1-Alkynylphosphonates

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. ... 

The platinum-catalyzed diboration has been applied to some functionalized alkynes such as 1,3-diynes,44 1-borylalkynes,45 1,2-diborylethynes,46,47 and alkynylphosphonates.45 In particular, diboration of 1,2-diborylethyne gives tetraborylethene, which is a potential precursor for new boron heterocycles (Equation (2)).46,47... 

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]. 

Triphenylphosphine with alkynyl iodonium salts in sunlight gave quantitatively the corresponding phosphonium salts, some of which could not be obtained by other methods [73]. Trialkyl phosphites were also reactive towards alkynyl iodonium salts several diaikyl alkynylphosphonates were prepared in good yield, e.g. [74] ... 

Of other classes of acetylenic compounds which have been prepared recently by alkylation, 1-alkynylphosphonates should be mentioned. They are prepared in moderate yields from alkynylmagnesium halides and dialkyl or diaryl phosphoro-chloridates in ether at room temperature (equation 145) . 

Reaction of an alkynylphosphonate with LiAlH reduces both the alkyne and the phosphoryl groups ... 

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). ... 

Di- or tri-substituted vinylphosphonates (461), (462), (463) and (464) were selectively synthesized from 1-alkynylphosphonates (465) via intermediate phosphonates containing titanacycle (466), manipulated by Ti(0-iPr)4/2i-Pr MgCl (Scheme lO ). ... 

Dialkyl 1-alkynylphosphonates (22) were formed in good to high yields by treatment of 1-alkynyliodonium tosylates (23) with trialkyl phosphites the reaction is exothermic with trimethyl phosphite but requires heating with triethyl or triisopropyl phosphite. The addition of trimethyl or triethyl phosphite to 3-alkylene-2-oxindoles (24) has led to new product types for a, -unsaturated carbonyl compounds, i.e. a stable tri-alkoxyphosphonium zwitterion (25), and a C-alkylated phosphonate (26). ... 

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... 

Early transformation of trialkyl phosphites and haloalkynes into dialkyl 1-alkynylphosphonates was lunited to haloalkynes in which R was an electron-withdrawing group.In 1990, two innovations worthy of merit were reported. " The first featured alkynylphenyliodonium salts as alkynylating agents, and the second featured NiCl2 as a catalyst. ... 

The difficulties associated with this approach, namely the conversion of the bromoalkynes into sodium acetylides and the subsequent reaction of the latter with thc bromophosphate byproducts, are effectively eliminated by working at low temperature. Thus, sodium diethyl phosphite reacts with 1-bromoalkynes in THF at low temperature to give diethyl I -alkynylphosphonates in fair to good yields (37-75%, Scheme 1.6). Usually, yields are improved by further lowering the temperature and adding the bromoalkyne slowly. ... 

Nevertheless, the Michaelis-Becker route does not always proceed cleanly, and dialkyl 1-alkynylphosphonates frequently contain undesired side products that are not easily removed. Because of the difficulties associated with the use of 1-bromoalkynes, it is unsurprising that this reaction is used infrequently, and the general synthetic utility of the procedure remains to be proven. Haloalkynes are triphilic, and the approach of anionic and neutral nucleophiles at the haloalkyne has been discussed and evaluated in terms of the three sites. ... 

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). 

The preparation of dialkyl 1-alkynylphosphonates by an appropriate P-elimination procedure was first recorded in 1957, when it was reported that the action of EtONa on diethyl 2-[3-(diethoxyphosphinyl)propenyl] phosphate in refluxing EtOH leads to diethyl 1-propynylphosphonate in 69% yield (Scheme 1.13). The experimental conditions are crucial, and it has been shown that successful elimination of phosphate takes place to the exclusion of the ethanolysis reaction only at elevated temperature. At room temperature, diethyl 2-[3-(diethoxyphosphinyl)propenyl] phosphate is reported to undergo competing ethanolysis to triethyl phosphate and diethyl 2-oxo-propylphosphonate. Because of the drastic reaction conditions required for the subsequent conversion to 1-alkynylphosphonates, this method was rarely used and remained underdeveloped for a sigiuficant period of time. Fortunately, many efforts have been made to discover bases that might cause elimination of the phosphate from the enol without also bringing about isomerization or hydrolysis. The development of a variety of milder alternative methods has led to the much more widespread adoption of this elimination sequence. ... 

Recently, the conversion of diethyl 2-oxoalkyIphosphonates into diethyl 1-alkynylphosphonates via transient enol phosphates has been shown to occur in good yields. Thus, treahnent of diethyl... 

Two variants of this rearrangement have been reported. One uses triethyl phosphite instead of diethyl chlorophosphite. Thus, in the presence of a catalytic amount of para-toluenesulfonic acid, triethyl phosphite reacts with propargyl alcohol in DMF at room temperature to give a mixture of diethyl allenylphosphonate (51%) and diethyl 1-propynylphosphonate (14%). The second variant is based on the conversion of dialkyl allenylphosphonates (R , R H, R = H, Scheme 1.19) into dialkyl 1-alkynylphosphonates by a photochemically allowed [l,3s]-sigmatropic shift in ( ,11, with 46-50% yields. ... 

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... 

Unfortunately, the subsequent step using the Lindlar catalyst met with little success, and nonstereoselective partial reduction of the triple bond is observed." It was reported that most catalytic hydrogenations of dialkyl 1-alkynylphosphonates in EtOH using 5% Pd/CaCOj poisoned with quinoline gave mixtures comprising cis- and fra i-l-alkenylphosphonate and starting material, from which the predominant cis isomer was isolated. 

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