Phosphonates benzylphosphonates

Scheme 2.18 gives some representative olefination reactions of phosphonate anions. Entry 1 represents a typical preparative procedure. Entry 2 involves formation of a 2,4-dienoate ester using an a, 3-unsaturated aldehyde. Diethyl benzylphosphonate can be used in the Wadsworth-Emmons reaction, as illustrated by Entry 3. Entries 4 to 6 show other anion-stabilizing groups. Intramolecular reactions can be used to prepare cycloalkenes.264... 

Methanesulfonates 844, obtained by addition of diphenyl phosphite to aldehydes At1 Cl IO and mesylation of the hydroxyl group of the adducts, react with benzotriazole to give diphenyl a-(benzotriazol-l-yl)benzylphosphonates 845. Lithiation and treatment with aldehydes Ar2CHO converts phosphonates 845 into stilbenes 846, which can eliminate benzotriazole to give diarylacetylenes 847 (Scheme 135) <2002ARK(xiii)17>. 

Preparation of benzylphosphonic acid — Preparation of a phosphonic acid from red phosphorus in aqueous acid23... 

Orthophosphoric and benzylphosphonic acids have been selectively alkylated with triethyl phosphite in a new synthesis of mono-, di-, and triethyl phosphates and of mono- and di-methyl phosphonates.62 A-Methylol carboxamides and sulphonamides react with trialkyl phosphites to give the phosphonate derivatives (78) and (80), respectively.63 However, the mechanism appears to be quite different in each case while the carboamides react by a transesterification-rearrange-ment pathway, the sulphonamides undergo elimination-addition via the imine (79). 

SYNS DI-N-BUTYL BENZYLPHOSPHONATE PHOSPHONIC ACID, BENZYL-, DIBUTYL ESTER PHOSPHONIC ACID, (PHENYLMETHYL)-, DIBUTYL ESTER... 

When the halogen compound employed in the first step has an activated halogen atom (RCH CHCHjX, QHjCHjX, XCH2CO2H) a simpler procedure known as the Horner phosphonate modification of the Wittig reaction is applicable. When benzyl chloride is heated with triethyl phosphite, ethyl chloride is eliminated from the initially formed phosphonium chloride with the production of diethyl benzylphosphonate. This phospho-... 

Fluorinations. Electrophilic fluorination of alkali metal enolates with (PhSOj) 2NF is facile. Benzylic a,a-difluoronitriles, sulfonates, and phosphonates are similarly prepared. Monofluorination of benzylphosphonates is achieved by prior silylation. ... 

The Stille cross-coupling reaction between various heteroarylstannanes and ring-brominated benzylphosphonates (107) has been used to prepare heterobiaryl phosphonates 108. A key step in the synthesis of individual optical isomers of 2-hydroxymethyl-4-[3-(diethoxyphosphinyl)propyl]-5-alkylpiperazines 109 as CPP analogues is the alkylation of protected 5-alkyl-2-hydroxymethylpiperazines with (3-bromopropyl)phosphonate (Scheme 5). Compound 110, a new member... 

Scheme 3.42). Di-tert-butyl phosphonates are too bulky to be fluorinated cleanly by this procedure, and side reactions such as elimination of phosphate or formation of isobutylene are observed. The electrophilic fluorination of a dimethyl benzylphosphonate having a (benzy-loxycarbonyl)methyl moiety in the para position was unsuccessful, with only unidentified nonfluorinated products being isolated. This may be a consequence of the elimination of fluorine from the first formed monofluorinated products, yielding quinodimethane derivatives, which may undergo further reaction. ... 

Nitration of benzyl- and 2-phenylethyl-phosphonic acids under the usual conditions gives, as expected, the o- and p-nitro-derivatives. ° Diesters of benzylphosphonic acid may be alkylated at the benzylic position by treatment with strong base and alkyl halide mercuric acetate, however, cleaves the C—P bond, giving (98) and benzyl acetate. The related phosphinate (99) is... 

Further esterification of monobenzyl benzylphosphonate may be carried through the Mitsunobu procedure, the best yields being achieved using the potassium salt of the substrate. Monoesters of iV-protected (1-aminoalkyl)phosphonic acids are further esterified by alcohols in the presence of BOP-type reagents [(l-aminoalkyl)alkylj- and [(l-aminoalkyl)aryl]-phosphinic acids, again as their potassium salts, have been converted into esters by reactive alkyl halides in the presence of 18-crown-6 ether (see also reference The... 

Michaelis-Becker reactions have been carried out in two-phase systems even under such mild conditions, isomerization of prop-2-ynylphosphonic diesters occurs to give a 90% combined yield consisting of a mixture of diethyl propadienylphosphonate and diethyl-propy-l-nylphosphonate (85 15). Some of the allylic halides furnish small amounts of phosphonic esters, but others, and also benzyl halides, only undergo reaction in the presence of a long-chain tertiary amine hydrochloride catalyst. Dialkyl hydrogenphospho-nates and tertiary benzylamines react together to give dialkyl benzylphosphonates ". ... 

Benzisoxazoles can readily be obtained by anaerobic, spontaneous transformation of carbanions of a-(ort/ o-nitroaryl)benzyl phosphonates, derived from the ONSH in nitroarenes with carbanion of diethyl benzylphosphonate, whereas oxygen oxidation of such carbanions gives nitrobenzophenones (Scheme 96) [232],... 

In the case of aromatic spacers, the synthesis was carried out in five steps with an overall yield of 56%. 4-(Bromomethyl)benzonitrile was first reduced using diisobutylaluminium hydride and followed by hydrolysis, to obtain the corresponding aldehyde. The latter was then reacted with triethyl phosphite. Subsequent reaction with methylamine and reduction with sodium borohydride of the resulting phosphonate allowed synthesis of the phosphonated secondary amine. Finally, the 4-(iV-methylaciylamido-methyl)benzylphosphonic acid monomer was obtained by an aciyloylation reaction, and hydrolysis of the phosphonated ester group with bromo-trimethylsilane and methanol finally led to the desired phosphonic acid moiety. 

Stilbazole derivatives and r-conjugated compounds with a pyridine unit have been extensively studied for a wide range of applications. The grafting of phosphonic acid-derived stilbazole (4-(2-pyridin-4-yl-vinylj-benzylphosphonic acid) on Sn02 or... 

Besides the cyclic acid anhydrides, the oxaphosphorinanone oxides, which are bioisostere of acid anhydrides and inhibitors of P-lactamase [47], have also been synthesized by palladium-catalyzed C-H carbonylation of phosphonic and phos-phinic acids (Scheme 3.23) [48]. In the presence of 5mol% Pd(OAc)2, l.Sequiv. of PhI(OAc)2, and l.Sequiv. of AgOAc, benzylphosphonic and phosphinic acid derivatives could give the corresponding oxaphosphorinanone oxides in moderate to high yields by incorporation of a carbonyl group. 

In 2014, Lee and coworkers also reported an efficient phosphaannulation by Pd-catalyzed carbonylation of C-H bonds of phosphonic and phosphinic acids for the synthesis of oxaphosphorinanone oxides (Scheme 4.29) [43]. In the reaction, AgOAc and PhI(OAc)2 gave the best result. In the transformation, ethyl hydrogen benzylphosphonate and methyl-substituted phosphonate were totally ineffective. It indicated that introduction of two substituents at the a-position was essential for successful carbonylation. Both electron-donating and electron-withdrawing groups on the aryl ring were tolerated. 

At this stage, we made an effort to prepare two enantiomers of open-chain 1-(substituted phenoxyacetoxy)- -(substituted phenyl)methylphosphonates lA, IE and IF series. The herbicidal activity of these optically active substituted benzyl phosphonates lA, IE, and IF were examined. In this section, the synthesis and herbicidal activity of optically active substituted benzylphosphonates lA, IE and IF are introduced. The structure-activity relationships of these optically active compounds together with their racemates are discussed. 

Asymmetric hydrogenation of 1,2-unsaturated phosphonates is a straightforward method for the asymmetric synthesis of some phosphonates [78-80], but this method is not suitable for the synthesis of substituted benzylphosphonates lA, IE, and IF. As stated in Sect. 6.2, three series of optically active 0,0-dialkyl 1-(substituted phenoxyacetoxy)- -(substituted phenyl)methylphosphonates lA, IE, and IF had been successfully prepared by the condensation of substituted phen-oxyacetyl chlorides MS and optically active 1-hydroxy (substimted phenyl)meth-ylphosphonate M2. 

Skropeta D, Schmidt RR (2003) Chiral, non-racemic a-hydroxyphosphonates and phosphonic stereoselective hydroxylation of diallyl benzylphosphonates. Tetrahedron Asymmetry 14 265-273... 

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