DePhI

Despite the prominence of phosphorus chemistry in modern science, phosphiranes and phosphiranium salts remain elusive species although these strained rings constitute appealing units with high potential for direct incorporation as phosphino ethylene units in molecules. Unlike their aziridinium analogues, which are transiently generated as synthetic intermediates of reasonable stability and always undergo selective nucleophilic ring-openings on carbons, phosphiraniums were shown in a very few number of seminal studies to be more unstable and prone to P-selective attacks by nucleophiles. The DePhI project aims at designing and revealing the chemistry of and phosphiranium salts in full, by interfacing in depth physical organic chemistry investigations with the development of a variety of completely new transformations, covering developments of reliable methods for phosphiraniums synthesis as well as original and very challenging C centered ring-openings or annulations under either polar or catalytic photoredox situations. We do hope to invert the trend to make phosphiranium ions a much more attractive target for both academia and industry. In a preliminary phase we plan to prepare an extended range of phosphiranium salts which will be used in extensive physicochemical studies and mechanistic investigations. From this crossover experimental/mechanistic approach should emerge new leads of electrophilic phosphiraniums and nucleophiles combinations, which are expected to perform efficiently in the C-selective ring-opening of phosphiraniums, and will thus be tested. A next phase of the project will address diverse and complementary strategies aimed at offering new opportunities in reaction couplings of phosphiraniums, with as three main objectives to solve site-selectivity issues (C- versus P-attack) of certain reactive nucleophiles, to enable reactions of weaker nucleophiles that normally display poor/no reactivity, and also to propose innovative annulation processes. The intermolecular ring-opening processes to be investigated will mostly stage the vectorization of nucleophiles by an organocatalyst or a directing group suitably chosen according to the nucleophile used. Regarding the annulation reactions, a diversity of sequences consisting in phosphirane quaternarization by a selection of 1,n-dipolar reaction partners, followed by subsequent intramolecular ring-opening of the in situ generated phosphiraniums by the nucleophilic fragment of the dipoles, are proposed. In a next phase we will address the potential of phosphiranes and phosphiraniums in photoredox catalysis. First of all and in a view of complementarity with our usual polar approaches,, we propose the original synthesis of phosphiranium ions by photoredox arylative and alkylative quaternarization of phosphiranes. Next, assuming that phosphiraniums hold promise for radical fragmentations, we will look at a variety of crossover radical-polar ring-opening/annulation sequences with diverse unsaturated partners. Interestingly, these reducing quenching photoredox processes should provide a new catalytic, mild access to diverse phosphorus scaffolds in a complementary way to polar methods considered in the preceding tasks. A closing task will be ultimately intended to emphasize both the synthetic and application potential of phosphiranium ions chemistry developped throughout the DePhI project.