Phosphonyl anions

Scheme 80). The reactions exhibit high diastereoselectivity, probably due to a 10-membered trans-decalyl-like transition state, and with chiral allyl phosphonyl anions of type (50) even good asymmetric induction could be accomplished. ... 

The intermediate N-acylpyridinium salt is highly stabilized by the electron donating ability of the dimethylamino group. The increased stability of the N-acylpyridinium ion has been postulated to lead to increased separation of the ion pair resulting in an easier attack by the nucleophile with general base catalysis provided by the loosely bound carboxylate anion. Dialkylamino-pyridines have been shown to be excellent catalysts for acylation (of amines, alcohols, phenols, enolates), tritylation, silylation, lactonization, phosphonylation, and carbomylation and as transfer agents of cyano, arylsulfonyl, and arylsulfinyl groups (lj-3 ). 

The rate of appearance of p-nitrophenolate ion from p-nitrophenyl methylphosphonate (7), an anionic substrate, is moderately accelerated in the presence of cycloheptaamylose (Brass and Bender, 1972). The kinetics and pH dependence of the reaction are consistent with nucleophilic displacement of p-nitrophenolate ion by an alkoxide ion derived from a cycloheptaamylose hydroxyl group to form, presumably, a phosphonylated cycloheptaamylose. At 60.9° and pH 10, the cycloheptaamylose-induced rate acceleration is approximately five. Interestingly, the rate of hydrolysis of m-nitrophenyl methylphosphonate is not affected by cycloheptaamylose. Hence, in contrast to carboxylate esters, the specificity of cycloheptaamylose toward these phosphonate esters is reversed. As noted by Brass and Bender (1972), the low reactivity of the meta-isomer may, in this case, be determined by a disadvantageous location of the center of negative charge of this substrate near the potentially anionic cycloheptaamylose secondary hydroxyl groups. 

Phosphonate peptides can be synthesized either by formation of the P—O bond or the O—C bond. The former coupling is typically carried out via reaction of an alcohol (e.g., an a-hydroxy acid) with an activated phosphonyl spedes in a manner similar to phosphonamidate synthesis (Section 10.10.2.1). The latter process employs the phosphonate anion as a nucleophile in a displacement reaction on an ester with a leaving group in the a-position. 

A different approach must be used for the photochemical hydrophosphination of electron-poor olefins, and this involves a PET reaction. Silyl phosphites (e.g., 30) were used as electron donors, whereas conjugated ketones have the double role of electron acceptors and absorbing species. Thus, the irradiation of a mixture containing 2-cydohexenone and 30 generated an ion pair. The phosphoniumyl radical cations decomposed to give trimethylsilyl cations (which in turn were trapped by the enone radical anion) and phosphonyl radicals. A radical-radical combination afforded the 4-phosphonylated ketones in yields ranging from 78% to 92% (Scheme 3.20) [49]. This reaction was exploited for the preparation of substituted phosphonates, which serve as key intermediates in the synthesis of a class of biologically active compounds. 

Michaelis-Arbnzov Reactions Phosphonylation of oc,P-Unsatnrated Aldehydes Anionic Phosphonylation... 

Michaelis-Arbnzov Reaction Anionic Phosphonylation Michael Addition Cyclopropanation Heck Conpling Oxidation... 

Thermal and Anionic Phosphonylation Phosphonomethylation Michael Addition Electrophilic Snbstitntion Heck Conpling Diels-Alder Reactions Oxidation Ozonolysis... 

More recently, another example involving the intermediacy of phosphonylated sul fines has been reported. Treatment of diethyl 3-methyl-l,2-butadienylphosphonate with LDA at low temperature followed by reaction with MejSiCl leads to the desired diethyl l-(trimethylsilyl)-3-methyl-l,2-butadienylphosphonate. The addition of alkyllithiums to the a,P-doublc bond of this very unstable compound gives the a-phosphonylated carbanions, which are allowed to react with an excess of SO2. The resulting sulfines are stirred overnight, and only low yields of diethyl 2-thienylphospho-nates (12-25%) are obtained, contaminated with protonated anion (Scheme 2.23). The separation of these two compounds proved to be problematic. The major disadvantage of the method is the incomplete reaction of the anion with S02. ... 

There are relatively few reports involving the Michael addition of cyanomethylphosphonate anions to unsaturated compounds. The reaction provides a methodology for the elaboration of new reagents but more frequently is used for the preparation of phosphonylated heterocycles. Under basic conditions, diethyl cyanomethylphosphonate adds to benzalacetophenone and 2-bcnzylidcne-3-methyl-4-nitro-3-thiolene-l,l-dioxide to give the addition products in modest yields.- - - " ... 

The previous reactions suggest that trialkyl phosphites are able to react with acylphosphonates. Effectively, it has been shown that the reaction of trimethyl phosphite with dimethyl aroylphos-phonates under appropriate conditions leads to the formation of anionic adducts that decompose to give phosphonyl carbenes and trimethyl phosphate. These carbene intermediates can react with further trimethyl phosphite to give ylidic phosphonates, or, when suitable < rt/z<9-substituents are present on the aromatic ring, intramolecular carbene insertion reactions can occur to give cychc systems (Scheme 7.4).38.4o,56,58-65... 

Michael addition of l-(alkoxycarbonyl)methylphosphonate anions to unsaturated compounds provides a methodology for the elaboration of new reagents and also for the preparation of phosphonylated heterocycles. Thus, in the presence of basic catalysts, diethyl l-(ethoxycarbonyl)alkyl- and l-(ethoxycarbonyl)methylphosphonates add to a.p-nnsaturatcd esters and nitriles.Addition of diethyl l-(ethoxycarbonyl)methylphosphonates under basic conditions to methyl or ethyl acrylates, acrylonitrile, and benzalacetophenone occurs readily and gives rise to products of addition to one and two molecules of the unsaturated compound (Scheme 8.14). ° - ° Reaction of a-substituted phosphonoacetates with acrylates is less vigorous, and attempts at addition to crotonic and methacrylic esters fail. mi-zos-zos... 

Hoye and Crawford (94JOC520) have reported the reaction of several enolates 145 derived from esters and amides as well as a-sulfonyl-, a-cyano-, and a-phosphonyl-substituted anions with cyclic sulfate 144 to give hydroxylated product 146. The nucleophilic attack occurred at the terminal carbon [Eq. (31)]. 

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