Phosphorus acid derivatives, substitution

A review on the reaction of tervalent phosphorus acid derivatives with halogens has appeared. Alkylbis(diisopropyl-amino) phosphines (41) react with carbon tetrachloride or bromotrichloromethane to give the P-halogeno ylides (42) below 0 The ylides rearrange to the substituted phosphines (43)... 

The nomenclature of tervalent phosphorus acid derivatives is difficult, and the literature abounds with ambiguous or misleading names. The lUPAC rules allow three methods to name the compounds (i) as substitution products of phosphine (ii) as derivatives of the parent acid or (iii) as coordination compounds of phosphorus. Of these, only the first two methods are in common use, and Table 1 gives the names of representative examples of compounds according to (i) and (ii), with the name which will be used in this chapter underlined. 

Electrophilic substitution reactions (Scheme 4) in many cases convert one derivative of a tervalent phosphorus acid into another and numerous examples have been given in Section II. Therefore, the following discussion will be limited to electrophilic reactions which are not treated in Section II because they give products that are not tervalent phosphorus acid derivatives, or because the reactions are of limited preparative value. 

In a search for tervalent phosphorus acid derivatives with better phosphitylation properties than usual aminophosphines or phosphoramidites Nifant ev et al. have prepared several new reagents. These include pyrazole derivatives, e.g. (51), 2-aminopyridine derivatives, e.g. (52), amidine derivatives, e.g. (53), and hydrazine derivatives, e.g. (54). They were prepared by standard methods and examined for their reactivity towards alcohols and, in the case of the amidine derivatives, for their tendency to isomerize by migration of the phosphorus group to the other nitrogen atom. Another type of reactive tervalent phosphorus acid derivative is phosphites derived from hydroxylamine. Several stable derivatives, e.g. (55) and (56), have been prepared and substitution reactions with alcohols studied. ... 

The reactions of bis(phosphoryl) disulphides with a variety of tervalent phosphorus acid derivatives or triphenylphosphine have been studied by means of low-temperature n.m.r. Intermediates were detected which indicated initial attack on one sulphur atom followed by substitution reactions at one of the phosphorus atoms, Arbuzov dealkylations, or phosphorane formation. An example is shown for the reaction of tributyl phosphite with bis(diethoxyphosphoryl) disulphide (25). In order to obtain solely thiophosphate products it is necessary to use bis(thiophosphoryl) disulphides, and one such compound (26) has been proposed as a highly effective reagent for the oxidation of oligonucleoside phosphites to phosphorothioates. A comparison of the efficiency of (26) with that of four other sulphurizing agents for use in... 

Several reports have been made of a successful catalyzed addition/ substitution reaction resulting in direct attachment of phosphorus to aromatic rings. The preparation of mixed triarylphosphines has been accomplished by the reaction of tin- or silicon-substituted diphe-nylphosphines with aryl halides catalyzed by palladium reagents.74 A similar transformation has also been reported using nickel catalysis.75 The addition/substitution of diphenylphosphine to triflate functionalized phenolic linkages has been of use for the preparation of substances as analogues of tyrosine-related amino acid derivatives, accomplished with catalysis by palladium acetate (Equation 4.29).76... 

Note that the reaction at the phosphorus atom is postulated to occur by an SN2 (no intermediate formed) rather than by an addition mechanism such as we encountered with carboxylic acid derivatives (Kirby and Warren, 1967). As we learned in Section 13.2, for attack at a saturated carbon atom, OH- is a better nucleophile than H20 by about a factor of 104 (Table 13.2). Toward phosphorus, which is a harder electrophilic center (see Box 13.1), however, the relative nucleophilicity increases dramatically. For triphenyl phosphate, for example, OH- is about 108 times stronger than H20 as a nucleophile (Barnard et al., 1961). Note that in the case of triphenyl phosphate, no substitution may occur at the carbon bound to the oxygen of the alcohol moiety, and therefore, neutral hydrolysis is much less important as compared to the other cases (see /NB values in Table 13.12). Consequently, the base-catalyzed reaction generally occurs at the phosphorus atom leading to the dissociation of the alcohol moiety that is the best leaving group (P-0 cleavage), as is illustrated by the reaction of parathion with OH ... 

In many examples, it is not necessary to prepare the phosphorane. Instead, the dicarbonyl compound is heated with a trialkyl or triaryl ester of phosphorus acid or, less commonly, with a diester of a phosphonous acid (RP(OH)2, where R is an organic group). For example, when the thioester 301 is heated with dipropyl ethylphosphonite the 2-substituted carbapenem 302 is produced in 80% yield (Equation 32) <1997CPB1439>. This general method has been used to prepare 2-sulfide-substituted 1/3-methylcarbapenems <2000CPB126, 2001SC587> and O-protected 2-hydroxymethyl derivatives < 1999JA11261 >. 

Step 1 Reaction of the diphosphate oxygen of GDP with the phosphorus of the acyl phosphate to produce an intermediate similar to the intermediates formed in nucleophilic acyl substitutions of carboxylic acid derivatives. 

The general method of organic sulfo- (RSO2OH) and various substituted phosphorus acids [R0P(0)(0H)2, RP(0)(0H)2, etc.] is their silylation. Analogous recommendations have been proposed for the determination of inorganic anions. The values of retention indices on standard nonpolar phases (SE-30) are known for TMS derivatives of most important inorganic acids ... 

An improved preparation of (61) and of the new (62) has been published.Some new dialkyl trichloromethylphosphonites (63) have been prepared by a simplified method.The new, chelating bis-phosphite (64) has been prepared as shown.Some (methylthiomethyl)phosphonous acid derivatives (65)-(67) have been synthesized from phosphorus trichloride and the (methylthio-methyl)stannane (68). A series of unsymmetrically substituted (thiophosphonomethyl)phosphonous acid derivatives (69) and (70) has been prepared as shown for use as ligands. 

The asymmetric catalyst is based on the chiral bisphosphine, / ,/ -DlPAMP (18), that has chirality at the phosphorus atoms and can form a hve-membered chelate with rhodium. The asymmetric reduction of the Z-enamide proceeds in 96% ee (Scheme 9.19)." The pure isomer of the protected amino acid intermediate 19 can be obtained upon crystallization from the reaction mixture as it is a conglomerate." Although the catalyst system is amenable to the preparation of a wide variety of amino acids, especially substituted phenylalanine derivatives," " a major shortcoming of the approach is the need to have just the Z-enamide isomer as the substrate. 

With few exceptions, derivatives of tervalent phosphorus acids are prepared from phosphorus trichloride by nucleophilic substitution of one or two of the chloro groups with organometallic compounds, followed by substitution of the remaining chloro groups with alkoxy, amino, alkylthio groups, etc., or vice versa (Scheme 1). Occasionally a tervalent compound is best obtained by reduction of a (thio)phosphoryl derivative which is prepared from (thio)phosphoryl chloride (Scheme 2), or from a P—H compound and an electrophilic reagent, e.g. Scheme 3. 

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