LIGAND-ASSISTED DEOXYGENATION OF PHOSPHATES TO FORM NITROGEN-CONTAINING PHOSPHORUS(V) PRECURSORS AND THEIR SUBSEQUENT CONVERSION TO VARIOUS OXYPHOSPHORUS COMPOUNDS

Abstract

The present invention relates to a method for synthesising nitrogen-containing phosphorus(V) precursors of formula (I), wherein a phosphate compound is reacted with an oxygen acceptor based on a sulfonic anhydride in the presence of a Lewis base L.sub.N capable of coordination via a nitrogen atom, wherein the Lewis base L.sub.N is a nitrogen-containing heteroaromatic compound containing a six-membered heteroaromatic ring. The present invention also relates to a method for synthesising oxyphosphorus compounds, wherein the method for synthesising nitrogen-containing phosphorus(V) precursors of formula (I) is carried out and the nitrogen-containing phosphorus(V) precursor of formula (I) is reacted with a nucleophile.

##STR00001##

Claims

1. A method for synthesizing nitrogenous phosphorus(V) precursors of Formula (I), ##STR00020## wherein the method comprises the following steps in the order indicated: a) preparing a phosphate compound; b) reacting the phosphate compound of step a) with an oxygen acceptor in the presence of a Lewis base L.sub.N that is capable of coordination via a nitrogen atom, wherein the oxygen acceptor is a cation of a sulfonic acid anhydride of Formula (II) and the sulfonic acid anhydride is according to Formula (III), ##STR00021## alternatively, according to step b), either b1) the phosphate compound of step a) is reacted with the sulfonic acid anhydride of Formula (III) in the presence of a Lewis base L.sub.N, or b2) the phosphate compound of step a) is reacted with a reaction product of a sulfonic acid anhydride of Formula (III) with a Lewis base L.sub.N, wherein the reaction product is Formula (IV) ##STR00022## wherein R is an aliphatic or aromatic hydrocarbon radical that can comprise heteroatoms, wherein the number of carbon atoms of the radical R is 1 to 21, and the heteroatoms are selected from the group consisting of oxygen, nitrogen, fluorine, chlorine, bromine, iodine, and mixtures thereof, wherein the Lewis base L.sub.N that is capable of coordination via a nitrogen atom is a nitrogenous heteroaromatic compound which comprises a six-membered heteroaromatic ring comprising a nitrogen atom capable of coordination, and wherein the number of carbon atoms of the Lewis base L.sub.N is from 4 to 19.

2. The method as claimed in claim 1, wherein the phosphate compound is selected from the group consisting of orthophosphate salts and acids, polyphosphate salts and acids, metaphosphate salts and acids, salts and acids of further condensed phosphates derivable therefrom, phosphorus pentoxide (P.sub.4O.sub.10), and mixtures thereof, wherein the polyphosphate salts and acids can be described by the Formula P.sub.mO.sub.3m+1.sup.(m+2) and wherein: m=2 to 10 000; and wherein the metaphosphate and salts and acids can be described by the Formula (PO.sub.3.sup.).sub.n and wherein: n=3 to 10.

3. The method as claimed in claim 2, wherein the polyphosphate salts and acids can be described by the Formula P.sub.mO.sub.3m+1.sup.(m+2) and wherein: m=2 to 10 000; and wherein the metaphosphate salts and acids can be described by the Formula (PO.sub.3.sup.).sub.n and wherein the following applies: n=3 to 10.

4. The method as claimed in claim 1, wherein the phosphate compound comprises phosphoric acid.

5. The method as claimed in claim 1, wherein R is an aliphatic hydrocarbon radical with 1 to 6 carbon atoms, which comprises 0 to 3 heteroatoms selected from the group consisting of oxygen, nitrogen and fluorine.

6. The method as claimed in claim 1, wherein R is an aromatic hydrocarbon radical defined by Formula (IIIa), ##STR00023## wherein the radicals R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are selected from the following combinations: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5=H, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5=CH.sub.3, R.sup.1, R.sup.2, R.sup.3, R.sup.4=H and R.sup.5=CH.sub.3, R.sup.1, R.sup.2, R.sup.3, R.sup.4=H and R.sup.5=F, R.sup.1, R.sup.2, R.sup.3, R.sup.4=H and R.sup.5=Cl, R.sup.1, R.sup.2, R.sup.3, R.sup.4=H and R.sup.5=OCH.sub.3, R.sup.1, R.sup.2, R.sup.3, R.sup.4=H and R.sup.5=NO.sub.2, R.sup.1, R.sup.2, R.sup.3, R.sup.4=H and R.sup.5=CF.sub.3, R.sup.1, R.sup.2, R.sup.4=H and R.sup.3, R.sup.5=CH.sub.3, R.sup.2, R.sup.4=H and R.sup.1, R.sup.3, R.sup.5=CH.sub.3, R.sup.2, R.sup.3, R.sup.5=H and R.sup.1, R.sup.4=CH.sub.3, or R.sup.1, R.sup.2, R.sup.4, R.sup.5=H and R.sup.3=CH.sub.3.

7. The method as claimed in claim 5, wherein R is trifluoromethyl.

8. The method as claimed in claim 1, wherein the Lewis base L.sub.N comprises one or two six-membered heteroaromatic rings, the Lewis base L.sub.N comprises one or two nitrogen atoms capable of coordination per six-membered heteroaromatic ring in the six-membered heteroaromatic ring, and wherein the Lewis base L.sub.N comprises a total of one or two nitrogen atoms.

9. The method as claimed in claim 1, wherein the Lewis base L.sub.N comprises, independently of each other, one or two nitrogen atoms, zero, one or two oxygen atoms, zero, one, two, three or four heteroatoms, which are selected from the group consisting of fluorine, chlorine, bromine, and iodine, and does not comprise any further heteroatoms.

10. The method as claimed in claim 1, wherein the Lewis base L.sub.N is selected from the group consisting of pyridines, picolines, lutidines, collidines, bipyridines, pyridazines, pyrimidines, pyrazines, quinolines and isoquinolines.

11. The method as claimed in claim 1, wherein the Lewis base L.sub.N is selected from the group consisting of pyridine, 4-dimethylaminopyridine, and mixtures thereof.

12. The method as claimed in claim 1, wherein the synthesis takes place in an aprotic solvent.

13. The method as claimed in claim 12, wherein the aprotic solvent is pyridine.

14. A method for synthesizing oxyphosphorus compounds, wherein the method comprises the following steps in the order indicated: c) synthesis of a nitrogenous phosphorus(V) precursor of Formula (I) according to the method as claimed in claim 1; d) reacting the nitrogenous phosphorus(V) precursor of Formula (I) with a nucleophile.

15. The method as claimed in claim 14, wherein the nucleophile is selected from the group consisting of alcohols, ammonia, primary amines, secondary amines, tertiary amines, azoles, organometallic compounds and fluoride.

16. The method as claimed in claim 1, wherein the phosphate compound is phosphoric acid.

17. The method as claimed in claims 6, wherein R is defined according to Formula (IIIa) and the following applies: R.sup.1, R.sup.2, R.sup.4, R.sup.5=H and R.sup.3=CH.sub.3.

Description

EXPERIMENTAL PART

[0175] All reactions were carried out in a dried inert gas atmosphere (N.sub.2 or Ar) using a glove box (Innovative Technology Pure Lab HE, MBraun Unilab) or by means of the Schlenk technique. Before use, glassware was stored at 150 C. or heated under a vacuum using a hot air blower. Microwave reactions were conducted in sealed glass tubes in the CEM Discover reactor. The solvents used were first distilled with suitable desiccants and stored over a molecular sieve. The deuterated solvents CD.sub.2Cl.sub.2, CD.sub.3CN, C.sub.6D.sub.6 and C.sub.7D.sub.8 were obtained from Merck, Deutero or Eurisotop and stored over a molecular sieve before use. Aqueous processing was carried out under normal conditions (no inert gas used). Aqueous solutions (distilled H.sub.2O, saturated NaCl solution) were degassed in advance in an ultrasonic bath.

.SUP.1.H-NMR, .SUP.13.C-NMR, .SUP.31.P-NMR, .SUP.19.F-NMR

[0176] Nuclear magnetic resonance experiments were carried out on the devices AVANCE III HD Nanobay 400 MHz Ultrashield (resonance frequencies: .sup.1H=400.13 MHZ, .sup.13C=100.61 MHZ, .sup.19F=376.50 Hz, .sup.31P=161.98 MHZ) or AVANCE III HDX 500 MHZ Ascend (resonance frequencies: .sup.1H=500. 13 MHZ, .sup.13C=125.75 MHZ, .sup.19F=470.59 MHz, .sup.31P=202.45 MHZ) from the firm Bruker and evaluated using the software Topspin. The values of the chemical shift refer to the external standards tetramethylsilane (.sup.1H, .sup.13C), trichlorofluoromethane (.sup.19F) or phosphoric acid 85% (.sup.31P) and are given in ppm rounded off to 1-2 decimal places. Scalar couplings via n bonds .sup.nJ are given in Hz rounded off to 1-2 decimal places. .sup.13C-NMR spectra were measured in all cases with .sup.1H broad band decoupling. For assignment of the signals, if necessary, additional 2D correlation experiments (HSQC, HMBC, HH-COSY, .sup.1H-.sup.31P-HMBC) were carried out. In order to describe multiplicity, the following abbreviations are used: ssinglet, s(br)broad singlet, ddoublet, ttriplet, qquartet, mmultiplet. Combinations of these abbreviations are given in all cases in decreasing order of coupling constants. Temperature-dependent measurements were recorded using a BCU II temperature unit (120 C. to 40 C.) or a nitrogen vaporizer (50 C. to 100 C.).

Chemicals

[0177] Chemicals and solvents were obtained from Merck, VWR, Alfa Aesar, Acros Organics or TCl. Trifluoromethanesulfonic anhydride (Tf.sub.2O) was donated by the firm Solvay.

TABLE-US-00001 Abbreviations BINOL 1,1-bi-2-naphthol DMAP 4-(dimethylamino)pyridine HOTf trifluoromethanesulfonic acid KOtBu potassium tert-butanolate MeOH methanol OTf.sup. trifluoromethane sulfonate PhMgBr phenyl magnesium bromide PhOH phenol Pyr pyridine Tf.sup.+ triflate cation Tf.sub.2O trifluoromethanesulfonic anhydride THF tetrahydrofuran 4-Me-Pyr 4-methylpyridine

EXAMPLES

Example 1: Synthesis of (L.SUB.N.).SUB.2.PO.SUB.2.[OTf] (L.SUB.N.=pyrdiniumyl) From H.SUB.3.PO.SUB.4

[0178] Pure phosphoric acid (610 mg, 6.22 mmol) is placed in pyridine (8 ml) and cooled to 30 C. Cold (30 C.) trifluoromethanesulfonic anhydride (Tf.sub.2O; 3.86 g, 13.7 mmol) is slowly added to this dropwise. The reaction solution turns orange/brown, and a colorless, sticky solid forms, which slowly dissolves in the course of the reaction. After 15 min, a colorless precipitate forms. The reaction mixture is then stirred for 12 h at 40 C. The solid is filtered through a glass frit, washed with pyridine (26 ml), and then vacuum-dried. The product is obtained as a colorless solid in quantitative yield [2.32 g; (>99%)].

[0179] The product is characterized by multinuclear NMR spectroscopy (NMR spectra are attached in the appendix; FIGS. 1-3). The product is soluble in CH.sub.3CN and freely soluble in CH.sub.3NO.sub.2.

[0180] .sup.1H NMR (CD.sub.3CN, 300 K, in ppm): 7.97 (4H, s(br), H2), 8.48 (2H, s(br), H3), 9.16 (4H, s(br), H1); .sup.19F NMR (CD.sub.3CN, 300 K, in ppm): 79.2 (3F, s, OTf.sup.); .sup.31P NMR (CD.sub.3CN, 300 K, in ppm): 15.8 (1P, s).

Example 2: Synthesis of (L.SUB.N.).SUB.2.PO.SUB.2.[OTf] (L.SUB.N.=pyrdiniumyl) From 85% H.SUB.3.PO.SUB.4

[0181] 85% phosphoric acid (400 mg; corresponds to 340 mg, 3.5 mmol, H.sub.3PO.sub.4) is prepared and placed in pyridine (5 ml) and cooled to 30 C. Cold (30 C.) trifluoromethanesulfonic anhydride (Tf.sub.2O; 3.15 g, 11.2 mmol) is slowly added to this dropwise. The reaction solution turns brown and a colorless, sticky solid forms, which slowly dissolves in the course of the reaction. After 15 min, a colorless precipitate forms. The reaction mixture is then stirred for 12 h at 40 C. The solid is filtered through a glass frit, washed with pyridine (26 ml), and then vacuum-dried. The product is obtained as a colorless solid in a very good yield [1.09 g; (85%)].

[0182] The product is characterized by multinuclear NMR spectroscopy. The product is freely soluble in CH.sub.3CN.

[0183] .sup.1H NMR (CD.sub.3CN, 300 K, in ppm): 7.97 (4H, s(br), H2), 8.48 (2H, s(br), H3), 9.16 (4H, s(br), H1); .sup.19F NMR (CD.sub.3CN, 300 K, in ppm): 79.2 (3F, s, OTf.sup.); .sup.31P NMR (CD.sub.3CN, 300 K, in ppm): 15.8 (1P, s).

Example 3: Synthesis of (L.SUB.N.).SUB.2.PO.SUB.2.[OTf] (L.SUB.N.=4-dimethylaminopyridiniumyl) From H.SUB.3.PO.SUB.4

[0184] Pure phosphoric acid (44 mg, 0.44 mmol) and [DMAP-Tf][OTf] (see S. Yogendra, F. Hennrsdorf, A. Bauz, A. Frontera, R. Fischer, J.J. Weigand, Chem. Commun. 2017, 53, 2954) (373 mg, 0.92 mmol) are weighed together and pyridine is then added (3 ml). The colorless reaction solution if stirred for 12 h at room temperature, and a colorless precipitate forms during this time. The solid is filtered, washed with CH.sub.2Cl.sub.2 (22 ml), and then vacuum-dried. The product is obtained as a colorless solid in 81% yield (163 mg). The product is sparingly soluble in various solvents (CH.sub.2Cl.sub.2, PhF, CH.sub.3CN).

[0185] The product is characterized by multinuclear NMR spectroscopy (NMR spectra are attached in the appendix; FIGS. 4-6). The product is soluble in CH.sub.3NO.sub.2.

[0186] .sup.1H NMR (MeNO.sub.2, C.sub.6D.sub.6 capillary, 300 K, in ppm): 4.55 (12H, s, H4), 8.17 (4H, d(br), .sup.3J.sub.HH=6.9 Hz, H2), 9.66 (2H, pseudo t(br), .sup.2J.sub.HH=7.0 Hz, H1); .sup.19F NMR (MeNO.sub.2, C.sub.6D.sub.6 capillary, 300 K, in ppm): 78.4 (3F, s, OTf.sup.); .sup.31P NMR (MeNO.sub.2, C.sub.6D.sub.6 capillary, 300 K, in ppm): 14.2 (1P, s).

Example 4: Synthesis of (L.SUB.N.).SUB.2.PO.SUB.2.[OTf] (L.SUB.N.=4-methylpyridiniumyl) From H.SUB.3.PO.SUB.4

[0187] Pure phosphoric acid (133 mg, 1.35 mmol) is prepared and placed in pyridine (6 ml) and cooled to 30 C. Cold (30 C.) trifluoromethanesulfonic anhydride (Tf.sub.2O; 817 mg, 2.9 mmol) is slowly added to this dropwise. The reaction solution turns orange/brown, and a colorless, sticky solid forms, which slowly dissolves in the course of the reaction. After 15 min, a colorless precipitate forms. The reaction mixture is then stirred for 12 h at 40 C. After this, 4-methylpyridine (377 mg, 4.05 mmol) is added, whereupon the cloudy reaction mixture slowly becomes clear. After 2 h, a solid precipitates, which is filtered, washed with n-pentane (4 ml), and dried in a vacuum to isolate it as a colorless powder. Yield [487 mg; (>91%)].

[0188] The product is characterized by multinuclear NMR spectroscopy (NMR spectra are attached in the appendix; FIGS. 7-9). The product is soluble in CH.sub.3CN.

[0189] .sup.1H NMR (CD.sub.3CN, 300 K, in ppm): 2.63 (6H, s, H4), 7.88 (4H, d, .sup.3J.sub.HH=6.3 Hz, H2), 9.06 (4H, m, H1); .sup.13C{.sup.1H} NMR (CD.sub.3CN, in ppm): 22.7 (s, 2C, C4), 122.1 (q, 1C, .sup.1J.sub.CF=320.9 Hz, OTf.sup.), 129.7 (s, 4C, C2), 145.2 (s, 4C, C1), 165.7 (s, 2C, C3); .sup.19F NMR (CD.sub.3CN, in ppm): 79.3 (s, 3F, OTf.sup.); .sup.31P NMR (CD.sub.3CN, in ppm): 16.0 (s, 1P).

Example 5: Reactions of Potassium Phosphate (K.SUB.3.[PO.SUB.4.])

Example 5a): Reaction at Elevated Temperature

[0190] Potassium phosphate (106 mg, 0.5 mmol) and [DMAP-Tf][OTf] (404 mg, 1.0 mmol) are weighed together and heated while stirring to 130 C. The initially colorless substance mixture takes on a beige color after approx. 90 min and becomes slightly pasty. Samples are taken from this mixture and examined by multinuclear NMR spectroscopy. The formation of [(DMAP).sub.2PO.sub.2].sup.+ is observed after only 3 h in the .sup.31P NMR spectrum (.sup.31P NMR (CD.sub.3CN, 300 K, in ppm): 15.8 (1P, s); .sup.31P NMR spectrum is attached in the appendix; FIG. 10).

Example 5b): Reaction Under Mechanical/Chemical Conditions

[0191] Potassium phosphate (50 mg, 0.236 mmol) and [DMAP-Tf][OTf] (190 mg, 0.471 mmol) are weighed together and mixed with each other in a ball mill (Ernst Hammerschmidt, Vibrator n.M.v. Ardenne). The initially colorless substance mixture takes on a beige color after 60 min. Samples are taken from this mixture and examined by multinuclear NMR spectroscopy. The formation of [(DMAP).sub.2PO.sub.2].sup.+ is detected after only 1 h and the only phosphate-containing product in the .sup.31P NMR spectrum (.sup.31P NMR (CD.sub.3CN, 300 K, in ppm): 15.7 (1P, s), which is confirmed by a further sample after 7 h).

Example 5c): Reaction With Tf.SUB.2.O in Pyridine Under Acid Catalysis

[0192] Potassium phosphate (500 mg, 2.36 mmol) is prepared and placed in pyridine (approx. 20 ml). Under cooling in an ice bath, Tf.sub.2O (1 ml, 5.89 mmol) is added to the mixture, followed by HOTf (0.02 ml, 0.12 mmol). After stirring for 24 h at room temperature, a probe is taken and examined by NMR spectroscopy. The formation of [(Pyr).sub.2PO.sub.2].sup.+ is detected as the only phosphorus-containing product in the .sup.31P NMR spectrum (.sup.31P NMR (pyridine, C.sub.6D.sub.6 capillary, 300 K, in ppm): 15.3 (1P, s)).

Example 6: Reaction of Na.SUB.3.P.SUB.3.O.SUB.9 .(Sodium Trimetaphosphate) With Tf.SUB.2.O in Pyridine

[0193] Sodium trimetaphosphate (Na.sub.3P.sub.3O.sub.9; 40 mg, 0.13 mmol) is suspended in 2 ml of pyridine, and Tf.sub.2O (110 mg, 0.39 mmol) is slowly added. The reaction mixture is heated for 12 h at 40 C. After cooling to room temperature, a sample is taken and examined by multinuclear NMR spectroscopy. The formation of [(Pyr).sub.2PO.sub.2].sup.+ is detected as the only phosphorus-containing product in the .sup.31P NMR spectrum (.sup.31P NMR (pyridine, C.sub.6D.sub.6 capillary, 300 K, in ppm): 15.3 (1P, s); .sup.31P NMR spectrum is attached in the appendix; FIG. 11).

Example 7: Reaction of (P.SUB.2.O.SUB.5.).SUB.x .(Phosphorus Pentoxide) With Tf.SUB.2.O in Pyridine

[0194] (P.sub.2O.sub.5).sub.x (2 g, 14.18 mmol; Alfa Aesar, 98%, Product No. A13348) is suspended in 10 ml of pyridine and refluxed for 20 h. After cooling to 0 C., Tf.sub.2O (4.37 g, 15.49 mmol) is slowly added. The dark reaction mixture is stirred for 72 h at 45 C., giving rise to a colorless precipitate. The precipitate is filtered, washed with pyridine, and then vacuum-dried. The colorless solid obtained is examined by multinuclear NMR spectroscopy, and the .sup.31P NMR spectrum shows clean formation of the triflate salt [(Pyr).sub.2PO.sub.2].sup.+ as the only product. Yield: 9.75 g (93%). (.sup.31P NMR (CD.sub.3CN, 300 K, in ppm): 15.7 (1P, s); .sup.31P NMR spectrum is attached in the appendix; FIG. 12).

Example 8: Reaction of H.SUB.3.PO.SUB.4 .With p-Toluenesulfonic Anhydride in Pyridine

[0195] H.sub.3PO.sub.4 (60 mg, 0.61 mmol) is suspended in 2 ml of pyridine, and p-toluenesulfonic anhydride (437 mg, 1.34 mmol) is slowly added. The reaction mixture is stirred for 12 h at room temperature. A sample is taken and examined by multinuclear NMR spectroscopy. The formation of [(Pyr).sub.2PO.sub.2].sup.+ is detected in the .sup.31P NMR spectrum (.sup.31P NMR (pyridine, C.sub.6D.sub.6 capillary, 300 K, in ppm): 15.3 (1P, s); cf. FIG. 13).

Example 9: Reactions of (L.SUB.N.).SUB.2.PO.SUB.2.[OTf] With Alcohols and Alcoholates

Example 9a): Reaction of (DMAP).SUB.2.PO.SUB.2.[OTf] With MeOH

[0196] (DMAP).sub.2PO.sub.2[OTf] (30 mg, 0.065 mmol) is dissolved in a mixture of CH.sub.3CN and MeNO.sub.2 (approx. 1 ml), and 2 drops of dry MeOH are added to the mixture. The reaction mixture is stirred over night and examined by NMR spectroscopy. The .sup.31P NMR spectrum shows the selective formation of dimethyl phosphate [(MeO).sub.2PO.sub.2.sup.] (.sup.31P NMR (CH.sub.3CN, MeNO.sub.2, C.sub.6D.sub.6 capillary, 300 K, in ppm): 4.6 (1P, s)).

Example 9b): Reaction of (DMAP).SUB.2.PO.SUB.2.[OTf] With PhOH

[0197] (DMAP).sub.2PO.sub.2[OTf] (40 mg, 0.08 mmol) and phenol (17 mg, 0.17 mmol) are suspended in CH.sub.3CN (approx. 1.5 ml) and stirred for 2 days at 40 C. The .sup.31P NMR spectrum of the reaction solution shows the selective formation of diphenyl phosphate [(PhO).sub.2PO.sub.2.sup.] (.sup.31P NMR (CH.sub.3CN, MeNO.sub.2, C.sub.6D.sub.6 capillary, 300 K, in ppm): 11.5 (1P, s)).

Example 9c): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With 2-Ethylhexanol

[0198] (Pyr).sub.2PO.sub.2[OTf] (500 mg, 1.35 mmol) is suspended in 2-ethylhexanol (5 ml) stirred for 3 days at 65 C. The .sup.31P NMR spectrum of the reaction solution shows the selective formation of bis(2-ethylhexyl)phosphate [(RO).sub.2PO.sub.2.sup.] (R=2-ethylhexanoyl) (.sup.31P NMR (neat, C.sub.6D.sub.6 capillary, 300 K, in ppm): 2.12 (1P, s)). The 2-ethylhexanol is drawn off in a vacuum, and the residue is taken up in n-hexane (6 ml) and degassed water (1 ml). After separation of the organic phase and subsequent drying in a vacuum, bis(2-ethylhexyl)phosphate is obtained with 97% purity and 81% (347 mg) yield.

Example 9d): Reaction of (DMAP).SUB.2.PO.SUB.2.[OTf] With KOtBu

[0199] A solution of potassium-tert-butanolate (25 mg, 0.22 mmol) in THF (1 ml) is slowly added to a cold (30 C.) suspension of (DMAP).sub.2PO.sub.2[OTf] (50 mg, 0.11 mmol) in THF (1 ml), causing the suspension to turn light yellow. After 3 h, the .sup.31P NMR spectrum of the reaction solution shows complete conversion to the corresponding di-tert-butyl phosphate [(tBuO).sub.2PO.sub.2.sup.] (.sup.31P NMR (THF, C.sub.6D.sub.6 capillary, 300 K, in ppm): 5.9 (1P, s)).

Example 9e): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With BINOL

[0200] (Pyr).sub.2PO.sub.2[OTf] (200 mg, 0.54 mmol) and BINOL (155 mg, 0.54 mmol) are weighed together and suspended in pyridine (5 ml). The reaction mixture is then stirred for 12 h at room temperature. After 12 h, the .sup.31P NMR spectrum of the reaction solution shows complete and clean conversion to the corresponding BINOL phosphate (.sup.31P NMR (pyridine, C.sub.6D.sub.6 capillary, 300 K, in ppm): 6.5 ppm (1P, s)). The aqueous workup provides the clean product in 88% yield.

Example 9f): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With HOCH.SUB.2.CF.SUB.3

[0201] (Pyr).sub.2PO.sub.2[OTf] (185 mg, 0.5 mmol) and 2,2,2-trifluoroethanol (110 mg, 1.1 mmol) are weighed together and suspended in pyridine (2.5 ml). The reaction mixture is stirred for 12 h at room temperature. After 12 h, the .sup.31P NMR spectrum of the reaction solution shows complete and clean conversion to the corresponding bis-(trifluoroethyl)phosphate [(CF.sub.3CH.sub.2O).sub.2PO.sub.2.sup.] (.sup.31P NMR (THF, C.sub.6D.sub.6 capillary, 300 K, in ppm): 2.8 (1P, s)). The aqueous workup provides the clean product.

Example 10: Reaction of (DMAP).SUB.2.PO.SUB.2.[OTf] With PhMgBr

[0202] To a cold (80 C.) suspension of (DMAP).sub.2PO.sub.2[OTf] (60 mg, 0.13 mmol) in CH.sub.2Cl.sub.2 (3 ml), 0.27 ml of a 1 M THF solution of phenylmagnesium bromide (0.27 mmol) is added. The reaction mixture is stirred overnight, giving rise to a brown, clear solution. NMR examination of the reaction solution shows the formation of diphenylphosphinate [(Ph).sub.2PO.sub.2.sup.] (.sup.31P NMR (CD.sub.3CN, 300 K, in ppm): 14.8 (1P, s)).

Example 11: Reactions of (L.SUB.N.).SUB.2.PO.SUB.2.[OTf] With Amines

Example 11a): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With Sodium Triazolide

[0203] To a suspension of sodium triazolide (74 mg, 0.81 mmol) in CH.sub.3CN (2 ml), solid (Pyr).sub.2PO.sub.2[OTf] (150 mg, 0.40 mmol) is added, and the reaction mixture is stirred for an additional 2 h. The colorless suspension is filtered, and the solid is washed with CH.sub.3CN and then vacuum-dried. The solid is examined by multinuclear NMR spectroscopy, thus confirming formation of the corresponding (triazole).sub.2PO.sub.2.sup.. The .sup.31P NMR spectrum shows two different isomers (.sup.31P NMR (DMSO-d.sub.6, 300 K, in ppm): 22.3 (1P, s; 85%), 24.4 (1P, s; 15%)).

Example 11b): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With Sodium Imidazolide

[0204] To a suspension of sodium imidazolide (54 mg, 0.54 mmol) in CH.sub.3CN (2 ml), solid (Pyr).sub.2PO.sub.2[OTf] (100 mg, 0.27 mmol) is added, and the reaction mixture is stirred for an additional 2 h. The colorless suspension is filtered, and the solid is washed with CH.sub.3CN and then vacuum-dried. The solid is examined by multinuclear NMR spectroscopy, and formation of the corresponding (imidazole).sub.2PO.sub.2.sup. is confirmed. The .sup.31P NMR spectrum shows two different isomers (.sup.31P NMR (DMSO-d.sub.6, 300 K, in ppm): 20.8 (1P, s; 11%), 21.4 (1P, s; 89%)).

Example 11c): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With Sodium Pyrazolide

[0205] To a suspension of sodium pyrazolide (49 mg, 0.54 mmol) in CH.sub.3CN (2 ml), solid (Pyr).sub.2PO.sub.2[OTf] (100 mg, 0.27 mmol) is added, and the reaction mixture is stirred for an additional 12 h. The colorless suspension is filtered, and the solid is washed with CH.sub.3CN and then vacuum-dried. The solid is examined by multinuclear NMR spectroscopy, and the formation of the corresponding (pyrazole).sub.2PO.sub.2.sup. is confirmed (.sup.31P NMR (DMSO-d.sub.6, 300 K, in ppm): 18.2 (1P, s)).

Example 11d): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With NH.SUB.3

[0206] (Pyr).sub.2PO.sub.2[OTf] (100 mg, 0.27 mmol) is dissolved in CH.sub.3CN (2 ml), and NH.sub.3 0.54 ml (0.5 M in dioxane) is added. The reaction mixture is stirred for an additional 12 h. The colorless suspension is filtered, and the solid is washed with CH.sub.3CN and then vacuum-dried. The solid is examined by multinuclear NMR spectroscopy, showing the formation, among other substances, of (NH2).sub.2PO.sub.2.sup. (.sup.31P NMR (DMSO-d.sub.6, 300 K, in ppm): 0.3 (1P, pent. .sup.2J.sub.PH=8 Hz)).

Example 12: Reactions of (L.SUB.N.).SUB.2.PO.SUB.2.[OTf] to Form Asymmetrically Substituted Products

Example 12a): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With an Equivalent Quinuclidine

[0207] (Pyr).sub.2PO.sub.2[OTf] (50 mg, 0.13 mmol) is suspended in THF (2 ml), and solid quinuclidine (40 mg, 0.35 mmol) is added. The reaction mixture is stirred for an additional 12 h. The colorless suspension is filtered, and the solid is washed then vacuum-dried. The solid is examined by multinuclear NMR spectroscopy and shows the formation of the mixed/substituted derivative (quin)(Pyr)PO.sub.2.sup.+ (.sup.31P NMR (CD.sub.3CN, 300 K, in ppm): 3.3 (1P, s)).

Example 12b): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With Choline Chloride and n-tetradecan-1-ol

[0208] The compound (Pyr).sub.2PO.sub.2[OTf] (2.20 g, 5.90 mmol) and choline chloride (826 mg, 5.90 mmol) are weighed together and suspended in pyridine (12 ml). The reaction mixture is stirred for 48 h at room temperature, and n-tetradecan-1-ol (1.14 g, 5.3 mmol) is added. After a further 24 h, all of the volatile components are removed under a vacuum to obtain a brown powder. The product is isolated by column chromatography with an eluent mixture of CHCl.sub.3/MeOH/NH.sub.3 (25%). The remaining ammonium salt is extracted with CH.sub.3CN, and a further drying step yields the product as a colorless powder as NH.sub.4[Cl]-cocrystallate with a 53% (1.35 g) yield. The solid is examined by multinuclear NMR spectroscopy and shows the formation of the mixed-substituted derivative.

[0209] .sup.1H NMR (D.sub.2O, in ppm): 0.81 (3H, t, .sup.3J.sub.HH=6.9 Hz, H17), 1.26-1.16 (20H, m, H7-H14), 1.33-1.26 (2H, m, H6), 1.56 (2H, quin, .sup.3J.sub.HH=6.8 Hz, H5), 3.18 (9H, s, H3), 3.64-3.58 (2H, m, H2), 3.78 (2H, pseudo q, .sup.3J.sub.HP=6.5 Hz, .sup.3J.sub.HH=6.5 Hz, H4), 4.22 (2H, s(br), H1); .sup.31P NMR (D.sub.2O, in ppm): 0.6 (quin, .sup.3J.sub.PH=5 Hz).

Example 12c): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With Choline Chloride and (R)-Solketal

[0210] (Pyr).sub.2PO.sub.2[OTf] (3.70 g, 10.0 mmol) and choline chloride (1.40 g, 10.0 mmol) are suspended in pyridine and stirred for 20 h at room temperature. The mixture is then mixed with (R)-Solketal (1.32 g, 10.0 mmol) and further stirred for several days at 40 C. in an oil bath, in which it becomes sharply more clear. After cooling to room temperature, all volatile components are removed in a vacuum to obtain a reddish oil. The product is isolated by column chromatography with an eluent mixture of CHCl.sub.3/MeOH/NH.sub.3 (25%). After drying in a vacuum, the product is obtained as a colorless powder as NH.sub.4[Cl]-cocrystallate with a 52% (1.91 g) yield. The solid is examined by multinuclear NMR spectroscopy and shows the formation of the mixed-substituted derivative.

[0211] .sup.1H NMR (CD.sub.3OD, in ppm): 1.33 (s, 3H, H8/8), 1.39 (s, 3H, H8/8), 3.23 (s, 9H, H1), 3.65 (m, 2H, H2), 3.82 (dd, 1H, .sup.2J.sub.HH=8.3 Hz, .sup.3J.sub.HH=6.1 Hz, H6), 3.88 (m, 2H, H4), 4.07 (dd, 1H, .sup.2J.sub.HH=8.3 Hz, .sup.3J.sub.HH=6.6 Hz, H6), 4.25-4.34 (m, 3H, H3/5); .sup.31P NMR (CD.sub.3OD, in ppm): 0.5 (quin, 1P .sup.3J.sub.PH=6.6 Hz).

Example 12d): Reaction of (Pyr).SUB.2.PO.SUB.2.[OTf] With Sodium Azide and 2,3-Isopropylidene Uridine

[0212] (Pyr).sub.2PO.sub.2[OTf] (370 mg, 1.0 mmol) and NaN.sub.3 (65 mg, 1.0 mmol) are suspended in CH.sub.3CN and stirred for 4 h at room temperature, causing a voluminous colorless precipitate to be deposited. A solution of 2,3-isopropylidene uridine (284 mg, 1.0 mmol) in pyridine is then added to the suspension, and the resulting mixture is stirred for another 16 h, resulting in a virtually clear solution. After removal of all volatile components in a vacuum, the residue obtained is washed with CH.sub.3CN and dried in a vacuum in order to obtain 334 mg of the raw product as sodium salt. The raw product is then purified by column chromatography with a CHCl.sub.3/MeOH mixture. After removal of all volatile components from the product-containing fractions, the free acid is obtained as a colorless hygroscopic powder. Yield 29% (111 mg). The solid is examined by multinuclear NMR spectroscopy and shows the formation of the mixed-substituted derivative.

[0213] .sup.1H NMR (DMSO-d.sub.6, in ppm): 1.29 (s, 3H, H7/8), 1.49 (s, 3H, H7/8), 3.83-3.96 (m, 2H, H5), 4.15-4.19 (m, 1H, H4), 4.77 (dd, 1H, .sup.3J.sub.HH=6.4/3.7 Hz, H3), 4.96 (dd, 1H, .sup.3J.sub.HH=6.4/2.4 Hz, H2), 5.60 (d, 1H, .sup.3J.sub.HH=8.1 Hz, H5), 5.83 (d, 1H, .sup.3J.sub.HH=2.4 Hz, H1), 7.76 (d, 1H, .sup.3J.sub.HH=8.1 Hz, H6), 11.38 (s(br), 1H, H3); .sup.31P NMR (DMSO-d.sub.6, in ppm): 5.6 (s, 1P).

[0214] The product of Example 1 (FIG. 1-3) shows one singlet each in the .sup.31P- and .sup.19F-NMR spectra. The resonance in the .sup.31P-NMR spectrum, with its chemical shift of (P)=15.8 ppm, indicates the phosphorus(V) precursor known from the literature (P. Rovnank, L. Kapika, J. Taraba, M. ernk, Inorg. Chem. 2004, 43, 2435). The resonance in the .sup.19F-NMR spectrum, with its chemical shift of (F)=79.2 ppm, indicates the triflate anion known from the literature. The chemical shifts in the .sup.1H-NMR spectrum at (H)=7.97 ppm, (H)=8.48 ppm and (H)=9.16 ppm indicate the presence of the pyridine ligand.

[0215] The product of Example 3 (FIGS. 4-6) shows one singlet each in the .sup.31P- and .sup.19F-NMR spectra. The resonance in the .sup.31P-NMR spectrum, with its chemical shift of (P)=14.2 ppm, indicates the phosphorus(V) precursor known from the literature (P. Rovnank, L. Kapika, J. Taraba, M. ernk, Inorg. Chem. 2004, 43, 2435). The resonance in the .sup.19F-NMR spectrum, with its chemical shift of (F)=78.4 ppm, indicates the triflate anion known from the literature. The chemical shifts in the .sup.1H-NMR spectrum at (H)=4.55 ppm, (H)=8.17 ppm and (H)=9.66 ppm indicate the presence of the DMAP ligand.