Spectroscopic, Structural, and Computational Characterization of Three Bispidinone Derivatives, as Ligands for Enantioselective Metal Catalyzed Reactions

Abstract

Three chiral derivatives of the alkaloid sparteine (bispidines), characterized by the 3,7-diazabicyclo[3.3.1]nonane moiety, were designed as efficient ligands in a number of enantioselective reactions due to their metal coordination properties. A full evaluation of the 3D properties of the compounds was carried out, as the geometrical features of the bicyclic framework are strictly related to the efficiency of the ligands in the asymmetric catalysis. The selected molecules have different molecular complexity for investigating the effects of different chiral groups on the bicycle conformation. We report here a thorough analysis of their molecular arrangement, by NMR spectroscopy, single crystal X-ray crystallography, and computational techniques, which put in evidence their conformational preferences and the parameters needed for the design of more efficient ligands in asymmetric synthetic routes. The results confirmed the high molecular flexibility of the compounds, and indicated how to achieve a control of the chair-chair/boat-chair conformational ratio, by adjusting the relative size of the substituents on the piperidine nitrogens.

Application of chiral bi- and tetra-dentate bispidine-derived ligands in the copper(ii)-catalyzed asymmetric Henry reaction

“…Ligands 1a-b and 4b had been previously investigated by our group. 10 In particular, single crystal X-ray structures of 1b and 4b were determined (Scheme 1), providing useful information on the spatial arrangement of the chiral N-naphthylethyl (1b) and N-phenylethyl residues (4b) with respect to the bispidine core, which influenced the chiral space around the metal-chelating center.…”

“…Compounds 1a,b, 6c 2a, 6e 4a,b 10 were prepared according to literature procedures. 8, 138.4, 137.6, 128.8, 128.6, 126.5, 125.9, 61.5, 60.5, 60.4, 55.1, 53.4, 47.4, 47.0, 45.1, 29.8, 22.3, 21.7.…”

“…Following our recent interest in the conformational behavior of chiral bispidines, 10 we decided to investigate new potential applications of chiral bispidines in the nitroaldol additions in order to explore the enantioselection in connection with the ligand asymmetry.…”

Synthesis and characterization of a tetradentate bispidine-based ligand and its zinc(II) complex

“…3,7-Diazabicyclo [3.3.1]nonanes, commonly known as bispidines, are heterocyclic compounds comprised by two condensed piperidine cores [1], existing in any of the three conformations showed in Figure 1 [2]. The chair-chair (cc) conformation, with a slight ring flattening, is generally favored [3], both in solution and in the solid state, as confirmed by X-ray studies on previous derivatives [4][5][6]. Bispidines have basic properties and, despite being diamines, they titrate as monoamines because the proton is coordinated to both the nitrogen atoms through an intramolecular hydrogen bond that leads them to carry a partial positive charge [7].…”

Strategies for tuning the catalytic activity of zinc complexes in the solvent-free coupling reaction of CO2 and cyclohexene oxide

“…4-(tert-butylphenyl)-2,2′:6′,2″-terpyridine [42], (1R,5S)-3-methyl-7-((S)-1-phenylethyl)-3,7diazabicyclo[3.3.1]nonan-9-one [43], and bis-triphenylphosphine-iminum azide ([PPN]N3) [44] were prepared according to the literature, whereas 2,9-dimesityl-1,10-phenanthroline [45] was prepared as Zn(CH 3 CO 2 ) 2 •2H 2 O in refluxing ethanol, as reported [46]. All the other zinc(II) complexes were prepared by reaction of the chelating ligand with an equivalent of the Zn salt in dichloromethane at room temperature (1,10-phenanthroline ligands [47]) or in methanol under reflux (terpyridine [48]), as described below.…”