Michaelis-Arbuzov phosphonate synthesis

MICHAELIS-ARBUZOV Phosphonate Synthesis Ni catalyzed phosphonate synthesis from phosphites and aryl halides. Reaction of alkyl halides with phosphites proceeds without nickel salts (see 1st edition). 

Sugars containing a carbon-phosphorus bond have been prepared by application of the Michaelis-Arbuzov reaction to bromodeoxy sugars. Thus, the reaction of 5-bromo-5-deoxy-l,2-0-isopropylidene-3-O-methyl-a-D-xylofuranose (131) with triethyl phosphite yields the corresponding diethyl phosphonate (132) compound 132 was employed for the synthesis of a sugar derivative having phosphorus as... 

The Michaelis-Arbuzov reaction is the most used and well-known method for the synthesis of phosphonates and their derivatives and may also be used to synthesize phosphinates and tertiary phosphine oxides. The simplest form of the Michaelis-Arbuzov reaction is the reaction of a trialkyl phosphite, 3, with an alkyl halide, 4, to yield a dialkyl alkylphosphonate, 6, and new alkyl halide, 7 (Scheme 2). During this transformation the phosphorus atom of a ter-valent phosphorus(III) species (3) acts as a nucleophile resulting in the formation of an intermediate alkoxy phosphonium salt 5, containing a new [P—C] bond. The precise structure of the intermediates 5 is a subject of debate—as reflected by common reference to them as pseudophosphonium salts —with a penta-coordinate species (containing a [P—X] bond) being proposed and detected in some cases.18 Decomposition (usually rapid under the reaction conditions) of the intermediate 5 by nucleophilic attack of X- on one of the alkyl groups R1, with concomitant formation of a [1 =0] bond yields the product pentavalent phosphorus(V) compound (6) and the new alkyl halide, 7. 

Protocol 2 produces the protected fi-formylphosphonate 12 f)-ketophospho-nates may also be synthesized by other methods,23 however, they may not be prepared in unprotected form by the Michaelis-Arbuzov reaction because the Perkow reaction, in which an a-haloaldehyde or ketone and a trialkyl phosphite yield an enol phosphate (e.g. 13, Scheme 5,24 i.e. [P—O] bond formation), competes and frequently dominates (see Section 4). Conversely halocarboxylic acid derivatives (e.g. see Table 7.1, entry 3) and acyl halides (see Protocol 3) react well in the Michaelis-Arbuzov reaction to yield useful functionalized phosphonates. fi-Ketophosphonates are useful reagents for the synthesis of a,fi-unsaturated carbonyl compounds by the Horner-Wadsworth-Emmons reaction,3,4 25 and have other applications.23... 

ALPER Carbonylalion 2 AMADORI Glucosamine rearrangement 3 ANGELl - RIMINI Hydroxarrw acid synthesis 4 ARBUZOV - MICHAELIS Phosphonate synthesis 5... 

Apart from their behaviour as ligands in metal catalyst systems, studies of the reactivity of phosphites towards a wide variety of other substrates have attracted attention. New aspects and applications of the classical Michaelis-Arbuzov reaction and its variants continue to appear. Evidence of the thermal disproportionation of methyltriaryloxyphosphonium halides formed in the reactions of triarylphosphites with alkyl halides, together with the formation of P-O-P intermediates, has been reported. The Michaelis-Arbuzov reaction has been used in the synthesis of phosphonate-based styrene-divinylbenzene resins and polyphosphonated chelation therapy ligands.Treatment of electron-rich benzylic alcohols dissolved in triethylphosphite with one equivalent of iodine affords a low-temperature one-pot route to the related benzylic phosphonates, compounds which are otherwise difficult to prepare. Upper-rim chloromethylated thiacalix[4]arenes have also been shown to undergo phosphonation on treatment with a phosphite ester in chloroform at room temperature. The nickel(II)-catalysed reaction of aryl halides with phosphite esters in high boiling solvents, e.g., diphenyl ether, (the Tavs reaction), has also... 

This reaction, discovered by Alichaelis and Kaehne (222) and explored later by Arbuzov (15), has been widely employed for the synthesis of phosphonate and phosphinate esters and phosphine oxides. The extensive literature on the Michaelis-Arbuzov reaction has been summarized through 1949 in two reviews by Kosolapoff (177,178). 

The use of trialkyl phosphites in the Michaelis-Arbuzov reaction has been so widespread during the decades following its discovery that it is almost impossible to select individual examples worthy of separate comment. Some examples of the preparation of benzylic phosphonic diesters may be noted these are of some interest since they are useful reactants in the Wadsworth-Emmons modification of the Wittig reaction, and are extensively used in the synthesis of alkenes It may also be noted that when the phosphite ester possesses different alkyl groups, some selectivity of reaction is possible. ... 

The scope of the normal Michaelis-Arbuzov procedure in the synthesis of polyunsaturated phosphonic acids has not been widely explored, but it has been reported that 2-chlorobuta-1,3-diene and triethyl phosphite react together to give about 10% of the ester 220. ... 

---