Recent advances in the synthesis of polysubstituted 3-pyrazolidinones

Abstract

An account of recent developments in the field of 3-pyrazolidinone chemistry is given with special focus on the synthesis and transformations of 5-substituted 4-benzyloxycarbonylamino-3-pyrazolidinones, pyrazolo[1,2-a]pyrazole-based peptide analogues, and tetrahydropyrazolo-[1,5-c]pyrimidine-2,7-diones. In terms of practical application, polyfunctionalized 3-pyrazolidinones as 'aza-deoxa' analogues of cycloserine, peptide mimetics based on 3-amino-2-oxo-1,5-diazabicyclo[3.3.0]octane-7-carboxylic acid, and 1,6-disubstituted tetrahydropyrazolo[1,5-c]-pyrimidine-2,7-diones as the first representatives of a novel saturated heterocyclic system were prepared by these newly developed synthetic methods.

Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a1-diazacyclopenta[cd]inden-2-ones

“…The regioselectivity of the cycloadditions to terminal ynones 21b – e and alkyl acrylates 22 was in agreement with the regioselectivity of closely related thermal ,, and Cu-catalyzed reactions. ,, The preferential formation of the regioisomers 24 and 25 is in line with the electrostatically controlled approach of the polarized dipolarophile 21 or 22 to the mesomeric structure 12 via the proposed transition states TS1 and TS2 (Scheme ). Facial selectivity of cycloadditions to 12a , b is explainable by the preferential attack of the dipolarophile 21 or 22 from the less hindered face of the dipole 12 via the proposed transition states TS1 – TS3 .…”

“…In the context of our ongoing work on the synthesis of 3-pyrazolidinones and pyrazole analogues of histamine, we recently reported two syntheses of tetrahydropyrazolo­[1,5- c ]­pyrimidine-2,7­(1 H ,3 H )-diones as the first representatives of a novel saturated heterocyclic system. , Subsequently, a library of related tetrahydropyrazolo­[1,5- c ]­pyrimidine-3-carboxamides as novel conformationally constrained pyrazole analogues of histamine was also synthesized . In continuation of that work, we focused on 1,7,7-trisubstituted hexahydropyrazolo­[1,5- a ]­pyridin-2­(1 H )-ones 5 and their tricyclic analogues (3,4,4a-trisubstituted octahydro-2 H -2a,2a 1 -diazacyclopenta­[ cd ]­inden-2-ones) 6 (Figure ).…”

Absolute Configuration Determination of 2,3-Dihydro-1H,5H-pyrazolo[1,2-a]pyrazoles Using Chiroptical Methods at Different Wavelengths

“…Later on, this would allow us to compare the influence of a given substituent on the specific rotation. Azomethine imines 1a – l with variable substituents at positions 4 and 5 and bearing typical aryl residues at position 1′ were prepared in good yields by condensation of racemic 3-pyrazolidinones 4a , 4b , 4c , 4d , and 4e and achiral compound 4f , with 5a – f following general literature procedures. ,, The Z configuration around the CN double bond in 3-oxopyrazolidin-1-ium-2-ides 1 and the trans configuration of 4,5-disubstituted pyrazolidinones 4a – c and dipoles 1 derived thereof were established previously. ,, Selected experimental data for dipoles 1a – l prepared from chemsets 4a – f and 5a – f are presented in Table .…”

Synthesis of 6,7-Dihydro-1H,5H-pyrazolo[1,2-a]pyrazoles by Azomethine Imine-Alkyne Cycloadditions Using Immobilized Cu(II)-Catalysts

“…In recent years, an important part of our ongoing research on the chemistry of 3-pyrazolidinones [ 55 ] has been focused on CuAIAC reactions catalyzed by Cu(0) [ 56 , 57 ], Cu(I) [ 58 , 59 , 60 , 61 ], and Cu(II) [ 27 ]. In extension, we were interested in the use of immobilized Cu(II) complexes with enaminone-type ligands attached to the solid support in CuAIAC reactions.…”