PMC

Trost–Doherty’s application of the Paal–Knorr reaction in the synthesis of roseophilin. The diketone and amine groups are coloured in red and blue, respectively.

Paal-Knorr pyrrole synthesis assisted by partially methyled β-cyclodextrins: (A) Paal-Knorr condensation of 1,4-diketones and amines; (B) Paal-Knorr condensation of 1,4-diketones and diamines.

Commercial synthesis of atorvastatin (Lipitor). The Paal–Knorr reaction plays a central role in the condensation of diketone 8 with amine 9 to afford pyrrole 10. Atorvastatin is then delivered through acetal deprotection.

Mechanochemical Paal–Knorr pyrrole synthesis [].

Atropselective Paal–Knorr pyrrole synthesis

Catalytic asymmetric Paal‐Knorr reaction for the synthesis of axially chiral N‐arylpyrroles.

Paal-Knorr synthesis of C₄H₄O.

Paal–Knorr synthesis of pyrrole-functionalized precatalysts. Ac = acetyl.

Synthesis of 2-(3′-furyl)azulenes 124a and 124b via Paal–Knorr reaction.

Synthesis of 3-(guaiazulen-3-yl)pyrroles 118 via Paal–Knorr reaction of 3-acetyl-4-(guaiazulen-3-yl)hexane-2,5-dione (117).

Paal-Knorr synthesis of 2,5-dimethylpyrrole as an amine protecting group

Synthesis of Paal–Knorr probe 1. a) Ph₃P = CHCO₂Me, THF, reflux, 20 h, 92 %; b) H₂, Pd/C, EtOH, RT, 24 h, 78 %; c) H₂SO₄ (trace), 50 % aq. HOAc, 110 °C, 15 h, 62 %; d) 0.5 MHCl, 1,4-dioxane, CH₂Cl₂, RT, 2 h, 98 %; e) EDAC, DMAP, DMF, CH₂Cl₂, 20 h, 86 %; f) AcOH, THF, RT, 5 h, 86 %. The IAF tag, 1,4-diketone, and amine are colored blue, red, and green, respectively.

In 2007, Williams and co-workers reported the Ru-catalyzed synthesis of pyrroles 3-245 from the corresponding 1,4-alkynediols 2-244 and aromatic or aliphatic amines (). Apparently, the reaction proceeds via a formation of diketone 3-246 and a subsequent Paal-Knorr reaction with amines to produce pyrrole 3-245. In general, the reaction is more efficient with aliphatic alkynediols and amines.

a. Members of the spongiane family of diterpene natural products including gracilin A (34). b. Macfarlandin E (39) and t-butyl derivative 40 bearing a related masked 1,4-ketoaldehyde and shown to undergo Paal-Knorr pyrrole synthesis with lysine in simulated physiological conditions.

Paal-Knorr condensation installs pyrrole unit.