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An efficient procedure is described that leads to pure (SP)-O-l-menthylphenylthiophosphinate. The absolute configuration of this diastereomer was assigned by chemical correlation and confirmed by X-ray crystallography. The reaction of the isomer with phenyl azide, leading to amidate, is a new variant of the stereoselective Staudinger reaction. Addition of elemental selenium to the (SP)-thiophosphinate led to diastereomeric O-l-menthylphenylselenophosphonothioic acid, which was finally oxidized to the diastereomeric (RP1,RP2)-bis-[O-l-menthylphenylphosphonothionyl] diselenide. The diselenide structure was unambiguously confirmed by 31P NMR spectroscopy.

Fluoroderivatives of phosphorus are important in the chemistry and biochemistry of both elements.1. Recently, our attention has been Focused on the synthesis of non-ionic oligodeoxynucleoside-phosphoro fluoridates and their thio− and selenoanalogues. Existing methods were, in our opinion, not suited for the synthesis of oligonucleoside− phosphorofluorides. So we devised new ones.

Trifluoroacetic anhydride reacts with organophosphorus compounds containing thiophosphoryl and selenophosphoryl groups converting them in high yield to the corresponding oxygenated systems.

Trimethylchlorosilane (TMSCl) is a remarkably efficient activator in the reaction of phosphorus(III) amides with nucleosides to give phosphorus(III) esters in excellent yield.

Stereoselective synthesis of phosphocarnitine has been achieved for the first time starting from R(−)-epichlorohydrin.

The reactions of azetidinium salts with phosphorus nucleophiles R2P(O)H have been investigated. Treatment of O-benzyl-N,N-diethyl-3-hydroxyazetidinium salt 2 with R2P(O)H in the presence of sodium hydride gave the corresponding γ-N,N-diethylamino-β-benzyloxypropylphosphonate 6a or phosphine oxide 6b. After debenzylation γ-N,N-diethylamino-β-hydroxypropylphosphonate 3a and phosphine oxide 3b were obtained. The compound 6a was converted into its sulfonate ester 8 which underwent elimination to yield 4. The structure 4 has been employed in Michael addition of R2P(O)H to form compounds 5 containing two phosphorus centers. Further compounds of type 3 have been transformed into compounds 5 by reaction with R2P(O)H in the presence of 1.1 equivalents of NaH in boiling toluene. Finally, azetidinium salts 1 have been converted into compounds 5a by reaction with two equivalents of R2P(O)H in the presence of 2.1 equivalents of NaH. Molecular mechanics with implementation of the Allinger MM2 force field and semiempirical AM1 and PM3 methods were used to investigate structures 5d and 5f.

We describe the convenient synthesis of thymidine cyclic 3', 5'-phosphorofluoridate 6, which is superior to that previously reported. Our procedure is based on a sequence of reactions utilizing 3 as the key substrate. Similar sequence of reaction leads to the sulfur analogues of 6 the thymidine cyclic 3',5'-phosphorofluoridothioate 7.

Activation of phosphoramidites as phosphitylating reagents in the synthesis of biophosphates and their structural analogues is of great importance. Tetrazole a customary activator can be conveniently replaced by trimethylchlorosilane (TMCS) or 2,4-dinitrophenol. Advantages of use of these reagents in the synthesis of biophosphates and their mechanism of action are discussed. Phosphites containing 4-nitrophenoxy leaving group are activated by DBU which role is revealed. Readily accessible P(III)-F structures, can be "activated" by their facile transformation into the corresponding bromides using trimethylbromosilane (TMBS). Application of phosphoramidites in synthesis of phosphates of biological interest and their activation by azolides and acids salts, including and stereochemical aspects was described in 'Topics in Current Chemistry.

The mechanistic and synthetic aspects of the addition reaction of thioxophosphorane sulfenyl bromide with ethyl vinyl ether were studied in detail by NMR techniques. It has been found that the regiospecific, primary product of the reaction, 1-bromo-1-ethoxy-2S(dialkoxythiophosphoryl)ethane I, is unstable and undergoes slow decomposition to give four compounds. The formation of thiophosphoryl derivatives, vinyl ethers II and III, aldehyde IV, and the symmetrical hemiacetal anhydride V, has been considered in terms of a carbocation intermediate. By choice of the appropriate reaction conditions, the aldehyde IV can be obtained in very high yield.

This chapter is concerned with preparation and applications of tricoordinate phosphorus compounds in synthesis of biophosphates and their structural analogues and illustrates the recent trends with a series of selected examples.

Ziel und Ergebnis der Untersuchung ist die Synthese der relativ unbestandigen phosphororganischen Thiocyanate vom Typ R2P(X)SCN (1,12: × = O; 8: × = S) und deren Umlagerung in die thermodynamisch stabileren Isothiocyanate R2P(X)NCS (3, 24: × = O, 6: × = S). Stereochemische Untersuchungen an cyclischen diastereomeren Modellen (2617) fuhren zu dem Ergebnis, das die Umlagerung Thiocyanat Isothiocyanat durch nucleophile Partner, z. B. SCN⊖, uber ein pentakoordiniertes Zwischenprodukt oder einem entsprechenden Ubergangszustand autokatalysiert wird. Synthesis, Chemistry and Stereochemistry of Phosphororganic Thiocyanatesand IsothiocyanatesRearrangement of Thio- into Isothiocyanates The aim and result of the investigation is the synthesis of the relatively unstable organic phosphorus thiocyanates of the type R2P(X)SCN (1,12; × = O; 8: × = S) and their tranformation into the thermodynamically more stable isothiocyanates R2P(X)NCS (3, 24: × = O; 6: × = S). Stereochemical studies of cyclic diastereomeric (26 17) have shown that the conversion thiocyanate isothiocyanate is autocatalyzed by nucleophilic partners, e. g. SCN⊖, via a pentacoordinated intermediate or a corresponding transition state.

Earlier works from this and other laboratories on phosphoric and phosphinic sulfonic anhydrides have been reinvestigated. It was found that no single reaction described in the past provides a general method for the production of mixed anhydrides RR′P(O)SO2R″ (3) in high yields of isolated products. The following three efficient synthetic procedures leading to pure anhydrides 3 are described: a) Trifluoromethanesulfonic acid promoted reaction of phosphinic acid 9 with sulfonic triazolides 10. b) Reaction of phosphinic and phosphoric imidazolides 13 with sulfonic acid 6. c) Reaction of 13 with sulfonic anhydride 15. All methods result in high yields. Some chemical properties of the anhydrides 3 are described. Phosphorsaure- und Phosphinsaure-sulfonsaure-anhydride – Neuuntersuchung und Korrekturen. Neue Synthese-Methoden Fruhere Ergebnisse aus unseren und anderen Laboratorien an Phosphorsaure- und Phosphinsaure-sulfonsaure-anhydriden wurden uberpruft. Es wurde jetzt gefunden, das sich keine einzige fruher beschriebene Reaktion als allgemeine Methode zur Darstellung gemischter Anhydride RR′P(O)SO2R″ mit hohen Ausbeuten an isolierten Produkten eignet. Die folgenden drei Verfahren zur Synthese von reinen Anhydriden 3 werden beschrieben: a) Die Trifluormethansulfonsaure-katalysierte Reaktion von Phosphinsaure 9 mit Sulfonsaure-triazoliden 10. b) Reaktion von Phosphinsaure- und Phosphorsaure-imidazoliden 13 mit der Sulfonsaure 6. c) Umsetzung von 13 mit Sulfonsaureanhydrid 15. Alle Methoden ergeben hohe Ausbeuten. Einige chemische Eigenschaften der Anhydride 3 werden beschrieben.

New applications of methods leading to anhydrides RR′P(O)OSO2R″ (1) are described: a) Reaction of acids RR′P(O)OH (2) with sulfonic imidazolides. b) Reaction of phosphorus imidazolides 4 with sulfonic acids and sulfonic anhydrides. New Methods of synthesis of anhydrides 1 have been developed. c) Reaction of phosphorus acid silyl esters RR′P(O)OSiMe3 (9) with methanesulfonic and trifluoromethanesulfonic anhydrides. d) Reaction of bis(trimethylsilyl) tert-butyl-phosphonate (10) with methanesulfonic acid leading to t BuP(O)(OSO2Me)2 (11). e) Reaction of stannyl phosphate (EtO)2P(O)OSnMe3 (15) with methanesulfonic anhydride. f) Reaction of phosphorus acid silyl esters 9 with trimethylsilyl trifluoromethanesulfonate. All methods result in high yields and can be adapted to a variety of anhydrides 1 derived from phosphoric, phosphonic, and phosphinic acids on the one hand and methanesulfonic, trifluoromethanesulfonic acids and sulfuric monoimidazolide on the other. Phosphonium intermediates have been demonstrated by low temperature FT 31P NMR spectroscopy for reaction b) and c). The anhydrides 1 are readily converted into imidazolides 4 by the reaction with N-(trimethylsilyl)imidazole which proceeds via two distinct phosphonium intermediates. With neutral and weakly basic nucleophiles, the anhydrides 1 behave as phosphorylating agents. Anhydride aus Sauren des Phosphors und des Schwefels, 2. Gemischte Anhydride von Phosphor-, Phosphon- und Phosphinsauren mit Sulfonsauren und Schwefelsaure-monoimidazolid. Neue Synthesen, neue Verbindungen und ihre Eigenschaften als Phosphorylierungsmittel Es werden neue Anwendungen der Methoden, die zu Anhydriden der Struktur RR′P(O)OSO2R″ (1) fuhren, beschrieben: a) Die Reaktion von Sauren RR′P(O)OH (2) mit Sulfonsaure-imidazoliden. b) Die Reaktion von Imidazoliden 4 von Sauren des Phosphors mit Sulfonsauren und Sulfonsaure-anhydriden. Neue Methoden zur Synthese von Anhydriden der Struktur 1 wurden entwickelt. c) Die Reaktion von Trimethylsilylestern von Sauren des Phosphors RR′P(O)OSiMe3 (9) mit Methansulfonsaure- und Trifluormethansulfonsaure-anhydriden. d) Die Reaktion von tert-Butylphosphonsaure-bis(Trimethylsilylester) (10) mit Methansulfonsaure zu tBuP(O)(OSO2Me)2 (11). e) Die Reaktion des Stannylphosphats (EtO)2P(O)OSnMe3 (15) mit Methansulfonsaure-anhydrid. f) Die Reaktion von Trimethylsilylestern 9 von Sauren des Phosphors mit Trifluormethansulfonsaure-trimethylsilylester. Alle Methoden ergeben hohe Ausbeuten und konnen an die Vielzahl der Anhydride 1 aus Phosphor-, Phosphon- und Phosphinsauren einerseits und Methansulfonsaure, Trifluormethansulfonsaure und Schwefelsaure-monoimidazolid andererseits angepast werden. Fur die Reaktionen b) und c) konnten durch Tieftemperatur-FT-31P-NMR- Spektroskopie Phosphonium-Zwischenstufen nachgewiesen werden. Die Anhydride 1 lassen sich durch Umsetzen mit N-(Trimethylsilyl)imidazol leicht in Imidazolide 4 uberfuhren; diese Reaktion lauft uber zwei verschiedene Phosphonium-Zwischenstufen. Die Anhydride 1 wirken gegenuber neutralen oder schwach basischen Nucleophilen als Phosphorylierungsmittel.

Die Synthese von Phosphorsaure-monoathylester, -diathylester und -triathylester (1–3) sowie von Phenylmethanphosphonsaure-monoathylester und -diathylester (4, 5) durch selektive Alkylierung der Orthophosphorsaure und Phenylmethanphosphonsaure mit Triathylphosphit wird beschrieben. Selective Alkylation of Polybasic Phosphoric Acids with Trialkyl Phosphite The synthesis of mono-, di-, and triethyl phosphate (1–3) as well as of mono- and diethyl phenylmethane phosphonate (4, 5) by selective alkylation of orthophosphoric and phenylmethane phosphonic acid with triethyl phosphite is described.

Die Alkoholyse von (Thiophosphorigsaure-O-athylester)-(phosphorsaurediathylester)anhydrid fuhrt zu gemischten Thiophosphorigsaure-O.O-dialkylestern und Phosphorsaure-diathylester. Thiophosphorigsaure-O-athylester-O-butylester ist auch durch Umsetzung von Phosphorigsaure-athylester-butylesterchlorid mit Schwefelwasserstoff erhaltlich.

Phosphorsaure-dialkylester, Carbonsauren und Sulfonsauren lassen sich durch Umsetzung mit Tetraalkylestern des Phosphorsaure-phosphorigsaure-anhydrids phosphorylieren. In allen Fallen entstehen die Anhydride des Phosphorsaure-dialkylesters und Dialkylphosphit mit hoher Ausbeute.

Ambident anions derived from phosphorus monothio acids have been glycosylated by 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl-, 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl- and 2,3,4-tri-acetyl-α-D-xylopyranosyl bromides, yielding β-S-glycosyl- and /gb-O-glycosylthioates. The S/O ratio of the glycosylated phosphorothioates depends markedly on the salt used. Ammonium salts favour the formation of S-derivatives, whereas silver salts give mainly O-derivatives. O-Glucosyl phosphorothioate undergoes thermal isomerisation to S-glucosyl phosphorothioate, with retention of configuration at the glycosylic centre. The implications of this stereochemical result are briefly discussed.

Phosphoroazolides, including nucleoside derivatives, can be converted smoothly into the corresponding phosphorofluoridates by reaction with benzoyl flouride. From these compounds oligonucleotides containing → P-F instead of → P-OH can be prepared.

Direct evidence by 31P-n.m.r. spectroscopy is presented for the formation of a five-co-ordinate intermediate in the Arbuzov reaction of tervalent phosphorus esters with elemental chlorine or elemental bromine and benzenesulphenyl chloride.

The remarkably selective reaction of O,O,O-dialkyltrimethylsilylselenophosphates (1) in the presence of equimolar amounts of dialkyltrimethylsilyl phosphites (2) with sulphuryl chloride leading to tetra-alkyl symmetrical selenopyrophosphates (3) in excellent yields is reported.

The ratio of desulphurisation to deoxygenation of oxophosphoranesulphenyl chlorides, >P(O)SCI, by trivalent phosphorus compounds depends on the nature of the PIII compounds and is accompanied by inversion of configuration at the chiral phosphorus atom of the sulphenyl chloride.

Ambident anions derived from phosphorus thioselcnoacids were glycosylated with 2,3,4,6 - tetra - O - acetyl - α - d - glucopyranosyl bromide, 2,3,4,6 - tetra - O - acetyl - α - d - galactopyranosyl bromide and 2,3,4 - tri- O - acetyl - α - d - xylopyranosyl bromide. The products were β-Se-glucosyl- and β-S-glucosylthioselenoates. The Se/S ratio of the glycosylated phosphorothioselenoates depends on the reaction conditions. At higher temperatures an equilibrium was observed. As a result of this equilibrium the Se/S ratio of the linkages formed in the glycosylated products was different from that observed under kinetic control. The structures of the glycosylated phosphorothioselenoates were confirmed by spectroscopy, independent synthesis and selective oxidation.