Common Reaction Types in Heterocyclic Chemistry 19Common synthetic equivalents of carbonyl compounds in ring synthesis
Quite frequently, and especially in heterocyclic ring synthesis, a reaction component is replaced with a molecule that
reacts in the same way – serves the same purpose – as the traditional or classical component. For example, a ring syn-
thesis might require a 1,3-diketone – a 3-alkoxy-enone would serve instead; a conjugated yne-one is also equivalent to
a 1,3-diketone and so is a 3-dialkylamino-enone.
Ene-ones carrying a -leaving group (like the 3-alkoxy-enone and the 3-dialkylamino-enone instanced above), usually
react with a nucleophile at the -carbon via an additionelimination sequence, as shown.
2,3,4,5-Tetrahydro-2,5-dimethoxyfuran is a convenient, protected form in which to supply butane-1,4-dial; 2,5-
dihydro-2,5-dimethoxyfuran similarly provides the equivalent of but-2-ene-1,4-dial.
Cycloaddition reactions
A very important synthetic protocol is the process known as the Diels–Alder reaction. In essence, a conjugated 1,3-diene
reacts with a dienophile – an alkene or an alkyne, for example – to generate a six-membered ring containing one (or
two) double bonds – a [4 2] cycloaddition. In the standard process, the diene is electron-rich (has electron-releasing
substituents) and the dienophile is electron-defi cient (has electron-withdrawing substituents). In ‘inverse-electron-
demand’ Diels–Alder cycloadditions, the diene is electron-defi cient and the dienophile electron-rich. We do not go
into the subtleties of the mechanism or stereochemistry here, but it is important to recognise that six -electrons are
redistributed in the process to form two new -bonds and to leave one -bond – the arrows on the general reaction
below show only this distribution and do not imply a fl ow of electrons in the clockwise direction shown.
In the heterocyclic context, some fi ve-membered heterocycles – notably furans – participate as electron-rich dienes in
Diels–Alder reactions.
Some six-membered heterocycles – in particular those with more than one nitrogen – participate as aza- or diazadienes
in inverse-electron-demand Diels–Alder cycloadditions and fi nal products are formed via the loss of a small stable
molecule (e.g. N 2 or HCN).