On the Ritter reaction of cyclic hydroxyamines: Synthesis of conformationally-restricted reduced amide dipeptide isosteres

The Ritter reactions of 3-alkyl-3-hydroxyazetidine or -piperidine derivatives give low yields of the desired products, whereas the 3-aIkyl-3-hydroxy-pyrrolidine and 4-alkyl-4-hydroxy-piperidine derivatives react smoothly to give the corresponding acetamides. An alternative route to 3-acylamino-3-alkylpiperidines, which were designed as conformationally-restricted reduced amide dipeptide isosteres, was devised from nipecotic acid via a Hofmann rearrangement.