From masked carbenes to heterocycles: Novel potentially biological active difluoromethylene phosphonates as versatile building blocks

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This innovative project is aimed at elaborating methods to synthesize for the first time a variety of (2-diazo-1,1-difluoroethyl)phosphonates as valuable building blocks and their further application as reactive intermediates in the preparation of more complex molecules bearing at least one difluoromethylene phosphonate unit which could impart bioactivity onto the selected substrates. By varying the structure of the starting diazo compounds, their stability, reactivity and selectivity will be then verified. In some cases, asymmetric synthesis will be performed either via exploitation of enantiopure substrates or by addition of appropriate chiral catalysts. The following research tasks are planned, namely (1) the synthesis of (beta-diazo-alpha,alpha-difluoroethyl)phosphonates starting from the corresponding beta-ketophosphonates, (2) the synthesis of various fluorinated amino-, hydroxyl and thiohydroxyphosphonates via catalytic NH, SH and OH insertion reactions on carbenoid centres, (3) intermolecular cyclopropanation of selected alkenes and alkynes with (2-diazo-1,1-difluoroethyl)phosphonates, (4) intermolecular aromatic cycloadditions and substitutions, (5) ylide formation and subsequent cycloaddition or rearrangements reactions, (6) the synthesis of 5-membered heterocycles via [3+2] cycloaddition.