Arbuzov-Michaelis-type

Example 69 Mlotkowska and Olejnik have described the synthesis of rac-S-(2-acetoxy-3-hexadecyloxypropyl)thiophospholine using an Arbuzov-Michaelis type reaction [109]. 

AUcoxyaminophosphines react with alkyl halides in an Arbuzov Michaelis type reaction to form phosphonic acid diamides via thermally unstable phosphonium intermediates (equation 5). ... 

In contrast to the Michaelis-Arbuzov reaction, triaryl phosphites prove to be quite useful for addition to a,(3-unsaturated carbonyl compounds in this type of reaction. A wide variety of unsaturated compounds have been utilized successfully as substrates for such additions, including condensation products of the simple carbonyl compounds with urea,229 thiourea,230-233 N-substituted thioureas,232 234 235 ethyl carbamate,236 2-imidazolidinone,237 2-imidazoli-dinethione,237 and benzyl carbamate.238-240... 

A related reaction that yields the same types of products as does the Michaelis-Arbuzov reaction begins with either a phosphinous acid or a monoester of a phosphonous acid. (The corresponding reaction may also be performed with a diester of phosphorous acid.) By treatment with an appropriate base, the conjugate base of the phosphorus-containing acid is generated that serves as the nucleophihc reagent for direct formation of the phosphonate or phosphine oxide product (or phosphonate product from a phosphorous acid diester). This procedure is commonly referred to as the Michaehs Becker reaction. ... 

Quasiphosphomum intermediate species are found to be involved in the transition metal-catalyzed reaction of haloaromatics and vinylic halides with trivalent phosphorus-containing esters. These reactions, while giving products that appear to be from a Michaelis-Arbuzov type reaction, actually involve addition-elimination reactions. 

Although the reaction of dialkyl phosphites with orthoformic esters has been extended to triethyl trithioorthoformate," the preferred synthesis of formylphosphonate dithioacetals is usually the high-yield Michaelis-Arbuzov reaction of trivalent phosphorus compounds with the appropriate chlo-rodithioacetals.""" For the corresponding hemithioacetals, a Pummerer-type reaction of a-phos-phoryl sulfoxides with alcohols in the presence of iodine is usually the method of choice (Scheme 5.3). " ° However, hemithioacetal formation is solvent dependent and generally gives a moderate yield of product in a mixture with several other byproducts arising from transesterification reactions. 

A reaction having significant synthetic importance for the construction of dialkyl 2-formylaIkyl-phosphonates involves the addition of trivalent phosphorus reagents to a,3-unsaturated aldehydes. s This Michael-Michaelis-Arbuzov strategy is the method of choice for incorporating, from readily available Michael-type substrates, one or two substituents at any position of the carbon chain between the phosphoryl and formyl groups. 

Several promising processes are applied to the synthesis of 2-cyanoethylphosphonates, including, for example, the thermally induced Michaelis-Arbuzov-type rearrangement of diethyl 2-cyanoal-lylphosphite to diethyl 2-cyanoallylphosphonate (Scheme 6.30).- " -4 ... 

In all cases mentioned at that time, the products were assumed to be phosphonates of the type expected from a normal Michaelis-Arbuzov reaction. - However, in light of the Perkow reaction, all the P-ketophosphonates described in numerous papers and patents have to be formulated as the isomeric vinyl phosphates. 

The reaction of 3,4-dinitrothiophenene 89 with Grignard reagents has been shown to give thienylphenols, as exemplified by the formation of 90. A mechanistic rationale was provided to account for this unusual transformation <04EJO3566>. Synthesis of a number of 2-thienylphosphonates has been achieved by treatment of 2-chloro-3-nitrothiophenes with triethyl phosphite via a Michaelis-Arbuzov type reaction <04S668>. 

Organic halides of other elements [tin (43-45), phosphorus (6,54), nitrogen (46,93,245,251), sulfur (232,233,252,256-259)1 also participateV in Michaelis-Arbuzov type reactions. Heating the organic lead compound EtsPbBr with (EtO)3P at 100° gave only an unidentified white amorphous solid (45). Petrov and SokoPskii (250), who observed the formation of phosphate esters from the reactions of ethyl hypochlorite with various phosphite esters, proposed the existence of a pentacovalent intermediate which decomposed by loss of alkyl halide. 

In the only reported examples (107) of the Michaelis-Arbuzov reaction with optically active halides (2-halooctane and 1-halophenyl-ethane), results were inconclusive. The halides underwent extensive racemization in preference to furnishing the expected phosphonate. The stereochemical nature of the attack by phosphite on alkyl halides could perhaps be clarified by the use of optically active primary deutero-halides (RC DHX), wherein steric hindrance is at a minimum, and one could more easily obtain phosphonate products. No experiments of this type have been reported. 

In 1952, Perkow reported (242) that a-haloaldehydes did not react with trialkyl phosphites according to the Michaelis-Arbuzov reaction, although this had been repeatedly reported, but that a new type of reaction occurred, yielding dialkyl vinyl phosphates isomeric with the expected phosphonates. 

On the basis of such evidence, it now seems to be widely accepted that the intermediates in valence expansion reactions of the Michaelis-Arbuzov type can have either an ionic, or a non-ionic, pentacoordinate structure, or both can be involved, possibly sequentially, or through equilibration, the choice being dependent on the ligands surrounding the central phosphorus atom, i.e. on the nature of the reactants. Thus reaction 1 might well be written as reaction 4. 

Several possible reactions may give rise to impurities in the preparation of phosphonic or phosphinic acid esters by the Michaelis-Arbuzov reaction, and it is possible that, in some cases, such reactions become preponderant. Triethyl phosphite, for instance, has been successfully used as a dehalogenating agent, in particular, for debrominations. Isomerization of allylic groups may occur through S T-type processes (reaction 5) or be induced thermally (reactions 6 and 7) 25,126... 

Many variations in the Michaelis-Arbuzov reaction have been observed they range from slight changes in the nature of the alkylating species to a recognition that certain reactions, of an apparently totally different type, are in essence of the same mechanistic type, and give rise to similar products. 

The classical procedure, and the one still extensively employed, consists in the alkylation of compounds containing the P(0)H moiety, as an appropriate metal salt, with an alkyl halide or similar type of compound such a procedure can sometimes be a successful alternative when the classical Michaelis-Arbuzov reaction fails, one such example being illustrated in equation 19. No reaction takes place between triethyl phosphite and 3-chloro-cyclopentadiene at below 120 °C, above which the main reaction is then dehydrochlorination the use of sodium dialkyl phosphites leads, however, to the desired dialkyl cyclopent-2-enylphosphonates. ... 

Although esters of (oxomethyl)phosphonic acid have proved to be so elusive, derived acetals (495 R = H, X = O) have been prepared with relatively little difficulty from the acid-catalysed interaction of dialkyl hydrogenphosphonates and orthoformic esters ", and from mixtures of phosphorus(III) chlorides and orthoformic esters when heated in sealed tubes the reaction is included here since the ultimate stage is presumably of the Michaelis-Arbuzov type. The current view (Scheme 48) appears to be that the phos-phorus(III) chloride reacts with triethyl orthoformate in a stepwise fashion where appropriate, and with the formation, in the penultimate step, of a phosphorus(III) triester and ClCH(OEt)2. Such reactions were observed in a highly detailed study, by P NMR spectroscopy, of the very slow reaction, even at 150 °C, between triethyl orthoformate and the chloride 496, from which the phosphinic ester 497 was isolated the reaction between the chloride 498 and triethyl orthoformate was much faster, but even so, took place over an... 

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