Metal-Free Photoredox Phosphonation of C–N and C–X Bonds in Aqueous Solvent Mixtures

Aryl phosphonate esters are valuable moieties for the pharmaceutical and agrochemical industries. Accessing such compounds from affordable and abundant phosphite reagents and a wide range of aromatic building blocks under metal-free, visible light-induced reaction conditions would represent a desirable technology. Herein, we present an efficient and mild methodology for the synthesis of aromatic phosphonate esters in good to excellent yields using DBU and phenothiazine as a photoredox catalyst. The reaction exhibits wide functional group compatibility enabling the transformation in presence of ketone, amide, ester, amine, and alcohol moieties. Importantly, the reaction proceeds using a green solvent mixture primarily composed of water, thus lowering the environmental footprint of this transformation compared to current methods.

A Sustainable Improvement of ω-Bromoalkylphosphonates Synthesis to Access Novel KuQuinones

Owing to the attractiveness of organic phosphonic acids and esters in the pharmacological field and in the functionalization of conductive metal-oxides, the research of effective synthetic protocols is pivotal. Among the others, ω-bromoalkylphosphonates are gaining particular attention because they are useful building blocks for the tailored functionalization of complex organic molecules. Hence, in this work, the optimization of Michaelis–Arbuzov reaction conditions for ω-bromoalkylphosphonates has been performed, to improve process sustainability while maintaining good yields. Synthesized ω-bromoalkylphosphonates have been successfully adopted for the synthesis of new KuQuinone phosphonate esters and, by hydrolysis, phosphonic acid KuQuinone derivatives have been obtained for the first time. Considering the high affinity with metal-oxides, KuQuinones bearing phosphonic acid terminal groups are promising candidates for biomedical and photo(electro)chemical applications.

Synthesis and Characterization of Amphiphilic Arenephosphonates as Water-Soluble Micellular Radioluminescent Probes

<div>Abstract</div><div>This work describes the synthesis and characterization of a series of arenephosphonic acid salts for use as water soluble down-converters in optogenetic assays.</div><div>Two phosphonate salts based on anthracene and naphthalene were synthesized through</div><div>cleavage of phosphonate esters. A third amphiphilic salt, developed from a long-alkylchain modified naphthalene, was produced in the same manner to demonstrate micelle</div><div>formation. Two techniques were used to determine if any of the salts showed micelle</div><div>behavior: 31P NMR and fluorescence spectroscopy. Interestingly, all three compounds</div><div>exhibited micelle formation in water. UV-induced fluorescence of NapPONa and</div><div>AntPONa revealed a secondary emission profile with maximum excitation wavelengths</div><div>that lie on top of the primary emission profile. This secondary emission can be attributed</div><div>to the emission of the micellular structure based on solid-state fluorescence experiments.</div><div>Moderate x-ray induced radioluminescence was observed in the solid forms of each</div><div>compound. A solution of amphiphilic NapPONa demonstrated both concentrationdependent and micelle-dependent radioluminescence, indicating the positioning of</div><div>aromatic rings in a micelle is inducive to a radioluminescent response. Furthermore, the</div><div>emission wavelength of this compounds lies on top of the excitation wavelength of</div><div>channelrhodopsin-2, a well-studied optogenetic target.</div>

Synthesis and Characterization of Amphiphilic Arenephosphonates as Water-Soluble Micellular Radioluminescent Probes

<div>Abstract</div><div>This work describes the synthesis and characterization of a series of arenephosphonic acid salts for use as water soluble down-converters in optogenetic assays.</div><div>Two phosphonate salts based on anthracene and naphthalene were synthesized through</div><div>cleavage of phosphonate esters. A third amphiphilic salt, developed from a long-alkylchain modified naphthalene, was produced in the same manner to demonstrate micelle</div><div>formation. Two techniques were used to determine if any of the salts showed micelle</div><div>behavior: 31P NMR and fluorescence spectroscopy. Interestingly, all three compounds</div><div>exhibited micelle formation in water. UV-induced fluorescence of NapPONa and</div><div>AntPONa revealed a secondary emission profile with maximum excitation wavelengths</div><div>that lie on top of the primary emission profile. This secondary emission can be attributed</div><div>to the emission of the micellular structure based on solid-state fluorescence experiments.</div><div>Moderate x-ray induced radioluminescence was observed in the solid forms of each</div><div>compound. A solution of amphiphilic NapPONa demonstrated both concentrationdependent and micelle-dependent radioluminescence, indicating the positioning of</div><div>aromatic rings in a micelle is inducive to a radioluminescent response. Furthermore, the</div><div>emission wavelength of this compounds lies on top of the excitation wavelength of</div><div>channelrhodopsin-2, a well-studied optogenetic target.</div>

The McKenna reaction – avoiding side reactions in phosphonate deprotection

The McKenna reaction is a well-known and popular method for the efficient and mild synthesis of organophosphorus acids. Bromotrimethylsilane (BTMS) is the main reagent in this reaction, which transforms dialkyl phosphonate esters into bis(trimethylsilyl)esters, which are then easily converted into the target acids. However, the versatile character of the McKenna reaction is not always used to its full extent, due to formation of side products. Herein, demonstrated by using model examples we have not only analyzed the typical side processes accompanying the McKenna reaction, but also uncovered new ones. Further, we discovered that some commonly recommended precautions did not always circumvent the side reactions. The proposed results and recommendations may facilitate the synthesis of phosphonic acids.

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

The incorporation of basic substituents into the structurally conserved domains of cell wall lipopolysaccharides has been identified as a major mechanism contributing to antimicrobial resistance of Gram-negative pathogenic bacteria. Inhibition of the corresponding enzymatic steps, specifically the transfer of 4-amino-4-deoxy-ʟ-arabinose, would thus restore the activity of cationic antimicrobial peptides and several antimicrobial drugs. C-glycosidically-linked phospholipid derivatives of 4-amino-4-deoxy-ʟ-arabinose have been prepared as hydrolytically stable and chain-shortened analogues of the native undecaprenyl donor. The C-phosphonate unit was installed via a Wittig reaction of benzyl-protected 1,5-arabinonic acid lactone with the lithium salt of dimethyl methylphosphonate followed by an elimination step of the resulting hemiketal, leading to the corresponding exo- and endo-glycal derivatives. The ensuing selective monodemethylation and hydrogenolysis of the benzyl groups and reduction of the 4-azido group gave the α-ʟ-anomeric arabino- and ribo-configured methyl phosphonate esters. In addition, the monomethyl phosphonate glycal intermediates were converted into n-octyl derivatives followed by subsequent selective removal of the methyl phosphonate ester group and hydrogenation to give the octylphosphono derivatives. These intermediates will be of value for their future conversion into transition state analogues as well as for the introduction of various lipid extensions at the anomeric phosphonate moiety.