Organophosphates are crucial in various organic transformations, serving as versatile intermediates in synthesizing biologically active compounds. Many of these compounds participate in major physiological processes and have drug discovery and agrochemical applications. In particular, α-ketol phosphates (α-hydroxyketone phosphate esters) synthesized in the presented research can be used as sugar analogs and serve as precursors of oligonucleotides and phospholipids.
The presented research involves the treatment of terminal alkynes with a heterocyclic hypervalent iodine (HVI) reagent, 1H-1-hydroxy-5-methyl-1,2,3-benziodoxathiole 3,3-dioxide (HMBI, 1) in the presence of a buffered mixture of diphenylphosphate. The reduced byproduct of HMBI is readily removed from the reaction mixture by simple liquid-liquid extraction and can be reoxidized for reuse. The application of HMBI over conventional HVI reagents is advantageous for two reasons: first, to avoid contamination of potentially pharmacologically interesting compounds with halogenated organics, and second, to streamline work-up procedures for potential combinatorial studies or lab-on-chip techniques. Furthermore, the ability to recycle reagents based on iodine is attractive from a sustainability viewpoint.
In a typical experiment, HMBI is added to an excess of a terminal alkyne in the presence of a buffered mixture of diphenylphosphate and its lithium salt in acetonitrile solvent at 60 ^oC. Aqueous work-up and concentration of the organic phase affords the α-ketol diphenylphosphates, 2, in reasonable purity in moderate yields (29-61%). Various aliphatic and aromatic terminal alkynes were studied.

Benjamin Greissinger

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