Silyl phosphites reactions

Preparation of 2,3-dioleoyloxypropylphosphonic acid — Reaction of an alkyl halide with a silyl phosphite ester... 

Sekine, M., Okimoto, K., Yamada, K., and Hata, T., Silyl phosphites. 15. Reactions of silyl phosphites with a-halocarbonyl compounds. Elucidation of the mechanism of the Perkow reaction and related reactions with confirmed experiments, /. Org. Chem., 46, 2097, 1981. 

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. 

Lithium phosphites also can catalyze the silyl benzoin reaction of acylsilanes. Its asymmetric version is successfully achieved by a lithium phosphite derived from a homochiral diol.236 Thiazolium salt 32 effectively promotes conjugate acylation of a, 3-unsaturated carbonyls with acylsilanes in the presence of DBU (Equation (61)).237,237a The active catalyst of this sila-Stetter reaction would be a carbene species generated from 32 by deprotonation. 

The reaction of a silyl phosphite with an a-haloaldehyde or ketone generally leads to a 1 1 adduct (i.e. addition at the carbonyl carbon atom to yield a silyloxyphosphonate by the Abramov reaction, cf. Section 5). However, both the Perkow and the Michaelis-Arbuzov pathways are significant and frequently dominate, the outcome depending on the nature of the reactants and the reaction conditions.47... 

No spectroscopic evidence for the structure of 40 (e.g., P-F coupling constants) has been reported the mechanism has been verified by Evans et al. (98) in the reaction of silyl phosphites with a wide variety of different ketones. At elevated temperatures C—O inversion has been postulated, and a vinyl phosphate 41 is formed with elimination of trimethylfluorosilane (161). 

Attack on Nitrogen. A new route to phosphoramidates, involving the reaction of silyl phosphites with the appropriate azide, followed by hydrolysis, has been developed. The mechanism (see Scheme 6) probably involves initial formation of the phosphite imine (36) followed by migration of a sUyl group from oxygen to nitrogen, and it is exemplified by the synthesis of the oligoazanucleotide (37). 

By contrast, reactions with silyl phosphites do not give the phosphazenes (26), for the silyl group readily migrates to nitrogen, leaving (27). The same tendency for migration of the silyl group has also been noted for intermediates derived from azides. ... 

Konovalova, I.V, Burnaeva, L.A., Saifullina, N.S., and Pudovik, A.N., On the reaction of trimethyl silyl phosphite with esters and nitriles of a-oxocarboxylic acids, Zh. Obshch. Khim., 46, 18, 1976 J. Gen. Chem. USSR (Engl. Transl.), 46, 17-19, 1976. 

Considerable research effort has been focused on the preparation of compounds of biochemical interest, using electrophilic reactions of phosphoramidites and phosphorochloridites to prepare modified phosphates of nucleosides or lipids. Intense interest has been shown in the synthesis of myoinositol phosphates, and also of aminoalkylphosphonic acids and their derivatives and analogues. Away from the biological emphasis, however, the first (recorded) syntheses of acetylenic phosphates have been described, and so have the first 1-alkoxyphosphole, the first cis amino-iminophosphine, and the first dithiaphospholium ions ex Phosphorus semper aliquid novi The use of silyl phosphites for synthetic purposes seems to be an increasing trend, while the number of papers on metaphosphate seems to be in decline. 

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... 

Although it has been stated that di- and tri-haloketones and a-haloaldehydes (irrespective of the degree of halogen substitution) tend to yield only enol phosphate esters, further qualification of this statement is appropriate. The formation of silyl ethers from aldehydes or ketones and silyl phosphites has already been noted (see section III.A). Reactions between silyl phosphites and trifluoroacetaldehyde or perfluoroacetone and other similar compounds initially lead to silyl ethers of (a-hydroxyalkyl)phosphonic diesters in which all the fluorine is retained, although subsequent change leads to fluorinated enol phosphate esters. Sekine et also observed the formation of (a-silyloxyalkyl)phospho-... 

Enol phosphates phosphonates were also obtained by the reaction of perfluoroalkanoyl chlorides with triethyl phosphite. In this case, it was not possible to isolate the putative intermediate perfluoroacylphosphonates. This result is in contrast with the facile formation of bis (trialkylsilyl) trifluoroacetylphosphonates (see previous section), and it indicates that acylphosphonates derived from carboxylic acids with strongly electron-withdrawing groups can be prepared using tris(trialkylsilyl) phosphites. Such silyl phosphites seem to be uniquely suitable for this purpose, by virtue of their high reactivity in the first step and their steric hindrance, which presumably retards the second step. 

Silyl phosphites such as (EtO)2POSiMe3 and (Et3SiO)3P are known. The latter compound can be prepared in 30% yield by reacting phosphorus tribromide with an organosilane in the presence of zinc chloride (9.282). Esters of the former type can be made by reaction (9.283). 

Tris(silyl)phosphites undergo Arbusov-type reactions (9.287). In a mixed phosphite ester, the alkoxy carbon is preferentially attacked (9.288). The silyl ester products are hydrolysed to phos-phonic acids (9.289). 

Room temperature imidazolium ionic liquids have been shown to be useful solvents for the Michaelis-Arbuzov rearrangement, sometimes allowing the reaction to be performed at room temperature in a short period of tirne. Halolactones, which are the products of halolactonisation of y,5-unsaturated acids, have been shown to be dehalogenated by trialkyphosphites in the presence of water. This makes a useful alternative to the commonly used reduction by tributyltin hydride. The reactions of dibromoethane and dibromopropane with silyl phosphites have been studied. Mono and diphosphonoalkanes (37) and (38) were prepared and their chemical properties were studied. In the reaction of trifluoromethylated P-alkoxyketones with tris(trimethylsilyl)phosphite, a mixture of the 1,2- and 1,4-adducts (39) and (40) is produced. 

In this context, it is interesting to note that the first synthesis of 2, 3 -0,0-cyclic phosphorothioate 22a was reported by Eckstein in 1968 [25], He also isolated pure Rp diastereomer by fractional crystallization of the triethylammonium salts [26] and used it as reference to determine the absolute configurations of the other phosphorothioate analogues [27], 2, 3 -0,0-Cyclic H-phosphonate 20a was used as a key substrate for the synthesis of uridine 2, 3 -0,0-cyclic boranophosphate 27. Silylation of H-phosphate 20a gave the phosphite triester 25 (two diastereomers). Its boronation, with simultaneous removal of the trimethylsilyl group, was achieved by its reaction with borane-A.A-diisopropylethylamine complex (DIPEA-BH3). 

Preparation of tris(trimethylsilyl) phosphite — Preparation of a silyl ester of a trivalent phosphorus acid for Michaelis-Arbuzov reaction... 

Preparation of [l-(diethoxyphosphinyl)ethoxy]dimethyl-silane — Reaction of an aldehyde with a trialkyl phosphite in the presence of a silyl halide... 

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