Recent Advances in H-Phosphonate Chemistry. Part 1. H-Phosphonate Esters: Synthesis and Basic Reactions

Abstract

This review covers recent progress in the preparation of H-phosphonate mono- and diesters, basic studies on mechanistic and stereochemical aspects of this class of phosphorus compounds, and their fundamental chemistry in terms of transformation of P-H bonds into P-heteroatom bonds. Selected recent applications of H-phosphonate derivatives in basic organic phosphorus chemistry and in the synthesis of biologically important phosphorus compounds are also discussed.

H-Phosphonate Chemistry in the Synthesis of Electrically Neutral and Charged Antiviral and Anticancer Pronucleotides

“…Successful realization of this strategy depends on synthetic access to the appropriate nucleoside H-phosphonates and the knowledge of their reactivity. Recently, the chemistry of Hphosphonates, including that of nucleoside H-phosphonates, was a subject of several comprehensive reviews from our laboratories (Stawinski, 1992a;Stawinski and Stromberg, 1993;Stawinski and Kraszewski, 2002a,b;Stawinski, 2003, 2007;Sobkowski et al, 2015). Herein we recall the most convenient methods for the synthesis of H-phosphonate mono-and diesters, and present in detail those most synthetically useful in the preparation of pronucleotides.…”

Synthesis of Phosphatidyl Glycerol Containing Unsymmetric Acyl Chains Using H-Phosphonate Methodology

“…Another advantage of this strategy is that the phosphite precursor to H-phosphonates can undergo transesterifications reactions under basic conditions with alcohols, an ideal circumstance for installation of the phosphorous species on the glycerol backbone to prevent acyl chain migration from the sn-2 to the sn-1 position. A third advantage is that H-phosphonate monoesters such as 9 are less susceptible to air oxidation, as well as base- and acid-catalyzed hydrolysis, due to the high level of electron density associated with the anionic form of the phosphonate, whereas the phosphonate proton needs to be removed before undergoing a nucleophilic attack [ 18 , 43 , 44 , 45 , 46 , 47 ]. Once activated, H-phosphonates have exhibited high rates of condensation, with alcohols approaching 10 5 M s −1 [ 47 , 48 ], further supporting the case for their use.…”

Tf2O/DMSO-Promoted P–O and P–S Bond Formation: A Scalable Synthesis of Multifarious Organophosphinates and Thiophosphates

“…Chemical structures possessing a P–O or P–S bond are ubiquitous motifs that display remarkable chemical and biological properties, which give them a broad utility in a range of diverse fields from the pharmaceutical chemistry to agrochemistry, organic synthesis, and materials chemistry . Accordingly, synthetic chemists have devoted considerable efforts to exploring efficient and convenient methods for the formation of P–O and P–S bonds, and remarkable progress has been made during recent years. − Among them, phosphinoylation of alcohols and thioalcohols continues to be a compelling and straightforward strategy (Scheme a), as chemicals containing an −OH or −SH group are abundant in nature and readily available.…”