104 Furans and Thiophenes
There are many examples of intramolecular furan cycloadditions and of the construction of complex polycycles using
this furan reactivity. Illustrated below is a process in which the second of the two cycloadditions is intramolecular – the
overall conversion proceeds in 95% yield!
Thiophene takes part in a cycloaddition with maleic anhydride only under extreme conditions. However, there is a way
in which thiophenes can be made ‘more like a diene’, by S-oxidation to thiophene S-oxides or S,S-oxides, which enter
into Diels–Alder cycloadditions readily.
The cycloaddition of furans with singlet oxygen gives cyclic peroxides (effectively ozonides of cyclobutadiene!). These
are important because they can be further utilised. A nice example is the reaction of furoic acid with singlet oxygen.
The adduct undergoes decarboxylation (as illustrated) leading to 5-hydroxy-2(5H)-furanone (‘malealdehydic acid’).
Furoic acid (furan-2-carboxylic acid) is readily available by oxidation of the 2-aldehyde (furfural), in turn available in
large amounts by acid treatment of residues from the manufacture of porridge oats and cornfl akes. The adduct breaks
down via loss of carbon dioxide, breaking the O-O bond, and revealing the cyclic hemiacetal of malealdehydic acid
(i.e. 5-hydroxy-2(5H)-furanone).
Oxygen substituents
3-Hydroxyfuran is entirely in the carbonyl tautomeric form and 3-hydroxythiophene is the minor tautomer in a
mixture (1:3) with the carbonyl form. 2-Hydroxythiophenes and 2-hydroxyfurans exist in carbonyl tautomeric forms,
with the remaining C-C double bond at C-3-C-4 or C-4-C-5 or as a mixture, depending on the substituents. In
some cases the tautomers are separable, for example the - and -angelica lactones. Generally, in the context of their
occurrence in natural products, these furan lactones are referred to as butenolides. A 4-hydroxybutenolide is known
as a tetronic acid.