α‐Unsubstituted Pyrroles by NHC‐Catalyzed Three‐Component Coupling: Direct Synthesis of a Versatile Atorvastatin Derivative

A practical one‐pot cascade reaction protocol provides direct access to valuable 1,2,4‐trisubstituted pyrroles. The process involves an N‐heterocyclic carbene (NHC)‐catalyzed Stetter‐type hydroformylation using glycolaldehyde dimer as a novel C1 building‐block, followed by a Paal‐Knorr condensation with primary amines. The reaction makes use of simple and commercially available starting‐materials and catalyst, an important feature regarding applicability and utility. Low catalyst loading under mild reaction conditions afforded a variety of 1,2,4‐substituted pyrroles in a transition‐metal‐free reaction with high step economy and good yields. This methodology is applied in the synthesis of a versatile Atorvastatin precursor, in which a variety of modifications at the pyrrole core structure are possible.