1,2,4-Diazaphospholes, synthesis

A further example of the diazaphosphole synthesis by [3 + 2] cycloaddition is given by the reaction of a phosphoranediyl diazomethane (26) (R = NPr j) with P-chloro-bis(trimethylsilyl)-phosphaethene. The adduct loses trimethylchlorosilane and yields a 3-phosphoranediyl-l,2,4-diazaphosphole (or 3-phosphonio-l,2,4-diazaphospholide) (27). The analogous addition to the trimethylsilyl substituted P-chloro-bis(methylene)phosphorane (28) yields a 4-methylene derivative (29) of this diazaphosphole (molecular structure in Table 1). It provides the only fully characterized example of this type up to 1995. Methyl triflate methylates the compound at N-1 and gives a phosphonio methylene diazaphosphole cation (30). 

Construction of isolated or benzannulated five-membered rings of NHPs can be accomplished by means of various condensation or cycloaddition reactions all of which involve interaction of an electrophilic Pj and a nucleophilic C2N2 building block. Salts containing 1,3,2-diazaphospholide anions or 1,3,2-diazaphospholenium cations can be directly accessed by some of these reactions but the products are in most cases neutral 1,3,2-diazaphospholes or NHP. A particularly concerted effort has been directed toward the synthesis of P-halogen-substituted NHP which are capable of undergoing further reactions via halide displacement or halide abstraction and serve thus as entry points for the preparation of a wide variety of neutral and cationic NHP derivatives. 1,3,2-Diazaphospholide anions are normally accessed by deprotonation of suitable iV-H-substituted precursors. 

The synthesis of new heterocyclic derivatives under conservation of a preformed cyclic structure is not only of particular importance for the synthesis of ionic 1,3,2-diazaphosphole or NHP derivatives but has also been widely apphed to prepare neutral species with reactive functional substituents. The reactions in question can be formally classified as 1,2-addition or elimination reactions involving mutual interconversion between 1,3,2-diazaphospholes and NHP, and substitution processes. We will look at the latter in a rather general way and include, beside genuine group replacement processes, transformations that involve merely abstraction of a substituent and allow one to access cationic or anionic heterocycle derivatives from neutral precursors. 

In the past, several general reviews on heterophospholes [2, 4-6] have covered the chemistry of diazaphospholes reported until early 1990s. Synthetic routes to different classes of diazaphospholes have been reviewed [7], Analogy between the synthesis of anellated diazaphospholes and their nonphosphorus analogs has also been reviewed [8], Some recent advances in the chemistry of anellated diazaphospholes made by our group have been included in a review on anellated azaphosp-holes [9], The reviews on the synthetic applications of phosphalkynes also describe the synthesis of diazaphospholes from these synthons [10-12], Present review aims to highlight and update important reports related to the chemistry of diazaphospholes which have mainly appeared during the last 15 years. 

Monocyclic 2H-[ 1,2,3 Idiazaphospholes (B) are easily accessible from the condensation of the four-membered chain incorporated in hydrazones or azoalkanes with phosphorus trichloride making available a large number of representatives that have been intensively studied [2, 4, 7], In contrast, their 1//-isomers (A) are less known and are obtained only as second minor product during the synthesis of 2//-[l,2,3]diazaphospholes in some cases. A facile synthesis for pyrido-anellated azaphospholes has been developed in our group by making use of 1,2-disubstituted pyridinium salts for condensation with phosphorus trichloride [8, 13-15], Accordingly, cyclocondensation of 2-alkyl-1-aminopyridinium iodides (1) with phosphorus trichloride in the presence of triethylamine affords pyrido-anellated l//-[l,2,3]diazaphospholes, i.e. l,2,3]diazaphospholo 1,5-a] pyridines (2) (Scheme 1) [16],... 

Baccolini et al. developed a novel method for the synthesis of 2-phenyl derivatives of 2//-[l,2,3 Idiazaphospholcs [17], which are otherwise difficult to obtain from the condensation of hydrazones and PC13. Fused benzothiadiphosphole 4 was used as a phosphorus furnishing reagent in its reaction with conjugated phenylazoalkenes 3 to obtain 2-phenyl-[l,2,3]diazaphospholes (6, R =Ph) via intermediacy of a spiro-cyclic adduct 5 (Scheme 2). 

Scheme 2 Synthesis of 2-phenyl-[l,2,3]diazaphospholes using fused benzothiadiphosphole...

Scheme 10 Synthesis of [l,2,4]diazaphosphole from transient phosphaalkene...

Scheme 19 Synthesis of monocyclic [l,4,2]diazaphospholes from [3+2] cyclocondensation...

Scheme 32 Synthesis and methanolysis of palladium/platinum complexes of [l,2,3]diazaphospholes...

In this chapter, synthesis, structure, and reactions of various classes of diazaphospholes have been reviewed. Recently used synthetic methods and variations for obtaining diversely substituted diazaphospholes have been discussed. On account of the cycloadditions on P=C bond of [1,4,2]- and [l,2,3]diazaphospholes, a number of organophos-phorus compounds incorporating a bridgehead phosphorus atom have become accessible. Recently reported complexation reactions of diazaphospholes, illustrate their capability to form transition metal complexes via different coordination modes. 

A cyclic silyl hydrazone derivative <83ZAAC(50i)57> as well as azo compounds isomeric to hydrazones <74PS197> have also been used for the synthesis of 2//-1,2,3-diazaphospholes by the PCI3 condensation. 2,4,5-Triphenyl-l,2,3-diazaphosphole is best prepared from the respective azoalkene and a fused benzothiadiphosphole as phosphorus donating reagent <95TL447>. 

The usual synthesis from a hydrazone and PCI3 has been applied to prepare p-(l,2,3-diazaphos-phol-5-yl)benzylphosphonates, analogues to Fostedil in which the benzothiazol unit is replaced by a diazaphosphole ring. However, their activity to inhibit calcium transfer through biological membranes is weak <93PS(85)225>. 

The potential usefulness of 3//-l,2,4-diazaphospholes for the synthesis of other phosphorus heterocycles was demonstrated using 234 (Scheme 8.55) which, after UV irradiation at —40°C, gave a 5 1 mixture of 4,5-dihydro-3//-phospholes 235 and 236. The latter compound is the hrst example of the previously unknown 2H-phosphirene system (288). This reaction probably proceeds via a photochemical ring opening of 234 and formation of a phosphavinyl carbene. 

A synthesis of 4-cyano-2,3-dihydro-3-hydroxy-2,5-diphenyl-l//-l,2,3-diazaphosphole 3-oxide from hydrazidoyl halide PhC(Cl)=NNHPh and diethylphosphonoacetonitrile in the presence of sodium ethoxide was reported <2004PS(179)521 >. 

In CHEC-II(1996), several applications of dihydro-2//-l,2,3-diazaphospholes, generated in situ from a ketone hydrazone and PC13, as useful intermediates for the synthesis of indoles, pyrroles, pyrrolylacetates, and 1,2-di-hydro-2-alkenyl-37/-pyrazol-3-ones are listed <1996CHEC-II(4)771>. 

As an example we describe here the synthesis of the l//-l,2,4-diazaphosphole 22 that, on account of its easy accessibility and as parent compound of the class, is of general interest. The synthesis proceeds through condensation of the cation 21. The reaction of 21 with hydrazine involves cleavage of an ammonium salt to furnish the phosphole 23.46 The cation 21 is obtained via a methanaminium chloride—generated as an intermediate from N, A-dimethylformamide and oxalyl chloride—by condensation with tris(trimethylsilyl)phosphine. 

This reaction sequence is representative for the synthesis of 1,2,4-diazaphospholes, which are the phosphorus analogues of the 1,2,4-triazoles. The reaction behaviour resembles that of pyrazoles with an additional reaction centre provided by the P=C double bond. 

Diazaphospholes metal coordination, 17-18 synthesis with phosphaalkenes, 17 Dienediones, synthesis, 221 Dihydrofuran-2-ylidene complexes, synthesis, 212... 

The formation of dialkyl phosphoramidates from trialkyl phosphites and benzothiazol-2 1 sulphenamides has been discussed. (Diaryloxyphosphlnyl)phosphoramidic acids have been prepared by a short conventional sequence.A convenient one-pot synthesis of 1,3-dihydro-l,3,2-diazaphosphole 2-oxides (90)... 

Analogous to the synthesis of anellated imidazoles [48-50], a method has been developed for the preparation of anellated [l,4,2]diazaphospholes from [3 + 2] cyclocondensation of 2-aminocycloimines with chloromethyldichlorophosphine in the presence of Et3N (Scheme 12) [51]. 

The reaction is highly regioselective and a-unsubstituted diazaphospholes are obtained in high yields. Nevertheless, it appears that the potential of the method has not been fully realized, possibly due to the cumbersome synthesis of 38 [52],... 

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