Synthesis of seven-membered oxacycles. Part 2: The furan approach

Article abstract of DOI:10.1016/S0040-4039(03)01027-X

We describe an efficient new approach for the synthesis of seven-membered oxacycles that is based on the oxidation of a furan ring with singlet oxygen followed by an intramolecular Michael addition.

Full text of DOI:10.1016/S0040-4039(03)01027-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4467–4469
Synthesis of seven-membered oxacycles. Part 2:
The furan approach
Yagamare Fall,* Beatriz Vidal, David Alonso and Generosa G o´ mez
Departamento de Qu ´ı mica Org a´ nica, Facultad de Ciencias, Universidad de Vigo, 36200 Vigo, Spain
Received 7 April 2003; accepted 19 April 2003
Abstract—We describe an efficient new approach for the synthesis of seven-membered oxacycles that is based on the oxidation of
a furan ring with singlet oxygen followed by an intramolecular Michael addition. © 2003 Elsevier Science Ltd. All rights reserved.
Seven-membered oxacycles are structural units that are1
present in a wide variety of bioactive natural products,
approaches share one of their starting materials, iodide
2 (Scheme 1), but differ in the other, which in the new
method is furan (1).
2
including the monocyclic zoapatanol, the polycyclic
3
hemibrevetoxin B (Fig. 1) and more complex polyether
4
5
Iodide 2 was easily obtained by reaction of THF with
sodium iodide and TBSCl (Scheme 2). Lithiation of
furan (1) and reaction with 2 afforded the alkylated
furan 7 in 81% yield. Oxidation of 7 with singlet oxygen
toxins such as ciguatoxin and brevetoxins A and B.
Because of their unusual molecular architecture, these
molecules are challenging synthetic targets for organic
chemists.
8
gave an 82% yield of hydroperoxide 8, which could be
purified by column chromatography but was rather
labile, undergoing slow decomposition even when
stored at low temperature. Hence freshly purified 8 was
immediately reacted with acetic anhydride in pyridine,
affording butenolide 9 in 72% yield from 7. Treatment
of 9 with TBAF then not only removed its TBS group,
We recently described the synthesis of seven-membered
oxacycles using methoxyallene as the key starting mate-
rial. The scope and limitations of this method are
6
being explored, and the results will be published in due
course. Prompted by the increasing interest in the syn-
7
thesis of seven-membered oxacycles in recent years, we
8
but also led to the bicyclic compound 4 through an
have now developed a second approach. The two
intramolecular Michael addition (yield 63%). Finally,
reduction of 4 in CH Cl with Et SiH (3.0 equiv.) in the
2
2
3
9
presence of TMSOTf (2.4 equiv.) gave lactone 3 in
3% yield, presumably via oxonium ion intermediate
5
1
0.
1
13
The structure of 4 was determined from its H and
C
NMR, NOE, NOESY, COSY and HMBC spectra (Fig.
2).
Figure 1. Hemibrevetoxin B.
Scheme 1. Retrosynthetic analysis: A, the methoxyallene approach; B, the furan approach.
*
Corresponding author. Fax: 34 986 81 23 82; e-mail: yagamare@uvigo.es
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01027-X

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Y. Fall et al. / Tetrahedron Letters 44 (2003) 4467–4469
t
1
Scheme 2. Reagents and conditions: (i) NaI, TBSCl, CH CN, rt (72%); (ii) 1, BuLi, THF, −78 to 0°C (81%); (iii) O , MeOH, rose
3
2
bengal, hw (82%); (iv) Ac O, py, DMAP (72%); (v) TBAF, THF, rt (63%); (vi) Et SiH, TMSOTf, CH Cl , rt, 6 h (52%).
2
3
2
2
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This work was supported by grants from the Xunta de
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4469
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