Non-Aromatic Heterocycles 151alcohols, thiols, hydride (LiAlH 4 ), malonate anions, and so on. The regiochemistry of nucleophilic attack is determined
mainly by steric effects. Assistance by protic solvents or O-coordinating metal cations (Lewis acids) further weaken the
C-O bond and can dramatically increase the rate of ring-opening reactions. Reagents such as tributyltin azide, which is
itself a Lewis acid (coordination to ‘Bu 3 Sn’), but also contains a nucleophilic function (N 3 ), are useful in this respect.
Under pure nucleophilic attack, steric effects dominate and nucleophilic opening of an epoxide takes place at the least
hindered position. Under acidic conditions, incipient carbonium ion formation tends to direct attack to the most
hindered position – it is often a fi ne balance.
‘Harder’ organometallic nucleophiles such as alkyllithiums can give rise to side reactions but their combination
(at78 °C) with boron trifl uoride gives very clean and effi cient reactions.
Ring-opening of epoxides by -elimination, on reaction with strong bases such as lithium amides, is a useful method
for the preparation of allylic alcohols, particularly as it can be carried out enantioselectively using a chiral base.
Acid-catalysed opening of aziridines is usually fairly rapid, but simple nucleophilic reactions, without acid catalysis, are
very slow due to the much poorer leaving ability of negatively charged nitrogen. However, N-acyl and N-sulfonyl aziridines
have similar reactivities to epoxides. Thiiranes similarly undergo ring-opening reactions with nucleophiles, such as amines.
In the opening of N-tosylaziridine with the anion of cyanoacetate, a second step, ring closure, produces a
2-amino-4,5-dihydropyrrole.