Resolution of P-Sterogenic 1-Phenylphosphin-2-en-4-one 1-Oxide into Two Enantiomers by (R,R)-TADDOL and Conformational Diversity of the Phosphinenone Ring and TADDOL in the Crystal State

The resolution of racemic 1-phenylphosphin-2-en-4-one 1-oxide (2), was achieved through the fractional crystallization of its diastereomeric complexes with (4R,5R)-(−)-2,2-dimethyl -α,α,α′,α′-tetraphenyl-dioxolan-4,5-dimethanol (R,R-TADDOL) followed by the liberation of the individual enantiomers of 2 by flash chromatography on silica gel columns. The resolution process furnished the two enantiomers of 2 of 99.1 and 99.9% e.e. at isolated yields of 62 and 59% (counted for the single enantiomer), respectively. The absolute configurations of the two enantiomers were established by means of X-ray crystallography of their diastereomerically pure complexes, i.e., (R)-2•R,R)-TADDOL and (S)-2•(R,R)-TADDOL. The structural analysis revealed that in the (R)-2•(R,R)-TADDOL complex, the P-phenyl substituent occupied a pseudoequatorial position, whereas in (S)-2•(R,R)-TADDOL, it appeared in both the pseudoequatorial and the pseudoaxial positions in four symmetrically independent molecules. Concurrent conformational changes of the TADDOL molecules were best described by the observed changes of a pseudo-torsional CO...OC angle that could be considered as a possible measure of TADDOL conformation in its receptor–ligand complexes. The structural analysis of the (R,R)-TADDOL molecule revealed that efficiency of this compound for use as an effective resolving factor comes from its ability to flexibly fit its structure to both enantiomers of a ligand molecule, producing a rare case of resolution for both pure enantiomers with one chiral separating agent. The resolved (R)-2 was used to assign the absolute configuration of a recently described (−)-1-phenylphosphin-2-en-4-one 1-sulfide by chemical correlation. In addition, an attempted stereoretentive reduction of (R)-2 by PhSiH3 at 60 °C revealed an unexpectedly low barrier for P-inversion in 1-phenylphosphin-2-en-4-one.

SEPARAÇÃO ENANTIOSSELETIVA DA OXIBUTININA: UMA INVESTIGAÇÃO TEÓRICA E EXPERIMENTAL

ENANTIOSELECTIVE SEPARATION OF OXYBUTYNIN: A THEORETICAL AND EXPERIMENTAL INVESTIGATION. In this work, we have studied both experimentally and theoretically the oxybutynin chiral discrimination. According to the main results, the enantioseparation of oxybutynin was efficiently achieved by high performance liquid chromatography in normal phase using the Chiralpak® AD column, which has amylose tris (3,5‐dimethylphenylcarbamate) as a chiral selector. The energetic and structural parameters obtained via density functional theory calculations pointed out the chiral discrimination as well as the enantiomeric elution order of oxybutynin, thus explaining, at molecular level, the experimental data. Finally, the strength of the hydrogen bonds played a key role in the discrimination between the oxybutynin diastereomeric complexes formed.

Crystal structures of [μ2-(Ra ,Sa ,3aR,7aR)-1,3-bis(2,7-dicyclohexylnaphthalen-1-yl)octahydro-1H-benzo[d]imidazolidin-2-ylidene]chlorido(η4-1,5-cyclooctadiene)iridium dichloromethane monosolvate and [μ2-(Sa ,Sa ,3aR,7aR)-1,3-bis(2,7-dicyclohexylnaphthalen-1-yl)octahydro-1H-benzo[d]imidazolidin-2-ylidene]chlorido(η4-1,5-cyclooctadiene)iridium

The title compounds, [Ir(C51H64N2)Cl(C8H12)]·CH2Cl2, (I), and [Ir(C51H64N2)Cl(C8H12)], (II), represent the first two examples of hexahydrobenzoimidazole-based N-heterocyclic carbene (NHC) iridium complexes. The diastereomeric complexes differing only in their axial chirality, which could be separated via column chromatography, show noticeable differences in their 1H NMR spectra. Compound (I) crystallizes in the monoclinic system (P21) with two independent complexes and two half-occupied dichloromethane molecules in the asymmetric unit, while compound (II) crystallizes in the orthorhombic system (P212121) with one complex in the asymmetric unit. The fused five-membered N-heterocycles of NHCs show unusually high backbone torsion angles of −34.1 (5) and −30.9 (5)° for (I) and −31.5 (7)° for (II), but the Ir—Ccarbene bond lengths of 2.046 (6) and 2.021 (6) Å for (I) and 2.045 (8) Å for (II) present typical NHC—Ir bond lengths. The solvent molecule in the crystal of (I) was found to be highly disordered and its contribution to the scattering was masked using the solvent-masking routine smtbx.mask in OLEX2 [Dolomanov et al. (2009). J. Appl. Cryst. 42, 339–341]. The solvent contribution is not included in the reported chemical formula and other crystal data.

Preparation of Enantiomerically Enriched P-Stereogenic Dialkyl-Arylphosphine Oxides via Coordination Mediated Optical Resolution

Optical resolution of several dialkyl-arylphosphine oxides was elaborated using the Ca2+ salt of (−)-O,O’-dibenzoyl-(2R,3R)-tartaric acid as the resolving agent. The conditions of crystallization and purification of the enantiomerically enriched phosphine oxides were optimized. Ethyl-phenyl-propylphosphine oxide and butyl-methyl-phenylphosphine oxide were prepared with an enantiomeric excess higher than 93%, whereas, three other dialkyl-arylphosphine oxides were obtained with an enantiomeric excess of 37–85%. It was also found that the sterically demanding alkyl chains hinder the formation of stable diastereomeric complexes, which consequently led to less efficient resolution procedures.

Solvent-triggered stereoselectivity of α,α-cyclopropanation of amino acids in the Ni(ii) chiral coordination environment

Unexpected solvent-controlled increase in stereoselectivity of glycine cyclopropanation within chiral Ni(ii) coordination environment was observed and rationalized. Cyclopropanated diastereomeric complexes exhibit stereodependent redox-activity.

Probing the chirality of oxidovanadium(v) centers in complexes with tridentate sugar Schiff-base ligands: solid-state and solution behavior

Configurations of oxidovanadium centers in diastereomeric complexes with chiral sugar ligands are assigned and in the solid state triggered by the coordination number at the vanadium center through the steric requirements of the chelate ligand.