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

Abstract

A correlation between the absolute configuration and chiroptical properties of nonracemic 1,6,7-trisubstituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazoles was studied. A series of 16 novel representatives were prepared by Cu-catalyzed [3 + 2] cycloadditions of racemic (Z)-2-benzylidene-5-oxopyrazolidin-2-ium-1-ides to tert-butyl (S)-(3-oxopent-4-yn-2-yl)carbamate, and their structures were determined by NMR, VCD, ECD, and X-ray diffraction. A clear correlation between the sign of specific rotation and configuration at position C(1) allows for easy determination of the absolute configuration of 1,6,7-trisubstituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazoles by ECD and NMR. While VCD, requiring milligram quantities, allowed the determination of the correct relative and absolute configuration without additional information from other methods, the stereochemical analysis by ECD required knowledge of the relative configuration derived from NMR at a comparable computational level.

Combinatorial Synthesis of Acacen-Type Ligands and Their Coordination Compounds

“…The isolated Cu­(II)-complexes 6 { 4 , 6 , 8 ; 1 ; 1 } and 6 { 1 , 4 ; 4 ; 1 } were tested as catalysts in CuAIAC reaction, which is usually catalyzed by Cu + . Recently, examples of Cu 0 -catalyzed and Cu 2+ -catalyzed reaction have also been reported.…”

“…A correlation between the E/Z -isomerism of chiral enaminones 4 { 1 ; 1 , 4 } and complexes 6 { 1 ; 1 , 4 ; 1–4 } and specific rotation was also observed. Evaluation of five isolated copper complexes 6 { 1 , 4 ; 4 ; 1 }, 6 { 4 ; 1 ; 1 }, and 6 { 6 , 8 ; 1 ; 1 } as catalysts in Cu-catalyzed 3 + 2 cycloaddition of azomethine imine 7 to methyl propiolate ( 8 ) clearly revealed 6 { 1 ; 4 ; 1 } as the outstanding library member performing comparably to the known Cu-catalytic systems. , This makes the Cu-complexes 6 suitable candidates for catalysts in CuAIAC reaction. In conclusion, a highly modular synthetic method for the preparation of acacen-type ligands was developed enabling an easy access to libraries of diamine-based bis-enaminones.…”

Comparison of different density functional theory methods for the calculation of vibrational circular dichroism spectra

“…Subsequent confinement of the conformer ensemble based on the relative energy might be useful. The Opatz group has particularly good experience with the hybrid density functionals B3LYP 22,76-78 and B3PW91 71,72,74,76,88,89 combined with the Pople basis set 6-311G(d,p) 79,80,86,87 and the IEFPCM 46,60,61 solvation model in the determination of the AC of natural products (e.g., dioxolanones, 115 hymenosetin, 116 caripyrin, 117 and oxalicumone C 118 ), pesticides (imazalil), 119 synthetic cannabinoids (MDMB-CHMCZCA), 120 and synthetic products (e.g., 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazoles, 121 an oxazinone derivative, 122 and cyclopenta[b] benzofurans 123 ).…”