Arbuzov reactions, carbon-phosphorus bond formation

The use of an electron-rich trivalent phosphorus center for addition to or substitution at an electrophilic site is a long-established approach to the formation of carbon-phosphorus bonds. The classical studies of the Michaelis-Arbuzov, Michaelis-Becker, Abramov, Pudovik, and related reactions and their mechanisms and synthetic utilities have been thoroughly reviewed. In this chapter, we present only a brief introduction to these reactions and provide several examples of their more facile uses from the older literature. More attention is given to relatively recent developments regarding such reactions that are seen as improvements in their general utility. 

From a synthetic viewpoint, the significant feature of the classical Michaelis-Arbuzov reaction of an alkyl halide with a P(III) ester is the formation of a carbon-phosphorus bond. Since its discovery by Michaelis and Kaehne (222) in 1898, it has been the principle synthetic route to the phosphonic acids, which, with their esters and amides, probably outnumber all other compounds containing the carbon-phosphorus bond (105). 

Arbuzov and Michaelis-Becker reactions provide facile and versatile procedures for the formation of carbon-phosphorus bonds. These methods, however, are not applicable to the formation of sp hybridized carbon-phosphorus bonds. Only few methods have been reported for the syntheses of arylphosphonates and vinylphospho-nates. Direct reaction of aryl or vinyl halides with trialkyl phosphite in the presence of nickel halide requires severe reaction conditions [21,22], and the stereochemistry of vinylphosphonates has not been clarified. Synthesis of dialkyl arylphosphonates 22 [23, 24] is achieved by the palladium-catalyzed reaction (Scheme 2.12), which is called by Hirao reaction . The stereoselective synthesis of dialkyl vinylphosphonates 23 [24-26] is similarly accomplished by this method (Scheme 2.13). A variety of modified procedures have been developed recently [27-37]. 

In contrast to the general lack of reactivity of ethenyl halides under Michaelis-Arbuzov conditions, except in catalysis by nickel(II), the formation of bonds from phosphorus to sp -carbon is observed when polyfluoroalkenes take part in Michaelis-Arbuzov reactions. 

Other examples of modification in the Michaelis-Arbuzov reaction in the formation of phosphorus-carbon bonds in compounds other than esters are reactions between dichlorophosphites " or difluorophosphites and organic halogen-containing compounds in the presence of iron(III) chloride (reactions 2 and 3). A similar reaction takes place with diethyl fluorophosphite A further variation is that of the photoinitiated reaction, a... 

Although those Michaelis-Arbuzov reactions which involve acyl halides and phospho-rus(III) esters are yet a further route to phosphorus-carbon bond formation and will be discussed later in Section VI, the use of halogenated acyl halides has led to some unusual results which, conveniently, can be summarized here. The products obtained from reactions between trialkyl phosphites and perfluoroacyl chlorides contain both phosphonate and phosphate moieties and are structurally dependent on reaction temperature. The initial product (Scheme 4) is thought to be the ylide 66. In an ethereal solvent at low temperature, decomposition of the ylide yields [l-(dialkoxyphosphinoyl)oxy-l/f-perfluo-roalkyl]phosphonates (67) exclusively, but at -20 °C and above, and in the absence of a solvent, the products consist of (Z)-[l-(dialkoxyphosphinoyl)oxyperfluoroalkene]phos-phonates (68) . The treatment of the compounds 67 with Ida yields 68, and the action of BuLi-CuI on 68 results in loss of the phosphate moiety to give the esters 69 The structural isomers 70 of the compounds 68 have been obtained as illustrated in equation... 

Fundamentally, the Michaelis-Becker reaction, and the first step in the mechanism of the Arbuzov reaction, involves 8 2 substitution at the carbon atom and as such should lead to stereospecific formation of the C—P bond (with inversion of configuration at the carbon atom) when chiral alkyl halides are used. Secondary alkyl halides, in most cases, favor elimination instead of substitution, in contrast to epoxides that react with phosphorus nucleophiles without elimination and with excellent stereoselectivity. The later reaction was successfiiUy used in a synthesis of glycosylphosphonate analog 3 of T>-myo-inositol-1,4,5-triphosphate (Scheme 47.2). ... 

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