Stereochemistry of Internucleotide Bond Formation by theH-Phosphonate Method. 5. The Role of Brønsted and H-Bonding Base Catalysis in RibonucleosideH-Phosphonate Condensation—Chemical and Stereochemical Consequences

Abstract

Efficiency and stereoselectivity of condensations of ribonucleoside 3'-H-phosphonates with ethanol promoted by pivaloyl chloride were investigated as a function of tertiary amines used. Side reactions leading to an increased demand for the condensing agent were identified as derived from an attack of the pivalate anion at carbonyl centers of reactive pivaloyl derivatives. The conditions that secured quantitative yields of H-phosphonate diester condensations were assessed. Several tertiary amines promoted condensations with stereoselectivity higher than that observed for pyridine derivatives. A correlation between diastereoselectivity of the product formation and Brønsted and H-bonding basicities of the amine used was found.

An acidic pH independent piperazine–TPE AIEgen as a unique bioprobe for lysosome tracing

“…Given the lysosomes’ acidic milieu, in lysosomes PIP–TPE will exist for the most part in its protonated form. Based on the p K a values of the structurally very similar dimethylpiperazine (p K a = 8.3) and diethylamine (p K a = 6.6) in water reported elsewhere, 48 it appears reasonable to assume that the peripheral tertiary nitrogen atom(s) of the piperazine moiety(ies) would be charge carriers in such a protonated species. Further experiments with PIP–TPE and concentrated aqueous HCl allowed the isolation and identification (NMR and MALDI-ToF) of the protonation product of PIP–TPE as its mono hydrochloride, PIP–TPE·HCl.…”

Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control

“…Furthermore, the amine reductant would be protonated, preventing it from serving as the reductant. We probed this possibility by use of N -ethyl morpholine as the amine reductant, which is estimated to be nearly 3–4 p K a units less basic (MeCN) than DIPEA, as the reductant . While the photo-HDF reaction of 6f still failed, the reaction of 6g took place smoothly, giving 6g′ in 75% yield.…”

“…We probed this possibility by use of Nethyl morpholine as the amine reductant, which is estimated to be nearly 3−4 pK a units less basic (MeCN) than DIPEA, as the reductant. 34 While the photo-HDF reaction of 6f still failed, the reaction of 6g took place smoothly, giving 6g′ in 75% yield. This result indicates that deprotonation of the directing group is one resolvable issue that can arise in the photo-HDF reaction.…”

Preparative Synthesis of an RP-Guanosine-3′,5′-Cyclic Phosphorothioate Analogue, a Drug Candidate for the Treatment of Retinal Degenerations

“…To preserve the desired kinetic product, 2,6-lutidine was explored, as it has been shown to reduce the rate of epimerization in comparison to pyridine . When performing the reaction in DCM with 5 equiv of 2,6-lutidine, our NMR experiments showed the cyclic H -phosphonate diastereomers in an initial 19:1 S P / R P ratio and 13:1 at 30 min…”