Acid-promoted fries rearrangements of benzannulated lactones

Article abstract of DOI:10.1071/C98023

The scope of acid-promoted Fries rearrangements of benzannulated lactones has been examined. The reaction is applicable to seven-membered lactones possessing a sufficiently activated aromatic ring but not to six-membered lactones, and it proceeds in higher yield for diterpenoid lactones than for lower molecular weight lactones. The structures of the 2,6-methano-bridged benzoxocin side products (23), (24), and (25) from rearrangement of the diterpenoid lactone (11) have been assigned.

Full text of DOI:10.1071/C98023

C S I R O P U B L I S H I N G
Australian Journal
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Volume 51, 1998
© CSIRO 1998
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Aust. J. Chem., 1998, 51, 1167–1174
.
Acid-Promoted Fries Rearrangements
of Benzannulated Lactones
Richard C. Cambie, Lorna H. Mitchell and Peter S. Rutledge
Department of Chemistry, University of Auckland,
Private Bag 92019, Auckland, New Zealand.
The scope of acid-promoted Fries rearrangements of benzannulated lactones has been examined. The
reaction is applicable to seven-membered lactones possessing a su ciently activated aromatic ring but
not to six-membered lactones, and it proceeds in higher yield for diterpenoid lactones than for lower
molecular weight lactones. The structures of the 2,6-methano-bridged benzoxocin side products (23),
(24), and (25) from rearrangement of the diterpenoid lactone (11) have been assigned.
Introduction
the product is a meta-acylated phenol due to the
constraints of the tethering. A Fries rearrangement of
a benzannulated lactone wherein the dihydrocoumarin
(4) was converted into 4-hydroxyindan-1-one (6) on
fusion with aluminium trichloride was rst reported in
1954.13 No yield was given for this transformation but
a more recent report14 cites a yield of 88%. Despite
this high yield, it has been reported that use of a
stepwise conversion of (4) into (6) is more convenient
for large-scale synthesis.15 Some photochemical Fries
rearrangements of benzannulated lactones have been
reported16,17 but limited use has been made of acid-
promoted Fries rearrangements of lactones possibly
Benzannulated lactones (2) can be opened and then
cyclized to give a product (3) in which the acyl
group is bound to the aromatic ring. The sequence is
especially useful when the lactone is generated from
a cyclic aryl ketone (1) by Baeyer–Villiger oxidation,
since the overall rearrangement (1) → (3) (Scheme 1)
allows regioselective introduction of a hydroxy group
and the transposition of functionality already on the
aromatic ring. Such opening of a lactone followed
by cyclization (2) → (3) has been carried out by a
four-step sequence in a number of diterpenoid syntheses
in order to introduce functionality into a hindered
because this method has never been mentioned in
7
position.1
We report here an examination of the
12
reviews9
of the rearrangement.
scope of an acid-promoted Fries rearrangement of a
lactone which e ects the transformation (2) → (3) in
one step. The rearrangement has been used as a key
step for functionalization at C 11 in the synthesis of
triptoquinones D, E, and F from podocarpic acid.8
Discussion
The initial compounds examined were a series of
diterpenoid benzannulated lactones (7)–(13), each of
which was prepared by Baeyer–Villiger oxidation of
the corresponding 7-ketone. In the present work the
lactone (7) which had been reported previously3 as
an oil without puri cation or characterization was
obtained as a crystalline solid, m.p. 126–128 , that
was completely characterized. The lactone (12) had
also been reported previously.6 Assignments for 13C
chemical shifts reported for this compound were reas-
signed from HMQC and HMBC experiments during the
current work. A minor product isolated from the
Baeyer–Villiger oxidation of sugiol methyl ether was
identi ed as the 11-chloro ketone (14) from high-
resolution mass spectrometry and an examination of
its n.m.r. spectra.18
The normal product from a Fries rearrangement9
12
In a standard procedure each of the diterpenoid
lactones was stirred with polyphosphoric acid at 80
for 3 h and the mixture then worked up. The lactones
(7) and (8),8 each possessing a methoxy group in the
of an aromatic ester is a phenolic ketone in which the acyl
residue has been directed to the ortho- or para-position
by the phenol. Where the ester side chain is tethered to
the aromatic ring, such as in a benzannulated lactone,
Manuscript received 13 February 1998
᭧ CSIRO 1998
0004-9425/98/121167$ 05.00

1168
R. C. Cambie, L. H. Mitchell and P. S. Rutledge
C 12 position, gave moderately high yields (71 and
76%) of the m-phenolic ketones (15) and (16). Their
structures followed from the replacement of the lactone
band in the i.r. spectra by a ketone carbonyl stretch,
the appearance of only two and one aryl proton signals
group. A mechanism to account for the appearance of
a methyl ester group would involve a methoxy group
migration, and indeed, there is literature precedence
for such a migration under acidic conditions. For
example, Ohtsuka and Tahara2 have postulated the
intermediacy of the methyl oxonium intermediate (17)
in the conversion of the acid (18) into the keto ester
(19) (Scheme 2).
1
respectively in the H n.m.r. spectra, and a down eld
shift of the C 20 methyl and C 1 protons as expected
for a C 11 substituted compound.18 In contrast, the
demethoxy lactones (9) and (13)2 as well as the C 4
gem-dimethyl compound (12)6 gave complex mixtures
from which meta-Fries rearrangement products were
not isolated. The 13-bromo lactone (10) possessing
an electron-withdrawing substituent in addition to
the electron-donating methoxy group was remarkably
stable under the reaction conditions, being recovered
unchanged after standard treatment.
Surprisingly, attempted Fries rearrangement of the
C 19 methyl ether (11) gave a mixture of compounds
which did not appear to include any of the desired
rearrangement product. Three products of lower RF
than the starting lactone were isolated as oils by
repeated chromatography. Despite being isomeric with
the starting material the major compound (19% yield)
had a 1H n.m.r. spectrum that showed a multiplet
in the aromatic region due to three rather than two
protons, while a triplet ( 0 91)/quartet (1 68) pattern
was typical of an ethyl group; this indicated that the
compound was a rearrangement product. The i.r.
spectrum showed an ester band at 1728 cm 1, and the
A similar methyl oxonium intermediate (20) can be
postulated from treatment of the lactone (11) with
acid (Scheme 3). Opening of the oxonium ion (20)
would give the primary carbocation (21). A 1,2-shift
of the adjacent C 18 methyl group would provide the
more stable tertiary carbocation (22) which on trap-
ping by the free phenolic hydroxy group would a ord
the methano-bridged benzoxocin (23). Con rmation
that (23) was indeed the structure of the rearranged
compound followed from HMQC, HMBC, and DQF-COSY
presence of methoxy signals at
3 29 and 51 3 in
1
the H and 13C n.m.r. spectra, respectively, suggested
the presence of a methyl ester group. The furthest
down eld methine signal in the 13C n.m.r. spectrum
was at 42 5 in contrast to that of the C 19 methylene
carbon signal in the spectrum of the parent lactone
(13) which occurred at 74 4. Together, this evidence
suggested that the C 19 methoxy ether of (11) had
been converted into, or replaced by, a methyl ester

Fries Rearrangements of Benzannulated Lactones
1169
two-dimensional n.m.r. experiments (Table 1). In
particular, the aliphatic quaternary carbon (C 6) sig-
heteroatom-substituted quaternary carbon (C 2) showed
similar correlations to H 3eq, (H 12)2, (H 14)2, and H 15,
thereby establishing the location of the methano bridge.
Attachment of the oxocin ring through oxygen to the
aromatic ring was con rmed by the presence of an ether
nal at
37 7–37 9 showed HMBC connections to
protons at C 5, C 7, C 11, C 12, and C 16 while the
1
absorption band in the i.r. spectrum at 1165 cm
and chemical shifts in the 13C n.m.r. spectrum for C 2
and C 10a which were consistent for an attached het-
eroatom. Moreover, the seven degrees of unsaturation
indicated a tricyclic structure once the aromaticity and
the carbonyl group were accounted for.
The other two compounds isolated from attempted
Fries rearrangement of the lactone (11) were isomeric and
had the molecular formula C21H28O5. Each contained
an acetyl group as shown by new carbonyl stretches at
1
c. 1660 cm
in the i.r. spectra, acetyl carbonyl and
methyl group signals at c. 200 1 and 32 2 in the 13C
n.m.r. spectra, and a new three-proton singlet at c. 2 61
in the H n.m.r. spectra. In each compound the acetyl
1
group had to be attached to the aromatic ring since the
1H n.m.r. and DEPT spectra showed only two aromatic
proton signals and a small mutual coupling constant
indicative of a meta-relationship between them. Other
spectroscopic and physical data for these compounds
and especially for the least polar of the two were
very similar to those observed for (23), so that the
compound of lower polarity was assigned the structure
(24). The more polar compound possessed most of
the spectroscopic characteristics of the previous two
compounds but di ered in the chemical shifts and
coupling pattern of the methano-bridge proton and
protons to the carboxy ester, results suggesting that
it was stereoisomeric at C 11. The chemical shifts of the
Table 1. N.m.r. correlations for (23)
A
B
A
B
Position
HMBC
C
C
H
H
2
78 7
36 2
78 8
36 5
—
 1 66, ax
—
 1 40, ax
H 15, H 14a, H 14b, H 3eq, H 12a, H 12b
H 14a, H 14b, H 5ax, H 5eq, H 12a, H 12b, H 11, H 7


3
4
5
 1 88, eq
 1 78, eq


19 3
42 5
19 7
42 7
 1 32, ax
 1 21, ax
 1 39, eq
1 35
H 5ax, H 5eq
 1 49, eq

 1 55, ax
 1 64, eq
—
H 4eq, H 3eq, H 11, H 16
6
6a
7
8
9
10
10a
11
12
37 7
128 0
111 6
153 0
112 3
115 0
150 2
42 0
37 9
128 0
112 1
153 9
112 9
115 6
150 6
42 4
—
—
6 78
—
6 59
6 89
—
H 5ax, H 5eq, H 12a, H 12b, H 11, H 7, H 16
H 16, H 5ax, H 5eq, H 11, H 10
H 9
8-OCH3, H 10, H 7, H 9
H 7
H 9
H 9, H 10, H 7
H 14a, H 14b, H 12a, H 12b
H 11
—
6 65–6 67
—
6 65–6 67
6 65–6 67
—
2 25
 2 01
 2 38
2 31


31 0
31 3
 2 10
 2 46
—
13
14
174 6
31 6
174 2
32 1
—
H 12a, H 12b, H 11, 13-OCH3
H 15, H 3eq, H 12a, H 12b, H 11

 1 58
 1 65
0 95
1 68
15
16
8-OCH3
13-OCH3
8 0
24 8
55 7
51 8
8 2
24 9
55 2
51 3
0 91
1 23
3 37
3 29
H 14a, H 14b
H 5ax, H 5eq, H 11
1 33
3 75
3 65
A
B
Spectrum run in CDCl3.
Spectrum run in C6D6.

1170
R. C. Cambie, L. H. Mitchell and P. S. Rutledge
methano-bridged proton (H 11) and the C 12 protons
in the 1H n.m.r. spectrum of the isomer were further
down eld than those of compound (24). From this
evidence the structure was assigned as the C 11 epimer
(25) since the pendant CH2CO2Me group would now
be deshielded by the aromatic ring. Compound (25)
could arise if an alkene intermediate (26) was formed
from the tertiary carbocation (22) so that inversion
of stereochemistry could take place at what was to
become the bridgehead carbon (Scheme 4). The origin
of the acetyl group in (24) and (25) is di cult to
explain but it may have arisen from fragmentation of
other components in the reaction mixture.
electron-donating methoxy substituent, and thus the
reaction appears to be complementary to that with
aluminium(III) chloride which e ects demethylation.
Experimental
For general experimental details see ref. 25. N.m.r. res-
onances bearing the same capital superscript letter may be
interchanged.
General Method for Fries Rearrangement
A stirred solution of the benzannulated lactone (0 007–
6 7 mmol) in polyphosphoric acid (5–25 ml) was heated at 80
for 3 h. The viscous solution was poured into ice–water with
vigorous stirring to give a precipitate which was then puri ed
by crystallization or chromatography. Further material was
obtained by extraction with ethyl acetate.
Methyl 12-Methoxy-7-oxo-7a-oxa-7-homopodocarpa-8,11,13-
trien-19-oate (7)
m-Chloroperbenzoic acid (0 82 g, 4 6 mmol) was added
to a solution of methyl 12-methoxy-7-oxopodocarpa-8,11,13-
trien-19-oate26 (1 0 g, 3 2 mmol) in chloroform (25 ml) and
the mixture was stirred at room temperature for 3 days.
Additional m-chloroperbenzoic acid (0 82 g, 4 6 mmol) was
added and the stirring continued for a further 3 days. The
solution was washed with aqueous sodium hydrogencarbonate,
dried, and solvent was removed under vacuum. The residue
was chromatographed on silica, and the column eluted with
ether/hexane (1 : 2) and then with ethyl acetate/hexane (1 : 5)
to give the lactone* (7) (0 64 g, 61%) as thick needles (lit.3 oil),
m.p. 126–128 , [ ]2D0 48 (c, 0 24) (Found: C, 68 7; H, 7 8%;
M+ , 332 1621. C19H24O5 requires C, 68 6; H, 7 3%; M+
332 1624) (correct i.r. data).3
1 05, ddd, J3 = J3
13 5, J3 4 4 Hz, H 3 ; 1 21, 1 22, 2s, (H 18)3, (H 20)3;
,
H
,3
,2
,2
1 55, ddd, J1
ddddd, J2
= J1
13 9, J2
13 3, J1
4 4, J2
4 0 Hz, H 1 ; 1 70,
4 0, J2 = J2
,2
,1
,1
,2
,3
,2
,1
,3
3 2 Hz, H 2 ; 1 75–1 93, m, H 1 ,2 ; 2 02, dd, J5
13 5, J3
,2
10 8,
= J3
,6
J5
3 2 Hz, H 3 ; 2 62, dd, J6
1 3 Hz, H 5 ; 2 33, ddd, J3
,6
,3
,2
The acid-promoted Fries rearrangement conditions
were applied to the lower molecular weight benzan-
nulated lactones (4), (5), (27), and (28) in order to
investigate the scope of the reaction further. The -aryl
lactone (27)19 a orded the known ketone (29)20 in a
yield of 23% which was increased to 43% when 90%
sulfuric acid was used in place of polyphosphoric acid.
The -aryl lactone (28)21 which lacks the electron-
donating methoxy group a orded only a 7% yield
of the known 5-hydroxy-1-tetralone (30),22 together
with a higher yield (55%) of the product of lactone
hydrolysis, namely 2-hydroxybenzenebutanoic acid.21
In contrast to (27), the -aryl lactone 6-methoxy-3,4-
dihydrocoumarin (5), derived from 5-methoxyindan-1-
one,23 failed to undergo Fries rearrangement and instead
gave an almost quantitative yield of the hydrolysis
product 2-hydroxy-5-methoxybenzenepropanoic acid.
Likewise dihydrocoumarin (4)13 gave only the prod-
uct of hydrolysis, 2-hydroxybenzenepropanoic acid24
(71%).
14 1, J6
10 8 Hz, H 6 ;
,6
,5
2 99, dd, J6
14 1, J6
1 3 Hz, H 6 ; 3 72, s, 19-OCH3;
,5
,6
3 78, s, 12-OCH3; 6 75, dd, J13,14 8 7, J13,11 2 9 Hz, H 13;
6 89, d, J11,12 2 9 Hz, H 11; 7 00, d, J14,13 8 7 Hz, H 14.
C
17 5, C 20; 19 1, C 2; 28 3, C 18; 31 7, C 6; 37 5, C 3; 39 1,
C 1; 40 2, C 10; 44 7, C 4; 51 2, 19-OCH3; 54 1, C 5; 55 5,
12-OCH3; 111 5, C 11A; 112 2, C 13A; 121 6, C 14; 139 7,
C 8; 145 0, C 9; 156 9, C 12; 171 2, C 7; 176 5, C 19. m/z 332
(M, 22%), 304 (M CO, 100), 177 (28), 175 (35), 164 (55),
151 (28).
Methyl 11-Hydroxy-14-methoxy-7-oxopodocarpa-8,11,13-
trien-19-oate (15)
Reaction of the lactone (7) (20 mg, 0 06 mmol) with
polyphosphoric acid (5 ml) and recrystallization of the product
from hexane gave the ketone (15) as small needles (15 mg, 76%),
m.p. 199–201 , [ ]2D0 +131 (c, 0 1) (Found: C, 68 7; H, 7 5%;
M+ , 332 1623. C19H24O5 requires C, 68 6; H, 7 3%; M+
,
332 1624).
1
228 nm (log 4 2).
1718 (ester CO),
max
max
1683 cm
J3
(ketone CO).
1 13, ddd, J3
= J3
,2
13 4,
H
,3
4 0 Hz, H 3 ; 1 26, 1 29, 2s, (H 18)3, (H 20)3; 1 30,
,2
ddd, J1
J2
= J1
14 0, J2
13 7, J1
4 0, J2
3 8 Hz, H 1 ; 1 59, ddddd,
= J2
,2
,1
,1
,2
,3
= J2
,3
3 8 Hz,
13 4,
,2
,1
H 2 ; 1 97, ddddd, J2
14 0, J2
13 7, J2
,3
,2
,1
In summary, the polyphosphoric acid promoted Fries
rearrangement of benzannulated lactones is applic-
able to -aryl lactones but fails for -aryl lactones.
Yields are higher when the aromatic ring possesses an
J2
= J2
3 8 Hz, H 2 ; 2 01, dd, J5
14 7, J5
,6
,1
,3
,6
2 5 Hz, H 5 ; 2 31, br ddd, J3
13 4, J3
= J3
2 5 Hz, H 6 ;
,3
,2
,2
3 8 Hz, H 3 ; 2 89, dd, J6
15 9, J6
14 7 Hz, H 6 ; 3 32, br ddd,
,5
,6
3 04, dd, J6
15 9, J6
,5
,6
* Methyl (7aR,8S,11aS)-2-methoxy-8,11a-dimethyl-6-oxo-6,7,7a,8,9,10,11,11a-octahydrodibenz[b,d]oxepin-8-carboxylate.

Fries Rearrangements of Benzannulated Lactones
1171
J1
13 7, J1
= J1
3 8 Hz, H 1 ; 3 69, s, 19-OCH3;
3 82, s, 14-OCH3; 5 35, br s, 11-OH; 6 74, d, J13,12 8 8 Hz,
H 13; 6 86, d, J12,13 8 8 Hz, H 12. 15 3, C 20; 19 5, C 2;
(H 18)3, (H 20)3; 1 75, m, J2
,2
13 4 Hz, H 2 ; 1 86–1 91, m,
,1
,2
,2
J1
J5
dd, J6
J6
3 4 Hz, H 3 ,1 ; 2 05, m, H 2 ; 2 06, dd, J5
1 1 Hz, H 5 ; 2 36, m, J1
10 7,
13 6 Hz, H 1 ; 2 65,
10 7 Hz, H 6 ; 3 03, dd, J6 14 2,
1 1 Hz, H 6 ; 3 74, s, 19-OCH3; 3 91, s, 12-OCH3;
17 4, C 20; 19 1, C 2; 28 2,
,2
,6
,6
C
,1
28 4, C 18; 35 6, C 6; 37 3, C 3; 39 2, C 1; 41 1, C 10; 43 6,
C 4; 51 2, C 5; 51 5, 19-OCH3; 56 5, 14-OCH3; 111 4, C 13;
122 6, C 12; 122 7, C 8; 140 3, C 9; 147 4, C 11; 154 6, C 14;
177 4, C 19; 199 0, C 7. m/z 332 (M, 100%), 257 (30), 239
(26), 217 (12), 203 (14), 191 (22).
14 2, J6
,5
,6
,6
,5
6 90, s, H 11; 7 30, s, H 14.
C
C 18; 31 7, C 6; 37 4, C 3; 39 3, C 1; 40 5, C 10; 44 7, C 4;
51 3, 19-OCH3; 54 0, C 5; 56 6, 12-OCH3; 109 1, C 11; 109 8,
C 13; 125 6, C 14; 138 7, C 8; 145 0, C 9; 153 4, C 12; 170 4,
C 7; 176 3, C 19. m/z 412/410 (M, 45%), 396/394 (M O, 12),
384/382 (M CO, 100), 380/378 (M MeOH, 15), 253/255
(30), 242/244 (50), 229/231 (30), 176 (50).
Methyl 7-Oxo-7a-oxa-7-homopodocarpa-8,11,13-
trien-19-oate (9)
m-Chloroperbenzoic acid (36 mg, 2 1 mmol) was added to a
solution of methyl 7-oxopodocarpa-8,11,13-trien-19-oate (40 mg,
1 4 mmol) in chloroform (8 ml) and the mixture was stirred at
room temperature for 6 days. Additional m-chloroperbenzoic
acid (36 mg, 2 1 mmol) was added and the stirring continued
for 3 days. The solution was diluted with dichloromethane,
washed with aqueous sodium hydrogencarbonate, and dried.
Solvent was removed at reduced pressure and the residue was
chromatographed on silica. Elution with ether/hexane (2 : 1)
gave the ketone* (9) (10 mg, 25%) as needles, m.p. 114–116
(lit.7 112–115 ) (expected i.r. and n.m.r. spectra).7
Treatment of the lactone (10) (30 mg, 0 007 mmol) with
polyphosphoric acid (15 ml) and chromatography of the product
on silica gave starting material (18 mg, 60%) and a complex
mixture of less polar products.
12-Methoxy-7-oxo-7a-oxa-7-homoabieta-8,11,13-triene (12)
m-Chloroperbenzoic acid (0 13 g, 7 5 mmol) was added
to a solution of sugiol methyl ether (0 15 mg, 4 8 mmol)
in chloroform (15 ml) and the mixture was stirred at room
temperature for 3 days. Additional m-chloroperbenzoic acid
(0 13 g, 7 5 mmol) was added and stirring was continued for 5
days. The solution was washed with aqueous sodium hydrogen-
carbonate, dried, and solvent was removed at reduced pressure.
The residue was chromatographed repeatedly on silica and the
column eluted with ethyl acetate/hexane mixtures to a ord the
following compounds. (i) The lactone‡ (12) (11 mg, 7%) was
obtained as needles, m.p. 145–146 (lit.6 145 ) (expected i.r. and
Treatment of the lactone (9) (10 mg, 33 mol) with polyphos-
phoric acid (5 ml) gave a complex mixture of products that
was unable to be separated by chromatography.
Methyl 7-Oxo-7a-oxa-7-homoabieta-8,11,13-
trien-18-oate (13)
1H n.m.r. spectra).6
1 19, 2d, J16,15 = J17,15 6 9 Hz, (H 16)3, (H 17)3; 1 22, ddd,
J3 = J3 13 2, J3 4 0 Hz, H 3 ; 1 49, s, (H 20)3;
= J3 H 3 ; 1 67–1 75,
0 89, s, (H 18)3; 1 13, s, (H 19)3; 1 18,
m-Chloroperbenzoic acid (0 46 g, 2 3 mmol) was added to
a solution of methyl 7-oxoabieta-8,11,13-trien-18-oate (0 5 g,
1 5 mmol) in chloroform (20 ml) and acetic acid (2 drops)
and the mixture was stirred at room temperature for 3 days.
Additional m-chloroperbenzoic acid (0 46 g, 2 3 mmol) was
added and the stirring continued for 3 days. The solution
was concentrated and the residue selectively recrystallized from
dichloromethane to remove most of the m-chlorobenzoic acid.
Further puri cation by column chromatography on silica, with
dichloromethane as eluent, gave the lactone (13) as a crystalline
solid (0 26 g, 49%), m.p. 96–98 (lit.2 98–99 ) (expected i.r.
H
,2
,3
,2
1 54, br ddd, J3
13 2, J3
,2
,3
,2
m, (H 2)2; 1 80–1 95, m, H 1 ,1 ,5 ; 2 55–2 63, m, (H 6)2;
3 25, dq, J15,16 = J15,17 6 9 Hz, H 15; 3 85, s, 12-OCH3; 6 78,
s, H 11; 6 92, s, H 14.
18 8, C 2; 20 3, C 20; 21 4, C 19;
C
22 4, 22 6, C 16,17; 26 4, C 15; 31 8, C 6; 33 2, C 18; 36 0,
C 4; 38 8, C 1; 39 9, C 10; 41 1, C 3; 55 5, C 5; 55 8, 12-OCH3;
106 8, C 11; 118 4, C 14; 136 4, C 13; 138 2, C 9; 144 9, C 8;
153 9, C 12; 173 7, C 7. (ii) 11-Chlorosugiol methyl ether (14)
and 1H n.m.r. spectra).
16 4, C 19; 17 8, C 2; 20 5, C 20;
(9 mg, 6%), m.p. 88–89 , [ ]2D0 +31 (c, 0 3) (Found: M+
,
C
350 1820, 348 1842.
348 1856). 1680 (ketone CO), 1278, 1210 cm
0 96, s, (H 18)3A; 0 99, s, (H 19)3A; 1 22, 1 26, 2d, J16,15
= J17,15 6 9 Hz, (H 16)3, (H 17)3; 1 29, ddd, J3 = J3
C
21H29ClO2 requires M+ , 350 1826,
23 7, 23 8, C 16,17; 33 3, C 15; 35 0, C 3; 36 5, C 6; 37 9,
C 1; 38 6, C 10; 49 1, C 5; 49 9, C 4; 52 2, CO2CH3; 118 6,
C 14; 123 6, C 12; 124 3, C 11; 137 2, C 9; 149 2, C 13; 151 1,
C 8; 172 4, C 7; 177 9, CO2CH3.
Treatment of the lactone (13) (50 mg, 0 15 mmol) with
polyphosphoric acid (10 ml) gave a complex mixture of prod-
ucts unstable to chromatography.
1
.
max
H
,3
,2
13 5, J3
3 9 Hz, H 3 ; 1 51, s, (H 20)3; 1 63, br ddddd,
= J2 = J2 13 6, J2 = J2 3 8 Hz, H 2 ;
,3
,2
J2
,2
,1
,1
,3
1 75, ddddd, J2
H 2 ; 1 84, dd, J5
13 6, J2
14 3, J5
3 9, J 3 5, 3 4, 3 2 Hz,
2 9 Hz, H 5 ; 1 86, m,
,3
,2
,6
,6
Methyl 13-Bromo-12-methoxy-7-oxo-7a-oxa-7-
homopodocarpa-8,11,13-trien-19-oate (10)
J1
13 6 Hz, H 1 ; 2 57, dd, J6
16 8, J6
14 3 Hz,
2 9 Hz, H 6 ; 3 28, dq,
J15,16 = J15,17 6 9 Hz, H 15; 3 46, br ddd, J3 13 5 Hz,
13 8 Hz, H 1 ; 3 84, s, 12-OCH3;
16 7, C 20; 18 9, C 2; 21 8, C 19; 23 2, C 16A;
,1
,6
,5
H 6 ; 2 66, dd, J6
16 8, J6
,5
,6
m-Chloroperbenzoic acid (0 60 g, 3 5 mmol) was added
to a solution of methyl 13-bromo-12-methoxy-7-oxopodocarpa-
8,11,13-trien-19-oate27 (0 90 g, 2 3 mmol) in chloroform (20 ml)
and the mixture was stirred at room temperature for 5 days.
Additional m-chloroperbenzoic acid (0 6 g, 3 5 mmol) was
added and the mixture stirred for 2 days. The solution
was washed with aqueous sodium hydrogencarbonate, dried,
and solvent was removed at reduced pressure. The residue
was chromatographed on silica, and the column eluted with
dichloromethane/ether (15 : 1) to give the lactone† (10) which
crystallized from ether–hexane as small needles (0 31 g, 33%),
m.p. 131–132 , [ ]2D0 60 (c, 0 9) (Found M+ , 412 0710,
,3
H 3 ; 3 57, br ddd, J1
7 99, s, H 14.
,1
C
23 5, C 17A; 27 2, C 15; 33 2, C 18; 35 1, C 1B; 35 6, C 6B;
36 7, C 4; 40 8, C 3; 42 2, C 10; 50 6, C 5; 61 1, 12-OCH3;
125 2, C 14; 127 8, C 11; 129 8, C 8; 141 1, C 13; 149 8, C 9;
159 0, C 12; 197 9, C 7. m/z 350, 348 (M, 35, 100%), 335,
333 (M CH3, 20, 60), 293, 291 (8, 20).
Treatment of the lactone (12) (10 mg, 30 mol) with
polyphosphoric acid (10 ml) gave a complex mixture of products
unstable to chromatography.
12,19-Dimethoxypodocarpa-8,11,13-trien-7-one
410 0729.
C
1762 (lactone), 1724 cm
19H23BrO5 requires M+ , 412 0708, 410 0729).
1
(ester).
4 2 Hz, H 3 ; 1 24, 1 25, 2s,
1 09, ddd,
Chromium trioxide (0 6 g, 6 0 mmol) in 80% aqueous acetic
acid (10 ml) was added dropwise to an ice-cold solution of
max
H
J3
= J3
13 4, J3
,2
,2
,3
* Methyl (7aR,8S,11aS)-8,11a-dimethyl-6-oxo-6,7,7a,8,9,10,11,11a-octahydrodibenz[b,d]oxepin-8-carboxylate.
† Methyl (7aR,8S,11aS)-3-bromo-2-methoxy-8,11a-dimethyl-6-oxo-6,7,7a,8,9,10,11,11a-octahydrodibenz[b,d]oxepin-8-carboxylate.
‡ (7aR,8S,11aS)-2-Methoxy-8,8,11a-trimethyl-3-(1-methylethyl)-7a,8,9,10,11,11a-hexahydrodibenz[b,d]oxepin-6(7H )-one.

1172
R. C. Cambie, L. H. Mitchell and P. S. Rutledge
12,19-dimethoxypodocarpa-8,11,13-triene (0 7 g, 2 4 mmol) in
glacial acetic acid (30 ml) and the mixture was warmed to room
temperature and stirred for 4 h. The solution was extracted
with dichloromethane, and the extract washed with brine, aque-
ous sodium hydrogencarbonate, and water, and dried. Solvent
was removed at reduced pressure and the residue was chro-
matographed on silica. Elution with ether/hexane (1 : 3) gave
12,19-dimethoxypodocarpa-8,11,13-trien-7-one (0 71 g, 96%) as
s, 6-CH3; 1 29–1 44, m, H 4eq,3ax,5eq,5ax; 1 68, 1 68, 2q, J
15 3, 7 6 Hz, CH2CH3; 1 78, m, H 3eq; 2 10, dd, J
0
17 6,
4 4 Hz, H 11;
4 4 Hz, H 0; 3 29, s, CO2CH3;
,
J
0
5 3 Hz, H ; 2 31, dd, J11, 5 3, J11,
,11
2 46, dd, J
3 37, s, 8-OCH3; 6 59, dd, J9,10 8 8, J9,7 3 0 Hz, H 9; 6 78,
d, J7,9 3 0 Hz, H 7; 6 89, d, J10,9 8 8 Hz, H 10. (see
0
17 6, J
0
,
,11
C
Table 1). m/z 318 (M, 100%), 177 (30), 154 (70). (ii) The
acetyl ester‡ (24) was obtained as a colourless oil (2 4 mg,
2%), [ ]2D0 19 (c, 0 2) (Found M+ , 360 1935. C21H28O5
small cubes, m.p. 79–80 (lit.27 80–85 ).
1 03, s, (H 18)3;
4 1 Hz, H 3 ; 1 26,
H
1 07, ddd, J3
s, (H 20)3; 1 57, ddd, J1
H 1 ; 1 68, ddddd, J2
= J3
13 6, J3
= J1
14 2, J2
requires M+ , 360 1937).
CO), 1458, 1432, 1222, 1212 cm
1732 (ester CO), 1660 (ketone
max
,2
,3
,2
1
13 6, J1
4 2 Hz,
4 1,
,3
.
0 99, t, J 7 6 Hz,
H
,2
,1
,2
4 2, J2
CH2CH3; 1 33, H 3ax; 1 36, s, 6-CH3; 1 51–1 55, m, 2H,
H 3eq,5ax; 1 65–1 75, m, 4H, CH2CH3, H 5eq,4ax; 1 95, m,
,1
,2
J2
J2
3 2, J2
13 6, J2
3 2 Hz, H 2 ; 1 76, ddddd, J2
14 2,
3 2 Hz, H 2 ; 1 87, dddd, J3
,1
,1
,3
,2
H 4eq; 2 03, dd, J
0
17 3, J
5 0 Hz, H ; 2 31, dd, J11,
,11
= J2
,1
,3
,3
,
13 6, J3
= J3
3 2, J3
,1
4 9 Hz, H 5 ; 2 32, dddd, J1
1 5 Hz, H 3 ; 1 94, dd,
13 6,
5 0, J11,
0; 2 61, s, COCH3; 3 66, s, CO2CH3; 3 77, s, 8-OCH3;
6 89, d, J 3 2 Hz, H 7; 7 12, d, J 3 2 Hz, H 9. 8 1,
0
4 6 Hz, H 11; 2 38, dd, J
0
17 3, J
0
4 6 Hz,
,2
,2
,
,11
J5
J1
13 0, J5
= J1
H
,6
,6
,2
,1
3 2, J1
13 0 Hz, H 6 ; 2 78, dd, J6
1 5 Hz, H 1 ; 2 72, dd, J6
18 2, J6
,2
,3
,6
,5
C
18 2, J6
CH2CH3; 19 1, C 3; 25 3, 6-CH3; 30 9, C ; 31 6, CH2CH3;
32 2, COCH3; 36 0, C 4; 37 8, C 6; 41 8, C 11; 42 5, C 5;
51 9, CO2CH3; 55 7, 8-OCH3; 80 4, C 2; 110 6, C 9; 118 5,
C 7; 125 6, C 10; 130 2, C 6a; 150 4, C 10a; 152 4, C 8; 174 3,
COCH3; 200 1, COCH3. m/z 360 (M, 62%), 217 (11), 206
(100), 177 (16), 43 (50). (iii) The C 11 epimer (25) of the
ester (24) was obtained as a colourless oil (3 6 mg, 3%), [ ]D20
+16 (c, 0 3) (Found: M+ , 360 1939. C21H28O5 requires
,5
,6
4 9 Hz, H 6 ; 3 33, s, 19-OCH3; 3 50, 3 37, 2d, J 9 2 Hz,
(H 19)2; 3 86, s, 12-OCH3; 6 80, dd, J13,14 8 7, J13,11 2 5 Hz,
H 13; 6 84, d, J11,13 2 5 Hz, H 11; 7 99, d, J14,13 8 7 Hz, H 14.
18 7, C 2; 23 7, C 20; 27 2, C 18; 36 07, C 3; 36 10, C 6;
C
37 6, C 10; 38 0, C 1; 38 3, C 4; 49 7, C 5; 55 3, 12-OCH3;
59 4, 19-OCH3; 76 0, C 19; 109 1, C 11A; 111 4, C 13A; 124 3,
C 8; 129 9, C 14; 158 4, C 9; 164 1, C 12; 197 9, C 7.
M+ , 360 1937).
1730 (ester CO), 1659 (ketone CO),
0 99, t, J 7 4 Hz, CH2CH3; 1 26, s, 6-CH3;
H
max
1
12,19-Dimethoxy-7a-oxa-7-homopodocarpa-8,11,13-trien-7-
one (11)
1603 cm
.
1 28–1 35, m, H 3,5; 1 36–1 54, m, H 3, CH2CH3; 1 60–1 80,
m, H 5, (H 4)2, CH2CH3; 2 30, m, H ; 2 55, m, H 11; 2 57,
m, H 0; 2 64, s, COCH3; 3 71, s, CO2CH3; 3 78, s, 8-OCH3;
m-Chloroperbenzoic acid (0 45 g, 2 6 mmol) was added
to a solution of 12,19-dimethoxypodocarpa-8,11,13-trien-7-one
(0 52 g, 1 7 mmol) in chloroform (15 ml) and the mixture
was stirred at room temperature for 2 days. Additional
m-chloroperbenzoic acid (0 45 g, 2 6 mmol) was added and
the mixture stirred for a further 3 days. The solution was
washed with aqueous sodium hydrogencarbonate, dried, and
the solvent was removed at reduced pressure. The residue
was chromatographed on silica and the column eluted with
ether/hexane (2 : 3) to give the lactone* (11) (0 36 g, 65%) as
a colourless oil, [ ]D20 125 (c, 2 5) (Found M+ , 318 1831.
6 94, dd, J 3 2 Hz, H 7; 7 14, dd, J 3 2 Hz, H 9.
6 7,
C
CH2CH3; 18 9, C 3; 23 8, 6-CH3; 31 0, C ; 32 2, COCH3;
32 5, C 4; 33 6, CH2CH3; 34 9, C 5; 36 3, C 6; 38 6, C 11;
52 1, CO2CH3; 55 8, 8-OCH3; 80 6, C 2; 110 7, C 9; 117 7,
C 7; 125 8, C 10; 132 7, C 6a; 150 4, C 10a; 152 1, C 8; 173 3,
CO2CH3; 200 0, COCH3. m/z 360 (M, 64%), 219 (12), 206
(100), 193 (11), 177 (15), 43 (64).
7-Methoxy-4,5-dihydro-1-benzoxepin-2(3 H)-one (27)
C
19H26O4 requires M+ , 318 1831).
1747 (lactone CO),
max
m-Chloroperbenzoic acid (1 5 g, 8 7 mmol) was added to a
solution of 6-methoxy-3,4-dihydronaphthalen-1(2H )-one (1 0 g,
5 7 mmol) in chloroform (25 ml) and the mixture was stirred at
room temperature for 3 days. Additional m-chloroperbenzoic
acid (1 5 g, 8 7 mmol) was added and the stirring continued
for 2 days. Workup gave a residue that was chromatographed
on silica. Elution with ether/hexane (3 : 2) gave the benzoxepin
(27) as a yellow oil (0 65 g, 60%) (expected i.r. and mass
1
1487, 1165 cm
J3 = J3
(COC).
13 7, J3
0 96, s, (H 18)3; 1 01, ddd,
3 6 Hz, H 3 ; 1 45, s, (H 20)3;
H
,2
,3
,2
1 67–1 94, m, H 1 ,1 ,2 ,2 ,3 ; 1 88, dd, J5
1 0 Hz, H 5 ; 2 57, dd, J6
2 72, dd, J6
OCH3; 3 50, dd, J19-pro-S,19-pro-R 9 2, J19-pro-S,1 1 1 Hz,
H 19-pro-S; 3 59, J19-pro-R,19-pro-S 9 2 Hz, H 19-pro-R; 3 80,
s, 12-OCH3; 6 75, dd, J13,14 8 7, J13,11 2 9 Hz, H 13; 6 89, d,
11 6, J5
,6
,6
13 8, J6 11 6 Hz, H 6 ;
1 0 Hz, H 6 ; 3 37, s, 19-
,6
,5
,5
13 8, J6
,6
spectra).19
2 17, quintet, J4,5 = J4,3 7 2 Hz, (H 4)2; 2 47,
H
J11,13 2 9 Hz, H 11; 7 00, d, J14,13 8 7 Hz, H 15.
18 4, C 2;
C
t, J3,4 7 2 Hz, (H 3)2; 2 79, t, J5,4 7 2 Hz, (H 5)2; 3 80, s,
7-OCH3; 6 73, d, J6,8 3 0 Hz, H 6; 6 76, dd, J8,9 8 4, J8,6
3 0 Hz, H 8; 7 01, d, J9,8 8 4 Hz, H 9.
C 5; 30 9, C 3; 55 6, 7-OCH3; 112 4, C 8; 115 0, C 6; 120 0,
C 9; 131 1, C 5a; 145 4, C 9a; 157 1, C 7; 166 3, C 2.
20 5, C 20; 27 4, C 18; 31 2, C 6; 35 5, C 3; 38 4, C 1; 39 5,
C 10; 40 4, C 4; 55 2, C 5; 55 4, 12-OCH3; 59 1, 19-OCH3;
74 4, C 19; 111 0, 111 1, C 11,13; 121 0, C 14; 141 6, C 8;
144 9, C 9; 156 7, C 12; 172 9, C 7. m/z (M, 100%), 177 (40),
175 (55), 164 (30), 151 (45), 45 (50).
26 2, C 4; 28 5,
C
Treatment of 12,19-Dimethoxy-7a-oxa-7-homopodocarpa-
8,11,13-trien-7-one (11) with Polyphosphoric Acid
5-Hydroxy-8-methoxy-3,4-dihydronaphthalen-1(2 H)-
one (29)
A solution of the lactone (11) (0 12 g, 3 8 mmol) was
treated with polyphosphoric acid (20 ml) and the product chro-
matographed on silica. Elution with dichloromethane and then
ethyl acetate/hexane (1 : 6) gave the following compounds. (i)
The ester† (23) (24 mg, 19%) was obtained as a colourless oil,
(A) Preparation with polyphosphoric acid. Reaction of
the lactone (27) (0 13 g, 6 7 mmol) with polyphosphoric
acid (25 ml) gave the naphthalenone (29) as a pale brown
solid (29 mg, 23%), m.p. 165–167 (lit.20 170 ) (Found M+
,
3350
2 07, quintet,
H
192 0786. Calc. for C11H12O3: M+ , 192 0786).
max
1
[ ]2D0 +15 (c, 0 2) (Found: M+ , 318 1831. C19H26O4 requires
(OH), 1676 (ketone), 1589, 1481, 1275 cm
.
1
M+ , 318 1831).
1728 (ester CO), 1600, 1487 cm
.
J3,4 = J3,2 6 5 Hz, (H 3)2; 2 63, t, J4,3 6 5 Hz, (H 4)2; 2 90,
t, J2,3 6 5 Hz, (H 2)2; 3 81, s, 8-OCH3; 5 70, br s, 5-OH;
max
H
(C6D6) 0 91, t, J 7 6 Hz, CH2CH3; 1 21, m, H 4ax; 1 23,
* (7aR,8S,11aS)-2-Methoxy-8-methoxymethyl-8,11a-dimethyl-7a,8,9,10,11,11a-hexahydrodibenz[b,d]oxepin-6(7H )-one.
† Methyl 2-ethyl-8-methoxy-6-methyl-3,4,5,6-tetrahydro-2,6-methano-2H -1-benzoxocin-11-ethanoate.
‡ Methyl 10-acetyl-2-ethyl-8-methoxy-6-methyl-3,4,5,6-tetrahydro-2,6-methano-2H -1-benzoxocin-11-ethanoate.

Fries Rearrangements of Benzannulated Lactones
1173
6 70, d, J7,6 8 9 Hz, H 7; 7 05, d, J6,7 8 9 Hz, H 6.
22 2,
panoic acid (42 mg, 95%) as small needles, m.p. 85–86 (Found:
C
C 3A; 23 7, C 4A,2; 56 2, 8-OCH3; 110 4, C 7; 120 7, C 6;
122 6, C 8a; 133 0, C 4a; 146 5, C 5; 154 3, C 8; 198 7, C 1.
m/z 192 (M, 100%), 174 (M H2O, 15), 164 (M CO, 50),
163 (M CHO, 50), 135 (24), 121 (26), 106 (29).
C, 61 9; H, 6 6%; M+ , 196 0737. C10H12O4 requires C,
61 2; H, 6 2%; M+ , 196 0736).
3013br (CO2H), 1705
max
1
(CO2H), 1503 cm
.
2 74, m, (H )2; 2 85, m, (H )2;
H
3 73, s, 5-OCH3; 6 6–6 8, m, 3H, H 3,4,6; 7 95, br s, 2H,
CO2H, 2-OH. 24 9, C ; 34 4, C ; 55 7, 5-OCH3; 112 9,
(B) Preparation with 90% sulfuric acid. A solution of the
lactone (27) (90 mg, 4 7 mmol) in 90% sulfuric acid (15 ml)
was stirred at room temperature for 30 min. Workup and
extraction with ethyl acetate gave the ketone (29) (39 mg, 43%)
(correct spectrometric data).
C
C 6; 115 8, C 4; 117 2, C 3; 127 9, C 1; 147 7, C 2; 153 6,
C 5; 179 7, CO2H. m/z 196 (M, 38%), 178 (M H2O, 90),
150 (M H2CO2, 52), 136 (M CH3CO2H, 100), 108 (30), 77
(21).
4,5-Dihydro-1-benzoxepin-2(3 H)-one (28)
Attempted Fries Rearrangement of 3,4-Dihydrocoumarin
(4)
3,4-Dihydronaphthalen-1(2H )-one (3 ml, 23 mmol) was
added slowly to a solution of m-chloroperbenzoic acid (6 8 g,
39 mmol) in chloroform (160 ml) and the mixture was stirred
at room temperature for 3 days. The solution was worked up
to give the ketone (28) as a yellow oil (1 8 g, 50%) (expected
i.r. and 1H n.m.r. spectra).21
Treatment of 3,4-dihydrocoumarin28 (0 10 g, 0 68 mmol)
with polyphosphoric acid (8 ml) gave a residue which was chro-
matographed on silica. Elution with ether/hexane (1 : 1) gave
2-hydroxybenzenepropanoic acid (75 mg, 75%) as a crystalline
solid, m.p. 79–80 (lit.29 82–83 ).
2 71, t, J 6 8, 7 0 Hz,
H
(H )2; 2 90, t, J 6 8, 7 0 Hz, (H )2; 6 75–6 90, m, 2H,
H 6,3; 7 05–7 12, m, 2H, H 4,5; 8 00, br s, 2H, CO2H, 2-OH.
5-Hydroxy-3,4-dihydronaphthalen-1(2 H)-one (30)
Reaction of the lactone (28) (0 1 g, 0 6 mmol) with polyphos-
phoric acid (20 ml) gave a residue which was chromatographed
on silica. Elution with ether/hexane (1 : 1) gave the fol-
lowing. (i) The ketone (30) (7 mg, 7%), m.p. 209–211
(lit.22 210–211 ) (expected i.r. and 1H n.m.r. spectra).22 (ii)
2-Hydroxybenzenebutanoic acid (59 mg, 55%), m.p. 65–66
24 6, C ; 34 4, C ; 116 6, C 3; 121 0, C 5; 126 7, C 1;
128 0, C 4; 130 5, C 6; 153 9, C 2; 179 4, CO2H.
C
References
1
Matsumoto, T., Imai, S., Aizawa, M., Kitagawa, H., and
Fukui, K., Chem. Lett. Jpn, 1972, 581.
Ohtsuka, Y., and Tahara, A., Chem. Pharm. Bull., 1973,
21, 643, 653.
Pelletier, S. W., and Ohtsuka, Y., Tetrahedron, 1977, 33,
1021.
Anderson, A., Neron-Desbiens, M., Savard, S., and Burnell,
R. H., Synth. Commun., 1980, 10, 183.
Burnell, R. H., Anderson, A., Neron-Desbiens, M., and
Savard, S., Can. J. Chem., 1981, 59, 2820.
Burnell, R. H., Jean, M., Poirier, D., and Savard, S., Can.
J. Chem., 1984, 62, 2822.
Burnell, R. H., Jean, M., and Poirier, D., Can. J. Chem.,
1987, 65, 775.
Cambie, R. C., Mitchell, L. M., and Rutledge, P. S., Aust.
J. Chem., 1998, 51, 931.
Martin, R., Org. Prep. Proced. Int., 1992, 24, 369.
Blatt, A. H., Org. React. N.Y., 1942, 1, 342.
Gerecs, A., ‘Friedel-Crafts and Related Reactions’ (Ed. G.
A. Olah) Vol. 3, Part 1, p. 499 (Interscience: New York
1964).
Patai, S., ‘The Chemistry of the Carbonyl Group’ (Inter-
science: New York 1966–1970).
Louden, J. D., and Razdan, R. K., J. Chem. Soc., 1954,
4299.
Kelly, T. R., Bell, S. H., Ohashi, N., and Armstrong-Chong,
R. J., J. Am. Chem. Soc., 1988, 110, 6471.
Johansson, A. M., Mellin, C., and Hacksell, U., J. Org.
Chem., 1986, 51, 5252.
Finnegan, R. A., and Mattice, J. J., Tetrahedron, 1965, 21,
1015.
Crump, D. R., Franck, R. W., Gruska, R., Ozorio, A. A.,
Pagnotta, M., Siuta, G. J., and White, J. G., J. Org.
Chem., 1977, 42, 105.
Brieskorn, C. H., Fuchs, A., Bredenberg, J. B.-son, McCh-
esney, J. D., and Wenkert, E., J. Org. Chem., 1964, 29,
2293.
Johnson, D. W., and Mander, L. N., Aust. J. Chem., 1978,
31, 1561.
Crawford, M., and Supanekar, V. R., J. Chem. Soc., 1960,
1985.
Nicolle, J. P., Haman, J. F., and Wakselman, M., Bull.
Soc. Chim. Fr., 1997, 83.
(lit.21 67 ).
1 93, tt, J 7 6, 6 9 Hz, (H )2; 2 44, t, J
H
2
7 6 Hz, (H )2; 2 67, t, J 6 9 Hz, (H )2; 6 78–6 87, m, 2H,
H 6,3; 7 04–7 12, m, 2H, H 5,4; 7 40, br s, 2H, CO2H, OH.
C
3
24 6, C ; 29 2, C ; 32 8, C ; 115 6, C 3; 120 6, C 5; 127 0,
C 1; 127 6, C 4; 130 3, C 6; 153 9, C 2; 180 2, CO2H.
4
5-Methoxyindan-1-one
5
Chromium trioxide (2 9 g, 29 7 mmol) in 80% aqueous acetic
acid (20 ml) was added slowly to an ice-cold stirred solution
of 5-methoxyindan (2 2 g, 14 9 mmol) in acetic acid (30 ml).
The mixture was warmed to room temperature and stirring
was continued for 4 5 h. The solution was then extracted with
dichloromethane, and the combined extracts were worked up
to give 5-methoxyindan-1-one as a pale yellow solid (2 1 g,
6
7
8
87%), m.p. 105–107 (lit.23 109–111 ).
2 66, t, J3,2 5 9 Hz,
9
H
(H 3)2; 3 08, t, J2,3 5 9 Hz, (H 2)2; 3 88, s, 5-OCH3; 6 88,
dd, J6,7 7 7, J6,4 2 1 Hz, H 6; 6 90, d, J4,6 2 1 Hz, H 4; 7 68,
10
11
d, J7,6 7 7 Hz, H 7.
25 8, C 3; 36 3, C 2; 55 5, 5-OCH3;
C
109 6, C 6; 115 2, C 4; 125 2, C 7; 130 3, C 7a; 158 1, C 3a;
165 1, C 5; 205 2, C 1.
12
6-Methoxy-3,4-dihydrocoumarin (5)
13
5-Methoxyindan-1-one (1 0 g, 6 2 mmol) in sulfuric acid/
acetic anhydride (1 : 10 ml) was added slowly to an ice-
cold solution of m-chloroperbenzoic acid (5 0 g, 29 mmol)
in dichloromethane (20 ml) and the mixture was kept in the
dark at room temperature for 4 days. The solution was washed
with aqueous sodium bisul te and then aqueous sodium hydro-
gencarbonate, and the solvent was removed under vacuum to
give a residue that was chromatographed on silica. Elution of
the column with ethyl acetate/hexane (1 : 4) gave 6-methoxy-
3,4-dihydrocoumarin (5) (0 75 g, 67%) as a sticky solid, m.p.
14
15
16
17
45–46 (lit.23 46–47 ) (expected i.r. spectrum).
4 40–4 47,
18
H
m, (H 4)2; 4 61–4 70, m, (H 3)2; 3 77, s, 6-OCH3; 6 71, d,
J5,7 2 8 Hz, H 5; 6 76, dd, J7,8 8 8, J7,5 2 8 Hz, H 7; 6 96,
19
d, J8,7 8 8 Hz, H 8.
23 9, C 4; 29 0, C 3; 55 5, 6-OCH3;
C
112 9, C 7A; 113 1, C 5A; 117 5, C 8; 123 5, C 8a; 134 4, C 4a;
161 7, C 6; 165 9, C 2.
20
2-Hydroxy-5-methoxybenzenepropanoic Acid
21
Treatment of the dihydrocoumarin (5) (40 mg, 0 22 mmol)
with polyphosphoric acid (10 ml) and crystallization of the prod-
uct from ether/hexane gave 2-hydroxy-5-methoxybenzenepro-
22
Valderrama, J. A., Pessoa-Mahana, H., and Tapia, R.,
Synth. Commun., 1992, 22, 629.

1174
R. C. Cambie, L. H. Mitchell and P. S. Rutledge
23
26
27
28
29
Chatterjee, A., Bhattachrya, S., Banerji, J., and Ghosh, P.
Cambie, R. C., Mander, L. N., Bose, A. K., and Manhas,
M. S., Tetrahedron, 1964, 20, 409.
Cambie, R. C., Robertson, J. D., Rutledge, P. S., and
Woodgate, P. D., Aust. J. Chem., 1981, 34, 2687.
Crichton, E. G., and Waterman, P. D., Phytochemistry,
1978, 17, 1783.
C., Indian J. Chem., Sect. B, 1977, 15, 214.
Buckingham, J., (Ed.) ‘Dictionary of Organic Compounds’
6th Edn, Vol. 4 (Chapman & Hall: London 1996).
Cambie, R. C., Franich, R. A., Larsen, D., Rutledge, P. S.,
Ryan, G. R., and Woodgate, P. D., Aust. J. Chem., 1990,
43, 21.
24
25
Davis, B. R., and Watkins, W. B., Aust. J. Chem., 1968,
21, 2769.