Intramolecular Diels-Alder reaction in 1-oxaspiro[2.5]octa-5,7-dien-4- one and sigmatropic shifts in excited states: Novel route to sterpuranes and linear triquinanes: Formal total synthesis of (±)-coriolin

Article abstract of DOI:10.1039/a908223i

A novel, stereoselective synthesis of sterpuranes and coriolin via modulation of the photochemical reactivity of a tricyclic system having a β,γ-enone chromophore, which was assembled via intramolecular p(4s)+ π(2s) cycloaddition of 1-oxaspiro[2.5]octa-5,

Full text of DOI:10.1039/a908223i

Intramolecular Diels–Alder reaction in 1-oxaspiro[2.5]octa-5,7-dien-4-one and
sigmatropic shifts in excited states: novel route to sterpuranes and linear
triquinanes: formal total synthesis of (±)-coriolin
Vishwakarma Singh* and S. Q. Alam
Department of Chemistry, Indian Institute of Technology Bombay, Powai Mumbai 400 076, India.
E-mail: vks.ether.chem.iitb.ernet.in
Received (in Cambridge, UK) 13th October 1999, Accepted 9th November 1999
A novel, stereoselective synthesis of sterpuranes and coriolin
via modulation of the photochemical reactivity of a tricyclic
system having a b,g-enone chromophore, which was as-
4s
2s
sembled via intramolecular p + p cycloaddition of
1-oxaspiro[2.5]octa-5,7-dien-4-ones, is presented.
The fungal metabolites 1–3 and coriolin 4 are natural products
of the sterpurane1 and triquinane2 families of sesquiterpenes,
respectively, which are biogenetically derived from humulene
Scheme 1
cyclopropane ring might lead to linearly fused cis+anti+cis-
+triquinanes. We report herein our exploratory results leading to
a novel and general entry to sterpuranes and a formal total
synthesis of coriolin from a common precursor.
Towards our objective, the key precursor 10 was prepared
from aldehyde 9a, which was obtained from alcohol 9b.10 Thus,
the addition of Grignard reagent prepared from 4-bromobutene
to aldehyde 9a and subsequent oxidation of the resulting
alcohol, followed by alkylation and removal of the acetonide
protection, readily furnished the desired precursor 10. Oxida-
tion of 10 with NaIO4 in MeCN–H2O at 0 °C smoothly
furnished the adduct 12 (Scheme 2) in excellent yield (71%).
The adduct 12 is formed as a result of in situ generation of 11
during the oxidation and subsequent intramolecular Diels–
Alder reaction. The structure and stereochemistry of the adduct
cyclization cascades.1f Coriolin3 and other triquinanes have
witnessed a high level of sustained interest which has led to the
development of several new and elegant methods for the
construction of tricyclopentanoids.3–5 However, sterpuranes
have elicited only modest interest6 despite their unique
structure, which contains a cyclobutane ring fused to a
hydrindane system, and their role in silver leaf disease1 and
phytotoxicity.6e There are only a few methods for the synthesis
of sterpuranes and most of these generate the carbocyclic
framework in an iterative fashion wherein the cyclobutane ring
is formed via intermolecular p2s + p2s photocycloaddition.6b–f
The elegant routes devised by Okamura6g and Krause,6h
although efficiently generating the framework, begin with a
precursor containing a cyclobutane ring. In continuation7 of
our efforts to develop new methods for the synthesis of natural
products derived from humulene cyclization cascades, we
contemplated a novel and general strategy to create the tricyclic
sterpurane framework in a single stereoselective sequence
which does not rely upon p2s + p2s photocycloaddition for the
formation of the cyclobutane ring. Remarkably, this strategy
also provides a new route to linearly fused triquinanes from the
same precursor via modulation of the chemical reactivity in the
excited state.
1
were deduced from its high field H NMR, COSY and NOE
spectra. † The orientation of the oxirane ring is suggested on the
basis of the general tendency of cyclohexa-2,4-dienones during
addition.7,11 It should be mentioned that there are only a few
The cornerstone of our strategy is the recognition of the
structural and functional relationship between the sterpurane
framework and the tricyclic system 6 containing a b,g-enone
chromophore. It was envisaged that a 1,3-acyl shift8 in 6 upon
singlet excitation would readily furnish the sterpurane frame-
work 5 in such a fashion as to create all three rings in the correct
relative stereochemical orientation and the double bond at the
desired position, in a single step (Scheme 1). It was further
thought that the key tricyclic precursor 6 might be synthesized
via intramolecular p + p cycloaddition of 1-oxaspiro-
[2.5]octa-5,7-dien-4-ones of type 8 and further manipulation of
the resulting adduct. In addition, we also visualized that triplet
sensitized 1,2-migration8,9 of the acyl group in 6 would lead to
the tetracyclic system 7 (Scheme 1), which upon cleavage of the
Scheme 2 Reagents and conditions: i, Mg, 4-bromobutene, THF, 85%; ii,
PDC, CH2Cl2, 87%; iii, NaH, THF, MeI, 93%; iv, HClO4, MeOH–H2O,
81%; v, NaIO4 MeCN–H2O, 71%; vi, Zn, NH4Cl, MeOH–H2O, 78%; vii,
Jones oxidation, 90%; viii, THF–H2O, D, 71%; ix, ethylene glycol,
benzene, TsOH, quant.; x, NaBH4, THF–MeOH–H2O, 85%; xi, HCl,
acetone–water, 86%.
4s
2s
Chem. Commun., 1999, 2519–2520
This journal is © The Royal Society of Chemistry 1999
2519

1.94 (d with str, J ~ 2 , allylic coupling, 3H), 1.50 (superimposed dd, J1
=
J2 = ~ 12 , 1H), 1.32 (ddd, J1 ~ 12, J2 ~ 7.5 , J3 ~ 1.7, 1H), 1.14 (s, 3H),
1.09 (s, 3H,); dC(75 MHz, CDCl3) 214.72 (CO), 197.55 (CO), 148.03,
118.25, 65.61, 56.87, 51.38, 48.24, 44.84, 42.39, 37.07, 27.81, 25.25, 23.92,
20.16; m/z 246 (M+).
‡ All yields refer to isolated yields. Some unchanged starting material was
recovered ( ~ 65% conversion).
§ Selected data for 15: nmax(film)/cm21: 3427,1773; dH(300 MHz, CDCl3)
5.54 (br s, 1H), 3.99 (br m, 1H), 3.0 (d, of part of an AB system, J1 18, J2
9, 1H), 2.77 (d of part of an AB System, J1 18, J2 7, 1H), 2.55 (m, 1H), 2.37
(m, 1H), 2.0–1.92 (complex m, 2H), 1.60 (br d, J ~ 6, 1H, O-H), 1.29 (s,
3H, CH3), 1.20 (dd, J1 12, J2 9, 1H, CH2), 1.07 (dd, J1 12, J2 ~ 5, 1H, CH2),
1.0 (s, 6H); dC(50 MHz, CDCl3–CCl4) 209.9, 150.5, 124.1, 82.5, 64.0,
46.14, 43.4, 41.3, 31.9, 31.5, 28.0, 27.8, 21.5, 21.1; m/z 220 (M+).
¶ Selected data for 16: mp 136–138 °C; nmax(KBr)/cm21 3395, 1691;
dH(300 MHz, CDCl3) 3.42 (br d, 1H), 2.70-2.45 (m, 3H), 2.7 (s,1H), 1.95
(dd, J1 12, J2 9, 1H), 1.86-1.68 (m, 3H),1.40 (s, 4H, CH3 and OH), 1.29 (dd,
J1 12, J2 ~ 7, 1H), 1.08 (s, 3H), 1.02 (s, 3H); dC(75 MHz, CDCl3) 215.25,
79.08, 56.53, 46.81, 46.56, 46.28, 46.23, 46.14, 45.43, 44.06, 42.10, 26.69,
21.98, 14.51; (m/z 220(M+).
Scheme 3 Reagents and conditions: i, hn, benzene, 0.5 h, 55%; ii, hn,
acetone, 1 h, 78%; iii, Bu3SnH, AIBN, benzene, D, 5 h, 70%.
methods12 for the preparation of bicyclo[2.2.2]octenones of
type 12 annulated through bridgeheads.
The reduction of 12 with zinc and NH4Cl in aqueous MeOH
1
gave the b-keto alcohol 13a [as a syn+anti mixture, H NMR
1 Isolation of 1–3: (a) W. A. Ayer and M. H. Saeedi-Ghomi, Can. J.
Chem., 1981, 59, 2536; (b) O. Sterner, T. Anke, W. S. Sheldrick and W.
Steglich, Tetrahedron, 1990, 46, 2389; (c) J.-L. Xie, L.-P. Li and Z.-Q.
Dai, J. Org. Chem., 1992, 57, 2313. Isolation of other sterpuranes: (d) C.
Abell and A. P. Leech, Tetrahedron Lett., 1987, 28, 4887; (e) G.
Cimino, A. D. Giulio, S. D. Rosa and S. D. Stefano, Tetrahedron, 1989,
45, 6479; (f) W. A. Ayer and L. M. Browne, Tetrahedron, 1981, 37,
2199.
2 T. Takeuchi, H. Iinuma, J. Iwanaga, S. Takahashi, T. Takita and H.
Umezawa, J. Antibiot., 1969, 22, 215; S. Takahashi, H. Naganawa, H.
Iinuma, T. Takita, K. Maeda and H. Umezawa, Tetrahedron Lett., 1971,
1955.
3 K. Domon, K. Masuya, K. Tanino and I. Kuwajima, Tetrahedron Lett.,
1997, 38, 465; V. Singh and B. Samanta, Tetrahedron Lett., 1999, 40,
383; H. Mizuno, K. Domon, K. Masuya, K. Tanino and I. Kuwajima,
J. Org. Chem., 1999, 64, 2648. For other references on synthesis of
coriolin see ref. 4(a).
4 (a) For excellent review on polyquinane natural products: G. Mehta and
A. Srikrishna, Chem. Rev., 1997, 97, 671 and references cited therein;
(b) R. D. Little, Chem. Rev., 1996, 96, 93; (c) V. Singh and B. Thomas,
Tetrahedron, 1998, 54, 3647; (c) L. A. Paquette, Top. Curr. Chem.,
1984, 119, 1.
(300 MHz)] which was oxidized with Jones’ reagent, and the
resulting b-keto acid 13b was subjected to decarboxylation to
furnish the tricyclic system 13c in good yield. Protection of the
carbonyl group at the ethano bridge as a ketal and subsequent
reduction of the resulting keto ketal with NaBH4 in THF–
MeOH–H2O followed by deprotection of the ketal group
efficiently gave the desired chromophoric system 14. The
stereochemical orientation of the hydroxy group is suggested
from the down field signal of the CHOH proton (d 4.06, br s)
which was further confirmed via its transformation to the
known triquinane 17 (vide infra).
Towards the synthesis of sterpuranes, a solution of 14 in dry
benzene was irradiated with a mercury vapour lamp (125 W,
Applied Photophysics) for about 30 min, upon which a clean
reaction occurred (TLC, IR). Removal of the solvent followed
by chromatography gave the tricyclic compound 15 in good
yield (55%)‡ as a result of 1,3-acyl shift (Scheme 3). The
structure of the photo-product 15 was clearly revealed from its
spectral data.§
On the other hand, the triplet sensitized irradiation of 14 in
acetone (sensitizer as well as solvent) in a Pyrex immersion well
under nitrogen furnished the tetracyclic compound 16 in good
isolated yield (78%) [83% conversion, unchanged starting
material was recovered] whose structure was deduced from
spectral data¶ and comparison with the spectral features of its
precursor.13 Cleavage of the peripheral cyclopropane bond with
Bu3SnH–AIBN14 in refluxing benzene gave triquinane 17 (mp
117–118 °C) (Scheme 3), which has already been elaborated to
coriolin.15 The physical and spectral characteristics of 17
compared well with the reported data.15 Thus, the formal
synthesis of coriolin was complete.
5 K. Masuya, K. Domon, K. Tanino and I. Kuwajima, J. Am. Chem. Soc.,
1998, 120, 1724; M. Lautens and J. Blackwell, Synthesis, 1998, 537; V.
Krishnamurthy and V. H. Rawal, J. Braz. Chem. Soc., 1998, 9, 341.
6 (a) Y. Murata, T. Ohtsuka, H. Shirahama and T. Matsumoto,
Tetrahedron Lett., 1981, 22, 4313; (b) L. Moens, M. M. Baizer and R. D.
Little, J. Org. Chem., 1986, 51, 4497; (c) L. A. Paquette, H.-S. Lin, B. P.
Gunn and M. J. Coghlan, J. Am. Chem. Soc., 1988, 110, 5818; (d) S.-K.
Zhao and P. Helquist, J. Org. Chem., 1990, 55, 5820; (e) G. M. Strunz,
R. Bethell, M. T. Dumas and N. Boyonoski, Can. J. Chem., 1997, 75,
742; (f) O. J. Birkenes, T. V. Hansen, S. M’dachi, L. Skattebol and Y.
Stenstrom, Acta. Chem. Scand., 1998, 52, 806; (g) R. A. Gibbs, K.
Bartels, R. W. K. Lee and W. H. Okamura, J. Am. Chem. Soc., 1989,
111, 3717; (h) N. Krause, Liebigs Ann. Chem., 1993, 521; (i) A. Arnone,
C. D. Gregorio, G. Nasini and O. V. D. Pava, J. Chem. Soc., Perkin
Trans. 1, 1997, 1523.
In summary, we have described a novel and stereoselective
method for the synthesis of sterpuranes which has wide
synthetic potential, and a formal total synthesis of (±)-coriolin
7 V. Singh, Acc. Chem. Res., 1999, 32, 324.
4s
2s
8 D. I. Schuster, in Rearrangement in Ground and Excited States, ed. P.
deMayo, Academic Press, New York, 1980, vol. 3; V. Singh and M.
Porinchu, Tetrahedron, 1996, 52, 7087.
9 H. E. Zimmerman and D. Armesto, Chem. Rev., 1996, 96, 3065.
10 K. Tsubaki, T. Otsubo, K. Tanaka, K. Fuji and T. Kinoshita, J. Org.
Chem., 1998, 63, 3260.
11 E. Adler and K. Holmberg, Acta. Chem. Scand., 1974, 28B, 465; V.
Singh, A. V. Bedekar and M. R. Caira, J. Chem. Res. (S), 1995, 452.
12 M. Demuth and W. Hinsken, Angew. Chem., Int. Ed. Engl., 1985, 24,
973; J.-T Hwang and C.-C. Liao, Tetrahedron. Lett., 1991, 32, 6583.
13 For synthesis of tetracyclic systems of type 16 by meta-photocycloaddi-
tion, P. A. Wender and J. J. Howbert, Tetrahedron Lett., 1982, 23,
3983.
14 E. J. Enholm and Z.J. Jia, J. Org. Chem., 1997, 62, 174.
15 R. L. Funk, G. L. Bolton, J. U. Daggett, M. M. Hansen and L. H. M.
Horcher, Tetrahedron, 1985, 41, 3479; L. V. Hijfte, R. D. Little, J. L.
Petersen and K. D. Moeller, J. Org. Chem., 1987, 52, 4647.
employing the intramolecular p + p cycloaddition of
1-oxaspiro[2.5]octa-5,7-dien-4-one and sigmatropic shifts in
excited states. This method, in turn, also provides a new and
efficient avenue to annulated bicyclo[2.2.2]octenones of type
12–14 which are not readily accessible otherwise.
We thank RSIC, I.I.T. Bombay, for the use of high field NMR
and mass spectral facilities. Financial support from BRNS is
gratefully acknowledged. S.Q. Alam is grateful to I.I.T.
Bombay for a Teaching Assistantship.
Notes and references
†All the compounds were thoroughly characterised with the help of spectral
and analytical data. Selected data for adduct 12: mp 66 °C; nmax(KBr)/cm21
1755, 1716; dH(300 MHz, CDCl3) 5.41 (br s, 1H), 3.16 (part of an AB
system, JAB ~ 7, 1H), 2.84 (part of AB system, JAB ~ 7, 1H), 2.75 (m, 1H),
2.47–2.38 (complex m, 1H), 2.34 (m, 1H), 2.02 (dd, J1 ~ 12, J2 ~ 6.5, 1H),
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