Alkyl, Cycloalkyl, Aralkyl and Related Acids

1 Alkyl, Cycloalkyl, Aralkyl and Related Acids. - Both alkane- and alkenephosphonates have been prepared by electrochemical phosphorylation of alkenes with a variety of P acid derivatives.  

A number of phosphonate and phosphinate derivatives where the phosphorus atom is directly bonded to non-aromatic cyclic systems have been reported. The synthesis and reactions of a number of compounds with the general structure 103 have been reported. Enantiomerically pure cyclopropanephosphonic acids which are constrained analogues of the GABA antagonist phaclophen, have been prepared by stereocontrolled Michael addition of a-anions derived from chiral chloromethylphosphonamides 104 to a,P-unsaturated esters followed by in situ cyclisation. Other asymmetric syntheses include those of (/ )- and (S)-piper-idin-2-ylphosphonic acid (105) via the addition to trialkyl phosphites to iminium salt equivalents and 4-thiazolidinylphosphonate 106 by catalytic asymmetric hydrophosphonylation of 3-thiazoline. In the latter case both titanium and lanthanoid (which give much better e.e. values) chiral catalysts are used. 

In Michaelis-Becker reactions between 2- or 3-(chloromethyl)furans and NaOP(OMe)2 in MeOH both the methoxymethyl derivatives and phosphonic diesters are produced, the latter in smaller proportions. Sodium ferf-butoxide affords even poorer yields of phosphonate esters but also less of the ethers.  

A detailed study of reactions between dialkyl phosphite anions and nitrobenzyl bromides has been described. In reactions between the halides and the phosphites (RO)2PONa in a solvent (THF, PriOH, or MeOD) the observed products (Z = 2-, 3-, or 4-nitro), apart from phosphonic diester (104), are those of reduction, (105) or (106), coupling (107), and ether formation (108). Phosphonate formation was moderate for Z = 2-nitro (R = Me), rather higher (51-97% isolated yields) for Z = 3-nitro (R = Me or Pr ), but extremely low for Z = 4-nitro (R = Me) and absent for R = Pr . In all cases when R = Me, ether formation also occurred. In cases where the yields of phosphonate were low, the yields of (107) were correspondingly high, and vice versa. Reactions performed in darkness, daylight or UV, produced little variation in the yields of phosphonate ester (R = Me) for Z = 3-nitro, but for Z = 2-nitro- or 4-nitro-, no diisopropyl phosphonates were obtained under various conditions. Probable mechanisms of reaction were discussed.  

More complex phosphinic derivatives e.g. (109) [R = CH2CH(CH2CH2Ph) COOR (R = Bn or Bu ), R = simple alkyl or functionalized alkyl] have been prepared by the alkylation of the corresponding species (110). Other examples will be encountered in later sections, in particular Section 3.1.9. 

The electrolysis of diisopropyl (l-chloro-l-cycloalkyl)phosphonates in MeOH and using a carbon cathode and magnesium anode, results in dehalogenation to esters of the cycloalkylphosphonic acid.  

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