Phosphono ester aldehyde

In the laboratory of T.R. Hoye, a HWE macmcyclic head-to-tail dimerization was used to construct the C2-symmetric macrocyclic core of (-)-cylindrocyclophane A. The monomer phosphono ester aldehyde was subjected to sodium hydride in benzene containing a catalytic amount of 15-crown-5 ether and 55% of the ( , )-macrocyclized product was obtained. None of the (Z,Z) stereoisomer was observed. Macrocyclization reactions usually require high-dilution conditions but even relatively concentrated solutions (0.02M) did not decrease the yield of the product in this case. 

Phosphonates. In a Homer-Emmons-based synthesis of di- and trisubstituted (Z)-Q(, -unsaturated esters, the strongly dissociated base system of potassium bis(trimethylsilyl)amide/18-Crown-6 was used to prepare the desired phosphonate anions. This base system, coupled with highly electrophilic bis(trifluoro-ethyl)phosphono esters, gave phosphonate anions which, when allowed to react with aldehydes, gave excellent selectivity for the (Z)-Q , -unsaturated esters (eq 15). ... 

Homer-Wadsworth-Emmons reactions of ketones and aldehydes with phosphono-acetate esters, (R20)2P(=0)CH2C02R1, produce E/Z mixtures of a, /Tunsaturated esters. Use of the conventional reagent, sodium hydride, gives some selectivity. The combination of tin(II) triflate and A -cthylpipcndine enhances—and sometimes also reverses—the selectivity in most cases studied.71 Six-membered oxo-coordinated tin intermediates are proposed to control the selectivities observed. A similarly selective synthesis of trisubstituted exocyclic alkenes from cyclic ketones has been reported.72... 

In the case of HWE reactions of phosphonate esters containing a charge-stabilizing electron-withdrawing group, for example, as in trimethyl phosphono-acetate, the carbanion is often generated by reaction with potassium fcrf-butoxide, sodium hydride, n-butyllithium or similar base. Direct reaction with an aldehyde or ketone then gives the ( )-a,P-unsaturated ester as the major product (see Protocol 6). The nature of the phosphonate (see Section 3), and the substitution of the aldehyde or ketone, can influence the stereochemical outcome of these reactions as can, to a lesser extent, the reaction temperature and solvent.16... 

Synthesis of Phosphoric Acids and Their Derivatives. - A series of monoalkyl and dialkyl phosphorus acid chiral esters have been synthesised for use as carriers for the transport of aromatic amino acids through supported liquid membranes. The compounds acted as effective carriers but enantio-separation was at best moderate. A range of phosphono- and phosphoro-fluoridates have been prepared by treatment of the corresponding thio- or seleno- phosphorus acids with aqueous silver fluoride at room temperature (Scheme 1). In some cases oxidation rather than fluorination occurred. Stereospecifically deuterium-labelled allylic isoprenoid diphosphates, e.g. (1), have been synthesised from the corresponding deuterium-labelled aldehyde by asymmetric reduction, phosphorylation and Sn2 displacement with pyrophosphate (Scheme 2). ... 

The syntheses of carbocyclic analogs of phosphononucleosides (29) and (30a-c) have been reported. Phosphonic acid (29) was obtained by introduction of the benzoylated thymine on the 2(4-hydroxycyclopent-2-enyl)ethyl phosphonic acid diisopropyl ester under Mitsunobu conditions while (30a-c) were prepared by building-up the base around a phosphono-cyclopentylamine moi-ety. The vinylphosphonate derivatives of uridine, cytidine and cytosine ara-binoside (31a-c) have been prepared by Wittig condensation of [(diethoxyphos-phinyl)methylidene]triphenylphosphorane with the appropriately protected 5-aldehydic nucleoside derivatives. Dihydroxylation of the novel vinyl phosphon-ates offered the dihydroxylated phosphonate derivatives (32a-c). Each of these novel compounds was evaluated as substrates for the enzyme nucleotide monophosphate kinase, and their toxicity to K562 cells. All analogues were found to be poorly phosphorylated by the kinase and exhibited poor in vivo toxicity. ... 

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