Catalysis is used in over 90% industrial processes, facilitating the production of materials for various applications and products for everyday life. Despite the wide scope and utility of the palladium-catalyzed reactions, economically and environmentally these processes are unsustainable as they require large amounts of the metals and other additives, and have to be conducted in harmful organic solvents and in a complete absence of water and air. In this context, we have developed a novel type of water soluble and thermally stable palladium complex with bidentate pyridyl-1,2,3-triazol-5-ylidene ligand. The complex has been identified as a highly efficient (pre)catalyst for the Sonogashira cross-coupling that enables C–C bond formation between aryl bromides and terminal acetylenes. This reaction now proceeds in air and in pure water, and in complete absence of amine, copper, phosphine and other additives. To prove the concept, we used the above pre-catalyst for the preparation of a key intermediate in industrial synthesis of Altinicline, a potential drug for neurodegenerative diseases. This is the first report on the Sonogashira catalysis with a cationic Pd-complex. Preliminary mechanistic investigation indicates that the catalysis with this compound proceeds by unprecedented mechanism via two connected palladium catalytic cycles. Featured on the Outside Cover.
COBISS.SI-ID: 1536664003
Mitsunobu reaction is one of the fundamental transformations for an inversion of a configuration at optically active alcohols in pharmaceutical industrial processes. Despite this, the process still suffers from high cost and environmental issues, generating large amount of wastes. The key step to the economically and ecologically sustainable process is thus a catalytic Mitsunobu reaction. In this direction, we have developed a catalytic Mitsunobu reaction, which is based on the application of arylazocarboxylates. In comparison to the classical diethyl azodicarboxylate, arylazocarboxylates are recyclable by aerobic re-oxidation of resulted hydrazines with air oxygen in the presence of cheap and nontoxic iron phthalocyanine catalyst [Fe(Pc)]. This outstanding ability enables green catalytic reactions with inversion of configuration and beyond – transformations of alcohols into a variety of other functional groups.
COBISS.SI-ID: 1536871619
Recently reported “fully catalytic Mitsunobu reaction” using catalytic amounts of a phosphine reagent and an azo reagent (Buonomo and Aldrich, Angew. Chem., Int. Ed., 2015, 54, 13041) has been subjected to discussion in chemical community. Based on our thorough reinvestigation of the process of Buonomo and Aldrich, as well as our expertise in the field (Hirose, Gazvoda, Košmrlj, Taniguchi, Chem. Sci. 2016, 7, 5148–5159; c.f. 4.2.), we have demonstrated that the fully catalytic Mitsunobu reaction has, unfortunately, not been realized yet. Unfortunately, the system catalytic in the phosphine reagent is incompatible with that in the azo reagent. This article was listed among the journal's top "20 most read articles in July and the second most read in August 2016".
COBISS.SI-ID: 1537051075
We have developed the first transformation of chiral β-amino acids into the corresponding β’-hydroxy-β-amino acid derivatives. The method utilizes principles of Evans aldol reaction and enables an independent synthesis of both the α,β-syn and the α,β-anti isomers separately, in stereochemically pure form and in excellent yields. The methodology is mild and robust, readily affording β’-hydroxy-β-amino acid derivatives that were previously inaccessible. This scaffold is of prime importance in the chemistry of β-amino acids, the corresponding peptides, β-aminolactones, and β-lactams. In the context of β-lactams a unified access to β′-hydroxy-β-amino acid derivatives is increasingly important for SAR studies in a search for new lead antibiotics, superior to thienamycin and other potent carbapenams, carbapenems, and carbacephems. The article was highlighted on HighBeam Research portal (https://www.highbeam.com/doc/1G1-408000548.html). This methodology is being used for a stereocontrolled, more than 20-step synthesis of some β-lactams that are of interest of pharmaceutical company Sandoz Austria.
COBISS.SI-ID: 1536171203
A simple and efficient method for the synthesis of solutions of high-purity hydrogen trioxide (HOOOH), released in the low-temperature methyltrioxorhenium(VII)-catalyzed transformation of the ozonized polystyrene-supported dimethylphenylsilane, is reported. High-purity hydrogen trioxide solutions in diethyl ether, separated from the polymer, and free of any reactants and by-products, can be stored at ‒20 degree Celsius for weeks. By removing the solvent in vacuo, HOOOH could be isolated in a highly pure form or transferred to other solvents, thus significantly extending the research perspectives of HOOOH for novel applications. The article was selected as a “Hot Paper” and featured on the outside cover of the printed journal Angewandte Chemie, 2015, Vol. 54(34). This work was selected among 10 most important research achievements of the University of Ljubljana in year 2015.
COBISS.SI-ID: 1536385475