Phosphonic acids, from phosphorus synthesis

Figure 2.5 Direct synthesis of a phosphonic acid from white phosphorus.

Another important source of chiral auxiliaries for the synthesis of optically active phosphorus derivates are the C2 symmetric diamines such as 1,2-diaminocyclohex-anes. In 1994, Hanessian and co-workers described the use of A,/V -dimethyl-(R,R)-1,2-diaminocyclohexane 93 as a chiral auxiliary in the synthesis of optically pure or enantiomerically enriched a-alkyl a-amino phosphonic acids [49], Starting from easily accessible optically pure diamine 93, they synthesized in good yield (75 %) enantiomerically pure (R,R)-ethylphosphonamide 94 by condensation with ethyl phosphonic dichloride in benzene in the presence of triethylamine (Scheme 43). 

An optimised solid-phase method for the generation of diverse a-amino-alkyl or -aryl phosphonates derived from peptides and polymer-assisted solution-phase parallel synthesis of dipeptide p-nitroanilides and dipeptide diphenyl phosphonates have been reported. A modular method for the construction of polypeptides containing the Phe-Arg phosphinic acid isostere has been described. A novel methodology for the solid-phase synthesis of phosphinic peptides has been developed in which the phosphorus-carbon bond was formed... 

Ohler, E., and Kanzler, S., Synthesis of phosphonic acids related to the antibiotic fosmidomycin from allylic a- and y-hydroxyphosphonates. Phosphorus, Sulfur Silicon Relat. Elem., 112, 71, 1996. Ohler, E., and Zbiral, E., Valence isomerism between 2,4-dienones and 2//-pyrans with dialkoxyphos-phinyl substituents. First synthesis of dialkyl 2//-pyran-4-ylphosphonates, Chem. Ber, 118, 2917, 1985. 

White phosphorus in THF reacts in a long radical chain reaction with carbon radicals derived from Barton s PTOC esters. Oxidation of the adducts (HgOg or SOg) provides a convenient synthesis of phosphonic acids. For sensitive products the further transformation to phosphonic acids is best carried out with an excess of SO2. The reaction is illustrated by the synthesis of L-2-amino-4-phosphonobutyric acid in 58% yield from L-glutamic acid using the appropriate protecting groups (Scheme 8.91). ... 

The Wittig reaction involves the interaction of an aldehyde or ketone with a phosphorus-containing carbanionic species, in which the phosphorus is bonded directly to the carbanionic site. At the time of discovery of the reaction, that specification described the triphenylphosphonium alkylides 343 later developments employed the anions from tert-phosphine oxides, the use of which has been described elsewhere in this series and also from a wide variety of phosphonic and phosphinic esters. This latter application will be considered more fully in Chapter 6. An early application of the reaction to the synthesis of alkenephosphonic acids, and which involved an ylide, employed the stable compound 344, generated from 345 by the action of a strong base. Reactions between 344 and aliphatic or aromatic aldehydes at 100 °C in toluene or dmso gave the diphenyl esters of (alk-1-enyl)phosphonic acids or (2-arylethenyl)phosphonic acids. ... 

There are only a few examples for the transformations of phosphorus-containing compounds witii baker s yeast [475, 476]. Thus baker s yeast has been used for the synthesis of a-aminophosphonates in a one-pot reaction from aldehyde, diethyl phosphite, and an amine [477]. The reduction of (3-chloro-2-oxo-propyl)-phosphonic acid diethyl ester by baker s yeast gave (2R)-3-chloro-2-hydrox5qjropyl-phosphoric acid diethyl ester, which could be used for the synthesis of (R)-camitine [478-480]. The... 

The pyrolysis of organoarsenic compounds containing the arsenyl moiety has some limited preparative applications [arsenyl (As=0) by analogy with phosphoryl (P=0)]. The compounds are based on the arsonic acid RAs(0)(0H)2, the arsinic acid R2As(0)0H and the arsine oxide R3As=0 structures. The acids are in interesting contrast with the phosphorus series. The phosphonic and phosphinic esters are prepared from the phosphorus(III) precursors via the Arbuzov synthesis. This synthetic route fails with the arsenic analogues, and further, if an alkyl halide or a salt is added in the pyrolysis of arsonic or arsinic acid esters a retro-Arbuzov reaction takes place . ... 

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 the phosphorus(V) acids area, there has been continued interest in the preparation of phosphates from elemental phosphorus, and also of compounds derived from the calixarenes. Apart from these, there has been little of real significance in the phosphate field. A much greater interest has been shown in enantio- or diastereo-selectivity in synthesis and reactivity of phosphonates and... 

Macomber and coworkers original observations provide a synthesis of 1,2-oxaphosph(V)ol-3-enes without the necessity for isolation of the (alka-l,2-dienyl)phos-phonic intermediates, although it is certain that these are formed during the course of the sequence (Scheme 56) The acid HX must be efficiently removed from the system (and not simply neutralized), otherwise side reactions lead to non-phosphorus by-products). When H, the products 450, from dibromophosphines, decompose to the phosphinic acids 451 even at slightly above room temperature, and cyclization occurs when the temperature is raised to about 100 Unusual properties are conferred upon the (alka-1,2-dienyl)phosphonic system by substituent tert-huiy groups the acid 452 (R = Bu r2 = r3 = underwent the expected cyclization, and with quantitative yields, when acted upon with trifluoroacetic acid but, by contrast, the acid 452 (R = R = Bu, R = H), in a slow reaction with trifluoroacetic acid, yields the acid 453. ... 

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