156 Non-Aromatic Heterocycles
TheHofmann–Löffl er–Freytag reaction is a neat method for the synthesis of pyrrolidines and does not require a difunc-
tionalised starting material – a radical process is used to introduce the second functional group. The six-membered size
of the cyclic transition state leads selectively to a 1,4-halo-amine, and thence to pyrrolidines.
Three-membered heterocycles from alkenes
By far the most widely used method for the preparation of oxiranes (epoxides) involves oxidation of an alkene by a peracid,
via a direct one-step transfer of an oxygen atom. More highly substituted alkenes react fastest showing that electronic effects
are more important than steric effects in this reaction. Steric effects do, however, control the facial selectivity of epoxidation.
Several other direct oxygen-transfer reagents have been developed of which by far the most important is the Sharpless
reagent – a mixture of a hydroperoxide with titanium isopropoxide and a dialkyl tartrate. The structure of the reagent
is complex but it reacts readily with alkenes containing polar groups, for example allylic alcohols, which can coordinate
the metal. The most important feature of this process is that when enantio-pure tartrate esters are used, a highly ordered
asymmetric reactive site results, leading in turn to high optical induction in the product.
N-Sulfonylaziridines can be obtained directly from alkenes by reaction with ‘Chloramine T’ (TsN(Cl)Na) or from other
sulfonamides by generating an N-halo-compound in situ, via reaction with t-butyl hypochlorite and sodium iodide.
Thiiranes via interchange of heteroatoms
The most common method for the preparation of thiiranes is via reaction of an epoxide with thiocyanate, thiourea, or
a phosphine sulfi de. As a consequence of the mechanism, the stereochemistry of the thiirane is opposite to that of the
starting epoxide – two SN2 inversions take place.