Synthesis and Reactivity of Azidoalkylphosphonates, -Phosphinates and -Phosphine Oxides

Abstract

This review will focus on the synthesis of -and -azidoalkylphosphonic and -phosphinic acids, -phosphine oxides and their derivatives as well as their reactions utilizing the azido group and/or phosphyl group. In the first part of this review synthetic routes to such azides will be reviewed. Generally, these compounds are achieved via nucleophilic substitution of hydroxy derivatives of phosphonates, -phosphinates, and -phosphine oxides by the Mitsunobu protocol or by the displacement of their sulfonates or halogen derivatives with azides. The ring-opening of phosphorus-containing oxiranes or cyclic vicinal sulfates with azides will also be discussed. Electrophilic azidation of the corresponding phosphorus-stabilized carbanions has also been described. In the second part of the review emphasis will be placed on the application of azido derivatives in organic synthesis. 1,3-Dipolar cycloaddition is an excellent tool in the construction of fivemembered heterocycles. Therefore, the formation of 1,2,3-triazoles from alkynes, enamines and 2-oxoalkylidenetriphenylphosphoranes will be discussed. Hence, the azido group is easily converted into amine, and phosphorus-containing azides can be considered to be azide-masked equivalents of amino derivatives or their N-protected derivatives. The application of such azides in the synthesis of phosphorus analogs of amino acids will be discussed. The synthesis of carbodiimides, imines, isothiocyanates and phosphonodipeptides has also been reviewed.

Mitsunobu and Related Reactions: Advances and Applications

“…Many enantiopure β-aminophosphonates could thus be synthesized. In the synthesis of sialyltransferase transition-state analogue inhibitors also, Mitsunobu azidation of α-hydroxyphosphonates via HN 3 with inversion has been found to be quite effective. , A recent review by Gajda and Gajda highlights the work on azidophosphonates that includes Mitsunobu azidation …”

“…1326,1327 A recent review by Gajda and Gajda highlights the work on azidophosphonates that includes Mitsunobu azidation. 1328 Azidation, benzoylation, and tosylation of syn-2,3-dihydroxy esters 425 under Mitsunobu conditions exhibit complete regioselection for the β-hydroxyl group, leading to 426 (Scheme 117). 1329 The configurational inversion accompanying the Mitsunobu protocol offers a means for syn/anti diastereochemical diversity.…”

α-Azido Bisphosphonates: Synthesis and Nucleotide Analogues

“…The present study and our previous interest in diazo transfer chemistry , prompted us to reinvestigate a reported azido transfer to triethyl phosphonoacetate using triflyl azide in the presence of triethyl amine . Triflyl azide is known to be a powerful diazo transfer reagent and attempts by other authors to extend the procedure to benzocyclic β-keto esters were unsuccessful; nevertheless, the original reaction has been cited as a viable azido transfer reaction in recent reviews. , In our hands, the procedure of Hakimelahi and Just produced triethyl diazophosphonoacetate, characterized by 1 H, 31 P NMR and MS (ESI and APCI) and generated no detectable amounts of azido transfer product. In light of these results and analysis of the literature, we propose that the reaction of triflyl azide with triethylphosphonoacetate is consistent with known diazo transfer chemistry and is not an anomalous case of azido transfer.…”

Synthetic methods : Part (iii) Heteroatom chemistry

“…3 The synthesis and reactivity of azidoalkylphosphonates, -phosphinates and -phosphine oxides, and their applications towards the synthesis of phosphorus analogues of amino acids, was reviewed by Gajda. 4 Holz presented a thorough overview of the synthesis of chiral heterocyclic phosphines, which play an important role as ligands and organocatalysts in asymmetric reactions. 5 Keglevich summarises the recent efforts on the synthesis and utilisation of phosphorus-containing ionic liquids, with some emphasis on discovering suitable 'green' replacements for traditional solvents with enhanced properties for a whole range of synthetic methodologies.…”