AbstractΔ2‐Pyrrolin‐4‐ones undergo organocatalyzed sulfa‐Michael/aldol domino spirocyclizations with mercaptoacetaldehyde dimer. The products contain three contiguous stereocenters (ee up to 99%, dr up to 95:5, 25 examples) and can be transformed into analogues of natural products. With the use of a single catalyst, the absolute configuration of the products were determined by the configuration of the exocyclic double bond of the starting material. These results point at the possibility of a widespread use of unsaturated Δ2‐pyrrolin‐4‐ones in various (organo)catalyzed (cascade) transformations for accessing libraries of 3D‐rich pyrrolone‐based (spiro)heterocycles.magnified image

Arilidene-Δ2-pyrrolin-4-ones undergo organocatalyzed double spirocyclization with 3-isothiocianato oxindoles in a domino 1,4/1,2-addition sequence. The products contain three contiguous stereocenters (ee up to 98%, dr up to 99:1, 12 examples). The absolute configuration of the major diastereomer was determined by single crystal X-ray analysis. Along with heterocyclic Michael acceptors based on oxazolone, isoxazolone, thiazolidinone, pyrazolone, and pyrimidinedione, the reported results display the applicability of unsaturated Δ2-pyrrolin-4-ones (pyrrolones) for the organocatalyzed construction of 3D-rich pyrrolone-containing heterocycles.

Ten novel bifunctional quaternary ammonium salt phase-transfer organocatalysts were synthesized in four steps from (+)-camphor-derived 1,3-diamines. These quaternary ammonium salts contained either (thio)urea or squaramide hydrogen bond donor groups in combination with either trifluoroacetate or iodide as the counteranion. Their organocatalytic activity was evaluated in electrophilic heterofunctionalizations of β-keto esters and in the Michael addition of a glycine Schiff base with methyl acrylate. α-Fluorination and chlorination of β-keto esters proceeded with full conversion and low enantioselectivities (up to 29% ee). Similarly, the Michael addition of a glycine Schiff base with methyl acrylate proceeded with full conversion and up to 11% ee. The new catalysts have been fully characterized; the stereochemistry at the C-2 chiral center was unambiguously determined.

Racemic D 2 -pyrrolin-4-ones (i. e. 4-pyrrolones), easily available in two steps from Nprotected a-amino acids, undergo organocatalysed asymmetric Mannich-type addition to isatin-derived ketimines to furnish the non-racemic oxindole-D 2pyrrolin-4-one adducts, stereoselectively (up to 96% ee, dr ! 15:1). The oxindole-pyrrolone products feature vicinal tetrasubstituted carbon stereocenters. The developed protocol has a broad substrate scope and tolerates diverse substituents at position C-5 in 4-pyrrolones and at positions N-1 and C-5/7 in isatin imines.

A total of 24 novel organocatalysts based on (S)-quininamine as a chiral tertiary amine and on enaminone or 1,2-benzenediamine as hydrogen bond donors were synthesized. The enaminone-type catalysts were prepared by the transamination of N,N-dimethyl enaminones with (S)-quininamine (9 examples) and the 1,2-benzenediamine-type catalysts were prepared in 3 steps from (S)-quininamine and ortho-fluoronitrobenzene derivatives (15 examples). Their organocatalytic activity was evaluated in the Michael addition of acetylacetone to trans-β-nitrostyrene. Enantioselectivities of up to 72% ee were observed.