Jean-Noël Volle

The development of new green methodologies and their broader adoption for promoting sustainable development in chemistry laboratories and industry play a significant role in society, due to the economic importance of chemistry and its and widespread presence in everyday life. Therefore, a sustainable approach to chemistry contributes to the well-being of worldwide population and comply with the United Nations Sustainable Development Goals (UN SDGs) and the European Green Deal. The review highlights how mechanochemical methods in batch and in continuous are an eco-friendly approach for organic synthesis, with a lower environmental footprint in most cases, compared to solution-based procedures. The assessment is objectively based on the use of green metrics (e.g. atom and real atom economy, E-factor, Process Mass Intensity, Material Parameter Recovery, Eco-scale, Stoichiometric Factor, etc.) and indicators (e.g. DOZN tool and Life Cycle Assessment, LCA, studies) applied to organic transformations such as synthesis of amide bond, carbamates, heterocycles, Active Pharmaceutical Ingredients (APIs), porphyrins, Porous Organic Polymers (POPs), metal- or acid-catalysed processes, multicomponent and condensation reactions, rearrangements, etc. The generalized absence of bulk solvents, the precise control over the stoichiometry (i.e., using agents in a stoichiometrically rather than in excess), and the more selective reactions enabling simplified work-up procedures are the distinctive factors marking the superiority of mechanochemical processes over solution-based chemistry.

Due to their biological activity and structural analogy to corresponding α-amino acids, α-aminophosphonates and their fluorinated derivatives provide an important source for drug discovery. Therefore convenient access to this class of compounds is still desirable. Four series of novel phosphonate analogues of fluorinated phenylalanine containing variable number of fluorine atoms in different positions of the phenyl ring were synthesized and subjected to solid state characterization by single-crystal X-ray diffraction analysis, and to studies with the use of NMR, HRMS and DFT methods. Such an approach provided valuable information in regard to preferable conformation, hydrogen bonds and also weak intermolecular interactions present in the crystals investigated. As analogues of naturally occurring compounds, the obtained α-aminophosphonates have a big potential for biological activity. Formation of some indolinylphosphonates as minor products arisen from intramolecular S_NAr reactions show that aminophosphonates exhibiting an electronically depleted aromatic group, and possessing a fluorine atom in ortho position of the phosphonoalkyl substituent may give an entrance to further derivatives that may exhibit entirely new properties.

Several novel phosphono-perfluorophenylalanine derivatives, as mimetics of phenylalanine, were synthesized by subjecting diethyl (2-(perfluorophenyl)-1-(phenylamino)ethyl)-phosphonate to S_NAr reactions with thiols, amines and phenols.

Two chiral C₂‐symmetric diphenylphosphine dioxides bearing an original bis(triazolyl) backbone were prepared starting from inexpensive and readily available precursors. The key step involves the simultaneous formation of five bonds in one chemical step with 100 % atom efficiency through a copper‐catalyzed tandem [3+2] cycloaddition/dimerization reaction. Interestingly, these chiral inducers exhibited good to excellent catalytic activities as chiral Lewis base organocatalysts to promote useful stereoselective reactions.

The synthesis of pseudodisaccharides based on an oxaphosphinane heterocycle is described. Disaccharide mimetics 5 and 6 were readily obtained through glycosylation of a hydroxy group with appropriately protected furanosyl or pyranosyl carbohydrates using a trichloroacetamidate coupling strategy. Selective or complete deprotection then produced the chiral pseudodisaccharides in good yields.

In drug discovery, structural modifications over the lead molecule are often crucial for the development of a drug. Herein, we reported the first in vivo bioisosteric effect of phosphinolactone function in relation to the lactol group constituting the bioactive molecule: Hydroxybupropion. The preparation of phosphinolactone analogues and their antidepressant evaluation towards forced swimming test in mice showed that biological activity was regained and even strengthen.