n.m.r. 7 15, m, 3H, ArH; 4 68, t, J
1
cm
(OH). 1H n.m.r.
6 6 Hz, OCH; 3 08, m, 2H, H 10 and H 30; 2 50, dt, J 12 1,
s, CHO. Major component: 7 20, s, 1H, ArH; 6 97, s,
1H, ArH; 6 44, br s, (6 38, d, J 4 0 Hz), 1H, H 1; 5 38,
7 0 Hz, 1H, H 20a; 1 95–1 20, m, 5H, H 2, H 3 and OH; 1 33,

Synthesis of ( )-Iso-trans-trikentrin B
181
m, (5 12, m), 1H, H 3; 3 05, m, 2H, H 5 and H 7; 2 81, m,
OH [exchangeable with D2O]; 2 52, m, 1H, H 6a; 1 8–1 2,
br m, 5H, H 10, H 20 and H 6b; 1 33, d, J 6 0 Hz, 2 CH3;
0 99, t, J 6 0 Hz, (0 97, t, J 5 8 Hz), 3H, H 30. 13C n.m.r.
150 5, 149 05, (148 98), 141 23, (141 17), 137 72, 4 Ar
1 : 9) to give the title compound (14a) as a colourless oil
(367 mg, 81%), b.p. 62 C/1 0 mmHg (Found: [M 1]+
,
289 1804.
1700s (CHO), 1610m cm
C
18H25O3 requires m/z, 289 1804).
1
(neat)
max
(ArH). 1H n.m.r. 10 33, (10 31),
s, 1H, CHO; 7 64, s, 1H, H 4; 7 40, s, 1H, H 7; 5 44, m, 1H,
OCH; 4 57, m, 2H, OCH2O; 3 38, (3 37), s, OCH3; 3 12,
m, 2H, H 1 and H 3; 2 54, dt, J 12 1, 6 2 Hz, 1H, H 2a;
1 94–1 16, m, 4H, H 20 and H 30; 1 36, (1 35), d, J 6 3 Hz,
CH3; 1 33, d, J 6 7 Hz, CH3; 1 22, m, 1H, H 2b; 0 95, t, J
7 2 Hz, 3H, H 40. 13C n.m.r. 192 37, (192 32), CHO; 155 27,
147 97, 144 42, 132 36, 4 Ar Cquat; 125 94, (125 81), 121 73,
(121 63), 2 Ar CH; 94 85, (94 74), OCH2O; 74 59, (74 33),
OCH; 55 67, OCH3; 44 82, (44 76), C 2; 41 09, (41 03),
C 20; 38 55, (38 46), 37 60, C 1 and C 3; 19 39, C 30; 19 02,
CH3; 18 81, (18 78), CH3; 13 79, C 40. Mass spectrum: m/z
289 ([M 1]+, 1%), 245 (100), 229 (29), 217 (15), 203 (70).
Chemical-ionization mass spectrum: m/z 291 (MH+, 11%),
289 (12), 259 (20), 245 (30), 229 (100).
Cquat; 117 11, (117 07), 115 43, (115 34), 2 Ar CH; 100 65,
(100 56), OCHO; 82 96, (82 22), OCH; 45 35, (45 32), C 6;
37 69, 37 65, C 5 and C 7; 19 17, 19 11, 2 CH3; 18 79,
(18 58), C 10; 18 44, (18 31), C 20; 14 03, (13 99), C 30. Mass
spectrum: m/z 246 (M+, 2%), 228 (35), 213 (70), 203 (100),
199 (91), 143 (27), 128 (32), 115 (30).
1-(cis-5 0-Bromo-1 0,3 0-dimethylindan-6 0-yl)butan-1-ol (12a)
The general lithiation procedure was followed. Reagents and
solvents used were as follows: alcohol (8a) (1 0 g, 4 6 mmol)
in heptane, 1 4 M t-butyllithium in pentane (50 mmol) and
carbon tetrabromide (50 mmol) in heptane. The residue was
chromatographed on silica (ethyl acetate/light petroleum, 1 : 9)
to give recovered starting material (8a) (240 mg, 24%) and
the title compound (12a) (1 02 g, 75%) as a colourless solid,
Preparation of the Azidocinnamate (15a)
m.p. 79–80 C (Found: C, 59 9; H, 7 3; Br, 26 8%; M+
296 0787. C15H21BrO requires C, 60 6; H, 7 1; Br, 26 9%;
15H2179BrO, M+ , 296 0776). 1H n.m.r. 7 35, s, 1H, ArH;
,
A mixture of the formylindan (14a) (350 mg, 1 21 mmol),
freshly prepared ethyl azidoacetate24 (2 50 g, 19 4 mmol) and
dry, distilled ethanol (1 5 ml) was added dropwise to a stirred
solution of sodium (345 mg, 15 mmol) and ethanol (20 ml)
under argon at 15 C. The reaction mixture was kept between
15 and 10 C over 5 5 h and then was allowed to slowly
warm to room temperature over 1 h. Water (20 ml) was
added and the solution was extracted with dichloromethane
(3 10 ml). The combined organic fraction was washed with a
phosphate bu er solution (pH 6 8, 2 10 ml), dried (MgSO4)
and the solvent removed. The residue was chromatographed
(silica; ethyl acetate/light petroleum, 1 : 9) to give (15a) as
C
7 30, (7 29), s, 1H, ArH; 5 10, m, 1H, OCH; 3 05, m, 2H,
H 10 and H 30; 2 47, m, 1H, H 20a; 1 89, m, 1H, OH; 1 71, m,
2H, H 2; 1 57–1 34, br m, 2H, H 3; 1 32, d, J 6 7 Hz, CH3;
1 29, d, J 6 9 Hz, CH3; 1 25, m, 1H, H 20b; 0 98, m, 3H, H 4.
13C n.m.r. 149 57, (149 46), 148 30, 141 42, (141 34), 3 Ar
Cquat; 126 91, (126 88), 121 40, (121 35), 2 Ar CH; 119 69,
(119 54), Ar CBr; 72 83, (72 64), OCH; 45 06, (44 97), C 20;
39 92, (39 86), C 2; 37 79, (37 71), 37 69, C 10 and C 30;
19 11, CH3; 19 07, (19 01), C 3; 18 97, CH3; 13 88, C 4.
Mass spectrum: m/z 298 (M+, 5%), 296 (M+, 5), 255 (91),
253 (100), 185 (25), 183 (26).
an unstable yellow oil (300 mg, 63%).
1
(CH2Cl2) 2130s
7 63, (7 62), s, 1H,
max
(N3), 1715s cm
(C=O). 1H n.m.r.
H 4; 7 31, (7 30), s, 1H, H 7; 7 26, s, 1H, =CH; 4 85, m,
1H, OCH; 4 59, d, J 6 7 Hz and 4 54, d, J 6 6 Hz, (4 50,
d, J 6 9 Hz), 2H, OCH2O; 4 38, q, J 7 1 Hz, OCH2CH3;
3 39, (3 38), s, OCH3; 3 06, m, 2H, H 1 and H 3; 2 50, dt,
J 11 9, 6 6 Hz, H 2a; 1 84–1 13, m, 5H, H 20, H 30 and H 2b;
1 40, t, J 7 1 Hz, 3H, OCH2CH3; 1 37, d, J 6 8 Hz, (1 36,
d, J 6 6 Hz), CH3; 1 31, d, J 6 6 Hz, (1 30, d, J 6 8 Hz),
CH3; 0 95, t, J 6 9 Hz, (0 94, t, J 7 2 Hz), 3H, H 40. 13C
cis-5-Bromo-6-(1 0-methoxymethyloxybutyl)-1,3-
dimethylindan (13a)
The same method was used as that detailed above for
preparing the methoxymethyl ether of (8a). The reagents and
amounts used were as follows: indan (12a) (511 mg, 1 72 mmol),
ethyldiisopropylamine (150 l, 850 mol) and methoxymethyl
chloride (65 l, 850 mol). The reaction was complete after
26 h. The crude product was chromatographed (silica; ethyl
acetate/light petroleum, 1 : 9) to give recovered starting material
(12a) (40 mg, 8%) and (13a) as a colourless oil (532 mg, 91%),
b.p. 70 C/1 3 mmHg (Found: M+ , 340 1037. C17H2579BrO2
requires M+ , 340 1038). 1H n.m.r. 7 27, s, 1H, ArH; 7 25,
s, 1H, ArH; 5 02, m, 1H, OCH; 4 55, d, J 6 5 Hz, (4 53,
d, J 6 3 Hz), 4 52, d, J 6 6 Hz, (4 51, d, J 6 6 Hz), 2H,
OCH2O; 3 41, (3 40), s, OCH3; 3 05, m, 2H, H 1 and H 3;
2 46, m, 1H, H 2a; 1 72–1 21, m, 4H, H 20 and H 30; 1 28, d,
J 7 0 Hz, 2 CH3; 1 17, dt, J 12 1, 10 8 Hz, 1H, H 2b; 0 97,
m, 3H, H 40. 13C n.m.r. 149 51, 148 23, 139 35 (139 29),
n.m.r.
129 20, (129 14), 125 94, 5
163 41, CO2Et; 150 15, 147 28, 139 84, (139 80),
quat; 123 82, (123 72), 123 66,
C
(123 61), 120 85, 3 CH; 94 15, OCH2O; 74 52, (74 49), OCH;
62 06, OCH2CH3; 55 50, OCH3; 44 94, (44 90), C 2; 39 95,
(39 89), C 20; 38 16, (38 08), 37 74, C 1 and C 3; 19 19, C 30;
19 07, CH3; 18 97, CH3; 14 05, OCH2CH3; 13 75, (13 64),
C 40. Mass spectrum: m/z 330 (1%), 288 (6), 270 (8), 245
(49).
Ethyl cis-4-(1 0-Methoxymethyloxybutyl)-6,8-dimethyl-1,6,7,8-
tetrahydrocyclopent[ g]indole-2-carboxylate (16a)
3
Ar Cquat; 126 80, C 4; 121 85, C 7; 120 44, Ar CBr; 94 73,
A solution of the azidocinnamate (15a) (300 mg, 750 mol)
in toluene (80 ml) was plunged into a preheated oil bath (140 C)
and allowed to re ux for 45 min. The mixture was cooled and
the toluene removed under reduced pressure. The residue was
chromatographed (silica; ethyl acetate/light petroleum, 1 : 9)
to yield as the major component the title compound (16a) as a
(94 59), OCH2O; 76 63, (76 58), OCH; 55 72, OCH3; 45 08,
(44 99), C 2; 39 41, (39 28), C 20; 37 78, 37 71, C 1 and C 3;
19 12, C 30; 19 07, CH3; 18 99, (18 94), CH3; 13 79, C 40.
Mass spectrum: m/z 342 (M+, 9%), 340 (M, 9), 299 (92), 297
(90), 269 (19), 267 (21), 253 (95), 251 (100), 239 (87), 237
(91).
yellow oil (228 mg, 81%), b.p. 82 C/1 8 mmHg (Found: M+
,
(neat)
373 2253. C22H31NO4 requires M+ , 373 2253).
3455m (N–H), 1700s cm
max
cis-6-(1 0-Methoxymethyloxybutyl)-1,3-dimethylindan-5-
carbaldehyde (14a)
(C=O). 1H n.m.r. 8 73, br s, 1H,
1
NH; 7 41, (7 40), d, J 1 9 Hz, 1H, H 3; 6 97, s, 1H, H 5; 4 94,
m, 1H, OCH; 4 56, m, 2H, OCH2O; 4 41, q, J 7 2 Hz, 2H,
OCH2CH3; 3 45, m, 1H, H 6; 3 43, (3 41), s, OCH3; 3 21,
m, 1H, H 8; 2 64, m, 1H, H 7a; 2 00, (1 80), m, 2H, H 20;
1 51, (1 35), m, 2H, H 30; 1 51, d, J 6 9 Hz, CH3; 1 43, t, J
7 2 Hz, 3H, OCH2CH3; 1 37, (1 36), d, J 6 9 Hz, CH3; 1 35,
m, 1H, H 7b; 0 94, t, J 7 3 Hz, 3 H, H 40. 13C n.m.r. 162 1,
For the general procedure for the lithiation reaction see
that used for the lithiation of the alcohol (8a). The amounts
of reagents used were as follows: aryl bromide (13a) (532 mg,
1 56 mmol), 1 6 M butyllithium in hexane (1 95 ml, 3 12 mmol)
and dimethylformamide (1 2 ml, 15 6 mmol). The crude prod-
uct was chromatographed (silica; ethyl acetate/light petroleum,

182
J. K. MacLeod, A. Ward and A. C. Willis
CO2Et; 146 0, 134 7, (134 6), 134 1, 129 0, 126 4, 124 9,
OCH2O; 3 46, m, 1H, H 6; 3 44, (3 43), s, OCH3; 3 26, m,
1H, H 8; 2 61, dt, J 12 4, 7 5 Hz, 1H, H 7a; 2 00, m, 1H,
H 20a; 1 82, m, 1H, H 20b; 1 50–1 25, br m, 3H, H 30 and
H 7b; 1 51, d, J 7 0 Hz, CH3; 1 36, d, J 7 0 Hz, (1 35, d,
J 6 8 Hz), CH3; 0 94, t, J 7 4 Hz, 3H, H 40. 13C n.m.r.
142 62, 132 69, 132 48, 128 39, 125 13, 5 Ar Cquat; 122 90,
113 86, (113 57), 101 74, 3 Ar CH; 93 98, OCH2O; 76 89,
OCH; 55 43, OCH3; 44 50, C 7; 39 26, C 20; 38 70, C 8; 37 13,
C 6; 20 84, CH3; 20 55, CH3; 19 56, C 30; 13 87, C 40. Mass
spectrum: m/z 301 (M+, 6%), 258 (9), 226 (8), 212 (8), 198
(100).
6
Ar Cquat; 115 4, (115 1), C 5; 108 1, (108 0), C 3; 94 0,
(93 9), OCH2O; 77 1, C 10; 60 8, OCH2CH3; 55 5, OCH3;
44 1, C 7; 39 5, (39 4), C 20; 39 0, C 8; 37 1, C 6; 20 8, CH3;
20 6, CH3; 19 6, C 30; 14 3, OCH2CH3; 13 9, C 40. Mass
spectrum: m/z 373 (M+, 11%), 330 (10), 312 (6), 284 (26),
270 (43), 258 (16), 240 (15), 228 (16), 224 (12), 212 (18), 86
(67), 84 (100).
The minor component was the isoquinoline (17a) which was
isolated as a colourless solid (12 mg, 5%), m.p. 119 5–120 C
(Found: M+ , 311 1886. C20H25NO2 requires M+ , 311 1885).
1H n.m.r. 8 39, s, 1H, H 4; 7 90, s, 1H, H 9; 7 67, s, 1H, H 5;
4 50, q, J 7 5 Hz, 2H, OCH2CH3; 3 41, m, 1H, H 6 or H 8;
3 36, t, J 7 7 Hz, 2H, H 10; 3 24, m, 1H, H 6 or H 8; 2 60,
dt, J 12 1, 7 2 Hz, 1H, H 7a; 1 91, m, 2H, H 20; 1 44, m,
9H, 3 CH3; 1 32, m, 1H, H 7b; 1 09, t, J 7 3 Hz, 3H, H 30.
13C n.m.r. 166 22, CO2Et; 162 07, C 1; 152 64, 151 62, Ar
cis-4-(1 0-Methoxymethyloxybutyl)-6,8-dimethyl-1,6,7,8-
tetrahydrocyclopent[ g]indole-2-methanol (20a)
To a solution of the ethyl indole-2-carboxylate (16a) (11 mg,
29 mol) in toluene (2 ml) at 74 C under argon was added
1 5 M diisobutylaluminium hydride in toluene (22 l, 32 mol).
The mixture was warmed to 41 C. After being stirred for
1 h at this temperature the reaction mixture was quenched
with saturated ammonium chloride solution. The mixture was
warmed to room temperature and extracted with diethyl ether
(3 2 ml). The organic layer was washed with water (2 ml),
dried (MgSO4) and the solvent evaporated to yield a yellow
oil (9 mg) that was identi ed as mainly starting material by
1H n.m.r. spectroscopy. Trace amounts of another compound
were present. The oil was then taken up in toluene (2 ml) and
1 5 M diisobutylaluminium hydride in toluene (48 l, 72 mol)
was added dropwise. The reaction mixture was stirred at
room temperature and monitored by t.l.c. The reaction was
complete after 75 min. It was then cooled (ice bath) and
saturated ammonium chloride solution (1 ml) was added. It
was extracted with diethyl ether (3 3 ml) and the organic
layer was washed with water (3 ml), dried (MgSO4) and the
solvent evaporated. The material was chromatographed (silica;
ethyl acetate/light petroleum, 1 : 9) to yield the title compound
(20a) as a yellow oil (7 mg, 88%) (Found: M+ , 331 2146.
Cquat; 139 90, C 3; 135 41, C 8a; 127 84, C 4a; 122 57, C 4;
121 61, C 5; 118 33, C 9; 61 34, OCH2CH3; 45 08, C 7; 38 10,
C 6 or C 8; 37 83, C 8 or C 6; 37 71, C 10; 23 12, C 20; 18 64,
CH3; 18 46, CH3; 14 30, CH3; 14 26, CH3. Mass spectrum:
m/z 311 (M+, 6%), 296 (7), 283 (100), 239 (11), 222 (19), 209
(69), 194 (30).
cis-4-(1 0-Methoxymethyloxybutyl)-6,8-dimethyl-1,6,7,8-
tetrahydrocyclopent[ g]indole-2-carboxylic Acid (18a)
A stirred solution of the ester (16a) (12 mg, 32 mol) in
methanol (2 5 ml) with added sodium carbonate (20 mg) and
water (1 5 ml) was heated to 50 C for 12 h. After the solution
was cooled, the methanol was removed and the aqueous layer
extracted with diethyl ether (3 3 ml). The aqueous layer was
acidi ed with 4 M hydrochloric acid solution and extracted
with diethyl ether (3 3 ml) and dichloromethane (3 ml). The
combined organic extracts were dried (MgSO4) and the solvent
was evaporated to give the title compound (18a) as a colourless
solid (12 mg). 1H n.m.r. 8 87, s, 1H, NH; 8 61, br s, 1H,
CO2H (exchangeable with D2O); 7 69, (7 68), d, J 1 8 Hz,
1H, H 3; 7 00, s, 1H, H 5; 4 97, m, 1H, OCH; 4 58, m, 2H,
OCH2O; 3 48, m, 1H, H 6; 3 43, (3 42), s, OCH3; 3 22, m,
1H, H 8; 2 65, dt, J 6 9, 11 3 Hz, 1H, H 7a; 2 02, m, 1H,
H 20a; 1 82, m, 1H, H 20b; 1 5–1 25, m, 3H, H 30 and H 7b;
1 52, d, J 6 3 Hz, CH3; 1 36, (1 35), d, J 6 4 Hz, CH3; 0 94,
t, J 7 0 Hz, 3H, H 40. 13C n.m.r. 166 15, CO2H; 146 77,
135 06, (135 02), 134 95, 134 73, (134 70), 129 07, (129 02),
125 33, (125 09), 6 Ar Cquat; 115 55, (115 24), C 5; 110 34,
(110 23), C 3; 93 93, OCH2O; 77 07, OCH; 55 44, OCH3;
44 00, C 7; 39 49, (39 38), C 20; 39 09, (39 04), C 8; 37 04,
C 6; 20 75, CH3; 20 62, (20 55), CH3; 19 50, C 30; 13 83,
C 40. Mass spectrum: m/z 345 (M+, 20%), 302 (23), 283 (25),
242 (100).
C
(NH), 3500–3200br cm
20H29NO3 requires M+ , 331 2147).
(neat) 3460m
max
1
(OH). 1H n.m.r. 8 41, br s, 1H,
NH; 6 91, s, 1H, H 5; 6 56, br s, 1H, H 3; 4 92, m, 1H, OCH;
4 81, s, 2H, CH2–OH; 4 57, d, J 6 5 Hz, (4 56, d, J 6 6 Hz),
and 4 52, d, J 6 7 Hz, (4 50, d, J 6 7 Hz), 2H, OCH2O; 3 42,
(3 41), s, OCH3; 3 42, m, 1H, H 6; 3 19, m, 1H, H 8; 2 60,
dt, J 12 3, 7 5 Hz, 1H, H 7a; 2 01, m, 1H, H 20a; 1 82, m,
1H, H 20b; 1 5–1 25, br m, 4H, H 30, H 7b and OH; 1 50, d,
J 6 8 Hz, CH3; 1 35, (1 34), d, J 6 9 Hz, CH3; 0 93, t, J
7 4 Hz, (0 88, t, J 7 5 Hz), 3H, H 40. 13C n.m.r. 142 89,
136 45, 133 37, 132 30, 128 45, 125 45, 6 Ar Cquat; 114 09,
(113 79), 99 95, (99 86), 2 Ar CH; 93 87, OCH2O; 77 14,
OCH; 58 73, CH2OH; 55 40, OCH3; 44 44, C 7; 39 17, C 20;
38 71, C 8; 37 09, C 6; 20 90, (20 81), CH3; 20 55, (20 48),
CH3; 19 57, C 30; 13 87, C 40. Mass spectrum: m/z 331 (M+,
68%), 270 (36), 256 (57), 228 (100), 226 (100), 198 (74).
Decarboxylation of the Indole-2-carboxylic Acid (18a)
The indole-2-carboxylic acid (18a) (18 mg, 52 mol), copper
(6 mg, 94 mol) and quinoline (4 ml) were stirred at 220–230 C
for 1 h.14 The mixture was cooled and poured onto an acid/ice
slurry (4 ml hydrochloric acid and c. 10 g ice). It was stirred
and extracted with dichloromethane (4 5 ml). The organic
layer was washed with water (5 ml) and 5% sodium bicarbonate
solution until the pH of the washings was 3–4. The aqueous
layer was further extracted with diethyl ether (4 15 ml) and
the organic fractions were combined, dried (MgSO4) and the
solvent was evaporated to give a red, viscous oil (17 mg).
The oil was subjected to repeated ash chromatography under
nitrogen (silica; ethyl acetate/light petroleum, 1 : 9 to 3 : 7)
cis-4-(1 0-Methoxymethyloxybutyl)-6,8-dimethyl-1,6,7,8-
tetrahydrocyclopent[ g]indole-2-carbaldehyde (21a)
Manganese dioxide (0 25 g, 2 63 mmol) was added to
a stirred solution of the indole-2-methanol (20a) (109 mg,
329 mol) and dichloromethane (50 ml) and the mixture
heated to re ux temperature. After 30 min, another portion
of manganese dioxide (0 25 g, 2 63 mmol) was added. After
6 h, the reaction mixture was ltered through a pad of Celite
and the Celite was washed with hot toluene (250 ml). The
toluene was removed and the residue was chromatographed
(Florisil; dichloromethane) to yield (21a) as a yellow solid
to yield (19a) as a pink oil (1 5 mg, 10%) (Found: M+
,
(71 mg, 65%) (Found: M+ , 329 1990. C20H27NO3 requires
301 2042. C19H27NO2 requires M+ , 301 2042). 1H n.m.r.
M+ , 329 1991).
(neat) 1660s cm
(C=O). 1H n.m.r.
1
max
8 11, s, 1H, NH; 7 16, m, 1H, H 2; 6 95, s, 1H, H 5; 6 69,
m, 1H, H 3; 4 98, m, 1H, OCH; 4 60, d, J 6 7 Hz, (4 59, d,
J 6 6 Hz), and 4 54, d, J 6 7 Hz, (4 53, d, J 6 6 Hz), 2H,
9 80, s, 1H, CHO; 8 82, br s, 1H, NH; 7 49, (7 48), d,
J 1 9 Hz, 1H, H 3; 6 98, s, 1H, H 5; 4 92, m, 1H, OCH;
4 57, 4 56, m, 2H, OCH2O; 3 44, m, 1H, H 6; 3 42, (3 40),

Synthesis of ( )-Iso-trans-trikentrin B
183
s, OCH3; 3 21, m, 1H, H 8; 2 65, dt, J 12 5, 7 7 Hz, 1H,
H 7a; 2 02, m, 1H, H 20a; 1 80, m, 1H, H 20b; 1 50–1 20,
br m, 3H, H 30 and H 7b; 1 50, d, J 6 9 Hz, CH3; 1 36, d,
J 6 9 Hz, (1 35, d, J 6 8 Hz), CH3; 0 95, t, J 7 2 Hz, 3H,
cis-1-Acetyl-4-(1 0-hydroxybutyl)-6,8-dimethyl-1,6,7,8-
tetrahydrocyclopent[ g]indole (23a)
To a stirred solution of acetamide (22a) (8 mg, 23 mol) in
dry dichloromethane (1 ml), under argon at 78 C, was added
an aliquot (200 l) of a solution of dimethylboron bromide
and dichloromethane (43 mg/ml). The solution turned green.
After the solution was stirred for 15 min, triethylamine (30 l)
was added and then water (100 l) was added dropwise. The
reaction mixture was slowly warmed to room temperature
and extracted with dichloromethane (3 3 ml). The combined
organic fractions were washed with water (1 ml), saturated
sodium chloride solution (1 ml) and dried (MgSO4). The
solvent was evaporated to give a colourless solid (15 mg). It
was chromatographed (silica; ethyl acetate/light petroleum,
1 : 9) under nitrogen to give (23a) as a colourless solid (4 5 mg,
65%). 1H n.m.r. 7 42, (7 41), d, J 2 1 Hz, 1H, H 5; 7 04,
(7 03), d, J 3 7 Hz, 1H, H 2; 6 89, (6 88), d, J 3 7 Hz, 1H,
H 3; 4 98, (4 93), m, 1H, OCH; 4 28, (4 18), m, 1H, H 6;
3 38, m, 1H, H 8; 2 63, m, 1H, H 7a; 2 61, (2 58), s, COCH3;
2 03, m, 1H, H 20a; 1 82, m, 1H, H 20b; 1 5–1 3, br m, 4H,
H 30, H 7b and OH; 1 23, d, J 7 2 Hz, CH3; 1 21, d, J 7 2 Hz,
CH3; 0 89, J 7 0 Hz, 3H, H 40. Mass spectrum: m/z 299 (M+,
4%), 281 (87), 266 (51), 239 (51), 224 (100).
H 40. 13C n.m.r.
181 70, CHO; 148 30, 135 74, (135 62),
135 44, 135 26, 129 41, 124 93, 6 Ar Cquat; 116 00, (115 70),
114 99, (114 89), 2 Ar CH; 93 97, OCH2O; 77 56, OCH;
55 51, OCH3; 43 93, C 7; 39 50, (39 40), C 20; 39 17, C 8;
37 01, C 6; 20 68, CH3; 20 53, (20 48), CH3; 19 52, C 30;
13 85, C 40. Mass spectrum: m/z 329 (M+, 12%), 286 (10),
276 (19), 244 (22), 226 (34), 201 (30), 184 (89), 130 (100).
cis-4-(1 0-Methoxymethyloxybutyl)-6,8-dimethyl-1,6,7,8-
tetrahydrocyclopent[ g]indole (19a)
A mixture of bis(triphenylphosphine)(carbonyl)rhodium(I)
chloride (27 mg, 40 mol) and mesitylene (40 ml) was heated
to 85 C under oxygen-free conditions. This temperature was
maintained until the rhodium complex had dissolved (20 min). A
mixture of 1,3-bis(diphenylphosphino)propane (33 mg, 80 mol)
and mesitylene (5 ml), also under oxygen-free conditions, was
added to the above rhodium solution. The mixture was stirred
at 85 C for a further 20 min. A solution of oxygen-free
indole-2-carbaldehyde (21a) (66 mg, 200 mol) and mesitylene
(2 ml) was added to the rhodium complex solution and it was
immediately plunged into a Woods metal bath at 200 C. The
bath temperature was maintained between 180 and 200 C.
After 30 min t.l.c. (silica; ethyl acetate/light petroleum, 1 : 4)
showed that the starting material had been consumed. The
reaction mixture was cooled (ice bath) and the mesitylene was
removed by distillation under reduced pressure. The residue
was dissolved in dichloromethane (2 ml) and chromatographed
(Florisil; dichloromethane, and then silica; ethyl acetate/light
petroleum, 1 : 4) to yield the title compound (19a) as a yellow
oil (39 mg, 65%). Its spectroscopic data were identical to
those of the compound obtained by decarboxylation of the
indole-2-carboxylic acid (18a). Attempted concomitant depro-
tection and dehydration of (19a) with p-toluenesulfonic acid in
benzene according to the method of Natsume et al.9,10 gave
an intractable product.
Attempted elimination of water from (23a) by using p-
toluenesulfonic acid in benzene failed to give any identi able
products.
3-Methylindan-1-one
A solution of crotonic acid (17 28 g, 201 mmol) in dry
benzene (50 ml) was added over 20 min to a stirred suspension
of aluminium trichloride (46 1 g, 345 mmol) in dry benzene
(70 ml) that was cooled in an ice bath. The mixture was
then heated to re ux for 17 h. The condensed solvent was
passed through activated molecular sieves (4 A) before being
returned to the reaction ask. The mixture was poured onto
ice (300 g) and stirred. It was extracted with dichloromethane
(3 150 ml). The combined organic fractions were washed with
water (200 ml), dried (MgSO4) and the solvent was removed.
The concentrate was distilled (100–105 C/0 8 mmHg) to give
3-methylindan-1-one as a colourless oil (22 7 g, 77%).
max
1
(neat) 1710s cm
(C=O). 1H n.m.r. 7 73, d, J 7 6 Hz, 1H,
N-Acetylation of (19a)
ArH; 7 61, t, J 7 6 Hz, 1H, ArH; 7 51, d, J 7 6 Hz, 1H, ArH;
7 39, t, J 7 6 Hz, 1H, ArH; 3 44, m, 1H, H 3; 2 93, dd, J
19 0, 7 4 Hz, 1H, H 2a; 2 29, dd, J 19 0, 3 3 Hz, 1H, H 2b;
To
a cooled suspension of potassium hydride (12 mg,
299 mol) in dry tetrahydrofuran (1 ml) was added the indole
(19a) (18 mg, 60 mol) in tetrahydrofuran (1 ml) and the mix-
ture heated to re ux temperature for 15 min. After the solution
was cooled, acetic anhydride (24 mg, 238 mol) was added and
the reaction mixture stirred for a further 1 h. Water (1 ml) was
then added and the solution extracted with dichloromethane
(3 3 ml). The combined organic fractions were washed with
saturated sodium chloride (3 ml) and dried (MgSO4). The
solvent was removed and the residue chromatographed (silica;
ethyl acetate/light petroleum, 1 : 9) to give (22a) as a yellow oil
1 42, d, J 7 1 Hz, CH3. 13C n.m.r.
206 6, C=O; 160 1,
136 4, 2 Ar Cquat; 134 8, 127 4, 125 3, 123 3, 4 Ar CH;
45 0, C 2; 32 4, C 3; 20 9, CH3. Mass spectrum: m/z 146
(M+, 65%), 131 (100), 117 (29), 103 (46), 91 (12), 77 (32).
cis-1,3-Dimethylindan-1-ol (24)
Iodomethane (17 31 ml, 278 mmol) in dry diethyl ether
(30 ml) was added dropwise to a stirred suspension of magne-
sium turnings (3 38 g, 139 mmol) in dry diethyl ether (100 ml)
under argon at a rate su cient to maintain gentle re ux. After
the addition was complete, the mixture was heated to re ux for
a further 1 h. It was cooled and the solution was transferred to
another ask, also under argon. A solution of 3-methylindan-
1-one (10 16 g, 69 5 mmol) in dry diethyl ether (40 ml) was
added dropwise to the stirred solution of Grignard reagent. The
mixture was heated to re ux for 18 h. The reaction mixture
was cooled and slowly poured onto a mixture of iced water
(300 g) and hydrochloric acid (5 ml). The mixture was stirred
vigorously and the aqueous layer was extracted with diethyl
ether (6 100 ml). The organic fraction was washed with water
(3 100 ml), saturated ammonium chloride solution (50 ml) and
water (3 50 ml). The organic fraction was dried (MgSO4),
the solvent was removed and the residue was distilled to give
the title compound (24) as a yellow oil (9 98 g, 89%). The
spectroscopic data corresponded to those previously obtained for
(12 mg, 60%) (Found: M+ , 343 2146. C21H29NO3 requires
1
M+ , 343 2147).
(neat) 1720s cm
(C=O). 1H n.m.r.
max
7 35, (7 34), d, J 3 9 Hz, 1H, H 2; 7 10, s, 1H, H 5; 6 85,
(6 84), d, J 3 9 Hz, 1H, H 3; 4 93, m, 1H, OCH; 4 52, m,
2H, OCH2O; 4 20, (3 95), m, 1H, H 6; 3 41, s, OCH3; 3 30,
m, 1H, H 8; 2 70, m, 1H, H 7a; 2 65, s, COCH3; 2 00, m, 1H,
H 20a; 1 78, m, 1H, H 20b; 1 6–1 3, br m, 3H, H 30 and H 7b;
1 35, (1 33), d, J 6 7 Hz, CH3; 1 10, (1 08), d, J 6 8 Hz,
CH3; 0 94, t, J 7 1 Hz, 3H, H 40. 13C n.m.r. 167 5, NCO;
146 78, (146 28), 134 95, (134 57), 132 56, 128 53, 4 Ar
Cquat; 125 15, 118 16, (117 83), 2 Ar CH; 110 73, Ar Cquat;
107 98, Ar CH; 93 9, OCH2O; 76 06, OCH; 55 4, OCH3;
42 76, (42 71), C 7; 39 53, (39 35), C 20; 38 89, 37 21, C 8 and
C 6; 24 52, (24 00), 23 17, (22 09), 21 36, (20 30), 3 CH3;
19 32, C 30; 13 81, C 40. Mass spectrum: m/z 343 (M+, 45%),
300 (25), 282 (19), 258 (40), 240 (64), 266 (57), 198 (100).

184
J. K. MacLeod, A. Ward and A. C. Willis
cis-1,3-dimethylindan-1-ol prepared from the radical cyclization
lowers the symmetry of the parent structure as the local
twofold axis need no longer hold exactly, nor need it be exactly
located or oriented. The t of the extra (l0 odd) re ections
con rms that the ordering is appropriate and unconstrained
re nement behaves well. The partial di raction enhancement
may be reexpressed in terms of the primitive triclinic cell as
of 2-(2-bromophenyl)pent-4-en-2-ol.3
X-Ray Structure Determination of (24) 3
A colourless block-shaped crystal of C11H14O, M r 162 23,
having dimensions of 0 23 by 0 21 by 0 13 mm was mounted
on a quartz bre. All measurements were made on a Rigaku
AFC6R di ractometer with graphite monochromatized Cu K
radiation and a 12 kW rotating anode generator. A liquid-
nitrogen-refrigeration xed tube low-temperature system was
used to cool the crystal to avoid sublimation. Data were
collected at a temperature of 73 1 C. Cell constants and
an orientation matrix for data collection, obtained from a
least-squares re nement by using the setting angles of 25 care-
fully centred re ections in the range 97 79 < 2 < 109 12 ,
corresponded to a primitive triclinic cell, space group P 1
(No. 2), with dimensions a 11 674(2), b 12 726(2), c 14 272(4)
I(h, k, l)
I( h, k, l h) if h k is even with the pseudo
c-glide absences associated with a C2/c parent symmetry corre-
sponding to re ections I(h, k, l), h = 2l, h k = 4n + 2. These
re ections are systematically weak but are clearly observed.
Full details, including tables of atomic coordinates for hydro-
gen and non-hydrogen atoms, are in an Accessory Publication
(available until 31 December 2003 from the Australian Journal
of Chemistry, P.O. Box 1139, Collingwood, Vic. 3066).
Preparation of Raney Nickel Reagent
Raney nickel was prepared by a modi cation of the method
of Pavlic and Adkins.28 To a stirred solution of sodium hydrox-
ide (32 g) and water (125 ml) at 50 C was added portions of
nickel aluminium alloy (25 g, over c. 1 h) so as to maintain the
temperature at 50 4 C. After the addition was complete, this
temperature range was maintained for 1 h. The mixture was
cooled, and washed with degassed water thoroughly until the
pH of the washings ranged between 7 5 and 8 5. The Raney
nickel suspension was washed with dried, distilled absolute
ethanol (3 100 ml) and stored under ethanol.
A, 86 67(2), 66 37(1), 83 04(1) , V 1928 2(6) A3, Z 8,
3
Dcalc 1 12 g cm
,
5 4 cm 1, F(000) 704.
The structure was solved by direct methods (SHELXS86)25
and expanded by using Fourier techniques (DIRDIF92).26 Non-
hydrogen atoms were re ned with anisotropic displacement
factors. The coordinates of the alcohol hydrogen atoms
were re ned, while the remaining hydrogen atoms were held
xed at geometrically determined positions. Least squares
re nement was performed by using the minimizing function
w(|Fo| |Fc|)2, where w = [ 2(Fo) + 0 000006Fo
]
1. Max-
2
Hydrogenolysis of cis-1,3-Dimethylindan-1-ol (24)
imum and minimum peaks on the nal di erence Fourier map
corresponded to 0 89 and 0 34 e/A3. Neutral atom scattering
factors were taken from Cromer and Waber.27 All calculations
were carried out with the teXsan Crystal Structure Analysis
Package (Molecular Structure Corporation).
To a solution of cis-1,3-dimethylindan-1-ol (24) (2 50 g,
15 mmol) in distilled, degassed ethanol (100 ml) was added
a suspension of freshly prepared Raney nickel (c. 25 g) and
the reaction mixture heated to re ux. After 2 h, the spent
Raney nickel was collected on a Celite pad. The solvent was
removed by distillation to give a clear oil (2 04 g), identi ed
as trans-1,3-dimethylindan (6b) by comparison of its 1H n.m.r.
spectrum with literature data.29
The nal R factor was 0 067 (Rw 0 064) for 4384 re ections
with I > 3 (I). The crystallographic asymmetric unit consists
of four chemically equivalent molecules of C11H14O, with very
similar conformations, arranged in a hydrogen-bonded tetramer
with an approximate 4 axis parallel to a 2c. A C-centred
pseudo monoclinic cell can be found that has this direction as
the unique b-axis. We have chosen the transformation: a0 = a0,
b0 = a 2c, c0 = a+b (a 0 11 674, b 0 26 152, c 0 16 194 A,
1-(trans-1 0,3 0-Dimethylindan-5 0-yl)butan-1-one (7b)
The procedure followed that used for the synthesis of the
cis-isomer (7a). The reagents and amounts used were as fol-
lows: trans-1,3-dimethylindan (6b) (10 3 g, 70 mmol), butyryl
chloride (11 ml, 106 mmol) and aluminium trichloride (14 09 g,
106 mmol). The resulting oil was chromatographed on silica
(ethyl acetate/light petroleum, 1 : 9) to give the title compound
(7b) as a colourless oil (10 6 g, 70%) (Found: M+ , 216 1514.
0
90 79,
128 73, 89 49 , Z 16), making a0 = a +b +c /2,
b0 = c /2, c0 = b , and h 0 = h, k 0 = h 2l, l0 = h + k,
x0 = x + y + z/2, y0 = z/2, z0 = y.
The centre of mass of the tetramer is at approximately x, y, z =
1/2, 3/8, 1/4 and this corresponds to x0, y0, z0 = 1, 1/8, 3/8.
Consequently, in the C-centred cell, there is an apparent local
C
15H20O requires M+ , 216 1514). 1H n.m.r.
7 82, d, J
symmetry operation 2 x0, y0, 3/4 z0 (1 25
x
z, 0 75 y, z
8 0 Hz, 1H, H 60; 7 78, s, 1H, H 40; 7 24, d, J 8 0 Hz, 1H H 70;
3 31, m, 2H, H 10 and H 30; 2 95, (2 94), t, J 7 3 Hz, 2H, H 2;
1 94, t, J 6 8 Hz, 2H, H 20; 1 76, sextet, J 7 3 Hz, 2H, H 3;
1 27, d, J 6 9 Hz, CH3; 1 25, d, J 6 9 Hz, CH3; 1 01, t, J
7 4 Hz, 3H, H 4. 13C n.m.r. 200 33, C=O; 153 90, 148 80,
135 84, 3 Ar Cquat; 126 88, 123 24, 122 99, 3 Ar CH; 42 76,
C 20; 40 48, C 2; 37 61, 37 28, C 10 and C 30; 20 41, 20 34,
for our reference cell) as well as the true symmetry operations
x0, y0, z0; x0, y0, z; 1/2+x0, 1/2+y0, z0; 1/2 x0, 1/2 y0, z0.
Closure under multiplication produces space group C2/c
for a unit cell a0, b0, c0/2 and may be thought of as the
true structure plus a pseudo-translation of c0/2. A glide plane
cannot be a symmetry element of the true structure as using the
operator twice produces a c0/2 translation which is not allowed.
2
CH3; 17 86, C 30; 13 88, C 40. Mass spectrum: m/z 216
0
0
and
are signi cantly di erent from 90 and the structure
(M+, 30%), 201 (3), 188 (7), 173 (100), 145 (14).
is de nitely triclinic, though half the re ection data have
approximate monoclinic di raction symmetry. The data were
separated according to whether l0 is even or odd, and merged
assuming monoclinic di raction symmetry. Rmerge on F for l0
even data was 36% while Rmerge(F) for l0 odd was 53%. This
shows the partial di raction enhancement of the l0 even data,
but also shows that the local twofold rotation does not hold all
that well. The structure can be described as an occupancy and
displacive modulation of a 1 : 1 disordered C2/c parent structure
for a cell a0, b0, c0/2 with associated monoclinic di raction
symmetry, viz. l(h0, k0, l0) = I( h0, k0, l0) if l 0 is even but
I(h0, k0, l0) = 0 if l0 is odd. Ordering, to select between
sites c/2 apart, creates extra re ections that do not have
monoclinic di raction symmetry, and displacive modulation
1-(trans-1 0,3 0-Dimethylindan-5 0-yl)butan-1-ol (8b)
This was prepared according to the method used for the
synthesis of the cis-isomer (8a). The reagents and amounts
used were as follows: butyroylindan (7b) (10 6 g, 49 mmol) and
sodium borohydride (2 78 g, 74 mmol). Compound (8b) was iso-
lated as a colourless oil (10 13 g, 95%), b.p. 130 C/0 02 mmHg
(Found: M+ , 218 1670. C15H22O requires M+ , 218 1671).
1H n.m.r. 7 16, d, J 6 2 Hz, 2H, H 60 and H 70; 7 15, s, 1H,
H 40; 4 66, m, 1H, OCH; 3 26, m, 2H, H 10 and H 30; 1 91, t,
J 6 7 Hz, 2H, H 20; 1 77, m, 2H, H 2a and OH; 1 69, m, 1H,
H 2b; 1 50–1 30, m, 2H, H 3; 1 25, (1 24), d, J 7 0 Hz, CH3;
1 23, d, J 7 0 Hz, CH3; 0 94, t, J 7 3 Hz, 3H, H 4. 13C n.m.r.
148 57, 147 7, 143 18, 3 Ar Cquat; 124 09, 123 16, 120 80,

Synthesis of ( )-Iso-trans-trikentrin B
185
(120 75), 3 Ar CH; 74 55, OCH; 43 02, C 20; 41 16, (41 11),
C 2; 37 43, 37 22, C 10 and C 30; 20 45, 2 CH3; 19 11, C 3;
13 88, C 4. Mass spectrum: m/z 218 (M+, 20%), 175 (100),
145 (11), 131 (16), 105 (54).
m, 2H, H 1 and H 3; 1 95, t, J 6 8 Hz, 2H, H 2; 1 80–1 20, br
m, 4H, H 20 and H 30; 1 27, d, J 6 6 Hz, (1 26, d, J 6 4 Hz),
CH3; 1 25, d, J 7 0 Hz, CH3; 0 95, t, J 7 3 Hz, 3H, H 40.
13C n.m.r. 192 23, (192 20), CHO; 155 07, 147 66, 144 43,
132 33, 4 Ar Cquat; 126 66, (126 63), 122 16, 2 Ar CH;
94 71, (94 56), OCH2O; 74 43, (74 14), OCH; 55 48, OCH3;
42 56, C 2; 40 88, C 20; 37 86, (37 78), 36 91, C 1 and C 3;
20 14, CH3; 19 95, (19 91), CH3; 19 25, C 30; 13 67, C 40.
Mass spectrum: m/z 289 ([M 1]+, 5%), 259 (7), 245 (100),
229 (34), 217 (25), 203 (58), 201 (56), 199 (57). Chemical
ionization mass spectrum: m/z 291 (MH+, 9%), 259 (27), 245
(57), 229 (100).
1-(trans-5 0-Bromo-1 0,3 0-dimethylindan-6 0-yl)butan-1-ol (12b)
This was prepared according to the procedure used for
the cis-isomer (12a). The reagents and amounts used were
as follows: hydroxybutylindan (8b) (2 0 g, 9 2 mmol), 1 7 M
t-butyllithium in pentane (27 ml, 46 mmol) and carbon tetra-
bromide (14 5 g, 44 mmol). The product was chromatographed
on silica (ethyl acetate/light petroleum, 1 : 9) to give recovered
starting material (8b) (0 74 g, 37%) and (12b) as a yellow oil
(1 44 g, 52%) (Found: M+ , 296 0776. C15H2179BrO requires
M+ , 296 0776). 1H n.m.r. 7 36, s, 1H, ArH; 7 30, s, 1H,
ArH; 5 08, m, 1H, OCH; 3 24, m, 2H, H 10 and H 30; 1 91, t,
J 6 8 Hz, 2H, H 20; 1 80–1 30, br m, 5H, H 2, H 3 and OH;
1 24, (1 23), d, J 7 4 Hz, CH3; 1 21, d, J 7 2 Hz, CH3; 0 96,
t, J 7 3 Hz, 3H, H 4. 13C n.m.r. 149 51, (149 28), 148 26,
(148 19), 141 456, (141 41), 3 Ar Cquat; 127 34, 121 92,
Ethyl trans-4-(1 0-Methoxymethyloxybutyl)-6,8-dimethyl-
1,6,7,8-tetrahydrocyclopent[ g]indole-2-carboxylate (16b)
via the Azidocinnamate (15b)
The azidocinnamate (15b) was prepared according to the
method used for the corresponding cis-azidocinnamate (15a).
The reagents and amounts used were as follows: dimethylin-
dancarbaldehyde (14b) (215 mg, 740 mol), ethyl azidoacetate
(1 75 g, 13 6 mmol) and sodium (218 mg, 9 5 mmol) in ethanol
(10 ml). After the usual workup and puri cation procedures,
2
Ar CH; 119 63, Ar CBr; 72 62, (72 58), OCH; 42 99, C 20;
39 90, (39 85), C 2; 37 75, (37 65), 37 25, (37 13), C 10 and
C 30; 20 31, (20 22), CH3; 20 18, CH3; 19 08, C 3; 13 82, C 4.
Mass spectrum: m/z 298 (M+, 14%), 296 (M+, 16), 255 (97),
253 (100), 185 (28), 183 (27).
(15b) was obtained as an unstable yellow oil (160 mg, 54%).
1
(neat) 2110s (N3), 1715s cm
(C=O). 1H n.m.r.
max
7 67, (7 66), s, 1H, H 4; 7 28, m, 2H; 4 83, m, 1H, OCH;
4 58, m, and 4 54, m, 2H, OCH2O; 4 38, q, J 7 1 Hz, 2H,
2H, OCH2CH3; 3 41, (3 38), s, OCH3; 3 27, m, 2H, H 1
and H 3; 1 92, t, J 6 8 Hz, 2H, H 2; 1 80–1 20, br m, 4H,
H 20 and H 30; 1 40, t, J 7 1 Hz, 3H, OCH2CH3; 1 27, d,
trans-5-Bromo-6-(1 0-methoxymethyloxybutyl)-
1,3-dimethylindan (13b)
To a stirred solution of indanol (12b) (0 80 g, 2 7 mmol)
and dichloromethane (75 ml) at 0 C were added 4-dimethyl-
aminopyridine (33 mg, 0 3 mmol), ethyldiisopropylamine (2 4
ml, 13 5 mmol) and methoxymethyl chloride (1 ml, 13 5 mmol).
The reaction mixture was warmed to room temperature and
stirred for 17 h. The usual workup and puri cation pro-
cedure (as for the corresponding cis-compound (13a)) gave
(13b) as a yellow oil (0 88 g, 95%) (Found: M+ , 340 1037.
J
6 8 Hz, CH3; 1 23, d, J 6 2 Hz, (1 19, d, J 6 6 Hz),
CH3; 0 94, t, J 7 2 Hz, (0 92, t, J 7 3 Hz), 3H, H 40. 13C
n.m.r. 163 37, CO2Et; 150 00, (149 97), 147 23, (147 19),
139 98, 129 26, 125 79, 5
3
OCH2CH3; 55 48, OCH3; 42 83, C 2; 39 89, C 20; 37 51,
37 30, (37 28), C 1 and C 3; 20 41, (20 37), CH3; 20 17,
(20 12), CH3; 19 17, (19 10), C30; 14 03, OCH2CH3; 13 70,
C 40.
Cquat; 124 46, 123 56, 121 61,
CH; 94 20, (94 15), OCH2O; 74 81, (74 26), OCH; 62 00,
C
17H2579BrO2 requires M+ , 340 1038). 1H n.m.r. 7 29, s,
1H, ArH; 7 26, (7 25), s, 1H, ArH; 5 03, m, 1H, OCH; 4 53,
m, 2H, OCH2O; 3 41, (3 39), s, OCH3; 3 23, m, 2H, H 1 and
H 3; 1 90, t, J 6 8 Hz, 2H, H 2; 1 75–1 20, br m, 4H, H 20
and H 30; 1 23, (1 21), d, J 7 0 Hz, CH3; 1 20, (1 19), d,
J 7 0 Hz, CH3; 0 96, t, J 7 4 Hz, 3H, H 40. 13C n.m.r.
148 18, 139 51, 2 Ar Cquat; 127 36, C 4; 122 46, (122 37),
C 7; 120 45, Ar CBr; 111 33, Cquat; 94 76, OCH2O; 76 09,
OCH; 55 72, OCH3; 42 98, (42 90), C 2; 39 36, (39 26), C 20;
37 70, (37 65), 37 24, (37 21), C 1 and C 3; 20 32, CH3;
20 27, (20 26), CH3; 19 06, C 30; 13 79, C 40. Mass spectrum:
m/z 342 (M+, 11%), 340 (M+, 12), 299 (99), 297 (100), 269
(20), 267 (22), 253 (89), 251 (84), 239 (73), 237 (75).
A solution of the azidocinnamate (15b) (42 mg, 105 mol)
in toluene (20 ml) was plunged into a reaction bath main-
tained at 135 C and heated for 2 h. The mixture was cooled
and the toluene removed by distillation. The residue was
chromatographed (silica; ethyl acetate/light petroleum, 1 : 9)
to yield the title compound (16b) as a yellow oil (31 mg,
79%) (Found: M+ , 373 2253. C22H31NO4 requires M+
,
1
373 2253).
(neat) 3455m (NH), 1700s cm
(C=O).
max
1H n.m.r. 8 73, br s, 1H, NH; 7 42, (7 41), d, J 1 8 Hz,
1H, H 3; 6 97, s, 1H, H 5; 4 93, m, 1H, OCH; 4 56, m, 2H,
OCH2O; 4 40, q, J 7 1 Hz, 2H, OCH2CH3; 3 53, m, 1H,
H 6; 3 43, (3 42), s, OCH3; 3 41, m, 1H, H 8; 2 06, 3H, H 7
and H 20a; 1 80, m, 1H, H 20b; 1 6–1 3, br m, 2H, H 30; 1 43,
t, J 7 1 Hz, 3H, OCH2CH3; 1 33, d, J 7 1 Hz, (1 30, d, J
7 0 Hz), CH3; 1 29, d, J 6 9 Hz, CH3; 0 95, t, J 7 3 Hz, 3H,
H 40. 13C n.m.r. 162 18, CO2Et; 145 44, 134 75, (134 67),
133 84, 129 45, 126 51, 124 70, 6 Ar Cquat; 115 36, (115 21),
108 26, (108 23), 2 Ar CH; 93 93, OCH2O; 77 07, (77 01),
OCH; 60 85, OCH2CH3; 55 46, OCH3; 43 35, C 7; 39 41,
(39 36), C 20; 37 93, (37 88), 35 91, C 6 and C 8; 20 30, CH3;
19 71, (19 67), CH3; 19 56, C 30; 14 34, OCH2CH3; 13 85,
C 40. Mass spectrum: m/z 373 (M+, 40%), 330 (49), 312 (27),
284 (61), 270 (100), 240 (24), 224 (17), 212 (22).
trans-6-(1 0-Methoxymethyloxybutyl)-1,3-dimethylindan-5-
carbaldehyde (14b)
To a stirred solution of the aryl bromide (13b) (0 60 g,
1 8 mmol) and heptane (50 ml) under argon at 78 C was
added 1 6 M butyllithium in hexane (2 2 ml, 3 5 mmol) drop-
wise. It was stirred for a further 10 min while slowly warming to
0 C. The reaction mixture turned dark yellow and a precipitate
formed. The mixture was stirred for a further 15 min and
then cooled to 78 C. Dimethylformamide (2 ml) was added
dropwise and the reaction mixture slowly warmed to room tem-
perature. The same workup and puri cation procedures were
employed as those used for the corresponding cis-compound
(14a), to provide the title compound (14b) as a colourless
oil (0 33 g, 65%) (Found: [M 1]+ , 289 1804. C18H25O3
trans-4-(1 0-Methoxymethyloxybutyl)-6,8-dimethyl-1,6,7,8-
tetrahydrocyclopent[ g]indole-2-methanol (20b)
This was synthesized according to the procedure used to
prepare the isomeric cis-compound (20a). The reagents and
amounts used were as follows: the ethyl indole-2-carboxylate
(16b) (160 mg, 428 mol) and 1 5 M diisobutylaluminium
hydride in toluene (860 l, 1 29 mmol). The usual workup and
requires m/z, 289 1804).
(neat) 1695s (CHO), 1610m
max
cm (Ar–H). 1H n.m.r. 10 30, s, 1H, CHO; 7 65, s, 1H, H 4;
7 41, s, 1H, H 7; 5 44, m, 1H, OCH; 4 58, d, J 6 7 Hz, and
4 53, d, J 6 6 Hz, 2H, OCH2O; 3 38, (3 36), s, OCH3; 3 30,
1

186
J. K. MacLeod, A. Ward and A. C. Willis
puri cation steps were employed to yield the title compound
(
)-Iso-trans-trikentrin B (5)
To a well stirred solution of the methoxymethyl ether (19b)
(20b) as a yellow oil (73 mg, 51%) (Found: M+ , 331 2146.
C
20H29NO3 requires M+ , 331 2147). 1H n.m.r. 8 42, br s,
(7 mg, 23 mol) and dry dichloromethane (2 ml), under argon
at 78 C, was added an aliquot (105 l) of a solution of
dimethylboron bromide and dichloromethane (80 mg/ml). The
reaction mixture darkened. After the mixture was stirred for
4 min, triethylamine (100 l) was added and the reaction mix-
ture turned orange. It was stirred for 5 min and water (1 ml)
was added. The mixture was warmed to room temperature
and extracted with dichloromethane (3 3 ml). The combined
organic fractions were washed with water (1 ml), saturated
sodium chloride solution (1 ml) and dried (MgSO4). The solvent
was evaporated to give an oil. Repeated ash chromatography
under nitrogen (silica; ethyl acetate/light petroleum, 1 : 9) of
the residue gave as the major fraction a yellow oil, identi ed
1H, NH; 6 91, s, 1H, H 5; 6 56, s, 1H, H 3; 4 94, m, 1H, OCH;
4 81, s, 2H, CH2OH; 4 58, d, J 6 8 Hz, (4 57, d, J 6 6 Hz),
and 4 52, d, J 6 7 Hz, (4 50, d, J 6 7 Hz), 2H, OCH2O; 3 50,
m, 1H, H 6; 3 42, (3 41), s, OCH3; 3 23, m, 1H, H 8; 2 02, m,
3H, H 20 and H 7; 1 83, m, 1H, H 20b; 1 60–1 20, br m, 3H,
a
H 30 and OH; 1 31, (1 29), d, J 7 0 Hz, CH3; 1 25, d, J 7 1 Hz,
(1 24, d, J 7 0 Hz), CH3; 0 94, t, J 7 3 Hz, 3H, H 40. 13C
n.m.r. 142 30, 136 56, 133 05, 132 34, 128 88, 125 09, 6 Ar
Cquat; 114 09, (113 98), 100 02, 2 Ar CH; 93 86, OCH2O;
77 12, OCH; 58 69, CH2OH; 55 41, OCH3; 43 61, C 7; 39 18,
C 20; 37 71, (37 33), C 8; 35 95, C 6; 20 68, (20 62), CH3;
20 60, (20 40), CH3; 19 59, C 30; 13 91, (13 90), C 40. Mass
spectrum: m/z 331 (M+, 67%), 288 (13), 271 (49), 270 (43),
256 (87), 228 (100), 226 (92), 198 (64).
as ( )-iso-trans-trikentrin B (5)1,5 (5 mg, 63%) (Found: M+
,
(CH2Cl2)
239 1673. Calc. for C17H21N: M+ , 239 1674).
max
1
3475s cm
(NH). 1H n.m.r. 8 04, br s, 1H, NH; 7 19, dd,
J 2 7, 3 0 Hz, 1H, H 2; 7 09, s, 1H, H 5; 6 80, d, J 15 7 Hz,
1H, H 10; 6 75, dd, J 2 3, 3 0 Hz, 1H, H 3; 6 41, dt, J 15 8,
6 6 Hz, 1H, H 20; 3 51, m, 1H, H 6; 3 44, m, 1H, H 8; 2 32, m,
2H, H 30; 2 00, m, 2H, H 7; 1 33, d, J 7 0 Hz, CH3; 1 31, d, J
7 2 Hz, CH3; 1 15, t, J 7 5 Hz, 3H, H 40. 13C n.m.r. 142 46,
Ar Cquat; 132 35, CH; 128 99, 128 38, 2 Ar Cquat; 127 22,
CH; 125 12, Ar Cquat; 123 17, 112 31, 2 CH; 110 73, Ar
trans-4-(1 0-Methoxymethyloxybutyl)-6,8-dimethyl-1,6,7,8-
tetrahydrocyclopent[ g]indole-2-carbaldehyde (21b)
This was synthesized according to the procedure used to
prepare the corresponding cis-compound (21a). The reagents
and amounts used were as follows: the indole-2-methanol
(20b) (123 mg, 371 mol) and manganese dioxide (0 60 g,
6 2 mmol). The usual workup and chromatographic proce-
dures were employed to give (21b) as a yellow oil (79 mg,
C
quat; 101 61, CH; 43 59, C 7; 37 68, C 8; 35 93, C 6; 26 40,
C 30; 20 68, CH3; 19 82, CH3; 13 88, C 40. Mass spectrum:
m/z 239 (M+, 89%), 224 (100), 198 (19), 182 (23), 154 (9).
65%) (Found: M+ , 329 1990. C20H27NO3 requires M+
,
1
329 1991).
(neat) 1600s cm
(C=O). 1H n.m.r. 9 80,
max
s, 1H, CHO; 8 90, (8 87), br s, 1H, NH; 7 49, d, J 2 1 Hz,
1H, H 3; 6 98, s, 1H, H 5; 4 92, m, 1H, OCH; 4 54, m, 2H,
OCH2O; 3 46, m, 1H, H 6; 3 42, (3 41), s, OCH3; 3 25, m,
Acknowledgments
We thank Dr Lilian Monahan for helpful advice
and the Commonwealth Government for an Australian
Postgraduate Research Award to A.W. We are grate-
ful to Professor A. D. Rae for his analysis of the
pseudo-symmetry within the X-ray crystal structure
determination.
1H, H 8; 2 00, m, 3H, H 7 and H 20a; 1 80, m, 1H, H 20
;
b
1 60–1 20, br m, 2H, H 30; 1 32, d, J 7 3 Hz, CH3; 1 28, d, J
7 0 Hz, CH3; 0 95, t, J 7 3 Hz, 3H, H 40. 13C n.m.r. 181 64,
CHO; 147 69, 135 69, 135 30, 129 78, 124 63, 5 Ar Cquat
;
115 78, 115 03, 2 Ar CH; 110 73, Cquat; 93 94, OCH2O;
77 04, OCH; 55 42, OCH3; 43 21, C 7; 39 34, C 20; 38 06,
C 8; 35 83, C 6; 20 13, CH3; 19 51, CH3, 19 43, C 30; 13 77,
C 40. Mass spectrum: m/z 329 (M+, 55%), 286 (33), 268 (26),
258 (40), 240 (35), 226 (100), 198 (62).
References
1
Capon, R. J., MacLeod, J. K., and Scammells, P. J.,
Tetrahedron, 1986, 42, 6545.
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1988, 29, 391.
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2
trans-4-(1 0-Methoxymethyloxybutyl)-6,8-dimethyl-1,6,7,8-
tetrahydrocyclopent[ g]indole (19b)
3
This was prepared according to the procedure used for the
synthesis of the corresponding cis-compound (19a). The reagents
and amounts used were as follows: the indole-2-carbaldehyde
(21b) (60 mg, 182 mol), bis(triphenylphosphine)(carbonyl)
rhodium(I) chloride (25 mg, 36 mol) and 1,3-bis(diphenyl-
phosphino)propane (30 mg, 72 mol). The usual workup and
puri cation procedures were followed to yield the title compound
(19b) as a yellow oil (35 mg, 64%) (Found: M+ , 301 2042.
4
5
6
7
C
19H27NO2 requires M+ , 301 2042). 1H n.m.r. 8 08, br
8
s, 1H, NH; 7 17, d, J 5 4 Hz, 1H, H 2; 6 95, s, 1H, H 5;
6 71, d, J 5 4 Hz, (6 70, d, J 5 4 Hz), 1H, H 3; 4 98, m,
1H, OCH; 4 61, d, J 6 7 Hz, (4 60, d, J 6 7 Hz), and 4 57,
d, J 6 6 Hz, (4 55, d, J 6 7 Hz), 2H, OCH2O; 3 56, m, 1H,
H 6; 3 44, (3 43), s, OCH3; 3 40, m, 1H, H 8; 2 00, m, 3H,
H 7 and H 20a; 1 85, m, 1H, H 20b; 1 60–1 30, br m, 2H,
H 30; 1 33, d, J 7 0 Hz, CH3; 1 30, d, J 6 8 Hz, (1 29, d,
J 6 8 Hz), CH3; 0 95, t, J 7 3 Hz, 3H, H 40. 13C n.m.r.
142 11, 132 64, 132 40, 128 78, 124 97, 5 Ar Cquat; 122 95,
113 95, (113 81), 101 89, 3 Ar CH; 94 02, OCH2O; 77 11,
OCH; 55 45, OCH3; 43 51, C 7; 39 28, C 20; 37 76, C 8; 36 00,
C 6; 20 67, CH3; 19 84, CH3; 19 60, C 30; 13 90, C 40. Mass
spectrum: m/z 301 (M+, 49%), 258 (53), 240 (27), 226 (35),
212 (27), 198 (100).
9
10
11
12
13
Moody, C. J., in ‘Studies in Natural Products Chemistry,
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therein.

Synthesis of ( )-Iso-trans-trikentrin B
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15
16
17
26
27
18
19
20
21
Perrin, S. D., Armarego, W. L. F., and Perrin, D. R.,
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28
29
22
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