Hydrogenphosphonates Hydrogenphosphonic diesters

The interaction of a hydrogenphosphonate diester and an alkene occurs under free radical conditions, arising either through the use of peroxide or azo catalysts, or by exposure to appropriate radiation. Cadogan has summarized some early examples of the procedure, although at the time, there appeared to be very few examples in which non-functionalized systems were used. The commonly accepted mechanism for homolytic addition seems to be that given in Scheme 7. 

In the reactions between diethyl hydrogenphosphonate and indantrione or 2-benzyli-deneindan-1,3-dione, the former substrate yields phosphate adducts,but in the latter case, addition affords the phosphonate 203 The additions of hydrogenphosphonic diesters to propynal and ethynyl methyl ketone and to the ketones RC=CCOMe (R = Me or Ph) ", give 1,2-adducts. 

The addition of hydrogenphosphonic diesters to ethenylphosphonic or ethenylphos-phinic derivatives follows equation 26, and that of the hydrogenphosphonates to the (1,2-butadiene)phosphonic system is represented by equation 27. 

The direct alkylation of hydrogenphosphonic diesters with a diazoketone has been recorded alongside that with diazoalkanoic esters, and explored particularly with methyl 2-diazo-3-oxobutanoate but also for several chloroacetones. Reactions involving 1-chloro-3-diazo-2-propanone are effectively catalysed by [Cu(acac)2], but more heavily chlorinated substrates suffer stepwise dechlorination. Thus l,l,l-trichloro-3-diazo-propan-2-one initially yields the expected dialkyl (3,3,3-trichloro-2-oxopropyl)phospho-nate, but under the experimental conditions, dechlorination then proceeds to give the dialkyl (3,3-dichloro-2-oxopropyl)phosphonate only the monochloroketone undergoes a reaction in which the original halogen content is retained in the final product ... 

In Section VILA, the 1,2-addition of a hydrogenphosphonic diester or related compound to an a,j5-unsaturated aldehyde or analogous ketone " " was discussed in relation to the synthesis of (l-hydroxyalkyl)phosphonic diesters. The latter are formed under condition of kinetic control whereas 1,4-addition (the so-called Pudovik reaction), which leads to the (2-oxoalkyl)phosphonic diester occur under thermodynamic controP" ". In general, reactions which involve ethylenic aldehydes, or acetylenic aldehydes or ketones, tend to result in adduct formation across the carbonyl group, whilst ethylenic ketones tend to take part in 1,4-additions and afford 3-oxoalkyl phosphonic (or phosphinic) acid systems 550 34,946-949 consistent with Markovnikov predictions. Such statements are a broad oversimplification, however, at least with regard to the formation of the oxoalkyl phosphonates. In practice, the manner of addition depends on experimental circumstances, the nature and even amount of catalyst and other factors For instance, for the additions of dimethyl hydrogenphosphonate to the ketones 561 ( = 1 or 2) and 559 (R" = H, R = 2-furyl, R = Me), carried out by the addition of a trace of saturated MeONa-MeOH solution to a mixture of reactants in diethyl ether, yielded (within 5 min) the respective 1,2-adducts (1-hydroxyalkylphosphonates) in yields of64,69 and 52% ... 

The interaction of an ethenyl ether and a trialkyl phosphite (trimethyl phosphite was actually used) under dry acid conditions (HCl gas in MeOH) leads to a phosphonic diester according to Scheme 2. Little dealkylation of the phosphite triester appears to occur, and the reaction appears therefore not to involve addition of dialkyl hydrogenphosphonate (the product of phosphite dealkylation), all the more so since triphenylphosphine also reacts under the same conditions to give related triphenylphosphonium salts. Ethenyl ethyl ether, 2,3-dihydrofuran and 2,3-dihydropyran were used as substratesThe ease of reaction under mild conditions, coupled with high yields, testifies to the importance of a cationic intermediate species. 

The addition of dialkyl hydrogenphosphonates to tetrafluoroethene occurs in the presence of di- r butyl peroxide to give the series of polyfluoroalkyl phosphonic diesters, H(CF2CF2) P(0)(0R)2 (n = 1-3) the free acids with n = 1-5 and the corresponding phosphonic dichlorides with n = 1-9 have also been recorded ... 

Reactions between dialkyl hydrogenphosphonates and (l-oxoalkyl)phosphonic diesters in the presence of a trace of basic catalyst, normally triethylamine or sodium alkox-ide, give rise to tetraakyl esters of (l-hydroxyalkylidene)bisphosphonic acids (269) in a manner similar to the behaviour of the hydrogenphosphonates towards simple aldehydes or ketones" ". However, following the initial observations of this interaction, it soon became apparent that, based on H NMR evidence, the isolated compounds did not possess the stated alkylidenebisphosphonate structure but were, in reality, the products of a... 

Several slightly more unusual examples are worth presenting. The very vigorous reaction between a dialkyl hydrogenphosphonate and penta-2,4-dienoic acid proceeds to the phosphonic diester 419 initially but which, with more reagent, affords the diphosphonic... 

X = Se ". These and other synthesis procedures will be considered in more detail later. Unfortunately, the acetals of (oxomethyl)phosphonic diesters do not liberate the free (oxomethyl)phosphonic esters under acidic conditions, but instead, tend to decompose with the formation of dialkyl hydrogenphosphonate. 

The addition of a hydrogenphosphonate to a symmetrical di(a,jS-unsaturated)-ketone occurs very readily, but is controllable to the extent that it occurs across only one of the C=C bonds. The addition of a dialkyl hydrogenphosphonate, in the form of its bromo-magnesium salt, to the ketones 564 (R = Me, Et or Pr ) leads to the oxoalkenyl phosphonic diesters 565 according to a mechanism suggested in Scheme 54. 

The practical difficulties sometimes encountered in Kabachnik-Medved -Fields syntheses of (a-aminoalkyl)phosphonic acids from amines, aldehydes or ketones, and dialkyl hydrogenphosphonates, have been traced to the rearrangement of dialkyl (1-hydrox-yalkyl)phosphonates to isomeric phosphate esters under the essentially basic conditions the reactions involved are summarized in Scheme 17. The direct conversion of a (hydrox-yalkyl)phosphonic diester into the corresponding (aminoalkyl)phosphonate by the action of the amine is known, generally, not to take place, and it seems much more likely that successful Kabachnik-Medved -Fields syntheses proceed by the addition of the hydro-... 

The reaction of acylphosphonate diesters with alcohols was reported early to lead to dialkyl hydrogenphosphonates and carboxylate esters In a more recent systematic study, conditions were developed to use acylphosphonates for the acylation of alcohols. It was found that 1,5-diazabicyclo [5.4.0] undec-7-ene (dbu) is a highly effective catalyst for acylation of alcohols by acylphosphonates. Two special aspects deserve mention (1) /er butyl alcohol could be acylated with diethyl benzoylphosphonate, in the presence of dbu and 4-dimethylaminopyridine, to give r r/-butyl benzoate in 57% yield (2) the primary hydroxy group of a diol (e.g. butane 1,3-diol) could be acylated fairly selectively in the presence of a secondary hydroxy group by this methodology (ratio of mono to diacyl product =88 12). 

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