Knorr pyrrole syntheses Acylation

In 1990 we initially became interested in the possibility of utilizing the acylative version of the Knorr pyrrole synthesis for the construction of pyrrolo[2,3-cf pyrimidines. Over the past 7 years this notion has been... 

When a -amino ketones with an additional acyl or alkoxycarbonyl substituent are used, the cyclization can follow one of two alternative courses (Scheme 6) (71JOC853). The first represents the normal Knorr cyclization. The product of the competing deacylation pathway is also a pyrrole and the utilization of the reaction gives a pyrrole synthesis, as is described in Section 3.06.3.5. The reaction does, however, constitute a limitation on the Knorr synthesis itself. 

Two other examples of microwave-assisted Paal-Knorr reactions were reported in 2004, describing the synthesis of a larger set of pyrroles with different substituents around the ring. The methods differ mainly in the syntheses employed to produce the 1,4 dicarbonyl compounds required for the cyclization. A variation of the Stetter reaction between an acyl silane and dif-... 

A different approach toward highly substituted pyrroles involving a one-pot sila-Stetter/Paal-Knorr strategy was realized by Bharadwaj and Scheidt (Scheme 6.182) [343]. In this multicomponent synthesis, catalyzed by a thiazolium salt, an acyl anion conjugate addition reaction of an acylsilane (sila-Stetter) was coupled in situ with the conventional Paal-Knorr approach. Employing microwave conditions at 160 °C for 15 min, the acylsilane was combined with the cx/l-unsaturated ketone in... 

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