Phosphorus III nucleophiles

Reactions of Aziridines, 4-Oxazolines, and Their Derivatives with Alkylidene Phosphoranes and Phosphorus(III) Nucleophiles... 

Rings containing Nitrogen. - The reactions of aziridines with alkylidene-phosphoranes and with phosphorus(III) nucleophiles and the reactions of... 

Reactions between fluorine-containing compounds and phosphorus(III) nucleophiles have been reviewed. ... 

In order to obtain examples of aminohydroxyalkyl phosphonic acids diastereoisomerically enriched at the hydroxy site, the aldehyde (196) (from L-phenylalanine) was subjected to reactions with phosphorus(III) nucleophiles (Scheme 21) with diethyl rcrf-butyidimethylsilylphosphite it gave the adducts (197) and (198) (X = Bn, Y = SiMe2Bu ), convertible conventionally into (197) and (198)(X = Bn, Y = H), and thence to (197) and (198)(X = Y = H). The diastereoisomeric composition of the mixture was determined through a conversion into the oxazolidin-2-ones (199). In this way it was found that the ratio of (197)/(198)(X = Y = H) was >98 <2, a degree of selectivity which... 

Stereospecific ring closure. 2/ -Azido-3a-iodocholestane in benzene added to tri-methyl phosphite, allowed to stand at room temp, until spectroscopy shows disappearance of the IR-azide band, solvent and most of the excess trimethyl phosphite removed in vacuo, the ethereal soln. of the residue added to a stirred soln. of LiAlH4 in anhydrous ether at a rate to maintain reflux, and stirred 2 hrs. at room temp. 2, 3i -iminocholestane. Y 16%. - This convenient reaction sequence may be successful in cases where other methods fail. F. e., also isolation of the intermediate, and ring closure with other phosphorus(III) nucleophiles such as phosphines, s. A. Hassner and J. E. Galle, Am. Soc. 92, 3733 (1970). 

The formation of this initial complex has been attributed to the base-catalyzed shift in the phosphonate-phosphite equilibrium of these compounds to produce the reactive phosphorus (III) nucleophile. Trialkyl phosphites, which also easily form this type of complex [408-410], undergo an additional transformation to the corresponding phosphonate form and rearomatization of the system. 

A number of reactions of fluoro-oleflns with phosphorus(iii) nucleophiles have been described (c/. Vol. 1, p. 135). Perfluoroisobutene reacts, for example, with compounds of the type R PCl (R = Et, EtO, McjN, or EtjN) ... 

Reactions of cyclophosphines may be divided into three types (a) those that involve retention of the initial ring size, (b) those in which a P-P bond is cleaved and (c) those that result in a change in ring size, i.e. ring expansion or ring contraction. The former type (a) is observed for reactions with electrophilic reagents in which the lone pairs on the phosphorus(III) centres provide the nucleophilic site. These may involve simple adduct formation or oxidation to phosphorus(V) in some cases this oxidation may be accompanied by ring... 

According to a report by Allen131, reaction of 2-bromothiazole as well as 2-iodothiazole with a tertiary phosphine or phosphorus(III) ester in alcohol solvents involves nucleophilic... 

This chapter covers the main synthetically useful phosphonylation reactions, the corresponding processes of phosphinylation and tertiary phosphine oxide formation along with some related reactions. In all these reactions the phosphorus reactant (a phosphite, phosphonite, phosphinite, or derivative or tautomer thereof) is the nucleophilic component, herein these reactants are referred to collectively as phosphorus(III) reactants/acids, as appropriate in general these reagents are best used freshly distilled. Syntheses of phosphonates, phosphinates and tertiary phosphine oxides by nucleophilic substitution at phosphorus is not covered (for reviews of this area see Refs 6 and 16). 

The Michaelis-Arbuzov reaction is the most used and well-known method for the synthesis of phosphonates and their derivatives and may also be used to synthesize phosphinates and tertiary phosphine oxides. The simplest form of the Michaelis-Arbuzov reaction is the reaction of a trialkyl phosphite, 3, with an alkyl halide, 4, to yield a dialkyl alkylphosphonate, 6, and new alkyl halide, 7 (Scheme 2). During this transformation the phosphorus atom of a ter-valent phosphorus(III) species (3) acts as a nucleophile resulting in the formation of an intermediate alkoxy phosphonium salt 5, containing a new [P—C] bond. The precise structure of the intermediates 5 is a subject of debate—as reflected by common reference to them as pseudophosphonium salts —with a penta-coordinate species (containing a [P—X] bond) being proposed and detected in some cases.18 Decomposition (usually rapid under the reaction conditions) of the intermediate 5 by nucleophilic attack of X- on one of the alkyl groups R1, with concomitant formation of a [1 =0] bond yields the product pentavalent phosphorus(V) compound (6) and the new alkyl halide, 7. 

Diphenyl phosphorochloridite hydrolyzes slowly in air and more rapidly in water, but it is less reactive toward nucleophilic reagents than most chlorine derivatives of phosphorus(III). The reaction with alcohols in the presence of a tertiary base is used to prepare diphenyl alkyl phosphites. Addition of sulfur occur.s on reaction with thiophosphoryl chloride. 

In the presence of phosphorus(III) reagents such as triphenylphosphine or hexamethyl-phosphorous triamide the trihaloethyl esters are reduced in situ yielding activated acyloxy-phosphonium intermediates that undergo trapping by amine and alcohol nucleophiles.h l... 

By far the most important type of reaction displayed by halophosphines is nucleophilic substitution. This is pivotal to the preparation of many other three-coordinate compounds containing either solely P—C, P—O, P—N bonds, or mixed combinations. These reactions are often exothermic and frequently carried out at low temperatures. For the synthesis of phosphorus(III) compounds containing a P—O or P—N bond it is often necessary to add a base (triethylamine or pyridine are frequently used) to capture the hydrogen halide eliminated from these condensation reactions. In the case of P—C bond formation, a variety of routes are possible using various carbon-derived nucleophiles. 

However, even the pre-synthesized tetrazolides were still too reactive to be routinely used in the automated solid phase synthesis. The major advance that solved the problem was made in 1981, when Beaucage and Caruthers, who were experimenting with the nucleoside 3 -phosphoramidite derivatives [83] following some previous Russian work on the phosphorus(III)-amino compounds [84], discovered that these otherwise pretty stable compounds can be rapidly and very efficiently coupled to a solid-supported nucleoside in the presence of a mildly acidic nucleophilic catalyst, tetrazole [85]. This discovery combined with the already existing solid-phase assembly layout [68, 69, 82] paved the way for the very rapid expansion of the polymer-supported oligonucleotide synthesis, which has been summarized in the timely book edited by Gait [12a]. 

It is evident that the interaction of a phosphorus(III) triester and the alkylating species RX can be pictured as an S 2 process (reaction 2) or, for those alkylating reagents capable of forming a carbocation, as an S l process (reaction 3). Several reactions testify to the importance of carbocationic carbon for the Michaelis-Arbuzov reaction in pursuance of its normal course they include the ease of reaction of cyclopropene dihalides, already encountered, and the ready formation of complexes with species having particularly weakly nucleophilic counter ions. Phosphonic acid formation also takes place with cyclic azonium salts and related ions. 9-Chloroacridine reacts with triethyl phosphite to afford a product thought to be the bisphosphonic acid ester 49 The related phosphonic esters 51 are obtainable when the onium salts 50 (X = NH, NR, O or S) are treated with trimethyl... 

In principle, the interaction of a phosphorus(III) ester with an co-haloalkylamine should lead to an (co-aminoalkyl)phosphonic diester or a phosphinic acid analogue (Scheme 11). Such examples in the classical Michaelis-Arbuzov mould have been widely reported, but success in their outcome depends on the relative nucleophilicities of nitrogen and phos-phorus(III) centres towards the displacement of halogen. The interaction of triethyl phosphite and a halogen-substituted tertiary amine, such as 2-chloroethyldiethylamine, does not lead to a phosphonic diester, and in this particular case the product is a piperazinium diquaternary salt. However, successful Michaelis-Arbuzov reactions have been carried out between the bis(bromomethyl)phthalazines 130 (to both the mono- and di-phosphonic acid stages) and the series of [co-(2-cyano-4-pyridine)alkyl]phosphonic diesters 132 (n = 1-4) have been prepared from the 4-pyridinealkyl bromides 131 as precursors to the phosphonoalkylpiperidinecarboxylic acids 133 . ... 

Katti et al. synthesized polyhydroxyphosphines (Stmctures 1-5) by the nucleophilic addition of PH3 or primary phosphines to formaldehyde or other carbonyl compounds (4). The utility of such ligands in the formation of water-soluble transition metal complexes was evidenced in several cases [5]. It should be noted that besides the phosphorus(III) atom, hydroxy groups also can coordinate with soft transitions metals [3, 6]. 

It is postulated that thermal decomposition of tetra-alkylphosphonium salts proceeds through four types of reactions [42, 43] (i) nucleophilic substitution at the a-carbon (Sn(C)) (ii) (3-elimination (iii) nucleophilic substitution at the phosphorus atom (Sn(P)) (iv) a-elimination. Sn(C) nucleophilic substitution involves the attack of the halide on the a-carbon, leading to the formation of an alkyl halide and a tertiary phosphine ... 

The other approach to P-ylides based on the nucleophilic addition of phosphorus(HI) reagents to the terminal carbon atom of 1,2-diaza-1,3-butadienes has continued to find application. The reaction with dialkyl-phosphonites or phosphorus(III) amides under solvent-free conditions (and in the presence of atmospheric moisture) was found to be a convenient approach to a-phosphanylidene hydrazones (42). The linear ylides (42) in THF solution undergo further intramolecular transformations to give 1,2,3X -diazaphospholes (43) in the case of phenylphosphinite as a starting substrate or 5-oxo-4-phosphoranyidene-4,5-dihydro-l/f-pyrazoles (44) using tris(dialkylamino)phosphine. 

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