Arbuzov-type reactions

An important steric hindrance of the carbon in the a-position to the oxygen (or a bicyclic structure) reduces or even inhibits formation of the phosphoryl group by substitution reaction on this carbon. It must be pointed out that phosphoryl formation occurs, generally, in Arbuzov-type reactions, by a substitution process, but can take place also by a -elimination which is favoured by major steric hindrance. 

Recently we have developed a more general approach to molecules exemplified by III. Thus the Diels-Alder cycloaddition of alkyne II and ct-pyrone, followed by aromatization by loss of carbon dioxide, led to the isolation of III (72%) (5). Alkyne II was obtained in high yields, in two steps from dichloroacetylene and triethylphosphite via Arbuzov-type reactions (5). Since the intermediate chloroalkyne phosphonate I was isolable (90%), phosphorus nucleophiles other than triethylphosphite could be used to give unsymmetrical alkyne diphosphoryl species. We have demonstrated this approach by the reaction of I with PhaPOEt and PhP(OEt)2 (5). 

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. 

This paper describes the electrophilic ring-opening polymerization of seven new cyclic phosphorus(III) compounds, 1-7. The polymerization of five- and slx-membered deoxophostones, 1 and and of a benzoxaphosphole 2, produced poly (phosphine oxldejs 11, and via Arbuzov type reactions. The polymerization of f e and slx-" membered deoxothlolphostones, 4 and 5, gave poly(phosphine... 

The electrophilic polymerization of for example. Involves stable phosphonlum species which reacts with monomer via an Arbuzov type reaction to Induce a C-S bond scission leading to a phosphine sulfide unit. 

The polymerizations of 4 and 5 are the first examples of the formation of polymers wTth a S group Involving an Arbuzov type reaction with C-S bond cleavage. 

In an Arbuzov-type reaction, 2,4-dichloropyrido[3,2-r/]pyrimidine (11) and trimethyl phosphite yield dimethyl 2-chloropyrido[3,2- /]pyrimidine-4-phosphonate (12).459... 

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. 

The displacement of a sulphonyloxy group, in this instance from an A-protected azeti-dine (176), is yet a further Michaelis-Arbuzov type reaction and yields the product 177 with retention of the ring deprotection of the latter is achieved by hydrogenolysis. ... 

The reaction of trialkyl phosphites with aldehydes or ketones in the presence of hydrogen chloride gives dialkyl-1-hydroxy alky Iphosphonates via Arbuzov-type reactions of oxonium salts derived from aldehydes or ketones. This reaction is an alternative to the Abramov reaction.Reduction of activated carbonyl groups, such as a-ketophosphonates by alkyl phosphine, afforded the corresponding reduced products. A new monomer, N-acyl pamidronate (152), which copol5merizes with N-isopropylamide provides a cross linked hydrogel (153) that serves as a substrate for direct biomineralization e.g. the formation of hydroxyapatites). 

Pummerer rearrangements leading to thiolesters are discussed in the later sections on sulphoxides. A superficially related Arbuzov-type reaction, with a 1,2-shift of sulphur, through the intermediate (5), has a similar outcome. 2-Thiopyridyl chloroformate has been advocated as a reagent for the conversion of carboxylic acids into their pyridine-2-thiolesters under mild conditions. 

The Arbuzov-type reaction of trialkylphosphites with N-acyl aziridines gives the phosphonates (126), whereas a similar reaction with a-chloro-oxirans gives (127). In contrast, activated olefins (X = CN or C02Et) produce the pentaco-ordinate species (128) in the presence of R" OH. ... 

Scheme 37 Michaelis-Arbuzov type reaction with fluoropyrimidine...

During the synthesis of a group of potential threonine synthase inhibitors, Zervosen studied the synthesis of allylic phosphonates through an Arbuzov-type reaction between allylic bromides and trialkyIphosphites (Scheme 4.48) [100]. Trimethylphosphite was nsed as a representative phosphorus nucleophile in this chemistry. Similar to many of the Arbuzov-type reactions, the chemistry was operationally simple and proceeded under solvent-free conditions. Although the temperature of this process was lower than several of the systems described previously, there are still many substrates that will not survive heating to 100 °C for 8h. 

The P-arylation of arynes is an interesting approach to the synthesis of arylphosphine oxides since it is typically a transition metal-free reaction that occurs at low temperatures (Scheme 4.193) [332]. In contrast to classic metal-mediated Arbuzov-type reactions between phosphinites and aryl halides that required high temperatures (150-2(X) °C), this... 

Qu and Guo reported that specific positions on purine rings would undergo an Arbuzov-type reaction under solvent-free conditions using a focused microwave reactor (Scheme 4.214) [353]. This chemistry was tolerant of a range of groups at the N9 position... 

The chemoselectivity of these metal-free Arbuzov-type reactions was investigated by Janeba (Scheme 4.215) [354]. Using a heterocycle that had both chloro and fluoro substituents, the authors found that simply heating the neat reagents using a focused microwave reactor without the addition of a metal catalyst afforded the phosphonylated material in moderate yields. Of interest was the observation that the fluoro group was replaced preferentially to the chloro. In addition to this example, a number of mono- and bisphosphonated compounds were prepared and characterized. 

One of the first uses of aryl triflates in an metal-mediated Arbuzov-type reaction was reported by Zhang. He used nickel chloride as the metal catalyst and various additives to promote the formation of arylphosphonates from triethylphosphite (Scheme 4.220) [367]. While a range of additives such as LiBr and KI promoted the formation of the arylphos-phonate, KBr was found to be superior. Most of the substrates screened in this work were hydrocarbon based however, a number of examples contained functional groups such as an ester, acetate, and protected amines. 

Nielsen, J and Caruthers, M H. (1988) Directed Arbuzov-type reactions of 2-cyano-l,l-dimethylethyl deoxynucleoside phosphites J Am. Chem Soc 110, 6275-6276. 

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