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9.13.1.5.2.1 Method 1: Condensation Reaction of α-Amino Ketones with Methylene-Active Carbonyl Compounds (The Knorr Pyrrole Synthesis)

DOI: 10.1055/sos-SD-009-00542

Black, D. StC.Science of Synthesis, (20019469.

The Knorr pyrrole synthesis is probably the most important in terms of its wide applicability and early discovery. Over the years it has received many modifications, mostly relating to the formation of crucial intermediates. The process is one of cyclizative condensation between an α-amino ketone and α,β-oxo ester or β-dicarbonyl compound. The α-amino ketone provides a nucleophilic nitrogen and an electrophilic carbonyl group, and the β-oxo ester or β-dicarbonyl compound provides an electrophilic carbonyl group and a nucleophilic carbon. Initial enamine formation occurs between the primary amino group and the dicarbonyl compound. This is followed by cyclization as the outcome of the enamine addition of its β-carbon to the carbonyl group of the amino ketone. The process is typified by the combination of amino ketones 177 and carbonyl compounds 178 to give the enamines 179, which undergo cyclization to the intermediates 180, which lose water to form the aromatic pyrroles 181 (Scheme 29).

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References


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