Rhodium(II)-Catalyzed Decomposition of 1-Diazo-4-(1- or 2-naphthyl)-2-butanones as a New Route to Rearranged Pimarane and Abietane Skeleta. Synthesis of Umbrosone

Article abstract of DOI:10.1021/jo970631k

The Rh₂(OAc)₄catalyzed intramolecular Buchner reaction of 1-diazo-4-(1- or 2-naphthyl)butan-2-ones was examined as a potential route to abietane and rearranged abietane derivatives. Treatment of the α-diazo ketone 26 with catalytic amount of dirhodium tetraacetate in CH₂Cl₂ at 0 °C furnished the tetracyclic derivative 27 in good yield. Addition of TFA to 27 (in CH₂Cl₂) resulted in an acid-induced opening of the cyclopropane ring to give the 4a- and 10a-methyldihydrophenanthrenones 28 and 29 in nearly equal amounts. These compounds and their analogs appear to be suitable intermediates for the synthesis of diterpenoids containing aromatic A or C rings. When the diazo ketone 34 was decomposed under Rh(II) catalysis, a 10-methyldihydroanthracenone (i.e., 36) was obtained as the main product, besides minor amounts of the expected tetracyclic ketone 35. The extension of this result to the preparation of the methoxy-substituted dihydroanthracenone 39 (52% yield) was exploited in a new total synthesis of umbrosone (6), an unusual diterpenoid possessing a rearranged linear skeleton.

Full text of DOI:10.1021/jo970631k

6
658
J . Org. Chem. 1997, 62, 6658-6665
Rh od iu m (II)-Ca ta lyzed Decom p osition of 1-Dia zo-4-(1- or
-n a p h th yl)-2-bu ta n on es a s a New Rou te to Rea r r a n ged P im a r a n e
a n d Abieta n e Sk eleta . Syn th esis of Um br oson e
2
Paolo Manitto,* Diego Monti, Simona Zanzola, and Giovanna Speranza
Dipartimento di Chimica Organica e Industriale, Universit a` di Milano,
and Centro di Studio per le Sostanze Organiche Naturali, CNR, via Venezian 21, I-20133 Milano, Italy
Received April 8, 1997X
The Rh
ones was examined as a potential route to abietane and rearranged abietane derivatives. Treatment
of the R-diazo ketone 26 with catalytic amount of dirhodium tetraacetate in CH Cl at 0 °C furnished
the tetracyclic derivative 27 in good yield. Addition of TFA to 27 (in CH Cl ) resulted in an acid-
induced opening of the cyclopropane ring to give the 4a- and 10a-methyldihydrophenanthrenones
8 and 29 in nearly equal amounts. These compounds and their analogs appear to be suitable
2 4
(OAc) -catalyzed intramolecular Buchner reaction of 1-diazo-4-(1- or 2-naphthyl)butan-2-
2
2
2
2
2
intermediates for the synthesis of diterpenoids containing aromatic A or C rings. When the diazo
ketone 34 was decomposed under Rh(II) catalysis, a 10-methyldihydroanthracenone (i.e., 36) was
obtained as the main product, besides minor amounts of the expected tetracyclic ketone 35. The
extension of this result to the preparation of the methoxy-substituted dihydroanthracenone 39 (52%
yield) was exploited in a new total synthesis of umbrosone (6), an unusual diterpenoid possessing
a rearranged linear skeleton.
The 4a-methyloctahydrophenanthrene system 1 and its
0a-methyl isomer 4 are present in a number of tricyclic
involved a stereospecific methyl group migration giving
1
rise to the 4a-center with a predetermined configuration.
1
12,13
diterpenoids with an aromatic C or A ring, such as
In the case of the less common system 4,
acid-
2
3
podocarpic acid (2a ), ferruginol (2b), ar-maximic acid
promoted 20(10-5)-abeo rearrangements of 8,11,13-abi-
4
5
14
(
3), and pygmaeocin C (5). If properly functionalized,
etatriene derivatives have been described.
1
and 4 could serve as useful intermediates in the
6
synthesis of policyclic diterpenoids as well as of a wide
range of triterpenoids, steroids, and steroidal alkaloids.
Although the preparation of the structural unit 1 has
been accomplished in a variety of ways,7
-11
none of them
X
Abstract published in Advance ACS Abstracts, August 15, 1997.
1) Hanson, J . R. Nat. Prod. Rep. 1996, 13, 59 and references cited
(
therein. Hanson, J . R. In Rodd’s Chemistry of Carbon Compounds, 2nd
ed.; Sainsbury, M., Ed.; Elsevier: Amsterdam, 1994; 2nd Supplement,
pp 419-439.
(2) Campbell, W. P.; Todd, D. J . Am. Chem. Soc. 1942, 64, 928.
(3) King, F. E.; King, T. J .; Topliss, J . G. J . Chem. Soc. 1957, 573.
(4) Tanaka, N.; Sakai, H.; Murakami, T.; Saiki, Y.; Chen, C.-M.;
Iitaka, Y. Chem. Pharm. Bull. 1986, 34, 1015.
(
5) Meng, Q.; Hesse, M. Helv. Chim. Acta 1990, 73, 455.
(6) Goldsmith, D. The Total Synthesis of Tri- and Tetracyclic
Diterpenes. In The Total Synthesis of Natural Products; ApSimon, J .,
Ed.; Wiley Interscience Publisher: New York, 1992; Vol. 8, p 1.
(7) CB f A sequence (Robinson annulation). Reviews: J ung, M. E.
Tetrahedron 1976, 32, 3. Gawley, R. E. Synthesis 1976, 777. Inter alia
cf. (a) Welch, S. C.; Hogan, C. P.; Kim, J . H.; Chu, P. S. J . Org. Chem.
1
977, 42, 2879. (b) Sinha, G.; Maji, S. K.; Ghatak, U. R.; Mukherjee,
M.; Mukherjee, A. K.; Chakravarty, A. K. J . Chem. Soc., Perkin Trans.
1983, 2519. (c) D’Angelo, J .; Revial, G.; Volpe, T.; Pfau, M.
Recently, we found15 that the 1,2-dihydrophenanthren-
3(4H)-one (9) can be obtained in almost quantitative yield
by TFA treatment of compound 8, which in turn was
easily prepared from 7 through a rhodium(II)-promoted
1
Tetrahedron Lett. 1988, 29, 4427. (d) Nerinckx, W.; Vandewalle, M.
Tetrahedron: Asymmetry 1990, 1, 265. (e) Chiu, C. K.-F.; Govindan,
S. V.; Fuchs, P. L. J . Org. Chem. 1994, 59, 311. (f) (Wenkert annulation)
Wenkert, E.; Stevens, T. E. J . Am. Chem. Soc. 1956, 78, 2318. (g) (acid
catalyzed cyclization) Karpha, T. K.; Basu, B. Synth. Commun. 1992,
1
6
intramolecular Buchner reaction (Scheme 1A).
An
2
2, 1505.
8) AB f C sequence; inter alia cf. (a) Spencer, T. A.; Weaver, T.
analogous reaction sequence, when performed starting
(
D.; Villarica, R. M.; Friary, R. J .; Posler, J .; Schwartz, M. A. J . Org.
Chem. 1968, 33, 712. (b) Spencer, T. A.; Friary, R. J .; Schmiegel, W.
W.; Simeone, J . S.; Watt, D. S. J . Org. Chem. 1968, 33, 719.
(12) CB f A sequence: Touboul, E.; Brienne, M.-J .; J acques, J . J .
Chem. Res. Synop. 1977, 106.
(13) AC f B sequence: Wang, X.-L.; Cui, Y.-X.; Pan, X.-F. Tetra-
hedron Lett. 1994, 35, 423.
(14) Matsumoto, T.; Tanaka, Y.; Terao, H.; Takeda, Y.; Wada, M.
Chem. Pharm. Bull. 1993, 41, 1960.
(15) Manitto, P.; Monti, D.; Speranza, G. J . Org. Chem. 1995, 60,
484.
(9) AC f B sequence, inter alia cf: (a) Sone, T.; Terashima, S.;
Yamada, S.-I. Chem. Pharm. Bull. 1976, 24, 1273. (b) Wisocka, W.;
Canonne, P.; Leicht, L. C. Synthesis 1977, 261. (c) Hao, X. J .; Node,
M.; Fuji, K. J . Chem. Soc., Perkin Trans. 1 1992, 1505. (e) Schultz, A.
G.; Wang, A. J . Org. Chem. 1996, 61, 4857 and references cited therein.
(10) C f BA sequence: (a) Stork, G.; Gregson, M. J . Am. Chem.
Soc. 1969, 91, 2373. (b) Smith, A. B., III; Dieter, R. K. J . Am. Chem.
Soc. 1981, 103, 2017.
(16) (a) Kennedy, M.; McKervey, M. A.; Maguire, A. R.; Tuladhar,
S. M.; Twohig, M. F. J . Chem. Soc., Perkin Trans. 1 1990, 1047. (b)
Doyle, M. P.; Protopopova, M. N.; Peterson, C. S.; Vitale, J . P.;
McKervey, M. A.; Garcia, C. F. J . Am. Chem. Soc. 1996, 118, 7865
and references cited therein.
(11) Reductive methylation of phenanthrene: Spanevello, R. A.;
Gonzalez-Sierra, M.; McChesney, J . D. Synth. Commun. 1993, 23, 2463
and references cited therein.
S0022-3263(97)00631-2 CCC: $14.00 © 1997 American Chemical Society

New Route to Rearranged Pimarane and Abietane Skeleta
J . Org. Chem., Vol. 62, No. 19, 1997 6659
Sch em e 1a ,b
Sch em e 2a ,b
a
Reaction conditions: (a) Rh2(OAc)4, CH2Cl2; (b) TFA, CH2Cl2,
b
rt. Phenanthrene numbering is arbitrarily used for the tetra-
cyclic derivatives to make clear their structural correlation and
comparison of their NMR data with those of dihydrophenan-
threnones.
a
b
R = H, Me, OMe. For clarity, one enantiomer is depicted.
Sch em e 3a ,b
from 1-diazo-4-(1-naphthyl)butan-2-one (10),17 gave the
tetracyclic ketone 11, whose structure was proved by
1
5
comparison of its NMR data with those of 8 (in addition
1
H NOEs were observed in 11 between H-1 and H-10 and
between H-5 and H-4). The 3,4-dihydrophenanthren-
2
(1H)-one (12)18 was then obtained by treating 11 with
TFA (Scheme 1B). The isolated yields of compounds 11
and 12 confirmed the applicability of the intramolecular
naphthalene cyclopropanation to synthesize dihydro-
phenanthrenones with the carbonyl function at 2- or 3-
position.
The high selectivity in the formation of 12 and 9 as
end products of the cyclopropane ring opening may be
understood if one considers the cation stabilization in the
1
pairs 17/18 (Scheme 2, R ) H) and 22/23 (Scheme 3, R
2
)
R ) H), respectively. All of them being in conjugation
with the phenyl group, it is likely that the tertiary
carbocations are favored with respect to the secondary
ones. In addition, the easy rearomatization of ring B by
subsequent deprotonation of the angular cation predomi-
nates over other possible routes having spiranic cations
as intermediates. Lacking aromatization as a driving
force, the electronic stabilization of the carbocation must
be the main guiding factor in determining the particular
a
R1 = H, Me. R2 = H, OMe. See note b of Scheme 2.
b
one, so that the spiro derivatives 25a ,b are formed as
the only reaction products; (ii) TFA treatment of the
cyclopropane bond that breaks under the attack of the
19c
electrophile.1
0,19
This appears to be consistent with two
on compounds
4a ,b the benzylic cation prevails over the unconjugated
facts: (i) by the action of dry HCl in CHCl
3
2
(17) Throughout this work R-diazo ketones were prepared from the
corresponding 3-arylpropionic acids via the standard procedure for
conversion to the acyl chloride followed by treatment with ethereal
diazomethane. Cf. Scott, L. T.; Sumpter, C. A. Organic Syntheses;
Wiley, New York, 1990; Vol. 69, pp 180-187.
(
18) Trost, B. M.; Hiroi, K.; Kurozumi, S. J . Am. Chem. Soc. 1975,
9
7, 438.
(
19) (a) Barton, D. H. R.; De Mayo, P.; Shafiq, M. J . Chem. Soc.
1
958, 140. (b) Shoulders, B. A.; Kwie, W. W.; Klyne, W.; Gardner, P.
D. Tetrahedron 1965, 21, 2973. (c) Dasgupta, S. K.; Sarma, A. S.
Tetrahedron 1973, 29, 309. (d) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-
W.; Yip, Y.-C.; Tanko, J .; Hudlicky, T. Chem. Rev. 1989, 89, 165 and
references cited therein.
1
tetracyclic compound 14 [ H NOE from Me to H-1 (1%);
from Me to H-10 (2%)] resulting from the decomposition
of the 1-diazo-4-(2-methoxy-1-naphthyl)butan-2-one (13)

6
660 J . Org. Chem., Vol. 62, No. 19, 1997
Manitto et al.
Sch em e 4a
26 or 34, followed by acid treatment of the resulting
tetracyclic ketones 27 or 35. It can be pointed out that
an extension of this procedure starting from analogs of
the R-diazo ketones 26 or 34 with appropriate substitu-
ents would provide convenient entries to the synthesis
of podocarpanes (e.g., 2a ), abietanes (e.g., 2b), and 20(10-
9
)-abeo-pimaranes (e.g., 3) as well as 20(10-5)-abeo-
abietanes (e.g., 5). In addition, the isolation of 10-methyl-
,4-dihydroanthracen-2(1H)-ones 36 and 39 as the most
3
abundant reaction products in the Rh(II)-induced decom-
position of the diazo ketones 34 and 37 (Scheme 5)
suggests a new way to obtain rearranged linear abiet-
anes.21 This opportunity has been exploited by us to
2
1b
achieve a formal total synthesis of umbrosone (6), an
unusual diterpenoid present in the roots of Hyptis um-
brosa and possessing antimicrobial activity.2
1c
a
Reaction conditions: (a) Rh2(OAc)4, CH2Cl2, 0 °C; (b) TFA,
CH2Cl2, rt.
Resu lts a n d Discu ssion
Sch em e 5a
Rh
2 4
(OAc) Decom p osition of 1-Dia zo-4-(2-m eth yl-
1
-n a p h th yl)-2-bu ta n on e (26). The diazo ketone 26 was
2
2
obtained from 1-bromo-2-methylnaphthalene (30a ) via
the Heck reaction2 with methyl acrylate, followed by
3a
23b
hydrogenation of the resulting (E)-unsaturated ester
(
31a ) and hydrolysis to 3-(2-methyl-1-naphthyl)propionic
1
7
acid (32a). When 26 was treated with catalytic amounts
a
Reaction conditions: (a) Rh2(OAc)4, CH2Cl2, 0 °C; (b) TFA.
2 2
of dirhodium tetraacetate in CH Cl at 0 °C for 3 h, the
reaction product (80% isolated yield) was shown to be the
furnished the spiro derivative 15 [IR (CHCl
3
) 1660, 1743
cm ; NOE association of H-2′ with H-8 (1.3%)] (Schemes
C and 2). The latter outcome is clearly due to a strong
-1
expected cyclopropane derivative 27 on the basis of NMR
1
1
analogies with compound 11 (in particular H NOE
stabilization of the cation 18 (R ) OMe) by the electron
donor methoxy group which eventually gives rise to the
carbonyl function.
correlations of Me with H-10). Addition of TFA (a few
drops) to a CH Cl solution of 27 at rt for 15 min afforded
2
2
nearly equal amounts of two compounds which were
separated by column chromatography. The more polar
of these (44% isolated yield) was shown to be the known
In view of the above findings our attention was directed
to the reactions of sequences B and A of Scheme 1
starting from diazo ketones with a methyl group in the
â- or R-position of the naphthalene nucleus, respectively.
The aim was to examine the effects of this substitution
both on the regioselectivity in the attack of the electro-
philic metal carbene20 upon the naphthalene nucleus and
on the evolution of cations resulting from cyclopropane
1
2,24
4a-methyl-4,4a-dihydrophenanthren-2(3H)-one (28)
while the structure 10a-methyl-1,10a-dihydrophenan-
thren-3(2H)-one (29) was assigned to the other reaction
product (47%) taking account of its spectral data: in
particular, the presence of an R,â-unsaturated carbonyl
1
opening in species such as 16 (R ) Me) and 21 (R ) Me,
(21) (a) Meng, Q.; Zhu, N.; Chen, W. Phytohemistry 1988, 27, 1151.
(b) Delle Monache, F.; Delle Monache, G.; Gacs-Baits, E.; Coelho, J .
D. B.; De Albuquerque, I. L.; Chiappeta, A. D. A.; De Mello, J . F.
Phytochemistry 1990, 29, 3971. (c) Gosh, K.; Gathak, U. R. Tetrahedron
Lett. 1994, 35, 5943. (d) Matsumoto, T.; Takeda, I.; Usui, S.; Imai, S.
Chem. Pharm. Bull. 1996, 44, 530. (e) Matsumoto, T.; Takeda, I.; Soh,
K., Gotoh, H.; Imai, S. Chem. Pharm. Bull. 1996, 44, 1318.
2
R ) H or OMe), rearomatization being precluded in any
case.
We report here a new route to 4a-methyl-4,4a-dihy-
drophenanthren-2(3H)-one (28) and 10a-methyl-1,10a-
dihydrophenanthren-3(2H)-one (29) (Schemes 4 and 5)
(22) Newman, M. S.; Dhawan, B.; Tuncay, A. J . Org. Chem. 1976,
based on the Rh
yl-substituted 1-diazo-4-(1- or 2-naphthyl)-2-butanones
2 4
(OAc) -catalyzed decomposition of meth-
41, 3924.
(23) (a) Melpolder, J . B.; Heck, R. F. J . Org. Chem. 1976, 41, 265.
(
b) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2 and references
cited therein.
(
20) (a) Doyle, M. P. Acc. Chem. Res. 1986, 19, 348. (b) Chem. Rev.
(24) (a) Britten, A.; Njau, E. J . Chem. Soc., Perkin Trans. 1 1976,
158. (b) Njau, E. Aust. J . Chem. 1976, 29, 2731.
1
986, 86, 919.

New Route to Rearranged Pimarane and Abietane Skeleta
1653 cm-1) and UV
J . Org. Chem., Vol. 62, No. 19, 1997 6661
group was supported by IR (CHCl
max (log ꢀ) (MeOH) 258 (4.38), 306 (3.96), 348 (3.68) nm]
3
same way used to prepare compound 26.17 On treatment
of 34 with dirhodium tetraacetate, as previously de-
scribed, two products were isolated from the reaction
mixture by flash chromatography. One of them was
found to be the expected tetracyclic ketone 35 by com-
[λ
spectra, while the position of the methyl group and of
1
the two olefinic bonds was confirmed by H NOE experi-
ments [correlations between H-8 (δ 7.13) with H-9 (δ
1
5
6
.43), H-4 (δ 6.34) with H-5 (δ 7.68), and Me (δ 1.27) with
parison of its NMR spectra with those of compound 8
H-10 (δ 5.86)] (cf. ref 5).
The origin of the two isomeric dihydrophenanthrenones
and by NOE correlations [from Me to H-5 (7.2%); from
H-5 to Me (1%)]. The other showed spectroscopic data
consistent with the presence of a methyl group linked to
an aromatic ring (δ 2.68), of an unconjugated keto group
2
8 and 29 can be rationalized as shown in Scheme 2 (R
Me), i.e., in terms of a tendency of cations 17 and 18,
resulting from the protonation of the cyclopropyl ketone
as in 16), to collapse to the more stable cations 19 or 20
)
-1
[IR(CHCl
3
) 1715 cm ], and of a naphthalene system [UV
(
λmax (log ꢀ) (MeOH) 232 (5.16), 276 (4.04) nm]. The
through the migration of the angular methyl group or of
the C(1′)-C(5′) bond, respectively.25 A ready deprotona-
tion of the initially formed enol group then concludes both
rearrangements. Apparently, the presence of the methyl
group both precludes the ring B aromatization and
stabilizes the spiranic cation 18 that becomes competitive
with 17. In principle, the conversion of 16 into the
rearranged carbocations 19 and 20 could occur via
concerted mechanisms.1
structure of 10-methyl-3,4-dihydroanthracen-2(1H)-one
(36) was assigned to it on the basis of additional H NOE
experiments (7.3% and 2.7% intensity enhancement of
H-5 and H-4, respectively, by irradiation of the methyl
protons, and 2.6% enhancement of H-9 by irradiation of
H-1).
1
The isolation of compound 36 as the more abundant
product (its ratio to 35 was found to be ca 2 by NMR
analysis of reaction mixture from repeated preparations)
deserves some comments. This result appeared to be
rather surprising in view of the well-recognized prefer-
ence for five-membered-ring formation exhibited by in-
tramolecular metal carbene reactions with dirhodium(II)
0a
Compound 28, first prepared by reaction between
7
f
1
-methyl-2-naphthol and methyl vinyl ketone, has been
shown to be a potential intermediate in the synthesis of
resin acids related to podocarpic acid (2a )27 since it can
be converted into the key synthon 33 by reduction with
lithium in liquid ammonia.2 In addition, the presence
of the diene system in compound 28 makes it (or its
analogs with appropriate substituents in ring C) par-
ticularly suitable for synthesizing ring B oxygenated
diterpenoids.1 The availability of the 10a-methyl-1,10a-
dihydrophenanthren-3(2H)-one (29) from the route of
Scheme 2 (and from that described in Scheme 3, vide
infra) opens a new access to the system 4. It can be
noticed that the functionality of rings A and B of 29 is
the same as in pygmaeocins B and C (5).5
1
6,31
carboxylates as catalysts.
However, exceptions are
7a
known which can be attributed to steric factors32 or to
31c
electronic stabilization of the developing electrophilic
3
3
center resulting from a six-membered ring closure.
Compound 36 may derive from an insertion reaction of
the carbenoid center into the C(3)-H bond of the aro-
matic nucleus,34 but the production of compounds of
formal aromatic C-H insertion is generally thought to
,6
3
1c,35
involve an addition-elimination mechanism.
The
intramolecular electrophilic addition of the rhodium
carbene to form a six-membered carbocation intermedi-
ate, which undergo ready deprotonation33 with concur-
rent dissociation of the catalyst to complete the overall
substitution reaction [as depicted in Scheme 6, path b],
seems the most likely explanation for the origin of 36.
In fact, it is improbable that a cycloaddition to the 2,3-
side of the naphthalene nucleus occurs giving rise to the
nonaromatic compound 43 (R ) Me) which then under-
goes cleavage of the cyclopropane ring under the action
of the electrophilic metal catalyst.20 A rapid rearomati-
zation of 43 (R ) Me) would take place via cycloreversion
with formation of the dihydrobenzoazulenone 44 (R )
Me). Such a norcaradiene-cycloheptatriene isomeriza-
tion36 does occur from 43 (R ) H) to 44 (R ) H) in the
,13,14
Considering the unquestionable stereospecificity in the
rearrangements outlined in Scheme 2, chiral compounds
such as 28 and 29 could be obtained in a stereochemically
defined configuration provided their tetracyclic precursor
is produced in enantiomerically pure form. In this
regard, efforts are being made in the light of recent
advances in the design and development of chiral cata-
2
8,29
lysts for asymmetric reactions of metal carbenes.
Rh (OAc) Decom p osition of 1-Dia zo-4-(1-m eth yl-
-n a p h th yl)-2-bu ta n on e 34 a n d 37. 2-Bromo-1-meth-
2
4
2
3
0
ylnaphthalene (30b) was converted into the R-diazo
ketone 34 through the intermediates 31b and 32b in the
(25) Carbocations at the 6-position of 1-methylbicyclo[4.4.0]decane
2 4
Rh (OAc) -induced decomposition of 7, whose reaction
systems are known to rearrange in different manners according to their
mixture was found to contain the compound 45 (8%
isolated yield) as the only stabilization product of 43 (R
1
4,26b,d
origin and structure: with methyl migration [(I)-Type]
, with a
26a
cyclohexane bond migration forming a spiranic cation [(II)-Type]
with cyclohexane ring cleavage [(III)-Type].
26) (a) Karanatsios, D.; Scarpa, J . S.; Eugster, C. H. Helv. Chim.
,
1
4,26b-e
15
) H).
(
Acta 1966, 49, 1151. (b) Tahara, A.; Akita, H.; Takizawa, T. Tetrahe-
dron Lett. 1974, 2837. (c) Matsumoto, T.; Imoi, S.; Masuda, H.; Fukui,
K. Chem. Lett. 1974, 1001. (d) Banerjee, A. K.; Carrasco, M. C.; Pena,
M. C. A. Tetrahedron 1990, 46, 4133. (e) Matsumoto, T.; Takeda, Y.;
Soh, K.; Matsumura, H.; Imai, S. Chem. Pharm. Bull. 1996, 44, 1588.
(30) Lambert, J . B.; Fabricius, D. M.; Hoard, J . A. J . Org. Chem.
1979, 44, 1480.
(31) (a) Adams, J .; Spero, D. M. Tetrahedron 1991, 47, 1765. (b)
Padwa, A.; Krumpe, K. E. Tetrahedron 1992, 48, 5385. (c) Padwa, A.;
Austin, D. J .; Price, A. T.; Semones, M. A.; Doyle, M. P.; Protopopova,
M. N.; Winchester, W. R.; Tran, A. J . Am. Chem. Soc. 1993, 115, 8669.
(32) (a) Cane, D. E.; Thomas, P. J . J . Am. Chem. Soc. 1984, 106,
5295. (b) Ceccherelli, P.; Curini, M.; Marcotullio, M. C.; Rosati, O.
Tetrahedron 1991, 47, 7403.
(27) (a) Wenkert, E.; Afonso, A.; Brendberg, J . B-son; Kaneko, C.;
Tahara, A. J . Am. Chem. Soc. 1964, 86, 2038. (b) Nakanishi, K.; Goto,
T.; Ito, S.; Natori, S.; Nozoe, S. Natural Products Chemistry, Vol. 1;
Academic Press: New York, 1974, p 193.
(
28) (a) Doyle, M. P. Recl. Trav. Chim. Pays-Bas 1991, 110, 305. (b)
(33) (a) Alonso, M. E.; Garcia, M. J . Org. Chem. 1985, 50, 988. (b)
Alonso, M.; Fernandez, R. Tetrahedron 1989, 45, 3313.
(34) (a) Hrytsak, M.; Etkin, N.; Durst, T. Tetrahedron Lett. 1986,
27, 5679. (b) Taber, D. F.; Ruckle, R. E. J . Am. Chem. Soc. 1986, 108,
7686. (c) Nakatani, K. Tetrahedron Lett. 1987, 28, 165. (d) Hrystak,
M.; Durst, T. J . Chem. Soc., Chem. Commun. 1987, 1150.
(35) (a) Doyle, M. P.; Shanklin, M. S.; Pho, H. Q.; Mahapatro, S. N.
J . Org. Chem. 1988, 53, 1017. (b) Rosenfeld, M. J .; Ravi Shankar, B.
F.; Shechter, M. J . Org. Chem. 1988, 53, 2699.
Doyle, M. P. Asymmetric Cyclopropanation in Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; VCH Publishers: New York, 1995. (c) Doyle,
M. P. Aldrichimica Acta 1996, 29, 3.
(
29) It can be noted that enantiomerically enriched 4a-methyl-
,4a,9,10-tetrahydrophenanthren-2(3H)-ones, e.g., 33, have so far been
prepared by enantioselective Michael addition reactions using a chiral
4
7
c,e,9a
7d
enamine as donor (80-93% ee)
and via asymmetric Heck reaction.
or a chiral phase transfer catalyst,
9e

6
662 J . Org. Chem., Vol. 62, No. 19, 1997
Manitto et al.
Sch em e 6
Steric interactions are presumably responsible for the
preference of path b over path a in Scheme 6. One can
presume that a relevant repulsion develops between the
bulky end37 of the tether and the adjacent methyl group
of the metal carbene 40, either at the π-complex or in
the transition state (formally represented by 41)20 pre-
ceding the formation of the cyclopropane ring.
In accordance with the dichotomic mechanism of
Scheme 6, a marked increase of the regioselectivity in
favor of the dihydroanthracenone derivative 39 was
observed in the Rh(II)-catalyzed decomposition of 37
tetralone (46) (8 steps, 24.1% yield) represents a new
(formal) synthesis of umbrosone (6). In addition, it can
be pointed out that the presence of a keto group in the
2-position of the 10-methyl-1,2,3,4-tetrahydroanthracene
skeleton makes 1-diazo-4-(1-methyl-2-naphthyl)butan-2-
ones suitable starting materials for the synthesis of
ring-A functionalized linear abietanes (e.g., pygmaeocin
E).2 These unusual diterpenoids are the subject of great
interest, due to their potential bioactivity.2
1a
1a-e
(Scheme 5). This result can be attributed to an extra
stabilization of the benzylic cation 42 (Scheme 6) by the
p-methoxy group. Compound 37 was prepared through
the reaction sequence from 7-methoxy-1-tetralone (46) to
5
0 followed by the usual conversion of the arylpropionic
1
7
acid into the corresponding diazo ketone.
As regards the acid-catalyzed opening of the cyclopro-
pane ring of 35 and 38 (Scheme 5), only compounds
resulting from a methyl shift, i.e., 29 and 51, respectively,
were obtained. The complete predominance of path a
over path b from 21 (Scheme 3), when compared to the
outcome from collapsing 16 (Scheme 2), may be explained
in terms of an additional stabilization of the nonspiranic
cation 22 by vinylology.
Syn th esis of Um br oson e (6). With compound 39 in
hand, we were able to transform it into 6-methoxy-1,1,10-
trimethyl-1,2,3,4-tetrahydroanthracene (53) through dim-
ethylation of C-1 and reduction of the carbonyl group of
Exp er im en ta l Section
All melting points are uncorrected. Elemental analyses
were obtained in-house. Solvents were purified and dried
according to standard literature procedures. Analytical TLC
was performed on silica gel F254 precoated aluminum sheets
(0.2 mm layer, Merck; eluent systems: A, hexane:ethyl acetate
1:1; B, hexane:ethyl acetate 2:1; C, hexane:ethyl acetate 8:1;
D, hexane:ethyl acetate:diethyl ether 75:10:15; E, hexane:ethyl
acetate 9:1; F, hexane:chloroform 1:3; G, hexane:ethyl acetate
5:1). Visualization was accomplished with UV light or sulfuric
acid solution (10% methanol). Silica gel (40-63 µm) from
Merck was used for flash chromatography.
5
2. Compound 53 had previously been prepared from
2
1c
the Hagemann’s ester (10 steps, 11.5% yield) and from
2
1d
(
+)-dehydroabietic acid (16 steps, 0.25% yield).
Since
2
1c,d
the conversion of 53 into 6 is described,
our prepara-
tion of the tetrahydroanthracene 53 from 7-methoxy-1-
P r ep a r a tion of d ia zo Keton es. All diazo ketones were
prepared from the corresponding 3-naphthylpropionic acids in
good yields (70-90% overall yields). The following procedure
is representative.
In a round-bottomed two-necked flask, under a nitrogen
atmosphere, 4.2 mequiv of acid were mixed with 24 mL of dry
(
36) (a) Liebman, J . F.; Greenberg, A. Chem. Rev. 1989, 89, 1225.
b) Lew, C. S. Q. J . Chem. Soc., Chem. Commun. 1995, 175 and
references cited therein.
37) (a) Cotton, F. A.; Deboer, B. G.; Laprade, H. D.; Pipal, J . R.;
(
17
(
Ucko, D. A. Acta Crystallogr. 1971, B27, 1664. (b) Padwa, A.; Austin,
D. J . Angew. Chem., Int. Ed. Engl. 1994, 33, 1797.

New Route to Rearranged Pimarane and Abietane Skeleta
CH Cl . The solution was cooled in an ice bath, and oxalyl
J . Org. Chem., Vol. 62, No. 19, 1997 6663
J ) 9 Hz, 1H), 6.86 (d, J ) 16 Hz, 1H), 4.05 (s, 3H); 13C NMR
(CDCl ) δ 173.00, 139.86, 132.07, 128.57, 127.56, 123.89,
3
2
2
chloride in 20% excess was added slowly. After the addition
was complete the mixture was heated to reflux. The reaction
was monitored by IR spectroscopy, following the disappearance
123.04, 122.00, 112.63, 56.14. Anal. Calcd for C14
(228.25): C, 73.67; H, 5.30. Found: C, 73.70; H, 5.34.
12 3
H O
-
1
of the band at ca. 1700 cm . At the end of the reaction, the
solvent was removed by rotary evaporation to give the acyl
chloride in 90-95% yield, which was used without further
purification.
Naphthylacrylic acid (4.7 g, 21 mmol) in ethyl acetate (250
mL) was hydrogenated at 1 atm and 23 °C in the presence of
10% palladium on charcoal (1 g). After 4 h the catalyst was
filtered off and the filtrate evaporated to provide 3-(2-methoxy-
1-naphthyl)propionic acid in 95% yield: mp 130-131 °C from
Under magnetic stirring, 1 mequiv of the acyl chloride in 8
mL of dry ether was dropped into 3 mequiv of CH
2
N
2
(0.5 M
ethanol-H
2
O 2:1; TLC (eluent A, R
f
0.5); IR (CHCl
3
) 2937,
-
1
in dry ether) under nitrogen atmosphere, cooling the solution
with an ice bath. The reaction mixture was left to stand at
room temperature for 2 h, monitoring the reaction progress
by TLC (eluent system B). After evaporation of the solvent
the crude product was purified by flash chromatography using
eluent B to give the diazo ketone pure enough for the next
transformation.
1707 cm ; UV λmax (log ꢀ) (MeOH) 230 (4.51), 282 (3.35), 294
1
(3.29); H NMR (CDCl ) δ 7.98 (d, J ) 9 Hz, 1H), 7.78 (t, J )
3
9 Hz, 2H), 7.50 (t, J ) 9 Hz, 1H), 7.34 (t, J ) 9 Hz, 1H), 7.27
(d, J ) 9 Hz, 1H), 3.95 (s, 3H), 3.45 (t, J ) 8.4 Hz, 2H), 2.67
(t, J ) 8.4 Hz, 2H); 13C NMR (CDCl
) δ 179.19, 154.45, 132.03,
3
129.15, 121.23, 128.58, 128.17, 126.66, 123.23, 122.63, 113.03,
56.27, 33.98, 21.00. Anal. Calcd for C14
H, 6.13. Found: C, 73.20; H, 6.16.
14 3
H O (230): C, 73.03;
1
-Dia zo-4-(1-n a p h th yl)-2-bu ta n on e (10). A well-stirred
mixture of 2-naphthaldehyde (24 g, 154 mmol), malonic acid
32 g, 306 mmol), and piperidine (12 mL) in pyridine (180 mL)
1
3: yellow solid (79% yield); mp 61.5-63 °C; TLC (eluent
B, R 0.6).
-Dia zo-4-(2-m eth yl-1-n a p h th yl)-2-bu ta n on e (26). Di-
acetatobis(triphenylphosphine)palladium(II) was prepared by
adding an eccess of triphenylphosphine (ca. 0.35 g) in 20 mL
(
f
1
was refluxed for 2 h. After cooling, the reaction mixture was
poured into concentrated HCl (250 mL) containing crushed ice.
The flocculent white precipitate was collected by suction
filtration and dried in a vacuum desiccator to give 3-(1-
naphthyl)acrylic acid (26.1 g, 86%) as a white solid: mp 212-
2
of benzene to a solution of Pd(OAc) (0.2 g) in 20 mL of benzene.
Addition of petroleum ether (60-80 °C) to the resulting pale
yellow solution gave, on shaking slowly, lemon yellow crystals
of the complex, mp 135-136 °C, which were washed with
petroleum ether and dried in vacuo (40 °C). Methyl acrylate
3
8
2
f
13 °C (lit. mp 214-215 °C); TLC (eluent A, R 0.46); EIMS
+
1
m/ e (rel intensity) 198 (M , 50), 153 (100), 79 (24); H NMR
(
(
7
acetone-d
d, J ) 15.0 Hz, 1H). Anal. Calcd for C13
8.70; H, 5.04. Found: C, 78.68; H, 5.11.
The naphthylacrylic acid (13 g, 65.6 mmol) in ethyl acetate
600 mL) was then hydrogenated at 1 atm and 23 °C in the
6
) δ 8.52 (d, J ) 15.0 Hz, 1H), 8.3-7.5 (m, 7H), 6.61
(
0.76 g, 8.8 mmol), 1-bromo-2-methylnaphthalene (30a ) (1.2
10 2
H O
(198.22): C,
g, 6.8 mmol), and triethylamine (0.84 g, 8.8 mmol) were
combined in a round-bottomed three-necked flask and the
catalyst was added. The flask was connected to a condenser
and the mixture heated to boiling in an oil bath keeping a
slight nitrogen pressure on the flask. When the boiling point
stopped increasing (from 96 to 106 °C), the reaction mixture
was cooled and diluted with water and ether. The organic
layer was washed with water, dried over anhydrous Na
SO ,
2 4
and distilled under reduced pressure. After purification by
column chromatography (eluent C), 31a (1.0 g, 66% yield) was
(
presence of 10% palladium on charcoal (4.3 g). After 4 h the
catalyst was filtered off and the filtrate evaporated to provide
the crude 3-(1-naphthyl)propionic acid which was recrystal-
lized from acetone (93% yield): mp 157.7-158.7 °C; TLC
1
(
7
(
eluent A, R
f
0.5); H NMR (CDCl
3
) δ 8.13 (d, J ) 8.5 Hz, 1H),
.91 (d, J ) 8.5 Hz, 1H), 7.78 (m, 1H), 7.57-7.40 (m, 4H), 3.43
13
t, J ) 7.5 Hz, 2H), 2.77 (t, J ) 7.5 Hz, 2H); C NMR (CDCl
3
)
obtained as a pale yellow oil: TLC (eluent C R
020, 2951, 1716 cm ; UV: λmax (log ꢀ) (MeOH) 226 (3.38), 314
f
0.5); IR (CHCl
3
)
δ 173.44, 137.23, 132.03, 129.00, 127.14, 126.15, 125.79,
-1
3
(
1
7
23.70, 34.60, 27.98. Anal. Calcd for C13
7.98; H, 6.04. Found: C, 77.76; H, 6.19.
12 2
H O (200.22): C,
1
2.51); H NMR (CDCl
3
) δ 8.20 (d, J ) 16.6 Hz, 1H), 8.05 (d, J
)
1
8.4 Hz, 1H), 7.90 (d, J ) 8.4 Hz, 1H), 7.70 (d, J ) 8.4 Hz,
1
B, R
0: yellow solid (90% yield); mp 56.5-57.5 °C; TLC (eluent
H), 7.46 (m, 2H), 7.30 (d, J ) 8.4 Hz, 1H), 6.40 (d, J ) 16.6
-1
f
0.6); IR (CHCl
3
) 2104, 1634 cm ; UV: λmax (log ꢀ) (MeOH)
1
13
Hz, 1H), 3.89 (s, 3H), 2.50 (s, 3H); C NMR (CDCl
3
) δ 166.77,
42.58, 133.84, 131.95, 131.27, 130.50, 128.43, 128.13, 127.84,
26.36, 125.00, 124.35, 51.52, 20.73. Anal. Calcd for C15
2
1
7
28 (4.72), 276 (3.90); H NMR (CDCl ) δ 8.02 (d, J ) 8.5 Hz,
3
1
1
(
H), 7.86 (d, J ) 8.5 Hz, 1H), 7.83 (d, J ) 8.5 Hz, 1H), 7.53-
.26 (m, 4H), 5.13 (br s, 1H), 3.43 (t, J ) 7.5 Hz, 2H), 2.79 (br
14 2
H O
226.27): C, 79.61; H, 6.24. Found: C, 79.41; H, 6.18.
1
3
t, 2H); C NMR (CDCl ) δ 193.81, 136.57, 133.84, 131.48,
3
3
1a (1 g, 4.4 mmol) in ethanol (50 mL) was hydrogenated
1
28.82, 127.02, 126.02, 125.52, 123.28, 54.50, 41.44, 27.89.
Anal. Calcd for C14 O (224.09): C, 74.97; H, 5.40; N,
2.50. Found: C, 75.03; H, 5.50; N, 12.25.
-Dia zo-4-(2-m et h oxy-1-n a p h t h yl)-2-b u t a n on e (13).
Carbethoxymethyl)-triphenylphosphonium bromide (8.9 g, 23
at 1 atm and 23 °C in the presence of 10% palladium on
charcoal (0.42 g). After 4 h the catalyst was filtered off and
KOH (0.5 g) was added. The reaction mixture was then heated
to reflux for 30 min, the solvent evaporated, and the residue
dissolved in water and extracted with ether. After acidification
of the aqueous layer and extraction with ether, the solvent
12 2
H N
1
1
(
mmol) in 50 mL of absolute ethanol was added slowly under
a nitrogen atmosphere and vigorous magnetic stirring to 30
mL of a solution of sodium (0.58 g, 25.2 mmol) in absolute
ethanol. After the precipitation of sodium bromide was
complete, 2-methoxy-1-naphthaldheyde (4.3 g, 23 mmol) in 10
mL of absolute ethanol was dropped and the reaction mixture
left to stand for 48 h. The disappearance of the aldehyde was
was removed, furnishing 32a as a white solid (90% yield): mp
-1
1
22 °C; TLC (eluent A, R
f
0.5); IR (CHCl
3
) 3223, 1711 cm
;
1
UV λmax (log ꢀ) (MeOH) 228 (4.90), 284 (3.73); H NMR (CDCl
3
)
δ 7.98 (d, J ) 9 Hz, 1H), 7.78 (t, J ) 9 Hz, 2H), 7.50 (t, J ) 9
Hz, 1H), 7.34 (t, J ) 9 Hz, 1H), 7.27 (d, J ) 9 Hz, 1H), 3.45 (t,
13
J ) 8.4 Hz, 2H), 2.67 (t, J ) 8.4 Hz, 2H), 2.54 (s, 3H);
C
f
monitored by TLC (eluent B, R 0.5). KOH (1 g) was then
NMR (CDCl
1
3
) δ 178.82, 133.26, 133.06, 132.68, 131.83, 129.18,
28.76, 126.80, 126.32, 124.70, 122.99, 34.02, 23.80, 19.98.
added and the reaction mixture heated to reflux for 30 min.
After the solvent was removed under reduced pressure, the
residue was dissolved in water and extracted with ether. The
aqueous layer was acidified with concentrated HCl and
extracted with ether (3 × 50 mL), and the solvent was
evaporated to give 3-(2-methoxy-1-naphthyl)acrylic acid (4.7
Anal. Calcd for C14
C, 78.44; H, 6.58.
14 2
H O (214.26): C, 78.48; H, 6.59. Found:
2
6: yellow solid (73% yield); mp 31-33 °C; TLC (eluent B,
0.6).
-Dia zo-4-(1-m eth yl-2-n a p h th yl)-2-bu ta n on e (34). 3-(1-
R
f
1
g) which was recrystallized from ethanol-H
0.5); IR (CHCl
972, 1678 cm ; UV λmax (log ꢀ) (MeOH) 234 (3.33), 318 (2.63),
2
O 2:1 (90%
Methyl-2-naphthyl)acrylic acid, methyl ester (31b) was pre-
pared by the Heck reaction as described above for 31a : yellow
yield): mp 163.5-165 °C; TLC (eluent A, R
f
3
)
-1
2
3
solid (71% yield); mp 49-52.5 °C; TLC (eluent C, R
f
0.5); IR
1
50 (2.62); H NMR (CDCl ) δ 8.53 (d, J ) 16 Hz, 1H), 8.23 (d,
3
-
1
(
CHCl
36 (2.76), 274 (3.18), 312 (3.01); H NMR (CDCl
J ) 15.8 Hz, 1H), 8.12 (m, 1H), 7.82 (m, 1H), 7.65 (m, 2H),
.53 (m, 2H), 6.46 (d, J ) 15.8 Hz, 1H), 3.85 (s, 3H), 2.78 (s,
3
) 2966, 1715 cm ; UV λmax (log ꢀ) (MeOH) 218 (2.72),
J ) 8.2 Hz, 1H), 7.90 (d, J ) 9 Hz, 1H), 7.82 (d, J ) 8.2 Hz,
H), 7.57 (t, J ) 7.4 Hz, 1H), 7.40 (t, J ) 7.4 Hz, 1H), 7.32 (d,
1
2
3
) δ 8.32 (d,
1
7
1
3
(38) Effenberger, F.; Wonner, J . Chem. Ber. 1992, 125, 2583.
3
3H); C NMR (CDCl ) δ 167.56, 143.07, 134.70, 134.06, 132.84,

6
664 J . Org. Chem., Vol. 62, No. 19, 1997
Manitto et al.
1
1
30.10, 128.5, 126.67, 126.51, 124.87, 123.55, 119.40, 51.70,
32.83, 29.41, 28.55, 27.61, 14.00. Anal. Calcd for C15
(246.13): C, 73.13; H, 7.37. Found: C, 73.00 ; H, 7.41.
18 3
H O
4.52. Anal. Calcd for C15
14 2
H O (226.10): C, 79.61; H, 6.24.
Found: C, 79.51; H, 6.18.
Catalytic hydrogenation and subsequent hydrolysis (see
A mixture of 49 (3.8 g, 15.3 mmol) and DDQ (3.46 g, 16.2
mmol) in benzene (80 mL) was stirred at room temperature
for 30 min. The mixture was diluted with ether, washed
with aqueous ammonium chloride, water, and brine, and then
dried over anhydrous sodium sulfate and evaporated to dry-
ness. The crude product was purified by flash chromatography
to give 3.3 g (88% yield) of pure 3-(7-methoxy-1-methyl-2-
naphthyl)propionic acid (50): mp 131-131.5 °C from diethyl
3
2a ) afforded 32b: white solid (72% yield); mp 88-90 °C; TLC
-
1
(
f 3
eluent A, R 0.5); IR (CHCl ) 3223, 2966, 1711 cm ; UV λmax
1
(
log ꢀ) (MeOH); H NMR (CDCl
.82 (dd, J ) 1.5, 7.6 Hz, 1H), 7.68 (d, J ) 8.4 Hz, 1H), 7.50
td, J ) 1.5, 7.6 Hz, 2H), 7.33 (d, J ) 8.4 Hz, 1H), 3.21 (t, J )
3
) δ 8.06 (d, J ) 8.4 Hz, 1H),
7
(
7
1
1
.6 Hz, 2H), 2.68 (s, 3H), 2.68 (m, 2H); 13C NMR (CDCl
78.77, 136.00, 133.00, 128.41, 127.73, 126.34, 125.95, 125.00,
23.97, 35.16, 29.21, 14.21. Anal. Calcd for
3
) δ
-
1
ether; TLC (eluent A, R
f
0.5); IR (CHCl
3
) 2934, 1697 cm ; UV
1
C
14
H
14
O
2
λ
max (log ꢀ) (MeOH) 234 (4.93), 280 (3.65), 330 (3.12); H NMR
(
214.26): C, 78.48; H, 6.59. Found: C, 78.40; H, 6.64.
4: yellow solid in 76% yield; mp 57.5-59.5 °C; TLC (eluent
B, R 0.6).
-Dia zo-4-(7-m e t h oxy-1-m e t h yl-2-n a p h t h yl)-2-b u t a -
n on e (37). A suspension of 7-methoxy-1-tetralone (46) (12 g,
8 mmol), sodium hydride (60%, 3.56 g, 89 mmol), and diethyl
(CDCl
3
) δ 7.72 (t, J ) 8.6 Hz, 1H), 7.61 (d, J ) 8.6 Hz, 1H),
3
7.31 (d, J ) 2.2 Hz, 1H), 7.20 (d, J ) 8.6 Hz, 1H), 7.14 (dd, J
) 2.2, 8.6 Hz, 1H), 3.96 (s, 3H), 3.19 (t, J ) 8 Hz, 2H), 2.70 (t,
f
J ) 8 Hz, 1H), 2.62 (s, 3H); 13C NMR (CDCl
) δ 178.54, 157.86,
1
3
135.68, 134.12, 129.91, 129.67, 127.92, 126.04, 125.42, 117.21,
6
103.10, 55.28, 35.16, 29.34, 14.34. Anal. Calcd for C15
(244.1): C, 73.74; H, 6.61. Found: C, 73.62; H, 6.54.
16 3
H O
carbonate (32 g, 27 mmol) was refluxed for 1 h and then poured
into ice-water, and the solution, adjusted with concentrated
HCl to pH 1.5, was extracted with ether. After evaporation
of the solvent, the residue was column chromatographed
37: yellow solid (75% yield); mp 94.5-96 °C; TLC (eluent
B, R 0.6).
Rh (AcO)
P r oced u r e. In a round-bottomed two-necked flask, 12 mg of
Rh (OAc) was dissolved in 36 mL of dry CH Cl , under a
f
2
4
Decom p osition of Dia zo Keton es. Typ ica l
(eluent E) to give pure 2-(ethoxycarbonyl)-7-methoxy-1-tetral-
one (47) (13 g, 83% yield): mp 36-37.5 °C; TLC (eluent E, R
f
2
4
2
2
-
1
0
.5); IR (CHCl
3
) 1736, 1682 cm ; UV λmax (log ꢀ) (MeOH) 226
nitrogen atmosphere and with magnetic stirring. The flask
was protected from the action of light and cooled at 0 °C. The
1
(4.30), 292 (4.10), 304 (4.10), 336 (4.09); H NMR (CDCl
3
) δ
.49 (d, J ) 2.6 Hz, 1H), 7.14 (d, J ) 8.3 Hz, 1H), 7.06 (dd, J
2.6; 8.3 Hz, 1H), 4.26 (q, J ) 7 Hz, 2H), 3.81, (s, 3H), 3.55
7
diazo ketone (0.42 mmol) was dissolved in 24 mL of dry CH
and added dropwise very slowly. The mixture was then kept
at rt for 2 h more and then diluted with 20 mL of CH Cl and
2 2
Cl
)
(
dd, J ) 4.7; 10 Hz, 1H), 2.94 (m, 2H), 2.50-2.40 (m, 1H),
2
2
2
.30-2.20 (m, 1H), 1.33 (t, J ) 7 Hz, 3H). Anal. Calcd for
(248.10): C, 67.71; H, 6.50. Found: C, 67.58; H, 6.46.
7 (13 g, 52 mmol) and ethyl acrylate (6.84 g, 68 mmol) were
washed with water. The organic layer was dried over anhy-
drous sodium sulfate and evaporated to give a crude product.
This was then flash chromatographed eluting with systems D
or F to afford the pure reaction product(s).
14 16 4
C H O
4
added to an ethanolic solution (500 mL) of sodium ethoxide
prepared from 362 mg (0.15 mmol) of sodium. The reaction
mixture was kept under stirring at room temperature for 4 h
and then poured into ice-water. After evaporation of the
ethanol, the residue was extracted with ether and the solvent
evaporated in vacuo. The crude diester was dissolved in 1.5
Tet r a cyclo[8.4.0.01 .02,7]t et r a d eca -2,4,6,8-t et r a en -12-
,11
on e (11): Pale yellow oil (78% yield from 10); TLC (eluent D,
R
f
0.34).
10-Met h oxyt et r a cyclo[8.4.0.01,11.02,7]t et r a d eca -2,4,6,8-
tetr a en -12-on e (14): pale yellow oil (70% yield from 13); TLC
N aqueous KOH (200 mL, H
2
O-dioxane 2:1) and the solution
f
(eluent D, R 0.31).
10-Meth yltetr a cyclo[8.4.0.01,11.02,7]tetr a d eca -2,4,6,8-tet-
heated under reflux for 8 h. After the pH was adjusted to 1.5,
extraction with ether and evaporation of the solvent afforded
pure 48 as a white solid (9.18 g, 95%): mp 112.5-113.5 °C;
r a en -12-on e (27): pale yellow oil (80% yield from 26); TLC
-
1
(eluent D, R
f 3
0.32); IR (CHCl ) 2930, 1711 cm ; UV λmax (log
-
1
TLC (eluent A, R
max (log ꢀ) (MeOH) 222 (4.34), 252 (3.97), 320 (3.49); H NMR
CDCl ) δ 7.48 (d, J ) 2.8 Hz, 1H), 7.13 (d, J ) 8.6 Hz, 1H),
.03 (dd, J ) 2.8, 8.6 Hz, 1H), 2.94 (dd, J ) 4.7, 7.4 Hz, 2H),
.55 (m, 1H; t, J ) 7.4 Hz, 2H), 2.28 (m, 2H), 1.88 (m, 2H); 13
) δ 199.58, 179.48, 158.28, 136.36, 133.06, 129.82,
21.62, 109.35, 46.39, 31.58, 28.92, 27.68, 24.84. Anal. Calcd
for C14 (248.10): C, 67.71; H, 6.50. Found: C, 67.68; H,
.53.
In a round-bottomed three-necked flask, under a nitrogen
atmosphere, methylmagnesium iodide was prepared in the
usual manner from 200 mg (0.83 mmol) of I -activated
magnesium and 1.2 g (0.81 mol) of CH I in 10 mL of anhydrous
f 3
0.5); IR (CHCl ) 2966, 1713, 1672 cm ; UV
ꢀ) (MeOH) 232 (4.37), 272 (3.89); EIMS m/ e (rel intensity) 210
1
+
1
λ
3
(M , 67), 195 (15), 182 (68), 181 (100); H NMR (CDCl ) δ 7.69
(
3
(d, J ) 7.7 Hz, H-8), 7.30 (td, J ) 1.3; 8 Hz, H-6), 7.25 (d, J )
8 Hz, H-5), 7.19 (td, J ) 1.3; 7.7 Hz, H-7), 6.42 (d, J ) 9 Hz,
H-9), 6.16 (d, J ) 9 Hz, H-10), 3.20 (td, J ) 5.6; 13.6 Hz, H-3),
7
2
C
NMR (CDCl
3
2.55 (m, H-3), 2.30-2.05 (m, H
2
-4), 1.45 (s, Me-11), 1.06 (s,
H-1); H NOE from H-1 to Me (0.5%); from Me to H-1 (0.8%)
and to H-10 (2.7%); from H-10 to Me (0.6%); 13C NMR (CDCl
)
3
1
1
H
16
O
4
6
δ 214.97 (C-2), 134.24, 132.61 (C-10), 130.66, 128.18 (C-5),
127.55 (C-6), 126.44 (C-7), 125.18 (C-9, C-8), 43.62, 39.21 (C-
1), 37.32 (C-4), 35.28, 21.37 (C-3), 16.92 (C-11). Anal. Calcd
for C15
6.74.
H14O (210.10): C, 85.67; H, 6.72. Found: C, 85.71; H,
2
3
10-Meth yltetr a cyclo[8.4.0.01,11.04,9]tetr a d eca -2,4,6,8-tet-
ether. 48 (0.8 g, 0.32 mol) in 6 mL of anhydrous ether was
added dropwise at a rate so as to mantain a gentle reflux.
When addition was completed, the reaction mixture was
refluxed for additional 90 min and then cooled and quenched
r a en -12-on e (35): pale yellow oil (14% yield from 34); TLC
(eluent D, R 0.31).
f
10-Meth yl-3,4-d ih yd r oa n th r a cen -2(1H)-on e (36): white
solid (28% yield from 34); mp 120-121 °C from hexane-
with 9 mL of ice and 6 mL of 20% H
slurry. After removal of the solvent, 20% H
added and the mixture heated under a vigorous reflux for 15-
0 min. The reaction mixture was then cooled and extracted
three times with ether. The combined organic portions were
washed with 10 mL of a saturated NaHCO solution and the
2
SO
4
to give a lime-colored
2
SO (6 mL) was
4
f
acetate 2:1; TLC (eluent D, R 0.38).
7-Meth oxy-10-m eth yltetr acyclo[8.4.0.01,11.04,9]tetr adeca-
2
2,4,6,8-tetr a en -12-on e (38): pale yellow oil (11% yield from
37); TLC (eluent F, R 0.29).
f
3
6-Me t h oxy-10-m e t h yl-3,4-d ih yd r oa n t h r a ce n -2(1H )-
on e (39): white solid (52% yield from 37); mp 135-136 °C
acqueous phase was adjusted to pH 1-2 with concentrated
hydrochloric acid. The white precipitated was extracted
with ether, dried, and evaporated to give 0.7 g (0.29 mmol) of
pure 3-(7-methoxy-1-methyl-3,4-dihydro-2-naphthyl)propionic
f 3
from hexane-acetate 2:1; TLC (eluent F, R 0.38); IR (CHCl )
-1
2361, 1707 cm ; UV λmax (log ꢀ) (MeOH) 236 (4.91), 280 (3.70),
+
334 (3.26); EIMS m/ e (rel intensity) 240 (M , 100), 225 (10),
1
acid (49) as a light pink solid in 88% yield: TLC (eluent A, R
f
212 (22), H NMR (CDCl
3
) δ 7.67 (d, J ) 8.8 Hz, H-8), 7.42 (s,
-1
0
2
.5); IR (CHCl
22 (4.31), 262 (3.89), 302 (3.53); H NMR (CDCl
3
) 2934, 2253, 1709 cm ; UV λmax (log ꢀ) (MeOH)
H-9), 7.28 (d, J ) 2.4 Hz, H-5), 7.13 (dd, J ) 2.4; 8.8 Hz, H-7),
3.95 (s, MeO), 3.72 (s, H -1), 3.27 (t, J ) 6.6 Hz, H -4), 2.64 (s,
Me), 2.57 (t, J ) 6.6 Hz, 2H); H NOE from Me to H -4 (3%)
and to H-5 (7%); from H-5 to Me (2.6%) and to MeO (2.1%);
from H -1 to H-9 (6.4%); from H-9 to H-1 (2.8%) and to H-8
(5.6%); from H-8 to H-9 (3%) and to H-7 (6.9%); from H-7 to
1
3
) δ 7.05 (d,
2
2
1
J ) 8 Hz, 1H), 6.85 (d, J ) 2.5 Hz, 1H), 6.70 (dd, J ) 2.5; 8
2
Hz, 1H), 3.85 (s, 3H), 2.75-2.54 (m, 4H), 2.55 (m, 2H), 2.25
1
3
(
m, 2H), 2.05 (s, 3H); C NMR (CDCl
3
) δ 179.59, 158.31,
2
1
37.92, 134.52, 127.82, 127.48, 126.71, 110.27, 109.86, 55.28,

New Route to Rearranged Pimarane and Abietane Skeleta
H-8 (6.6%); 13C NMR (CDCl
J . Org. Chem., Vol. 62, No. 19, 1997 6665
3
) δ 210.82 (C-2), 157.70 (C-6),
purified by flash chromatography using eluent G to give pure
1
(
3
(
33.45, 132.98, 129.00, 128.84, 129.47 (C-8), 128.32, 124.75
C-9), 117.53 (C-7), 103.28 (C-5), 55.29 (C-12), 46.36 (C-1),
8.30 (C-3), 25.26 (C-4), 14.67 (C-11). Anal. Calcd for C16
240.12): C, 79.96; H, 6.72. Found: C, 80.00; H, 6.76.
TF A Decom p osition of Cyclop r op a n e Der iva tives.
52 (0.98 g, 88% yield) as a yellow solid: mp 79.5-80 °C; TLC
-
1
f 3
(eluent G, R 0.5); IR (CHCl ) 2970, 1713 cm ; UV λmax (log ꢀ)
H
16
O
2
(MeOH) 238 (4.89), 282 (3.62); EIMS m/ e (rel intensity) 268
+
1
(M , 100), 253 (60), 225 (92); H NMR (CDCl
9 Hz, H-8), 7.65 (s, H-9), 7.28 (d, J ) 2.1 Hz, H-5), 7.13 (dd, J
) 2.1; 9 Hz, H-7), 3.95 (s, MeO-12), 3.30 (t, J ) 7.3 Hz, H -4),
2.72 (t, J ) 7.3 Hz, H -3), 2.62 (s, Me-11), 1.53 (s, Me-13, Me-
14); H NOE from Me to H -4 (4.5%) and to H-5 (9.2%); from
Me-13,14 to H-9 (14.7%); 13C NMR (CDCl
) δ 214.89 (C-2),
3
) δ 7.71 (d, J )
Typ ica l P r oced u r e. In a round-bottomed two-necked flask,
the tetracyclic ketone (0.41 mmol) was dissolved in 20 mL of
2
2
1
CH
2
Cl
2
, under magnetic stirring. After addition of TFA (5 µL)
2
the mixture was kept under magnetic stirring for 10 min at
3
rt and then washed with water (2 × 10 mL). The organic layer
157.77 (C-6), 139.69, 132.13, 132.12, 129.90 (C-8), 129.10,
128.10, 122.98 (C-9), 117.55 (C-7), 102.66 (C-5), 55.25 (C-12),
48.17, 37.37 (C-3), 27.21 (C-13, C-14), 25.57 (C-4), 14.77 (C-
2 4
was dried over anhydrous Na SO and evaporated to give a
residue which was flash chromatographed by eluting with
systems A or B or D to give the pure product(s).
11). Anal. Calcd for C18
Found: C, 80.44; H, 7.48.
20 2
H O (268.15): C, 80.55; H, 7.52.
3
,4-Dih yd r op h en a n th r en -2(1H)on e (12): yellow solid
1
8
(
95.5% yield from 11); mp 65.2 °C (lit. mp 61-62 °C); TLC
eluent A, R 0.78).
N a p h t h a le n -2(1H )-o n e -1-s p ir o -(1′-c y c lo p e n t a n -3′-
on e) (15): colorless solid (78% yield from 14); mp 71-72 °C;
TLC (eluent C, R 0.31).
a -Met h yl-4,4a -d ih yd r op h en a n t h r en -2(3H)-on e (28):
pale yellow solid (44% yield from 27); mp 98 °C from hexane
6-Me t h o x y -1,1,10-t r im e t h y l-1,2,3,4-t e t r a h y d r o a n -
th r a cen e (53). p-Toluenesulfonohydrazide (119 mg, 0.64
mmol) was added to a stirred solution of 52 (86 mg, 0.32 mmol)
in acetic acid (5 mL). The mixture was manteined for 2 h at
rt and then diluted with water (8 mL). The precipitate was
isolated by suction, washed with water, and dried to give the
(
f
f
4
tosylhydrazone (137 mg, 98% yield): TLC (eluent G, R
f
0.28);
1
2,24a
-1
(
lit.
1
mp 98-99 °C); TLC (eluent E, R
f
0.26).
IR (CHCl
334 (3.18); EIMS m/ e (rel intensity) 436 (M , 25), 281 (20),
266 (20), 252 (100). Anal. Calcd for C25 SO (436.57):
3
) 1714, 1628 cm ; UV λmax (log ꢀ) (MeOH) 238 (4.92),
+
0a -Me t h y l-1,10a -d ih y d r o p h e n a n t h r e n -3(2H )-o n e
(
29): white solid (47% yield from 27); mp 99-100 °C from
H
28
N
2
3
-
1
hexane; TLC (eluent E, R
f
0.29); IR (CHCl
3
) 2928, 1653 cm
;
C, 68.78; H, 6.46; N, 6.42; S, 7.34. Found: C, 68.80; H, 6.47;
N, 6.48.
A stirred solution of the tosylhydrazone prepared above (109
mg, 0.25 mmol), NaBH CN (1 mmol), and p-toluensulfonic acid
3
(12.5 mg) in 4 mL of a 1:1:2 mixture of DMF-sulfolane-
cyclohexane was heated at 110 °C. Additonal portions of
UV λmax (log ꢀ) (MeOH) 258 (4.38), 306 (3.96), 348 (3.68); EIMS
+
m/ e (rel intensity) 210 (M , 69), 195 (37), 182 (53), 177 (100);
1
H NMR (CDCl
3
) δ 7.60 (d, J ) 7.7 Hz, H-5), 7.38 (t, J ) 7.7
Hz, H-6), 7.26 (td, J ) 1.5; 7.7 Hz, H-7), 7.13 (d, J ) 7.7 Hz,
H-8), 6.43 (d, J ) 9.6 Hz, H-9), 6.34 (s, H-4), 5.86 (d, J ) 9.6
Hz, H-10), 2.64-2.55 (m, H
2
-2), 2.21 (td, J ) 5; 13.6 Hz, H-1),
3
NaBH CN (1 mmol) were added every 2 h and for three times
1
2
.01 (ddd, J ) 1.9; 5; 13.6 Hz, H-1), 1.27 (s, Me-11); H NOE
from H-4 to H-5 (6.5%); from H-5 to H-4 (8.6%) and to H-6
-6%); from H-8 to H-7 (-5%) and to H-9 (2.8%); from H-9 to
and heating was continued. Upon completion (monitored by
TLC) the reaction mixture was diluted with water and the
layers were separated. The organic phase was dried over
(
H-8 (2.7%) and to H-10 (3.7%); from H-10 to H-9 (3.3%) and
2 4
anhydrous Na SO and the solvent removed by evaporation
to Me (1.1%); from Me to H-10 (3.7%) and to H-1 (δ 1.99, 4%);
to give a crude product. This was purified by flash chroma-
1
3
C NMR (CDCl
3
) δ 198.60 (C-3), 163.54, 138.00 (C-10), 134.00,
tography using eluent G to furnish 53 as a colorless solid in
85% yield: mp 111 °C from hexane (lit.2 mp 110 °C; lit.
1c
21d
1
1
31.24 (C-6), 128.06 (C-7), 129.67, 126.97 (C-8), 125.46 (C-5),
24.15 (C-9), 122.74 (C-4), 37.26, 35.18 (C-1), 34.01 (C-2), 24.11
mp 112-113 °C).
(C-11). Anal. Calcd for C15H14O (210.10): C, 85.67; H, 6.72.
Found: C, 85.70; H, 6.75.
Ack n ow led gm en t. Thanks are due to MURST
(Italy) and to the Research National Council (CNR,
Progetto Strategico Tecnologie Chimiche Innovative) for
financial support.
6
-Me t h oxy-10a -m e t h yl-1,10a -d ih yd r op h e n a n t h r e n -
(2H)-on e (51): yellow oil (75% yield from 38); TLC (eluent
E, R 0.29).
-Meth oxy-1,1,10-tr im eth yl-3,4-dih ydr oan th r acen -2(1H)-
3
f
6
on e (52). Methyl iodide (0.118 g, 0.83 mmol) was added
slowly, under magnetic stirring, to a solution of 39 (0.1 g, 0.42
mmol) in dry t-BuOH (5 mL) containing t-BuOK (0.93 g, 0.84
mmol). The reaction mixture was left to react at rt for 10 min
and then poured into 20 mL of water. After neutralization
with dilute HCl and extraction with ether, the organic layer
was washed with water, dilute sodium hydroxide, and water
Su p p or tin g In for m a tion Ava ila ble: Experimental data
1
13
for compounds 11-15, 26, 28, 34-38, and 51 and H and
NMR spectra for compounds 11, 14, 15, 27-29, 35, 36, 38,
9, and 51-53 (31 pages). This material is contained in
C
3
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
again. Drying over anhydrous Na
2 4
SO and removal of the
solvent furnished the crude product as a dark oil. This was
J O970631K