Synthetic potential of heteroatomic ring systems
The synthesis of aziridine-2-carboxylic acid derivatives of high enantiopurity is described and their synthetic utility is discussed. Ring-opening and ring-expansion reactions of both oxirane and aziridine carboxylic esters are highlighted. Convenient syntheses of a- hydroxy, b-amino and a-amino, b-hydroxy carboxylic acids with defined stereochemistry are presented. The preparation of pyrrolidinone and azetidinone derivatives from functionalized three-membered heterocycles is described. Small-ring heterocycles also serve as the basis for the synthesis of catalysts, e.g. for an asymmetric reduction and for cyclopropanation reactions. Functionalized small-ring heterocycles are highly attractive compounds from the synthetic point of view (1). Aziridine-2-carboxylic esters, for instance, are of interest as they are structurally related to a-as well as b-amino acids (2), and ring-opening reactions of oxiranecarboxylic acid derivatives allow the preparation of sterically defined a,b-functionalized carboxylic acids. The strain present in these three- membered ring compounds ensures high reactivity in ring-opening and ring-expansion reactions (2). We have developed a general and convenient synthesis of aziridine-2-carboxylic esters 1 from the corresponding oxiranecarboxylates 2 by successive treatment with sodium azide and triphenylphosphine (3). The required starting materials in turn were prepared by Sharpless epoxidation of appropriate allylic alcohols (4), followed by oxidation of the 2,3-epoxy alcohols to the corresponding carboxylic acids using either ruthenium tetroxide or a two-step process involving a Swern oxidation and subsequent oxidation with sodium chlorite (3). The sequence for the conversion of epoxy esters 2 into the aziridine esters 1 is depicted in Scheme 1.