Paal-Knorr synthesis

Although the Paal-Knorr synthesis has seen widespread use, the mechanism wasn't fully understood until it was elucidated by V. Amarnath et al. in the 1990s.

After ring-closing metathesis and alkene reduction, the 1,4-dicarbonyl product was converted to a pyrrole via the Paal-Knorr synthesis and further elaborated to the natural product.

Classic "named reactions" are the Knorr pyrrole synthesis, the Hantzsch pyrrole synthesis, and the Paal-Knorr synthesis.

Together with Carl Paal, he discovered the Paal-Knorr synthesis, and the Knorr quinoline synthesis and Knorr pyrrole synthesis are also named after him.

The Stetter reaction is commonly used in sequence with the Paal-Knorr synthesis of furans and pyrroles, which a 1,4-dicarbonyl undergoes condensation with itself or in the presence of an amine under high temperature, acidic conditions.

Several laboratory syntheses of roseophilin (e.g., those of Trost, Furstner, Salamone) are based upon the Paal-Knorr synthesis, and two others are based on the Nazarov cyclization reaction (those of Tius, Frontier).

Unlike 1,3-dicarbonyls, which are easily accessed through the Claisen condensation, or 1,5-dicarbonyls, which are commonly made using a Michael reaction, 1,4-dicarbonyls are challenging substrates to synthesize, yet are valuable starting materials for several organic transformations, including the Paal-Knorr synthesis of furans and pyrroles.