Esters, phosphonate, from

The main problem here is removing the phenyl ester groups from the phosphonic moiety.We have found that convenient routes for deblocking are hydrogenation on Adams catalyst and transesterification methods followed by hydrogen bromide in glacial acetic acid treatment. The best results ewre obtained if transesterification was carried out using potassium fluoride-crown ether-methanol system. 

Alkylphosphonate esters. Phosphonate esters with P-alkyl groups of different chain lengths can be prepared from iodoalkylphosphonates (alkyl being methyl, ethyl, propyl) and 1 -alkenes by a radical addition process, using an initiating system comprising BujSnCl, NaBH, and EtjB (Oj). 

Comins, D.L., Jacobine, A.E. Marshall, J.A., and Turnbull, M.M., Phosphonate ester preparation from active methylene compounds and phosphorochloridate esters, Synthesix, 309, 1978. 

The readily available OO-dialkyl phosphorodithioic acids (13) are converted into the corresponding phosphorothioic acids by reaction with nitriles in the presence of limited amounts of waterX In view of the initial difficulty encountered in preparing the sulphur analogue, the simple synthesis of the selenopyrophosphate ester (14) from selenious acid and the cyclic phosphonate (15) is remarkableX ... 

The construction of the alkenyl side chain and the control of the C9, CIO and Cll stereogenic centers was achieved from (5)-(+)-methyl 3-hydroxy-2-methylpropionate 1. (Scheme 21) This compound was transformed to aldehyde 99 in three steps. Bis(2,2,2)trifluoroethyl)[(methoxycabonyl)methyl]-phosphonate [23] was employed for the selective formation of the cA-a, 3-unsaturated ester 100. From this Z-unsaturated ester 100, the three consecutive asymmetric units were constructed via epoxide 101 (m-CPBA), which was selectively opened by lithium dimethylcuprate to produce 102. After deprotection-protection, the alcohol 102 was converted to the phosphonium iodide 103 via a tosylate intermediate(Scheme 21). 

The same phosphonate with the anhydride (138) gave the phosphonate (139 X = CN), existing as the acid (139) in the solid and as an equilibrium between (139) and the lactone (140) in solution. The corresponding product from the ester phosphonate is the lactone (140 X = C02Et) both in the solid and in solution. 

It has recently been demonstrated in our own laboratory that negatively substituted olefins of the type known as dienophiles react smoothly with phosphite, phosphonite, and phosphinite esters in the presence of a suitable proton donor (123,127). With the use of phenol for this purpose, reactions are exceptionally clean and high yields may be realized. Some representative examples are included in Table I. While ethanol or methanol are often satisfactory substitutes for phenol, the yields of phosphonate are generally lower and side reactions often occur, possibly due to the lessened efficiency of alcohol as a protonating agent. Yields of phosphonate for reactions in ethanol are indicated in brackets in Table I. Thus, in addition to the expected phosphonate from reaction of acrylamide and triethyl phosphite in ethanol, there were also ob-... 

Benzyloxypropyl)phosphonic and (2-trimethylsilyloxyethyl)phosphonic diethyl esters are obtained from the appropriate alkyl bromide and triethyl phosphite. Deprotection at the side-chain substituent (debenzylation with H2, Pd-C desilylation with MeOH-HCl) leaves the diethyl (2-hydroxypropyl)- and (2-hydroxyethyl)-phosphonates from which the free acids are readily obtainable by acid hydrolysis. Both procedures were adapted by Hammerschmidt for the preparation of deuterium-labelled compounds of known chirality for biosynthetic studies. The acetyl group can also be used for protection purposes ... 

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... 

The formation of diethyl (3-oxobutyl)phosphonate from triethyl phosphite and 3-oxobutyl acetate can be formulated also as taking place through a phosphorane intermediate. As further examples, the phosphoranes 587 have been prepared from the benzylidene derivatives 583, 584 585 and 586 Careful hydrolysis of the phosphoranes 587 with one equivalent of water in diethyl ether leads to the corresponding 588, which in turn tautomerize to the ketonic alkylphosphonic dimethyl esters 589, which can also be obtained independently by the addition of dimethyl hydrogenphosphonate to the original benzylidene compounds the latter, when heated, generate the dihydro-1,2-oxaphosph(V)oles 590. In the same way, the esters 593 have been obtained from the eth-ylidene compounds 591 via the respective oxyphosphoranes 592 (R = Me, Et, or EtO) ". ... 

Now, the C-D-E phosphonate fragment 1511 was coupled with an in situ-generated boronate ester derived from 1512 and 1508 to afford 1516 as a mixture of four diastereomers (Scheme 1.386). This mixmre of diastereomers was then... 

Insertions into Aldehyde C-H Bonds. The a-diazo ketones (and esters) derived from diazomethane and an acid chloride (or chloroformate) will also insert into the C-H bond of aldehydes to give 1,3-dicarbonyl derivatives. The reaction is catalyzed by SnCL, but some simple Lewis acids, such as BF3 etherate, also work. The reaction works well for ahphatic aldehydes, but gives variable results with aromatic aldehydes, at times giving none of the desired diketone (eq 32). StericaUy hindered aldehydes will also participate in this reaction, as illustratedin eq 33 with the reaction of ethyl a-diazoacetate and pivaldehyde. In a related reaction, a-diazo phosphonates and sulfonates will react with aldehydes in the presence of SnCL to give the corresponding -keto phosphonates and sulfonates. This reaction is a practical alternative to the Arbuzov reaction for the synthesis of these species. 

The Cs-phosphonium ester salts 95 + 99 and the Cs-phosphonate ester 100 (Scheme 11), as well as their corresponding methyl esters, are key building blocks for the manufacture of various polyenecarboxylic acid esters for use in the carotenoid field [34-36]. An efficient route uses as an intermediate 2-hydroxy-2-methylbut-3-enoic acid ethyl ester (101) [37,38], which can be prepared from methylvinyl ketone (102) by acidic ethanolysis of the cyanohydrin 103, prepared by reaction of 102 with HCN (104). Reaction of 101 with thionyl chloride under reflux conditions led to a 76% yield of distilled 4-chloro-2-methyl-but-2-enoic acid ethyl ester (105), from which the phosphonium chloride 98 was obtained in good yield [36]. 

Compound 11 is, however, unexpectedly unreactive with Wittig-Horner reagents. Upon heating with the carbanion of ester phosphonates an addition across the allenic bond occurs [14]. In contrast, a slow normal 1,2-addition takes place [14] with the ylide from cyano-methylphosphonate but, unexpectedly, this proceeds with concomitant inversion at the chiral axis as shown in Scheme 3, to give a mixture of 6R or 6S, and (9E)- or (9Z)-isomers 12-15. However, a fast and very clean 1,2-addition occurs with the ethynyl ketone 18 to yield the esters 19 and 20 (Scheme 4). DIB AH reduction of the separated stereoisomers gives the allenic alcohols 21 and 22 in high yield. Mild oxidation to the aldehydes 23 and 24, followed by their condensation with the acetylenic Cio-bis-ylide 25, leads to the stereoisomeric 15,15 -didehydromimulaxanthins 26 and 28, respectively (Schemes 5 and 6). The optically active. 

Figure 5. The Arbuzov reaction applied to synthesise the phosphonate ester (5) from the corresponding bromide. The norbomene compounds shown are racemates.

Phosphonate esters derived from trialkyl phosphites and bromoesters, for example, are deprotonated by strong bases to give resonance stabilized ions which attack aldehydes or ketones as follows. This provides a useful synthesis of ajS-unsaturated esters. 

Because the Wittig reaction is so useful for the preparation of alkenes, chemists have explored several variations of it. One of the most useful of these, known as the Homer-Emmons-Wadsworth modification, uses a phosphonate ester derived from an a-haloester or a ketone to generate the Wittig carbanion. 

The hydrolysis of phosphonic acid esters in Brij-35 micelles by cerium(IV) was investigated by Moss and Ragunathan (1999). The phosphonic esters differ from the phosphodiesters by the presence of only one ester bond and by a direct bond between phosphorus and the carbon atom of an alkyl or aryl group. Cerium(IV) ions also accelerate the hydrolysis of these diesters (Moss and Morales-Rojas, 2001 Moss et al., 2004). The phosphonoformate diesters show structural similarities with the phosphodiesters. Whereas zirconium(IV) and hafnium(IV) hydrolyze mainly the P-OR bond, cerium(IV) and thorium(IV) hydrolyze principally the C-OR bond in the phosphonoformate diesters. This chemoselective ester hydrolysis was not observed for the phosphodiester compounds. 

---