A-silyl phosphonates

Anions of a-silyl phosphonates of type (153) also undergo additions to carbonyl compounds. The corresponding addition products, 3-silyl alkoxides, can react with ketones to yield the product of the Peterson alkenation or the Wittig reaction. In practice only the Peterson product (154) is obtained, indicating that loss of OSiMes is faster than elimination of C PPhs (Scheme 68). 72 If the a-silyl carbanion is adjacent to a chlorine atom (155), an internal displacement reaction follows the initial formation of the -silyl alkoxide, and epoxides (156) are formed (Scheme 69). 74... 

In the Peterson reaction of an a-silyl carbanion bearing a phosphorus substituent on the anionic carbon atom, there are two possibilities for alkene formation, that is, the Peterson reaction to form phosphorus-substituted alkenes and the Wittig-Horner reaction and the Wadsworth-Emmons reaction to form silicon-substituted alkenes. Most of the reports on these competing reactions have been focused on the reactions of a-silyl phosphonates with carbonyl compounds. It is noteworthy that the alkenylphosphonates have been exclusively obtained in almost every case. That is, the Peterson reactions override the Wittig and Wadsworth-Emmons reactions. 

Me(Ph)SiCl2 reacts with dimethyl phosphonate in a 1 1-mixture at 100°C to the O.O-disilylated phosphonate. In contrast to this observation the O-alkyl O-silyl phosphonate is formed solely by reaction of both compounds in acetonitrile at 80°C (line 7,8). An excess of the corresponding phosphonate as polar solvent leads to the mixed ester 2 only. The excess of the dialkyl phosphonate is removed from the mixture by vacuum distillation (line 9). 

The insertion of the oxiranes into a P-O-C- bond of the mixed ester takes place in the reaction of the O-alkyl O-silyl phosphonates 3 with oxiranes in contrast to the reaction above. The formed 0-(2-siloxyethyl) O-alkyl phosphonates 11 show the typical PH-reactivity with the protected HO-group for further reactions. 

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. 

Of course, the use of tris(trimethylsilyl) phosphite213 214 provides facile access to the free a-hydroxyphosphonic acids. These silyl reagents have been used for the preparation of a wide range of a-substituted phosphonates and -phosphonic acids, starting with ketene,215 a-ketophosphonates,216 ketoesters,217 218 and a,P-unsaturated carbonyl compounds,207/219-221 as well as simple aldehydes and ketones.205 210/219 224 Their use for the preparation of compounds of significant biological interest has been reviewed.125... 

A solvent blank is used to eliminate the possibility of contamination arising from outside the sample, for example, from the syringe or from the instrument. It is recommended to use the sample solvent as solvent blank and run this test at the beginning and at the end of each sample series and whenever contamination is suspected. The memory effect is possible, for example, in the analysis of alkyl phosphonic acids. If the derivatization of these chemicals has not been complete, the nonderivatized acids are adsorbed on the injector liner. A silylation reagent may in such case react in situ with the adsorbed acids in the liner yielding false positive results. 

Olefination of aldehydes with a-silyl- and a-stannyl-stabilized phosphonate carbanions derived from cyclo-[L-AP4-D-Val] allow a (Z)-selective access to a,p-substituted vinyl phosphonates (343) that have been transformed into enantiomerically pure 4-alkylidene 4PA derivatives (344) (Figure 54). " Electrophilic fluorination of lithiated bis-lactim ethers derived from cyclo-[L-AP4-D Val] (345) with commercial NFSi allow direct access to a-monofluor-inated phosphonate mimetics of naturally occurring phosphoserine (346) and phosphothreonine (347), in enantiomerically pure form and suitably protected for solid-phase peptide synthesis (Figure 55). ... 

Generally alkylidenephosphoranes that carry in addition to the ylidic function another reactive site (e.g. a second ylide function, an additional phosphonate group, a halogen or a silyl substituent) may react at this additional functional group thus providing a derivative of the original ylide. 

Silylated phosphonates have been known since 1956, but their use as reagents in phosphorus chemistry has become important only in recent years.The first participation of the trimethylsilyl group in phosphonate chemistry was reported in 1972, as an extension of the Peterson reaction, and trimethylsilyl was first used as a protecting group in 1988. Undoubtedly, the combination of phosphonate and trimethylsilyl groups has given rise to new synthetic developments and applications for phosphonate chemistry. 

Allspach, T., Gtimbel, H., and Regitz, M., Studies on diazo compounds and azides. Part 63. Silylation of a-diazo phosphonates and carboxylates with silyl triflates, J. Organomet. Chem., 290, 33, 1985. 

Al-Badri, H.. About-Jaudet. E., and Collignon, N., Reaction of in situ generated a-silylated allylic phosphonate carbanions with aldehydes. An unexpected cyclization reaction, J. Chem. Soc., Perkin Trans. 1, 931. 1996. 

Trifluoroethanol is an efficient and recyclable solvent in helping one-pot, three-component coupling reactions of aldehydes or ketones, amines, and trimethyl-silyl cyanide or trimethyl phosphate to yield the corresponding a-amino nitriles or a-amino phosphonates in high yields (Equation 4.18). This method does not require the use of either an add or base catalyst [40],... 

Wenzel and Jacobsen reported the thiourea 15b-catalyzed Mannich-type reaction of a ketene silyl acetal with an N-Boc-aldimine, furnishing (3-amino esters with excellent enantioselectivities (Equation 10.30) [59]. Subsequently, Jacobsen and co-workers reported the hydrophosphonylation of dialkyl phosphites with aldimines to yield a-amino phosphonates [60]. 

The use of silyl phosphite esters in the Abramov reaction is well established, but a practical modification involves the addition of MesSiCl to a mixture of triethyl phosphite and carbonyl reactant at room temperature. The addition of a silyl phosphite (R = Si-containing group) to a chiral hydroxyaldehyde derivative (138) (R is also a Si-containing group) affords a mixture of the diprotected diastereoisomeric (l,2-dihydroxyalkyl)phosphonic esters (139) and... 

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