Phosphorus reaction with silyls

As well as the Bingel reaction and its modifications some more reactions that involve the addition-elimination mechanism have been discovered. 1,2-Methano-[60]fullerenes are obtainable in good yields by reaction with phosphorus- [44] or sulfur-ylides [45,46] or by fluorine-ion-mediated reaction with silylated nucleophiles [47]. The reaction with ylides requires stabilized sulfur or phosphorus ylides (Scheme 3.9). As well as representing a new route to l,2-methano[60]fullerenes, the synthesis of methanofullerenes with a formyl group at the bridgehead-carbon is possible. This formyl-group can be easily transformed into imines with various aromatic amines. 

The phosphorus ylides of the Wittig reaction can be replaced by trimethylsilylmethyl-carbanions (Peterson reaction). These silylated carbanions add to carbonyl groups and can easily be eliminated with base to give olefins. The only by-products are volatile silanols. They are more easily removed than the phosphine oxides or phosphates of the more conventional Wittig or Homer reactions (D.J. Peterson, 1968). 

Early attempts to produce cephalosporin analogs by varying the 7-acylamino substituent were frustrated because, in contrast to previous experience with penicillins, a good method for producing the necessary 7-amino compound (33a) could not be found. This problem was finally solved when it was discovered that diazotization of the a-aminoadipyl residue produces an iminolactone (33b) which can be hydrolyzed to the free amine in good yield. Subsequently an improved procedure was developed which involves silylation of the carboxyl groups followed by reaction with phosphorus pentachloride to yield iminochloride (33c)... 

The reaction of silylated phosphorus(V) itnides with anhydrous hydrogen fluoride gives high yields of alkylenebis(ditluorophosphoranes) [Sf] (equation 19). 

The /J-silyl phosphorus ylides 9 undergo highly cnantioselective addition reactions with aromatic and aliphatic aldehydes51. 

As the phosphonium diylides, lithium phosphonium yldiides, first described by Schlosser and Corey (Ph3P=CR-Li R=H, C3H7) [60-62], have a high nucleophilicity and reactivity. Recently, the a-silylated lithium phosphonium yldiide 20 has been prepared from the stable phosphanyl-(silyl)carbene 19 and alkyl-lithium (Scheme 13). The first crystal X-ray diffraction study of such a reagent was proposed for 20 and its reaction with methyl iodide or phosphorus elec-... 

This section deals with reactions that correspond to Pathway C, defined earlier (p. 64), that lead to formation of alkenes. The reactions discussed include those of phosphorus-stabilized nucleophiles (Wittig and related reactions), a a-silyl (Peterson reaction) and a-sulfonyl (Julia olefination) with aldehydes and ketones. These important rections can be used to convert a carbonyl group to an alkene by reaction with a carbon nucleophile. In each case, the addition step is followed by an elimination. 

Isomerization of betaines 20k, 1 to silylated phosphorus ylides was also confirmed by their reaction with methanol-Ji, which occurs rather rapidly at room temperature to give Me2Si(OMe)2 and mixtures of a-deuterated phosphonium salts 72k, 1 (Scheme 33). It is most probable that, in this case, the reaction occurs mainly through the intermediate formation of a-silylated... 

The intermediate formation of betaines and their subsequent irreversible isomerization to silylated phosphorus ylides have previously been postulated for the reactions of phosphorus ylides with hexamethylsilirane,107 sila-108 and disilacyclobutanes109 with different substituents at the silicon atom (Schemes 34 and 35). 

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... 

As with other reactions, silyl esters of phosphorus acids constitute an important and useful category of reagents for conjugate addition reactions. With aldehydes, ketones, and esters, the silyl ester linkage is transferred to the carbonyl oxygen, facilitating the completion of the reaction, generating the free carbonyl or ester upon workup with a protic solvent (Equation 3.25). 

Some [hydroxy(tosyloxy)iodo]perfluoroalkanes, RFI(OH)OTs, were prepared from RfI(02CCF3)2 by reaction with either a sulfonic acid, e.g.p-TsOH, or a silyl sulfonate, e.g. Me3SiOTf [30,31]. Several organic acids derived from phosphorus... 

In the first example, nitration of the benzoate (140) with nitric acid affords the nitro derivative. Hydrogenation converts this to the anthranilate (141). In one of the standard conditions for forming quinazolones, that intermediate is then treated with ammonium formate to yield the heterocycle (142). Reaction of 142 with phosphorus oxychloride leads to the corresponding enol chloride (143). Condensation of 143 with m-iodoaniline (144) leads to displacement of chlorine and consequent formation of the aminoquinazoline (145). Reaction with the trimethylsilyl derivative of acetylene in the presence of tetrakis-triphenylphosphine palladium leads to replacement of iodine by the acetylide. Tributylammonium fluoride then removes the silyl protecting group to afford the kinase inhibitor erlotinib (146). ... 

Other examples of functionalization at C-2 via phosphorus ylides and phosphonate carbanions are described in Section 4.12.11. Utilization of 2-non-phosphorus-containing carbanions was also exemplified. Thus, 2-silicon-substituted 1,3-benzodithioles were synthesized via deprotonation of benzo-l,3-dithiole 245 with -BuLi and subsequent treatment of the resulting anion with trimethylsilyl chloride (TMSCl) to give 2-(trimethylsilyl)-benzo-l,3-dithiole 246 (Scheme 29). The second silyl group was introduced by further deprotonation of 246 ( -BuLi) followed by the reaction with an additional equivalent of TMSCl. Tin-substituted benzo-l,3-dithioles were synthesized in a similar way but the deprotonation of the monostannyl derivative was carried out with LDA (Scheme 29) <1996CL171>. 

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