Phosphorylation of alcohols is a fundamentally important reaction in both life science and physical science. Product phosphate monoesters play key roles in living organisms, natural products, pharmaceuticals, and organic materials. Most of the chemical methods to date for synthesizing phosphate monoesters, however, require multistep sequences or are limited to specific types of substrates possibly due to harsh conditions. An alternative way to enable the simple production of phosphate monoesters from highly functionalized precursor alcohols is, thus, highly desired. We report herein a catalytic phosphorylation of alcohols with high functional group tolerance using tetrabutylammonium hydrogen sulfate (TBAHS) and phosphoenolpyruvic acid monopotassium salt (PEP-K) as the catalyst and phosphoryl donor, respectively. This method enables the direct introduction of a nonprotected phosphate group to the hydroxy group of a diverse menu of alcohol substrates, including functionalized small molecules, carbohydrates, and unprotected peptides. Nuclear magnetic resonance, mass spectrometric, and density functional theory analyses suggest that an unprecedented mixed anhydride species, generated from PEP-K and TBAHS, acts as an active phosphoryl donor in this reaction. This operationally simple and chemoselective catalytic phosphorylation allows for the efficient production of densely functionalized O-phosphorylated compounds, which are useful in diverse fields including biology and medicine.

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Phosphodiesters are important structural motifs observed in a diverse field of molecular science. It is, thus, important to develop a simple and robust way to synthesize them from corresponding alcohols. Here we report a single-step asymmetric phosphodiester synthesis from alcohols with phosphoenolpyruvate phosphodiesters as phosphoryl donors. This transformation allows for the use of various functionalized alcohols as substrates, and would be useful for diverse fields including biology and medicine.

Lithium naphthalene reacts with acetic acid to give ex -anion of lithium acetate. The reaction of this anion with various ketones gives the corresponding l3-hydroxy-acids in good yield.

Aus Cyclohexanon (I) und Essigsäure (II) wird in Gegenwart von Lithium/Naphthalin in hoher Ausbeute 1‐Hydroxy‐1‐cyclohexyl‐essigsäure (III) erhalten.