GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 112

a collection of other synthetic applications that could not be classified in the
previous sections. This chapter covers the literature up to September 2010.

4.2. GOLD-CATALYZED FORMATION OF
OXYGEN-CONTAINING HETEROCYCLES

A series of gold-catalyzed transformations involving the formation of an oxygen-
containing heterocycle has been applied to the synthesis of natural products. Furan
and pyran derivatives, as well as spiroketals, are the most frequently encountered
structures (Scheme 4.4). They basically arise from the intramolecular addition of a
nucleophilic oxygen species on an allene or an alkyne. The formation of spiroketals is
the result of an intramolecular dialkoxylation of an alkyne.

4.2.1. Cyclizations Leading to Furan and Pyran Derivatives
4.2.1.1. From Allenes Allenes can be easily activated by an electrophilic gold
species for the intramolecular addition of an oxygen nucleophile. In the case of
hydroxyallenes, an exo or endo cyclization can proceed depending on the length of the
linker (Scheme 4.5).
Dihydrofurans and dihydropyrans can thus be obtained from a - and b -hydroxy-
allenes [4], while the reactions of g - and d -hydroxyallenes lead to the formation of
tetrahydrofurans and tetrahydropyrans, respectively [5]. The hydroalkoxylation of
allenes has been used on several occasions for the synthesis of natural products, more
especially for those possessing a tetrahydrofuran moiety. The first application was
reported in 2001 by Krause and Hoffmann-R oder for the formal synthesis of

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citreoviral 8 , a key intermediate in the synthesis of the antiparasitic mycotoxins

citreoviridin 9 and verrucosidin 10 (Scheme 4.6). a -Hydroxyallene 6 , which is easily

OR

n

n

HO OH

OH OH

m

n

n = 1 or 2 n = 1 or 2

O O

O O

O O O O

n
OR

n

m m

O O O O

OR

SCHEME 4.4

n = 1, 2 n = 3, 4

Au(I) or Au(III) Au(I) or Au(III)

n

n m

O 5- or 6 -endo OH 5- or 6 -exo O

n = 1, 2,5-Dihydrofuran
n = 2, 3,6-Dihydropyran

n = 1-4 m = 1, Tetrahydrofuran

m = 2, Tetrahydropyran

Hydroxyallene

SCHEME 4.5