A new method for the synthesis of 3-oxoisoindolin-1-ylphosphine oxides bearing same or different substituents on the phosphorus atom is described. The one-pot three-component reaction of 2-formylbenzoic acid, primary amines and achiral or P-stereogenic secondary phosphine oxides provided the target compounds under catalyst-free, mild conditions and for short reaction times. The deoxygenation of a 3-oxoisoindolin-1-ylphosphine oxide was also studied, and the phosphine obtained could be converted to a sulphide and to a platinum complex. The crystal structures of a selected phosphine oxide and the corresponding platinum species were investigated by X-ray diffraction analysis. The biological activity, such as in vitro cytotoxicity on different cell lines and antibacterial activity of the 3-oxoisoindolin-1-ylphosphine oxides was also investigated. Based on the IC₅₀ values obtained, several derivatives showed moderate activity against the HL-60 cell line and two compounds containing 3,5-dimethylphenyl groups on the phosphorus atom showed promising activity against Bacillus subtilis bacteria.

Several dialkyl‐arylphosphine oxides were prepared, and the enantioseparation of the corresponding racemates was elaborated with host–guest complexation using TADDOL‐derivatives. The crystallization conditions were optimized and two separate crystallization methods, one in organic solvent, and the other in water, were found to yield five examples of phosphine oxides with enantiomeric excess values higher than 94 %. A gram scale resolution was performed, and both enantiomers of the methyl‐phenyl‐propyl‐phosphine oxide were separated with (R,R)‐ or (S,S)‐spiro‐TADDOL. The intermolecular interactions responsible for the enantiomeric recognition between the chiral host and guest molecules were investigated by single‐crystal X‐ray diffractional structural determinations. The similarities in the structural patterns of a few diastereomeric crystals were checked by powder X‐ray diffraction, as well. Organic solvent nanofiltration (OSN) was used as a scalable technique for the decomposition of the corresponding phosphine oxide–spiro‐TADDOL molecular complexes, and for the recovery of the phosphine oxide enantiomers and resolving agents.

An enantioseparation method for the preparation of P-stereogenic H -phosphinates was elaborated. In stereoselective reactions, various chiral P-stereogenic compounds were prepared and their applications as chiral NMR solvating agents were assessed.

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.

A focused library of 1-adamantyl arylthiophosphonates was prepared in racemic form. An enantioseparation method was developed for P-stereogenic thiophosphonates using (S)-1-phenylethylamine as the resolving agent. Under optimized conditions, three out of the five arylthiophosphonates were prepared in enantiopure form (ee > 99%). The subsequent desulfurization of optically active arylthiophosphonates gave the corresponding H-phosphinates without significant erosion of enantiomeric purity (ee = 95–98%). Hence, this reaction sequence can be considered an alternative method for the preparation of 1-adamantyl aryl-H-phopshinates. The absolute configuration of the (S)-1-adamantyl phenylphosphonothioic acid was assigned using single-crystal XRD and it allowed the confirmation that the removal of the P = S group proceeds with retention of configuration. The organocatalytic applicability of (S)-1-adamantyl phenylphosphonothioic acid was also evaluated as a P-stereogenic Brønsted acid.

The resolution methods previously developed for the enantioseparation of heterocyclic phosphine oxides were extended to dialkyl-aryl-, diaryl-alkyl- and triarylphosphine oxides. The resolution of the phosphine oxides were elaborated with TADDOL-derivatives or with the acidic Ca²⁺-salts of the (R,R)-O,O’-dibenzoyl- and (R,R)-O,O’-di-p-toluoyl-tartaric acid. The main parameters influencing the efficiency of the resolution procedures were also optimized. Moreover, a correlation was found between the efficiency of the resolution and molecular structure. In a few instances, the purification and the racemization possibilities of the enantiomeric mixtures were also investigated. Graphical Abstract