Alkynylphosphonates synthesis

Braga, A.L., Alves, E.E, Silveha, C.C., and de Andrade, L.H., Stereoselective addition of sodium organyl chalcogenolates to alkynylphosphonates. Synthesis of diethyl 2-(organyl)-2-(organochalcog-enyl)vinylphosphonates. Tetrahedron Lett., 41, 161, 2000. 

Konno T, Morigaki A, Ninomiya K, Miyabe T, Ishihara T. Convenient and efficient access to fluoroalkylated vinyl-phosphonates via highly regio and stereoselective hydrome-talation or carbometalation reactions of fluorine-containing alkynylphosphonates. Synthesis 2008 564—572. 

Enamine phosphonates (172) have been prepared by the addition of amines to alkynylphosphonates and used as shown in the synthesis of ajS-unsaturated ketones. The corresponding diphenylphosphine oxides have been prepared and used in a similar manner. ... 

Recent examples of the rearrangement or alkynylation pathway include conversions of arylethynyl- and er -butylethynyl(phenyl)iodonium tosylates 24 and 25 to alkynylphosphonates, -selenides, and -tellurides with the appropriate anion salts in DMF (Scheme 50) [145-147], and a similar synthesis of push-pull selenides and tellurides from alkynyliodonium triflates containing electron-withdrawing groups in the alkynyl moiety [148]. 

Hydrazines reacted with 4-, 5-, and 6-chloro-l-alkynylphosphonates to provide the corresponding 4,5-dihydropyr-azolo-3-methylphosphonates <2007TL3213>. A novel one-pot synthesis of substituted pyrazoles from chalcones and hydrazines in a tandem cyclization-dehydrogenation approach on Pd/C/K-10 catalyst has been described <2007SL1600>. 

Alkenyl, Alkynyl, Aryl and Related Acids. Vinylphosphonates are an important group of compounds that have found use in organic transformations. They are also useful reagents for the synthesis of biologically active systems. The synthesis of vinylphosphonates is varied. However additional convenient routes to them are always welcome. Four recent reports demonstrated that zirco-nacycles (180), readily available from diethyl 1-alkynylphosphonates, are very useful precursors of different vinylphosphonates. They react with alkynes, aldehydes, ketones acyl chlorides and nitriles to produce, in a highly stereo- and regio-selective manner, substituted vinylphosphonates (181), (182), (183) (184) and (185) respectively (Scheme 46). 

A method for the palladium - catalysed synthesis of alkynylphosphonates (206) from 1,1-dibromo-l-alkenes (207) has been developed. The best catalyst system for this transformation was Pd(OAc)2, dppf, H-phosphonate (208). The reaction appears tolerant of a range of functional groups in both (207) and (208) (Scheme 53). ... 

The methods developed for the synthesis of 1-alkynylphosphonates use synthetic concepts such as charge affinity inversion and positive halogen abstraction. Four main reaction categories allow the preparation of 1-alkynylphosphonates the apparent Michaelis-Arbuzov and Michaelis-Becker reactions, the propargyl phosphite-allenylphosphonate rearrangement, carbanionic displacements at quinquevalent phosphorus centers SNPfV), and conversions of vinyl- to alkynylphosphonates by addition-elimination reactions. 1-Alkynylphosphonates possess remarkable potential, and cycloaddition reactions appear to offer very attractive synthetic procedures. ... 

In view of the supposed inertness of halo-unsaturated substrates in the Michaelis-Arbuzov reaction, it is remarkable that arylalkynyl halides are more reactive than comparable alkyl, aryl, or vinyl halides toward trialkyl phosphites. The success of the Michaelis-Arbuzov reaction in the synthesis of dialkyl 1-alkynylphosphonates from 1-haloaIkynes has provoked a number of mechanistic studies. Three sites, the halogen, oc-carbon, and P-carbon have been investigated as the zone of the initial nucleophilic attack by trialkyl phosphites. Studies to date suggest that the reaction proceeds by at least two different mechanisms, and that probably the most important of these involves positive halogen-abstraction (path a) as outlined in Scheme... 

Because heteroatom-substituted vinylphosphonates such as enol phosphates and vinyl halides are masked acetylenic compounds, a variety of methods have been developed for their elaboration and subsequent use in the synthesis of dialkyl 1-alkynylphosphonates. These eliminations usually have the leaving group P to the phosphoryl group, although cases in which the leaving group is a to the phosphorus center are also known (Scheme 1.12). 

Partial reduction of the triple bond is used for the selective conversion of dialkyl 1-alkynylphosphonates into f/.v-l-alkcnylphosphonatcs. The first racemic synthesis of the antibiotic fosfomycin in 1969 serves as an illustration. The methodology is based on the stereospecific reduction of dibutyl... 

Zhang, J.-L., and Chen, Z.-C., Hypervalent iodine in synthesis. Part 25. Alkynylphenyliodonium tosylates as alkynylating reagents. Direct conversion of alkynylphenyhodonium tosylates to dialkyl alkynylphosphonates with sodium dialkylphosphonates, Synth. Commun., 28, 175, 1998. 

Diziere, R., and Savignac, P., A new simple method for the synthesis of 1-alkynylphosphonates using (EtOljPfOjCCL as precursor. Tetrahedron Lett., 37, 1783, 1996. 

Ohler, E. and Zbiral, E., Synthesis, reactions and NMR spectra of dialkyl 2-bromo-3-oxo-l-alke-nylphosphonates and dialkyl 3-oxo-l-alkynylphosphonates, Monatsh. Chem., 115, 493, 1984. 

Pergament, 1., and Srebnik, M., Control of hydroboration of 1-alkynylphosphonates, followed by Suzuki couphng provides regio- and stereospecific synthesis of di-substituted 1-alkenylphosphonalcs, Tetrahedron Lett.. 42. 8059, 2001. 

Eliminations. A convenient one-pot synthesis of 1-alkynylphosphonates involves enolphosphorylation of P-keto phosphonates and elimination with f-BuOK. 

The Pechmann pyrazole synthesis has also found similar utility for the preparation of perfluoroalkylated heterocyclic phosphonates, as demonstrated by the Shen group. Reaction of EDAC (30) with trifluoromethyl alkynylphosphonate 32 resulted in the formation of regioisomers 33 and 34 in high yield. The two regioisomers, isolated in a ratio of 85 15 (33 34) could be separated by column chromatography. 

The alkynylation of phosphorus nucleophiles has been less investigated (Scheme 7). Ochiai and co-workers first demonstrated in 1987 that the alkynylation of triphenyl-phosphine was possible with alkynyliodonium tetrafluoroborate salts under light irradiation (Scheme 7, A) [69]. The reaction most probably involves radical intermediates. In 1992, Stang and Critell showed that light irradiation was not needed if alkynyliodonium triflates were used [70]. Later, this methodology could be extended to other triaryl- or alkyl phosphines [71, 72]. In 1990, Koser and Lodaya also reported the synthesis of alkynylphosphonates by the Arbusov reaction of alkynyliodonium tosylates with trialkyl phosphites (Scheme 7, B) [73]. Alternatively, the same compotmds can be obtained by the reaction of alkynyliodonium tosylates with sodium phosphonate salts [74]. 

SCHEME 4.365 Synthesis of an alkynylphosphonate through an oxidative coupling reaction [550],... 

The copper-catalyzed oxidative coupling approach for the synthesis of alkynylphosphonates has also been reported using discrete copper acetyhdes and hydrogen phosphonates (Scheme 4.365) [550]. One of the most attractive aspects of this chemistry was its tolerance to a wide range of functional groups. The conditions were quite mild (room temperature), and the isolated yields of the alkynylphosphonates were moderate to excellent with the exception of a substrate containing a primary alcohol. 

SCHEME 4.367 Transition metal-free synthesis of alkynylphosphonates in open vessels [541]. 

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