Solid phase synthesis of 3-acyl-2,4-pyrrolidinediones (3-acyl tetramic acids) via mild cyclative cleavage

The solid phase synthesis of 3-acyl-2,4-pyrrolidinediones (3-acyl tetramic acids) has been reported. Cyclative cleavage of the penultimate intermediat e via a Dieckmann cyclization yields the 3-acyl-2,4-pyrrolidinediones. Rema rkably mild conditions are required for the cyclative cleavage; treatment o f the resin-bound acyclic precursor with one equivalent of potassium hydrox ide in methanol at room temperature for 5-30 minutes affords the product. T he synthetic route routinely provides high yields in greater than 95% purit y and is compatible with acid-labile protecting groups. Virtually any hydro xy-functionalized resin can be utilized for this synthesis.