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This mini-review shows that the origin and evolution of life might be governed by a chemical process in which the formation of cyclic pentacoordinated phosphorus intermediates is activated of a factor 106–8 over other similar collateral processes containing acyclic phosphorus compounds. It follows that primordial cyclic phosphorylating reagents such as phosphoric anhydride (P4O10), produced from volcano magma, and its natural derivative trimetaphosphates (TMP) could be used to obtain very important biochemical molecules such as proteins, natural heterocyclic bases, adenosine mono- and triphosphate (AMP and ATP) isomers, etc. very rapidly in prebiotic conditions. In addition, some results demonstrated that it is possible to generate, with high chemio-, regio-, and stereoselectivity, AMPs and their oligonucleotides together with small amounts of ATP, by mixing in a one-pot reaction, D-ribose, adenine, and TMP in aseptic water as a solvent. This process might explain the spontaneous generation of pre...

In this article, we present a study about the non-enzymatic hydrolysis of phosphoenolpyruvate (PEP) by following the reaction course through 31P NMR spectroscopy. We have demonstrated that PEP in water exists mainly as a very stable cyclic pentacoordinate phosphorus compound in equilibrium with other cyclic forms. This explains the PEP stability in water. In contrast, after addition of an alcohol to a PEP aqueous solution, other very unstable cyclic pentacoordinated intermediates are formed, which immediately collapse, giving a feasible phosphorylation of the alcohol. It is known that cyclic pentacoordinated phosphorus intermediates are favored over the corresponding acyclic intermediates by a factor of 106–108, and this preference, found also in this study, might be the “driver mechanism” able to overcome the clutter of abiotic chemistry, thus permitting formation of pre-RNA molecules probably with a “self-organized process.”

Asymmetric alkyl phospholanes have been diastereoselectively synthesized by addition of an unsymmetrical bis-Grignard reagent and of a mono-Grignard reagent to benzothiadiphosphole (1) and isolated as sulfides. The relative cis/trans ratio of the products depends on the steric hindrance of the mono-Grignard used. An accurate analysis of NMR and stereoselective data revealed the fundamental role played by hexacoordinated phosphorus intermediates in driving the stereochemical outcome of the reaction. The particular bicyclic and folded structure of reagent 1 strongly stabilizes hypercoordinated phosphorus species involved in the reaction and favors their formation. Pentacoordinate and metastable hexacoordinate phosphorus species have been detected and their evolution studied through (31)P NMR spectroscopy. The diastereoselective outcome of the reaction between reagent 1 and the couple bis-Grignard reagent 5/mono-Grignard reagent has been explained through a pathway involving hexacoordination of the phosphorus as a key step.

The reaction of benzothiadiphosphole 1 with an equimolar mixture of R 1 MgBr and R 2 MgBr gave intermediate A¢, which, after only 4-5 min, was treated with an equimolar amount of R 3 MgBr, giving the asymmetric phosphine PR 1 R 2 R 3 in 45% overall yield (75-80% yield when R 1 ) R 2 and 85-90% yield when R 1 ) R 2 ) R 3 ) and the byproduct 6 in 90% yield. The treatment of 6 with PCl3 quantitatively regenerates the starting reagent 1. Treatment of the phosphines with elemental sulfur gave the corresponding sulfides.

This letter describes a new one-pot method for the synthesis of unsymmetrical aryl methylphoshinates by insertion of phosphorus moiety into the OMe bond of anisoles. These products are very difficult to obtain with other reported methods requiring several steps.

The use of a PCl3/hydrazone/dicarboxylic acid combination can be applied in an efficient one-pot procedure for the synthesis at room temperature of the title ring compounds that are also a new family of stable enamines. The phthalazinediones 7 were obtained in good yields by reaction of PCl3 with phthalic acid and hydrazones 1a,b,c containing hydrogen atoms only in one α position. Two structurally isomeric phthalazinediones (7 and 8) were obtained with hydrazones 1d,e,f,g containing hydrogen atoms in the two different α positions. When we used a methyl ketone hydrazone 1c,d,e,f,i, it was possible also to isolate the isomer containing an N-alkenyl group with two terminal hydrogen atoms. Where E,Z isomers are possible, the exclusive formation of the E isomer was always observed. As a rule, changing the order of addition of reagents gave almost identical results; however, in the case of phthalic acid, it is better to use the procedure in which PCl3 is added last to prevent the formation of the corresponding anhydride. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 291–296, 1999

A fresh look has been taken at the reaction of PCl3 with thioanisole 1b and AlCl3 that gives, after treatment with water, the title compounds cis-2b in 38% yield together with small amounts of the isomeric cis-3b (2%). The course of this reaction has been studied by 31P-NMR spectroscopy. A multistep pathway, governed by the formation of several AlCl3 complexes with sulfur and phosphorus containing intermediates, has been proposed. The crucial step of this reaction is very reasonably an intramolecular electrocyclic ring closure of a diphosphane intermediate. From this plausible mechanism, an improved procedure that gives only the cis-2b isomer in 42% yield has been realized. In addition, an alternative synthesis using p-thiocresol that gives compounds cis-2b and cis-3b in a ratio of about 2:1 has been effected. © 1997 John Wiley & Sons, Inc. Heteroatom Chem 8:551–556, 1997

Conjugated azoalkenes 2 react at reflux toluene with fused benzothiadiphosphole 1 (or 4) to give the diazaphosphole 3 in 25–52% yields. With this route it is possible to isolate the so far unknown 3a which is difficult to obtain in other reported conditions. The P atom involved in this cycloaddition is the one between the two S atoms.

Fused 1,3-benzothiaphospholes 2 (cis-2,6,10-trimethyl-[1, 3]benzothiaphospholo[2,3-b][1, 3]benzothiaphosphole) reacts with H2O2 and S8, giving the corresponding oxide and sulfide, respectively. The reactions of 2 with diethyl azodicarboxylate (DEAD)/catechol or DEAD/o-aminophenol, o-azidophenol, and tetrachloro-o-benzoquinone (TOB) give the first examples of spiro pentacoordinated phosphorus derivatives of this heterocyclic system. The X-ray structural analysis of spiro compound 3 showed a trigonal bipyramidal configuration at phosphorus in which the three rings assume axial-equatorial positions.

4-Bromodiazaphosphole-3-oxides or sulfides can be obtained by reaction of the corresponding unsubstituted derivative with appropriate reagents. PTAB was demonstrated to be very regio- and stereoselective, allowing bromination exclusively at the 4-position of the ring with prevalent or exclusive formation of one of the two possible isomers. However, when regioselectivity is not required, cheaper and more available bromine or NBS can be used conveniently. 4-Chlorodiazaphosphole-3-oxides can be obtained by reaction of the corresponding unsubstituted derivative with NCS. 4-Bromodiazaphosphole-3-oxides undergo stereoselective methanolysis as well as parent unsubstituted oxides.

Conjugated azoalkenes 2 react at reflux toluene with fused benzothiadiphosphole 1 (or 4) to give the diazaphosphole 3 in 25–52% yields. With this route it is possible to isolate the so far unknown 3a which is difficult to obtain in other reported conditions. The P atom involved in this cycloaddition is the one between the two S atoms.

Fused 1,3-benzothiaphospholes 2 (cis-2,6,10-trimethyl-[1, 3]benzothiaphospholo[2,3-b][1, 3]benzothiaphosphole) reacts with H2O2 and S8, giving the corresponding oxide and sulfide, respectively. The reactions of 2 with diethyl azodicarboxylate (DEAD)/catechol or DEAD/o-aminophenol, o-azidophenol, and tetrachloro-o-benzoquinone (TOB) give the first examples of spiro pentacoordinated phosphorus derivatives of this heterocyclic system. The X-ray structural analysis of spiro compound 3 showed a trigonal bipyramidal configuration at phosphorus in which the three rings assume axial-equatorial positions.

The use of a PCl3/hydrazone/dicarboxylic acid combination can be applied in an efficient one-pot procedure for the synthesis at room temperature of the title ring compounds that are also a new family of stable enamines. The phthalazinediones 7 were obtained in good yields by reaction of PCl3 with phthalic acid and hydrazones 1a,b,c containing hydrogen atoms only in one α position. Two structurally isomeric phthalazinediones (7 and 8) were obtained with hydrazones 1d,e,f,g containing hydrogen atoms in the two different α positions. When we used a methyl ketone hydrazone 1c,d,e,f,i, it was possible also to isolate the isomer containing an N-alkenyl group with two terminal hydrogen atoms. Where E,Z isomers are possible, the exclusive formation of the E isomer was always observed. As a rule, changing the order of addition of reagents gave almost identical results; however, in the case of phthalic acid, it is better to use the procedure in which PCl3 is added last to prevent the formation of the corresponding anhydride. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 291–296, 1999

4-Bromodiazaphosphole-3-oxides or sulfides can be obtained by reaction of the corresponding unsubstituted derivative with appropriate reagents. PTAB was demonstrated to be very regio- and stereoselective, allowing bromination exclusively at the 4-position of the ring with prevalent or exclusive formation of one of the two possible isomers. However, when regioselectivity is not required, cheaper and more available bromine or NBS can be used conveniently. 4-Chlorodiazaphosphole-3-oxides can be obtained by reaction of the corresponding unsubstituted derivative with NCS. 4-Bromodiazaphosphole-3-oxides undergo stereoselective methanolysis as well as parent unsubstituted oxides.

The reaction of 1,2-diaza-1,3-butadienes with dialkyl phenylphosphonites under solvent-free conditions proceeds via zwitterionic intermediate and gives, by precipitation, the stable ylidic α-phosphanylidene-hydrazones that, in turn, can be transformed into the corresponding 3-phenyl-2 H -1,2,3λ 5 -diazaphospholes. The latter compounds are converted by hydrolytic cleavage in methanol–water (95:5) into E -hydrazonophosphonates that are useful for the preparation of the corresponding β-ketophosphonates and 4-[alkoxy(phenyl)phosphoryl]-1,2-diaza-1,3-butadienes. These peculiar 1,2-diaza-1,3-butadienes, bearing an alkoxy(phenyl)phosphoryl group on the carbon atom in position 4 are also able to add different nucleophiles, such as methanol or thiourea, giving 2-[alkoxy(phenyl)phosphoryl]-2-methoxyhydrazones and 5-phosphinate-substituted thiazol-4-ones, respectively.

New arsenic-, antimony- and bismuth-donor reagents are used in a one-pot synthesis of cyclic arsanes, stibanes and bismutanes through a procedure in which the simultaneous formation of three C As, C Sb or C Bi bonds is achieved. At the end of the reaction, the element-donor reagent can be easily re-formed in situ and recycled, as in a catalytic process.

The reaction of 1,2-diaza-1,3-butadienes with dialkyl phenylphosphonites under solvent-free conditions proceeds via zwitterionic intermediate and gives, by precipitation, the stable ylidic α-phosphanylidene-hydrazones that, in turn, can be transformed into the corresponding 3-phenyl-2 H -1,2,3λ 5 -diazaphospholes. The latter compounds are converted by hydrolytic cleavage in methanol–water (95:5) into E -hydrazonophosphonates that are useful for the preparation of the corresponding β-ketophosphonates and 4-[alkoxy(phenyl)phosphoryl]-1,2-diaza-1,3-butadienes. These peculiar 1,2-diaza-1,3-butadienes, bearing an alkoxy(phenyl)phosphoryl group on the carbon atom in position 4 are also able to add different nucleophiles, such as methanol or thiourea, giving 2-[alkoxy(phenyl)phosphoryl]-2-methoxyhydrazones and 5-phosphinate-substituted thiazol-4-ones, respectively.

The reaction under mild conditions of fused cis-1,2,3-benzothiadiphospholes (1) with RCOCl–AlCl3(R = Me, Et, Pri, CH2(CH2)2CH2Cl, hexyl, CH2Ph) gave fused cis-6-R-1,3-benzothiaphospholes (2)via a phosphorus carbon exchange, in good yields. Use of a variety of acyl chlorides showed that the reaction does not occur when the R group is very bulky. Following the reaction by g.l.c.–m.s., it was noted that, initially, trans-(2) is formed and this isomerizes to cis-(2). A mechanism for this unusual phosphorus–carbon exchange is reported.

[reaction: see text] A general new method for the one-pot preparation of secondary phosphines 11 and in situ generation of their borane complexes 12 is described. This method consists of the sequential addition, at room temperature, of equivalent amounts of R(1)MgBr and R(2)MgBr to 1 equiv of the phosphorus atom donor reagent 1. Final treatment with water gives secondary phosphines R(1)R(2)PH (or the corresponding phosphine-borane complexes if treated with BH(3).THF) and the end product 6, which can be recycled.

Treatment, at room temperature, of benzothiadiphosphole 1 with BrMg(CH2)5MgBr gives intermediate A, which was allowed to stand for about 3 h at room temperature. The subsequent addition of RMgX to the reaction mixture and the final treatment with an excess of S8 and water affords the dithiaphosphepine sulfide 8 in good yields. The structure of this new heterocyclic system, containing both an SS unit and a PS group, is confirmed by an single crystal X-ray structure determination. If the reaction is carried out without final treatment with sulfur we obtain, using PhMgBr as mono-Grignard reagent, the corresponding ring-opened product 11b, which can be easily transformed into the corresponding ring-opened sulfide 12b by simple treatment with elemental sulfur. Further addition of sulfur to 12b gives quantitatively the cyclic dithiaphosphepine sulfide 8b. The two phosphanethiols 11b and 12b are of considerable interest. In fact, recently, attention has increasingly been paid to the coordination chemistry of polydentate ligands incorporating both thiolate and tertiary phosphine groups, also known as SPS pincer ligands. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:339–345, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20099

[structures: see text] The present article describes the reaction between 1,2-diaza-1,3-butadienes and trialkyl phosphites, under an atmosphere of nitrogen and under solvent-free conditions, to give alkyl 3,3-dialkoxy-2H-1,2,3lambda5-diazaphosphole-4-carboxylates that, in turn, are converted into corresponding E-hydrazonophosphonates by treatment with THF:water (95:5). These latter compounds are obtained directly by the reaction of 1,2-diaza-1,3-butadienes with trialkyl phosphites in the presence of air. These compounds are useful for the further preparation of dialkyl (5-methyl-3-oxo-2,3-dihydro-1H-4-pyrazolyl)phosphonates and 2-dialkoxyphosphoryl-1,2,3-thiadiazoles.

Phosphanes: No pain, all gain. A regenerable phosphorus donor is the key to an efficient and economic one-pot synthesis of five- and six-membered secondary cyclic phosphanes. The reaction, at room temperature, of 1 with 1 equivalent of bis(Grignard reagent) 2 followed by treatment with aqueous acid gives cyclic phosphanes 3 in 70-80 % yield and the new compound 4. Simply treating 4 with PCl3 quantitatively regenerates the starting reagent 1, which can be reused without further purification.

The reaction under mild conditions of fused cis-1,2,3-benzothiadiphospholes (1) with RCOCl–AlCl3(R = Me, Et, Pri, CH2(CH2)2CH2Cl, hexyl, CH2Ph) gave fused cis-6-R-1,3-benzothiaphospholes (2)via a phosphorus carbon exchange, in good yields. Use of a variety of acyl chlorides showed that the reaction does not occur when the R group is very bulky. Following the reaction by g.l.c.–m.s., it was noted that, initially, trans-(2) is formed and this isomerizes to cis-(2). A mechanism for this unusual phosphorus–carbon exchange is reported.

The title reaction between substituted phenyl azides 2 and diastereomeric diazaphospholenes 1 gives the corresponding cyclic phosphazenes 3 with different stereochemical results. Hydrolysis of some phosphazenes 3 yield the corresponding ring-opened compounds Z-4I together with small amounts of diazaphospholene-oxide 5 and anilines 6. The configuration of the compounds obtained are established by 1H n.m.r. spectroscopy. The results are explained invoking the formation of pentacoordinate phosphorus intermediates.

Thermal substitution reactions of M(CO)5Br (M=Mn, Re) with cis (L c ) and trans (L t ) diazaphosphole ligands (L=3,4-dihydro-2,3,4,5-tetraphenyl-2H-1,2,3-diazaphosphole) have been studied. It has been found that L c behaves as generally found for bulky phosphines affording to cis-M(CO)4(Lc)Br, mer-M(CO)3(L c )2Br and fac-Re(CO)3(L c )2Br which has been thermally isomerized to mer-Re(CO)3(L c )2Br. In contrast the corresponding reaction with the bulkier trans diazaphosphole isomer L t have only afforded cis-M(CO)4(L t )Br and mer-M(CO)3(L t )2Br. All the different stereochemical results are rationalized on the basis of the size of the central metals and of the steric demand of the ligands. The nature of the complexes has been established essentially by IR spectra which, in the case of cis-Re(CO)4(L c )Br presents in cyclohexane solution a doubling of all the characteristic v(CO) bands expected for the C 2v local symmetry. This unexpected result has been tentatively discussed also on the light of a...

Reaction of cis-[ReBr(CO)4( Lc)] with chiral Lc(cis-3,4-dihydro-2,3,4,5-tetraphenyl-2H-1,2,3-diazaphosphole) afforded fac-[ReBr(CO)3(Lc)2] which, owing to the racemic nature of Lc(R,S-L), should be a mixture of three predictable diastereoisomers: fac-[ReBr(CO)3(R-L)(S-L)][meso-(A) or meso-(B)] and the enantiomeric pair fac-[ ReBr(CO)3(R,S-L)2]. Two of these forms, meso-(A) and the enantiomeric pair, have been separated by column chromatography and their nature unambiguously attributed by X-ray studies. fac-[ReBr(CO)3(R-L)(S-L)] crystallizes in the monoclinic space group P21/n, with a= 19.481(4), b= 13.204(3), c= 20.083(8)A, β= 110.56(3)°, and Z= 4; R′= 0.046. fac-[ReBr(CO)3(R,S-L)2]·C6H14·C7H16 crystallizes in the monoclinic space group P21/n, with a= 12.191(3), b= 20.939(4), c= 21.713(5)A, β= 93.93(3)°, and Z= 4; R′= 0.048. Attempts to separate or detect spectroscopically isomers of fac-[ReBr( CO)3( L)2](L = racemic PMeEtPh) failed, indicating that interligand interactions are the determining factors in achieving the separation.

Reaction of diphenylnitrilimine (6) with phosphites (7) leads to the formation of α-phenylhydrazonophosphonates (9), whose configurational assignment about the CN bond has been determined.αβ-Bis(phenylhydrazono)phosphine oxide (10I)[or (10II)] is obtained by the reaction of (6) with diazaphospholen cis-(8)[or trans-(8)], a mixture of (10I and III)[or (10II and IV)] being formed only after work-up. Configurational assignments about the two CN bond have been determined and the relative configuration of the two chiral centres in (10I–IV) has been tentatively assigned. The stereospecificity of this reaction is explained in terms of spirocyclic pentaco-ordinate phosphorus intermediates whose formation may be favoured by ligand subset symmetry.

Treatment of fused 1,2,3-benzothiadiphospholes with acetyl chloride, in the presence of AlCl3, leads to fused 1,3-benzothiaphospholes, in which an unexpected phosphorus-carbon exchange has occurred; a single crystal X-ray diffraction of the dimethyl derivative of this new heterocycle confirmed its structure and showed the cis-configuration between the phosphorus Ione pair and the 6-substituent.