Phosphorus reagents

RCHO + H2C=CHCH=PPh3 + CICH=CHX RCH=CHCH=CHCH=CHX 

RCHO + H2C=CHCH=PPh3 + C1CH=CHX----- RCH=CHCH=CHCH=CHX 

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Fluoroolefins may he prepared by the reaction of Wittig reagents and other pho sphorus-containtng y tides with fluorinated carbonyl compounds. (A discussion of the fluorinated Wittig reagents or other fluonnated phosphorus reagents with nonfluorinated carbonyl compounds is on page 581.) Tnphenylphosphoranes, derived from alkyltriphenyl phosphonium salts, react with 1,1,1-trifluoroacetone [3/] or other trifluoromethyl ketones [32, iJ] (equation 26) (Table 10). 

Whereas the production of arylnitrenes by the deoxygenation of nitrosobenzenes or nitro-benzenes by trivalent phosphorus reagents and their subsequent intramolecular ring expansion to 3//-azepines are well-known processes, the corresponding intermolecular reactions to form 1//-azepines have been exploited only on rare occasions and appear to be of little preparative value. For example, the highly electrophilic pentafluorophenylnitrene, obtained by deoxygenation of pentafluoronitrosobenzene with triethyl phosphite in benzene solution, produced a low yield (2-10%) of l-(pentafluorophenyl)-l//-azepine, which was isolated as its [4 + 2] cycloadduct with ethenetetracarbonitrile.169 With anisole as the substrate l-(pentafluorophenyl)-l//-azepin-2(3//)-one (16% bp 128 —130 C/0.4 Torr) was obtained. 

Cydization of P-hydroxy-a-amino esters under Mitsunobu reaction conditions is an alternative approach to aziridine-2-carboxylic esters [6b, 13-16], In this case the P-hydroxy group is activated by a phosphorus reagent. Treatment of Boc-a-Me-D-Ser-OMe 13 (Scheme 3.5) with triphenylphosphine and diethyl azodicarboxylate (DEAD), for example, gave a-methyl aziridinecarboxylic acid methyl ester 14 in 85% yield [15]. In addition to PPh3/DEAD [13b, 15], several other reagent combi-... 

Another versatile approach, which nicely complements these Mannich-based procedures, incorporates a preformed symmetrical hexahydro-l,3,5-triazine (HHT) intermediate. In this case the phosphorus reagent reacts with HHT as a trimeric form of the normal aldimine species generated in situ between the amine or amino acid and formaldehyde. These HHT reagents can often be puritied and isolated prior to the reaction with phosphites. They are reasonably stable under neutral or slightly basic conditions, but they can readily revert back to the original amine and formaldehyde after heating with aqueous acid (25). Several can be purchased commercially. 

Substitution reactions using neutral trivalent phosphorus reagents... 

Addition of a monobasic trivalent phosphorus reagent to an unsaturated ester in the presence of base... 

All of these reagents also undergo reaction spontaneously with acyl halides to generate the corresponding acyl-phosphoryl products (Figure 3.4). Reaction is easily accomplished by the slow addition of the acyl halide to the stirred phosphorus reagent, upon which an exothermic reaction ensues. This approach has been extensively exploited for the preparation of a wide range of a-ketophospho-nates.31-52... 

Simple reaction occurs with aryl halides only when the ring is sufficiently substituted with electron-withdrawing functions to allow attack by the nucleophilic phosphorus.53-56 Generally, reaction with aryl halides requires the presence of a Lewis acid catalyst or some other means of reaction initiation. These reactions will be considered in detail in Chapter 6 of this work. Interestingly, while reactions involving vinylic halides seem to correlate with those of aromatic halides (see Chapter 6), acetylenic halides undergo facile reaction with these phosphorus reagents.57 58... 

In the instances of phosphorous and phosphonous acid systems, the generation of a new C-P bond via the classical Michaelis-Arbuzov reactions as noted above leads to products that are esters themselves. Isolation of the free acid product requires cleavage of the ester linkage in a separate reaction step, generally after isolation and purification of the initial product. The advent of silyl phosphorus reagents for the Michaelis-Arbuzov reaction allowed free acid products to be isolated simply by water workup of the reaction system. Further, since the byproduct was a silyl-halide, the general concern that the by-product halide would participate in an extraneous Michaelis-Arbuzov reaction was obviated. 

Several methods for the preparation of the parent compound in this system, tris(trimethylsilyl)phosphite, have been reported.114 118 The application of this and related reagents in reaction with alkyl halides has been reported and used for the preparation of a variety of phosphonic acid analogues of phospholipids.114119-124 Interestingly, alkyl chlorides appear to be more reactive with the silyl reagents than do alkyl iodides, a reversal of the normally observed trend with alkyl esters of the phosphorus acids. (The particular use of silyl phosphorus reagents for the synthesis of biologically significant compounds has... 

Intramolecular alkyl transfer is a fundamental problem with this reaction this problem can be addressed with modification in structure of the reagents. Neutral trivalent phosphorus reagents do react with carbonyl compounds at much lower temperatures, but lead to several types of pentacoordinated phosphorus products.190-198 More will be noted about the use of such pentacoordinated phosphorus species for carbon-phosphorus bond formation in Chapter 5. 

A logical extension of the Abramov- and Pudovik-type reactions at carbonyl carbon is the conjugate addition of the phosphorus reagents at distant sites of conjugated carbonyl and related systems. A wide range of such Michael addition reactions, many of significant practical... 

A variety of substrates has been used in this type of conjugate addition reaction with trialkyl phosphites, with assorted proton sources.361 384 Other types of trivalent phosphorus reagents without acidic (or conjugate base of acidic) sites have also been used successfully for this conjugate addition process, including triaryl phosphites (without dealkylation),369 phosphoramidites,385 389 phospho-nites,363 380 390 and phosphinites.360 380... 

Anionic trivalent phosphorus reagents have also been found to be of use in the preparation of some intriguing species. For example, an approach to L-phosphinothricin and related materials has been accomplished by addition of the conjugate base of alkyl methylphos-phonites to protected L-vinylglycine species (Equation 3.31).450 The starting protected L-vinylglycine species are readily available from l-methionine and L-glutamic acid. 

The addition of anionic forms of trivalent phosphorus reagents (diethyl phosphite or diphenylphosphinite) to quinonemethides bearing two phosphoryl linkages on the exocyclic double bond provides a,a,a-triphosphoryl species (Equation 3.32).451... 

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