Highly stereoselective ring expansion of enantiopure α-hydroxyalkyl azetidines

Stereodefined alpha-hydroxyalkyl azetidines, prepared in a few steps from enantiopure beta-amino alcohols, are chlorinated or transformed into methanesulfonyloxymethyl derivatives in good yields. Heating of these compounds in chloroform or dimethylformamide induces a stereospecific ring enlargement to give 3-chloro or 3-methanesulfonyloxy pyrrolidines. The ease of this rearrangement depends on the nature of the migrating group (Cl- or MsO-), of the class of the starting alcohol (primary or secondary) and of the relative stereochemistry of the starting material. (C) 2003 Elsevier Science Ltd. All rights reserved.