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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...

A simple and very fast process of transfer of a phosphorus atom, performed by a simple molecule acting as catalyst in an almost infinite catalytic cycle is described. The catalyst donates a P atom to a mixture of two different Grignard reagents giving, in a very fast and in a highly selective manner, only one phosphorus-containing compound with an enormous rate enhancement with respect to the corresponding no-catalyzed reaction which gives a final cluttered mixture of many organophosphorus products. The focal factor to explain this highly selective process of P transport lies in the folded structure of the reagent with particular angles around the phosphorus atom which can facilitate the formation of cyclic trigonal bipyramidal pentacoordinated species and then its catalytic activity. In a similar manner, RNA can adopt, in a precise position, a particular three-dimensional structure that might facilitate the formation of pentacoordinated species leading to the catalytic function.

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 1,2-diaza-1,3-butadienes with dibenzyl diisopropylphosphoramidite, methyl tetraisopropylphosphorodiamidite or tris(dimethylamino)phosphane under solvent-free conditions gave stable α-phosphoranylidene-hydrazones that, in turn, were transformed into the corresponding 5-oxo-4-phosphoranylidene-4,5-dihydro-1H-pyrazoles. X-ray diffraction analysis of one of these derivatives is reported. α-Phosphoranylidene-hydrazones, derived from the reaction between 1,2-diaza-1,3-butadienes with dibenzyl diisopropylphosphoramidite, were converted by hydrolytic cleavage into (E)-hydrazono-phosphonates, which are useful for the preparation of the corresponding (3-oxo-2,3-dihydro-1H-pyrazol-4-yl)phosphonamidates.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The reaction between tert-butylmagnesium chloride (or tert-pentylmagnesium chloride) and the particular phosphorus–sulfur bond of a benzothiadiphospholic system showed, for the first time, evidence of formation of intermediates with a four-center structure. The possibility, for the phosphorus atom, to have very stable hypervalent coordinations makes it possible to observe its hypervalent states during the course of a reaction. The benzothiadiphosphole, with its bicyclic folded structure, further stabilizes the hypervalent coordinations thus making the intermediates sufficiently stable to be detected during the course of the reaction by 31P NMR spectroscopy, which revealed the nature and the stability of the species involved in this reaction, carried out also using other Grignard reagents.

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.

The synthesis of the title compounds at room temperature in a one-pot reaction involves the transfer of a phosphorus atom from a benzothiadiphosphole to incoming nucleophilic bis- and mono-Grignard reagents.

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

The use of diazaphosphole derivatives generated in situ or the PCl3/hydrazone combination can be applied in a novel efficient one-pot procedure for the synthesis at room temperature of the title six-, seven- and eight-membered rings using always high concentration of the reagents (0.2–0.5M). N-alkenyl derivatives of 1,2-diazaheterocycles such as 8 (perhydro-pyridazine-3,6-diones), 9 (perhydro-1,2-diazepin-3,7-diones), 10 (perhydro-1,2-diazocin-3,8-diones) and 11 (1,2-dihydro-pyridazine-3,6-diones) were obtained by reaction of PCl3, ketone methylhydrazones and succinic, glutaric, adipic and maleic acids respectively. Changing the order of addition of reagents, or their simultaneous addition, gave identical results. In all the procedures the yields were good. The exclusive or prevalent formation of the E isomer was always observed. The E-configuration of the exocyclic double bond was deduced from some NOE experiments carried out on a E,Z mixture obtained by isomerization of the E isomer. Mechanism for the reaction is also proposed.

A series of glycoluril derivatives have been synthesized in water at room temperature from urea and 1,2-dicarbonyl compounds in the presence of phosphoric anhydride. The reaction time is about 10 minutes using one mole of 1,2-dicarbonyl compound, three moles of urea, and half mole of P4O10, but the reaction occurs also, even if with longer reaction times, with very small amounts of P4O10 which is recovered at the end of reactions. In fact, several catalytic turnovers can be performed using the same reaction solution obtained after separation by simple filtration of the glycolurils.

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.

For understanding the mechanism involved in the Wittig reaction, it is important to know the factors which influence the stability of 1,2-oxaphosphetane intermediates with pentacoordinate phosphorus; in these intermediates, the steric factor plays a predominant role. Studying the Wittig reaction between nonstabilized ylides and different aldehydes, we noted that the stereochemical outcome driving toward Z-olefin formation was influenced only by different steric factors. The proposed mechanism differs from those previously reported because it underlines the fundamental role of the two cis/trans oxaphosphetane intermediates with the oxygen atom in equatorial position.

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.

P4S10-induced reaction of urea derivatives with aldehydes results in formation of the title compounds in a short time.

Adenosine monophosphate isomers are obtained by self-assembling of adenine, D-ribose and trimetaphosphate in aqueous solution in good yields. This generation of a ribonucleotide from its three molecular components occurs in a one-pot reaction at room temperature for about 30-40 days and with high chemio-, regio-, and stereo-selectivity. Similar results are obtained with guanine. A mechanism is also proposed.

Phospha-Michael additions of a series of methylene-bridged phosphorus bidentate nucleophiles to 1,2-diaza-1,3-dienes gave monoadducts and bisadducts in high yields under mild conditions. In particular, a series of new ylides and symmetrical diylides have been obtained from bis(diphenyl)phosphanes. The use of diphenylphosphanylamino derivatives gave, through phospha-Michael addition, ylide intermediates that underwent spontaneous intramolecular attack by the amino group belonging to the Michael donor reagent moiety, thus giving access to new heterocycles.

New derivatives of 1,2-dihydro-2-alkenyl-3H-pyrazol-3-ones 6 and 7 have been synthesized at room temperature by a one-pot two-step reaction of PCl3, a ketone methylhydrazone, and a β-keto ester. With ketone methylhydrazones bearing at least a phenyl group in the α-positions to the CN bond and in the second step β-keto esters, such as propionyl- or butyrylacetates, we obtained 2-pyrrolylacetates 8 as unexpected products together with pyrazolones 7. The ratio of the two products depends on the nature of the groups in the α-positon to the CN bond. A chlorodiazaphospholine 1 is the key intermediate of this new reaction, and a plausible mechanism of formation of the azaheterocycles is reported.

The title compound 2b was obtained as a minor product in the reaction between a thioanisole and PCl3/AlCl3. The crystal and molecular structure has been determined by single crystal X-ray techniques. The compound crystallizes in the space group P 21/c, with α = 9.004(2), b = 13.416(3), c = 11.662(3) A, and β = 93.1 (1)°. The molecule adoptes a “butterfly” arrangement.

The title compounds have been synthesized by the one-pot reaction at room temperature of ketone alkylhydrazones, PCl3 and methyl acetoacetate; a single crystal X-ray structure determination of the minor isomer of one derivative permitted the assignment of its structure and showed the Z-configuration of the alkenyl group.

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.

New derivatives of 1,2-dihydro-2-alkenyl-3H-pyrazol-3-ones 6 and 7 have been synthesized at room temperature by a one-pot two-step reaction of PCl3, a ketone methylhydrazone, and a β-keto ester. With ketone methylhydrazones bearing at least a phenyl group in the α-positions to the CN bond and in the second step β-keto esters, such as propionyl- or butyrylacetates, we obtained 2-pyrrolylacetates 8 as unexpected products together with pyrazolones 7. The ratio of the two products depends on the nature of the groups in the α-positon to the CN bond. A chlorodiazaphospholine 1 is the key intermediate of this new reaction, and a plausible mechanism of formation of the azaheterocycles is reported.

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 title compounds 3 , a new series of 3,5-pyrazolidinediones, have been synthesized at room temperature by a one-pot reaction between ketone hydrazone 1, PCl 3 and malonic acid. Changing the order of addition of reagents, or their simultaneous addition, gave identical results. In all the procedures the yields are good and in the cases a,b,c and g the E -alkenyl isomer was obtained as the exclusive isomer. A dual mechanism which depends on the order of addition of the reactants is hypothesised.

The use of diazaphosphole derivatives generated in situ or the PCl3/hydrazone combination can be applied in a novel efficient one-pot procedure for the synthesis at room temperature of the title six-, seven- and eight-membered rings using always high concentration of the reagents (0.2–0.5M). N-alkenyl derivatives of 1,2-diazaheterocycles such as 8 (perhydro-pyridazine-3,6-diones), 9 (perhydro-1,2-diazepin-3,7-diones), 10 (perhydro-1,2-diazocin-3,8-diones) and 11 (1,2-dihydro-pyridazine-3,6-diones) were obtained by reaction of PCl3, ketone methylhydrazones and succinic, glutaric, adipic and maleic acids respectively. Changing the order of addition of reagents, or their simultaneous addition, gave identical results. In all the procedures the yields were good. The exclusive or prevalent formation of the E isomer was always observed. The E-configuration of the exocyclic double bond was deduced from some NOE experiments carried out on a E,Z mixture obtained by isomerization of the E isomer. Mechanism for the reaction is also proposed.

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

Anisoles 4 react with AlCl3 and PCl3 to yield the new fused bicyclic system derivatives 5 and 6 as major products in a one-pot procedure. An alternative multi-step synthesis of this system is also reported in which bis(o-methoxyaryl)phosphane oxides 11 are treated with AlCl3 and PCl3; the diarylphosphane oxides 11 are obtained by a new simple method.

The synthesis of the title compounds at room temperature in a one-pot reaction involves the transfer of a phosphorus atom from a benzothiadiphosphole to incoming nucleophilic bis- and mono-Grignard reagents.

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.

Phosphorus-31 NMR static powder spectra and high-resolution magic angle spinning spectra have been obtained for a new heterocyclic compound, cis-2,10-dimethyl[1,2,3]benzothiadiphospholo[2,3b][1,2,3]benzothiadiphosphole (1), which contains a P(III)—P(III) single bond. The homonuclear 31P–31P dipolar interaction manifests itself in both the magic angle spinning spectra and the non-spinning line shape. Under the AX spin pair approximation, analysis of the spinning sidebands in the MAS experiment yields a full characterization of the two 31P chemical shielding tensors. This approximation is confirmed by the exact powder line shape simulation for a homonuclear spin pair. Analysis of the dipolar subspectra also yields the absolute sign of 1J(P,P), which is found to be negative. Keywords: phosphorus–phosphorus single bond, chemical shielding tensors, dipolar NMR, MAS, static line shape.

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