A straightforward synthesis of enantiopure 2-cyano azetidines from β-amino alcohols

Enantiopure 2-cyano azetidines were prepared in high yields from beta-amino alcohols. This synthesis was shown to be general and is based on two important steps: (i) chlorination of a N-cyanomethylated beta-amino alcohol and (ii) a 4-exo-trig ring closure through the alkylation of a lithiated alpha-amino nitrile. The former step is stereoselective when ephedrine-derived beta-amino alcohols are used. In the case of a phenylglycinol-derived beta-amino alcohol, this step also involves a rearrangement. (C) 2002 Elsevier Science Ltd. All rights reserved.