Péter Bagi

Green chemical syntheses and applications within organophosphorus chemistry

Application of the microwave (MW) technique offers many advantages in organophosphorus syntheses. Reluctant reactions may take place on MW irradiation. In most cases, MWs make the reactions more efficient in respect of rate, selectivity and yield. The benefits are shown via representative examples. MW irradiation may replace a catalyst, or simplify catalytic systems. The synthesis of catalysts incorporating heterocyclic P-ligands is also discussed. Where it was relevant, structural chemical details were also provided.

Selecting Resolving Agents with Respect to Their Eutectic Compositions.

In order to develop a resolution procedure for a given racemic compound, the first and the most important step is finding the most suitable resolving agent. We studied 18 individual resolutions that were carried out with resolving agents having high eutectic composition. We found that very high enantiomeric excess values were obtained in all cases. We assume that the eutectic composition of a given resolving agent is one of the most important properties that should always be considered during the search for the most efficient resolving agent.

The resolution of acyclic P-stereogenic phosphine oxides via the formation of diastereomeric complexes: A case study on ethyl-(2-methylphenyl)-phenylphosphine oxide

As an example of acyclic P-chiral phosphine oxides, the resolution of ethyl-(2-methylphenyl)-phenylphosphine oxide was elaborated with TADDOL derivatives, or with calcium salts of the tartaric acid derivatives. Besides the study on the resolving agents, several purification methods were developed in order to prepare enantiopure ethyl-(2-methylphenyl)-phenylphosphine oxide. It was found that the title phosphine oxide is a racemic crystal-forming compound, and the recrystallization of the enantiomeric mixtures could be used for the preparation of pure enantiomers. According to our best method, the (R)-ethyl-(2-methylphenyl)-phenylphosphine oxide could be obtained with an enantiomeric excess of 99% and in a yield of 47%. Complete racemization of the enantiomerically enriched phosphine oxide could be accomplished via the formation of a chlorophosphonium salt. Characterization of the crystal structures of the enantiopure phosphine oxide was complemented with that of the diastereomeric intermediate. X-ray analysis revealed the main nonbonding interactions responsible for enantiomeric recognition.

Milestones in microwave-assisted organophosphorus chemistry

GRAPHICAL ABSTRACT ABSTRACT The microwave (MW) technique become an important tool in organophosphorus chemistry. On the one hand, otherwise reluctant reactions, such as the Diels–Alder cycloadditions, inverse Wittig-type reactions, esterification of P-acids, alcoholysis of P-esters, may be promoted on the effect of MW, while on the other hand, catalysts may be omitted, or catalyst systems may be simplified on MW irradiation. This later group includes the Kabachnik–Fields and the Pudovik reactions, deoxygenation, as well as the Hirao- and the Arbuzov reactions.

The pH-dependency of diastereomeric salt resolutions with amphoteric resolving agents

We have analysed the role of pH in the diastereomeric resolution of racemic mandelic acid with (S)-phenylalanine and (R)-3-(aminomethyl)-5-methylhexanoic acid [(R)-Pregabalin] enantiomers. The adjusted pH had an effect on the optical purity and yield of the mandelic acid enantiomeric mixtures isolated from the diastereomeric salts. We showed that the pKa of the carboxyl group of the amphoteric resolving agents should be considered during the pH optimisation of diastereomeric salt resolutions.

Resolution of 5- and 6-Membered P-Heterocycles: Racemic and Optically Active Platinum(II)-3-Phospholene Complexes

Abstract Methods were developed for the resolution of several five- and six-membered phosphorus heterocycles (1c-e, 2, 4). It was investigated if the optical activity is preserved during the 1a→2→3→4 reaction sequence. Racemic and optically active 1b-e 3-phospholene 1-oxides were converted to the corresponding platinum-complexes (10b-e), which are potential catalysts. GRAPHICAL ABSTRACT

Resolution of P-Heterocycles with Tartaric Acid Derivatives

Abstract 3-Phospholene 1-oxides were efficiently resolved by tartaric acid derivatives.

Access to Fluorazones by Intramolecular Dehydrative Cyclization of Aromatic Tertiary Amides: A Synthetic and Mechanistic Study

An efficient synthesis has been developed for the preparation of 9H-pyrrolo[1,2-a]indol-9-ones (fluorazones) from readily available anthranilic acid derivatives via a one-pot amide- and pyrrole-formation step, followed by an intramolecular cyclodehydration. The cyclodehydration process is mediated by the activation of aromatic tertiary amides by triflic anhydride (Tf2O). Comparison of various benzo-substituents is shown to demonstrate the high functional group tolerance of this transformation. In addition, study of the reaction mechanism is also presented to unfold the exact role of the applied base additive. Herein, as a first example, we report our findings that Tf2O-mediated amide activation is obstructed by the easy protonation of amides by the formed triflic acid during the activation step. Additionally, it has been also proven that the base additive is not involved in the transformation of O-triflyliminium triflates into reactive species (e.g., nitrilium triflates) and is only responsible to neutralize the superacid to avoid the protonation of both the secondary or tertiary amides.

An aspect of selecting resolving agents: The role of differences in molecule length in diastereomeric salt resolutions

ABSTRACT In the course of 49 individual experiments of diastereomeric salt resolution we have examined the effect of the difference between the racemic and resolving agent molecule lengths on the resolution. We concluded that using resolving agents with the molecule length differing by 3 to 6 from the racemic molecule produces the best result.

Preparation of P-heterocyclic phosphine boranes and optically active phosphine oxides via phosphonium salts

GRAPHICAL ABSTRACT ABSTRACT The preparation of 3-phospholene boranes and optically active 3-phospholene oxides was elaborated via the corresponding cyclic chloro-phosphonium salt intermediates. The 3-phospholene oxides were reacted with oxalyl chloride to afford the corresponding chloro-phosphonium salts, which were reacted with LiBH4 to afford 3-phospholene boranes. This procedure is a practical one-pot method for the deoxygenation and borane complex formation of 3-phospholene oxides without using silanes. It was shown that 3-chlorophospholenium salts can be reacted with chiral alcohols to give diastereomerically enriched cyclic alkoxy-phospholium salt intermediates, which were converted to enantiomerically enriched 3-phospholene oxides by Arbuzov collapse.